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Song, Yue. "Study of membrane-related effects of TSH in thyrocytes: TSH receptor localization and action, and Duox-TPO interaction." Doctoral thesis, Universite Libre de Bruxelles, 2009. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210241.
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1. Sphingolipid-cholesterol domains (lipid rafts) in normal human and dog thyroid follicular cells are not involved in thyrotropin receptor signalling. <p>Thyroid hormone regulates growth and development throughout the animal kingdom. The thyroid which secretes it, is controlled by TSH and its receptor TSHR. TSH and its receptor TSHR act through TSHR-coupled G proteins to control thyroid functions, with a stronger coupling of the TSHR with Gs protein than with Gq protein in human thyrocytes. Gq is not activated by TSH/TSHR in dog, whereas dog TSHR activates it in CHO transfected cells. To better understand TSHR and its downstream effectors G proteins, we attempted to answer the questions by the role of “lipid rafts/caveolae” in TSH action.<p>Lipid rafts/caveolae are sphingolipids-cholesterol-enriched microdomains on plasma membrane that have been proposed to play a role in signal transduction. By concentrating the signal molecules, lipid rafts/caveolae increase the efficiency of the interactions between the molecules and sequestrate them from the bulk membranes. The compartmentation of signal proteins in lipid rafts/caveolae might provide a possible explanation for the relationship between TSHR and G proteins in human and dog thyroctyes.<p>To answer these questions, we first tested the existence of such lipid microdomains in human and dog thyrocytes. By northernblot and RT-PCR of caveolin-1 mRNA, we demonstrated its existence in thyrocytes. The immunohistochemistry of caveolin-1 showed that caveolin/caveolae are present on the apical membrane of thyrocytes, opposite to the TSHR localization on the basolateral membranes. The isolation of lipid rafts/caveolae by Triton X-100/OptiPrep density experiments showed that TSHR and Gq are not in the rafts, even though other proteins such as insulin receptor, flotillin-2 and partially Gs are present in these lipid domains, as expected. Testing the function of the TSH receptor on its main cascade (Gs-Adenylyl cyclase-cAMP) after treating the follicles with Methyl β-cyclodextrin (a cholesterol chelator), we observed no modification of the cAMP levels by this treatment. This is in agreement with our conclusion that the TSHR-Gs-cAMP pathway does not involve the lipid rafts/caveolae domain.<p>TSH-activated signalling does not take place in these membrane domains. Therefore, the differences between species, concerning the TSHR-G proteins coupling cannot be explained by the presence of these membrane domains.<p>2. Species specific thyroid signal transduction: conserved physiology, diverged mechanisms<p>As mentioned above, Gq proteins are activated in human but not in dog thyroid, in response to TSHR. However the dog TSH receptor is able to activate Gq, as demonstrated in transfected CHO cells. Thus, different thyroid signal transduction pathways exist in different species. <p>In this study, we investigated the effects of TSH on its two signal transduction cascades, the cAMP pathway and the phospholipase C – IP3 – DAG pathway, as measured by cAMP levels and inositol phosphate generation. We also measured the effects of TSH and of agents stimulating specifically one of these cascades, forskolin for the cAMP pathway and Ca++ ionophore (ionomycin) and phorbolmyristate ester (TPA) for the phospholipase C pathway, on markers of thyroid hormone synthesis (H2O2 generation and iodide binding to proteins) and on thyroid hormone secretion in vitro in the various thyroids. <p>We demonstrated that in all species investigated, the TSH receptor activates both hormone synthesis and secretion. While in some species, including humans, rats and mice, the TSH receptor activates both the cAMP and phospholipase C– IP3 – DAG cascades, in others (e.g. dog) it only stimulates the first. The cAMP pathway activates the limiting step in thyroid hormone synthesis, the generation of H2O2, in dog, rat and mice but not in human, pig, horse and beef. Thus physiology remains but the pathways to achieve it differ. On a practical point of view, these results allow to choose adequate animal models for investigating different aspects of human thyroid signalling.<p><p>3. Duoxes -TPO association and its regulation in human thyrocytes: the thyroxisome<p>Duox (Dual Oxidase) and TPO (thyroid peroxidase) are the crucial enzymes for the thyroid hormones biosynthesis (T3/T4). TPO uses the hydrogen peroxide (H2O2) produced by Duox1 and Duox2 isoenzymes to covalently link oxidized iodide to tyrosines of thyroglobulin and couple the iodinated tyrosines to form triiodothyronine (T3) and thyroxine (T4). An excess of H2O2 is considered to be toxic for cells although at appropriate concentrations H2O2 may carry out signalling functions. Even though thyrocytes show a better resistance to H2O2 than other cells, it would be beneficial for thyrocytes if Duox and TPO localize closely to increase the working efficiency and avoid an excessive H2O2 spillage. In this study, we explored the association of Duox with TPO, and the possible factors affecting their interaction in the human thyrocyte model. This association was established by co-immunoprecipitation approaches on purified plasma membranes from human thyrocytes and COS-7 transfected cells. <p>Our results show that 1) Duox and TPO localize closely at the plasma membranes of human thyrocytes, 2) this association is up-regulated through the Gq-PLC-Ca2+-PKC pathway and down-regulated through the Gs-cAMP-PKA pathway. 3) H2O2 directly increases the association of Duox and TPO. 4) Partial NH2- or COOH-terminal Duox1 and Duox2 proteins show different binding abilities with TPO in COS-7 transfected cells.<p>The association of the two proteins Duox and TPO thus supports our previous hypothesis of the thyroxisome, a pluriprotein plasma membrane complex in which elements of the iodination apparatus localize closely, thus optimizing working efficiency and minimizing H2O2 spillage. Defect in this association, independently of the catalytic efficiency of the enzyme, could therefore impair thyroid hormone synthesis and be harmful to thyroid cells, leading to thyroid insufficiency.<p><br>Doctorat en Sciences biomédicales et pharmaceutiques<br>info:eu-repo/semantics/nonPublished
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Lee, Kok-Onn. "The biological activity of TSH (Thyrotropin)." Thesis, Queen's University Belfast, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335319.
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Larsen, Donald A. "Quantification and regulation of thyroid stimulating hormone (TSH) and TSH messenger RNA in salmon /." Thesis, Connect to this title online; UW restricted, 1997. http://hdl.handle.net/1773/5343.
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Devlin, Marni Allison. "The characterization of TSH-mediated phospholipase D activity in thyroid cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0017/MQ47020.pdf.
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Typlt, Eva. "„Heiße“ Schilddrüsenknoten bei Kindern: Mutationshäufigkeiten und Mutationsmuster aktivierender TSH-Rezeptor- und Gs alpha- Mutationen." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-196346.
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Szintigrafisch heiße Schilddrüsenknoten (HTNs) bei Kindern sind selten. Ihre Malignitätsrate wird als höher beschrieben im Vergleich zu der Erwachsenenpopulation. Es wurden in dieser Dissertation klinische und molekulare Daten von 33 Kindern (29 benigne und 4 maligne HTNs) untersucht.
In 17 der 29 benignen HTNs (59%) konnte eine TSHR- Mutation nachgewiesen werden. Die häufigste Mutation war die M453T (8 von 29 Proben). T632I- und D633Y- Mutationen konnten jeweils in zwei Fällen detektiert werden. Alle anderen gefundenen TSHR- Mutation wurden jeweils nur in einer Probe festgestellt, inklusive die neu aufgetretene Mutation A538T. Eine NRAS- Mutation wurde in einem HTN mit einer M453T- Mutation gemeinsam nachgewiesen. Ein PAX8/PPARγ- Rearrangement konnte in einem malignen Knoten (follikuläre Variante eines papillären Schilddrüsenkarzinoms; fvPTC) detektiert werden. Ebenfalls konnte in einem malignen HTN (papilläres Schilddrüsenkarzinom; PTC) eine T632I- Mutation nachgewiesen werden.
Der Prozentsatz an TSHR- mutations-positiven HTNs in Kindern und Heranwachsenden lag in dem bei Erwachsenen beschriebenen Bereich. Auffällig war die signifikante Häufung der M453T- Mutation in der Kinderpopulation. Die beschriebene erhöhte Malignitätsrate der HTNs bei Kindern scheint nicht mit RAS- , BRAF- , RET/PTC- oder PAX8/PPARγ- Mutationen assoziiert zu sein.
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Johnsen, Hanna. "The Importance of the TSHR-gene in Domestic Chicken." Thesis, Linköpings universitet, Biologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-103687.
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Thyroid hormones are known to be important in several processes in chicken, such as growth, metabolism and reproductive system. In previous studies the thyroid stimulating hormone receptor (TSHR)-gene has been identified as a target for a selective sweep in commercial breeds of chicken such as broiler and White Leghorn. The evolution of domesticated species can be split into three periods. The first is the natural selection in their natural habitat, the second the beginning of the domestication process, when humans started to tame and breed the wild animals and the third is when animals were bred for commercial interests such as egg laying properties and meat production in chicken. Landraces, which are domesticated but not commercially bred races, are a great resource for identifying during which period a specific gene, which differs between wild type and commercial bred breeds, were selected. In this study Swedish landrace chickens were used in order to analyze the importance of a mutation in the TSHR-gene in the domestication process. The results of this study gave that all, except two individuals from the Bohuslän-Dals svarthöna were homozygous for the mutation known from commercial breeds. The two individuals from Bohuslän-Dals svarthöna were both heterozygous for the mutation. These results suggest that the TSHR mutation is important for the domestication process and were already more or less fixed at the commencement of commercial breeding. The mutation is thought to be dominant and to have an inhibitory impact on the TSHR activity. This might result in hypothyroidism which would make alterations in the reproductive system. This is plausible because the constant availability of food in captivity makes the seasonal reproductive system no longer critical for survival of progeny.
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Esapa, Christopher Tarh. "Mutation analysis of the TSH receptor, GTP-binding proteins and protein kinase A in thyroid disease." Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322665.
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DAMIANI, RENATA. "Expressao estavel de tireotrofina humana (r-hTSH) em celulas de mamifero (CHO) que expressam 'alfa'2,6-sialiltransferase." reponame:Repositório Institucional do IPEN, 2009. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9436.
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Durand, Jason AJ. "Regulation of Adipocyte Lipolysis by TSH and its Role in Macrophage Inflammation." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/22694.
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Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.
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Cristo, Ana Patrícia de. "Avaliação do TSH sérico como fator preditivo de malignidade em nódulos tireoidianos de pacientes submetidos à punção aspirativa por agulha fina." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/71619.
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Nódulos de tireoide são achados clínicos comuns e, atualmente, o método diagnóstico de escolha para diferenciar lesões benignas de lesões malignas é a análise citopatológica dos nódulos através de punção aspirativa por agulha fina (PAAF). Estudos prévios já indicaram que os níveis séricos de TSH podem estar associados ao risco de malignidade nodular. O objetivo deste estudo foi avaliar se o TSH sérico é um preditor de malignidade em nódulos de tireoide em pacientes submetidos à PAAF. A amostra contemplou 100 indivíduos puncionados consecutivamente no Centro de Pronto Diagnóstico Ambulatorial, CPDA, HCPA e que apresentavam níveis de TSH dentro da normalidade. Todos os pacientes foram submetidos à PAAF da tireoide com controle ultrassonográfico e tiveram, posteriormente, a análise citopatológica da PAAF e a avaliação histopatológica do bloco celular. A análise estatística baseou-se em dados de frequências e testes não-paramétricos foram utilizados para correlacionar as variáveis. A população de estudo foi composta por 100 pacientes, sendo 89 mulheres e 11 homens. A média de idade foi de 54,1 ± 14,2 anos e o tamanho médio dos nódulos foi de 2.53 ± 1.36 centímetros. Vinte e seis % destes pacientes apresentavam algum tipo de doença tireoidiana prévia. A média do nível de TSH sérico entre os 100 indivíduos foi de 1.81 ± 1.08 uUI/mL. De acordo com o diagnóstico citopatológico da PAAF complementado pelos achados do bloco celular foram classificados como malignos 8% dos nódulos, 70% benignos, 11% suspeitos/ indeterminados, 8% insuficientes e 3% lesões foliculares. A média de TSH para os grupos maligno, benigno, suspeito/indeterminado, insuficiente e lesão folicular foi de, respectivamente, 2.48, 1.59, 2.21, 2.35 e 2.20 uUI/ml (p>0.05). Não houve diferença estatística significante entre os grupos diagnósticos avaliados, apesar de haver uma variação entre os níveis de TSH entre os grupos refletindo, provavelmente, o pequeno tamanho da amostra.<br>Thyroid nodules are common and currently the first choice of investigation in distinguishing benign from malignant disease is the cytological analysis of fine needle aspiration biopsy (FNAB). Previous studies have indicated that serum TSH levels might be associated with the likelihood of malignancy. The aim of this study was to evaluate whether serum TSH is a predictor of malignancy of thyroid nodules in patients undergoing FNAB. One hundred consecutive patients, who underwent FNAB as part of clinical investigation of thyroid nodule in a multidisciplinary setting tertiary hospital, underwent ultrasonography followed by FNAB, cytology and cell block analysis. Independent-Samples Kruskal-Wallis test was used to compare the groups. The study population comprised of 89 female and 11 male patients. The mean age was 54.1 ± 14.2 years. 26% had previous thyroid disease. Mean TSH levels was 1.81 ± 1.08 uUI/mL and the mean nodule size was 2.53 ± 1.36cm. Final cytology/cell block diagnosis classified 8% as malignant, 70% as benign, 11% suspicious/indeterminate, 8% insufficient and 3% follicular lesion. The mean TSH values for malignant, benign, suspect, insufficient and follicular lesion group were as follows: 2.48, 1.59, 2.21, 2.35 and 2.20 uUI/ml, respectively. No statistical significance was detected between TSH levels and final cytology/cell block diagnosis, possibly reflecting the small sample size (P>0.05). We observed a variation between TSH levels among the groups covered in this study, but there was no statistically significant difference among them.
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Maquet, Emilie. "Zebrafish as a model to study thyroid development and congenital hypothyroidism." Doctoral thesis, Universite Libre de Bruxelles, 2011. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209821.
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Congenital Hypothyroidism (CH) is the most common endocrine disorder, affecting one out of 2000-4000 newborns. Most CH are due to a defect in thyroid embryonic development and they can lead to severe phenotypes if not treated correctly. Multiple observations argue in favor of a genetic cause in a minority of thyroid dysgenesis, but to date, only few cases could be explained by a mutation in one of the genes coding for the factors known to be important in thyroid development and/or function (NKX2-1, PAX8, FOXE1, TSHR). This is the reason why it was important to develop new models allowing the discovery of new genes/mechanisms potentially implicated in the gland organogenesis. To that purpose, we set up in the laboratory a structure enabling the use of zebrafish as an animal model. The latter is indeed more and more used by developmental biologists, including by scientists interested in thyroid development.<p><p>The first step of our project consisted in a deeper characterization of the model, notably by the study of the expression patterns of the thyroid functional differentiation markers. Furthermore, the exact role of the Tsh/Tshr signaling – main regulator of thyroid growth and function in mammals – was dissected. In a second part of the project, we generated a stable transgenic line (tg(tg:mCherry)) allowing the visualization of thyroid development in living embryos and in a dynamic manner, thanks to real-time imaging techniques. On the one hand, this tool enabled us to better understand the morphological aspect of the different stages of thyroid development, such as the budding, evagination, relocalization or folliculogenesis. On the other hand, the use of double transgenic fishes obtained by crossing tg(tg:mCherry) with other lines expressing GFP in surrounding structures of interest, allowed us to highlight the contacts between the cardiovascular system and thyroid, and this along the whole gland development. The introduction of this model within the laboratory paves the way for the discovery and the study of thyroid intrinsic and extrinsic genes/mechanisms which might play a role on its development.<p><p>L’hypothyroïdie congénitale (HC) est une maladie relativement fréquente, touchant un nouveau-né sur 2000-4000. La majorité des HC sont dues à un défaut dans le développement embryonnaire de la glande, et peuvent mener à des phénotypes sévères si elles ne sont pas correctement traitées. Il existe plusieurs arguments en faveur d’une cause génétique dans une minorité de ces dysgénésies thyroïdiennes mais, à ce jour, seuls quelques cas ont pu être reliés à une mutation dans un des gènes codant pour des facteurs connus pour être importants dans le développement/la fonction de la glande (NKX2-1, PAX8, FOXE1, TSHR). C’est pour cette raison qu’il est important de développer de nouveaux modèles pouvant permettre la découverte de nouveaux gènes/mécanismes potentiellement impliqués dans l’organogénèse de la glande. A cette fin, nous avons mis en place au sein du laboratoire une structure permettant l’utilisation du poisson-zèbre comme modèle animal. Ce dernier est en effet de plus en plus utilisé par les biologistes du développement, y compris par les scientifiques qui s’intéressent au développement thyroïdien.<p><p>La première étape de notre travail a consisté en une caractérisation approfondie du modèle, notamment par l’étude du réseau d’expression des marqueurs de différenciation fonctionnelle de la glande. En outre, le rôle exact de la signalisation par la TSH – principal régulateur de la croissance et de la fonction de la thyroïde des mammifères – a été étudié. Dans la deuxième partie du projet, nous avons généré une ligne transgénique stable (tg(tg:mCherry)) permettant la visualisation du développement thyroïdien dans des embryons vivants et ce, de manière dynamique, grâce au principe d’imagerie en temps réel. D’une part, cet outil nous a permis de mieux comprendre l’aspect morphologique des différentes étapes du développement thyroïdien, telles que la formation du bourgeon, l’invagination, la relocalisation ou la folliculogénèse. D’autre part, l’utilisation de poissons doublement transgéniques obtenus par le croisement de tg(tg:mCherry) avec d’autres lignées où les structures environnantes d’intérêt expriment la GFP nous a permis de mettre en avant les contacts entre le système cardiovasculaire et la thyroïde, et ce, tout au long de son développement. La mise en place de ce modèle au sein de notre laboratoire ouvre la voie à la découverte et à l’étude de mécanismes/gènes extrinsèques à la thyroïde mais pouvant jouer un rôle sur son développement.<br>Doctorat en Sciences agronomiques et ingénierie biologique<br>info:eu-repo/semantics/nonPublished
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Hamilton, Kristina. "The serum concentrations of anti-Mullerian hormone (AMH), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) during early pregnancy." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2016. https://ro.ecu.edu.au/theses/1791.
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The first trimester of pregnancy is a dynamic time of change involving the implantation and development of the fetus, together with a wide range of related endocrine changes arising from the ovary and feto-placental unit, as well as other changes in maternal and fetal physiology. The present longitudinal study has investigated two main areas of endocrinology in circulating maternal serum from positive pregnancy test to the detection of a fetal heartbeat, namely (i) AMH and (ii) thyroid function. Women attending Fertility North and conceiving during fertility investigation or treatment underwent phlebotomy twice weekly and AMH, TSH, fT3 and fT4 levels were measured, in addition to the reproductive hormones oestradiol (E2), progesterone (P4) and human chorionic gonadotropin (hCG).
AMH is a well-established biomarker for assessing the age-related decline of the oocyte pool in healthy women, but has many other clinical uses including the assessment of polycystic ovary syndrome (PCOS), estimating response to ovarian stimulation with exogenous gonadotrophins, detection of granulosa cell tumours and identification of premature ovarian insufficiency. AMH also influences follicle growth, but the precise mechanism by which it does this is unknown and its role during pregnancy has not been adequately characterised.
In this study the key findings regarding AMH were the differences between preovulatory and luteal phase AMH levels in pre pregnant women and the three distinct patterns of changing AMH noted in women once pregnancy was confirmed. Prior to pregnancy, mean AMH levels peaked at time of ovulation (gestation week 2) and then dropped at mid-luteal phase (gestation week 3). 86.1% of women had their maximum AMH level at or before ovulation, with 13.9% of women having their maximum AMH at mid-luteal phase. However, once pregnancy was achieved, AMH levels for each woman did not remain constant, but moved significantly away from their first non-pregnant measurement, with a trend in viable pregnancies of an AMH level that either consistently increased or decreased from gestation week 4 (time of first positive hCG measurement) through to week 7. The difference between women with rising AMH compared to those with falling AMH significantly increased (p=0.000) during early pregnancy. In general terms women with rising AMH levels, had continually rising AMH iii levels and these levels became increasingly divergent from those women who had falling AMH levels and whose AMH levels continued to decrease. In contrast, AMH levels in women with non-viable pregnancies were very inconsistent, with no definitive rising or falling trend observed. Instead, AMH levels in women with non-viable pregnancies showed erratic and sporadic changes, both rising and falling in the same individual from gestation weeks 4 to 7. There was a significant negative correlation between baseline (day 2 of the menstrual cycle) AMH and patient age (r=-0.507, p=0.000). No associations were observed between AMH and patient body mass index (BMI), stimulation medications (follicle stimulating hormone dose), treatment type or fetal sex. There were weak negative correlations between AMH and P4 (r=-0.220, p=0.000,) and TSH (r=-0.155, p=0.001), but not E2, hCG, fT3 or fT4. This study was not designed to determine causative factors for the AMH changes observed and further investigations would be required to address possible causes of these reported changes.
The importance of normal maternal thyroid function in pregnancy and fetal development is well characterised and thyroid dysfunction can result in adverse effects on the unborn child, including a higher risk of miscarriage. Throughout the first trimester, the fetus is dependent on maternal thyroxine as the fetal thyroid is not fully functional until approximately gestation week 16. Despite this important role, the changes, if any, occurring during this vibrant period are poorly documented and often are limited to cross-sectional sampling.
In this study the key findings regarding thyroid function were of stable fT3, fT4 and TSH levels between gestation weeks 0 to 4 (pre pregnancy) with subsequent changes in thyroid function once pregnancy was established at gestation week 4 (hCG >25mU/ml). From gestation weeks 4 to 6.5 some significant changes in thyroid hormone levels were observed with a gradual decrease in fT3 (r=-0.104, p=0.005) and TSH levels (r=-0.123 p=0.013). In contrast, fT4 levels remained constant during early pregnancy (gestation weeks 4 to 6.5). No markers of thyroid function appeared to affect pregnancy outcome. Despite TSH levels ranging from 0.27 - 4.93mU/L, only 6 patients (7.0%) had TSH levels >4.0mU/L, of whom only 3 (3.5%) miscarried. Reference ranges were calculated for fT3, fT4 and TSH for gestation weeks 4 to 6.5 and were iv found to be comparable to later first trimester ranges reported in other studies. There were two patients who tested positive for thyroid peroxidase antibody (TPOAb) who were excluded from the study (both were viable pregnancies with normal thyroid hormone levels).
In summary, this study was able to directly follow the changes in AMH and thyroid hormone levels within the same individual over time, resulting in the identification of unique changes in very early pregnancy.
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Veltri, Flora. "Variables influencing thyroid function during pregnancy and their potential use in clinical practice." Doctoral thesis, Universite Libre de Bruxelles, 2020. https://dipot.ulb.ac.be/dspace/bitstream/2013/313347/4/TDM.pdf.
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Pregnancy is a condition leading to an important strain on thyroid morphology and function.A normal functioning of the thyroid gland in the mother is essential for the early fetal development, since the fetal thyroid does not produce thyroid hormones until the end of the first trimester (approximately 12 to 14 weeks).The impact of thyroid dysfunction (and especially hypothyroidism) during pregnancy is well documented and has been associated with a number of obstetrical complications, such as premature delivery, low birth weight and even fetal death. In view of all changes in thyroid physiology during pregnancy the ATA (American Thyroid Association) guidelines recommend using trimester- and population-specific normality ranges, to define thyroid dysfunction. It is proposed to determine them in pregnant women without thyroid antibodies (TPO) and without severe iodine deficiency. Due to the few numbers of randomized clinical trials, there is still no consensus whether all pregnant women should be screened or only women at risk for the development of thyroid dysfunction during pregnancy.Thyroid dysfunction during pregnancy is caused in most cases by the presence of thyroid autoimmunity (TAI) and also the altered pregnancy outcomes in most studies are associated with the presence of TAI.Besides the presence of TAI, other factors might also change, influence and/or modify thyroid function. When we started our research, there were only few studies that investigated the impact of other variables, such as iron, BMI, smoking habit and/or the background of the pregnant women on the prevalence of thyroid dysfunction during the first trimester of pregnancy.The aims of the thesis were therefore, to investigate: • the association between the iron reserve status (ferritin levels), thyroid (dys)function and autoimmunity, corrected for confounders such as age, BMI, smoking habit and the time of blood sampling;• the impact of the ethnic background of the pregnant woman on thyroid function and autoimmunity, corrected for confounders such as age, BMI, smoking habit, and the time of blood sampling. Furthermore, to determine ethnic-specific reference ranges and investigate their impact on the diagnosis of thyroid dysfunction;• the impact of changes in thyroid function within the normal reference range in women free of thyroid autoimmunity on pregnancy outcomes, corrected for established covariates (age, BMI, smoking) and iron reserve as candidate new variable.• whether targeted high-risk screening for thyroid dysfunction during pregnancy could be improved with the inclusion of iron status and ethnicity to the actual risk factors defined in the ATA-GL.The results can be summarized as follows:Thyroid function during pregnancy can be influenced by variables others than thyroid antibodies such as the iron status and the ethnical background of the women. However, their impact on thyroid function is less important compared to that of thyroid antibodies. No significant impact of well-known variables (BMI, age, smoking) and others such as iron has been shown on clinical pregnancy outcomes when thyroid function remained within the normal range and no thyroid antibodies were present.We have shown that adding variables such as iron deficiency, ethnic background and obesity to the currently provided list of factors leading to a high-risk for the development of thyroid dysfunction during pregnancy, might improve the detection rate of subclinical hypothyroidism to comparable rates obtained in case of universal screening.<br>Doctorat en Sciences médicales (Médecine)<br>info:eu-repo/semantics/nonPublished
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Paternot, Sabine. "Différents mécanismes d'activation de la CDK4 par l'AMP cyclique et les facteurs de croissance dans les cellules épithéliales thyroïdiennes." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210826.
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La progression dans le cycle cellulaire est gouvernée par l’activation séquentielle d’une série de complexes cycline/CDK. La CDK4 initie le passage du point de restriction (point R, à partir duquel l’achèvement du cycle cellulaire devient indépendant des facteurs extracellulaires) en phosphorylant les protéines « antioncogéniques » de la famille pRb. Dans les thyrocytes de chien en culture primaire, l’AMPc (TSH ou forskoline) induit la prolifération et la différenciation alors que la voie mitogénique des facteurs de croissance (l’EGF, par exemple) est associée à une dédifférenciation. Dans ce modèle physiologiquement relevant, la stimulation mitogénique par l’AMPc diffère des cascades des facteurs de croissance puisqu'elle n’induit pas les cyclines D mais au contraire augmente l’accumulation de l’inhibiteur de CDK p27 kip1. Le contrôle positif du cycle cellulaire par l’AMPc requiert néanmoins l’activité de la CDK4. L’AMPc stimule l’assemblage des complexes cycline D3-CDK4 ainsi que leur translocation nucléaire associée à leur liaison à p27. Notre but était d’élucider les différents mécanismes menant au passage du point de restriction dans les cellules épithéliales thyroïdiennes stimulées par l’AMPc ou les facteurs de croissance. <p>Dans ce travail, nous montrons que l’arrêt de la stimulation des thyrocytes de chien par l’AMPc entraîne une diminution rapide de la phosphorylation de pRb et de l’activité de la CDK4 sans affecter la formation des complexes cycline D3-CDK4-p27. Par une approche utilisant le haut pouvoir de résolution de l’électrophorèse bidimensionnelle, nous avons identifié la phosphorylation activatrice de la CDK4 comme cible du contrôle par l’AMPc du passage du point de restriction. Ceci constitue un premier exemple d’une régulation de la phosphorylation et de l’activité de la CDK4 indépendante de son association avec une cycline ou un inhibiteur de CDK. Ces résultats contrastent avec l’absence de modulation d’expression, de localisation subcellulaire et d’assemblage des complexes cycline H-CDK7-Mat1, la CAK considérée comme responsable de la phosphorylation activatrice de la CDK4. Ceci suggère que les CAKs régulées activant la CDK4 n’ont pas encore été identifiées.<p>D’autre part, alors que la TSH induit une accumulation de p27, nous montrons à présent que l’expression de la p21 apparentée est augmentée par l’EGF + sérum et réprimée par la TSH. En réponse à l’EGF + sérum ou à la TSH, respectivement, la p21 ou la p27 supportent la localisation nucléaire, la phosphorylation et l’activité de la CDK4. Les « inhibiteurs » de CDK p21 et p27 pourraient donc être utilisés différentiellement comme régulateurs positifs de la CDK4 lors des stimulations des cellules épithéliales thyroïdiennes de chien par la TSH (p27) ou par l’EGF + sérum (p21). <p>Nous avons également montré que les complexes cycline D1-CDK4 et cycline D3-CDK4 phosphorylent pRb sur des sites partiellement différents. Cette nouvelle observation a été reproduite pour des complexes cycline D-CDK4 surexprimés en cellules CHO ainsi que pour des complexes exprimés de manière endogène dans différents types cellulaires. Cette différence de spécificité de substrat entre la cycline D1 et la cycline D3 conduit à différents profils de phosphorylation de pRb dans les thyrocytes de chien stimulés par la TSH ou les facteurs de croissance, ce qui est dû à l’utilisation préférentielle de la cycline D3 dans les thyrocytes stimulés par la TSH alors que les facteurs de croissance induisent surtout la cycline D1. Comme différentes fonctions de pRb sont régulées par phosphorylation sur différents résidus, ce résultat indique que les complexes cycline D1-CDK et cycline D3-CDK pourraient affecter de manière partiellement différente la fonction de cette protéine. <p>Enfin, nous avons comparé les stimulations mitogéniques par la TSH ou l’EGF + sérum dans les thyrocytes humains normaux en culture primaire. En accord avec leurs modulations différentes, la cycline D3 et la cycline D1 sont utilisées différentiellement dans les voies mitogéniques stimulées par la TSH ou l’EGF + sérum respectivement. De plus, ce système nous a permis de confirmer la régulation de l’activité de la CDK4 au niveau de sa phosphorylation activatrice comme mécanisme déterminant de la réponse mitogénique.<p><p><br>Doctorat en sciences biomédicales<br>info:eu-repo/semantics/nonPublished
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Melo, Thaís Gomes de 1979. "Análise da densidade mineral óssea de pacientes pós-menopausa com terapia supressiva do TSH por carcinoma diferenciado da tireóide." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310391.
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Orientadores: Lígia Vera Montalli da Assumpção, Denise Engelbrecht Zantut-Wittmann<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas<br>Made available in DSpace on 2018-08-21T14:23:09Z (GMT). No. of bitstreams: 1
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Previous issue date: 2012<br>Resumo: Introdução: A supressão do hormônio tireoestimulante (TSH) com doses suprafisiológicas de levotiroxina é um dos pilares do tratamento do carcinoma diferenciado de tireóide (CDT), levando os pacientes a um estado de tireotoxicose exógena subclínica (TES). Tal situação pode exercer uma influência negativa sobre a densidade mineral óssea (DMO), mas os resultados dos estudos que analisaram as implicações da supressão do TSH sobre a DMO em pacientes com CDT são conflitantes. Objetivos: Avaliar a relação entre terapia supressiva de TSH por CDT e DMO em mulheres pósmenopausa e investigar os fatores que afetam a DMO nessa população. Métodos: Estudo transversal envolvendo 109 mulheres pós-menopausa sob terapia supressiva de TSH devido a CDT seguidas em único centro terciário submetidas à análise de DMO durante seu seguimento. A DMO das pacientes foi comparada à de um grupo de controle composto por mulheres pós-menopausa, comprovadamente eutireoideanas, pareadas por idade, na proporção 1:1. Mulheres portadoras de condições que poderiam reduzir a DMO foram excluídas de ambos os grupos. A análise estatística foi realizada com teste de qui-quadrado de Pearson, teste de Mann-Whitney, coeficiente de correlação de Spearman, análises de regressão linear univariada e multivariada, conforme aplicável. A análise da curva ROC (Receiver Operating Characteristic) foi usada para obtenção de valores limiares de TSH que diferenciassem pacientes com DMO normal daquelas com osteopenia ou osteoporose. O nível de significância adotado foi de 5% (p< 0,05). Resultados: As pacientes apresentaram idade de 58,4 ± 8,3 anos, índice de massa corporal (IMC) de 27,9 ± 4,5 kg/m2 e níveis médios de TSH no ano anterior à análise da DMO de 0,21 ± 0,28 ?UI/ml. Os valores médios de T-scores das pacientes foram de -1,09 ± 1,43 desvios-padrão (DP) na coluna lombar e -0,12 ± 1,18 DP no fêmur total. Não observamos diferenças significativas entre a DMO lombar ou femoral entre os grupos. A análise de regressão multivariada identificou o IMC e o nível médio de TSH como fatores significativamente correlacionados à DMO lombar e femoral. O uso prévio de anticoncepcional oral também foi um fator correlacionado com maior DMO femoral. A análise da curva ROC para valores de TSH que diferenciassem pacientes com DMO normal daquelas com osteopenia ou osteoporose identificou o limiar significativo de TSH < 0,185 ?UI/ml para DMO normal em relação à osteopenia, com uma área sob a curva (ASC) significativa (0,625; intervalo de confiança de 95% = 0,508 - 0,742; p = 0,043)<br>Abstract: Background: Suppression of thyrostimulating hormone (TSH) with supraphysiological doses of levothyroxine is part of the treatment of differentiated thyroid carcinoma (DTC), leading the patient to a status of exogenous thyrotoxicosis state. This may exert a potential negative influence on bone mineral density (BMD), but the results of trials that analyzed the implications of TSH suppression on BMD of patients with DTC are conflicting. Objectives: We aimed to evaluate the relationship between TSH suppressive therapy and BMD in postmenopausal women and investigate the factors that affect BMD in this population. Methods: This was a cross-sectional study involving 109 postmenopausal women under TSH suppressive therapy for DTC in a single tertiary hospital, who underwent BMD measurement during followup. They were compared to a control group of 109 postmenopausal euthyroid women, matched by age. Women with conditions that could be related to bone loss were excluded from both groups. Statistical analysis was performed with Pearson's chi-square test, Mann-Whitney test, Spearman correlation coefficient, linear regression analysis with univariate and multivariate models and stepwise criteria for variable selection, as applicable. Receiver operating characteristic (ROC) curve analysis was used to obtain the cutoff points for TSH values to differentiate patients with normal BMD from those with osteopenia and osteoporosis. Level of significance was 5% (p < 0.05). Results: Patients were 58.4 ± 8.3 years-old, with body mass index (BMI) of 27.9 ± 4.5 kg/m2, mean TSH level of 0.21 ± 0.28 ?UI/ml. Average T-scores of patients were -1.09 ± 1.43 SD in lumbar spine and -0.12 ± 1.18 SD in total femur. No significant differences were found between lumbar (p = 0.940) or femoral (p = 0.105) T-scores between groups. Multivariate regression analysis evidenced BMI and mean TSH as significant factors correlated to lumbar BMD. For femoral BMD, significant correlation factors were BMI, TSH, and oral contraceptive use. ROC curve analysis for TSH values that differentiated patients with normal BMD from osteopenia and osteoporosis identified the significant cutoff of TSH < 0.185 ?UI/ml for normal BMD versus osteopenia, with significant area under the curve (0.625; 95% confidence interval = 0.508 - 0.742; p = 0.043). Conclusion: The TSH threshold that discriminates normal BMD from osteopenia in DTC patients treated with exogenous LT4 is unprecedented. Our data provide a rationale for maintaining TSH levels less suppressed in patients at low risk for tumor recurrence, aiming to preserve their BMD<br>Mestrado<br>Clinica Medica<br>Mestra em Clínica Médica
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Schmidt, Claudia. "Wird der szintigrafische Befund der disseminierten Schilddrüsenautonomie durch mangelnde Sensitivität der TSHRAK- Assays, intrathyreoidalen Iodmangel, Schilddrüsenvergrößerung oder TSH-Rezeptor-Keimbahnmutationen verursacht?" Doctoral thesis, Universitätsbibliothek Leipzig, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-86879.
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Das Krankheitsbild der disseminierten Schilddrüsen(SD)-Autonomie ist nur in Mitteleuropa bekannt und wird in der englischsprachigen Literatur nicht beschrieben.
Die exakte Pathogenese der disseminierten SD-Autonomie, insbesondere ob es sich um ein eigenständiges Krankheitsbild oder nur um ein szintigrafisches Phänomen handelt, ist nicht geklärt.
Daher war es Ziel dieser Arbeit, die klinische Entität der disseminierten Autonomie genauer zu klassifizieren, mit anderen SD-Autonomien zu vergleichen und weitere Erkenntnisse über die Pathogenese, insbesondere bezüglich des intrathyreoidalen Iodgehalts sowie TSH-Rezeptorkeimbahnmutationen dieser Erkrankung zu
gewinnen.
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Campos, Tatiane de. "Avaliação da função e do volume da tireoide em crianças saudáveis." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2011. http://hdl.handle.net/10183/139197.
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Durante a vida fetal e a infância, os processos fisiológicos da tireoide são peculiares, sendo os hormônios tireoidianos (T3 e T4) essenciais para o crescimento e o desenvolvimento da criança. Os níveis séricos de tireotrofina (TSH) são determinantes no diagnóstico de disfunção tireoidiana. Os dados de normalidade e os fatores que influenciam os níveis de TSH em crianças são pouco conhecidos, sendo que os estudos que disponibilizam esses dados nem sempre são bem conduzidos. A síntese de hormônios tireoidianos é dependente de iodo, e a deficiência desse elemento associa-se a alterações morfológicas e volumétricas da glândula. Os valores de normalidade para volume tireoidiano na infância são influenciados pelas medidas antropométricas e variam entre populações. Atualmente, a deficiência grave de iodo tem dado lugar a patologias relacionadas à ingestão excessiva desse elemento. É importante conhecer as particularidades e os valores de referência para função tireoidiana na infância a fim de evitar prejuízos antropométricos e cognitivos.<br>Distinct physiological processes occur in the thyroid gland during intrauterine life and childhood, with thyroid hormones (T3 and T4) playing an essential role in growth and development. Serum levels of thyroid-stimulating hormone (TSH) are determining factors of the diagnosis of thyroid dysfunction. Little is known about the normal range of TSH in children and the factors that influence TSH levels in this population, and the few studies that have addressed this issue have not all been well designed and conducted. Thyroid hormone synthesis is iodine-dependent, and iodine deficiency is associated with pathological changes in the morphology and volume of the thyroid gland. The normal range of thyroid volume in children is influenced by anthropomorphic parameters, and varies among populations. Severe iodine deficiency has now been surpassed by conditions associated with excessive iodine intake. Knowledge of the peculiarities of thyroid function in childhood and of the reference ranges of thyroid function tests in this period is important for the prevention of anthropometric and cognitive impairments.
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Souza, Paula Bargi de. "Ações não genômicas da triiodotironina (T3) sobre a expressão, poliadenilação e distribuição dos grânulos de TSH nos tireotrofos de ratos hipotireiodeos." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-20052010-142135/.
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O hormônio tireotrófico (TSH) é o principal regulador da síntese e da secreção dos hormônios tireoidianos (HTs), os quais exercem um mecanismo de feedback negativo na hipófise reduzindo a síntese das cadeias <font face=\"Symbol\">β e <font face=\"Symbol\">α (CGA - Glycoprotein hormones Alpha Chain) por meio de mecanismos que envolvem modificações na transcrição de genes que codificam essas proteínas (ações genômicas). Na última década tem aumentado o número de evidências de que, em paralelo as ações genômicas clássicas, algumas ações dos HTs são desencadeadas na presença de inibidores da transcrição gênica e em curto espaço de tempo (segundos a minutos), caracterizando-se assim as ações não genômicas dos HTs. Este trabalho tem como foco avaliar a possibilidade de que os HTs regulem a expressão desses genes não genomicamente. Para tal avaliamos as alterações decorrentes do hipotiroidismo, seguido ou não do tratamento agudo com T3 em dose fisiológica ou saturante, sobre o grau de poliadenilação e a expressão do mRNA das subunidades alfa (CGA) e <font face=\"Symbol\">βTSH, bem como sua repercussão sobre a síntese e secreção de <font face=\"Symbol\">βTSH. Através da metodologia de PCR em Tempo Real observamos nos animais tireoidectomizados tratados com salina (Tx) um aumento de 10 e 4 vezes no conteúdo de mRNA do <font face=\"Symbol\">βTSH e CGA, respectivamente, e na razão <font face=\"Symbol\">βTSH/CGA quando comparado ao animal eutireoideo. A administração da dose saturante de T3 em 30 min não alterou o conteúdo do mRNA de <font face=\"Symbol\">βTSH e CGA, enquanto a dose fisiológica reduziu 52 e 34%, respectivamente, sem alterar a razão <font face=\"Symbol\">βTSH/CGA, comparando com o grupo Tx. Com o ensaio RACE-PAT, observou-se que o grupo Tx apresentou um aumento no comprimento da cauda poli-A do mRNA de <font face=\"Symbol\">βTSH, não havendo alterações semelhantes para o mRNA de CGA. A administração aguda de T3, apenas na dose saturante, provocou uma redução de 17% no comprimento da cauda poli-A do mRNA do <font face=\"Symbol\">βTSH nos animais hipotiroideos comparados com o grupo Tx. Nenhuma alteração foi observada no comprimento da cauda poli-A do mRNA de CGA, indicando um possível efeito específico do T3 sobre a poliadenilação da subunidade <font face=\"Symbol\">β. Através dos ensaios Western Blot / ECL, Imunohistoquímica e Histoquímica foi observado que as duas doses de T3 utilizadas promoveram um aumento de 30% no conteúdo protéico de TSH, uma redução na marcação de <font face=\"Symbol\">βTSH na periferia dos tireotrofos e aumento na polimerização de actina na hipófise dos animais hipotiroideos tratados, possivelmente por inibir a secreção deste hormônio. Como estes resultados foram observados em 30 min, e parte deles envolveu alterações em etapas pós-transcricionais da regulação da expressão de genes (poliadenilação), podemos inferir que o T3 esteja agindo por uma via não genômica regulando a síntese e secreção do TSH.<br>The thyroid-stimulating hormone (TSH) is the main regulator of the synthesis and secretion of thyroid hormones (TH), which exert a negative feedback mechanism in the pituitary by reducing the synthesis of <font face=\"Symbol\">β and <font face=\"Symbol\">α (CGA - Glycoprotein hormones alpha chain) chains through mechanisms that involve changes in the transcription of genes that encode these proteins (known as genomic action). However, in the last decade, an increasing body of evidence has shown that, in parallel with the classical genomic mechanisms, some TH actions might be elicited in a short period time (seconds to minutes), and in the presence of gene transcription inhibitors, which indicates that TH can also act nongenomically. In the present study we evaluate if TH could regulate some steps of the expression of <font face=\"Symbol\">β TSH and CGA in a short period of time, which might provide evidence that they could act by non genomic mechanisms. For this, the expression and polyadenylation of alpha (CGA) and <font face=\"Symbol\">β subunits of TSH mRNA, and TSH content, were evaluated by real time PCR and western blot, respectively, in thyroidectomized (hypothyroid) rats, 30 min after they were subjected or not to physiological or saturating doses of T3. It was observed that hyroidectomyzed animals treated with saline (Tx) presented an increase of 10 and 4 times in the content of <font face=\"Symbol\">βTSH and CGA mRNA, respectively, and in the <font face=\"Symbol\">βTSH / CGA ratio compared with control group. The saturating dose of T3 did not alter the <font face=\"Symbol\">βTSH and CGA mRNAs content, but the physiological dose reduced them at 52 and 34% respectively, without changing the <font face=\"Symbol\">βTSH / CGA ratio, compared with Tx group. The RACE-PAT assay showed that the Tx rats presented an increase in the mRNA <font face=\"Symbol\">βTSH poly-A tail length, whereas no change was observed to the mRNA of CGA. The acute and saturating dose of T3 caused a 17% reduction in the length of mRNA <font face=\"Symbol\">βTSH poly-A tail in hypothyroid animals compared with hypothyroid group. No changes were observed in the length of the poly-A tail of mRNA CGA, suggesting a specific effect of T3 on the <font face=\"Symbol\">β subunit polyadenylation. Through the Western blot/ECL, histochemistry and immunohistochemistry methods we could observe that T3 (in both doses used) promoted a 30% increase in TSH protein content, a decrease in <font face=\"Symbol\">βTSH labeling near thyrotrophs plasma membrane and increased the actin polymerization in the pituitary of hypothyroid animals, possibly by inhibiting the secretion of this hormone. Considering that these results were observed in 30 min, and some of them involve changes in post-transcriptional regulation of gene expression (polyadenylation), we can infer that in parallel to its genomic action, T3 acts by non genomic pathways in the regulation of the TSH synthesis and secretion.
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Lan, Ling [Verfasser]. "Adult stem cells derived from human goiters form spheres in response to intense growth stimulation and differentiate TSH-dependently into thyroid cells / Ling Lan." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2008. http://d-nb.info/1022824856/34.
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Carrazza, Leonardo Gomes. "Hormônios tireoidianos, TSH, desempenho e qualidade de carcaça e carne em suínos imunocastrados alojados em diferentes sistemas de criação." Universidade Federal de Uberlândia, 2012. https://repositorio.ufu.br/handle/123456789/13021.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>This study aimed to evaluate the influence of pig housing systems on serum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH), correlating with characteristics of animal performance, meat quality and carcass. Therefore, 48 male pigs with an average age of 84 days were divided into two distinct housing systems, the Intensive System of Rearing Pig (conventional system) and the Intensive System of Swine Raised Outdoors (SISCAL), being 24 animals per environment divided into six plots of four pigs each. The experiment lasted 105 days. Blood was collected at the beginning and end of the experiment when the animals were sent to slaughter in a slaughterhouse, where it proceeded to collect material and data for analysis. There were no statistical differences between the two systems, for percentage of intramuscular fat (GIM), pH 45 minutes, pH 24 hours, Intestinal length (CI), carcass length (CC), Backfat Thickness 1 (ET1), Backfat Thickness 2 (ET2), Backfat Thickness in Half Moon (ETML) Hot Carcass Weight (PCQ), carcass yield (RC) and Lean Meat Yield (RCM). Animals housed on the conventional system had higher values of weight gain (GP) (63.49 vs. 54.14 kg, P <0.05) and Average Daily Weight Gain (GPMD) (0.6163 vs. 0, 5255 kg P <0.05) than animals raised on SISCAL. The TSH serum level increased from the beginning to the end of the experiment (0.12 to 0.30 μIU, P <0.05), whereas T4 decreased (6.44 to 3.11 mg/dL, P <0.05) did not differing between the two systems. The T3 level at the end of the housing was higher at SISCAL than in the conventional system (vs. 1.10. 0.75 ng/mL) at P <0.05. The concentrations of T3 and T4 had correlation of 0.48, while moderate and negative correlations were found between the levels of T3 and features of PCQ (-0.48), GP (-0, 48) and ET2 (-0.39) and between T4 and PCQ (-0.53), GP (-0.57) and ET2 (-0.34) P<0.005.<br>Objetivou-se avaliar a influência dos sistemas de criação de suínos sobre concentrações séricas de triiodotironina (T3), tiroxina (T4) e hormônio estimulante da tireóide (TSH), correlacionando com características de desempenho zootécnico, qualidade de carne e carcaça. Para isto, 48 suínos machos com idade média de 84 dias foram alocados em 2 sistemas de criação distintos, o Sistema Intensivo de Criação de Suínos (sistema convencional) e o Sistema Intensivo de Suínos Criados ao Ar Livre (SISCAL), sendo 24 animais por ambiente, divididos em 6 parcelas de 4 suínos cada. O experimento teve duração de 105 dias. O sangue foi coletado no início e fim do experimento, quando os animais foram encaminhados ao abate em matadouro frigorífico, onde procedeu-se coleta de material e dados para análises. Não foram encontradas diferenças estatísticas entre os 2 sistemas, para porcentagem de Gordura Intramuscular (GIM), pH 45 minutos, pH 24 horas, Comprimento Intestinal (CI), Comprimento de Carcaça (CC), Espessura de Toucinho 1 (ET1), Espessura de Toucinho 2 (ET2), Espessura de Toucinho na Meia Lua (ETML), Peso de Carcaça Quente (PCQ), Rendimento de Carcaça (RC) e Rendimento de Carne Magra (RCM). Animais alojados sobre o sistema convencional obtiveram maiores valores de Ganho de Peso (GP) (63,49 vs. 54,14 kg, P<0,05) e Ganho de Peso Médio Diário (GPMD) (0,6163 vs. 0,5255 kg P<0,05) que animais criados sobre o SISCAL. O nível sérico de TSH aumentou do início ao fim do experimento (0,12 para 0,30 μIU, P<0,05), enquanto T4 diminuiu (6,44 para 3,11 μg/dL, P<0,05), não diferindo entre os 2 sistemas. O nível de T3 ao final do alojamento foi maior no SISCAL que no sistema convencional (1,10 vs. 0,75 ng/mL) com P<0,05. As concentrações entre T3 e T4 tiveram correlação de 0,48, enquanto correlações moderadas e negativas foram encontradas entre os níveis de T3 e características de PCQ (-0,48), GP(-0,48) e ET2 (-0,39) e entre T4 e PCQ (-0,53), GP(-0,57) e ET2 (-0,34) P<0,05.<br>Mestre em Ciências Veterinárias
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Beltrão, Cristine Barboza. "Contribuição da dosagem de tireoglobulina e de exames de imagem para o diagnóstico de hipotireoidismo congênito: pesquisa dos genes PAX8 e receptor do TSH na disgenesia tireoidiana." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-06112009-150013/.
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INTRODUÇÃO: O hipotireoidismo congênito (HC) é uma doença, de acometimento neonatal, caracterizada por diminuição nos níveis de hormônios tireoidianos. As causas mais comuns de HC primário permanente são as alterações no desenvolvimento da glândula tireóide (disgenesia) e os defeitos de síntese dos hormônios tireóideos (disormonogênese). A determinação da etiologia do HC tem papel importante na determinação da gravidade da doença, evolução e tratamento. Essa investigação é feita através de exames como ultrassonografia e cintilografia (CINT) da tireóide. Além disso, com o conhecimento do genoma humano, diversas mutações foram descritas, sendo a investigação molecular importante para a determinação da etiologia da doença. OBJETIVOS: 1. Determinar o diagnóstico etiológico dos pacientes com HC a partir de dosagens hormonais, tireoglobulina e exames de imagem; 2. Estabelecer a importância do uso da ultrassonografia com Doppler colorido (USDC) no diagnóstico etiológico; 3. Estabelecer a importância do uso do teste do perclorato de sódio intravenoso (PSIV) no diagnóstico diferencial de HC por disormonogênese; 4. Estudar os genes PAX8 e receptor do TSH (TSHR) em pacientes com HC causado por disgenesia tireoidiana MÉTODOS: Avaliamos 40 pacientes acompanhados na APAE - São Caetano com diagnóstico de HC primário e permanente acima de 3 anos de idade. Os pacientes realizaram dosagens de T3, T4, T4 livre, TSH, tireoglobulina (TG) e anticorpo anti-TG pelo método imunofluorimétrico, além de USDC e CINT. Os pacientes com suspeita de disormonogênese foram submetidos ao teste PSIV e avaliação com otorrinolaringologista e audiometria tonal, se necessário. Os pacientes que apresentavam disgenesia tireoidiana tiveram o DNA extraído a partir de leucócitos periféricos para o estudo dos genes PAX8 e TSHR através de PCR e sequenciamento automático. RESULTADOS: Avaliamos 28 pacientes do sexo feminino e 12 do sexo masculino, após suspensão do tratamento com levotiroxina por 4 semanas. A idade média foi de 6,5 anos. O TSH médio foi 129,9 UI/mL (normal: 0,7-6,0). Os valores de T3, T4 e T4 livre variaram de 14 217 ng/dL (normal: 105-269), <1,6 15,8 g/dL (normal: 1,5-15) e < 0,3 2,7 ng/dL (normal: 0,7-1,5), respectivamente. A TG variou de <1 287 ng/dL (normal: 1,7-35). A USDC mostrou 21 pacientes com tireóide tópica (53%), 8 pacientes com tireóide ectópica (20%) e 11 pacientes com atireose (27%). Na CINT, o mapeamento identificou tireóide tópica em 20 pacientes (51%), tireóide ectópica em 13 pacientes (32%), e atireose em 7 pacientes (17%). A captação mostrou-se aumentada em 2 horas em 10 pacientes. O teste PSIV foi realizado em 9 pacientes com bócio ou glândula de tamanho normal ao USDC, cuja captação foi aumentada. Apenas um paciente apresentou vômito ao início do teste. Seis pacientes apresentaram teste positivo, considerando uma queda maior que 20%. Nenhum desses pacientes apresentava surdez neurossensorial. Encontramos discrepância entre USDC e CINT em 9 pacientes, principalmente nos casos de ectopia. A dosagem de TG auxiliou na confirmação de atireose. Os níveis mais altos de TG encontrados foram nos casos de disormonogênese causados por defeito na organificação. Assim, determinamos o diagnóstico de ectopia em 32,5% dos pacientes, hipoplasia em 20%, defeito na organificação (defeito de TPO ou THOX2) em 17,5%, atireose em 15%, defeito na TG em 7,5% e 3 casos a esclarecer (7,5%). Vinte e sete pacientes foram diagnosticados como portadores de disgenesia tireoidiana e não apresentaram mutações nos genes PAX8 e TSHR. CONCLUSÃO: Estabelecemos o diagnóstico etiológico em 37 dos 40 pacientes estudados. A USDC mostrou-se importante no diagnóstico etiológico do HC, especialmente associada à dosagem de TG. O teste PSIV mostrou-se seguro no diagnóstico diferencial do HC por disormonogênese. Não identificamos nenhuma mutação nos genes PAX8 e TSHR nos casos estudados de disgenesia<br>INTRODUCTION: Congenital hypothyroidism (CH) is a disease at neonatal period characterized by low thyroid hormones levels. Most common causes of primary CH are alterations at thyroid gland development (dysgenesis) and thyroid hormone synthesis defects (dyshormonogenesis). The establishment of CH etiology has important role to define the severity, evolution and treatment of the disease. This investigation is based on thyroid ultrasound and radiouptake and radionuclide imaging (RAIU). With human genome knowledge, several mutations were described, becoming molecular investigation so important to etiology definition. OBJECTIVES: 1. Establish the etiologic diagnosis of CH patients using hormonal measurements, thyroglobulin and imaging exams. 2. Establish the importance of color Doppler ultrasound (CDUS) in etiologic diagnosis. 3. Establish the importance of intravenous perchlorate sodium test in differential diagnosis of CH due to dyshormonogenesis. 4. Study PAX8 and TSH receptor (TSHR) genes in patients with CH due to thyroid dysgenesis. METHODS: We evaluated forty patients followed-up at APAE - São Caetano with primary and permanent CH diagnosis above 3 years-old. Patients performed T3, T4, free T4, TSH, thyroglobulin (TG) and anti-TG antibody using immunofluorimetric assays, besides thyroid CDUS and RAIU. Patients with thyroid dysgenesis had their DNA extracted from peripheral leukocytes to study PAX8 and TSHR genes using PCR and automatic sequencing. Patients with dyshormonogenesis suspected were submitted to intravenous perchlorate sodium test and otorhinolaryngologist and tonal audiometric evaluation, if necessary. RESULTS: We evaluated 28 female and 12 male after levothyroxine treatment off for 4 weeks. Mean age of studied patients was 6.5 years-old. Mean TSH was 129.9 UI/mL (normal: 0.7-6.0). T3, T4 and freeT4 ranged from 14 217 ng/dL (normal 105-269) , <1.6 15.8 g/dL (normal: 1.5- 15) and < 0.3 2.7 ng/dL (normal: 0.7-1.5) respectively. TG level ranged from < 1 287 ng/dL (normal 1.7-35). CDUS showed normally located thyroid in 21 patients (53%), ectopy in 8 patients (20%), and athyrosis in 11 patients (27%). At RAIU, thyroid scan identified normal located gland in 20 patients (51%), ectopy in 13 patients (32%) e athyrosis in 7 patients (17%). Two-hours uptake was elevated in ten patients. Intravenous perchlorate sodium test was performed in 9 patients with goiter or normal volume at CDUS, with normal or elevated uptake. Only one patient presented vomit. Six patients had positive test, considering more than 20% of decline. None from these patients had neurosensorial deafness. We found discrepancy between CDUS and RAIU in 9 patients, especially in ectopic cases. Thyroglobulin measurement helped to confirm athyrosis. Highest TG levels were found in dyshormonogenesis patients due to organification defects. Therefore we determined etiologic diagnosis of ectopic gland in 32,5% of patients, hypoplasia in 20%, organification defect (TPO or THOX2 defects) in 17,5%, athyrosis in 15%, thyroglobulin defect in 7,5% and three cases were undefined (7,5%). Twenty seven patients were diagnosed with thyroid dysgenesis and had no mutation in PAX8 and TSHR genes. CONCLUSION: We established the etiologic diagnosis in 37 from 40 patients here studied. CDUS was useful on etiologic diagnosis of CH, especially associated to thyroglobulin level. Intravenous perchlorate sodium test was safe and efficient in CH differential diagnosis of dyshormonogenesis. We identified no mutation in PAX8 and TSHR genes in dysgenesis cases
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Souza, Amanda de Moura. "Relação entre índice de massa corporal e tireotrofina sérica em mulheres eutiróideas residentes no município do Rio de Janeiro: diferenças segundo tabagismo, raça e menopausa." Universidade do Estado do Rio de Janeiro, 2010. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=1740.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico<br>As disfunções tireoidianas estão associadas com alterações no peso corporal, no entanto, não está estabelecido na literatura se pequenas alterações na função tireoidiana dentro dos valores de referência das concentrações séricas de tireotrofina (TSH) poderiam afetar o índice de massa corporal (IMC). A associação entre as concentrações séricas de TSH e o IMC em indivíduos eutireóideos tem sido foco de recentes e conflitantes estudos e uma possível explicação para os achados conflitantes é a existência de subgrupos da população onde essa associação se expressa de forma diferente. O objetivo desse trabalho foi investigar a associação entre o IMC e as concentrações séricas de TSH em mulheres com função tireoidiana normal e avaliar possível modificação de efeito da associação entre IMC e as concentrações séricas de TSH pelo tabagismo, menopausa e raça. Os dados foram obtidos em um estudo de base populacional realizado na cidade do Rio de Janeiro, Brasil, entre junho de
2004 e abril de 2005, com amostragem probabilística por conglomerado em três estágios. No primeiro estágio foram selecionados 100 setores censitários, no segundo 15 domicílios de cada setor e no terceiro uma mulher por domicílio. Das 1500 mulheres com 35 anos ou mais selecionadas, 1298 participaram do estudo, dentre estas, 1084 apresentavam função tireoidiana normal. Uma associação positiva e estatisticamente significante foi observada entre o IMC e o TSH sérico (β=0,90; p-valor=0,02) na população como um todo. A análise exploratória de subgrupos com diferentes graus de associação foi obtida pela análise de interações estatísticas. Os subgrupos de mulheres na pré-menopausa (β=1,04; p-valor=0,04), de raça negra (β=1,39; p-valor=0,14) e fumantes (β=1,78; p-valor=0,04), apresentaram associações de maior magnitude. Em conclusão, o TSH parece ter um papel modulador das mudanças no peso corporal, mesmo em mulheres com função tireoidiana normal. O tabagismo e a raça são fortes modificadores de efeito da associação entre TSH e IMC e futuros estudos devem considerar estes fatores.<br>Although, overt thyroid dysfunction is associated with weight changes, it is not known whether minor changes in thyroid function within normal serum thyrotropin (TSH) concentration could affect body mass index (BMI). The association between serum TSH and BMI in euthyroid subjects has been focus of recent and controversial studies. A possible explanation for these controversial findings could be the differences on this association between population subgroups. The aim of this study was to investigate the association between BMI and TSH in women with normal thyroid function and to evaluate a potential effect modification on the association between BMI and TSH by smoking, race, and menopause status. A population-based study was carried out in the city of Rio de Janeiro, Brazil, in 2004-2005. Sample selection was based on a three-stage cluster design. In the first stage, 100 primary sample units (PSU) were selected. In the second stage, 15 households were select from each PSU and in the third stage one woman was selected from each household. Of a sample of 1500 women aged 35 years or older, 1298 agree to participate. For the present study, a final sample of 1084 women without thyroid disease was investigated. Overall, BMI was positively and significantly associated with serum TSH (β=0.90; p- value=0.02) and stronger association between BMI and serum TSH among premenopausal women (β=1.04; p-value=0.04), Black women (β=1.39; p-value=0.14) and smokers (β=1.77; p-value=0.04) was found. In conclusion, TSH appears to modulate body weight among women even in the normal range. Smoking and race are strong effect modifiers of the association between TSH and BMI and future studies should take these effect modifiers into account.
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Jacobs, Christine. "Contribution à la caractérisation de protéines impliquées dans la transduction des signaux: C3VS, le récepteur de la TSH et SHIP2." Doctoral thesis, Universite Libre de Bruxelles, 2004. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211173.
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Dans le thyrocyte normal, la TSH active une voie dépendante de l’adénylyl cyclase/AMPc, qui représente l’une des trois voies mitogéniques de la thyroïde. La cascade de signalisation de la TSH diffère des deux autres voies dans sa capacité à induire à la fois la prolifération et la différenciation, comprenant la synthèse et la sécrétion des hormones thyroïdiennes. Identifier les acteurs de cette cascade de signalisation, ainsi que les interactions entre effecteurs, est donc très important pour la compréhension de la fonction de la cellule thyroïdienne. C’est dans ce cadre que s’insère notre travail au cours duquel nous nous sommes intéressés au récepteur de la TSH ainsi qu’à une protéine récemment identifiée dans le laboratoire et dont l’expression est modulée en réponse à la TSH dans la thyroïde :C3VS. <p>C3VS est une protéine qui présente six motifs ankyrine et une tirette à leucine et dont la fonction était inconnue à l'époque. Dans un premier temps, nous avons contribué à l’obtention de la séquence codante complète du C3VS de chien, puis, l'identification des partenaires d'une protéine pouvant aider à caractériser sa fonction, nous nous sommes proposé de rechercher les partenaires potentiels de la région N-terminale de C3VS par la méthode double-hybride. Nous avons étudié la distribution tissulaire et la régulation par la TSH de différents partenaires isolés. Parmi eux, SUG1, une ATPase du protéasome 26S, a été étudiée plus avant mais l’interaction n’a pas pu être confirmée par "GST-pulldown assay". Simultanément, une remise en question de la position de la méthionine initiale de C3VS, couplée à une impossibilité d’exprimer la protéine en cellules COS par transfection mettait en péril le travail. En l’absence de plus d’arguments fonctionnels permettant d’orienter l’étude des positifs, cette partie du travail a été suspendue au profit de notre étude sur le récepteur de la TSH. L'activation de cascades différentes dans le thyrocyte humain et canin pouvant être due à l'action de protéines intracellulaires, nous avons tenté de rechercher par double-hybride des partenaires protéiques autres que les protéines G pour le récepteur de la TSH. Nous avons ainsi identifié PRA1 mais nous n’avons pas pu confirmer l'interaction entre les deux protéines par "GST-pulldown assay". Pour tenter de comprendre le rôle de cette interaction, nous avons réalisé des essais fonctionnels en transfectant des cellules pour évaluer l'implication de PRA1 sur la synthèse d’AMPc. Ces expériences ne nous ont pas permis de montrer un rôle pour PRA1 au niveau de la cascade, mais en revanche, nous avons mis en évidence le fait que la co-transfection de deux ADNc codant pour des protéines membranaires sature la machinerie de traduction et diminue l'expression du RTSH. <p>Dans une deuxième partie de notre travail, nous avons étudié la 5-phosphatase SHIP2, dont l’implication dans la cascade de réponse à l’insuline était suggérée, entre autres, par le travail d’Isabelle Vandenbroere qui avait montré l’interaction de cette protéine avec CAP et c-Cbl. Nous avons développé au laboratoire la culture de la lignée pré-adipocytaire 3T3-L1 et étudié la localisation de SHIP2 au niveau des rafts de ces cellules. Nous avons montré que SHIP2 n’y est pas recrutée. CAP et c-Cbl ne semblent pas non plus y être recrutées, tandis que nous y avons détecté le récepteur de l'insuline. La localisation de différentes protéines impliquées dans la cascade de l'insuline dans les rafts est une question controversée à l’heure actuelle et notre étude montre que l’implication fonctionnelle de SHIP2 dans la cascade de l'insuline n'est probablement pas dépendante des rafts.<p><br>Doctorat en sciences, Spécialisation biologie moléculaire<br>info:eu-repo/semantics/nonPublished
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Milesi, Sébastien. "Rôle de la signalisation hypothalamique TSH/T3 dans la reproduction saisonnière chez les hamsters Djungariens (Phodopus sungorus) et Syriens (Mesocricetus auratus)." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ023/document.
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Chez les hamsters, les jours longs activent la reproduction. Cette activation photopériodique (AP) impliquerait la mélatonine, l’hormone thyroïdienne (HT) et les RFamides hypothalamiques. Si les jours courts inhibiteurs sont maintenus au-delà de 20 semaines, une réactivation photoréfractaire (RP) de l’axe hypothalamo pituitaire gonadotrope (HPG) est déclenchée. Les mécanismes de cette RP sont inconnus. Notre analyse de la cinétique des changements moléculaires induits par l’AP et la RP montre dans les deux cas une inhibition précoce de l’expression de la Désiodinase 3 (Dio3), l’enzyme catabolisant les HT, dans les tanycytes. Associée à une inhibition tardive du transporteur MCT8 des HT, la diminution de Dio3 pourrait créer un pic d’HT dans l’hypothalamus. Dans les 2 activations, Kisspeptine et RFRP3 augmentent plusieurs semaines après l’inhibition de Dio3 et l’activation de l’HPG. Aussi, une inhibition d’RFRP3 lors de l’AP n’affecte pas l’HPG, mettant en cause le rôle du RFRP3. Nous avons donc découvert une inhibition précoce de Dio3 pouvant induire l’activation saisonnière de l’HPG. Le régulateur saisonnier précoce de Dio3 reste à découvrir<br>In hamsters, reproduction is activated by long days. This photoactivation (PA) supposedly involves melatonin, hypothalamic thyroid hormones (TH) and RFamide peptides. Maintaining inhibitory short days for over 20 weeks triggers a photorefractory reactivation of the hypothalamo pituito gonadotropic axis (HPG) The mechanisms of this PR are so far unknown. Our cinetic analysis of the dynamic molecular changes in PA and PR revealed a conserved early inhibition of tanycytic deiodinase 3 (Dio3), which catabolizes TH, in both activation mechanisms. Associated with a late decrease of the TH transporter MCT8, the inhibition of Dio3 could generate an early peak of hypothalamic TH. In both activations, RFamide upregulation occurs several weeks after the initial Dio3 inhibition. Also, pharmacological inhibition of RFRP3 during PA does not influence the HPG activity, questioning the role of RFRP3 in HPG activation. We have thus uncovered a so far unreported early Dio3 inhibition that could be sufficient to seasonally reactivate the gonadotropic axis. The seasonal regulator of Dio3 remains to be discovered
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Lidén, Pauline. "Kan selentillskott behandla autoimmun tyreoidit? : En litteraturstudie." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-77978.
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Introduktion. Autoimmun tyreoidit (AITD) är en kronisk autoimmun sjukdom där immunförsvarets antikroppar (ab) attackerar tyreoideaproteinerna tyreoideaperoxidas (TPO) och/eller tyreoglobulin (TG). Studier visar att selentillskott hos patienter med AITD kan minska tyreoideaantikroppar, storleken och antalet noduler hos en förstorad tyreoidea. Syftet med detta arbete var att undersöka hur selentillskott påverkar serumnivåer av TPOab, samt tyreoideahormonnivåer vid AITD. Metod. Arbetet är en litteraturstudie och därför har metoden varit att samla relevant litteratur genom PubMed med sökningar som ”selenium autoimmune thyroiditis”, ”selenium thyroid” och ”autoimmune thyroiditis”. Bland sökresultaten valdes nio artiklar ut baserat på studiekvalitet, publikationsår och relevans. Bland artiklarna granskades och sammanställdes uppmätta nivåer av TPOab samt tyreoideahormonnivåer, vilka valdes som indikation på effekt utav selentillskott. Resultat. Resultaten var inkonsekventa. Majoriteten av studierna (7 av 9) tydde på att oral administrering av selentillskott effektivt minskade serumkoncentrationerna av TPOab hos patienter med AITD i alla åldersgrupper. De studier som resulterade i störst minskning av TPOab pågick i 3-12 månader. Utav de 9 studerade artiklarna var det endast en studie som inte rapporterade någon som helst positiv klinisk effekt hos patienterna. Två av studierna visade att selen förhindrar vidare försämring av tyreoideans ekogenitet, vilket tyder på att selen kan hejda inflammationsprocessen men ej reversera tyreoideaskadorna den orsakat. Majoriteten av studierna (7 av 9) visade att selentillskott ej ger några signifikanta förändringar i tyreoideahormonerna: TSH, fT4 och fT3. Diskussion. Varför AITD-patienter svarar olika på selenadministrering är ännu okänt, men kan misstänkas bero på selenbehandlingens varaktighet, patienternas intratyroidnivåer av selen vid studiens början, förekomst av jodbrist, samt patienternas ålder och sjukdomsprogression. Slutsats. Att ha adekvata fysiologiska nivåer av selen är av stor vikt för att bevara tyreoideans hälsa och förebygga tyreoidearelaterade sjukdomar. Majoriteten utav de granskade studierna visar att tillskott av selen kan minska antalet TPOab. Selentillskott kan även ha immunrelaterade fördelar men verkar inte påverka nivån tyreoideahormonnivåer. Inga negativa effekter påvisades vid intag av selentillskott vilket gör dess administrering säker. Fler studier behöver dock göras för att fastställa effektiviteten av selentillskott vid AITD.<br>Introduction. Autoimmune thyroiditis (AITD) is a chronic autoimmune disease in which the immune system's antibodies (ab) attack the thyroid proteins thyroid peroxidase (TPO) and/or thyroglobulin (TG). Studies show that selenium supplementation in patients with AITD can reduce thyroid antibodies and the size and number of nodules in an enlarged thyroid. The purpose of this study was to investigate how selenium supplementation affects the serum levels of thyroid peroxidase antibodies (TPOab) and thyroid hormone levels in autoimmune thyroiditis. Method. This is a literature study and therefore the method has been to gather relevant literature through searches on PubMed such as "selenium autoimmune thyroiditis", "selenium thyroid" and "autoimmune thyroiditis". Among the search results, nine articles were selected based on quality, publication year and relevance. Among the articles, measured levels of TPOab and thyroid hormone levels were examined and compiled, and were chosen as an indication of the effect of selenium supplementation. Results. The results were inconsistent. The majority of the studies (7 of 9) suggest that oral administration of selenium supplements effectively reduced serum concentrations of TPOab in patients with AITD in all age groups. The studies that resulted in the largest decrease in TPOab lasted for 3-12 months. Out of the 9 examined studies, only one study did not report any positive clinical effect in patients. Two of the studies showed that the selenium prevents further impairment of thyroid echogenicity, suggesting that selenium can inhibit the inflammatory process but not reverse the pre-existing thyroid damage it’s caused. The majority of studies (7 out of 9) show that selenium supplementation does not produce significant changes in the thyroid hormones: TSH, fT4 and fT3. Discussion. Why AITD-patients respond differently to selenium administration is still unknown, but it may be due to the duration of selenium treatment, the patients' intrathyroid levels of selenium at the onset of the study, the presence of iodine deficiency, as well as the age and disease progression of the patients. Conclusion. Having adequate physiological levels of selenium is of great importance in preserving thyroid health and preventing thyroid-related diseases. The majority of the studies show that selenium supplementation can reduce the number of TPOab. Selenium supplementation may also have immune related benefits but does not appear to affect the thyroid hormone levels. No adverse effects were observed during selenium supplementation, which makes its administration safe. However, more studies are needed to determine the effectiveness of selenium supplementation for AITD.
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Felske, David. "Extra-Thyroidal Action of TSH on Adipocyte Insulin Signaling." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/31906.
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In subclinical hypothyroidism (SH), high levels of circulating thyroid stimulating hormone (TSH) maintain normal thyroid hormone levels, despite mild thyroid failure. SH is associated with cardiovascular disease and insulin resistance, although the underlying pathophysiology is not fully understood. We hypothesized that TSH may inhibit insulin action in adipocytes. To investigate this relationship, we studied primary human differentiated adipocytes. Abdominal subcutaneous adipose tissue samples were obtained (approved by OHSN-REB) from 16 weight-stable patients undergoing elective abdominal surgery. We stimulated adipocytes differentiated from stromal preadipocytes with 5 mU/ml TSH and/or 100 nM insulin, and assessed acute insulin signaling, lipogenesis and glucose uptake. Immunoblot analysis revealed that TSH suppressed insulin-stimulated Akt phosphorylation by 45% (n=5; p = 0.01). When adipocytes were pre-incubated with conventional protein kinase C (cPKC) inhibitor Gö6976, TSH inhibition was blocked. Our data indicate that TSH inhibits insulin-stimulated lipogenesis (up to 37%), but depends on BMI. Insulin-stimulated glucose uptake was enhanced by 36% and also correlated with BMI. This data suggests that TSH can modulate adipocyte insulin signaling.
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Bach, Albert. "Techniques de stimulation par la tsh dans la surveillance du cancer differencie de la thyroide : comparaison de 2 methodes." Nancy 1, 1990. http://www.theses.fr/1990NAN11193.
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Axling, Johanna. "Effects of a mutation on the TSHR gene on social and fear related behaviours in chickens." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69120.
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It has been shown that thyroid hormones are important in development and growth in birds and further that thyrotropin (TSH) signaling regulated photoinduced seasonal reproduction. In addition to controlling the development of certain physiological traits, TSH can affect a wide range of phenotypes related to domestication such as behaviour, growth rate, more frequent reproductive cycle’s, pigmentation and also behaviour. Studies indicate that thyroid hormone physiology could potentially be responsible for differences in individual stress response as well as differences in social dominance. This project investigated behaviours expressed in the different genotypes on the Thyroid stimulating hormone receptor (TSHR) gene in chickens. Standard test such as Fear of human, Aerial predator, Tonic immobility and Social hierarchy were carried out with White leghorn (WL) as a domesticated species and Red Junglefowl (Rjf) as their wild counterpart; these were considered to be the control group. There was no significant result on genotype effect for the TSHR animals observed in those variables tested. The TSHR mutants were expected to mirror the White leghorn behavioural response and the TSHR wildtype the behaviour of Rjf. This was however not confirmed. There were a significant interaction between genotype effect and sex effect for TSHR for stand alert in the Aerial predator test which mirrored the results seen in the control groups. The male wildtype followed the male Rjf pattern however the mutant did not mirror the WL male. This study would benefit from more individuals to be tested, for stronger statistical results, plus also to have all genotypes represented to fully investigate the affect the TSHR mutation have on domesticated chickens and potentially the domestication process in a range of species.<br>TSHR
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Dominguez, Jean-Marie. "Valeur du dosage de la TSH ultrasensible dans l'évaluation de l'équilibre de la fonction thyroi͏̈dienne." Montpellier 1, 1989. http://www.theses.fr/1989MON11049.
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Saer, Ben. "Modulation of central thyroid hormone regulation during seasonal heterothermia." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-central-thyroid-hormone-regulation-during-seasonal-heterothermia(fbd06ae7-3d27-4959-a677-c938ba2f878f).html.
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Pronounced seasonal adaptations in physiology and behaviour are exhibited by mammals living in polar and temperate habitats. These include the development of a winter coat, altered fat reserves, reproductive quiescence and food hoarding. Maintaining constant body temperature (Tb) during winter is energetically very costly, and so many small mammals periodically abandon homeothermy in favour of heterothermy. The two principal heterothermic strategies are daily torpor and seasonal hibernation, in which bouts of profound hypothermia range from a few hours to several days (respectively). It is now clear that hypothalamic thyroid hormone (TH) regulation, and specifically the availability of the active metabolite triiodothyronine (T3), is a critical regulator of seasonal reproductive cycles in many species including birds and mammals. The impact of this signal as a switch for seasonal changes in physiology has been highlighted by the demonstration that blockade of this pathway prevents seasonal adaption in hamsters. Peripheral TH signalling is also a principle regulator of metabolic rate in mammals. Despite these findings nothing is yet known about the involvement of central (hypothalamic) and peripheral TH cycles in the expression of torpor and hibernation. Within this thesis, the role of TH dynamics both in the brain and peripheral circulation is examined within three models of heterothermia: the Siberian (Phodopus sungorus) and European (Cricetus cricetus) hamsters, which employ daily torpor and hibernation, respectively, and the laboratory mouse (Mus Musculus) which exhibits torpor in response to metabolic stress such as food restriction. To delineate TH regulation and signalling in the context of both seasonal and acute physiological responses, the expression of genes involved in thyroid hormones conversion (e.g. Deiodinase type II (Dio2) and type III (Dio3) and transport (e.g. Monocarboxylate transporter 8, Mct8) within the ependymal layer of the ventral 3rd ventricle have been detailed across seasonal (long (LD) and short day (SD)) photoperiods, and during normothermic and hypothermic conditions. Furthermore, TH concentrations have been directly measured within the hypothalami of P. sungorus and C. cricetus, and TH responsive genes (e.g. Hairless (Hr) and Thyrotropin releasing hormone (TRH) to determine the potential impact of regional T3 signalling. As expected, Dio2 and Dio3 expression in P. sungorus exhibited a strong seasonal cycle indicative of elevated T3 production during SD (reduced Dio2 and elevated Dio3). Unexpectedly, total T3 measures from hypothalamic extracts revealed no significant alteration either seasonally or during torpor/hibernation in hamsters. However, Hr expression in the ependymal layer and TRH expression in the paraventricular nucleus (PVN) suggests low T3 concentrations during SD are localised to specific regions and does not encompass the whole hypothalamus per se. In addition, altered serum TH concentrations implicate seasonal and torpor associated dynamics that may play a role in seasonal adaptation and hypothermia. Finally, data from transgenic mice strongly implicate the melatonin-related receptor (GPR50) in leptin signalling and aberrant thermogenesis in mice.
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Haubold, Kathrin. "Aspekte der Schilddrüsenphysiologie am Beispiel von Iod, TSHR und IGF-IR." Doctoral thesis, Universitätsbibliothek Leipzig, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-108132.
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Im Rahmen der vorliegenden Arbeit wurden zentrale Aspekte der Schilddrüsenphysiologie am Beispiel von Iod, TSHR und IGF-IR untersucht.
Der Pathologie der Schilddrüsenautonomie liegen konstitutiv aktivierende Mutationen des TSHR zugrunde. Die Prävalenz der Schilddrüsenautonomie ist in Iod armen Regionen deutlich erhöht. Als Ursache für Mutationen im TSHR wird vermehrter oxidativer Stress unter Iodmangel angenommen (Krohn et al. 2007; Maier et al. 2007). Die genauen molekularen Mechanismen konnten bisher noch nicht hinreichend aufgeklärt werden. In diesem Zusammenhang interessierte uns inwiefern eine ausreichende Iodversorgung die Entwicklung bereits autonomer Zellen beeinflussen kann. Das verwendete in vitro Modell der Schilddrüsenautonomie mit konstitutiv aktivierenden Mutationen im TSHR wurde bereits in früheren Arbeiten charakterisiert (Führer et al. 2003). Mit Hilfe von Microarray Untersuchungen und Funktionsanalysen, konnten wir deutliche Genregulationen durch Iod an Hand von normalen und autonomen Thyreozyten erkennen. Besonders auffällig war die differentielle Regulation von Genen, die z.B. in der Proliferation, dem Zellzyklus und metabolischen Prozessen involviert sind. Wesentlich ist, dass trotz einer konstitutiven Aktivierung des TSHR Iod dennoch die Proliferation und Funktion einer frühzeitigen Schilddrüsenautonomie herabsetzt.
Die physiologische Rolle des IGF-IR in der Schilddrüsenphysiologie in vivo wurde noch nicht systematisch erforscht. Um die Rolle des IGF-IR in der Schilddrüse im Hinblick auf deren Entwicklung und Metabolismus näher zu untersuchen, wurde ein Mausmodell generiert bei dem der IGF-IR schilddrüsenspezifisch über eine durch den TG Promoter regulierte Cre Rekombinase (Igf1rTgCre) ausgeschaltet wurde. Ziel war es nun zu untersuchen, welche Folgen ein thyreoidaler Igf1r Knockout auf die Funktion, Morphologie und Entwicklung der murinen Schilddrüse und metabolischer Parameter hat. Dieser Knockout zeigte in den Mäusen keine Veränderungen des Schilddrüsengewichtes und der Serum T3 Werte, wobei das Serum T4 nach 8 Wochen leicht absank, nach 4 Monaten aber wieder Normalwerte zeigte. Allerdings waren die Serum TSH Werte bis zu 9fach erhöht. Die Histologie der Igf1r-/- Mäuse zeigten mit einer Rate von 86% papilläre Schilddrüsenhyperplasien sowie eine starke Heterogenität der Follikelstruktur, die auch bei den Igf1r-/- Mäuse zu finden war. Die molekulare Kompensation des Igf1r Knockouts in der Schilddrüse besonders durch TSH konnte durch unsere Untersuchungen nicht hinreichend geklärt werden. Die Daten aus unseren Ergebnissen und eines reversen Mausmodells (Überexpression des IGF-IR und IGF-I) (Clement et al. 2001) weisen daraufhin, dass das IGF-IR Signal weniger essentiell für die Schilddrüsenhormonsynthese ist als für das Aufrechterhalten einer Homöostase und normaler Schilddrüsenmorphogenese.
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Svemer, Frida. "A mutation in the TSHR gene - how does it affect social and fear related behaviours in chickens?" Thesis, Linköpings universitet, Biologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-77975.
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Thyroid hormones are well known important to be in development and growth in birds and that signaling of thyrotropin (TSH) regulates the photo induced seasonal reproduction. A mutation at the thyroid stimulating hormone receptor (TSHR) gene in domestic breeds of chicken could be involved in the release of the photoperiodic regulation. Furthermore, TSH can affect a wide range of domestication related phenotypes, such as behaviour, growth rate and pigmentation. The aim of this study was to investigate the behaviours expressed in the different genotypes on the TSHR gene in chickens. Four standard tests were conducted, aerial predator, fear of human, social dominance and tonic immobility. An advanced intercross line of chickens between red junglefowl and White leghorn was used. Male domestic type chickens explored more, showed more less fear behaviours and showed least fear behaviours in the fear of human test. Increased activity and flight response has been interpreted as a lower fear response, which is in line with this study. The wild type chickens showed more social dominance than domestic type chickens which are in line with previous results. In tonic immobility there was a difference between the wild type male and heterozygous male chickens in latency until first head movement. The conclusion of this study is that there is a difference between the wild type and domestic type chickens. This indicates that the TSHR gene is involved in behavioural changes during domestication, but whether it is due to passive or active selection is the question.
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Ropars, Armelle. "Production, caractérisation fonctionnelle et moléculaire d'anticorps anti-récepteur de la thyrotropine et d'anticorps anti-idiotypes de la TSH humaine." Paris 5, 1994. http://www.theses.fr/1994PA05P601.
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Szinnai, Gabor. "Mécanismes moléculaires et cellulaires du développement normal et pathologique de la glande thyroïde." Paris 7, 2008. http://www.theses.fr/2008PA077217.
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L'hypothyroïdie congénitale (HC) est la maladie endocrinienne congénitale la plus fréquente, elle touche 1:3'400 nouveau-nés. L'HC est due soit à des anomalies du développement thyroïdien, la dysgénésie thyroïdienne (85% des HC) ou soit à des troubles de l'hormonogénèse (15% des HC). Dans le contexte de la recherche clinique et fondamentale dans le domaine de l'HC, ce travail a eu deux objectifs : 1)améliorer la compréhension de la physiopathologie moléculaire des mutations de TITF1 et NIS. Les résultats de notre travail donnent une revue détaillée du spectre clinique de ces deux formes d'HC et suggèrent de possibles mécanismes moléculaires responsables de la variabilité de la sévérité de l'HC de ces patients. 2)d'établir une stratégie pour rechercher des nouveaux gènes et mécanismes moléculaires impliqués dans le développement normale et pathologique de la thyroïde. Pour ce faire, nous avons étudié dans une première étape le transcriptome de la différenciation thyroïdienne normale chez l'Homme. Par cette approche, nous avons obtenu une signature moléculaire restrictive qui représente une source unique pour générer des hypothèses sur le rôle de gènes et des cascades de signalisation. Dans une deuxième étape, nous avons établi un modèle de culture de la thyroïde murine en différenciation. Un tel modèle est indispensable pour étudier et valider la fonction des gènes et les mécanismes moléculaires issus de notre étude du transcriptome pendant le développement thyroïdien normal in vitro. En perspective, après validation dans notre modèle de culture, la recherche de mutations chez des patients avec HC doit prouver l'implication de gènes candidats dans l'étiologie de l'HC<br>Congenital hypothyroidism (CH) represents the most frequent congenital endocrine disorder with 1:3'400 newborns affected. It is caused by defects in any of the essential steps of thyroid development or thyroid hormone synthesis. Such defects result in morphologic abnormalities leading to thyroid dysgenesis (85% of CH), or impaired hormone production, causing thyroid dyshormonogenesis (15% of CH). In the context of clinical and fundamental research on congenital thyroid disease, this work had two aims: 1)to gain more insight into the molecular pathophysiology of mutations in TITF1 and NIS. Our results provide a detailed review of the clinical spectrum of both forms of CH and suggest possible molecular explanations for the variability of CH severity in these patients. 2)to establish a developmental multistep strategy to search for new mechanisms and genes possibly involved in normal and pathologic thyroid development and function. For this, we first studied the transcriptome of normal thyroid differentiation in the human. We obtained a restrictive molecular signature representing a unique resource to generate hypotheses on the role of individual genes, and active pathways and biological processes. In a second step, we established a murine culture model of the differentiating thyroid gland. Such a developmental model is a prerequisite to perform functional studies of putative candidate genes and validate their implication in thyroid development. In perspective, after functional validation in our in vitro model, mutational screening in CH patients will have to proof relevance of candidate genes and molecular mechanisms for CH
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Cholet, Philippe. "Intérêt du dosage systématique de la TSH ultra sensible dans les troubles du rythme auriculaire : étude prospective à propos de 184 observations à l'hôpital de Cherbourg." Caen, 1990. http://www.theses.fr/1990CAEN3078.
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Marez, Arnaud. "Résultats et intérêts du dosage systématique de la thyroxine libre et de la thyréostimuline hormone en médecine interne et moyen séjour gériatrique." Bordeaux 2, 1989. http://www.theses.fr/1989BOR25033.
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Morand, Stanislas. "La NADPH oxydase DUOX2, composante catalytique du système générateur d'H2O2 associé à la thyroperoxydase : études de régulation et de maturation." Paris 11, 2006. http://www.theses.fr/2006PA114809.
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L'élaboration et la sécrétion des hormones T3 et T4 s'opèrent au sein des follicules thyroïdiens. Sur le plan histologique, un follicule se compose d'une monocouche de cellules épithéliales, les thyrocytes, délimitant un espace clos sphérique appelé lumière folliculaire. L'hormonosynthèse s'effectue dans la lumière folliculaire, plus précisément à la surface externe du pôle apical des thyrocytes. L'étape initiale est la liaison d'un atome d'iode sur une protéine matrice, la thyroglobuline. Cette réaction, catalysée par la thyropéroxydase (TPO), requiert du péroxyde d'hydrogène fourni par une NADPH:O2 oxydoréductase dont la composante catalytique est vraisemblablement la Dual oxydase 2 (Duox2). C'est une glycoprotéine à sept domaines transmembranaires d'environ 1550 résidus organisés en trois régions successives : un ectodomaine N-terminal homologue aux hémopéroxydases, une longue boucle intracellulaire renfermant deux EF-hands, et un domaine C-terminal dédié au transfert des électrons du NADPH cytosolique au dioxygène extracellulaire.
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Croizet, Karine. "Identification et caractérisation d'une population de cellules dendritiques (DC) dans les cultures primaires de thyrocytes : mise en évidence d'un contrôle des fonctions différenciées des DC par la TSH via les thyrocytes." Lyon 1, 1999. http://www.theses.fr/1999LYO1T200.
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SANTANA, PATRICIA M. "Expressão de tireotrofina humana em células de embrião de rim humano (HEK293)." reponame:Repositório Institucional do IPEN, 2016. http://repositorio.ipen.br:8080/xmlui/handle/123456789/26947.
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Submitted by Marco Antonio Oliveira da Silva (maosilva@ipen.br) on 2016-12-22T16:39:39Z
No. of bitstreams: 0<br>Made available in DSpace on 2016-12-22T16:39:39Z (GMT). No. of bitstreams: 0<br>Neste trabalho foi transfectada uma linhagem de células embrionárias de rim humano (HEK293) com os genes das subunidades α e β da tireotrofina humana (hTSH), hormônio glicoproteico secretado pela hipófise. Após 5 dias de cultivo obteve-se uma concentração de hTSH no meio condicionado de 0,95μg/mL. O material foi concentrado e purificado utilizando uma estratégia envolvendo duas etapas, uma cromatografia de troca catiônica e uma cromatografia líquida de alta eficiência (HPLC) de fase reversa, que permitiu uma recuperação de 55% e uma pureza >90%. O produto purificado (hTSH-HEK) foi analisado e comparado a uma preparação comercial obtida em células CHO (hTSH-CHO) e a uma preparação hipofisária (hTSH-Pit). A identidade e a pureza do hTSH-HEK foram avaliadas por métodos físicoquímicos e imunológico (espectrometria de massa MALDI-TOF, HPLC de exclusão molecular e de fase reversa, SDS-PAGE e ensaio imunoradiométrico). A porção glicídica do hTSH-HEK foi avaliada pela análise do perfil dos N-glicanos e o comportamento biológico deste hormônio foi avaliado por bioensaio in vivo e estudo farmacocinético. As 3 preparações apresentaram pureza equivalente (97%) e a massa molecular relativa do hTSH-HEK foi 2,1% menor do que a do hTSH-CHO e 2,7% maior do que a do hTSH-Pit. A maior hidrofobicidade relativa, avaliada por RP-HPLC, foi a do hTSH-HEK. Os N-glicanos identificados no hTSH-HEK foram do tipo complexo, apresentando predominantemente estruturas tri-antenárias, enquanto no hTSH-CHO e no hTSH-Pit as estruturas bi-antenárias foram predominantes. Foram detectadas diferenças significativas relacionadas à composição dos carboidratos para estas preparações, um teor muito menor de ácido siálico e muito maior de fucose foram observados no hTSHHEK. Foi confirmada a atividade biológica das 3 preparações, sendo a bioatividade do hTSHHEK 39% e 16% inferior à do hTSH-CHO e hTSH-Pit, respectivamente. A meia-vida circulatória do hTSH-HEK foi menor (1,5 X) que a do hTSH-CHO e a do hTSH-Pit (1,2 X). De acordo com esses resultados o hTSH-HEK pode ser considerado uma alternativa viável para aplicações clínicas especialmente por sua origem humana e composição de carboidratos.<br>Dissertação (Mestrado em Tecnologia Nuclear)<br>IPEN/D<br>Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP
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Κουλούρης, Αριστείδης. "Η νυχθημερήσια διακύμανση της TSH σε νεογνά και βρέφη". Thesis, 1991. http://nemertes.lis.upatras.gr/jspui/handle/10889/2799.
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Typlt, Eva. "„Heiße“ Schilddrüsenknoten bei Kindern: Mutationshäufigkeiten und Mutationsmuster aktivierender TSH-Rezeptor- und Gs alpha- Mutationen: „Heiße“ Schilddrüsenknoten bei Kindern:Mutationshäufigkeiten und Mutationsmuster aktivierender TSH-Rezeptor- und Gs alpha- Mutationen." Doctoral thesis, 2015. https://ul.qucosa.de/id/qucosa%3A14411.
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Szintigrafisch heiße Schilddrüsenknoten (HTNs) bei Kindern sind selten. Ihre Malignitätsrate wird als höher beschrieben im Vergleich zu der Erwachsenenpopulation. Es wurden in dieser Dissertation klinische und molekulare Daten von 33 Kindern (29 benigne und 4 maligne HTNs) untersucht.
In 17 der 29 benignen HTNs (59%) konnte eine TSHR- Mutation nachgewiesen werden. Die häufigste Mutation war die M453T (8 von 29 Proben). T632I- und D633Y- Mutationen konnten jeweils in zwei Fällen detektiert werden. Alle anderen gefundenen TSHR- Mutation wurden jeweils nur in einer Probe festgestellt, inklusive die neu aufgetretene Mutation A538T. Eine NRAS- Mutation wurde in einem HTN mit einer M453T- Mutation gemeinsam nachgewiesen. Ein PAX8/PPARγ- Rearrangement konnte in einem malignen Knoten (follikuläre Variante eines papillären Schilddrüsenkarzinoms; fvPTC) detektiert werden. Ebenfalls konnte in einem malignen HTN (papilläres Schilddrüsenkarzinom; PTC) eine T632I- Mutation nachgewiesen werden.
Der Prozentsatz an TSHR- mutations-positiven HTNs in Kindern und Heranwachsenden lag in dem bei Erwachsenen beschriebenen Bereich. Auffällig war die signifikante Häufung der M453T- Mutation in der Kinderpopulation. Die beschriebene erhöhte Malignitätsrate der HTNs bei Kindern scheint nicht mit RAS- , BRAF- , RET/PTC- oder PAX8/PPARγ- Mutationen assoziiert zu sein.:I. Bibliografische Zusammenfassung - 4 -
II. Abkürzungsverzeichnis - 5 -
III. Abbildungs- und Tabellenverzeichnis - 6 -
1 Einleitung - 7 -
1.1 Epidemiologie, Klinik und Diagnostik - 8 -
1.1.1 Maligne Knoten - 9 -
1.1.2 Benigne Knoten - 9 -
1.2 Molekulare Pathogenese von Schilddrüsentumoren - 10 -
1.2.1 Schilddrüsenspezifische Pathogenese - 10 -
1.2.1.1 TSHR - 10 -
1.2.1.2 Gsα - 10 -
1.2.2 Allgemeine Tumorgenese - 11 -
1.2.2.1 RAS- und BRAF- Punktmutationen - 11 -
1.2.2.2 PAX8/PPARγ- und RET/PTC- Rearrangements - 12 -
2 Aufgabenstellung - 13 -
3 Material und Methoden - 14 -
3.1 Patientenkohorte - 14 -
3.2 Nukleinsäure- Isolation - 18 -
3.3 cDNA- Synthese - 18 -
3.4 Nachweis von Rearrangements mittels quantitativer Polymerase-Kettenreatktion (qPCR) - 19 -
3.5 Nachweis von Punktmutationen mittels High- Resolution- Melting (HRM) - 19 -
3.6 Nachweis von Punktmutationen mittels Pyrosequenzing - 22 -
3.7 Funktionelle Charakterisierung der TSHR- Mutation A538T - 24 -
3.7.1 Zielgerichtete Mutation - 24 -
3.7.2 Zellkultur und Expression der TSHR- Mutation - 24 -
3.7.3 FACS- Analyse - 24 -
3.7.4 cAMP- Akkumulationsassay - 25 -
3.7.5 IP- Akkumulationsassay - 25 -
3.7.6 Lineare Regressionsanalyse (LRA) - 25 -
3.8 Statistische Auswertung - 26 -
3.9 Datenbankrecherche - 26 -
4 Ergebnisse - 27 -
4.1 Mutationsanalyse - 27 -
4.2 Funktionelle Charakterisierung der neu identifizierten TSHR-Mutation A538T - 29 -
4.3 Vergleich mit Literaturdaten - 31 -
5 Diskussion - 34 -
6 Zusammenfassung - 42 -
7 Referenzen - 44 -
IV. Erklärung über die eigenständige Abfassung der Arbeit - 53 -
V. Publikation - 54 -
VI. Lebenslauf - 55 -
VII. Danksagung - 56 -
VIII. Erklärung über die Vorbehaltlichkeit der Verfahrenseröffnung zur Verleihung des Titels Dr. med. - 57 -
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ZHANG, GING-ZHONG, and 張慶忠. "Serum thyrotropin (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) in patients with thyroid, adrenal and pituitary diseases." Thesis, 1986. http://ndltd.ncl.edu.tw/handle/79665522155501982441.
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Farinha, José Maria Martins do Rêgo. "Etiology of hypothyroidism and its differential diagnosis : a case series of TSH elevation with negative thyroid antibodies." Master's thesis, 2015. http://hdl.handle.net/10451/25776.
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Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2015<br>Context: The etiology of hypothyroidism may be primary or central, congenital or acquired, or resulting from thyroid hormone consumption or peripheral resistance. Some other causes of an altered TSH value must be taken into account in the differential diagnosis.
Design: Based on a specific database (781 patients), we searched for patients who presented with hypothyroidism and negative thyroid antibodies at the first appointment. We studied each one of these individuals retrospectively, investigating possible causes of a TSH elevation besides Hashimoto’s thyroiditis.
Results: Within 60 patients presenting with hypothyroidism at the first visit, we found 13 with subclinical hypothyroidism and negative thyroid antibodies. 8 of these patients (62%) eventually developed positive thyroid antibodies during the follow-up period, although values were always only borderline or slightly increased and sometimes became negative again. All the patients presented with diseases, conditions or drugs possibly related to hypothalamic-pituitary-thyroid axis dysfunction.
Conclusions: In all these patients, other possible causes of an elevated TSH value should also be investigated. In those who eventually developed positive thyroid antibodies, autoimmunity by itself may not completely justify thyroid dysfunction. However, because the progression to overt autoimmune hypothyroidism is a gradual process taking several years, this can be the initial presentation of the disease.<br>Contexto: O hipotiroidismo pode ter uma causa primária ou central, congénita ou adquirida, ou resultar do consumo ou resistência periférica às hormonas tiroideias. No diagnóstico diferencial importa considerar outras causas que provoquem alterações nos valores da TSH.
Plano: Utilizando uma base de dados específica (781 pacientes), procurámos os pacientes com hipotiroidismo e anticorpos antitiroideus negativos na primeira consulta. Estudámos cada um desses pacientes retrospectivamente, investigando possíveis causas para a elevação da TSH para além da Tiroidite de Hashimoto.
Resultados: Em 60 pacientes apresentando-se com hipotiroidismo na primeira consulta, encontrámos 13 com hipotiroidismo subclínico e anticorpos antitiroideus negativos. 8 desses pacientes (62%) acabaram por desenvolver anticorpos antitiroideus durante o período de seguimento, apesar dos valores estarem sempre apenas no limite superior ou ligeiramente aumentados e, por vezes, voltarem a tornar-se negativos. Todos os pacientes se apresentavam com doenças, condições ou fármacos possivelmente relacionados com disfunção do eixo hipotálamo-hipófise-tiróide.
Conclusões: Em todos estes pacientes, devem ser investigadas outras causas possíveis de um valor aumentado da TSH. Naqueles que acabaram por desenvolver anticorpos antitiroideus, a autoimunidade por si só pode não justificar completamente a disfunção tiroideia. No entanto, uma vez que a progressão para hipotiroidismo clínico autoimune é um processo gradual levando vários anos, esta pode ser a apresentação inicial da doença.
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Συκιώτης, Γεράσιμος Π. "Ανίχνευση μεταλλάξεων του υποδοχέα της θυρεοειδοτρόπου ορμόνης (TSH-R)σε αυτόνομα αδενώματα του θυρεοειδούς". Thesis, 2003. http://nemertes.lis.upatras.gr/jspui/handle/10889/3294.
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Jones, Richard Alan. "Regulation of Thyrotropin mRNA Expression in Red Drum, Sciaenops ocellatus." Thesis, 2012. http://hdl.handle.net/1969.1/ETD-TAMU-2012-08-11859.
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The role of thyroid-stimulating hormone (TSH) in the regulation of peripheral thyroid function in non-mammalian species is still poorly understood. Thyroxine (T₄), the principal hormone released from the thyroid gland in response to TSH stimulation, circulates with a robust daily rhythm in the sciaenid fish, red drum. Previous research has suggested that the red drum T₄ cycle is circadian in nature, driven by TSH secretion in the early photophase and inhibited by T₄ feedback in the early scotophase. To determine whether TSH is produced in a pattern consistent with driving this T₄ cycle, I developed quantitative real time RT-PCR (qPCR) techniques to quantify the daily cycle of expression of the pituitary TSH subunits GSU[alpha], and TSH[beta]. I found that pituitary TSH expression cycled inversely to, and 6-12 hours out of phase with, the T₄ cycle, consistent with the hypothesis that TSH secretion drives the T₄ cycle. To examine the potential role of deiodinases in negative feedback regulation of this TSH cycle, I also utilized qPCR to assess the pituitary expression patterns of the TH activating enzyme outer-ring deiodinase (Dio2) and the TH deactivating enzyme inner ring deiodinase (Dio3). Whereas Dio2 was not expressed with an obvious daily cycle, Dio3 was expressed in the pituitary mirroring the TSH cycle. These results are consistent with T₄ negative feedback on TSH and suggest that TH inactivation by pituitary cells is an important component of the negative feedback system. To further examine the TH regulation of this Dio3 cycle, I developed an immersion technique to administer physiological doses of T₃ and T₄ in vivo. Both hormones persist in static tank water for at least 40 hours. Immersion in 200ng/ml T₄ significantly increased both plasma T₄ and T₃ within physiological ranges above control at 4.5 hours. Immersion in 100ng/ml T₃ increased plasma T₃ within physiological ranges over control by 22 hours while significantly decreasing plasma T₄ below control, presumably through inhibition of TSH secretion. T₄ also significantly inhibited the expression of the TSH [alpha] and [beta] subunits at 4.5 and 22 hours of immersion whereas T₃ immersion significantly inhibited the expression of the [alpha] and [beta] subunits of TSH by 22 hours. Both Dio2 and Dio3 expression were significantly diminished by T3 and T₄ at 22 hours. Inhibition of circulating THs with the goitrogen methimazole significantly increased the expression of TSH. These results indicate that both T₄ and T₃ are capable of negative feedback regulation of TSH expression in red drum on a time scale consistent with the T₄ daily cycle, and further support Dio3 destruction of THs in the pituitary, potentially regulated by circulating T₄, as a critical component of negative feedback on TSH. This study supports the importance of central mechanisms acting through pituitary TSH secretion in regulating thyroid function in red drum.
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Decker, Andrea H. "Associations between Butylparaben and Thyroid Levels in Females Aged 12 and over (NHANES, 2007-2008)." 2015. http://scholarworks.gsu.edu/iph_theses/370.
Full textAbstract:
Background: Paraben exposure occurs everyday to most people unknowingly. Parabens are present in most personal care products in varying amounts. Presently, parabens are not listed as endocrine disruptors; however, some research has shown parabens associated with decreases in thyroid hormone levels. The chemical and adsorption mechanism for parabens in association with thyroid hormones is not well understood. Determining whether parabens are associated with a change in thyroid hormone levels can help reduce the incidence of possible adverse health effects with exposure to parabens.
Methodology: The selected study variables were analyzed using SAS version 9.2. Data were obtained from the 2007-2008 National Health and Nutrition Examination Survey (NHANES). Analyses were performed separately for adolescent females (12-19) and adult females (20+). Weighted means were performed for the main independent and dependent variables of interest stratified by race/ethnicity groups and by smoking status. Independent samples t-test and ANOVA was used to test significance of differences of weighted means. Weighted bivariate linear regression was performed for each dependent variable (Thyroid Stimulating Hormone [TSH], Triiodothyronine [T3], and Thyroxine [T4]) regressed on butylparaben. Weighted multiple linear regressions were performed and parameter estimates with 95% confidence intervals were used to ascertain the measure of effect. Separate regression models stratified by age group (adolescent vs. adult) were ran for each dependent variable (TSH, T3, and T4) regressed on butylparaben level and covariates, race/ethnicity and smoking status (ever smoked).
Results: Weighted bivariate linear regression showed that among adult females, for each ng/ml increase in butylparaben, there was a -1.07 decrease in ng/dL T3 (p
Weighted multiple linear regression showed higher butylparaben levels among adult females were associated with 0.12 ug/dL lower than average T4 levels (p
Conclusion: While parabens are currently not considered endocrine disruptors, the human metabolism of and effects from exposure to parabens are not well understood. Results from this study showing decreased levels of some thyroid hormone levels (TSH, T3, and T4) associated with increased levels of butylparaben was found, as well as differences in thyroid hormone levels among racial/ethnic groups. Although not many human studies have found significant results, 10 some rodent studies have found butylparaben associations with thyroid hormone changes.4, 6, 19, 54 The results of this study indicating no statistically significant association between butylparaben and decreases in thyroid hormone levels are consistent with results of some rodent studies.7, 8, 54, 55 In light of these findings, additional human studies with paraben exposure and thyroid hormone levels are needed to increase knowledge of the mechanism and effect of parabens in the human body.
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Chaves, Rita Domingues. "Determinação de valores de referência de T4 e TSH em Catatuas Galah (Eolophus roseicapilla)." Master's thesis, 2020. http://hdl.handle.net/10437/11875.
Full textAbstract:
Orientação: Nazaré Pinto da Cunha ; co-orientação: Rui Filipe Galinho Patrício<br>Nos últimos anos vários clínicos têm levantado suspeitas de doenças endócrinas em
aves, nomeadamente doenças da tiroide, no entanto a falta de valores de referência para cada
espécie dificulta ou mesmo impossibilita um diagnóstico final.
A falta de inúmeros parâmetros analíticos em aves, com valores de referência para cada
espécie faz com que o diagnóstico das mais variadas doenças nestes animais seja um desafio.
Levando muitas vezes à cronicidade da condição ou até à mesmo morte do animal
Com este trabalho, pretendeu-se criar um intervalo de referência de Tiroxina (T4) e
Hormona estimulante da tiroide (TSH), para a espécie de Catatua Galah (Eolophus
roseicapilla), comumente mantida em cativeiro em todo o mundo, e para qual já foram
apresentados vários ‘case reports’ de suspeita de hipotiroidismo.
Para tal, foram realizadas análises de T4 e TSH a 30 aves adultas e sem sinal de doença.
O intervalo de referência para a hormona T4 foi (1,46 - 2,41μg/dl), para TSH não foi possível
determinar um intervalo de referência devido à falta de sensibilidade do instrumento usado.
Esta informação permite-nos o início da exploração da patologia tiroideia nesta
espécie. Contudo, serão necessários estudos futuros para que o diagnóstico desta patologia
possa ser realizado com segurança, de forma a poder ser instituída a terapêutica adequada.<br>In recent years several clinicians have raised suspicions of endocrine diseases in birds,
especially thyroid disease, however the lack of reference values for each species makes it
difficult or even impossible to make a final diagnosis.
The lack of numerous analytical parameters in birds, with reference values for each
species makes the diagnosis of the most varied diseases in these animals a challenge. Often
leading to the chronicity of the condition or even the death of the animal.
The aim of this work was to create a reference interval of Thyroxine (T4) and Thyroidstimulating
Hormone (TSH) for the Galah Cockatoo (Eolophus roseicapilla) species,
commonly held in captivity worldwide, and for which several case reports of suspected
hypothyroidism have already been presented.
For this purpose, T4 and TSH analysis were performed in 30 healthy adult birds. The
reference interval for T4 hormone was (1.46 - 2.41μg / dl), for TSH it was not possible to
determine a reference interval due to the lack of sensitivity of the instrument used.
This information allows us to begin exploring thyroid pathology in this species. However,
future studies will be necessary for the diagnosis of this pathology to be safely made, and so
that appropriate therapy can be instituted.
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Schmidt, Claudia. "Wird der szintigrafische Befund der disseminierten Schilddrüsenautonomie durch mangelnde Sensitivität der TSHRAK- Assays, intrathyreoidalen Iodmangel, Schilddrüsenvergrößerung oder TSH-Rezeptor-Keimbahnmutationen verursacht?: Wird der szintigrafische Befund der disseminierten Schilddrüsenautonomie durch mangelnde Sensitivität der TSHRAK-Assays, intrathyreoidalen Iodmangel, Schilddrüsenvergrößerung oder TSH-Rezeptor-Keimbahnmutationen verursacht?" Doctoral thesis, 2011. https://ul.qucosa.de/id/qucosa%3A11404.
Full textAbstract:
Das Krankheitsbild der disseminierten Schilddrüsen(SD)-Autonomie ist nur in Mitteleuropa bekannt und wird in der englischsprachigen Literatur nicht beschrieben.
Die exakte Pathogenese der disseminierten SD-Autonomie, insbesondere ob es sich um ein eigenständiges Krankheitsbild oder nur um ein szintigrafisches Phänomen handelt, ist nicht geklärt.
Daher war es Ziel dieser Arbeit, die klinische Entität der disseminierten Autonomie genauer zu klassifizieren, mit anderen SD-Autonomien zu vergleichen und weitere Erkenntnisse über die Pathogenese, insbesondere bezüglich des intrathyreoidalen Iodgehalts sowie TSH-Rezeptorkeimbahnmutationen dieser Erkrankung zu
gewinnen.
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Haust, Merle. "Assoziation der Autoimmunthyreoiditis mit depressiven Störungen." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-0006-B2DE-6.
Full text
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DUŠOVÁ, Hana. "Vliv jódu na funkční parametry ovcí." Doctoral thesis, 2014. http://www.nusl.cz/ntk/nusl-178094.
Full textAbstract:
The aim of this work was to assess the long-term effect of excessive iodine intake on thyroid activity and selected immunological, haematological and biochemical parameters in blood of ewes and their lambs. The experiment was conducted from August 2009 to February 2010 in an experimental barn of Faculty of Agriculture, University of South Bohemia in České Budějovice. Into the experiment were used Šumava sheep breed ewes and their born lambs. Group A (control) consisted of 6 ewes after lambing was extended to 7 born lambs, group B (experimental) 6 of 6 ewes and lambs. Lambs were put into the experiment from the 1st to the 60th day after birth and received iodine in the milk of their mothers. Iodine supplementation to the diet of ewes was launched during the first to second months of pregnancy and finished 60 days after birth. During the experiment, a group of ewes A received 3,1 and group B 5,1 mg iodine per kg of dietary dry matter in the form of calcium iodate. During the experiment was regularly collected blood of ewes (before lambing and 1st, 10th, 30th and 60th day after birth) and lambs (1st, 3rd, 10th, 30th and 60th day after birth) to determine the concentration of thyroid stimulating hormone and immunoglobulin G (ELISA) in blood serum, thyroid hormones (RIA), total protein, urea and alkaline phosphatase activity in the blood plasma (biochemical analyser), the content of haemoglobin, white blood cell´s and red blood cell´s counts and haematocrit values in blood (haematological analyser), percentage of albumin, -1-globulins, -2-globulins, -globulins, and -globulins in blood serum (electrophoresis) and the content of iodine in the blood plasma, urine and milk of ewes (colorimetric method Sandell-Kolthoff). During the experiment were not observed in ewes and lambs clinical symptoms associated with an excessive intake of iodine. In experimental group of ewes with iodine intake 5,1 mg/kg of dietary dry matter were found higher values of thyroid stimulating hormone, lower values of free triiodothyronine, free thyroxine, IgG, white blood cells, -1-globulins, -2-globulin and -globulin, significantly lower values of -globulins after parturition, significantly higher values of urea and alkaline phosphatase activity. The iodine content in blood plasma, milk and urine of ewes is increased in direct proportion to its concentration in diet. Lambs of mothers with iodine intake of 5,1 mg/kg of dietary dry matter were significantly higher values of thyroid stimulating hormone from the 10th day after birth, significantly lower values of free triiodothyronine and free thyroxine first day after birth, immunoglobulin G and -globulins in 30th day after birth, lower (statistically significant in middle samples) values of total protein and white blood cells, higher values of urea and alkaline phosphatase activity. The weight gains of lambs were not significantly affected by iodine supplementation. These results in ewes with iodine intake of 5,1 mg/kg dietary dry matter and especially their lambs drawn to risk of reduce the activity of the thyroid gland and the negative impact of parameters of humoral immunity, mainly IgG and -globulins.