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1
Hobbs-Mallyon, David. "Synthetic studies on tricyclospirodienones." Thesis, University of Nottingham, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315042.
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Khan, Usman 1980. "Peroxidase-catalysed oxidation of natural and synthetic hormones." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98980.
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One of the fastest growing concerns in the wastewater treatment industry is the presence of estrogenic compounds in wastewater effluents that may threaten the reproductive success and development of aquatic organisms. The fact that such contaminants have been detected in surface waters at potentially detrimental levels indicates that conventional treatment plants are unable to effectively remove them; hence, supplementary treatment technologies must be considered. As one of these, enzymatic treatment offers numerous advantages which make such a treatment methodology almost tailor-made for the selective removal of such contaminants. In order to evaluate the potential for enzymatic treatment to be used to target important estrogenic compounds, the enzyme-catalysed oxidation of selected potent estrogens including estradiol, estriol and ethinylestradiol was studied. Horseradish peroxidase (HRP) enzyme was selected as the candidate enzyme since it is amongst the most studied oxidative enzymes and has been investigated extensively in waste treatment applications. Experiments were conducted at concentrations higher than those found in typical effluents in order to characterize the reactivity of the enzymes toward these compounds without being hampered by analytical difficulties. In order to gauge the importance/relevance of the data obtained for the enzymatic oxidation of estrogens parallel experiments were also conducted with phenol, which has been the subject of many past studies as a substrate of HRP and for which the technical feasibility of enzymatic treatment has been well established.HRP was able to effectively catalyse the oxidation of estrogens over a wide range of pHs, with optimal performance in the pH range typically experienced in wastewaters. Measurements of the stoichiometry of the reaction between estrogens and peroxide and also the enzyme dose required to achieve certain target levels of substrate removal suggested that the enzymatic oxidation of estrogens consistently had lower peroxide and enzyme requirements than phenol. In fact, phenol required between 2.5 and 5 times more enzyme than the estrogens to achieve various target levels of removal. For all substrates studied, similar kinetics of removal were found, provided that sufficient enzyme was added to reactions to compensate for differences in substrate affinity. In contrast to earlier studies conducted with HRP, minimal inactivation of the enzyme was observed during the treatment of all substrates. The lesser inactivation observed in the present study was probably due to the very low concentration of target substrates used. Collectively, the results indicate that the removal of estrogens is likely to be more feasible than phenol itself. It is also suggested that since the estrogen concentrations utilized here were an order of magnitude higher than environmentally-relevant concentrations and since the enzyme dose required and the level of inactivation observed are directly related to the amount of substrate targeted for treatment, the feasibility of removing estrogens may be more favourable at environmentally relevant values, except where kinetic limitations may dominate.
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Jabbar, Ghulam. "Melengestrol acetate and norgestomet for the induction of synchronized estrus in seasonally anovular ewes." Thesis, This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-06232009-063050/.
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Fang, Min. "Removal of Natural and Synthetic Steroid Hormones through Constructed Wetland Microcosm." University of Toledo / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1292943388.
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Koubovec, Dominique J. B. M. "An investigation into the molecular mechanism of action of the progestins, medroxyprogesterone acetate and norethisterone acetate." Thesis, Stellenbosch : Stellenbosch University, 2004. http://hdl.handle.net/10019.1/70116.
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Thesis (PhD)--Stellenbosch University, 2004.ENGLISH ABSTRACT: Although the progestins medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A) are widely used in reproductive therapy, the steroid receptors and their target genes involved in the actions of MPA and NET-A are not well understood. Surprisingly, it had not yet been investigated whether doses of MPA and NET-A used for contraception and HRT cause significant side effects through various target genes via the glucocorticoid receptor (GR). In this thesis results of in vitro studies showed that, MPA, like dexamethasone (dex) and prog, significantly repressed tumour necrosis factor (TN F)-stimulated IL-6 protein production, and IL-6 and IL-8 promoter reporter constructs at the transcriptional level in L929sA cells, via interference with nuclear factor KB (NFKB) and activator protein-1 (AP-1) transcription factors. Like dex and prog, MPA did not affect NFKB DNA-binding activity. Furthermore, unlike dex and prog, MPA did not inhibit mitogen-activated protein kinase (MAPK) activity. The antagonistic effects of the GR and progesterone receptor (PR) antagonist, RU486, as well as the MPAinduced nuclear translocation of the GR, strongly suggest that the actions of MPA in these cells are mediated at least in part via the GR. Although the mechanism was not investigated as extensively as for MPA, NET-A was shown to repress IL-8 promoter reporter activity very weakly relative to dex, MPA and prog in Hek293 cells stably transfected with the rat GR. Furthermore, NET-A, like MPA, dex and prog did not interfere with the DNA-binding activity of NFKB. Significant transactivation of a GRE-driven promoter reporter construct by MPA and dex in L929sA via endogenous GR and COS-1 cells via expressed rat GR, and by MPA, dex and prog in Hek293 cells via expressed rat GR was also observed. In contrast, NET-A, unlike MPA, dex and prog showed no transactivation in Hek293 cells. MPA, NET-A and prog were shown to compete with dex for binding to the endogenous human GR in human lung carcinoma A549 cells. Similarly, MPA and NET-A were shown to compete with dex for binding to expressed rat GR in COS-1 cells. MPA displayed a higher relative binding affinity than NET-A for the GR in both systems, and a higher relative binding affinity than prog in A549 cells. Equilibrium dissociation constants (Ki values) for MPA (Ki = 10.8 ± 1.1 nM), NET-A (Ki = 270 ± 1.3 nM) and prog (Ki = 215 ± 1.1 nM) towards the human GR in A549 cells were also established. Furthermore, dose-response curves showed that MPA displays significantly greater GC agonist potency and efficacy than NET-A and prog for both transactivation of a synthetic GRE-reporter construct and transrepression of a synthetic IL-8 reporter construct via expressed rat GR in Hek293 cells, as NET-A showed no transactivation and very weak partial agonist activity for transrepression. Based on these observations, MPA behaves as a GR agonist whereas NET-A is proposed to be a weak antagonist. These results show that MPA and NET-A are not alike and not the same as prog in their mechanism of action via the GR, which may have serious health implications in vivo. Such insights may provide women and their clinicians with more information to facilitate the selection of contraception or reproductive therapy regimes with fewer side effects.
AFRIKAANSE OPSOMMING: Alhoewel MPA en NET-A algemeen gebruik word in hormoontherapie, is dit nie duidelik watter steroïedreseptore en teikengene betrokke is by die werking van MPA en NET-A nie. Verrassend is dat geen studie nog gedoen is om te bepaal of die dosisse van MPA en NET-A wat gebruik word in voorbehoeding en hormoonvervangingsterapie (HVT), newe-effekte veroorsaak deur die glukokortikoïedreseptor (GR) en verskeie teikengene nie. In hierdie tesis is in L929sA selle aangetoon dat MPA, net soos deksametasoon (dex) en prog, TNF-gestimuleerde IL-6 produksie onderdruk, en dat IL-6 en IL-8 promoter-rapporteerderkonstrukte op transkripsionele vlak onderdruk word deur middel van inmenging met NF-KB en AP-1 transkripsie-faktore. Net soos dex en prog het MPA nie die DNA-bindingsaktiwiteit van NF-KB beïnvloed nie. Anders as dex en prog het MPA egter nie MAPK aktiwiteit onderdruk nie. Die antagonistiese effekte van RU486, asook die MPA-geïnduseerde translokasie van die GR na die selkern, dui sterk daarop dat die effekte van MPA in hierdie selle ten minste gedeeltelik deur die GR geskied. Alhoewel die meganisme vir NET -A nie so breedvoerig bestudeer is as dié van MPA nie, is tog aangetoon dat, in Hek293 selle wat stabiel getransfekteer is met die rot GR, die onderdrukking van die IL-8 promoter deur NET-A baie swakker is as met dex, prog en MPA. Verder is daar ook gevind dat NET-A, net soos MPA, dex en prog, nie kon inmeng met die DNA-bindingsaktiwiteit van NF-KB nie. Beduidende transaktivering van 'n GRE-bevattende promoterrapporteerderkonstruk deur MPA en dex in L929sA en COS-1 selle, en deur MPA, dex en prog in Hek293 selle, is ook gevind. Daarteenoor het NET-A, anders as MPA, dex en prog, geen transaktivering in Hek293 selle getoon nie. Verder moes die relatiewe bindingsaffiniteit (ewewigs-dissosiasiekonstantes) van MPA, NET-A en prog vir die GR, asook die relatiewe sterkte en effektiwiteit vir transaktivering en transonderdrukking van verskeie teikengene deur die GR, ook bepaal word. Daar is gevind dat MPA, NET-A en prog meeding met dex vir binding aan die endogene GR in mens longkarsinoom A549 selle. Soortgelyk hieraan is ook gevind dat MPA en NET-A meeding met dex vir binding aan rot GR wat in COS-1 selle uitgedruk is. MPA het in beide sisteme 'n hoër relatiewe bindingsaffiniteit vir die GR getoon as NET-A, asook 'n hoër relatiewe bindingsaffiniteit as prog in A549 selle. Ewewigs-dissosiasiekonstantes (Ki waardes) vir MPA (Ki = 10.8 ± 1.1 nM), NET- A (Ki = 270 ± 1.3 nM) en prog (Ki = 215 ± 1.1 nM) vir die mens GR in A549 selle is ook bereken. Dosisrespons-grafieke het ook aangedui dat MPA 'n beduidend beter GC sterkte en effektiwiteit as NET-A en prog het, vir beide transaktivering van 'n sintetiese GRE-rapporteerderkonstruk en transonderdrukking van 'n sintetiese IL-8 rapporteerderkonstruk via rot GR wat uitgedruk is in Hek293 selle. Dit kon afgelei word aangesien NET-A geen transaktivering en slegs baie swak gedeeltelike agonisaktiwiteit vir transonderdrukking getoon het. Op grond van hierdie waarnemings tree MPA op as 'n GR agonis, terwyl dit lyk asof NET-A 'n swak antagonis is. Hierdie resultate dui aan dat MPA en NET-A nie dieselfde is nie, en ook nie dieselfde meganisme van werking deur die GR het as prog nie. Dit kan ernstige gesondheidsimplikasies inhou in vivo. Hierdie insigte kan dus meer inligting aan vroue en kliniese personeel verskaf om sodoende die keuse van voorbehoeding of voortplantingsterapie met minder newe-effekte te vergemaklik.
6
Fraser, Joanne Louise. "Influence of synthetic progestogens on platelet aggregation and arrhythmias associated with myocardial ischaemia." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343753.
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Riman, Tomas. "An epidemiologic study of epithelial ovarian malignancies : with a focus on hormone-related factors /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-362-7/.
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Tanner, T. M. "An investigation of the interactions of the androgen receptor with a non-steroidal compound and two synthetic progestins." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/52683.
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Thesis (MSc)--Stellenbosch University, 2002.ENGLISH ABSTRACT: The aim of this thesis was to define the interactions of the androgen receptor (AR) with an analog of a non-steroidal plant compound, Compound A (CpdA), as well as two synthetic progestins, medroxyprogesterone acetate (MPA) and norethindrone acetate (NET-A). The data presented indicates that CpdA has antiandrogenic properties, as it represses androgen-induced activation of both specific and non-specific androgen-responsive reporter constructs. It was found that CpdA exerts these effects by a mechanism other than competition with androgen for binding to the ligand-binding domain (LBD) of the receptor. On the other hand, it is demonstrated that both MPA and NET-A compete with androgen for binding to the AR and induce partial agonist activity via the receptor. Using mammalian two-hybrid assays it was revealed that CpdA, similar to anti-androgenic compounds that are able to compete with androgens for binding to the receptor, represses the androgen-induced interaction between the NH2- and COOH-terminals of the AR (N/C-interaction) without competing for binding to the LBD. Furthermore, it was shown that CpdA slightly represses the androgen-dependent recruitment of steroid receptor co-activator 1 (SRC1) to the activation function (AF2) domain of the AR. When the effects of MPA and NET-A on the N/C-interaction were studied, intriguing results were obtained. NET-A, as expected, induced this AR agonist-induced interaction. MPA, however, repressed this AR agonist-induced interaction, an effect previously associated with anti-androgenic activity, despite displaying partial agonist activity in transctivation experiments. On the other hand, both MPA and NET-A induced the interaction between SRC1 and the AF2 domain. In additional experiments with CpdA, it was found that CpdA did not affect the recruitment of SRC1 to the AF1 domain of the receptor; neither did it influence the constitutive activity of the NH2-terminal domain. The anti-androgenic activities of CpdA were confirmed by the toxic effect that this compound had on the androgen-dependent lymph node carcinoma of the prostate (LNCaP) cell-line as well as its ability to repress the androgen-induced expression of the prostate specific antigen (PSA) protein. Taken together, the results presented in this thesis, in combination with the knowledge available on AR function, contribute to an improved understanding of AR function. Furthermore, the importance of defining the precise mechanism by which individual compounds exert their effects is highlighted. In this regard it is demonstrated that two compounds (MPA and NET-A) that display partial agonist activity, can exert their effects via different mechanisms at the molecular level. Detecting such differences in the molecular mechanisms of action could facilitate the improved design of progestins as well as aid clinicians and their patients in selecting the best method of contraception. Lastly, the insights gained into the mechanisms of the anti-androgenic action of CpdA could be useful in therapeutic drug design for diseases, such as prostate cancer, that have an androgen-dependent etiology.
AFRIKAANSE OPSOMMING: Die doel van hierdie tesis was om die interaksies van die androgeen reseptor (AR) met ‘n analoog van ‘n nie-steroiediese plant verbinding, Verbinding A (VbgA), sowel as met twee sintetiese progestogene, medroksiprogesteroon asetaat (MPA) en noretiendroon asetaat (NET-A), te definieer. Die data verskaf dui daarop dat VbgA anti-androgeniese eienskappe besit deurdat dit androgeen-gei'nduseerde aktivering van beide spesifieke- en nie-spesifieke androgeen-responsiewe rapporteerderkonstrukte onderdruk. VbgA veroorsaak hierdie effekte deur ‘n meganisme wat nie kompetisie met androgeen vir binding aan die ligand-bindingsdomein (LBD) van die reseptor behels nie. In teenstelling hiermee word getoon dat beide MPA en NET-A kompeteer met androgeen vir binding aan die AR en gedeeltelike agonistiese aktiwiteit induseer via hierdie reseptor. Deur gebruik to maak van ‘n soogdier twee-hibried essai word getoon dat VbgA, soos ander anti-androgeniese verbindings wat kompeteer met androgeen vir binding aan die reseptor, die androgeen-gei'nduseerde interaksies tussen die NH2- en COOH-terminale van die AR (N/C-interaksie) onderdruk, sonder om te kompeteer vir binding aan die LBD. Daarby is dit bewys dat VbgA die androgeenafhanklike werwing van steroied reseptor ko-aktiveerde 1 (SRC1) na die aktiverings funksie (AF2) domein van die AR gedeeltelik onderdruk. Die studie van die effekte van MPA en NET-A op die N/C-interaksie het interessante resultate opgelewer. NETA, soos verwag, het hierdie AR agonis-gei'nduseerde interaksie geinduseer. MPA, aan die ander kant, het hierdie AR agonis-gei'nduseerde interaksie onderdruk, ‘n effek wat tevore met anti-androgeniese aktiwiteit geassosieer is, al het die transaktiveringseksperimente daarop gedui dat MPA ‘n AR agonis is. Aan die ander kant, het beide MPA en NET-A die interaksie tussen SRC1 en die AF2 domein geinduseer. In addisionele eksperimente met VbgA is gevind dat VbgA geen effek het op die werwing van SRC1 na die AF1 domein van die reseptor nie en ook geen invloed het op die konstitutiewe aktiwiteit van die NHh-terminaal domein nie. VbgA se antiandrogeniese eienskappe is bevestig deur die toksiese effekte op die androgeenafhanklike limfknoop karsinoom van die prostaat (LNCaP) sellyn sowel as deur sy vermoe om die androgen-gei'nduseerde uitdrukking van die prostaat spesifieke antigeen (PSA) protei'en te onderdruk. Die resultate aangebied in hierdie tesis, in kombinasie met die beskikbare kennis oor AR funksie, dra by tot ‘n verbeterde kennis van AR funksionering. Verder word die belang van die definiering van die meganisme waardeur individuele verbindings hulle effekte veroorsaak, getoon. In hierdie verband is getoon dat twee verbindings (MPA en NET-A), wat gedeeltelike agonistiese aktiwiteit besit, hulle effekte via verskillende meganismes op die molekulere vlak veroorsaak. Deur hierdie verskille in die molekulere meganismes van aksie uit te wys, kan beter progestogene ontwikkel word, en verder sal dit vir dokters en hul pasiente help om die beste voorbehoedmiddel te kies. Laastens, die insig wat verkry is ten opsigte van die meganismes van anti-androgeniese aktiwiteit van VbgA mag nuttig wees in die ontwerp van terapeutiese middels vir die behandeling van siektetoestande met androgeen-afhanklikke etiologie (bv. prostaatkanker).
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Zarkawi, Moutaz. "The influence of naturally occurring and synthetic anabolic hormones on growth and reproduction in female cattle and guinea-pigs." Thesis, University of Aberdeen, 1987. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU499216.
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A series of six experiments was conducted on female cattle and guinea-pigs to investigate the effects of some anabolic compounds on both growth and reproductive functions in the two species. The results indicate that trenbolone acetate increased significantly, the live-weight gains of heifers and improved the efficiency of food conversion. Zeranol and oestradiol-17 treatments had no effect on growth performance. Trenbolone acetate inhibited or delayed ovulation and resulted in elevation of plasma oestradiol-17 concentrations. Zeranol and oestradiol-17 had no effect on estrous cycle occurrence nor ovulation as determined by plasma progesterone concentrations. It is concluded from studies investigating the response to gonadotrophin releasing hormone (Gn-RH), oestradiol benzoate (OE2-B) and pregnant mares' serum gonadotrophins (PMSG) that trenbolone acetate acts (1) on the pituitary gland to decrease the sensitivity to Gn-RH, (2) on the ovary to decrease the sensitivity of the ovarian follicles to gonadotrophins and (3) acts on the pituitary gland and/or the hypothalamus to block the positive feedback effect of oestrogen to release the LH-surge. In the guinea-pig, trenbolone acetate at dose levels of 2 and 10 mg/kg body-weight inhibited ovulation. At a dose level of 0.4 mg/kg body weight, trenbolone acetate prolonged the length of the oestrous cycle. When trenbolone and testosterone, at dose levels of 3.1 and 15.7 mmol/l each, were compared, trenbolone was shown to have more general promoting activity than testosterone. The high dose of both hormones inhibited ovulation and increased the rate of occurrence of atretic follicles. However, only testosterone at the higher dose decreased the weight of the ovaries and lowered the number of follicles. From studies measuring the response to follicles stimulating hormone (FSH) and human chorionic gonadotrophin (HCG), it is concluded that, in the female guinea-pig, trenbolone acetate had no effect on LH-surge mechanism, but it may act on the pituitary gland to block the release of FSH.
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Meendering, Jessica Rae. "The influence of progestins on biomarkers of cardiovascular risk in young women /." view abstract or download file of text, 2007. http://proquest.umi.com/pqdweb?did=1400968571&sid=4&Fmt=2&clientId=11238&RQT=309&VName=PQD.
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Thesis (Ph. D.)--University of Oregon, 2007.Typescript. Includes vita and abstract. Includes results of four studies conducted at the University of Oregon. Includes bibliographical references (leaves 221-244). Also available for download via the World Wide Web; free to University of Oregon users.
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Balthasar, Nina. "Transgenic studies of growth hormone secretagogues physiology." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248212.
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Rodway, Marie R. "Effector mechanisms in the endocrine control of steroidogenesis." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/31411.
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Production of hormones in the ovary is controlled by endocrine, paracrine, autocrine and intracrine influences. Similar controls may exist in the placenta. I wished to investigate the involvement of second messengers in the action of hormones in control of hormonogenesis in rat ovary and human placenta. The second messengers involved in the action of gonadotropin-releasing hormone (GnRH) and prostaglandin (PG) F₂[formula omitted] were investigated in rat granulosa and luteal cells. As well, the endocrine role of GnRH in the placenta and the possible second messengers involved were investigated.
Monolayer cultures of rat granulosa and luteal cells and human placental cells were prepared. Rat granulosa cells were mechanically dispersed; rat luteal cells were enzymatically dispersed with collagenase and DNase. Rat granulosa cells were treated during the first 24 hours in culture; rat luteal cells were treated up to 3 days after dispersion. Radioimmunoassay of medium was used to determine the effect of treatments on hormone production. Studies which examined the effect of hormones on the intracellular free calcium concentration ([Ca²⁺]i) in single cells using the calcium sensitive fluorescent dye, Fura-2, were done in monolayer rat granulosa and luteal cell cultures. Human placental cells, from first trimester and term placentae, were dispersed using trypsin-DNase or collagenase-DNase. Cells were cultured for 2 days prior to treatment. The effects of treatments on production of steroid (progesterone and estrogen),
glycoprotein (human chorionic gonadotropin; hCG) and protein (human placental lactogen; hPL) hormones were determined by radioimmunoassay of the medium.
In rat granulosa and luteal cell cultures, I examined the effect of a number of hormones and second messengers. Effects of follicle-stimulating hormone (FSH), luteinizing hormone (LH), cyclic adenosine monophosphate (cAMP), GnRH and PGF₂[formula omitted] on ovarian hormonogenesis have been previously reported. Changes in cytosolic free calcium concentrations ([Ca²⁺]i) in response to PGF₂[formula omitted] were measured in single rat granulosa and luteal cells. I found that in 34% of granulosa cells, and 53% of luteal cells, there was a 3 to 4 fold increase in resting [Ca²⁺]i within 30 seconds of administration of PGF₂[formula omitted]. Many cells which responded to PGF₂[formula omitted] also responded to GnRH (39% of granulosa cells; 67% of luteal cells). The immediate source of the increased [Ca²⁺]i appeared to be common intracellular stores.
No change in hormone production in response to GnRH in placental cell cultures was seen. Trypsin dispersion may have damaged cell surface receptors, therefore the effect of second messengers on hormone production in these cultures was examined. In term and first trimester trophoblast cultures, I observed the following effects with 8-bromo-cyclic adenosine monophosphate (8-br-cAMP): inhibited estrogen production from the supplied androgen precursors; stimulated hCG production; stimulated hPL production in first trimester placental cell cultures (hPL was not measured in enough term cultures to determine the effect of 8-br-cAMP), and stimulated progesterone production. I also
investigated the effects of activators and inhibitors of the phosphoinositide (PtdIns(4,5)P₂) breakdown second messenger pathway (TPA, A23187, arachidonic acid); no effects of these agents were seen. Other hormones suspected of having endocrine, paracrine or autocrine effects in the placenta were tested without effect.
I conclude that GnRH and PGF₂[formula omitted] cause increases in [Ca²]i in rat ovarian cells, from common intracellular stores of calcium, and that the production of hormones by the human placenta may be under regulation of an agent or agents which induce production of cAMP.Medicine, Faculty of
Obstetrics and Gynaecology, Department of
Graduate
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Morais, Ruiter Lima. "Remoção de hormônios sexuais sintéticos por carbonização hidrotermal e por fungos de decomposição branca." Universidade Federal de Goiás, 2012. http://repositorio.bc.ufg.br/tede/handle/tede/4271.
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Contaminations of water and wastewater with endocrine disrupters from domestic and industrial discharges have been proven in several regions of the planet. Among the endocrine disruptors, the synthetic sex hormones cause great concern because the presence of phenolic rings in their structures makes them stable and recalcitrant in the environment. In Goiás, the presence of synthetic sex hormone concentrations of ethinylestradiol in mg.L-1 in the Meia Ponte River, which goes accross the metropolitan area of Goiânia, was recently confirmed. Studies have shown that concentrations of ng.L-1 can affect sexual differentiation and cause serious damage to the reproductive system in fish and humans. Further, there are few techniques that are proven of being effective on removing this type of substance. The aim of this study was to evaluate the removal of synthetic sex hormones ethinylestradiol, gestodene, and cyproterone acetate by the hydrothermal carbonization process and biological treatment with fungi decomposing white Pycnoporus sanguineus and Trametes villosa. For this purpose, solutions were prepared, individually and in combination with a concentration of 1,0 μg.mL-1 and pH correction into the range of 2-3 with solutions of phosphoric acid or citric acid for treatment with hydrothermal carbonization. For the treatment with the fungus in liquid culture medium and under the condition of stirring, a solution was prepared containing all three hormones (ethinyl estradiol, cyproterone acetate and gestodene) in concentrations of 0,333 μg.mL-1. The carbonization treatments by the process of hydrothermal three hormones with pH correction made with phosphoric acid and reaction time of 90 minutes showed satisfactory removal of Ethinylestradiol and Gestodene, above 90%. Already in the individual treatments, removal achieved was higher than 99% for all three hormones. The biological treatment with Pycnoporus sanguineus and Trametes villosa show significant removal of hormones and cyproterone acetate Ethinylestradiol above 99% and 78.9% for Gestodene for both fungi. It was possible to notice that the presence of hormones increased the enzymatic production of laccase, with peak production anticipated for the fungus Pycnoporus sanguineus. The toxicity test with Artemia salina was observed that the solution with the three hormones after carbonization hydrothermal treatment had fewer dead larvae of Artemia salina, than the solution with hormones without treatment. In test germination of Allium cepa, the solution treated with hormones hydrothermal carbonization showed the same germination rate of the control group, however, less vigor of the shoots. As the control group, the solution to the three hormones before treatment and after biological treatment, the 9.09% concentration, showed no mortality of larvae of Artemia salina. These results show that both the hydrothermal carbonization process as with the fungus Pycnoporus sanguineus and Trametes villosa, show potential for future applications of synthetic sex hormones removal of contaminated waters and effluents.
A contaminação de águas e esgotos com interferentes endócrinos proveniente de lançamentos domésticos e industriais tem sido comprovada em diversas regiões do planeta. Entre os interferentes endócrinos, os hormônios sexuais sintéticos causam grande preocupação, pois a presença de anéis fenólicos nas suas estruturas, os tornam estáveis e recalcitrantes no meio ambiente. Em Goiás, a presença do hormônio sexual sintético Etinilestradiol em concentrações de μg.L-1 no Rio Meia Ponte, que corta a região metropolitana de Goiânia, foi confirmada recentemente. Estudos mostraram que concentrações de ng.L-1 podem afetar a diferenciação sexual e causar sérios danos ao sistema reprodutor em peixes e humanos. Existem, ainda, poucas técnicas comprovadamente eficazes na remoção desse tipo de substância. O objetivo desta pesquisa foi avaliar a remoção dos hormônios sexuais sintéticos Etinilestradiol, Gestodeno e Acetato de Ciproterona através do processo de carbonização hidrotermal e por enzimas oxidativas produzidas pelos fungos de decomposição branca Pycnoporus sanguineus e Trametes villosa. Para tanto, foram preparadas soluções, individuais e em mistura, com concentração de 1,0 μg.mL-1 e correção de pH para a faixa de 2-3, com soluções de ácido fosfórico ou ácido cítrico, para o tratamento com carbonização hidrotermal. Para o tratamento com os fungos, em meio de cultura líquido e sob a condição de agitação, foi preparada uma solução contendo os três hormônios (Etinilestradiol, Acetato de Ciproterona e Gestodeno) em concentração de 0,333 μg.mL-1. O tratamento pelo processo de carbonização hidrotermal dos três hormônios com correção de pH feita com ácido fosfórico e tempo de reação de 90 minutos apresentou resultados satisfatórios de remoção do Etinilestradiol e do Gestodeno, acima de 90%. Já nos tratamentos individuais, a remoção alcançada foi maior que 99% para os três hormônios. O tratamento biológico com Pycnoporus sanguineus e Trametes villosa apresentou resultados significativos de remoção dos hormônios Etinilestradiol e Acetato de Ciproterona, acima de 99% e 78,9% para o Gestodeno, para ambos os fungos. Foi possível notar ainda que a presença dos hormônios aumentou a produção enzimática de Lacase, com pico de produção antecipado para o fungo Pycnoporus sanguineus. No teste de toxicidade com Artemia salina observou-se que a solução com os três hormônios após o tratamento com carbonização hidrotermal apresentou menor número de larvas mortas de Artemia salina, do que a solução com os hormônios sem tratamento. No teste de germinação de sementes de Allium cepa, a solução de hormônios tratada com carbonização hidrotermal apresentou a mesma taxa de germinação do Grupo Controle, no entanto, menor vigor dos brotos. Assim como o Grupo Controle, a solução com os três hormônios do antes do tratamento e que após o tratamento biológico, a 9,09% de concentração, não apresentaram mortalidade de larvas de Artemia salina. Esses resultados mostram que tanto o processo de carbonização hidrotermal quanto o fúngico com Pycnoporus sanguineus e Trametes villosa, apresentam potencial para futuras aplicações de remoção de hormônios sexuais sintéticos de águas e efluentes contaminados.
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Davis, Danyetta Denise. "Investigation of the pleiotrophic effects of a series of isoflavonoid analogues in hormone dependent and hormone independent breast cancer cells." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180124283.
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Athmani, Salah. "Synthesis of cytokinin analogues." Thesis, University of Salford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304608.
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Harrison, Polly A. "Partial synthesis of selected gibberellins." Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294577.
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Thomas, Charles Abidemi Adewale. "Synthetic approaches to anti-hormonal steroids." Thesis, City University London, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316056.
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Sienna, Nancy. "Regulation of ribosomal protein L32 synthesis by hormones." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0027/NQ51047.pdf.
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Hares, Owen. "Synthetic methodology towards inhibitors of aromatase." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278530.
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Sheward, William John. "Thyrotrophin releasing hormone, somatostatin and luteinizing hormone releasing hormone : aspects of their synthesis, release and actions." Thesis, University of Edinburgh, 1986. http://hdl.handle.net/1842/20183.
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Childerhouse, Emma. "The effect of a natural plant extract and synthetic plant growth regulators on growth, quality and endogenous hormones of Actinidia chinensis and Actinidia deliciosa fruit : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Horticultural Science at Massey University, New Zealand." Massey University, 2009. http://hdl.handle.net/10179/1052.
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Kiwifruit are of huge economic importance for New Zealand representing 29 percent of total horticultural exports. Fruit size is the biggest determinant of what consumers are willing to pay, and there is also a positive relationship between consumer preference for flavour and percentage dry matter. The two main cultivars exported from New Zealand are Actinidia chinensis ‘Hort 16A’ (gold kiwifruit) and A. deliciosa ‘Hayward’ (green kiwifruit). Under current commercial practice the only product allowed for use on kiwifruit to increase fruit size in New Zealand is Benefit®. Benefit® has been shown to induce different results when applied to A. chinensis and A. deliciosa, whereas synthetic plant growth regulators such as the cytokinin-like substance N-(2- chloro-4-pyridyl)-N’-phenylurea (CPPU) have been found to promote similar increases in fresh weight of fruit in both cultivars. Final fruit size is determined by both cell division and cell enlargement. It was been shown that fresh weight can be increased in both of the major Actinidia cultivars even though their physiology differs. Hormonal control of fruit size in relation to cell division and cell enlargement phases of fruit growth was studied in both A. chinensis and A. deliciosa. CPPU was applied to both cultivars in a growth response experiment where fruit were collected throughout the growing season. The objective of this experiment was to create growth curves, to compare and contrast the effect on A. chinensis and A. deliciosa, and to provide material for hormone analysis. Application of CPPU was found to significantly increase the fresh weight of both A. chinensis and A. deliciosa fruit (46.98 and 31.34 g increases respectively), and alter the ratio of inner and outer pericarps of A. chinensis fruit. CPPU and Benefit® were applied individually and together to both cultivars. It was found that only A. chinesis fruit were affected by the application of Benefit®; fresh weight was increased by 26.38 g, and percentage dry matter was significantly reduced. There was a statistically significant (p < 0.05) interaction between CPPU and Benefit® when applied to A. chinensis. 3,5,6-trichloro-2-pyridyloxyacetic acid (3,5,6-TPA) was applied to A. deliciosa on two application dates at three concentrations and was found to decrease fresh weight of fruit, but significantly increase percentage dry matter regardless of application date or concentration. Lastly CPPU and 1-naphthalene acetic acid (NAA) were applied to A. deliciosa at two application dates and in all combinations. Application date affected the response to both a low concentration of CPPU and NAA. A synergistic interaction was observed when CPPU was applied early plus NAA late (CPPU early (4.53 g increase) plus NAA late (13.29 g) < CPPU early plus NAA late (33.85 g). Finally endogenous hormone content was studied. Methods were developed and tested for the simultaneous analysis of both indole-3-acetic acid (IAA) and cytokinins. Freeze dried fruit were purified using Waters Sep-pak® cartridges and Oasis® columns then IAA was quantified by high pressure liquid chromatography. Preliminary results indicate a correlation between application of CPPU and endogenous IAA, high concentrations of IAA correlated well with periods of rapid fruit growth particularly for CPPU treated fruit.
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Arslan, Ali. "Parturient hormones : cytokine, and oxytocin effects on prostaglandin synthesis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0005/NQ29877.pdf.
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Grundler, Claudia. "Design and synthesis of ring D modified steroidal hormones." Doctoral thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/17372.
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Bibliography: pages 183-190.Cycloadditions of steroidal 14,16-dienes with ketene equivalents were investigated, as routes to estradiol and estriol analogues. The cycloadduct of 3-methoxyestra-1,3,5(10), 14,16-pentaen-17-yl acetate and 2-chloroacrylonitrile underwent an unprecedented tandem rearrangement, on attempted alkaline hydrolysis to the corresponding ketone. This product, obtained in ca. 90% yield, was formulated as (16¹R)-3-methoxy-17-oxo-15β,16¹-cyclo-14,16β-ethano-14β-estra-1,3,5(10)-triene-16¹-carbonitrile. The chemistry of the 16¹-carbonitrile was extensively studied and, in addition, the derived estradiol analogues were prepared and evaluated for receptorbinding affinity. The 16¹-carbonitrile, and its derivatives, could be transformed into 14,15-dihydrocyclobutano or 14β,16β-bridged compounds by cleavage of a cyclopropyl bond. Indeed, a 14,15-dihydrocyclobutano estradiol analogue was synthesised and submitted for biological evaluation. The cycloadduct of 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate and 2-acetoxyacrylonitrile afforded the corresponding 17-hydroxy 16-oxo compound on alkaline hydrolysis. The 17-hydroxy 16-oxo compound was efficiently converted to the 14α,17α-ethano 15,16-etheno compound by the Shapiro reaction. Reduction of the 17- hydroxy 16-oxo compound led to the formation of the corresponding 16,17-diols, which gave the derived 14β-compounds on glycol cleavage. Furthermore, under acidic conditions the 16,17-diols were found to undergo high yield 16(17 --> l7¹)abeo rearrangements, to afford 14,16-etheno compounds.
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Moss, Cheryl Anne. "Structure-conformation-activity studies of the melanin concentrating hormone (MCH)." Thesis, University of Bath, 1990. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.237223.
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Sattler, Maya R. "Developing Synthetic Peptide-Based Inhibitors of Human Growth Hormone Receptor." Ohio University Honors Tutorial College / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1524838355466962.
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WILKES, BRIAN CRAIG. "SYNTHESIS AND COMPARATIVE ACTIVITIES OF POTENT ALPHA-MELANOTROPIN ANALOGUES AND PREPARATION OF MELANIN CONCENTRATING HORMONE." Diss., The University of Arizona, 1985. http://hdl.handle.net/10150/188060.
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A number of α-melanotropin analogues have been prepared. Insight towards the development and understanding of the functional roles of each of the amino acid residues important for high melanotropic potency in a number of biological systems was studied. The melanotropin analogue Ac- α-MSH₄₋₁₂-NH₂ contains all of the structural requirements necessary for obtaining full biological potency on the lizard (Anolis carolinensis) melanophore and S-91 mouse melanoma. On the frog (Rana pipiens) melanophore, the melanotropin analogue Ac-[Nle⁴]-α-MSH₄₋₁₃-NH₂ possesses full melanotropic potency relative to the native hormone. The smallest melanotropin analogue capable of eliciting any biological response was Ac-α-MSH₆₋₉-NH₂ (Ac-His-Phe-Arg-Trp-NH₂) on all biological systems studied. The low biological activity found in previous studies for smaller melanotropin analogues may have been due to a trace contamination of a potent melanotropin. The importance of each of the thirteen amino acid residues of α-melanotropin in contributing to the melanotropic actions in a number of biological systems is discussed. We were unable to confirm the reported presence of a second independent active sequence in α-melanotropin. The structural requirements for prolongation of biological activity (following removal of exogenous hormone from the assay medium) and enzyme stability have been studied. Analysis suggests species-dependent differences in the structural relationships of the amino acid residues in the 4, 7 and 11 positions for prolonged melanotropic response. Analogues prepared with D-phenylalanine in place of its L-enantiomer in the seventh positions of α-melanotropin analogues generally results in an increased resistance to enzymatic degradation towards rat brain homogenate, rat serum, and to the purified enzymes, trypsin and chymotrypsin. Some of these analogues have been shown to be useful probes for the understanding of melanotropic actions in a number of biological systems. Two α-melanotropin analogues have been prepared which possess partial agonism on the mouse melanoma adenylate cyclase assay. A number of these analogues should prove useful in future studies directed towards a more detailed study of melanotropin receptor systems in a large variety of biological systems. The first known synthesis of melanin concentrating hormone (MCH) is reported. The overall synthetic yield of this cyclic heptadecapeptide was 14%. The chemical, physical and biological properties of synthetic MCH and naturally occurring telost MCH were in agreement. MCH was found to be a full agonist in stimulating melanosome dispersion in both the frog and lizard bioassay. Therefore MCH can stimulate melanosome dispersion or contraction depending upon the bioassay studied. Preliminary studies were done towards understanding the mechanisms of MCH action on telost fish.
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Reddie, Kim. "Chemistry of 19-Norsteroids : synthetic approaches to ring modified hormone analogues." Thesis, University of Cape Town, 1990. http://hdl.handle.net/11427/23326.
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Jardine, Mogamad Anwar. "Synthesis and structure activity relationships of ring D modified steroidal hormones." Doctoral thesis, University of Cape Town, 1995. http://hdl.handle.net/11427/17900.
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Includes bibliographical references.The synthesis of steroidal 14α,16-methano, 14α,17-methano-, 14α,17-ethano- and 14α,17-propano estradiol analogues as well as 14α-alkyl and 14α-functionalised-alkyl estradiol analogues was investigated. Furthermore, the synthesis of 17β-hydroxy-17α, 14-(epoxymethano)androst-4-en-3-one was undertaken and acid-mediated rearrangement of the 14,17-etheno bridged testosterone analogue gave the 14,16-ethano analogue of androst-4-en-3,17-dione. Established ring D cycloaddition and oxidative cleavage methodology gave ring D 14α-formyl and 14α, 17α-diformyl compounds as key intermediates in the overall synthetic plan. Chemoselective- and stereoselective nucleophilic addition at C-14¹ of the 14α-formyl-3-methoxyestra-1,3,5(10)-trien-17-one provided access to 14α-alkyl- and 14α-alkyl-functionalised 19-norsteroids for elaboration toward 14α,17-propano- and 14α-alkylamide estradiol analogues. Synthesis of the 14α,17-methano bridged steroid was attainable indirectly through intramolecular pinacol coupling between the 17-oxo- and 14-formyl group of 14αformyl- 3-methoxyestra-1,3,5(10)-trien-17-one. The 14α, 16-methano bridged steroid was synthesised via base-mediated intramolecular cyclisation of 14-(toluene-p-sulfonyloxy)methyl-3-methoxyestra-1,3,5( 1 0)-trien-17-one. Novel compounds were characterised with the aid of high field NMR techniques. A X-ray crystal structure determination of the strained ring D 14α, 17-methano bridged estriol analogue corroborated its structure. The minimum energy conformation of novel estradiol analogues were superimposed on estradiol, and their least square fit values determined and discussed in relation to biological activity. These analogues will contribute toward defining the structural parameters responsible for certain pattern of hormonal activity, and hence, the ultimate goal of predictive drug design.
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Duncan, Kenneth William. "Development of a synthetic methodology towards novel bile acid and cholesterol analogues." Thesis, University of Strathclyde, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248838.
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Marashi, Khadijeh Kathy 1960. "SOLID PHASE SYNTHESIS OF UNSATURATED ANALOGUES OF OXYTOCIN AND THEIR MEDICINAL APPLICATION (PEPTIDES, HORMONES, ANTAGONISTS, CONFORMATION, RECEPTORS)." Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/275515.
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Feng, Jun. "A kinetic investigation of recombinant xenopus laevis amidating enzymes." Diss., Georgia Institute of Technology, 1999. http://hdl.handle.net/1853/30084.
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Wrigley, J. O. L. "Protein synthesis in isolated muscle preparations from carp (Cyprinus carpio) : The influence of amino acids and hormones." Thesis, University of Bradford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379815.
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SOARES, CARLOS R. J. "Sintese de prolactina humana em celulas de ovario de hamster chines (CHO)." reponame:Repositório Institucional do IPEN, 2000. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10770.
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Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Areiza, Maria. "Ecdysis Triggering Hormone and its Role in Juvenile Hormone Synthesis in the Yellow-fever Mosquito, Aedes aegypti." FIU Digital Commons, 2014. http://digitalcommons.fiu.edu/etd/1147.
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Ecdysis triggering hormone (ETH) is a neuropeptide known for its role in the orchestration of ecdysis. However, its role in the regulation of Juvenile Hormone (JH) synthesis is unknown. In Aedes aegypti, JH is synthesized by the corpora allata (CA) and titers are tightly regulated by allatoregulatory factors. In this study I describe the effect of ETH on JH synthesis during the late pupal stage and in the adult female after blood feeding. Analysis of ETH receptor (ETHRs) expression showed that ETHRs are present in both the CA and the corpora cardiaca (CC), a neurohemal organ. The data suggest that ETH regulates JH synthesis directly through its receptors in CA. Our results show that in pupa, ETH has a stimulatory effect on JH synthesis while in adult blood fed females, ETH is inhibitory. These findings constitute the first evidence of ETH as a regulatory peptide in mosquito JH synthesis.
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Talbi, Oussama. "Synthesis of Homo A-CD Estrogens for Potential Use in Hormone Replacement Therapy." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32082.
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Hormone replacement therapy (HRT) has been subject to much debate due to concerns that long term use of such treatment of menopause increases the risk of breast and uterine cancer. This is thought to be caused by estradiol (1) binding to the estrogen receptor α (ERα) resulting in increased cell proliferation. Another possible mechanism relates to toxicity of the estrodiol metabolites, which are thought to be genotoxic ortho-quinones. In a previous project, a series of A-CD estrogens (2) were synthesised as non-carcinogenic estradiol agonists where the cis CD ring junction was thought to be the cause of the desirable selectivity for ERβ. In this thesis, homo A-CDs were synthesised (3) with expansion of the D ring thought to increase the selecitivty for ERβ. Relative Binding Affinities (RBA) were determined with selectivity to ERα and ERβ. Most ligands showed decreased selectivity when compared to the original A-CD series. However, compounds carrying the CF3 moiety continued to show very high potency. In addition, novel synthetic routes were employed in the preparation of certain compounds.
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Ververidis, Philippos. "Characterisation and partial purification of the enzyme responsible for ethylene synthesis from 1-aminocyclopropane-1carboxylic acid in plant tissues." Thesis, University of Reading, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303175.
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Russell, Keith Casey. "Design and asymmetric synthesis of unusual amino acids for incorporation into peptide hormones." Diss., The University of Arizona, 1992. http://hdl.handle.net/10150/185750.
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One of the central goals of peptide and protein chemistry is the development of peptides with specific biological, chemical, and physical properties. An important method directed towards attaining this goal is the use of conformationally restricted amino acids. The conformationally restricted amino L-isomers of 2'-methyltyrosine, 2',6'-dimethyltyrosine, erythro- and threo-2',β-dimethyltyrosine, and erythro- and threo-2',6',β-trimethyltyrosine were asymmetrically synthesized in good yields and high optical purities. The synthesis of these compounds was based on the chiral boron imidate methodology. Acid precursors were prepared from either 5-methyl-2-nitrophenol, 3-methylanisole, or 3,5-dimethylansole and coupled to optically active 4-phenyl-2-oxazolidinone. Unsaturated coupled products were subjected to 1,4 conjugate additions to set the stereochemistry at the β-carbon with superior stereoselectivity (88-99% de). The Michael adducts and other acyloxazolidinones were asymmetrically brominated to set the chirality at the α-carbon also with excellent stereoselectivity (80-98% de). The bromides were displaced with azide ion to afford the α-azidocyloxazolinones without any detectable racemization. The chiral auxiliary was hydrolyzed and recovered. The azido acids were reduced and methyl ether hydrolyzed to yield the tyrosine derivatives with high optical purity. The absolute stereochemistry of three of the bromide intermediates was determined by X-ray crystallography providing evidence for the selective reactions. The superiority of 4-phenyl-2-oxazolidinone over 4-phenylmethyl-2-oxazolidinone for asymmetric induction was also demonstrated. To examine the sensitivity of the 2' position of tyrosine in oxytocin, (D,L-2'-methylTyr²) oxytocin was synthesized using the standard techniques of solid phase synthesis. Racemic 2'-methyltyrosine was prepared via the classical malonate synthesis. Computer models suggest that the [L-2'-methylTyr²] oxytocin should be a weak agonist.
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SUZUKI, MIRIAM F. "Síntese e caracterização de prolactina de camundongo (mPRL) e de seu análogo (S177D-mPRL)." reponame:Repositório Institucional do IPEN, 2011. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9955.
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Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
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Beswick, Naomi Simone. "The influence of recombinant bovine growth hormone and growth hormone releasing factor on fat synthesis in primiparous Holstein cows." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq22570.pdf.
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Fan, Xiaohui. "Uroguanylin : molecular cloning and characterization of a potential natriuretic hormone /." free to MU campus, to others for purchase, 1997. http://wwwlib.umi.com/cr/mo/fullcit?p9841285.
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Monteserin, Garcia Jose Luis. "Regulation of pituitary growth hormone synthesis by NAD+ dependent deacetylase Sirt1." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-171129.
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Lundåsen, Thomas. "Studies on the hormonal regulation of bile acid synthesis /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-053-4/.
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Foster, Michael Scott. "Design, synthesis, kinetic analysis, molecular modeling, and pharmacological evaluation of novel inhibitors of peptide amidation." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/31816.
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Thesis (Ph.D)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009.Committee Chair: Dr. Sheldon W. May; Committee Member: Dr. James C. Powers; Committee Member: Dr. Nicholas Hud; Committee Member: Dr. Niren Murthy; Committee Member: Dr. Stanley H. Pollock. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Zingsheim, Morgan Robert. "Structure-Activity Study of a-N-Methylated SHU9119 Analogues, hMC4R/TNF-a Antagonists, and Mutational Studies of the Melanocyte Stimulating Hormone Receptor." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/193426.
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The human melanocortin receptors (hMCRs) play a fundamental role in human behavior such as satiety, feeding, sexual and more. A set of SHU9119 peptide derivatives were studied for their structure-activity relationships. These peptides contained a sequential a-N-methylation amino acid scan.A second set of peptide derivatives intended to be used to create TNF-a; inhibition, via the melanocortin receptors. These peptides were shown to bind to all of the hMCR receptors, and only exhibit cAMP stimulation at hMC1R/hMC5R.The data from both of the sets of compounds illustrate that small changes in the stereochemistry of the SH9119 and TNF-a; derivatives cause drastic changes in the binding and the agonistic/antagonist properties of the compounds.This thesis determined the effect that hMC1R mutations have on the binding and cAMP response of well characterized ligands. This study ruled out 9 different residues for being the required for the cAMP response of the hMC1R.
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CODY, WAYNE LIVINGSTON. "SYNTHESIS, BIOLOGICAL ACTIVITY AND CONFORMATIONAL ANALYSIS OF FRAGMENT ANALOGUES OF ALPHA-MELANOTROPIN (PEPTIDE, STRUCTURE-FUNCTION, PHENYLGLYCINE, NMR, TETRAHYDROISOQUINOLINE-3-CARBOXYLATE)." Diss., The University of Arizona, 1985. http://hdl.handle.net/10150/188044.
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α-MSH (α-melanotropin) is a naturally occurring linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH₂) that is primarily known for its ability to stimulate integumental melanocytes and more recently has been implicated in a variety of physiological and neurological processes. It has been shown that substitution of D-phenylalanine in the seven position of this hormone led to an analogue with increased potency and prolonged biological activity. Furthermore, cyclization between the four and ten positions via a cystine bridge led to analogues with enhanced potency. In this regard, a series of conformationally restricted linear and cyclic fragment analogues of α-MSH have been prepared and carefully analyzed by both biological and biophysical methods. Conformational restriction was incorporated in α-MSH fragment analogues, by: (1) substitution of sterically restricted amino acids into the native sequence; or (2) cyclization of the peptide via a disulfide bridge. Due to the biological differences observed for these synthetic α-MSH fragment analogues, a complete conformational analysis by both proton and carbon-13 NMR was performed. The conformational preferences of the backbone were examined by analyzing: (1) the alpha proton chemical shifts; (2) the amide proton chemical shifts; (3) the amide proton coupling constants; and (4) the amide proton temperature dependencies. The data suggests that the peptide backbone in both linear and cyclic analogues possesses a great amount of conformational flexibility with no hydrogen-bonded stabilization. The three-dimensional orientations of individual amino acid side chains have been examined by analyzing: (1) the chemical shifts of the side chain protons; (2) the alpha-beta coupling constants (corresponding rotamer populations); and (3) the carbon-13 spin lattice relaxation times (T₁). A careful examination a the chemical shifts of the side chains of individual amino acids in linear α-MSH fragments reveals that incorporation of an aromatic D-amino acid in the seven position results in an interaction of the side chains of the six, seven and eight positions. In addition, the low carbon-13 spin-lattice relaxation times for the β-carbons of the 5-9 sequence for both Ac-[Nle⁴]-α-MSH₄₋₁₁-NH₂ and Ac-[Nle⁴, D-Phe⁷]-α-MSH₄₋₁₁-NH₂, provides further evidence for an interaction of these side chains. Similar shielding patterns have been observed for the cyclic α-MSH fragment analogues depending upon whether L- or D-phenylalanine is incorporated in the seven position. Considering the differences in biological potency and the similarities in the NMR parameters between the linear and cyclic homologs, it can be concluded that the conformational properties that determine biological potency are too subtle to be measured by present NMR methodology. Furthermore, the similarity of the NMR shielding patterns suggests that a 23-membered ring is too large to impart significant conformational constraints on the peptide backbone or amino acid side chains.
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Ma, Liying. "Regulatory factors of milk fat synthesis in dairy cows." Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/29120.
Full textAbstract:
The objective of these studies was to investigate the milk fat synthesis regulation by transcription factors. In the first study, bovine mammary epithelial (MAC-T) cells were treated with sterol regulatory element binding protein-1 (SREBP-1) specific siRNA. The mRNA and protein expression of SREBP-1 were decreased by more than 90% by siRNA. Fatty acid (FA) synthesis, uptake, and selected lipogenic enzyme expression were reduced in cells treated with SREBP-1 siRNA. Therefore, SREBP-1 plays an important role in integrated regulation of lipid synthesis in MAC-T cells through regulation of key enzymes. In the second study, MAC-T cells treated with hormones or FA were transfected with luciferase reporter constructs containing response elements for SREBP-1, peroxisome proliferator-activated receptor γ (PPARγ), or liver X receptor (LXR). The activation of PPARγ and SREBP-1 were stimulated by insulin and insulin combined with leptin, respectively. Trans-10, cis-12 conjugated linoleic acid (CLA) inhibited SREBP-1 activation, and this inhibition was not attenuated by insulin and leptin. Neither trans-10 nor cis-12 double bond inhibited SREBP-1 activation. Taken together, trans-10 and cis-12 double bonds need to be conjugated in CLA to reduce SREBP-1 activation and this inhibition cannot be overcome by insulin and leptin combination in MAC-T cells. In the third study, lactating dairy cows were intravenously infused with 0.625 g/h trans-10, cis-12 CLA for 14 h. We confirmed the appearance of trans-10, cis-12 CLA in the milk of CLA treated cows. Milk and component yield were not affected by the CLA treatment. The desaturation of stearic acid was reduced by CLA. The mRNA and protein expression of transcription factors or lipogenic enzymes were not affected by trans-10, cis-12 CLA. DNA-binding activities for PPARγ and LXR and the activation of SREBP-1 to its mature form were not changed by the treatment. The infusion time in this study was probably too short to induce any changes in transcription factors and lipogenic enzymes. We confirmed DNA-binding activities of PPARγ and LXR in bovine mammary gland. Overall, a prominent role for SREBP-1 in mammary epithelial cell lipid synthetic pathways was described and regulation of transcription factor activation by trans-10, cis-12 CLA was specific to SREBP-1.Ph. D.
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Cline, Mark Andrew. "Efficacy of Synthetic Gonadotropin Releasing Hormone Analogs for Control of Ovulation During Estrus Synchronization Protocols." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/31372.
Full textAbstract:
Two experiments were conducted to determine efficacy of GnRH analogs, Cystorelin (CYS, gonadorelin diacetate tytrahydrate) and Factrel (FAC, gonadorelin hydrochloride), for use in beef timed AI synchronization. In Experiment one 342 beef cows from 7 herds were assigned CYS or FAC treatment as part of the Ovsynch protocol (GnRH d 0 and 9, Lutalyse d 7). Cattle treated with FAC had greater tendency (P=.09) to be pregnant at d 45. One individual herd demonstrated FAC-treated cows had more pregnancies at day 45. In Experiment two, 18 beef cows received either CYS or FAC as part of the Ovsynch protocol, intensive blood samples, from time -30 to 525 min post GnRH, were collected at each GnRH injection. Ultrasounds were conducted daily over the course of the protocol. A treatment by phase interaction (P=.03) was found for the time to maximum LH concentration, where CYS-treated follicular cows had a shorter interval than did FAC treated follicular or luteal cows. The duration of detectable LH response showed a treatment by phase interaction (P = .02) where follicular and luteal CYS-treated cows had shorter interval than follicular or luteal FAC-treated cows. The variables maximum LH concentration, and area under LH curve did not differ. Cows treated with CYS had more (P=.02) non-dominant follicles. In Experiment three, 16 ewes randomly received either CYS, FAT or Fertagyl (FER; gonadorelin diacetaate tytrahydrate), and FAT's induced LH maximum concentration occurred sooner (P=.02) than CYS. We conclude that either product may be used in beef cows without compromising fertility.Master of Science
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Dodd, S. C. "The hormonal control of #alpha#-lactalbumin and #beta#-lactoglobulin in pig mammary gland." Thesis, University of York, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234448.
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Thompson, Jeremy. "Pharmacological evaluation of in vivo inhibitors of peptide amidation : 2 Biological synthesis of poly(3-hydroxybutyrate)." Thesis, Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/27075.
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Wicks, Joan R. "Phosphorylation of prolactin and growth hormone: Investigation into synthesis and biological role /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487942476409454.
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