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McCarthy, Anna Rose. "Biological Activity of Steroid Analogues:Synthesis and Receptor/Enzyme Interactions." Thesis, University of Canterbury. Chemistry, 2006. http://hdl.handle.net/10092/1293.
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This thesis investigates the biological activity of selected non-steroidal analogues of sex steroid hormones by examining two different effects of analogues on endogenous sex hormone activity. Non-steroidal analogues of sex hormones were synthesised to study their biological interactions with a sex steroid receptor and a sex steroid metabolising enzyme. Chapter One introduces the steroid hormones and their physiology, which leads to a review of the mechanisms by which steroids exert their effects. Their implication in disease is discussed, with particular emphasis on the sex steroids. As the biological activity of steroids is related to their chemical structure, the important features of steroid structure are identified, including the cyclopentanoperhydrophenanthrene nucleus, arrangement of ring substituents and ring junction conformation. The concept of non-steroidal analogues of steroids is introduced, and the harmful or beneficial effects analogues have on endogenous steroid activity are considered. Alteration of steroid activity and its consequences are focussed on two main areas; the potential adverse effects of environmental chemicals which mimic sex steroid activity, and the use of non-steroidal analogues in medicinal chemistry for treating sex steroid related disease. Chapter Two describes an investigation into the 17β-estradiol mimicking activity of non-steroidal analogues. Exogenous chemicals that mimic estradiol are of concern as they may alter endogenous estradiol activity and disrupt endocrine systems. Firstly, an introduction to the field of research concerned with environmental chemicals that mimic steroid hormones is given. The interaction of xenoestrogens with the estrogen receptor is described, as are the methods available for assessing the estrogen mimicking activity of xenoestrogens. The concern for insecticides mimicking estrogen activity is described by reviewing reported activities of insecticides, which leads into a discussion of work carried out as part of this thesis. Metabolites of the pyrethroid insecticides permethrin and cypermethrin, 2.14, 2.15, and 2.16 were synthesised while others were commercially obtained. The interaction of pyrethroid insecticide metabolites with the human estrogen receptor expressed in recombinant yeast (Saccharomyces cerevisiae) was studied, following the establishment and validation of the assay. Metabolites 2.11, 2.12, and 2.14 were found to weakly stimulate estrogen receptor-mediated estradiol responsive gene expression in the yeast assay (105 less active than 17β-estradiol). Since the activity of the metabolites using the yeast assay was greater than for the parent compounds, metabolic pathways need to be considered when assessing the impact of exposure to environmental estrogens. The low estrogenic activity suggests these compounds are not individually contributing significantly to the xenoestrogenic impact on humans, but will add to total xenoestrogen exposure. Chapter Three describes the inhibition of a sex steroid metabolising enzyme, steroid 5a-reductase, by novel non-steroidal compounds. Inhibitors of this enzyme are potentially useful therapeutic agents for regulating the activity of an androgen in prostate disorders. A review of the literature on non-steroidal inhibition of 5a-reductase identified three key structural features known to enhance inhibitor potency; ring substitution, position and nature of ring unsaturation and angular methyl group presence. These features were taken into account in the design of inhibitors synthesised in this thesis (3.55-3.57, 3.59, 3.61, 3.62, 3.110 and 3.111). Inhibitors consisting of non-steroidal 5- or 1-aryl pyridone scaffolds were synthesised to investigate SAR for 4'-substituents. The 5-aryl 1-methyl-2-pyridone/piperidone scaffold of compounds 3.55-3.57 and 3.59 was constructed by Suzuki cross coupling methodology, while the 1-aryl 2-methyl 2,3-dihydro-4-pyridone scaffold of 3.61 and 3.62 was constructed by aza Diels-Alder methodology. Long carbon chain olefin containing tethers 3.107 and 3.108 were synthesised for conjugation to inhibitor 3.57 by cross metathesis to give conjugates 3.110 and 3.111. Compounds 3.55-3.57, 3.59, 3.61, 3.62, 3.110 and 3.111 inhibited the type 1 5a-reductase isozyme expressed by HEK-I cells, with activities comparable to those of related literature compounds. The 1-aryl 2,3-dihydro-4-pyridone 3.62 inhibited both the type 1 and 2 isozymes (expressed by HEK-II cells) of 5a-reductase. The presence of bulky hydrophobic groups (benzoyl, long chain tethers) at the 4' position enhanced the potency of type 1 inhibition by 5-aryl pyridone type compounds in comparison to N,N-diisopropyl- and N-allylacetamide groups. This information provides further understanding of SAR within and across different classes of non-steroidal inhibitors of steroid 5a-reductase towards improved drug design.
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Panter, Grace Heather. "The oestrogenicity of steroids and steroid conjugates to fish." Thesis, Brunel University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246165.
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Awah, Edmund Kpabi. "Regulation of the indoleamines by sex steroids." Thesis, Rhodes University, 1992. http://hdl.handle.net/10962/d1004114.
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Alteration of serum tryptophan leads to parallel alterations in brain tryptophan levels. Such changes in brain tryptophan levels has been shown to lead to mood disturbances. The primary enzyme responsible for altering serum tryptophan levels is the liver cytosolic enzyme, tryptophan pyrrolase. Activation of this enzyme is responsible for the enhanced catabolism of circulating tryptophan. The purpose of the present study was firstly to establish whether there is a link between sex steroids and tryptophan pyrrolase activity especially since sex steroids are also known to cause mood disturbances and secondly to determine the effects of sex steroids on brain indolamine metabolism. The results show that all three sex steroids induce the activity of tryptophan pyrrolase implying that they decrease serum tryptophan levels by the activation of tryptophan pyrrolase, thus making less tryptophan available for uptake by the brain. It was also shown that the sex steroids enhance the uptake of ¹⁴C-tryptophan by brain synatopsomes. In addition, the sex steroids influenced the pattern of metabolism of serotonin by organ cultures of rat pineal glands. It is possible that the sex steroids regulate the availability and uptake of indoleamines in the brain.
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Lund-Pero, Margaretha. "Nonspecific esterases in human tissues evidence for their involvement in steroid metabolism and in carcinogenesis /." Lund : Dept. of Molecular Ecogenetics, the Wallenberg Laboratory, University of Lund, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39781861.html.
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Junker, Julia [Verfasser], and Franz [Akademischer Betreuer] Bracher. "Method development for the analysis of steroids, steroid acids and sterol sulfates in biological samples / Julia Junker ; Betreuer: Franz Bracher." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2021. http://d-nb.info/1234389185/34.
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Rebuffat, Alexandre G. Bernasconi Alessio Giacomo Ferdinando. "Steroid mediated gene delivery /." Bern : [s.n.], 2000. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Hejaz, Hatem Amin Moh'd. "The synthesis of steroidal and non-steroidal steroid sulphatase inhibitors for endocrine therapy of breast cancer." Thesis, University of Bath, 1998. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445677.
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Janer, Gual Gemma. "Steroid levels, steroid metabolic pathways and their modulation by endocrine disruptors in invertebrates." Doctoral thesis, Universitat Autònoma de Barcelona, 2005. http://hdl.handle.net/10803/3671.
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El invertebrats constitueixen el 95% de les espècies animals i, com en el cas dels vertebrats, són susceptibles a l'efecte dels disruptors endocrins (DEs). Tot i això, la comprensió d'aquest fenomen està limitada pel desconeixement del sistema endocrí dels invertebrats. L'alteració de la síntesis i metabolisme d'hormones esteroides és un dels possibles mecanismes d'acció dels DEs. En aquesta tesi s'ha caracteritzat el metabolisme d'hormones esteroides en diferents espècies d'invertebrats per tal d'avaluar l'efecte in vitro de DEs en aquestes espècies, i finalment investigar l'efecte in vivo de DEs en els nivells i el metabolisme d'esteroides en espècies d'un filum seleccionat (Mol·lusca). Les espècies investigades (Mollusca: Marisa cornuarietis, Mytilus sp., i/o Crassostrea virginica; Crustacea: Hyalella azteca; i Echinoderma: Paracentrotus lividus) van metabolitzar la testosterona a una sèrie de metabolits de fase I que també són formats per vertebrats, amb l'excepció de 4-androstene-3?,17?-diol, un metabolit format per P. lividus i H. azteca. Una de les diferències més importants amb els vertebrats va ser la baixa contribució de les hidroxilacions en el metabolisme de testosterona, i en el cas dels mol·luscs, el metabolisme d'androstenediona (reducció en 5??en comptes de reducció en 17?). Pel que fa al metabolisme de testosterona de fase II, les sulfotransferases es trobaven en nivells alts en P. lividus, però baixos o indetectables en H. azteca i totes les espècies de mol·luscs investigades. En canvi, tots els invertebrats estudiats presentaven una gran capacitat de conjugació d'hormones esteroides amb àcid grassos, una via que sembla que ha estat ben conservada al llarg de l'evolució. Els nivells d'hormones esteroides i algunes de les vies enzimàtiques que les metabolitzen van mostrar diferències estacionals, entre diferents teixits i entre sexes, fet que recolza la possible funció fisiològica de les hormones esteroides en invertebrats. Alguns xenobiòtics van interferir in vitro amb els enzims que metabolitzen les hormones esteroides. Entre les vies investigades, la 5?-reductasa i la sulfotransferasa, van mostrar la sensibilitat més alta a inhibició/activació per tributilestany (TBT), trifenilestany (TPT) i fenarimol. Per últim es va investigar l'efecte de l'exposició a estradiol, petroli, i la barreja de petroli i compostos alquilfenòlics en bivalves Mytilus sp., i l'exposició a metiltestosterona, TBT, TPT i fenarimol en el gasteròpode M. cornuarietis. El tipus d'efectes induïts per l'estradiol van dependre en gran mesura de la seva concentració. Algunes de les respostes observades en els musclos exposats a petroli o la barreja de petroli i alquilfenols, van ser similars a les que s'havien observat per concentracions altes d'estradiol. En aquests experiments es va observar també el possible rol que juga la conjugació d'esteroides amb àcid grassos en la regulació dels nivells d'esteroides lliures. L'exposició als compostos organoestànnics (TBT i TPT) va causar l'aparició d'imposex i va resultar en una reducció del nivell d'esteroides en forma esterificada en femelles de M. cornuarietis, però no en mascles. Els altres compostos avaluats (metiltestosterona i fenarimol) van induir imposex en femelles, però no van mostrar alteracions en els nivells d'esteroides esterificats, de manera que no es va poder demostrar la connexió entre la davallada dels nivells d'esteroides conjugats amb àcids grassos i el fenomen de l'imposex. L'exposició a TPT va inhibir 5?-reductasa en femelles de M. cornuarietis. Tot i així, cap dels dos organoestànnics va alterar el dimorfisme sexual en el metabolisme d'androstenedione que existeix en el complex glàndula digestiva/gònada d'aquest gasteròpode. En resum, aquesta tesi contribueix al coneixement del metabolisme d'andrògens en invertebrats i identifica dianes on poden actuar els disruptors endocrins.Ninety-five percent of all animal species are invertebrates, and like vertebrates, they are susceptible to endocrine disruption. Nevertheless, there are important gaps on the knowledge of the endocrine system of invertebrates that hinder the understanding of the endocrine disruption phenomena in those species. Steroid synthesis and metabolism is one of several possible targets of endocrine disruptors. This thesis aimed to characterize sex steroid metabolism in different invertebrate species, to test the in vitro effect of model endocrine disruptors in those species, and to test the in vivo effect of model endocrine disruptors on steroid levels and metabolism in species from a selected phyla (Mollusca). The species investigated (Mollusca: Marisa cornuarietis, Mytilus sp., and/or Crassostrea virginica; Crustacea: Hyalella azteca; and Echinoderma: Paracentrotus lividus) were able to form a series of phase I metabolites of testosterone that are also formed by vertebrates, with the exception of 4-androstene-3?,17?-diol, a metabolite formed by P. lividus and H. azteca. One of the major differences with vertebrate species was the lower contribution of hydroxylases in the metabolism of testosterone, and the metabolic fate of androstenedione in molluscs (5?-reduction instead of 17?-reduction). Regarding phase II metabolism of testosterone, sulfotransferases were found at high levels in P. lividus, but low or undetectable levels were present in H. azteca and the molluscan species investigated. In contrast, the conjugation of steroids with fatty acid moieties was present in all invertebrates investigated, showing that acyl-CoA:steroid acyltransferases are well-conserved through evolution. Steroid levels and the enzymatic activities for some metabolic pathways showed differences between males and females, among tissues, and between seasons in some invertebrate species, which adds further evidence for a physiological role of sex steroids in invertebrates. Some xenobiotics modulated steroid metabolic pathways in invertebrates in vitro. Among the pathways investigated, 5?-reductase and sulfotransferase showed the highest sensitivity to inhibition/activation by tributyltin (TBT), triphenyltin (TPT) and fenarimol. Finally, the effects of the exposure to estradiol, crude oil, and the mixture of crude oil and alkylphenolic compounds in Mytilus sp. and the exposure to methyltestosterone, TBT, TPT and fenarimol in the gastropod M. cornuarietis were investigated. The type of effects induced by estradiol depended greatly on the concentration. Some of the responses observed in mussels exposed to crude oil and the mixture of crude oil and alkylphenols were similar to those observed in mussels exposed to the highest concentrations of estradiol. Those experiments also showed that esterification seems to play a key role in the regulation of free steroid levels in bivalve molluscs. The exposure to the organotin compounds (TBT and TPT) caused imposex and decreased esterified steroid levels in females of M. cornuarietis, but not in males. Methyltestosterone and fenarimol induced imposex in females, but did not lead to alterations in esterified steroid levels. Therefore, the connection between a decrease of esterified steroids and the phenomena of imposex could not be proved. The exposure to TPT inhibited???-reductase in female M. cornuarietis. However, neither TPT nor TBT altered the sexual dimorphism in androstenedione metabolism that exists in the digestive gland/gonad complex of this snail species. Overall, this thesis contributes to the knowledge of androgen metabolism in invertebrate species and identifies possible targets of endocrine disruption.
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Opoku-Edusei, Justicia. "ROLE OF NEWLY SYNTHESIZED STEROID HORMONE ANTAGONISTS IN ADRENOCORTICO-STEROID HORMONE-INDUCED HYPERTENSION." VCU Scholars Compass, 1990. http://scholarscompass.vcu.edu/etd/4986.
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Excess adrenocorticosteroid hormones such as glucocorticoids and mineralocorticoids is well known to induce hypertension in several animal species as well as in humans. Therefore, the development of potent and specific glucocorticoid and mineralocorticoid antagonists with antihypertensive effects is clinically necessary. steroid hormone antagonists being used therapeutically present serious endocrinology side effects such as the widely used antimineralocorticoid, spironolactone. The antiglucocorticoids available so far have been active only in vitro or only weakly in viva. Recently, three new exciting adrenocorticosteroid hormone antagonists have been synthesized. RU 486 is a potent antiglucocorticoid (and antiprogesterone with potential as an abortifacient), RU 26752 and mespirenone, are novel mineralocorticoid antagonists. I studied the antihypertensive effect of RU 486, RU 26752 and mespirenone in Sprague- Dawley rats with dexamethasone- or aldosterone-induced hypertension. In addition, the effect of these antagonists on the hypertension developed by genetic model, spontaneously hypertensive rats (SHR) were also studied. The SHR is the closest animal model to human essential hypertension and it is believed that adrenocorticosteroid hormones are involved in the induction and maintenance of the hypertension. The results obtained from my studies showed that RU 486 administered simultaneously with dexamethasone prevented the hypertension induced by dexamethasone treatment. However, RU 486 had no effect on mineralocorticoid-induced hypertension. The administration of the antimineralocorticoid RU 26752 or mespirenone in combination with aldosterone successfully presented aldosterone-induced hypertension but not dexamethasone- induced hypertension. Surprisingly, RU 486 caused a significant increase in the blood pressure of the SHR whilst mespirenone caused a slight decrease in blood pressure as compared to control SHR.
The effect of these antihormones on body/organ weights, fluid intake and urinary output was observed. Morphologically examination of the heart and kidney showed no abnormalities with treatment. These results suggest that 1) RU 486 is specific in preventing dexamethasone-induced hypertension; 2) RU 26752 and mespirenone are successful in preventing aldosterone-induced hypertension and 3) mineralocorticoids may be involved in the development and maintenance of hypertension in the SHR.
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Whitmarsh, Samuel David. "Steroid based toroidal facial amphiphiles." Thesis, University of Bristol, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500447.
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The fields of anion recognition and anion transport are active areas of research within supramolecular chemistry. This project utilised choiic acid as an advanced starting material to produce a family of macrocyclic oligosteroids. The aim was to apply these novel materials to three separate supramolecular applications; firstly, to bind anions, secondly, to form pseudorotaxanes of DNA, and thirdly to effect the transport of anions across membrane bilayers.
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Stanway, Susannah J. "Steroid Sulphatase and Breast Cancer." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511888.
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Hearing, Stephen David. "Steroid resistance in ulcerative colitis." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324259.
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Di, Mambro A. J. "Cellular mechanisms of steroid resistance." Thesis, University of Bristol, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.683463.
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Inflammatory diseases of the bowel and liver form an important part of my clinical work as a gastroenterologist. Absent or reduced clinical response to steroids is detrimental to patient outcome in these conditions. This thesis serves to investigate the correlation between in vitro and in vivo steroid response in these inflammatory diseases and to elaborate further on the intracellular mechanisms by which a patient may fail to respond clinically to steroids with particular emphasis on the role of IL-2 and its effect on the glucocorticoid receptor. A greater understanding of these mechanisms may allow the development of diagnostic techniques and targeted therapies to enhance glucocorticoid response in steroid resistant patents and thus improve clinical outcome
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Biddle, Simon. "Steroid metabolism in racing greyhounds." Thesis, Loughborough University, 2014. https://dspace.lboro.ac.uk/2134/14878.
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The metabolism of androgenic anabolic steroids has been studied in the racing greyhound. Various drug preparations have been investigated utilising different derivatisation techniques, coupled with gas chromatographic analysis, to enable the identification of key metabolites in canine post administration samples. This has led to an increased understanding of some of the generic routes of steroid metabolism that take place in the greyhound. This valuable information can help to support metabolism studies in the future. The identification of specific metabolites for each compound investigated, has provided a means for controlling the misuse of these compounds, and contributed valuable enhancements to screening protocols utilised in the canine sports drug testing industry. Utilisation of the techniques described, resulted in the identification of specific major metabolites of the anabolic steroid methyltestosterone, namely 17??-methyl-5??- androstan-3??-17??-diol and 17??-methyl-5??-androstan-3??,16??,17??-triol. 16??- hydroxylation was shown to be a major phase I metabolic pathway in the canine along with phase II conjugation with glucuronic acid. Similar results were obtained during the metabolism study of the progestatgenic steroid norethisterone. Several di- and trihydroxy metabolites were detected in the glucuronic acid fraction of the post administration urines from this study. The norethisterone metabolism study also provided some insight, into the area of trace contaminants of pharmaceutical preparations. Low levels of nandrolone metabolites were also detected in the norethisterone post administration urine samples, leading to the discovery that the administered pharmaceutical tablets contained small quantities of nandrolone and 19- norandrostenedione, albeit below FDA approved contaminant levels. Modern methods of drug screening employ such highly sensitive techniques, that they allow for the detection of metabolites of such trace contaminants, following administration of the drug preparation to the greyhound. It is therefore important to have a broad understanding of the metabolism of various drug preparations, both banned and permitted substances alike; as detection of a trace amount of a banned substance metabolite, arising from the administration of a permitted medication, whose iii metabolite profile is unknown, and therefore potentially not detected, could present an interesting case. In conjunction with research into controlling the use of banned substances for the purposes of suppressing oestrus in the greyhound bitch, an investigation into normal/reference levels of endogenous hormones has been carried out. The endogenous steroid levels in a population of 212 greyhound bitches have been studied with a view to establishing a method for the detection of the exogenous administration of the endogenous anabolic steroid testosterone. The major urinary metabolites investigated were epiandrosterone, 5??-androstane-3??,17??-diol and 5??-androstane-3??,17??-diol. Statistical evaluations have been carried out to support the implementation of a suitable threshold for the key testosterone metabolites, namely 5??-androstane-3??,17??-diol and epiandrosterone. The detection of 5??-androstane-3??,17??-diol was found to be a very good indicator of the exogenous administration of testosterone to the greyhound bitch, when compared with the reference population data for this metabolite. However, further statistical/analytical data evaluation was deemed necessary before an absolute threshold could be implemented for this analyte, for the purposes of controlling the misuse of testosterone in the racing greyhound bitch. To support the understanding of endogenous steroid levels in the female greyhound, yet further, the endogenous reproductive steroid profiles were measured throughout the entire oestrus cycle of a cohort of 33 racing bitches. The results of the study clearly indicate a surge in androgen metabolites during the first 7-10 days of the oestrus cycle, in particular epiandrosterone and 5??-androstane-3??,17??-diol. This unique set of data has provided detailed information regarding the fluctuating concentrations of androgen and progesterone metabolites (following ovulation), at key stages of the canine oestrus cycle. The information obtained from this research can be used to support regulatory decisions regarding the misuse of testosterone in the racing greyhound bitch.
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Dybowski, Richard. "A steroid profiling expert system." Thesis, University of Leeds, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235634.
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Maclean, Andrew George. "Steroid modulation of neutrophil function." Thesis, University of Glasgow, 1997. http://theses.gla.ac.uk/38970/.
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Dexamethasone, a glucocorticoid, is used extensively in clinical medicine in the treatment of respiratory diseases, notably asthma. This medical effect is probably due in part to a down-regulation of many cytokines, e.g. IL-8. However, the side effects of steroids often may outweigh the beneficial effects, especially if the disease in question is of a chronic nature. This combined with steroid resistance has led to an increase in the use of non-steroidal anti-inflammatory drugs. These tend to be aspirin derivatives, and many have side-effects. I have investigated a factor that is naturally produced by the body which may alleviate the symptoms of inflammation without many of the side- effects, with an aim to providing a viable alternative. A novel steroid induced monocyte derived factor was described twenty years ago by Stevenson as part of an MD thesis submitted to this university. This remains an unusual phenomenon, as most of the effects of steroids are due to a down-regulation of release; here is one of the few examples of the reverse. Although it raised many interesting points about dispersive motility of populations of polymorphonuclear leukocytes (PMN) it did not look at individual cells, nor at many of the interesting properties of neutrophils. One of the known effects of some steroids (though not Dexamethasone), and many NSAIDs, is a reduction of adhesion of PMN to venous endothelium. Human umbilical vein endothelial cells (and bovine aorta endothelium) were used as an ex vivo model for this, and my results show there is a marked decrease in this adhesion. This effect was observed not only on resting endothelium, but also when the endothelial cells had been pre-treated with ILip or thrombin. This decreased adhesion was due to an interaction with the PMN and the factor, as shown by adhesion being reduced when protein coated coverslips were used as the substrate for adhesion. It is suspected that the reasons for this may be due to an inactivation of integrins such as Mac-1, although a role for selectins cannot be ruled out. Recent work by Diaz-Gonzalez suggests that some NSAIDs act by inducing PMN to shed L-selectin. Other effects of this steroid induced monocyte derived factor on human PMN were determined using biological and biochemical techniques. Previous work has shown a novel dispersive effect of this factor on PMN when used in a uniform concentration, and so I decided to look at the moiphology of treated PMN. Using scanning electron microscopy I observed a polarisation of the PMN, but without any raffling of the membrane, a feature that is normally observed with polarisation. This morphology was not observed with control supernatants taken from monocytes cultured in the absence of Dexamethasone. This moiphology was conserved using cells in suspension and adhered to bovine aorta endothelium. The underlying actin cytoskeleton was examined using confocal microscopy, and the microfilamentous airay was noted as being devoid of spikes, observed with activation, for example with fMLP. Late cytoskeletal controlled effects, the release of granule contents, were also investigated, and it was noted that the release of primary granule contents could be inhibited by this factor in a dose dependent manner. This fusion of granules with the plasma membrane is controlled by the activation of numerous tyrosine kinases, and follows a strict order. Secondary granule release was shown to be inhibited also, as assayed by the cleavage of type I collagen, and analysis of SDS gels. The effects on the metabolic burst showed conflicting results with inhibition being present, again in a dose dependent manner, but much of this activity was removed with increasing purification, leaving only very slight inhibition.
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RECCHIA, DEBORAH. "Steroid Myopathy: Understanding the pathogenesis." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1301291.
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Muscle plasticity is a key element in human health and disease. Exercise is an important element that leads to many positive adaptations, which improve survival and quality of life. Conversely, muscle atrophy is a condition found in many chronic diseases. Atrophy is the oucome of an imbalance between the processes that lead to protein synthesis (MPS) and the processes that lead to muscle protein breakdown (MPB) resulting in net muscle mass loss.
Chronic administration of glucocorticoids causes steroid myopathy characterized by muscle weakness, fatigue and atrophy. The primary pathogenetic phenomenon causing such condition is still unknown. The present study aims to identify the molecular phenomena involved in triggering the myopathic process.
To achieve such goal, the adapations of intracellular signalling pathways which have been previously shown to be potentially involved in steroid myopathy were studied. A single dose of desametasone (DEX) was administered intravenously to healthy subjects. Muscle biopsies were taken from vastus lateralis muscle 1h, 4h and 8h after DEX injection. Western blot and real time PCR were used to assess the adaptations of markers related to the ubiquitine-protesome degradation pathway (UPS),
protein synthesis, autophagy, muscle metabolism, redox status and mitochondrial remodelling.
Results suggest that DEX induced increased gene expression of Atrogin1, mitochondrial dysfunction and impairment of oxidative metabolism. The latter phenomenon would cause redox imbalance. Redox imbalance could further stimulate muscle MPB. This vicious loop results in an increased activation of the
autophagy pathway. The activation of the autophagy process together with the activation of the pathway of protein degradation would finally lead to muscle atrophy.
The ability by two-week intake of a mixture of branched chain amino to counteract the effects of DEX on intracellular pathways have been also tested. Preliminary data are reported.Muscle plasticity is a key element in human health and disease. Exercise is an important element that leads to many positive adaptations, which improve survival and quality of life. Conversely, muscle atrophy is a condition found in many chronic diseases. Atrophy is the oucome of an imbalance between the processes that lead to protein synthesis (MPS) and the processes that lead to muscle protein breakdown (MPB) resulting in net muscle mass loss. Chronic administration of glucocorticoids causes steroid myopathy characterized by muscle weakness, fatigue and atrophy. The primary pathogenetic phenomenon causing such condition is still unknown. The present study aims to identify the molecular phenomena involved in triggering the myopathic process. To achieve such goal, the adapations of intracellular signalling pathways which have been previously shown to be potentially involved in steroid myopathy were studied. A single dose of desametasone (DEX) was administered intravenously to healthy subjects. Muscle biopsies were taken from vastus lateralis muscle 1h, 4h and 8h after DEX injection. Western blot and real time PCR were used to assess the adaptations of markers related to the ubiquitine-protesome degradation pathway (UPS), protein synthesis, autophagy, muscle metabolism, redox status and mitochondrial remodelling. Results suggest that DEX induced increased gene expression of Atrogin1, mitochondrial dysfunction and impairment of oxidative metabolism. The latter phenomenon would cause redox imbalance. Redox imbalance could further stimulate muscle MPB. This vicious loop results in an increased activation of the autophagy pathway. The activation of the autophagy process together with the activation of the pathway of protein degradation would finally lead to muscle atrophy. The ability by two-week intake of a mixture of branched chain amino to counteract the effects of DEX on intracellular pathways have been also tested. Preliminary data are reported.
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Fischer, Katharina. "The mineralocorticoid receptor amino terminal transactivation domain investigation of structural plasticity and protein-protein interactions /." Thesis, Available from the University of Aberdeen Library & Historic Collections Digital Resources, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=24694.
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Thesis (Ph.D.)--Aberdeen University, 2008.Title from web page (viewed on Feb. 23, 2009). With: Natural disordered sequences in the amino terminal domain of nuclear receptors : lessons from the androgen and glucocorticoid receptors / Iain J. McEwan ... et al. Nuclear Receptor Signalling. 2007: 5. Includes bibliographical references.
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Seymour, Beverley Lesley. "The effect of steroid hormones on the size of myometrial cells : a morphometric study." Thesis, Cape Technikon, 1997. http://hdl.handle.net/20.500.11838/1503.
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Thesis (MTech (Biomedical Technology))--Cape Technikon, Cape Town,1997The aims of this study were to measure: 1. Myometrial cells of menopausal uteri to establish whether they atrophy after the menopause. 2. Myometrial cells at different phases of the menstrual cycle to investigate the influences of oestrogen and progesterone during the cycle. 3. Myometrial cells in the fundus and lower uterine segment to establish whether they differ in size. 4. Myometrial cells of pregnant uteri to investigate the effect of the hormonal status of pregnant women on the size of myometrial cells. 5. Neoplastic cells of leiomyomas of the uterus to investigate whether these benign tumours behave in the same manner as myometrium or, because they are neoplastic, they react differently. A preliminary investigation was undertaken to establish the optimal methodology for this study to measure myometrial and leiomyoma nuclei in the uterus. The aims of this preliminary investigation were: 1. To test the reproducibility of measurements of myometrial and leiomyoma nuclei in transverse and cross section. 2. To test five histological staining methods to ascertain the best method for a morphometric study on uterine cells. 3. To find the minimum sample size of nuclei per section of myometrium or leiomyoma in order to yield statistically significant results. This preliminary study found that the Haematoxylin and Eosin stain gave the most statistically reproducible measurements. Subjective assessment of the five staining methods also found Haematoxylin and Eosin to be optimal. It was also found during the preliminary study that measuring the myometrial nuclei in cross rather than transverse section gave the most statistically reproducible measurements. It was also found that it was best to use an axial ratio criterion of 0,9 when measuring cross-sectioned myometrial nuclei. The optimum sample size per section was also investigated and it was found that measuring 100 nuclei was optimal. It was found that in the uteri used in this study there was no statistically significant decrease in nuclear size after the menopause. It was also found that there was no statistically significant difference in nuclear size during the different phases of the menstrual cycle. There was also no notable difference in nuclear size between nuclei in the fundus and lower segment of the uteri in this study. It was found that there was a significant increase in the size of nuclei in leiomyomas compared to the normal myometrial nuclei from the same patient. The myometrial nuclei from pregnant uteri were also significantly larger than those from non-gravid uteri.
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Schwarcz, Leslie Esther. "Linking steroid hormone and Wnt signaling /." view abstract or download file of text, 2006. http://wwwlib.umi.com/cr/uoregon/fullcit?p3211226.
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Thesis (Ph. D.)--University of Oregon, 2006.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 71-82). Also available for download via the World Wide Web; free to University of Oregon users.
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Rosenberg, Zand Rachel Stacey. "Flavonoids and steroid hormone-dependent cancers." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ63739.pdf.
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Gunnarsson, Cecilia. "Steroid converting enzymes in breast cancer /." Linköping : Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med908s.pdf.
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Yingling, Eric P. "Professional Sports and Congress: Steroid Abuse." Scholarship @ Claremont, 2012. http://scholarship.claremont.edu/cmc_theses/413.
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I have examined the relationship between the U.S. Congress and professional sports—specifically, Major League Baseball. The focus of this examination was on the abuse of steroids in professional sports, and how certain constitutional limitations on Congress inhibited direct mandates on drug testing for individual players due to the Fourth Amendment. I have concluded that due to major league sports being for-profit ventures, economic motivations in the form of tax incentives were the most effective way for Congress to implement a tougher drug testing policy without violating the Fourth Amendment.
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Ndonji, John Kayombo. "Removal of steroid oestrogens form wastewater." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531993.
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Li, Warren. "Steroid mimics as inhibitors of aromatase." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319665.
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Saket, M. M. "Percutaneous absorption of some steroid esters." Thesis, Cardiff University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372583.
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Uyanik, Cavit. "Stereochemical studies in the steroid series." Thesis, University of Sussex, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390130.
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Al-Mana, D. "Ovarian steroid hormones and auditory function." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1386639/.
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Considerable anecdotal evidence and information from previous studies suggest that auditory function may be influenced by hormones. This thesis reviews in detail the potential role of hormones in modulating the auditory system and in the development of pathological conditions in the auditory system with an emphasis on the effect of the ovarian hormones. Ovarian steroids may influence auditory function directly through their receptors, which have been detected in the auditory system, or indirectly through their effects on the blood supply, the fluid electrolyte balance of the cochlea, and the neurotransmitters of the auditory system. Effects on other parts of the central nervous system connected to the auditory system may also be of importance. The aim of the study was to investigate whether physiological alterations in ovarian hormones in women with normal hearing, during the natural ovarian cycle and assisted conception treatment were associated with changes in auditory function at the cochlear and brain stem level, and whether these variations were not seen in men over a similar period of time. The auditory tests evaluated auditory function from the outer ear to the brainstem in both the afferent and efferent system. Hormone levels were assayed only in the female subjects at the same time as the auditory testing, four times during the ovarian cycle, or three times during the assisted conception treatment. Auditory tests were undertaken in the male subjects once a week for four consecutive weeks to correspond with the ovarian cycle measurements. A number of changes in auditory function were observed during the ovarian cycle and assisted conception treatment, and gender differences were noted. The OAE results may suggest either excitation of the cochlea with higher levels of oestrogen, or suppression of the cochlea with higher level of progesterone. The longer ABR latency following ovarian stimulation and in the follicular phase of the ovarian cycle is consistent with the inhibitory effect of neurosteroids on ABR associated with higher levels of oestrogen. The variation in auditory function were not observed in men.
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Farquharson, Roy G. "Fetal abstraction of placental steroid hormones." Thesis, University of Aberdeen, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328653.
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Angell, Peter James. "Cardiovascular consequences of anabolic steroid use." Thesis, Liverpool John Moores University, 2011. http://researchonline.ljmu.ac.uk/6126/.
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With the increase in the prevalence of anabolic steroid (AS) use for non-medical performance and image enhancement purposes, the impact of AS on cardiovascular health is an issue of growing public concern. AS use has long been associated with a number of negative CV outcomes such as acute myocardial infarction, stroke, thrombo-embolisms and sudden death. These associations, however, are largely assumed from case study findings where no cause and effect can be apportioned. Small cohort studies have suggested a negative effect of AS on a number of established CV disease risk factors including, blood pressure (BP), lipid profiles (e.g total cholesterol, LDL and HDL), C-reactive proteins and homocysteine, although data is limited both in number of studies and number of participants and is often contradictory. Another potential mechanism to link AS use to cardiac events has been to assess cardiac structure and function. Available data is contradictory but recent developments in imaging technologies suggest that new mechanistic insights could be developed and/or tested. In study one we investigated the impact of AS use on a broad profile of CV risk factors as well as an in-depth cardiac assessment utilising speckle tracking echocardiography which can assess regional and global cardiac deformation in multiple planes. In AS users we observed an increase in resting heart rate and low- density lipoprotein concomitant to a decrease in high-density lipoprotein levels. 2D and speckle-tracking echocardiography revealed a significant effect of AS use on cardiac function, most notably a decreased diastolic (relaxation) function that suggests a stiffer left ventricle in the AS users. This imposes a greater workload on the heart and increases the risk of CV events. In study two we developed the assessment of cardiac structural assessment in AS users by adopting state-of-the-art magnetic resonance imaging that provides a greater accuracy in morphology assessment as well as allowing us to determine the presence of perfusion defects and interstitial fibrosis. We observed that AS users had a hypertrophy of both the left and right ventricles that was concomitant with diastolic dysfunction in the left ventricle and a reduction in right ventricular contractility. Despite these findings no AS user presented with any perfusion defect or evidence of interstitial fibrosis, suggesting that these pathways to CV events were not apparent in the current group of AS users. The final study comprised two pilot or feasibility studies of the impact of resistance exercise on left ventricular function in AS users. Trial 1 assessed blood pressure and cardiac tissue velocities during an acute leg press with and without valsalva. Systolic blood pressure was significantly elevated even after one repetition and this was mediated by AS use. In trial 2 cardiac function and blood biomarkers of cardiac cell damage were assessed before and after a standard resistance exercise training session. Left ventricular systolic function was maintained in recovery in both AS and NAS participants. Diastolic function was reduced in both groups with some evidence that AS use exaggerated this effect. Multiple technical, design and participant lessons were gained to take these feasibility studies forward to full studies. Overall we add new data to the concept that AS use can place the participant at an increased CV risk. It is probably not obligatory that AS use leads to increased CV risk but in some the route from AS use to CV event may be mediated by changes in structure and function of both the L V and RV. Exercise stress may add an additional CV risk to the AS user.
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Liman, Mansur D. "Directing effects in some steroid reactions." Thesis, University of Sussex, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335508.
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Neunzig, Jens [Verfasser], and Rita [Akademischer Betreuer] Bernhardt. "The role of sulfonated steroids and parmaceutical compouds in steroid hormone biosynthesis / Jens Neunzig. Betreuer: Rita Bernhardt." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2014. http://d-nb.info/1064305865/34.
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Emanuelsson, Ida. "Steroids and steroid-metabolizing enzymes in the nervous system : Special focus on cell survival and sex hormone synthesis." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-328767.
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Some steroids in the brain and peripheral nervous system have been shown to have neuroprotective effects but the knowledge is limited. The present study examines the effects of steroids including oxysterols, vitamin D and vitamin D analogs on cell viability/growth and steroidogenesis in the nervous system. Both 24- and 27-hydroxycholesterol reduced staurosporine-induced toxicity in human neuroblastoma SH-SY5Y cells. In addition, 27-hydroxycholesterol decreased the staurosporine-mediated induction of caspases, known to be important in apoptotic events. From the findings it may be concluded that effects of oxysterols on cellular viability are dependent on the concentration and on the type of oxysterol. 24-Hydroxycholesterol was also found to attenuate oxidative stress both in SH-SY5Y cells and astrocytes. The results indicate that during some conditions, oxysterols may have neuroprotective effects. The vitamin D analogs tacalcitol and calcipotriol strongly reduced proliferation, cell viability and migration of human glioblastoma T98G cells, similarly as 1,25(OH)2D3 , the physiological form of vitamin D. Glioblastoma is the most lethal type of primary tumors in the CNS. These findings suggest that vitamin D analogs are potential candidates in treatment of brain tumors, most likely in combination with other therapies. Astrocytes were found to be a major site for expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) whereas expression of CYP17A1 was found in both astrocytes and neurons. 3β-HSD and CYP17A1 are important steroidogenic enzymes. Vitamin D inhibited both CYP17A1- and 3β-HSD -mediated activity and mRNA levels, with a stronger effect on mRNA expression than on enzyme activity. This indicates that 1,25(OH)2D3 could affect the production of sex hormones in the brain. In summary, results from this thesis contribute to the knowledge on the effects of oxysterols on cell viability and oxidative stress in cells from the CNS. Also the results provide data on the effects of vitamin D in the brain and suggest that vitamin D analogs may be promising candidates for treatment of certain brain tumors.
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Lee, Yan-yee Jacinta. "Ultrastructural basis of steroid-induced ocular hypertension." Click to view the E-thesis via HKUTO, 2010. http://sunzi.lib.hku.hk/hkuto/record/B43957869.
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Peter, Martin G., Peter C. Boldt, Yvonne Niederstein, and Jasna Peter-Katalinić. "Synthesen von Galactose-Cluster-haltigen Steroid-Derivaten." Universität Potsdam, 1990. http://opus.kobv.de/ubp/volltexte/2008/1678/.
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The synthesis of galactose clusters that are linked to a steroid moiety by a peptide-like spacer unit is described. The galactose cluster is obtained by Koenigs-Knorr glycosylation of TRIS-Gly-Fmoc (2b) under Helferich conditions. Peptide and ester bonds are formed after activation of carboxylic acids as diphenylthiophene dioxide (TDO) esters. 6a is synthesized in a convergent way by coupling of (Ac4Gal)3-TRIS-Gly (3e) with cholesteryl TDO succinate (5b). Coupling of (Ac4Gal)3-TRIS-Gly hydrogen succinate (3f) with Gly-O-Chol (5d) by means of EEDQ yields 6d. Reaction of (Ac4Gal)3-TRIS-Gly-SUCC-O-TDO (3g) with 25-hydroxycholesterol leads in a linear sequence to the oxysterol derivative 6f. Selective cleavage of the acetyl groups from galactose units yields the known compound 6b and the new derivatives 6e and 6g.
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McDonald, Sarah E. "Steroid pre-receptor signalling in human endometrium." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/24938.
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This work has shown that 11βHSD-1 mRNA is present at highest levels in the menstrual phase of the cycle and in first trimester deciduas, the times when an inflammatory response is evident. 11βHSD-2 mRNA and protein are present at all stages of the cycle, and also in first trimester deciduas. GR mRNA and protein are highly expressed throughout the cycle. MR mRNA expression varies across the cycle in a pattern similar to progesterone expression. 11βHSD-1 mRNA expression is increased in response to IL-1α and cortisol, and GR mRNA shows a similar trend. 11βHSD-1 and MR expression are not altered by IL-1α or cortisol.3βHSD-1 mRNA has been shown to be present only in first trimester deciduas; 3βHSD-1 is not detectable by these methods. Immunohistochemistry using an antibody which detects both 3βHSD-1 and -2 has shown low levels of protein in the tissues studied. AKR1C1-3 mRNAs are expressed throughout the menstrual cycle; all three enzymes are predominantly expressed in the secretory phase. AKR1C3 is localised to the glandular and surface epithelial cells, and vascular endothelium. AKR1C4 mRNA is not detectable in the endometrium at any stage of the menstrual cycle. Expression of steroid-metabolising enzymes is perturbed in the endometrium of users of a Levonorgestrel intra-uterine system, and also the following GnRH antagonist treatment for sub-fertility. These studies have shown that the endometrium has the ability to precisely regulate its balance of steroid hormone availability at a local level, and that this balance may be altered following administration of exogenous steroids. Further functional studies such as knockout or knockdown of these enzymes would expand this knowledge and fully elucidate steroid hormone metabolism and pre-receptor signalling.
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Wake, Deborah Jane. "Intra-adipose steroid metabolism in human obesity." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/27586.
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Glucocorticoid excess causes obesity, dyslipidaemia, insulin resistance and hypertension as seen in Cushing's syndrome. In idiopathic obesity, circulating Cortisol levels are not elevated but Cortisol metabolism is altered. liphydroxysteroid dehydrogenase type 1 (11HSD1) is an intracellular enzyme that converts inactive cortisone into active Cortisol. Data from animals suggests that elevated adipose 11HSD1 may generate more glucocorticoid within adipose tissue and be an important mediator of obesity and the associated metabolic consequences (diabetes, dyslipidaemia and hypertension). This thesis addresses whether adipose IIHSD1 is elevated in human obesity, investigates if this occurs through altered transcription, and assesses the downstream impact (changes in downstream target genes and metabolic outcomes). Regulation of 11HSD1 mRNA in animal and cell models (eg by high fat feeding, insulin, and PPAR agonists), and putative control of enzyme direction by NADPH generation (via hexose-6-phosphate dehydrogenase), suggest a dynamic role for 11HSD1 in the adaptive response of adipose to altered nutrition. The importance of these potential regulators in lean and obese humans is also addressed in this thesis. In subcutaneous adipose biopsies from male and female healthy volunteers from Finland (n=19), Sweden (n=27) and USA (n=35) 11HSD1 activity (in vitro conversion of Cortisol to cortisone in presence of NADP) and mRNA (by real time PCR) was increased in association with generalised and 'central' obesity (which is most strongly associated with increased cardiovascular risk), and predicted insulin resistance. However, glucocorticoid receptor mRNA was negatively associated with obesity and insulin resistance. Adipose mRNAs for a number of key functional adipose targets (adiponectin, LPL, HSL, angiotensinogen, resistin, aromatase, PPARy) were not significantly associated with 11HSD1 expression or activity. To investigate 11HSD1 regulation, a series of randomised controlled studies in vivo in healthy male volunteers were performed to assess the regulatory effects of insulin (euglycaemic clamp) or lipid (20% Intralipid iv) over 3.5 hours and PPAR agonists (rosiglitazone or fenofibrate for 7 d). Deuterated-cortisol tracer with GCMS analysis was used to measure whole body Cortisol turnover and urinary metabolite excretion, and intra adipose microdialysis was used to assess in vivo s.c. adipose 11HSD1 activity and directionality. Hyperinsulinaemia increased the rate of appearance of 9,12,12-[2H]3-cortisol in plasma, indicating increased regeneration of Cortisol by 11HSD1. Within adipose tissue, the predominant reaction was conversion of cortisone to Cortisol rather than Cortisol to cortisone; both activities fell during the first hour of hyperinsulinaemia but subsequently increased. Intralipid infusion had no significant effects on deuterated Cortisol metabolism, but increased intra-adipose conversion of cortisone to Cortisol. The PPARy agonist rosiglitazone lowered adipose 11HSD1 reductase activity. The PPARa agonist fenofibrate had no effect on adipose 11HSD1 activity although urinary ratios of Cortisol/ cortisone metabolites and endogenous Cortisol clearance were reduced. These findings may be suggestive of decreased liver 5alpha-reductase activity. There were no significant changes in plasma tracer kinetics with PPAR agonists. In addition to altered glucocorticoid metabolism, changes in sex steroid metabolizing enzymes dictating oestrogen (aromatase) and androgen (AKR1C2/3) action were found to be associated with fat distribution in s.c biopsies from Swedish (n=27) and Finnish (n=19) volunteers. Further studies to determine the functional relevance of these associations are planned. These studies implicate dysregulation of 11HSD1 transcription in the pathogenesis of human obesity and the metabolic syndrome although the downstream impact of enzyme dysregulation remains unclear. They also suggest that 11HSD1 is involved in the adaptive response to nutrition, and that alteration in tissue glucocorticoids may contribute to the therapeutic action of PPAR agonists. This understanding of enzyme regulation in humans will allow further studies to dissect the basis of dysregulation in obesity. Inhibition of adipose 11HSD1 remains an intriguing target for the treatment of obesity and its metabolic complications but its physiological importance will best be determined by the development of specific adipose 11HSD1 inhibitors.
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Gingnell, Malin. "Ovarian Steroid Hormones, Emotion Processing and Mood." Doctoral thesis, Uppsala universitet, Obstetrik & gynekologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-199791.
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It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones. The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids. In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported. In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex.
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Sideso, Odafe. "Biotransformation of steroid by a thermophilic bacillus." Thesis, Queen Mary, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243904.
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Brady, P. "A thermodynamic approach to steroid-based receptors." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596861.
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Chapter 1 begins with a brief overview of molecular recognition and then presents a review of recently developed methods for lead generation and the synthesis of self-defining host molecules. Chapter 2 describes a strategy for the synthesis of functionally active molecules which combines advantageous features of some of the methods described in Chapter 1. Relevant literature and precedents are then introduced followed by a discussion of theoretical considerations. In Chapter 3, after an introduction to the use of cholate building blocks in supramolecular chemistry, the synthesis of the new steroidal molecules studied is described, together with a discussion of their structural properties. Chapter 4 outlines the development of an effective method for the reversible macrocyclisation of steroidal building blocks by transesterification. The application of this method to the thermodynamically-controlled, and metal ion-templated, cyclisation of the steroid derivatives is then discussed in Chapter 5. An investigation into the metal ion building properties of the steroid derivatives using electrospray mass spectrometry is described in Chapter 6. The chapter begins with initial experiments to explore the circumstances in which the technique can generate meaningful information and then summarises the metal ion binding characteristics of the steroids investigated. Chapter 7 explores transorthoesterification as a milder reversible reaction for the synthesis of macrocycles and then describes initial studies towards a host capable of binding a porphyrin guest. In Chapter 8, the results of the cyclisation experiments and the binding study are compared with each other and put into the wider context of the long term goals of the project. That is followed by some ideas for future directions of this work.
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Lee, Yan-yee Jacinta, and 李茵怡. "Ultrastructural basis of steroid-induced ocular hypertension." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B43957869.
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Rayat, Harnak Singh. "The synthesis of potential steroid receptor antagonists." Thesis, University of Warwick, 1995. http://wrap.warwick.ac.uk/56111/.
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The first section of this thesis presents a review of the literature on endocrine hormones, synthetic steroids, and synthetic steroid receptor antagonists. Particular emphasis is placed upon the estrogen, progesterone and glucocorticoid activity of these compounds. The structure, activity and preparation of some progesterone/glucocorticoid receptor antagonists is also reviewed. The second section of this thesis presents a route for the synthesis of 19-aryl substituted androstanes. These compounds have been designed to explore their potential antiprogestational and antiglucocorticoid activity. It is demonstrated that a bulky aromatic functionality may be introduced at the sterically hindered C-19 methyl group, by the nucleophilic attack of an organometallic nucleophile on a 10~-formyl-19-norandrostane, which is suitably protected at positions C-3 and C-17. The subsequent careful manipulation of the C-3 and C-17 functionalities has led to a succesful 11 step synthesis (scheme 4.19) of 17~-hydroxy-17a-(prop-l-yne)-19-(p-N,N- dimethylaminophenyl)androst-5-en-3-one (3.1), which should be of interest for biological evaluation.
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Nahar, Luftan. "Synthesis and some reactions of steroid dimers." Thesis, University of Aberdeen, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274795.
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The main aims and objectives of this project have been to (i) synthesise pregnane (C21), dinorcholane (C22) and cholane (C24) steroidal monomers as precursors for the synthesis of steroid dimers, (ii) synthesis symmetrical and unsymmetrical steroid dimers via oxalate and simple ester linkages and (iii) perform flash vacuum pyrolysis (FVP) studies on synthesised oxalate steroid dimers in order to generate new steroidal derivatives. The chapter 1 of this thesis reviews the literature since the early part of 1997 on the synthesis of steroid dimers connected directly or via spacer groups in different ring systems as well as side chain through spacer groups. It also reviews the uses of synthetic dimers as molecular umbrellas and their potential applications in drug delivery in the lipid bilayer, and the occurrence of steroid dimers in various natural sources, such as plants and marine organisms, and their biological and pharmacological properties including anticancer activities. The synthesis of pregnane (C21), dinorcholane (C22) and cholane (C24) derivatives by several classical methods has been described in the chapters 2 and 3. The difficulties for the synthesis of C22 amino nitrile using Strecker synthesis and its corresponding acid have been explained. The synthetic routes for several new mixed C18, C21 and C24 anhydrides via oxalate ester formation have also been presented. The chapter 4 depicts the synthesis of several symmetrical oxalate dimers from various natural steroidal hormones such as estrone (C18), testosterone (C19), androstane (C19), pregnenolone (C21), bile acid (C24), cholesterol (C27) and stigmasterol (C29). The importance of the use of pyridine for the formation of oxalate dimers from primary alcohol has been evaluated experimentally. The synthesis of unsymmetrical dimers via side chain and ring A through simple ester linkage has also been presented in this chapter. Flash Vacuum Pyrolysis (FVP) technique and its use for the synthesis of dimers from oxalate dimers have been evaluated. It has been observed that none of the steroid oxalate dimers has produced any new dimers, instead yielded only monomeric olefins. The oximinyl oxalate dimers have been pyrolysed in similar fashion but the reaction has produced some volatile gas and no steroid derivative has been isolated. Interestingly, it has been noted that 5a-derivatives have produced 90% 2-end and 10% 3-ene compounds but 5b-derivatives have yielded solely 3-ene compounds. It has been easy to break 3-oxalate linkages at 600°C but 17-oxalate linkages have needed higher temperature. Possibly this has been because of the steric hindrance at 17-positon.
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Brotherton, Clare. "Synthesis and oxidation of tricyclic steroid analogues." Thesis, University of Aberdeen, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362235.
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The subject of this thesis is the synthesis and oxidation of tricyclic steroid analogues. The synthesis of the tricyclic derivatives, 1,2-dihydro-5-hydroxy-3H-benz[e]inden-3-ones, is described in chapter 1. The synthetic route involves the initial condensation of readily available acetophenone precursors with furfuraldehyde. Subsequent acidic hydrolysis of the resulting furanyl compounds afforded a diketo acid and/or furan acid depending on the nature and position of the substituent on the aromatic ring. Intramolecular condensation of the diketo acids provides a versatile intermediate in the cyclopentene acetic acid derivatives, the hydrogenation and alkylation of which is discussed in chapter 2. Cyclisation of the acetic acid derivatives with acetic anhydride and subsequent deacetylation provided the tricyclic phenolic compounds. The introduction of angular methyl groups in the cyclopentene acetic acid derivatives is discussed in chapter 2. Reductive methylation of these compounds using lithium in liquid ammonia failed, therefore, hydrogenation, followed by direct alkylation was investigated. Hydrogenation of the esters of the cyclopentene acetic acids gave a mixture of the desired reduced compounds along with the super hydrogenated cyclopentane derivatives. It has been shown that hydrogenation of such systems gives rise to two products, namely the trans cyclopentanone and the cis cyclopentane, the trans cyclopentanone arising through 1,4 addition. Permethylation of these cyclopentanones was achieved using KH, NaH and tBuOK. Chapter 3 deals with the oxidation of the phenols prepared in chapter 1 and the trimethyl compounds prepared in chapter 2. A short review on the oxidation of phenols forms the introduction. The oxidation of the tricyclic compound, 1,2-dihydro-5-hydroxy-3H-benz[e]inden-3-one, using a variety of different oxidising agents did not lead to quinone formation, however phenolic coupling was observed to give a biphenol. Oxidation of the permethylated compounds prepared in chapter 2 with DDQ gave the expected dehydrogenation products via a quinone methide intermediate.
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Yang, Chun. "Removal of steroid oestrogens in wastewater treatment." Thesis, Loughborough University, 2007. https://dspace.lboro.ac.uk/2134/33847.
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Intersex in river fish has been associated with unbiodegraded oestrogens in sewage treatment works (STW) effluents, leading to the proposal that they be regulated by Environmental Quality Standard. Previous literature indicated trickling filters (TF) were not as good as the activated sludge process (ASP) at removing steroid oestrogens. TF were more sustainable than ASP and there are more of them in the UK. One aim of this project was to investigate the performance of TF at removing these oestrogens. The removals of oestrone (E1), 17-β-oestradiol (E2) and 17-α-ethinyl oestradiol (EE2) by a well-controlled pilot-scale trickling filter were 41%–59% for once-through filtration.
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Smith, Gary D. "Steroid regulation of neuropeptides in sensory neurons." Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/20198.
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Primary afferent neurons with perikarya in the dorsal root ganglia (drg) mediate the transmission of sensory information from the periphery and viscera to the spinal cord. A number of neuropeptides, including substance P (SP), somatostatin (SS) and calcitonin gene related peptide (CGRP) have been localised in discrete but often overlapping subpopulations of drg neurons. These neuropeptides have been implicated in nociception and neurogenic inflammation, both processes which can be influenced by steroid hormones. Whilst steroid hormones have been shown to regulate synthesis of a number of neuropeptides including SP, SS and CGRP in the central nervous system, it is not known if they influence neuropeptides in the drg. In this thesis I have investigated the regulation of SP, SS and CGRP by steroids in vivo and in dissociated primary cultures of adult drg neurons. The SP, SS and CGRP content of drg from C1 to L6 was determined and a differential distribution of the three neuropeptides was found. Drg wet weight and SP content were greatest in drg from the cervical (C6 - T1) and lumbar (L4 - L6) enlargements. CGRP content tended to be greater in drg from more caudal areas (T10 - L6) and SS content was uniform in most drg but was notably lower in drg from area C5 - C7. The regulation of neuropeptides in the drg by two classes of steroid, adrenal steroids and androgens, was investigated. Adrenalectomy (ADX) of adult male Wistar rats increased SP and CGRP and decreased SS content of cervical drg. The effects of ADX were reversed by subcutaneous implantation of pellets containing corticosterone (B) or by daily subcutaneous injection of dexamethasone (DEX). The neuropeptide content of drg was not regulated by androgens; no significant change in the SP, SS or CGRP contents of drg were found following castration or administration of supraphysiological testosterone.
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Gans, Markus. "Synthese des antimykotisch aktiven Steroid-Alkaloids Plakinamin B - Azasteroide als Inhibitoren der Sterol-C-24-Methyltransferase." Diss., lmu, 2003. http://nbn-resolving.de/urn:nbn:de:bvb:19-14015.
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Janabi, Joseph. "Investigating Small Amine Molecules as Ice Recrystallization Inhibitors." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37779.
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Cryopreservation is a technique used to store cells and tissues for long time. It requires the addition of a cryoprotectant, which prevents damage to cells caused by the formation of large ice crystals. Few compounds have been classified as cryprotectants, and some of them are very toxic like DMSO. Our lab is interested in the synthesis of small, non-toxic cryoprotectants that possess ice recrystallization inhibition (IRI) activity. Much attention has been drawn towards small molecules that contain an amine group because they have some activity towards inhibiting ice recrystallization. Herein we have examined few monoamine and diamine molecules as well as PAMAM dendrimer for IRI activity. Some of the small molecules tested contain an aryl ring, and we found that changing the position of groups around the ring can have some impact in the IRI activity. We have also found that increasing the number of amines in a molecule can have little effect of the IRI activity. It is hoped that these findings can open new doors for further investigation in small amino molecules and the development of novel cryoprotectants.
Corticosteroids were first identified and isolated from both teleost and elasmobranch fish. Corticosterone and cortisol were measurable in the plasma of elasmobranchs and 1α-hydroxycorticosterone (1α-OH-B) was the dominant corticosteroid produced by the internal tissue. Limited amount of 1α-OH-B was synthesized because available supplies were exhausted in the early 1990s. Synthetic 1α-OH-B was used in steroid receptor studies to examine the evolution of the corticosteroid receptor system and measure stress levels.
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Stafford, M. A. "Epidural steroid injections for the treatment of sciatica." Thesis, Queen's University Belfast, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411804.
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Xu, Kai Harper Willie F. "Thermodynamics of steroid estrogen sorption to activated sludge." Auburn, Ala, 2008. http://repo.lib.auburn.edu/EtdRoot/2008/FALL/Civil_Engineering/Thesis/Xu_Kai_29.pdf.
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