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Ödmark, Inga-Stina. "Hormone replacement therapy : benefits and adverse effects." Doctoral thesis, Umeå universitet, Obstetrik och gynekologi, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-243.
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Background: Numerous studies have shown that estrogen replacement therapy (ERT) is an effective treatment for vasomotor symptoms, insomnia and vaginal dryness. Beneficial effects have also been shown on lipid patterns and on the incidence of osteoporotic fractures. As ERT increases the risk of endometrial adenocarcinoma, combinations with various progestogens have been developed in order to protect the endometrium. However, the addition of progestogens tends to reduce the beneficial effects of estrogens on mood, cognition and lipid metabolism. The added progestogen often causes side effects such as irritability and depression. There is evidence that the effect on wellbeing varies between women and with the type of progestogen used. Women who prefer to avoid withdrawal bleedings can be given continuous combined hormone replacement therapy (HRT). Unfortunately, irregular bleedings are common at the beginning of treatment and reduces compliance. Recently, several studies have reported an increased risk of breast cancer and venous thrombosis, and therefore long-term treatment with HRT for women without climacteric symptoms is no longer recommended. The ongoing debate has, for the time being, resulted in a recommendation that improving quality of life (QoL) by treatment of climacteric symptoms should be the only indication for prescribing HRT. Aims and methods: The aims of the study were to investigate bleeding patterns, changes in wellbeing at onset and during long-term treatment, and lipid and lipoprotein profiles with two different types of continuous combined HRT. In addition, women starting, and women switching from mainly sequential HRT were compared. The design was a randomised, double-blind, one year, prospective, multicentre study including 249 healthy postmenopausal women who were given continuous daily oral treatment with either combined 0.625mg conjugated estrogen (CE) and 5mg medroxyprogesterone acetate (MPA) or combined 2mg 17β - estradiol (E2) and 1mg norethisterone acetate (NETA). Bleedings, if any, were recorded daily throughout the study. The main outcome measures (changes in wellbeing and climacteric symptoms) consisted of daily ratings of 12 items on a validated symptom scale. Serum concentrations of lipids and lipoproteins were measured at baseline and after one year of treatment. Results and conclusions: The majority of drop-outs were confined to the first three months, and the main reasons were bleedings and/or decreased wellbeing. Drop-outs were three times more common in the E2/NETA group. During the first month, 67% of the women reported irregular bleedings. The number of bleeding days decreased on both treatments during the first four months. Treatment with CE/MPA resulted in less irregular bleedings and a shorter time to amenorrhoea compared to E2/NETA. As expected, "starters" experienced more sweats than "switchers" at the onset of treatment, but both groups improved significantly. Side effects such as breast tenderness, swelling, depression and irritability appeared during the first treatment week in both groups. The side effects of HRT appeared much more quickly than the benefits and were more frequent in women with a history of premenstrual syndrome (PMS). Breast tenderness was more common in the E2/NETA group throughout the whole study period. Apart from that, there were no differences between the two treatment regimens as regards effects on well-being at the end of the study. Lipoprotein(a) levels, an important risk factor for cardiovascular disease, decreased in both treatment groups. Triglyceride levels increased in women treated with CE/MPA, and levels of total cholesterol, high density lipoprotein and low density lipoprotein fell in the E2/NETA group. In conclusion, treatment with E2/NETA caused more bleeding problems than treatment with CE/MPA. CE/MPA was better tolerated than E2/NETA at the beginning of the study, but among the women remaining in the study there was no difference in QoL between the two treatment groups. HRT counselling should take into account that a history of PMS increases the likelihood of side effects and that these may precede any beneficial effects. Both treatments produced beneficial effects on lipid and lipoprotein levels, and neither of the regimens was superior in this respect.
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Ödmark, Inga-Stina. "Hormone replacement therapy : benefits and adverse effects /." Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-243.
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Melkersson, Kristina. "Influence of antipsychotic drugs on hormone levels /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4089-4/.
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Mahajan, Tripti. "Diagnosis of growth hormone deficiency and study of the effects of growth hormone treatment in growth hormone deficient adults." Thesis, University of Bristol, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247557.
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Björn, Inger. "Hormone replacement therapy and effects on mood." Doctoral thesis, Umeå universitet, Obstetrik och gynekologi, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-94115.
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Background: During the past 5 decades, hormone replacement therapy (HRT) has been used, and appreciated for its beneficial effects, by millions of women in their menopause. As treatment for climacteric symptoms, estrogen is outstanding, and effects on hot flushes, vaginal dryness, and insomnia have been widely documented. The increased risks of venous thrombosis and breast cancer, however, restrict the use of estrogen. Estrogen treatment in women with a remaining uterus includes a progestin, added to protect the endometrium from hyperplasia and malignancies. The long-standing clinical impression, that progestin addition negatively influences mood, has been discussed in previous studies. Mood deterioration is, however, not mortal, although mood is important to the wellbeing and daily functioning of women treated with hormones. Studies of the mental side effects of HRT add to our understanding of steroid effects in the brain. Aims and methods: In our studies, we aimed to establish to what extent negative side effects cause women to discontinue HRT, and find out which drug compounds lead to mood deterioration. The questions asked were whether the type and dose of progestin and the estrogen dose during the progestin addition influence the mood and physical symptoms during sequential HRT. Compliance with HRT and reasons for discontinuing the therapy were evaluated in a retrospective longitudinal follow-up study. Treatment effects were studied in three randomized, double-blind, cross-over trials. During continuous estrogen treatment, effects of sequential addition of a progestin were studied by comparing two different progestins, medroxyprogesterone acetate (MPA) andnorethisterone acetate (NETA), comparing different doses of the same progestin, MPA, and comparing two doses of estrogen during addition of the same dose of MPA. The main outcome measure was the daily rating on mood and physical symptoms kept by the participants throughout the studies. The clinical trials were carried out at three gynecological centers in northern Sweden. Results and conclusions: Besides fear of cancer and a wish to determine whether climacteric symptoms had meanwhile disappeared, negative side effects was the most common reason or discontinuing HRT. Tension in the breasts, weight gain, a depressed mood, abdominal bloating, and irritability were the most important side effects seen both in women who continued HRT and in women who had discontinued the therapy. In our clinical trials, we showed that addition of a progestin to estrogen treatment induces cyclic mood swings characterized by tension, irritability, and depression, as well as increased breast tension, bloatedness, and hot flushes. Women with a history of premenstrual syndrome (PMS) appeared to be more sensitive to the progestin addition and responded with lower mood scores compared with women without previous PMS. In our studies, MPA provoked depressed mood to a lesser extent than did NETA. Surprisingly, the higher dose of MPA (20 mg) enhanced the mood, compared with 10 mg, when added to estrogen treatment. In women continuously treated with 3 mg estradiol, mood and physical symptoms worsened during the progestin addition, as compared with treatment with 2 mg estradiol. The negative side effects seen during sequential HRT have much in common with symptoms seen in the premenstrual dysphoric disorder (PMDD), which is a psychoneuroendocrine disorder with psychiatric expression. Explanations for treatment effects on mood are likely to be found in drug interactions with neurotransmitter systems of the brain.Diss. (sammanfattning) Umeå : Umeå universitet, 2003
digitalisering@umu
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Pagano, Christopher. "Role of the truncated form of the human growth hormone receptor in regulating growth hormone effects." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114445.
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The binding of human Growth Hormone (GH) to its receptor (GHR) on target cells leads to activation of three major intracellular signaling pathways: JAK2/STAT5, PI3K/AKT and ERK/MAPK. However, in addition to the full length (FL) GHR, there exist two truncated (Tr) GHR isoforms, GHR1-279 and GHR1-277, that lack the majority of their intracellular domain as a result of alternative splicing of GHR mRNA. While both in vitro and in vivo studies suggest that the Tr GHR isoforms have a dominant negative effect on FL GHR by forming stable heterodimers, little is known about their normal physiological functions and their effects on the three major GH signaling pathways. We hypothesized that Tr GHR isoforms play a functionally significant role in human cells and tissues, fine-tuning the ability of GH to activate intracellular signaling and, thus, its biological effectiveness. In HEK293 cells, GH stimulation resulted in rapid and transient effects on pSTAT5b, pAKT and pERK1. Increasing the Tr/FL GHR ratios by transient transfection of a Tr GHR1-279 expression vector resulted in a significant dose-related inhibition of GH's ability to phosphorylate STAT5b, but with no significant inhibition of its ability to phosphorylate AKT and ERK1.These data suggest that Tr GHR can limit the target cell's STAT5b signaling in response to GH, while there is likely an alternative mechanism through which GH is able to activate AKT and ERK. This reveals a possible physiological role for Tr GHR in modulating GH's biological activity differentially in its target tissues.La liaison de l'Hormone de Croissance humaine (GH) à son récepteur (GHR) sur les cellules cibles conduit à l'activation de trois voies de signalisation intracellulaires majeures: JAK2/STAT5, PI3K/AKT et ERK/MAPK. Cependant, en plus de la forme intégrale (FL) du GHR, il existe deux isoformes tronquées (Tr) du GHR, GHR1-279 et GHR1-277 qui ont perdu la majorité de leur domaine intracellulaire dû à l'épissage alternatif de l'ARNm du GHR. Alors que les études in vitro et in vivo suggèrent que les isoformes tronqués du GHR auraient un effet de dominant négatif sur le GHR FL en formant des hétérodimères stables, peu d'éléments sont connus au niveau de leurs fonctions physiologiques normales et de leurs effets sur les trois voies de signalisation majeure de GH. Nous avons émis l'hypothèse que les isoformes de GHR Tr auraient un rôle fonctionnel significatif dans les cellules et les tissus humains, en régulant de façon précise la capacité de GH à activer la signalisation intracellulaire et donc son efficacité biologique. Dans les cellules HEK293, la stimulation par GH a conduit à des effets rapides et transitoires sur pSTAT5b, pAKT and pERK1. L'augmentation des ratios Tr/FL du GHR par transfection transitoire du vecteur exprimant le GHR1-279 Tr a résulté en une inhibition significative et dépendante de la dose sur la capacité de GH à phosphoryler STAT5b, mais cependant sans inhibition significative sur sa capacité à phosphoryler AKT et ERK1. Ces données suggèrent que le GHR Tr peut limiter la signalisation par STAT5b dans la cellule cible en réponse à GH, tandis qu'il existerait probablement un mécanisme alternatif par lequel GH serait capable d'activer AKT et ERK. Cela révèle un possible rôle physiologique pour le GHR Tr dans la modulation de l'activité biologique de GH de façon différentielle dans ses tissus cibles.
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Smith, Jamie C. "The effects of growth hormone on vascular reactivity and oxidative stress in hypopituitary adults with growth hormone dificiency." Thesis, Cardiff University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402851.
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Almeida, Nisha. "Measures of maternal tobacco smoke exposure and foetal growth." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112375.
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Objective. Most biomarker studies of maternal smoking have been based on a single blood or urinary cotinine value, which is inadequate in capturing maternal tobacco exposure over the entire pregnancy. This thesis used maternal hair biomarkers to investigate the association between maternal active and passive smoking, and birthweight for gestational age (BW for GA).Methods. Subjects were 444 term controls drawn from 5,337 participants of a multi-centre nested case-control study of preterm birth in Montreal. Maternal hair, collected after delivery, was measured for average nicotine and cotinine concentration across the pregnancy, assuming hair growth of 1 cm/month. The BW for GA z-score used Canadian population-based standards. Multiple linear regression was used to assess effects on the z-score, after controlling for potential confounders.
Results. In regression models for maternal active smoking analysis, the addition of hair nicotine to models containing either self-report or hair cotinine or both self-report and cotinine explained significantly more variance in the BW for GA z-score (p=0.009, p=0.017, and p=0.033, respectively). In maternal passive smoking analysis, no significant effect of ETS on BW for GA was found using hair biomarkers.
Conclusion. These results indicate that hair biomarkers are sensitive tools capable of predicting reductions in birthweight for maternal active smoking. The stronger results obtained for nicotine are reflective of the fact that hair nicotine is a better measure of maternal smoking, but it could also suggest that nicotine plays an aetiologic role in affecting foetal growth.
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Lindgren, Ann Christin. "Prader-Willi syndrome : diagnosis and effects of growth hormone treatment /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3135-6/.
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Westbrook, Reyhan Marcus. "The Effects of Altered Growth Hormone Signaling on Murine Metabolism." OpenSIUC, 2012. https://opensiuc.lib.siu.edu/dissertations/549.
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Growth hormone signaling influences longevity but the mechanism through which decreased GH action extends lifespan in mice is unknown. It is likely that the key to understanding this phenomenon, and the process of aging itself, is to understand the alterations in metabolism caused by decreased GH action. We investigated changes in energy metabolism in long-lived mice, in hope that these findings can suggest means of improving human health and longevity. These studies consisted of three projects. The influence of altered GH signaling on metabolism was tested by monitoring oxygen consumption, respiratory quotient, and heat production. Intriguingly, long-lived mice have increased oxygen consumption, and decreased respiratory quotient; while short lived mice had opposite effects. These data indicate that decreased GH signaling associates with increased metabolism per unit of body weight and may beneficially affect mitochondrial flexibility by increasing the capacity for fat oxidation; while GH excess generally produces opposite metabolic effects. We then hypothesized that the metabolic characteristics observed in young long-lived mice would persist into old age. Further, we investigated whether caloric restriction or every-other-day diet, two life extending feeding regimens, had any interaction with the metabolic phenotype observed in long-lived mice. The results support our hypothesis that the alterations in metabolism observed in young long-lived mice persist into old age. Neither dietary regimen significantly altered oxygen consumption in GHRKO mice, however, every-other-day diet reduced 24-hour oxygen consumption per gram body weight. These experiments showed that GHRKO mice had increased oxygen consumption regardless of age and life extending dietary interventions we placed them on. We hypothesized that increased oxygen consumption in long-lived mice is the result of increased thermogenesis. To test this hypothesis, we measured oxygen consumption in long-lived mice and controls at the standard lab temperature 23°C, and at 30°C, the murine thermoneutral temperature. When the oxygen consumption of long-lived mice was measured at 30°C, the differences between long-lived and normal mice measured at 23°C were abrogated. These data indicate that increased energy utilization for thermogenesis may contribute to extended longevity of these mutants. Collectively, our results provide important insights into the metabolic characteristics of long-lived mice.
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Vijeyta, Fnu. "Effects of Growth Hormone on Circulating Resistin Levels in Mice." Ohio University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1346947127.
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Young, Jonathan A. "The Effects of Growth Hormone Action on the Mouse Intestine." Ohio University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1534865806561942.
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Grönbladh, Alfhild. "Growth Hormone and Anabolic Androgenic Steroids : Effects on Neurochemistry and Cognition." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-206069.
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Growth hormone (GH) stimulates growth and metabolism but also displays profound effects on the central nervous system (CNS). GH affects neurogenesis and neuroprotection, and has been shown to counteract drug-induced apoptosis in the brain. Anabolic androgenic steroids (AAS), mainly abused for their anabolic and performance-enhancing properties, can cause several adverse effects, such as cardiovascular complications, sterility, depression, and aggression. GH and AAS are both believed to interact with several signaling systems in the CNS. The aim of this thesis was to further investigate the impact of GH and AAS on neurochemistry and cognitive functions. Recombinant human GH (rhGH) and the steroid nandrolone decanoate (ND) were administered, separately and in combination with each other, to male rats. The results demonstrated that administration of GH improved spatial memory, assessed in a water maze test. Furthermore, GH induced alterations of the GABAB receptor mRNA expression, density, and functionality in the brain, for example in regions associated with cognition. GH also altered the mu opioid peptide (MOP) receptor, but not the delta opioid peptide (DOP) receptor functionality in the brain. Thus, some of the GH effects on cognition may involve effects on the GABAB receptors and MOP receptors. ND, on the contrary, seemed to induce impairments of memory and also altered the GABAB receptor mRNA expression in the brain. Furthermore, ND lowered the IGF-1 plasma concentrations and attenuated the IGF-1, IGF-2, and GHR mRNA expression in the pituitary. In addition, significant effects of GH and ND were found on plasma steroid concentrations, organ weight, as well as body weight. In conclusion, this thesis contributes with further knowledge on the cognitive and neurochemical consequences of GH and ND use. The findings regarding ND are worrying considering the common use of AAS among adolescents. GH improves memory functions and affects signaling systems in the brain associated with cognition, hence the hypothesis that GH can reverse drug-induced impairments is further strengthened.
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Festen, Dederieke Anne Maria. "Prader-Willi syndrome clinical aspects and effects of growth hormone treatment /." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10645.
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McDonnell, Lisa. "The effects of growth hormone on primary bovine mammary cell models." DigitalCommons@CalPoly, 2012. https://digitalcommons.calpoly.edu/theses/868.
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The ability of exogenous growth hormone (GH) to increase milk yield through insulin-like growth factor-1 (IGF-I) in dairy cows is well characterized. However, recent studies utilizing mammary epithelial cell lines indicate a direct effect of GH on mammary epithelial cells (MEC). To test if these observations are relevant in vivo and if this response differs between dairy breeds, three mammary models were utilized. Mammary explants from a lactating Jersey cow were cultured in classical lactogenic media (dexamethasone, insulin, and prolactin) with 0 or 10 ng/mL of recombinant bovine GH for 12h. Primary MEC from lactating Holstein and Jersey cows were cultured in classical lactation media with 0 or 10 ng/mL of GH for 2, 4, and 7 days. And lastly, MEC isolated from pooled Holstein or pooled Jersey milk were cultured in the same conditions as primary MEC. The response to GH was quantified by the relative abundance of mRNA for two milk protein genes (α-lactalbumin and αS1-casein), the GH receptor, IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) as determined by quantitative RT-PCR. The abundance of α-lactalbumin mRNA in explants was increased in response to GH. After 2 days, Jersey primary MEC showed an increase in GH receptor mRNA, in addition to a noteworthy trend of increasing abundance of IGFBP-3 regardless of GH treatment. After 4 days, Holstein primary cells cultured with GH had decreased IGFBP-3 mRNA. After 7 days, primary cells isolated from Holstein and Jersey mammary tissue showed a slight response to GH. Mammary cells from milk mirrored the responses to GH observed in primary cells: MEC isolated from Holsteins had decreased IGFBP-3 mRNA after 4 days of treatment with GH and MEC isolated from Jerseys showed the same trend of increasing IGFBP-3 abundance between 2 and 4 days, but with no difference between GH treatments. These results indicate that the effect of GH may differ between breeds and indicate GH has a direct effect on mammary epithelial cells, possibly including effects on the abundance of IGFBP-3 mRNA.
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Hyzy, Sharon Leigh. "Adverse effects of bone morphogenic protein-2 during osseointegration." Thesis, Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44728.
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Modifications of biomaterial surface properties are employed to increase osteoblast differentiation and bone formation. Microtextured metallic surfaces promote osteoblast differentiation and high surface energy- achieved by controlling surface hydrocarbon contamination- increases osteoblast differentiation and peri-implant bone formation. Recombinant human bone morphogenic protein 2 (BMP2) is approved to induce bone formation in a number of applications. It is used clinically in combination with biomaterials to improve peri-implant bone formation and osseointegration. The amount of BMP2 that is required is large and inflammatory (swelling/seroma) and bone-related (ectopic bone/bone resorption) complications have been reported after BMP2 treatment. The aim of this study was to examine potential deleterious effects of BMP2 on the inflammatory environment and apoptosis of osteoblasts.
Surface roughness and energy decreased pro-inflammatory interleukins and increased anti-inflammatory interleukins. In contrast, BMP2 abolished the surface effect, increasing pro-inflammatory interleukin (IL) 6, IL8, and IL17 in a surface roughness-dependent fashion and decreasing anti-inflammatory IL10 on rough surfaces. 5Z-7-Oxozeaenol and Dorsomorphin, but not H-8, blocked the effect of BMP2 on IL1A expression. There was an increase in expression of IL6 when treated with BMP2 for the control and H-8 groups, but both 5Z-7-Oxozeaenol and Dorsomorphin blocked the effect. Both 5Z-7-Oxozeaenol and H-8 blocked the effect of BMP2 on IL10 expression.
BMP2 treatment had little effect on apoptosis in human mesenchymal stem cells (MSCs). Exogenous BMP2 had no effect on TUNEL. Caspase-3 activity was increased only at 200ng/ml BMP2. BAX/BCL2 decreased in MSCs treated with 50 and 100ng/ml BMP2. In contrast, BMP2 increased caspase-3 activity and TUNEL at all doses in normal human osteoblasts (NHOst). BAX/BCL2 increased in NHOst treated with BMP2 in a dose-dependent manner. Cells treated with 200 ng/ml BMP2 had an 8-fold increase in BAX/BCL2 expression in comparison with untreated cells. Similarly, BMP2 increased DNA fragmentation in NHOst cells. The BMP2-induced increase in DNA fragmentation was eliminated by 5-Z7-Oxozeaenol and Dorsomorphin.
The results suggest that while surface features modulate an initial controlled inflammatory response, the addition of BMP2 induces a pro-inflammatory response. The effect of BMP2 on apoptosis depends on cell maturation state, inducing apoptosis in committed osteoblasts. BMP2 together with microtextured orthopaedic and dental implants may increase inflammation and possibly delay bone formation. Dose, location, and delivery strategies are important considerations in BMP2 as a therapeutic and must be optimized to minimize complications.
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Padidela, R. N. R. "Effects of polymorphisms in the growth hormone and insulin-like growth factor axis on intrauterine and postnatal growth." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1396005/.
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Context: Intrauterine and postnatal growth influences future risks for metabolic syndrome. Body size and blood pressure (BP) are polygenic traits. The role for genetic variations in growth hormone (GH)-insulin-like growth factor (IGF) axis genes on intrauterine and early childhood growth and blood pressure, as well as gene loci identified through Genome Wide Association Studies (GWAS), are unclear. Objective: To determine whether common variations in the genes of the GH-IGF axis associate with antenatal growth and birth size and play a role in the determination of body size and blood pressure at 3 years of age. Study design: Pregnant women from white European families were recruited by the University College London Fetal Growth Study (n = 774). Fetal growth was measured by ultrasonography at each trimester. Postnatal growth data were collected prospectively at 6 months, 1 year, 2 years and 3 years of age. BP was measured at 3 years of age. Genotyping was performed by a combination of restriction fragment length polymorphism analysis, KBioscience Competitive Allele specific PCR genotyping System (KASP) analysis and multiplex polymerase chain reaction (PCR). Results: The GHR exon 3 deletion genotype was significantly associated with birth weight and placental weight. IGF1 SNPs did not demonstrate significant consistent longitudinal association with parameters investigated. IGF2 SNPs were significantly associated with intrauterine growth (rs680), birth weight (rs680), placental weight (rs680) and BP (rs3842759) at 3 years of age. Several SNPs in genes found to be associated with adult BMI and BP from GWAS were significantly associated with early childhood size (MTCH2, SH2B3), body composition (SH2B1, TMEM18) and BP (FTO). Conclusion: These data suggest that several polymorphisms in the GH-IGF axis and in GWAS-identified genes for adult BMI and BP are significantly associated with intrauterine and early childhood size and BP at 3 years of age.
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Sahin, Merve. "Regulatory Gene Effects On Recombinant Human Growth Hormone Production By Bacillus Subtilis." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612312/index.pdf.
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In this study, regulatory gene effects on recombinant human growth hormone (rhGH) production by Bacillus subtilis were investigated. For this purpose, firstly Bacillus strains, which are deficient in abrB, aprE, degQ, degS, degU, scoC, sinI, sinR, and spo0A genes, were selected according to the regulatory gene network of aprE gene (serine alkaline protease gene of B. subtilis) since due to the degQ promoter and the pre-signal sequence of subC gene cloned in front of
the hGH gene, hGH is produced by mimicking the serine alkaline protease synthesis. R-Bacillus strains were constructed by transformation of pMK4::pre(subC)::hGH plasmid to the selected strains. Thereafter, by the
laboratory scale experiments, strains having the highest hGH production capacity were determined as scoC, aprE, sinR, and degU knockout strains. Using these strains, fermentation experiments were carried out in pilot-scale bioreactor in
defined medium. Effect of pH control was also investigated and the highest cell and hGH concentration was obtained by scoC knockout strain in pH controlled operation as 1.62 kg m-3 and 126 g m-3, respectively. By this strain, the overall
product and cell yield on total substrate were found as 16.12 g kg-1 and 0.15 g g-1, respectively. Furthermore, the highest total protease activity was attained by degU knockout strain as 65 U cm-3. On the other hand, maximum total organic acid
secretion was determined as 1.31 kg m-3 in aprE knockout strain.
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Morales, Orlando. "Effects of 1,25-dihydroxyvitamin D3 and growth hormone on osteoblast-like cells /." Stockholm,, 2003. http://diss.kib.ki.se/2003/91-7349-639-1/.
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Lall, Sabrina. "Long and short term effects of growth hormone secretagogues on body composition." Thesis, University of Cambridge, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621283.
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Murray, Robert Douglas. "The effects of varying degrees of growth hormone deficiency on adult health." Thesis, Queen Mary, University of London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531572.
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Yamauchi, Ichiro. "Effects of growth hormone on thyroid function are mediated by type 2 iodothyronine deiodinase in humans." Kyoto University, 2019. http://hdl.handle.net/2433/242373.
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Hanson, Andrea M. "Effects of Environmental Estrogens on the Growth Hormone-Insulin-Like Growth Factor System in Rainbow Trout (Oncorhynchus Mykiss)." Diss., North Dakota State University, 2013. https://hdl.handle.net/10365/27175.
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The increasing production, use, and disposal of an expanding array of chemicals that enter the environment pose a serious threat to terrestrial and aquatic animals, as well as to humans. Fish in aquatic habitats are exposed to increasing concentrations of environmental contaminants, including environmental estrogens (EE). In this work, rainbow trout were used to assess the effects of EE on the growth hormone (GH)-insulin-like growth factor (IGF) system, specifically focusing on osmoregulation, organismal growth, and growth at the molecular level. Juvenile trout were exposed to varying concentrations of 17?-estradiol (E2), ?-sitosterol (?S), and 4-n-nonylphenol (NP) in vivo and in vitro. Real-time quantitative-PCR was used to measure levels of mRNA expression (GH receptor 1 (GHR1), GHR2, IGF-1, IGF-2, IGF receptor 1A (IGFR1A), and IGFR1B) in multiple tissues, including liver, gill, and muscle. Western blotting was used to elucidate signaling pathways affected by EE-treatment (e.g., JAK-STAT, MAPK, PI3K). Environmental estrogen-treated fish displayed depressed growth in terms of body mass and body length. The observed effects on organismal growth appeared to be due to a decrease in food conversion, as food consumption was not significantly different between treatment groups. Hepatic, gill, and muscle levels of mRNAs encoding GHR1, GHR2, IGF-1, IGF-2, IGFR1A, and IGFR1B decreased in a concentration-, time-, and compound-dependent manner in vivo and in vitro. Furthermore, EE-treated fish displayed decreased osmoregulatory function when subjected to a salt water challenge, as evaluated by measuring plasma chloride levels and mRNA expression of GHRs, IGFs, and IGFRs. The suppression of mRNA expression of components of the GH-IGF system by EE was linked to suppressed phosphorylation of JAK-STAT, MAPK, and PI3K-Akt in a concentration- and time-dependent manner in hepatocytes and gill filaments, an effect that was ER-dependent. Classically, the ER has been thought to function as a nuclear receptor; however, the observed results support the notion that the ER (and thus EE) may have nongenomic effects as well. The results of this dissertation indicate that EE suppress growth at the organismal and molecular level via inhibition of growth-related signaling cascades and repression of gene expression elements of the GH-IGF system.National Science Foundation (IOS 0920116 to M.A.S.)
NDSU Doctoral Dissertation Fellowship
NDSU Department of Biological Sciences Teaching Fellowship
North Dakota Water Resource Research Institute
North Dakota State University Gordon A. Larson Agricultural Research Fund
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Chrisoulidou, Alexandra. "Effects of growth hormone treatment on intermediary metabolism and cardiovascular risk factors in adult hypopituitarism." Thesis, Imperial College London, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268361.
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Painson, Jean-Claude. "Effects of intracellular glucopenia on pulsatile growth hormone secretion : mediation in part by somatostatin." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63392.
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Schuenke, Mark D. "Effects of growth hormone (GH) disruption on muscle fiber type composition in mouse hindlimb /." View abstract, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3234227.
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Parini, Paolo. "Hormonal regulation of hepatic cholesterol and lipoprotein metabolism : effects of estrogen and growth hormone /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3372-3/.
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Moftah, Souad A. M. "The effects of growth hormone receptor-associated ERK activation on adipocyte differentiation and function." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/46265/.
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Growth hormone (GH) modulates adipocyte function to promote lipolysis via a cell surface GH receptor (GHR) which activates multiple signalling cascades including STAT5 and p42/44 MAP kinase (MAPK) pathways. The growth promoting effects of GH are mediated primarily by STAT5 activation but little is known about pathways mediating the effects of GH on adipocyte function. We therefore studied the effect of GH on STAT5 and MAPK (ERK) activation in the 3T3-L1 mouse pre-adipocyte cell line during adipogenesis. Cells were plated, allowed to reach confluence and cultured in adipogenic medium containing the PPARg agonist, pioglitazone. GH induced activation (10 minutes exposure) of STAT5 and MAPK was analysed on days 0, 2, 5 and 8 during adipogenesis by phospho-specific western blotting and densitometry. During adipogenesis, GH progressively loses the ability to activate p42/44 MAPK despite elevated GHR and unaltered total ERK levels. In contrast, GH-stimulated STAT5 activation increases as 3T3-L1 differentiation proceeds. Subsequently we investigated possible explanations for the altered GHR signalling. The adapter protein p66Shc is thought to be necessary to link GHR activation to the ERK pathway. However levels of this protein, measured by western blotting and densitometry, did not decrease as 3T3-L1 cells underwent adipocyte differentiation. GHR levels increase with adipogenic differentiation of 3T3-L1 cells leading us to hypothesize that this may lead to preferential association with JAK2-STAT5. This was tested by overexpressing the GHR in 3T3-L1; similar GH-stimulated ERK pathway activation was obtained in cells transfected with the GHR vector and in those transfected with the empty vector. Finally, we have investigated whether changes in GHR signalling also occur during adipogenesis of primary pre-adipocytes from mice and various human depots. There was minimal GH-induced phosphorylation of ERK at all-time points before and during differentiation (required up to 15 days in primary cells) and no depot, either murine or human, demonstrated a reduction in p ERK, suggesting that this feature is unique to 3T3-L1. Furthermore, ERK phosphorylation may be the stimulus for mitotic clonal expansion which occurs in the cell line but not in human primaries. GH-stimulated STAT5 activation increases as human and mouse primary pre-adipocytes differentiation progresses, as in the 3T3-L1 cell-line, and may be the result of increased GHR transcript levels as differentiation proceeds. Future studies could investigate the mechanisms responsible for these similarities and differences.
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Sayeed, Sabina. "The effects of topical thyroid hormone application on growth factor expression in human fibroblasts." Thesis, Boston University, 2013. https://hdl.handle.net/2144/12215.
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Thesis (M.A.)--Boston UniversityIt has long been known that thyroid hormones (TH) are essential for normal growth, development and cell metabolism. Studies have also shown that topical TH application can increase epidermal cell proliferation and accelerate the process of cutaneous wound healing. Despite these promising results, few researchers have examined the mechanisms and mediators through which TH may exert its effects on skin cells. In this study, human fibroblasts were stimulated with increasing triiodothyronine (T3) concentrations. A western blot was then conducted on the stimulated cell samples to determine whether two key growth factors – epidermal growth factor (EGF) and fibroblast growth factor (FGF-7) – that have been implicated in wound healing were upregulated due to topical T3 stimulation. It was found that while EGF (indirectly detected via the presence of the epidermal growth factor receptor (EGFR)) trended towards being upregulated at higher T3 concentrations, no such effect was observed with FGF-7. It was therefore determined that the EGF pathway may be an important mechanism through which TH exerts its effects on human fibroblasts and the process of cutaneous wound healing.
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Joseph, Franklin. "Parathyroid hormone sensitivity, parathyroid hormone circadian rhythm and phospho-calcium metabolism in the development of osteoporosis : the effects of age, bone mineral density, gender and growth hormone." Thesis, University of Liverpool, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631692.
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Thomas, Julia Dominique Janine. "The characterisation of growth hormone-related cardiac disease with magnetic resonance imaging & The effects of growth hormone dysregulation on adenosine monophosphate-activated protein kinase in cardiac tissue." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/5391.
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Chronic growth hormone (GH) excess, acromegaly, causes a specific cardiomyopathy, which remains poorly understood. The pattern of hypertrophy is distinct from other forms of cardiac disease and begins to appear before hypertension or diabetes. GH deficiency (GHD) also causes cardiovascular problems, with reduced ability to mount a cardiovascular response to exercise. Acromegaly and GHD patients have increased cardiac mortality. Cardiac magnetic resonance imaging (CMR) is the gold standard for assessment of cardiac mass and provides data on cardiac function, fibrosis, valve function and ischaemia. This study used CMR to assess 23 patients with acromegaly or GHD, before and after treatment of their GH disorder, and 23 healthy controls. Patients with acromegaly demonstrated increased left ventricular mass index (LVMi), end diastolic volume index, stroke volume index and cardiac index, which persisted at one year, despite treatment of underlying disease. Patients with GHD demonstrated LVMi at the bottom (males) or beneath (females) published normal references ranges, which increased with one year of GH replacement. The mechanisms by which GH influences cardiac tissue are poorly understood. Adenosine monophosphate-activated protein kinase (AMPK) is an energy-regulator enzyme, which interacts with several metabolic hormones. Mutations in AMPK cause arrhythmias and cardiac hypertrophy. AMPK activation may be a mechanism by which GH causes some of its cardiac effects. This study used primary cardiomyocytes and mouse and rat models of GH excess and deficiency to study the effects of GH on cardiac AMPK. Acute GH treatment increased AMPK activity in both in vivo and in vitro studies; acute IGF-I treatment had the opposite effect. In 2 and 8 month old bovine GH-overexpressing (bGH) and GH receptor knock out (GHRKO) mice, functional AMPK assay did not demonstrate any difference in cardiac AMPK activity between transgenics and controls. However, Western blotting for Threonine-172 phospho (p)AMPK levels, a marker of AMPK activity, demonstrated increased cardiac pAMPK in 2 month old bGH mice and a reduction in cardiac pAMPK levels in 8 month old animals. A trend towards the same findings was seen in GHRKO mice. This indicates that both GH and IGF-I interact with myocardial AMPK, apparently via different mechanisms.
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Louis, Audreen. "Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=2016041531&sid=1&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Thesis (M.S.)--Southern Illinois University Carbondale, 2008."Department of Molecular Biology, Microbiology, Biochemistry and Cell Biology." Includes bibliographical references (p. 55-63). Also available online.
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Hennig, Mathias. "Effects of bovine growth hormone on the resistance of rainbow trout, Oncorhynchus mykiss, to vibriosis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq37547.pdf.
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Saenz, Christopher M. "Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/70385.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 37-42).
Chronic stress has been linked to variation in gene regulation in the hippocampus (HIP) among other areas. These lead to cytoskeletal and volumetric rearrangements in various nuclei of the central nervous system and are thought to contribute to several stress-sensitive disorders. One such gene that has been shown to be downregulated in HIP in response to stress is somatotropin, colloquially known as growth hormone (GH). These experiments were conducted to develop a novel assay for examination of working memory in rats and explore the nature of stress-induced impairment of hippocampal function and determine whether infusion of a modified herpes simplex virus (HSV) carrying the recombinant rodent growth hormone (GH) would be sufficient to restore normal hippocampal function. After 21 days of chronic immobilization stress (CIS), animals received bilateral infusions into the dorsal HIP of 2[mu]l HSV carrying either GH with green florescent protein (GFP) or GFP only. On the second day following the infusion, the animals received trace conditioning, a HIP-dependent task, with five tone-shock pairings of a 16 second tone followed by a 30 second trace interval terminating with a 1 second 0.85 milliamp footshock. An inter-trial interval of 3 minutes was used to separate the tone-shock pairings. The following day the animals were tested for fear to the context and for fear to the tone in a novel context, measured by amount of time the animal spent freezing. Using this criterion, animals that had undergone stress that received the control vector were less likely to freeze when presented with the tone, indicating an impairment of hippocampal function. Viral-mediated overexpression of GH in the dorsal HIP was able to reverse the CIS-related impairment in hippocampal function. ELISA was used to verify the expression of GH from the infused vector. These experiments may yield future directions of investigation for stress-based disorders.
by Christopher M. Saenz.
S.M.
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De, Jesus Kristine. "The effects of IGF-I overexpression on somatic growth and bone deficiency caused by growth hormone receptor knockout in mice." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66804.
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Growth hormone (GH) and IGF-I are essential for somatic growth, while exerting distinct effects on energy homeostasis. GH controls IGF-I production, but whether IGF-I exclusively mediates the growth effect is still debated. To explore the in vivo interactions of GH and IGF-I, we crossed IGF-I-overexpressing mice (MT-IGF) onto the GHR-/- background. We found that bitransgenic mice (GHR-/- and MT-IGF positive) exhibited fully restored body weight, lumbar, and body lengths, and normalized bone area, mineral content, and density. IGF-I overexpression also corrected glucose intolerance in GHR-/- mice. Significant changes in fasting glucose levels, glucose tolerance, lean/fat mass, and adipose histology were also observed. Intriguingly, on a GHR+/- background, overexpression of IGF-I significantly increased body weight. Our results establish that the growth defect caused by GHR gene deficiency can be restored by increasing IGF-I in vivo, and strongly supports the notion that IGF-I mediates most of the growth promoting effects of GH.L'hormone de croissance et IGF-I jouent un rôle essentiel dans la croissance somatique et sont également impliques dans l'homéostasie énergétique. L'hormone de croissance (GH) contrôle la production d'IGF-I, mais l'action exclusive d'IGF-I sur la croissance reste discutée. Pour étudier in vivo les interactions entre GH et IGF-I, nous avons croisé un modèle de souris transgénique surexprimant IGF (MT-IGF) avec des souris knock-out GHR-/-. Nous avons trouvé une récupération complète du poids corporels, de la longueur des lombaires et de la taille des souris, ainsi qu'une normalisation de la composition minérale et de la densité osseuses, chez les souris bitransgeniques (GHR-/- et MT-IGF). Il y avait également une correction de l'intolérance au glucose chez les souris bitransgenique. Des changements significatifs de la glycémie à jeun, de la tolérance au glucose, des masses grasse et maigre ainsi que l'histologie du tissue adipeux ont également été observés. Étrangement, la surexpression d'IGF-I chez des souris transgéniques GHR+/-, augmente significativement leur poids corporel. Nos résultats établissent qu'une perturbation de la croissance induite par déficience en GHR peut être rétablie par l'augmentation in vivo d'IGF-I, et induisent fortement qu'IGF-I est un médiateur des effets promoteurs sur la croissance de GH.
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Madon, R. J. "A study of insulin secretion, and the galactopoietic effects of growth hormone in the lactating rat." Thesis, University of Liverpool, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381368.
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Pisoni, Lucia Pisoni. "The Effects of Supplementing Prebiotics on Gut Permeability, Hormone Concentration, and Growth in Newborn Dairy Calves." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1530630980235327.
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Riley, Jr Lawrence G. "Growth regulation in the euryhaline Tilapia, oreochromis mossambicus: effects of gonadal steroid hormones and salinity on the growth hormone/insulin-like growth factor-I axis." Thesis, University of Hawaii at Manoa, 2003. http://hdl.handle.net/10125/6873.
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The Mozambique tilapia grows significantly faster and larger when raised in seawater (SW) than in fresh water (FW). Furthermore, there is a gender difference in the growth rates, with males growing significantly larger than females. The main objective of these studies was to investigate the endocrine mechanisms that regulate these differences in growth. Tilapia raised in SW grew significantly larger than those raised in FW, and treatment with 17a-methyltestosterone (MT) augmented growth in both salinities. There was a significant correlation between pituitary growth hormone (GH) mRNA and body weight. By contrast, plasma GH levels did not vary significantly among the groups. Plasma levels of insulin-like growth factor-I (IGF-I) and fish size varied in a correlated pattern, however not significantly. These results indicate that SW rearing and MT treatment stimulate the GH/IGF-I axis, and suggest that pituitary GH mRNA, at this stage of development, is a better indicator of growth than plasma levels of GH and IGF-I. Transfer from SW to FW for forty days, however, resulted in a significant decrease in growth rate compared with the SW control. The activity of the GH/IGF-I axis was elevated after transfer offish from SW to FW, suggesting a greater metabolic cost of osmoregulation in FW than in SW in tilapia. Tilapia exhibit a sexually dimorphic pattern of growth, males growing larger than females. Estrogen~) treatment in vivo induced a female-like GH/IGF-I profile in males, elevated plasma and mRNA levels of GH and vitellogenin (VTG), and suppressed plasma and liver mRNA IGF-I levels. In contrast, the androgen, Sa-dihydrotestosterone (DHT), induced a male-like GHlIGF-I profile in females, elevated plasma and liver mRNA levels of IGF-I, and suppressed plasma and mRNA levels of GH. Estradiol and DHT exhibited direct effects on liver production of VTG and IGF-I in a similar fashion to that observed in the in vitro studies. These findings suggest that E2 re-directs metabolic energy from growth (IGF-I production) and toward reproduction (VTG production). Collectively these data provide evidence that the increased growth observed in SW and in males is a result of more available metabolic energy directed toward growth.x, 121 leaves
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Acik, Eda. "Effects Of Carbon Sources And Feeding Strategies On Human Growth Hormone Production By Metabolically Engineered Pichia Pastoris." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12610881/index.pdf.
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In this study, effects of different carbon sources and their feeding strategies on recombinant human growth hormone (rhGH) production by Pichia pastoris were investigated by means of cell growth, recombinant protein production and expression levels of hGH and alcohol oxidase (AOX) genes. In this content, firstly, the strain to be used for high level rhGH production was selected between the two phenotypes, i.e., P. pastoris hGH-Mut+ and P. pastoris hGH-MutS. In this selection both phenotypes were compared in two different media containing glycerol/methanol or sorbitol/methanol and P. pastoris-hGH-Mut+ strain grown on medium containing 30 g/L sorbitol with 1% (v/v) methanol was found to have the highest hGH expression level and rhGH production level, 9.84x109 copies/mg CDW and 120 mg/L, respectively.
Thereafter, effects of sorbitol, mannitol, fructose, lactose, sucrose, citric acid, lactic acid and acetic acid were investigated by using P. pastoris hGH-Mut+ strain in laboratory scale bioreactors. Among them sorbitol and sucrose were selected to be compared for production in pilot scale bioreactors by adding them batch-wise at the beginning of induction phase with fed batch methanol feeding scheme at μ
=0.03h-1. It was shown that sucrose does not support cell growth as sorbitol although it does not repress recombinant protein production. Then three different feeding strategies were applied to develop sorbitol/methanol mixed feeding i) single sorbitol addition at t=0, ii) besides at t=0, adding second batch-wise sorbitol at t=9 h, iii) giving pulse methanol at t=24 h to trigger AOX promoter. These three strategies were compared with a production without addition of co-substrate sorbitol. Substrate consumption, cell growth, recombinant protein production and expression levels of hGH and AOX were investigated for these different feeding strategies. The highest cell concentration was achieved in third strategy as 55 g/L where the highest extracellular rhGH production (301 mg/L) was achieved in the second strategy, with addition of two times of sorbitol. For this highest recombinant protein production case, overall cell and product yield on total substrate were found as 0.17 g/g and 1.71 mg/g, respectively. Moreover, the highest hGH and AOX expression levels were obtained in this strategy.
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Zarkesh-Esfahani, Sayyed Hamid. "Effects of growth hormone and leptin on cytokine production and proliferation of human peripheral blood mononuclear cells." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392501.
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Schumm, Sean R. "Effects of Growth Hormone, IGF-1, or Combination Therapy on Muscle Fiber Type Composition in Diabetic Mice." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1308848028.
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Gibney, James. "The effects of long-term treatment with and withdrawal of growth hormone (GH) in GH deficient adults." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428027.
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Hill, Cristal M. "THE METABOLIC EFFECTS OF DIET-INDUCED OBESITY AND GROWTH HORMONE TREATMENT IN LONG-LIVED MICE WITH ALTERED INSULIN AND INSULIN-LIKE GROWTH FACTOR -1 SIGNALING." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/dissertations/1251.
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AN ABSTRACT OF THE DISSERTATION OF Cristal M. Hill, for the Doctor of Philosophy degree in Molecular Biology, Microbiology, and Biochemistry, presented on January 22nd 2016, at Southern Illinois University Carbondale. THE METABOLIC EFFECTS OF DIET-INDUCED OBESITY AND GROWTH HORMONE TREATMENT IN LONG-LIVED MICE WITH ALTERED INSULIN AND INSULIN-LIKE GROWTH FACTOR -1 SIGNALING MAJOR PROFESSOR: Dr. Andrzej Bartke It is well established that high calorie diets providing mostly fat and simple carbohydrates as nutrients promote obesity and are associated with metabolic syndromes such as type 2 diabetes and cardiovascular disease. However, the effects of these types of diets in genetically long lived mice remain to be fully elucidated. The effects of high calorie diets have been reported to induce inflammation and alter longevity. However, when viewed in the context of the growth hormone (GH) pathway, these types of diets that have negative impact on IGF-1 and insulin signaling. To examine high calorie diet and GH-treatment effects in long-lived mice, we designed a three part study using hypopituitary Ames dwarf mice that have primary altered endocrine signaling and Pregnancy Associated Plasma Protein-A knockout mice that have normal endocrine signaling. Most importantly, together these studies investigate the detrimental effects of high energy feeding promoting obesity and influencing adipokine profiles that regulate or alter insulin/ IGF-1 signaling that may possibly impair glucose homeostasis in the context of the GH-axis. Longevity and aging are influenced by common intracellular signals of the insulin/insulin-like growth factor (IGF)-1 (IIS) pathway. Abnormally high levels of bioactive IGF-1 increase the development of various cancers and may contribute to metabolic diseases such as insulin resistance. Enhanced availability of IGF-1 is promoted by cleavage of IGF binding proteins (IGFBPs) by proteases, including the pregnancy associated plasma protein-A (PAPPA). In vitro, PAPPA is regulated by pro-inflammatory cytokines (PICs) such as interleukin (IL)-6 and tumor necrosis factor -a (TNF-a). Mice born with deficiency of the Papp-a gene [PAPP-A knockout (KO) mice] live ∼30–40 % longer than their normal littermates and have decreased bioactive IGF-1 on standard diets. In the first study, our objective was to elucidate how the effects of high-fat, high-sucrose diet (HFHS) promote obesity, induce metabolic dysfunction, and alter systemic cytokine levels in PAPP-A KO and normal mice. We show that PAPP-A KO mice fed HFHS diet for 10 weeks were more glucose tolerant and had enhanced insulin sensitivity compared to normal mice fed identical diet. PAPP-A KO mice fed HFHS diet had lower levels of pro-inflammatory cytokines (IL-2, IL-6, and TNF-α) compared to normal mice fed the same diet. Moreover, anti-inflammatory cytokine (IL-4 and adiponectin) levels were higher in PAPP-A KO mice fed HFHS diet compared to normal mice fed HFHS. Circulating PAPP-A levels were elevated in normal mice fed an HFHS diet compared to normal mice fed a standard, low-fat, low-sucrose (LFLS) diet. Indirect calorimetry, at 10 weeks of feeding HFHS diet, showed significantly increased oxygen consumption (VO2) in PAPP-A KO mice fed HFHS diet compared to normal mice fed the same diet. Furthermore, respiratory quotient (RQ) was significantly lower in PAPP-A KO mice fed HFHS diet compared to normal (N) mice fed HFHS diet indicating PAPP-A KO mice fed HFHS diet are able to rely on fat as their primary source of energy more so than normal controls. We conclude that PAPP-A KO mice are resistant to the HFHS diet induction of metabolic dysfunction associated with higher levels of anti-inflammatory cytokines and have a remarkably metabolically flexible phenotype and that some of the effects of HFHS diet in normal animals may be due to increased levels of PAPP-A. We continued our investigations of high calorie diet effects in long-lived endocrine disrupted Ames dwarf mice. Ames dwarf mice are hypopituitary, thus lacking the production of GH. GH stimulates the production of IGF-1; induces insulin resistance, alters inflammatory cytokine levels and can reduce life expectancy in both humans and mice. Disruption of GH signaling by reducing plasma GH levels significantly or deleting GH receptors extends health span and life span in mice as observed in Ames dwarfs. Metabolic stressors such as high-fat diet (HFD) may alter longevity through the GH signaling pathway. Our objective was to investigate the effects of HFD in Ames dwarf and control mice to elucidate the interactions on environmental (diet) and genetic mechanisms that regulate metabolism in aging processes. We show that Ames dwarf mice fed HFD for 12 weeks are sensitive to weight gain and increase in subcutaneous and visceral adiposity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed either standard diet (STD) or HFD. Interleukin 6 levels were lower in Ames dwarf mice fed HFD than control mice fed either STD or HFD. Energy expenditure was higher in Ames dwarf mice fed HFD than control mice fed STD or HFD. Moreover, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD is able to improve insulin sensitivity in control mice fed the same diet. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and the visceral adipose tissue of Ames dwarf mice can recuse metabolic dysfunction in control mice. In the third study, we investigated the effects of early-life GH-treatment in Ames dwarf mice starting at 1week of age. The focus of this study was to examine the metabolic effects of GH- treatment and HFD feeding during young age, which is the most critical time for biological maturation. In this study, one week old Ames dwarf and control mice were injected with either GH or saline for 6 weeks and fed STD. At 7 weeks of age, test for insulin sensitivity and calorimetric measurements were performed and the animals were subjected to diet switch from STD to HFD for 12 weeks post GH-treatment. With these preliminary data, we focus on the detrimental effects of GH-treatment during development and on the interaction of the effects of GH and diet. We first show that early-life-GH treatment in hypopituitary Ames dwarf mice induces a slight reduction of insulin sensitivity and decreased use of fatty acids as indicated by indirect calorimetry, thus promoting metabolic dysfunction. In addition, we show that the effects of early-life GH-treatment and high fat diet in Ames dwarf mice worsen insulin sensitivity and impair substrate utilization. We will continue to investigate the expression of genes that are associated with metabolism and longevity in these animals. Inhibition of proteases, such as PAPP-A, may be a therapeutic treatment to decrease the activity of biologically active IGF- to induce protection from metabolic dysfunction, including insulin resistance, in humans. Furthermore, it is not likely to inhibit GH/insulin/ IGF-1 signaling in healthy humans at young age, decreasing the activity of the insulin/ IGF-1 pathway at middle age may be beneficial in human therapies in the aims of protecting against metabolic dysfunction. Combined, these studies provide novel information on the interaction of the GH pathway and diets that induce obesity and metabolic dysfunction. Thus, mice with either primarily altered endocrine signaling or deletion of proteases that increase local IGF-1 signaling are protected from the detrimental effects of high calorie diets on metabolic function and energy expenditure.
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Bayraktar, Eda. "Effects Of Ph On Human Growth Hormone Production By Pichia Pastoris Considering The Expression Levels Of Regulatory Genes." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12610882/index.pdf.
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In this study, the aim was to investigate the effects of pH on therapeutically important protein, recombinant human growth hormone (rhGH), production by Pichia pastoris considering the expression levels of regulatory genes. In this frame, firstly the host microorganism was selected between two different methanol utilization phenotypes of P. pastoris, Mut+ and MutS on media containing glycerol/methanol or sorbitol/methanol. The highest rhGH production, 120 g L-1, and hGH gene expression, 9.84x109 copies mg-1 CDW, were achieved in the medium containing 30 g L-1 sorbitol and 1% (v/v) methanol by P. pastoris hGH-Mut+ strain. Thereafter, effects of pH on rhGH production and stability were investigated in laboratory scale bioreactors. RhGH was more stable at pH 5.0. Throughout the production, it is seen that medium of pH decreased.
Thereafter, effects of pH on rhGH were investigated in pH controlled pilot-scale bioreactor. In addition to rhGH concentration, AOX intracellular enzyme activity, extracellular proteases concentrationsexpression levels of hGH, AOX, pep4, prb1 and prc1 genes were determined. The highest cell concentration was obtained as 53 g L-1 at pH 6.0 but hGH concentration was found as 24 mg L-1 at t=24 h. The highest rhGH concentration was obtained as 271 g L-1 with 42 g L-1 cell density at pH 5.0 in medium containing sorbitol at t=24 h. At this condition, the overall product and cell yield on total substrate were found as 2.08 mg g-1 and 0.15 g g-1. Furthermore, the highest expression levels of hGH and AOX were attained at pH 5.0. Moreover, by keeping pH at 5.0, expression levels of three types of vacuolar proteases were minimized.
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Brabant, Peter J. III. "Effects of methoprene on the survivorship of adult Aedes mosquitoes: a strategy or inactivating released mosquitoes." UKnowledge, 2012. http://uknowledge.uky.edu/entomology_etds/1.
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Methoprene is a Juvenile Hormone (JH) analogue commonly used for the control of mosquito larvae. When applied to a mosquito breeding site, methoprene enters the haemolymph, where it mimics the function of JH and interferes with normal metamorphosis, resulting in larval mortality. Methoprene is commonly used for the control of larvae and has not been used as an adulticide, due to an absence of acute effects. This study evaluated possible chronic effects caused by the exposure of adult Aedes mosquitoes to methoprene. Methoprene was applied, in both technical grade and the commercially available Altosid®, topically to adults through droplet application on the abdomen and as a spray application. Mosquitoes were examined for treatment effects on ovary development, adult male and female mortality, and fecundity. The results demonstrate that relatively high doses are required to affect adult survivorship. In contrast, significant impacts on both fecundity and egg hatch were observed for females treated at the lower dosages. I discuss the results in relation to autocidal strategies for mosquito control in which the release of fecund females is to be avoided.
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Carroll, Paul Victor. "The metabolic effects of insulin-like growth factor-1 (IGF-1) in type 1 diabetes mellitus and the effects of glutamine supplementation, growth hormone and IGF-1 in critical illness." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391630.
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Lin, Chia-Hui. "The Effects of Growth Hormone in the Inner Ear of Zebrafish (Danio rerio) during Hair Cell Regeneration." TopSCHOLAR®, 2010. http://digitalcommons.wku.edu/theses/191.
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Although deafness is a universal problem, effective treatments have remained elusive. In order to develop potential treatments, an overall understanding of the cellular process of auditory hair cell regeneration, which occurs in fish but not mammals, must be established. A previous microarray analysis and qRT-PCR validation of noise-exposed zebrafish showed that growth hormone (GH) was significantly upregulated during the process of auditory hair cell regeneration. Thus, GH may play an important role during hair cell regeneration. However, cellular effects of exogenous GH in the zebrafish auditory hair cell regeneration have not been examined after noise exposure. To understand the effect of GH in hair cell regeneration, adult zebrafish were exposed to a 150 Hz pure tone at a source level of 179 dB re 1 μPa RMS for 36 hours. Afterward the fish were immediately injected intraperitoneally with carp recombinant GH (20 μg/gram of body mass) or buffer (0.1 M, pH 7.4 phosphate buffer) and then placed in a recovery tank. The effect of GH on apoptosis in fish inner ear end organs were examined using TUNEL-labeling. Cell proliferation was measured by BrdU incorporation assay. Hair cell regeneration was determined by phalloidin-labeling to allow visualization of hair cell stereociliary bundles. After GH injection, the numbers of TUNEL-labeled cells showed a significant decrease in all three inner ear end organs (saccule, lagena, utricle), suggesting GH may suppress hair cell death induced by acoustic trauma. Higher levels of cell proliferation were also observed in the ears of GH-injected fish, indicating that GH is capable of activating cell mitosis in the zebrafish auditory system. Following sound exposure, the GH-injected group exhibited greater numbers of saccular hair cell bundles compared to the buffer-injected group. These results indicate that GH promotes hair cell regeneration following acoustic damage. Future studies are needed to examine the potential therapeutic benefits of GH in the mammalian ear.
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Wang, Yajie. "The Time-Course of the Effects of Growth Hormone During Zebrafish (DANIO RERIO) Auditory Hair Cell Regeneration." TopSCHOLAR®, 2012. http://digitalcommons.wku.edu/theses/1171.
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Growth hormone (GH) was upregulated in the zebrafish inner ear following sound exposure in a previous study. To identify the specific role of GH in hair cell regeneration and the possible cellular mechanisms of this regeneration, groups of zebrafish were divided into baseline (no sound exposure, no injection), buffer-injected and GH-injected groups. Buffer- and GH-injected fish were exposed to a 150 Hz tone at a source level of 179 dB re 1 μPa root mean squared (RMS) for 36 h. Phalloidin-staining was used to assess the effects of GH on hair cell bundle density; BrdU-labeling was used to assess the effects of GH on cellular proliferation; TUNEL-labeling was used to assess the effects of GH on apoptosis in the zebrafish inner ear following acoustic trauma. The time-course of hair cell bundle density, cell proliferation, and apoptosis was established by combining data for baseline fishes and sound-exposed fishes at post-sound exposure day 1 (psed1), psed2, and psed3. GH-injected fish exhibited greater densities of hair cells than bufferinjected controls. In addition, GH-injected fish had higher levels of cell proliferation and lower levels of apoptosis than buffer-injected controls. This suggests that GH may play an important role in zebrafish inner ear hair cell regeneration by stimulating cellular proliferation and inhibiting cellular apoptosis.
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Zhou, Yinli. "Effects of Growth Hormone and Insulin-Like Growth Factor-I on Milk Protein Gene Expression and Nutrient Uptake and Cell Proliferation in Clonal Bovine Mammary Epithelial Cells." Diss., Virginia Tech, 2007. http://hdl.handle.net/10919/28940.
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The overall objective of this research was to further understand the mechanism by which growth hormone (GH) stimulates milk production in cattle. Three studies were conducted toward this objective. In the first study, the effects of GH and insulin-like growth factor-I (IGF-I), a major mediator of GH action in vivo, on cell proliferation, nutrient transport, and milk protein gene expression in bovine mammary epithelial cell line MAC-T cells were determined. GH increased (P < 0.01) expression of four major milk protein genes in MAC-T cells transfected with GHR expression plasmid. Cotransfection analyses indicated that GH also stimulated (P < 0.01) luciferase reporter gene expression from the promoters of the four milk protein genes in MAC-T cells. These findings together with the fact that GHR mRNA and protein are expressed in the epithelial cells of the bovine mammary gland suggest that GH may directly stimulate milk protein gene expression in the mammary gland. This study also showed that IGF-I increased the proliferation (P < 0.01) and amino acid transport (P < 0.05) in MAC-T cells. Because GH is known to stimulate IGF-I production in animals, IGF-I-mediated mammary epithelial cell proliferation and amino acid uptake may be additional mechanisms by which GH increases milk production in cattle. In the second study, the role of connective tissue growth factor (CTGF) on IGF-I-stimulated proliferation of MAC-T cells was investigated. A microarray analysis revealed that IGF-I decreased CTGF mRNA expression in MAC-T cells (P < 0.01). This effect of IGF-I was further found to be mediated through the PI-3 kinase/Akt signaling pathway from the IGF-I receptor (IGF-IR). CTGF alone stimulated MAC-T cell proliferation (P < 0.01). However, together with IGF-I, CTGF attenuated the proliferating effect of IGF-I on MAC-T cells, and this attenuation was reversed by additional IGF-I. Therefore, IGF-I inhibition of CTGF expression may benefit IGF-I stimulation of MAC-T cell proliferation. CTGF had no effect on IGF-I-induced phosphorylation of IGF-IR or total IGF-IR expression in MAC-T cells, suggesting that CTGF may attenuate IGF-I stimulation of MAC-T cell proliferation through a postreceptor inhibition of the IGF-IR signaling pathway. In the third study, whether a milk yield-associated T/A polymorphism in exon 8 of the bovine GHR gene affected GHR signaling was determined. It was found that the two corresponding GHR variants did not differ in mediating GH induction of gene expression, suggesting that the two GHR variants are not functionally different and hence are unlikely to mediate different effects of GH on milk production. In summary, the results of this dissertation research suggest that GH may directly stimulate milk protein gene expression and indirectly stimulate mammary epithelial cell proliferation and amino acid uptake through IGF-I, thereby stimulating milk production in cattle. The results also suggest that IGF-I stimulation of mammary epithelia cell proliferation may involve an inhibition of CTGF expression in the cells.Ph. D.
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Gardner, Christopher. "Mechanisms and effects of growth hormone deficiency (due to subarachnoid haemorrhage and traumatic brain injury) on quality of life and regional body composition, and the influence of hormone replacement." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2006206/.
Full textAbstract:
Aims of Thesis • Section 1 – To ascertain the incidence of non alcoholic fatty liver disease in patients with growth hormone deficiency and the impact of hormone replacement. • Section 2 – Validation of the glucagon stimulation test in healthy subjects and hypopituitary patients. • Section 3 – A prospective longitudinal study of pituitary function in survivors of Subarachnoid Haemorrhage and evaluation of changes in Quality of life following growth hormone replacement. • Section 4 – An analysis of the Pfizer KIMS database to evaluate changes in Quality of Life and Body Composition following Growth Hormone Replacement in patients with Traumatic Brain Injury.