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1
Järvenpää, Paula. "Intestinal metabolism of estrogens including some studies on medroxiprogesterone acetate and megestrol acetate." Helsinki : Finnish Society of Sciences and Letters, 1991. http://books.google.com/books?id=ee5qAAAAMAAJ.
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Lee, Isaish Chi Kin. "Measuring the binding kinetics of estrogen receptor alpha and dietary estrogens." HKBU Institutional Repository, 2014. https://repository.hkbu.edu.hk/etd_oa/28.
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Anti-estrogen drugs such as Tamoxifen and Raloxifene are widely prescribed for breast cancer patients. While they are effective, they also have serious side effects. Alternative drugs are therefore being developed. In the drug discovery process, the in vitro binding of estrogen receptors and lead compounds were studied. The binding strength was conventionally quantified in terms of equilibrium dissociation constants (K0 ). However, the binding kinetic rates and especially off-rates (k0 ff) were recently shown to be better indicators of drug potency. In this thesis, we identified a few dietary estrogens as candidate lead compounds. We studied the binding of full-length human recombinant ERa with these dietary estrogens. In particular, we measured for the first time their binding kinetics rate constants. We also measured the change in the receptor-ligand binding kinetics upon its recruitment of co-activators, as a means to gauge agonist/antagonist propensity ofthe ligand. Our results showed that the following dietary estrogens, a-Zearalenol, Zearalenone, and Coumestrol bind favorably to the estrogen receptor alpha.
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Wade, Christian Bernard. "Mechanisms of estrogen rapid signaling /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/6272.
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Scherr, Frank. "Sorption, degradation and transport of estrogens and estrogen sulphates in agricultural soils." Diss., Lincoln University, 2009. http://hdl.handle.net/10182/1017.
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The fate and behaviour of estrogens in the environment are of concern due to the compounds’ endocrine disruption potential. Estrogens, namely 17β-estradiol (E2), estrone (E1), and estrogen sulphates, i.e. 17β-estradiol-3-sulphate (E2-3S) and estrone-3-sulphate (E1-3S) excreted by livestock constitute a potential source for estrogen contamination in the environment. A method was developed to separate and quantify the hormones by high-performance-liquid-chromatography (HPLC) and ultraviolet detection (UV). A combination of dichloromethane (DCM) and dicyclohexylamine hydrochloride (DCH·HCl) gave recoveries from 97.3 to 107% for E1-3S extraction from aqueous solutions. The recoveries from soil samples ranged from 80.9 to 95.2% (E2-3S), and from 86.3 to 91.7% (E1-3S), respectively. Results of batch sorption studies showed that Freundlich isotherms were nonlinear (N ≠ 1) with Kf values ranging from 34.2 to 57.2, and from 3.42 to 4.18 mg¹-N LN kg⁻¹ for E1, and E1-3S, respectively, indicating the sorption affinity of E1-3S was about an order of magnitude lower than that of E1. The hydrophilic sulphate group of E1-3S possibly shielded the compound from hydrophobic interactions with the soil organic matter and allophanic clay minerals that were proposed as sorbents for E1. Contraction of clay minerals, “salting out” and competitive sorption of artificial urine constituents were likely to have been responsible for observed changes in Freundlich parameters when artificial urine was used as mediator matrix. Plotting the effective distribution coefficient as a function of hypothetical exposure concentrations facilitated the comparison of the sorption behaviour of both compounds as influenced by the mediator solution. The results emphasized that using the CaCl₂ matrix might result in false inferences for the sorption behaviour of these compounds in a dairying environment. The four hormones rapidly degraded in the agricultural soils under aerobic conditions, and the majority of the compounds degraded > 50% within the first 24 hrs. Soil arylsulphatase activities were directly correlated with degradation rate constants of the estrogen sulphates. Estrone was identified as a metabolite of E2 and E1-3S, and these three compounds were observed as metabolites of E2-3S. Single-first order (SFO) and double first-order in parallel (DFOP) kinetics were used to model the degradation and metabolite formation data. The results showed that the DFOP model was in most cases better able to predict the parent compound degradation than the SFO model, and also enabled to estimate accurate degradation endpoints. ER-CALUX® analysis revealed the formation of estrogenicity during E2-3S degradation, which could partly be explained by the formation of the metabolites E2 and E1. Transport studies with E1-3S and E1 showed that the transport and retention of both compounds were significantly influenced by the mediator matrix. While no breakthrough curves (BTCs) were recorded during hormone application in CaCl₂ (10 mM) both hormones were detected in the leachate when applied in artificial urine. Rate-limited sorption processes were proposed for the delayed arrival of the hormone BTCs compared with a conservative bromide tracer. Intense colouration of the leachate during the artificial urine experiments suggested the hormones were likely to be moved by colloid-facilitated transport. Furthermore, the detection of residue hormone and metabolite concentrations implied that degradation of E1-3S and E1 was hampered by urine constituents such as glycine and urea.
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Graham, Lisa Anne. "Environmental Estrogens: Assessing Human Gestational Exposure and Interactions with the Estrogen Receptor." Thesis, University of Canterbury. Chemistry, 2012. http://hdl.handle.net/10092/7173.
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Environmental xenoestrogens (EEs) are chemicals that when they enter the body, the body
responds to them as it would to endogenous estrogens. Humans are exposed to these
chemicals on a daily basis via natural components, additives and contaminants in food and
water, through the use of pharmaceuticals and personal care products such as sunscreens,
lotions and toothpaste. Exposure to EEs is thought to result in adverse effects on humans
such as decreased fertility, increased susceptibility to hormone-sensitive cancers, deformities
of the male genitalia and precocious puberty in females. The critical window of exposure is
thought to be early fetal development, when tissues are rapidly differentiating under the
control of endogenous estrogens. However, there is limited data in the literature on human
fetal exposure to EEs. The first objective of this study was to assess human fetal exposure to
a suite of 35 EEs by analysis of paired samples of amniotic fluid and maternal urine were
collected from 32 New Zealand women between 14 and 20 weeks gestation. The analytical
chemistry methods required for this study were developed and validated. The results
demonstrate that fetal exposure is highly correlated with maternal exposure. This study is the
first to report maternal urine levels of two UV filters and amniotic fluid levels of parabens,
UV filters and triclosan. A model based on simple additivity of effect was developed that
combined the measured concentrations with literature data on relative estrogenic potency to
assess the magnitude of the estrogen signal that may be attributed to the EEs. This model
suggests that the fetus may experience an estrogen signal due to the measured EEs that could
be as large as the endogenous estrogen signal. A second objective was to use computational
docking to study the interactions of the EEs with the human estrogen receptor (hER) protein.
The docking studies show that the rigid endogenous ligand, 17β-estradiol (E2) interacts with
the hER to produce a single, well-defined complex with the receptor and the flexible EEs
produce multiple, distinct energy-equivalent complexes. EEs are not able to interact with the
binding cavity to stabilise the rigid hER-E2-like topology of the complex. As a result, the
hER-EE complexes can be thought of as more pliable or ‘floppy’ and thus able to respond to
the cell context in multiple ways, leading to variations in gene expression in different target
tissues. These multiple pathways may explain the range of physiological responses attributed
to exposure that depend on the timing of exposure and the sex of the individual exposed.
6
Lambert, K. Chad. "The effects of estrogen signaling in innate and adaptive immune cells /." Free to MU Campus, others may purchase, 2005. http://wwwlib.umi.com/cr/mo/fullcit?p3189934.
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Nilsson, Ola. "The role of estrogen in growth plate chondrogenesis /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-410-0/.
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Van, Wyk Susan. "The effects of growth stimulants used at cattle feedlots, on reproductive health and thyroid function of Sprague-Dawley rats." Diss., University of Pretoria, 2011. http://hdl.handle.net/2263/24885.
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Reports of endocrine disrupting potential of common environmental chemicals and the effects on reproductive health are well documented in literature. It has been suggested that deteriorating male reproductive health could be due to in utero exposures to these chemicals. The effects mediated through endocrine disrupting chemicals (EDCs) are on the fetus and may therefore be trans-generational. Ultimately, these chemicals land up in aquatic systems and affect wildlife and humans. Humans are exposed to these chemicals through multiple routes including atmosphere, water, occupational, domestic and food consumption. South Africa (SA) is an important livestock producer with about 13.8 million cattle within the feedlot industry contributing up to 80% of the total beef production. Veterinary growth stimulants (VGS) are used by beef producers to enhance growth in cattle. In SA, the following five VGS have been approved for use in beef products under the Register Act 36 of 1947, estradiol, progesterone and testosterone (natural), α'-zearalanol and trenbolone (synthetic). These VGS and their metabolites are environmentally stable compounds. The excretions from the animals are not treated and land up in the local aquatic systems, indirectly posing a health risk. In SA no research has been done on VGS associated with feedlot activities. The aim of this study was to investigate the effects of a mixture of VGS, as possible EDCs on the reproductive health and thyroid function in male rats in utero, during lactation and life-time exposure. The (anti)estrogenic and (anti)androgenic activity in water from specific feedlots was determined by using a battery of screening bio-assays. Water samples were collected over a period of a year and assessed for EDC activity in the recombinant yeast screen (YES), the T47D-KBluc (estrogenic) and the MDA-Kb2 (androgenic) bioassays. The OECD (Organization for Economic Co-operation and Development) 415 protocol, (1983) for a one-generation reproduction toxicity study, was modified to accommodate one control and three experimental groups. The experimental groups were orally gavaged with mixtures of: zilpaterol, diethylstilbestrol (DES) and α-zearalanol (Group 2; estogenic); with β'-trenbolone and methyltestosterone (MT) (Group 3; androgenic); a combination of compounds (Group 4; estrogenic and androgenic) and the Control group received cottonseed oil only. The bio-assay results indicated that water samples analysed from selected feedlots contained compounds with estrogenic activity. The shorter anogenital distance (AGD) (Group 3), decreased seminal vesicle mass (Group 4), decreased prostate mass (Group 4), increased lumen diameter (Group 3 and 4), lowered sperm concentration (Group 3), and increased T4 (Group 2 and 3) differed significantly from the control. The body weight of the males in Group 2 in the F2 generation was significantly lower than the control. The F2 females in Group 2, 3 and 4 were also significantly lower than the control. The reduced AGD, decreased seminal vesicle and increased T4 (thyroxine) might be the result of an estrogenic effect. The reduced sperm concentration might be the result of in utero and lactation exposure to these VGS. The bio-assays confirmed estrogenic activity in the feedlot water sources. The reproductive toxicology study findings confirm the hypothesis that VGS can act as EDCs and could therefore be responsible for negative reproductive effects and thyroid function. More research is needed to investigate the effects of VGS mixtures at different concentrations on male reproductive health, thyroid function and their offspring. AFRIKAANS : Goed gedokumenteerde literatuur dui aan dat chemikalieë wat algemeen in die omgewing gevind word, die potensiaal het om die manlike voortplantingstelsel aan te tas. Dit word gespekuleer dat in utero blootstelling verantwoordelik kan wees vir hierdie agteruitgang. Die fetus en daarop- volgende geslagte se gesondheid kan ook beÏnvloed word deur chemikalieë. Hierdie chemikalieë het die potensiaal om die watersisteme te bereik en gevolglik dier en menslike gesondheid te beÏnvloed. Blootstelling kan plaasvind deur verskeie roetes wat die atmosfeer, water, werksomstandighede, huishoudelike produkte en gekontamineerde voedsel insluit. Suid-Afrika (SA) is 'n belangrike produsent van vleisprodukte met omtrent 13.8 miljoen beeste wat bydra tot 80% van die vleisproduksie. Veterinêre-groei-stimulante (VGS) word gebruik om die vleisproduksie te verbeter. Vyf groei stimulante naamlik estradiol, progesteroon, testosteroon (natuurlike), α-zearalanol en trenboloon (sinteties) is goedgekeur onder die Wet 36 van 1947, vir groei produksie van beeste. Hierdie VGS en hul metaboliete is stabiel in die natuur. Die fekale en urinere uitskeidingsprodukte van die diere word nie behandel nie en eindig op in ons waterstelsels. Geen navorsing is nog in SA gedoen om die potensiële bydraes wat voerkrale tot die besoedeling van water lewer, te bestudeer nie. Die doel van die studie was om die gesamentlike effekte van mengsels VGS as moontlike endokrien-ontwrigtende chemicalieë (EOC) op die manlike voortplantingstelsel en tiroïdhormone van mannetjiesrotte na in utero-, gedurende laktasie- en na 'n leeftyd-blootstelling te bepaal. Die (anti)estrogeniese en (anti)androgeniese aktiwiteit in water vanaf spesifieke voerkrale is met behulp van 'n reeks biologiese seltoetse bepaal. Watermonsters is geanaliseer met die gisseltoets (YES)(estrogenies), die T47D-KBluc (estrogenies) en die MDA-Kb2 (androgenies). Die OECD 415 protokol (1983) vir een generasie reproduktiewe toksologie toets was aangepas om een kontrole en drie eksperimentele groepe te huisves. Die eksperimentele groepe rotte is oraal gedoseer met 'n mengsel van zilpaterol, dietielstilbestrol (DES) en α-zearalanol (Groep 2); β-trenboloon en metieltestosteroon (Groep 3); 'n kombinasie van al bogenoemde (Groep 4); en 'n kontrole groep wat katoensaad olie VGS ontvang het nie. Estrogeniese aktiwiteit en sitotoksisiteit was teenwoordig in die water vanaf die voerkrale. Die verkorte anogenitale afstand (AGD) (Groep 3), kleiner seminale vesikel (SV) massa (Groep 4), kleiner prostaat massa (Groep 4), groter lumen deursneë (Groep 3 en 4), laer spermtelling (Groep 3), verhoogde T4 (Groep 2 en 3), het almal statisties-betekenisvol van die kontrole groep verskil. In die F2 generasie het die liggaamsmassas van die mannetjies in Groep 2 en liggaamsmassas van die wyfies in Groepe 2, 3 , 4, almal statisties-betekenisvol laer as die kontrole Groep. Die verkorte AGD, kleiner SV en verhoogde T4 kan moonlik wees as gevolg van 'n estrogeniese effek en die verlaagde sperm konsentrasie weens 'n in utero en laktasie blootstelling. Die biologiese seltoetse het die teenwoordigheid van estrogeniese aktiwiteit in voerkrale se water bevestig. Die gevolge van die blootstelling van EOC mengsels op voortplantings-parameters bevestig die moontlikheid van EOC effek geassosieer met VGS. Verdere navorsing is nodig om die dosisresponsverhoudings van verskillende VGS te ondersoek. Copyright<br>Dissertation (MSc)--University of Pretoria, 2011.<br>School of Health Systems and Public Health (SHSPH)<br>Unrestricted
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Zhang, Qiu-Xia. "Estrogen receptor gene alterations in human breast cancer." Lund : Jubileumsinstitutionen, Dept. of Oncology,Lund University, 1997. http://catalog.hathitrust.org/api/volumes/oclc/39738537.html.
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Linford, Nancy J. "Effects of estrogenic compounds on neuronal apoptotic pathways /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/6289.
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Foryst-Ludwig, Anna [Verfasser]. "Obesity-related cardiovascular and metabolic diseases : the role of estrogens, estrogen receptors and PPARgamma / Anna Foryst-Ludwig." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052530788/34.
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Ansell, Peter James. "Regulation of the antioxidant response element by estrogens : a potential mechanism to help explain estrogen-induced cancer? /." free to MU campus, to others for purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p3137674.
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Stavréus-Evers, Anneli. "Implantation : morphological and biochemical characterization of the receptive human endometrium /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-313-9.
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Trauernicht, Amy Michelle. "The role of the deleted in breast cancer 1 gene product, DBC-1, in estrogen-independent breast cancer cell survival : a dissertation /." San Antonio : UTHSC, 2007. http://proquest.umi.com/pqdweb?did=1407489201&sid=1&Fmt=2&clientId=70986&RQT=309&VName=PQD.
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Harrell, Joshua C. "Dissecting roles of estrogen receptors in breast cancer lymphatic metastasis /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Reproductive Sciences) -- University of Colorado Denver, 2007.<br>Typescript. Includes bibliographical references (leaves 125-140). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Philips, Brian John. "Protein interactions with the catechol estrogens 4-hydroxyestrone and 4-hydroxyestradiol in mouse tissue lysate : binding and metabolism studies /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3036851.
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Constantinidou, Demetra. "Investigation of the role of phosphorylation of the estrogen receptor, its relevance to breast cancer and involvement in resistance to anti-estrogens." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408430.
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Orajärvi, M. (Marko). "Effect of estrogen and dietary loading on rat condylar cartilage." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526207377.
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Abstract The temporomandibular joint (TMJ) is a synovial joint which attaches the mandible to the skull. The head of the mandibular condyle is covered by condylar cartilage, which functions as both growth and articular cartilage. Masticatory forces are transmitted to the condylar cartilage, and the consistency of a person’s diet partly defines the loading force. Condylar cartilage acts as a load-absorbing structure together with the articular disc. Temporomandibular disorders (TMDs) are a wide group of pathological conditions involving pain and dysfunction in the masticatory system. Females comprise the majority of patients, having more symptoms and clinical signs than men. Because of this gender distribution, it has been suggested that the female sex hormone estrogen has an influence on the pathogenesis of TMJ osteoarthrosis. However, little is known about how estrogen affects condylar cartilage. The effect of estrogen deficiency and altered dietary loading on condylar cartilage was studied with female rats, which were distributed to four groups depending on ovariectomy and diet consistency, and further to two distinct age groups. Expression of type II and X collagens, adiponectin, ERα, MMP-3, MMP-8, TRAP, and cathepsin K was investigated. Markers of apoptosis and proliferation of cartilage cells were investigated. A lack of estrogen increased and a soft diet decreased the thickness of condylar cartilage. Expression of proliferating cell nuclear antigen (PCNA, proliferation marker) was higher in ovariectomized rats fed a normal diet when compared with control rats. The area of type II and X collagens in condylar cartilage was larger when estrogen was not present and smaller when the diet consistency was soft. Expression of MMP-3 was higher in ovariectomized rats than in control rats. Ovariectomized rats fed a soft diet had higher expression of MMP-8 than ovariectomized rats fed a normal diet. However, control rats fed a soft diet had lower proportional expression of MMP-8 than normal diet controls. The proportional amount of cartilage cells stained against adiponectin was higher in rats fed a soft diet when compared with rats fed a normal diet. The proportional amount of cartilage cells expressing ERα was higher in ovariectomized rats than in control rats. Osteoclast markers cathepsin K and TRAP showed that ovariectomized rats had fewer osteoclasts than control rats had. The average size of osteoclasts was smaller in ovariectomized rats when compared with control rats. The results of this study show that estrogen and altered dietary loading have an effect on condylar cartilage. Further studies are needed to evaluate the significance of these changes, and especially their association with TMJ disorders<br>Tiivistelmä Leukanivel on synoviaalinivel, joka liittää mandibulan eli alaleuan kalloon. Alaleuan nivellisäkkeen eli kondyylin päässä oleva rustokerros toimii sekä kasvu- että nivelrustona. Purentavoimat välittyvät kondyylirustoon, ja kuormituksen määrä on riippuvainen ruoan kovuusasteesta. Kondyylirusto toimii kuormituksen vastaanottajana yhdessä nivelvälilevyn kanssa. Purentaelimistön toimintahäiriöihin (TMD) kuuluu laaja joukko patologisia tiloja, joihin liittyy kipua ja dysfunktiota purentaelimistössä. Potilaista suurin osa on naisia, ja heillä on oireita sekä sairauden kliinisiä tunnusmerkkejä enemmän kuin miehillä. Sukupuolijakaumasta johtuen on arveltu, että naissukupuolihormoni estrogeenilla voisi olla vaikutusta leukanivelartroosin patogeneesiin. Tällä hetkellä tietoa on hyvin vähän siitä, miten estrogeeni vaikuttaa leukanivelrustoon. Estrogeenin puutoksen ja muunnellun purentarasituksen vaikutusta leukanivelrustoon tutkittiin naarasrotilla, jotka jaettiin neljään eri ryhmään munasarjojen poiston ja dieetin kovuusasteen mukaan sekä lisäksi kahteen eri ikäryhmään. Tyypin II ja X kollageenin, adiponektiinin, estrogeenireseptori α:n, MMP-3:n, MMP-8:n, TRAP:n ja katepsiini K:n ekspressio tutkittiin. Rustosoluista tutkittiin apoptoosin ja proliferaation merkkiaineet. Estrogeenin puute lisäsi ja pehmeä dieetti pienensi kondyyliruston paksuutta. PCNA:n (proliferating cell nuclear antigen) ekspressio oli suurempi normaalilla dieetillä olleilla ovariapoistetuilla rotilla kuin kontrollirotilla. Tyypin II ja X kollageenien osuus oli suurempi ovariapoistettujen rottien kondyylirustossa kuin pehmeällä dieetillä olleilla. MMP-3:n ekspressio oli korkeampi ovariapoistetuilla rotilla kuin kontrolleilla. Ovariapoistetuilla rotilla, jotka olivat pehmeällä dieetillä, oli suurempi MMP-8:n ekspressio kuin normaalilla dieetillä olleilla ovariapoistetuilla rotilla. Kuitenkin MMP-8:n ekspressio oli pienempi pehmeällä dieetillä olleilla kontrollirotilla kuin normaalilla dieetillä olleilla. Adiponektiinin tunnistavalle vasta-aineelle positiivisten solujen suhteellinen lukumäärä oli suurempi pehmeällä dieetillä olleilla rotilla kuin normaalilla dieetillä olleilla. Estrogeenireseptori α:a ekspressoivien solujen suhteellinen lukumäärä oli suurempi ovariapoistetuilla rotilla kuin kontrolleilla. Osteoklastien merkkiaineet katepsiini K ja TRAP osoittivat, että ovariapoistetuilla rotilla oli vähemmän osteoklasteja kuin kontrollirotilla. Osteoklastien keskimääräinen koko oli pienempi ovariapoistetuilla rotilla kuin kontrolleilla. Tutkimuksen tulokset osoittavat, että estrogeeni ja muunneltu purentarasitus vaikuttavat leukanivelrustoon. Lisätutkimuksia tarvitaan, jotta voidaan arvioida näiden muutosten merkitsevyys ja erityisesti niiden yhteys leukanivelen toimintahäiriöihin
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Stygar, Denis. "The impact of estrogens on leukocyte function in remodeling of extracellular matrix /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-572-0/.
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Tanemura, Mai. "The role of estrogen and estrogen receptor β in choroidal neovascularization". Kyoto University, 2005. http://hdl.handle.net/2433/144767.
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Stewart, Ceri Elisabeth. "Estrogen receptor beta and estrogen response in breast cancer cell lines." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491371.
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Ced Stewart: Estrogen receptor beta and estrogen response in breast cancer cell lines Breast cancer affects 1 in 9 women in Britain and its development and treatment are greatly influenced by hormonal status, such as exposure to endogenous estrogen and expression of estrogen receptors (ERs). ERa is an established prognostic marker in breast cancer, but the role of ERp is less certain. The ERs act to regulate gene transcription via a highly complex variety of mechanisms in response to stimuli such as estrogen, tamoxifen or fulvestrant. In order to further define the role of ERp isoforms in breast cancer, their role in the estrogen response must be characterised. This thesis has used a set of four breast cancer cell lines, as well as an MCF7 cell line engineered to over-express ERpl mRNA (MCF7PIx), to investigate the role of ERp in estrogen response. Cells were - treated with a variety of stimuli (estrogen, tamoxifen, fulvestrant, epidermal growth factor and fibroblast growth factor-2) and expression of a panel of ER isoforms, estrogen responsive genes and housekeeping genes was measured using real-time, quantitative PCR. Estrogen response is cell line specific, both in terms of the genes affected and the level of response. These responses can be partly, but not fully, related to the levels of ERa expressed by the cell lines. Expression of individual ER isoforms varies in response to treatment in a time, stimulus and cell line specific manner. Different cell lines vary expression of different subsets of ER isoforms and MCF7pIx, which constitutively over-expresses ERpl mRNA, shows down-regulation of ERpl mRNA expression in response to estrogen. Together these data suggest that regulation may occur at the level of splicing and mRNA stability, as well as at the transcription level. MCF7 and MCF7P Ix showed.remarkably similar responses to treatments. In both cell lines, similar sets of genes were both up- and down-regulated by estrogenic and growth factor treatments. Most -genes showed a similar pattern of transcriptional activation at 0 to 8 h as at 24 h, except for ERpl and ERp2, indicating the importance of control of ERp expression. It was not possible to measure the levels of ERpl protein in the cells, therefore the similarity in responses in MCF7 and MCF7pIx may indicate that, despite the higher levels of ERpl rnRNA, MCF7pIx cells do not overexpress ERPI protein. Measurement of endogenous expression of a set of estrogen responsive genes in a panel of breast cancer cell lines in response to various stimuli has afforded new insights into the levelS and variation in the response achieved in this system. Expression of ERp mRNA was shown to be controlled in a cell line and treatment specific manner, as has previously been shown for ERa. Additionally, it was shown that this regulation was isofonn specific and was maintained when the ERp was overexpressed under the control of an exogenous promoter. This is particularly interesting, as it suggests various levels of regulation, indicating the important role of ERp in downstream estrogen responses. - Supplied by The British Library - 'The world's knowledge'
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Lau, Kin-Mang. "Estrogen and Antiestrogen Actions on Human Prostate Cancer: A Dissertation." eScholarship@UMMS, 2001. https://escholarship.umassmed.edu/gsbs_diss/37.
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Prostate cancer increases its incidence with age after men in their fifth decade as the ratio of estrogen to androgen rises. Epidemiological studies indicated that high levels of estrogens are associated with the high-risk ethnic groups for prostate cancer. Therefore, estrogens may be involved in prostatic carcinogenesis. It is widely believed that the actions of estrogens are mediated by estrogen receptors. However, expression of estrogen receptor in normal prostate and lesions of the gland was controversial. With the recent discovery of second estrogen receptor (ER-β), this issue became more complicated and it needs to be readdressed. In addition, the biological involvement of ER-β in human prostate remains to be investigated. In this study, we demonstrated that human normal prostate epithelial cells express ER-β but not ER-α, suggesting that estrogens act directly on these epithelial cells via ER-β. Using RT-PCR analysis, the transcripts of ER-β were detected in our primary human prostatic epithelial cell cultures that were derived from the ultrasound-guided peripheral zone biopsies and the cells express two estrogen-regulated genes such as progesterone receptor (PR) and pS2. Moreover, we had developed an ER-β antibody with fully characterizations and used it for immunohistochemistry. Results indicated that ER-p protein is expressed in the basal compartment of prostatic epithelium of the gland. Our findings lead to a new hypothesis that estrogens directly act on human prostatic epithelial cells to modulate its biological functions.
To investigate expression of ERs in prostate cancer, RT-PCR analysis was used. We found that all three human prostate metastatic cancer cell lines, DU145, PC-3 and LNCaP, express ER-β transcripts while ER-α mRNA expression only in PC-3 cells. Expressions of PR and pS2 in these cell lines are various. LNCaP cells express both PR and pS2 mRNAs but DU145 cells with only PR and PC-3 cells with only pS2. Our immunohistochemical results on prostatic lesions revealed down-regulation of ER-β expression in high-grade of dysplasia and carcinoma of peripheral zone of the prostate compared to their low-grade lesions. This down-regulation in high-grade carcinoma was verified in transcriptional level by RT-PCR analysis on micro dissected normal epithelium and lesion samples of the gland. In the metastasis, ER-β was found to be reactivated as we observed ER-β mRNA expression in prostate cancer cell lines.
Recent evidence suggests that ER-β may be antiproliferative factor for a protective effect against the mitogenic activity of estrogens in breast and androgens in prostate. Activation of the receptor may exhibit cell growth inhibition. We demonstrated that antiestrogens [ICI-182,780 (ICI) and 4-hydroxytamoxifen], raloxifene and phytoestrogen (resveratrol), but not estrogens (17β-estradiol and diethylstilbestrol), inhibit growth of DU145 cells which express only ER-β while PC-3 cells with both ERs showed growth inhibition in response to estrogen and antiestrogen treatments. In DU145 cells, the ICI-induced cell growth inhibition was prevented by blockade of ER-β expression using antisense oligonucleotide. It indicated that the inhibition is mediated via ER-p associated pathway. Using flow cytometry, we found that ICI-treatment could induce accumulation of cells at GO-G1 phase of cell cycle. Similarly, this GO-G1 cell accumulation was also induced by raloxifene in DU145 cells. For resveratrol, the treatment exhibited dual effects on cell cycle distribution in DU145 cells. In the early treatment, resveratrol induced cell cycle arrests at GO-G1phase. The prolonged treatment leads to S-phase cell cycle arrest.
To study the molecular mechanism of this ER-p associated cell growth inhibition, real-time RT-PCR analysis was used to semi-quantitate the transcript levels of tentative ER-β regulated genes such as telomerase reverse transcriptase (TERT), survivin and thymidylate synthase (TS) in the treated cells compared to those in control. Results demonstrated that the treatment of ICI could down-regulate TERT and survivin mRNA expressions with dose-dependent fashion. As the ICI-treatment, resveratrol downregulated expression levels of TERT, survivin and TS in DU145 cells. Down-regulation of TS may be related to the S-phase cell cycle arrest observed in the prolonged treatment of resveratrol.
Taken together, our findings support the concept that ER-β participates in cell cycle regulation in normal and malignant prostatic epithelial cells. Presence of ER-β in basal cells of the prostate acini indicates that the direct actions of estrogens may be involved in the normal physiology of the gland. Loss of this receptor in primary prostate cancer and its re-expression in metastasis suggests the roles of ER-β in the cancer progression. Activation of the receptor by antiestrogen and phytoestrogen induced cell growth inhibition in prostate cancer cells. The mechanism may be mediated by reduction of cell survival factors and eventually decrease in cell viability and induction of cell cycle arrests.
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Pettersson, Katarina. "Signal transduction via estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4184-X/.
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Lee, Chun-lun. "Actions of estrogen and estrogen-related compounds on prostate cancer cell growth /." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38297061.
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Lee, Chun-lun, and 李振倫. "Actions of estrogen and estrogen-related compounds on prostate cancer cell growth." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011266.
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Karolczak, Magdalena. "Estrogen synthesis and novel mechanisms of estrogen action in the developing brain." Ulm : Universität Ulm, Medizinische Fakultät, 2000. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB9394023.
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Lee, Annie S. (Annie Sang) 1975. "Molecular mechanism of interactions between estrogen receptor and estrogen receptor selective genotoxins." Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/73348.
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Thesis (S.M.)--Massachusetts Institute of Technology, Division of Bioengineering and Environmental Health, 2000.<br>Includes bibliographical references (leaves 43-47).<br>Although one million new breast cancer cases arise each year worldwide, therapies to treat the disease are limited. Conventional treatments including the chemotherapeutic agent, Tamoxifen, have had only limited success, often showing uncomfortable side effects. Our group has proposed a new scheme for a rational drug design. This scheme utilizes recent findings on the mechanism of cisplatin, the drug found to cure in excess of 93% of all testicular cancer cases. Cisplatin forms DNA adducts that are toxic. The toxicity of these adducts is enhanced by the recruitment of proteins that bind to the adducts and impede adduct repair. This thesis was an attempt to duplicate this "repair shielding" mechanism with another cytotoxin. Specifically, this toxin will be programmed to kill breast cancer cells. Breast cancer cells often overexpress the estrogen receptor protein. By synthesizing a drug that not only binds and damages the DNA but also binds the abundant proteins in the cells, thereby blocking the damaged site from DNA repair proteins, a selective treatment of cancer cells can be achieved. In this study, the human estrogen receptor (hER) and the ligand binding domain of the hER genes were cloned into baculovirus expression vectors, establishing a system where a large quantity of the proteins can be expressed. The proteins expressed in insect cells were purified in one step, using the FLAG-epitope, yielding homogeneous proteins. The proteins were tested for binding to p-estradiol and were confirmed to be functional in ligand binding. They were also tested for their ability to bind the novel drugs synthesized to bind both the protein and the DNA. It was found that the ligand binding domain of the hER was capable of binding the drugs adducted to the DNA. In an effort to elucidate the mechanism of the protein-drug-DNA complex formation, an association experiment was carried out, which showed that the drug more readily bound to the protein than to DNA. However, a significant amount of the drug-protein complex still bound the DNA, if the ratio of the protein to the drug did not exceed 1.5.<br>by Annie S. Lee.<br>S.M.
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Andersson, Therése. "Estrogen and Glucocorticoid Metabolism." Doctoral thesis, Umeå universitet, Medicin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33165.
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Background: Cardiovascular disease (CVD) is the leading cause of death among women in Sweden. The risk of CVD increases rapidly after the menopause. A major contributing factor may be the redistribution of adipose tissue, from the peripheral to central depots, associated with menopause. This change in body composition is commonly attributed to declining estrogen levels but may also be affected by tissue-specific alterations in exposure to other steroid hormones, notably glucocorticoids – mainly cortisol in humans. Indeed, adipose tissue-specific overexpression of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) induces central obesity, insulin resistance and hypertension in mice. Interestingly, estrogen may regulate this enzyme. The aim of this thesis was to investigate putative links between estrogen and glucocorticoid activation by 11βHSD1. Materials and Methods: 11βHSD1 expression and/or activity in adipose tissue and liver, and adipose estrogen receptor α and β (ERα and ERβ) gene expression, were investigated in lean pre- and postmenopausal women and ovariectomized rodents with and without estrogen supplementation. In lean women measures of 11βHSD1 were correlated to risk markers for CVD. The association between adipose 11βHSD1 and ER mRNA expression was investigated in both lean women and rats and in an additional cohort of obese premenopausal women. In vitro experiments with adipocyte cell lines were used to explore possible pathways for estrogen regulation of 11βHSD1. Results: Subcutaneous adipose tissue transcript levels and hepatic activity of 11βHSD1 were higher in postmenopausal vs. premenopausal women. In rodents, estrogen treatment to ovariectomized rats decreased visceral adipose tissue 11βHSD1, resulting in a shift towards higher subcutaneous (vs. visceral) 11βHSD1 mRNA expression/activity. Increased adipose and hepatic 11βHSD1 were associated with increased blood pressure and a disadvantageous blood lipid profile in humans. We found significant positive associations between 11βHSD1 and ERβ transcript levels in adipose tissue. The in vitro experiments showed upregulation of 11βHSD1 mRNA expression and activity with estrogen or ERβ-agonist treatment at low (corresponding to physiological) concentrations. Conclusions: Our studies show for the first time increased local tissue glucocorticoid activation with menopause/age in women. This may contribute to an increased risk of CVD. Estrogen treatment in rodents induces a shift in 11βHSD1 activity towards the subcutaneous adipose tissue depots, which may direct fat accumulation to this metabolically “safer” depot. The in vitro studies suggest that low-dose estrogen treatment upregulates 11βHSD1 via ERβ. In summary, estrogen - glucocorticoid metabolism interactions may be key in the development of menopause-related metabolic dysfunction and in part mediate the beneficial effects of postmenopausal estrogen treatment on body fat distribution.
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Ljunggren, Ribom Eva. "Muscles, Estrogen, and Bone." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3779.
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Curran, Edward M. "Regulation of the estrogen receptor in human breast cancer cells /." free to MU campus, to others for purchase, 1998. http://wwwlib.umi.com/cr/mo/fullcit?p9901231.
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Karolczak, Magdalena [Verfasser]. "Estrogen synthesis and novel mechanisms of estrogen action in the developing brain / Magdalena Karolczak." Ulm : Universität Ulm. Medizinische Fakultät, 2001. http://d-nb.info/1015473156/34.
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Islander, Ulrika. "Immunomodulation by estrogen and estren /." Göteborg : Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at Göteborg University, 2007. http://hdl.handle.net/2077/3123.
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Gagniac, Laurine. "Physiologie et physiopathologie des effets membranaires du récepteur des œstrogènes alpha (ERα) dans la glande mammaire". Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30101.
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It is well established that the 17-estradiol is involved in the development and homeostasis of reproductive and extra-reproductive tissues, particularly the mammary gland. Estradiol classically binds to Estrogen Receptor (ERα), which is a member of the nuclear receptor superfamily. ER mediates nuclear (transcription) and plasma membrane (signaling) ERα function. Interestingly, the membrane initiated steroid signaling (MISS) required a post translational modification of the receptor: palmitoylation of the human Cys-447 or the murine Cys-451 counterpart. The main objectives of my PhD thesis were to decipher the physiological role of membrane ERα in mammary gland development and to understand how the membrane ER signaling impact breast cancer. To do so, we used the transgenic mouse model C451A-ER in which the single point mutation (C451A) was introduced to abolish palmitoylation of ER (membrane addressing signal). We demonstrate that the point mutation of the palmitoylation site of ER alters the paracrine signaling of luminal epithelial cells and by consequence the repopulation properties of the mammary stem cells. We also studied the involvement of the membrane effects of the Estrogen Receptor ERα in the 17β-estradiol response dose of the mammary gland. Finally, by breeding the C451A-ER mice with the widely used transgenic mice model of tumorigenesis (PyMT), we provide the first evidence that the membrane ERα influences tumorigenesis. These findings pave the way on an unexpected role of non-genomic function of ERα in the mammary gland physiology and physiopathology<br>It is well established that the 17-estradiol is involved in the development and homeostasis of reproductive and extra-reproductive tissues, particularly the mammary gland. Estradiol classically binds to Estrogen Receptor (ERα), which is a member of the nuclear receptor superfamily. ER mediates nuclear (transcription) and plasma membrane (signaling) ERα function. Interestingly, the membrane initiated steroid signaling (MISS) required a post translational modification of the receptor: palmitoylation of the human Cys-447 or the murine Cys-451 counterpart. The main objectives of my PhD thesis were to decipher the physiological role of membrane ERα in mammary gland development and to understand how the membrane ER signaling impact breast cancer. To do so, we used the transgenic mouse model C451A-ER in which the single point mutation (C451A) was introduced to abolish palmitoylation of ER (membrane addressing signal). We demonstrate that the point mutation of the palmitoylation site of ER alters the paracrine signaling of luminal epithelial cells and by consequence the repopulation properties of the mammary stem cells. We also studied the involvement of the membrane effects of the Estrogen Receptor ERα in the 17β-estradiol response dose of the mammary gland. Finally, by breeding the C451A-ER mice with the widely used transgenic mice model of tumorigenesis (PyMT), we provide the first evidence that the membrane ERα influences tumorigenesis. These findings pave the way on an unexpected role of non-genomic function of ERα in the mammary gland physiology and physiopathology
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Zushin, Peter-James H. "The selective effect of estrogen receptor alpha and beta on activity and social behavior in neonatal male praire voles." Akron, OH : University of Akron, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1248102221.
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Thesis (M.S.)--University of Akron, Dept. of Biology, 2009.<br>"August, 2009." Title from electronic thesis title page (viewed 10/7/2009) Advisor, Bruce Cushing; Committee members, Qin Liu, Todd Blackledge; Department Chair, Monte Turner; Dean of the College, Chand Midha; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.
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Russell, Nancy. "Estrogen Receptor Alpha in the Medial Preopic Area Mediates Male Rat Sexual Responses to Estrogen." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/biology_theses/25.
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Male rat sexual behavior requires aromatization of testosterone (T) to estradiol (E2) in the medial preoptic area (MPO) where estrogen receptors (ER) exist in two isoforms, ERα and ERβ. We hypothesized that E2 acts through estrogen receptor α (ERα) in the MPO to promote male mating behavior. Four groups of male rats were castrated, administered DHT s.c. and bilateral MPO implants delivering either: cholesterol, E2, propyl pyrazole triol (PPT, ERα agonist), diarylpropionitrile (DPN, ER β agonist), or 1-methyl-4-phenyl pyridinium (MPP, ERα antagonist). Additional gonadally intact males received bilateral MPO DPN implants. PPT maintained sexual behavior equally as well as E2, whereas mating was not maintained by cholesterol or DPN MPO implants. Exogenous T did not reinstate mating in animals that received MPP MPO implants. These findings indicate that, in the MPO, ERα is necessary and sufficient to promote copulatory behavior in male rats and ERβ is not sufficient for mating.
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Couse, John Floyd. "THE ROLE OF ESTROGEN RECEPTOR-a AND ESTROGEN RECEPTOR-b IN THE HYPERLUTEINIZED MOUSE OVARY." NCSU, 2004. http://www.lib.ncsu.edu/theses/available/etd-05212004-123339/.
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The hypothalamic-pituitary-gonadal (HPG) axis was characterized in female mice lacking one or both forms of estrogen receptor (ERa, ERb) with the aim of elucidating the contribution of each receptor form to gonadotropin homeostasis and ovarian function. These studies consisted of a thorough evaluation of gene expression for the gonadotropin subunits in the pituitary and the components necessary for steroidogenesis in the ovary. These data were corroborated with evaluations of the plasma levels for each of the relevant pituitary and gonadal hormones. Females lacking ERb (bERKO) exhibit minimal disruption in HPG axis function but do exhibit deficits in gonadotropin responsiveness in the ovary. Females lacking ERa (aERKO) exhibit dramatic ovarian phenotypes of hemorrhagic and cystic follicles and exaggerated steroid synthesis in the ovaries. The phenotypes in the aERKO ovary are attributable to chronically elevated LH due to the loss of ERa function in the hypothalamus. Pharmacologic reduction of plasma LH levels in aERKO females abates the ovarian phenotypes. These studies indicate that the hypothalamic functions of ERa are most critical to ovarian function. To better understand the contribution of ERb to the manifestations of LH-hyperstimulation in the ovary, females lacking functional ERb but possessing elevated LH via a transgene (bERKOLHCTP) were generated. Characterization of bERKOLHCTP animals indicates the intraovarian functions of ERb are necessary for the induction of LH-associated cystic follicles but not amplified steroidogenesis. An additional novel finding in aERKO ovaries was ectopic expression of the Leydig cell specific enzyme, 17b-HSD III and correlating male-like testosterone synthesis. This phenotype is dependent on LH-hyperstimulation of ovaries lacking ERa function to manifest. In summary, the predominant contribution of ERa to ovarian function occurs in the hypothalamus, whereas ERb is more important within the ovary itself. Presence of Leydig cell specific gene expression in aERKO ovaries indicates a potential role for estradiol and ERa in gonadal differentiation.
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Shen, Minqian. "Roles of estrogen hormones and estrogen receptors on regulation of liver and liver cancer metabolism." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1492612390075921.
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Björnström, Linda. "Molecular mechanisms of alternative estrogen receptor signaling /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-509-3/.
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Toll, Karin. "Pregnancy rhinitis : pathophysiological effects of oestrogen and treatment with oral decongestants /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-358-0/.
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Rafi, Ali. "Estrogen action in growth plate cartilage." Thesis, Högskolan i Skövde, Institutionen för vård och natur, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-5463.
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Park, Se Hyung. "Estrogen in ovarian cancer cell metastasis." Thesis, University of British Columbia, 2008. http://hdl.handle.net/2429/1287.
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Benign ovarian tumors and majority of epithelial ovarian cancers possess steroid receptors including estrogen receptors (ERs). However, the estrogen-ER signaling in ovarian carcinomas is not completely understood. Tumorigenesis is a multiple-step process involving dysregulated cell growth and metastasis. Tumor cells acquire the capacity of migration and invasion by temporal phenotypical and genotypical changes termed epithelial-mesenchymal transition (EMT). Considerable evidence implicates a mitogenic action of estrogen in early ovarian carcinogenesis. In contrast, its influence in the metastatic cascade of ovarian tumor cells remains obscure. In this study, I have focused on the role of 17β-estradiol (E2) in ovarian tumorigenesis. EMT related genes including E-cadherin, Snail, Slug, and Twist were examined. E2 treatment led to clear morphological changes and an enhanced cell migratory propensity. These morphologic and functional alterations were associated with changes in the abundance of EMT-related genes. Upon E2 stimulation, expression and promoter activity of the epithelial marker E-cadherin was strikingly suppressed, whereas EMT-associated transcription factors Snail and Slug were significantly up-regulated. This up-regulation was attributed to the increase in gene transcription activated by E2. Depletion of the endogenous Snail or Slug using small interfering RNA (siRNA) attenuated E2-mediated control in E-cadherin. In addition, the E2-induced cell migration was neutralized by Snail and Slug siRNAs, implying that both transcription factors are indispensable for the pro-metastatic actions of E2. Importantly, by using selective ER agonists as well as over-expression and siRNA approaches, it was identified that E2 triggered the metastatic behaviors exclusively through an ER⍺-dependent pathway. In contrast, overexpression of ERβ opposed the phenotypic changes and down-regulation of E-cadherin induced by ER⍺. In addition, microarray analysis was performed to characterize more putative downstream mediators of E2. Expression levels of 486 genes were found to be altered by at least 50% upon E2 treatment, and included several genes involved in oncogenesis, cell cycle control, apoptosis, signal transduction and the gene expression machinery. These candidate genes may be valuable for better delineating the ER pathways and functions. In summary, this study provides compelling arguments that estrogen can potentiate tumor progression by EMT induction, and highlight the crucial role of ER⍺ in ovarian tumorigenesis.
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Eng, Frank Chung Sing 1972. "Molecular mechanisms of estrogen receptor signaling." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38483.
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The estrogen receptor (ER) is a ligand dependent transcriptional activator that belongs to the steroid/nuclear receptor superfamily. To probe the structure and function of the ER ligand binding domain (LBD), we developed a genetic screen in yeast Saccharomyces cerevisiae using a library of reverse ERs screened with a low affinity estrogen agonist, 2-methoxyestrone. Mutants isolated from this screen demonstrated altered ligand binding and/or transactivation properties. One of these mutants, L536P, showed high levels of constitutive activity in several transiently transfected cells and a HeLa line that stably propagates an estrogen-sensitive reporter gene. This suggests that substitution of a proline at position 536 in the wild type ER (HEGO) induces a reversible conformational change in the region of AF-2 that partially mimics activation of the receptor by hormone binding.<br>Activation of transcription by the ER requires the recruitment of different classes of coactivators. L536P interacted with coactivators in the absence of hormone and this constitutive interaction can be abolished by antiestrogens. We conclude that constitutive activity of L536P-HEGO is manifested to in part from constitutive coactivator binding. We also demonstrated that different classes of coactivators do not recognize the ER LBD in the same manner and can compete for binding to the ER LBD suggesting that different classes of coactivators recognize distinct but overlapping binding sites. Interestingly, coexpression of RIP140 blocked enhanced transactivation by HEGO observed in the presence of TIF-2, suggesting that RIP140 may play a negative role in ER signaling.<br>Using a yeast two-hybrid system with the ER LBD as bait, we isolated a novel estrogen receptor cofactor (ERC) that interacts with the ER LBD in a hormone dependent manner. The primary structure of ERC consists of 4 ankyrin repeat domains, 2 LXXLL motifs and an ATP/GTP binding domain. ERC is highly expressed in ovary, testes, and spleen, with moderate levels in heart, brain, and placenta. ERC repressed ER transactivation in several cell lines in the presence of estradiol suggesting that ERC may function as a novel estrogen dependent repressor of the ER. Immunohistochemistry and confocal microscopy localized ERC to the cytoplasm with partial nuclear staining. Recently, synphilin-1, a novel protein that has been implicated in the pathogenesis of Parkinson's disease was isolated and is identical to ERC. A role for ERC in intracellular signaling through a membrane bound ER in the brain is currently being investigated.
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Greiwe, Kelly. "Effects of estrogen on aggressive behavior." Connect to resource, 2006. http://hdl.handle.net/1811/6576.
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Thesis (Honors)--Ohio State University, 2006.<br>Title from first page of PDF file. Document formatted into pages: contains 18 p.; also includes graphics. Includes bibliographical references (p. 16-18) Available online via Ohio State University's Knowledge Bank.
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Mhyre, Andrew James. "Mechanisms of estrogen signaling in astrocytes /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/6266.
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Heldring, Nina. "Molecular basis of estrogen receptor antagonism /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-634-4/.
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Singer, Cherie A. "Neurotrophic and neuroprotective effects of estrogen /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/6301.
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Jain, Disha. "New approaches to estrogen receptor modulation." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 157 p, 2009. http://proquest.umi.com/pqdweb?did=1818417411&sid=4&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Nelson, Adam William. "Estrogen receptor beta modulates prostate carcinogenesis." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267736.
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Prostate cancer (PC) is characterised by dependence upon androgen receptor (AR) as its driving oncogene. When organ-confined, radical treatment can be curative, however there is no cure for advanced, castration-resistant prostate cancer (CRPC). There is therefore a need to better understand the biology of PC, and how influencing AR can modify disease progression. Estrogen is essential for prostate carcinogenesis with evidence from epidemiological, in vitro, human tissue and animal studies. Most suggests that estrogen receptor beta (ERβ) is tumour-suppressive, but trials of ERβ-selective agents have not improved clinical outcomes. ERβ has also been implicated as an oncogene, therefore its role remains unclear. Additional evidence suggests interplay between ERβ and AR, the mechanisms of which are uncertain. The study hypothesis ‘ERβ is an important modulator of prostate carcinogenesis’ was developed to establish whether targeting ERβ could affect PC progression. Much of the confusion around ERβ stems from use of inadequately validated antibodies and cell line models. The first phase of this work was to test ERβ antibodies using an ERβ-inducible cell system. Eight ERβ antibodies were assessed by multiple techniques, showing that commonly used antibodies are either non-specific or only specific in one modality. Two reliable antibodies were identified. Next, cell lines previously used to study ERβ were assessed using validated antibodies and independent approaches. No ERβ expression was detected; an important finding that casts doubt on previously published ERβ biology. Subsequently, a PC cell line with inducible ERβ expression (LNCaP-ERβ) was developed and validated to enable controlled experiments on the effects of ERβ on proliferation, gene expression and ERβ/AR genomic cross-talk. Phase three of this work focused on ERβ biology in PC and its relationship to AR. Interrogation of clinical datasets showed that greater ERβ expression associated with favourable prognosis. Gene expression data from men treated with androgen deprivation therapy revealed that AR represses ERβ. This was confirmed in vitro. The LNCaP-ERβ cell line was treated with androgen and/or ERβ-selective estrogen. Activated ERβ in the presence of androgen-stimulated AR inhibited cell proliferation and down-regulated androgen-dependent genes. Genome-wide mapping of ERβ binding sites reveals that ERβ antagonises AR through competition for shared DNA binding sites. In conclusion, ERβ expression is down-regulated by AR during malignant transformation of prostate epithelium. We reveal an antagonistic relationship between ERβ and AR whereby sustaining or replacing ERβ may inhibit tumour growth through down-regulation of AR-target genes. In future, an ERβ-selective compound may be used to slow or abrogate PC progression.
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Mobley, James Austin. "Oxidative mechanisms of estrogen induced carcinogenesis /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu148819623490807.
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Zilmer, Johansen Anne Katrine. "Estrogen metabolism in pulmonary arterial hypertension." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5199/.
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Pulmonary arterial hypertension (PAH) is a devastating and progressive vasculopathy of the pulmonary arteries for which there is no cure. There is an urgent need for more effective therapies. PAH is characterised by elevated pulmonary arterial pressures and obstructive vascular lesions in the distal vasculature by excessive cellular proliferation. As a result, the right ventricle is placed under excessive strain resulting in adaptive hypertrophy which progresses to maladaptive hypertrophy and failure. PAH is more common in women than in men suggesting that estrogens may be integral to disease pathogenesis. Understanding the biological basis for this sex difference would offer a new treatment paradigm in this devastating cardiovascular disease. Here, we challenged the concept that the estrogen metabolic axis is dysregulated in PAH New insights have revealed a potential contribution of the estrogen metabolizing enzyme, cytochrome P450 1B1 (CYP1B1) in the development of PAH. 17β-estradiol (17β-E2) and estrone (E1) are metabolized by the activity of CYP1B1 to the 2-, 4- and 16-hydroxylated estrogens. Here, we defined the role of CYP1B1 in the pathogenesis of PAH. CYP1B1 expression was increased in both experimental (hypoxia and SU5416+hypoxia) and in heritable and idiopathic PAH (HPAH and IPAH, respectively). Both male and female CYP1B1 knockout mice (CYP1B1-/-) were challenged with chronic hypoxia to induce PAH as assessed by right ventricular systolic pressures (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodeling. CYP1B1-/- mice were protected against hypoxia-induced pulmonary hypertension (PH). CYP1B1 inhibition with the highly potent and selective inhibitor 2,3',4,5'-tetramethoxystilbene (TMS; 3 mg/kg/day by intra-peritoneal injection) attenuated the development of hypoxia-induced PH. Only moderate effects were observed with CYP1B1 inhibition in monocrotaline-induced PH, despite improving survival rates. Female mice that over-express the human serotonin transporter gene (SERT+ mice) develop a spontaneous PAH phenotype at 5 months of age which is dependent on circulating levels of 17β-E2. Here, we provide evidence that the estrogen metabolic axis is dysregulated in these mice and this may underlie their PAH phenotype. The estrogen synthesizing enzyme aromatase and CYP1B1 was increased in whole lung homogenates of female SERT+ mice compared to wild-type mice. Despite increased expression of aromatase, 17β-E2 concentrations were unchanged. CYP1B1 inhibition with TMS (1.5mg/kg/day by intra-peritoneal injection) attenuated the PAH phenotype in female SERT+ mice as assessed by RVSP and pulmonary vascular remodeling Other studies have identified that the 16-hydroxylated metabolites of estrogens (17β-E2 and E1) are the only CYP1B1 metabolites to induce cellular proliferation, with the most profound effects observed with 16α-hydroxyestrone (16α-OHE1). In mice exposed to chronic hypoxia, urinary concentrations of 16α-OHE1 were increased. Chronic dosing of 16α-OHE1 in mice (1.5mg/kg/day by intra-peritoneal injection for 28 days) resulted in the development of a PAH phenotype in female mice only. 16α-OHE1 induced cellular proliferation in human pulmonary arterial smooth muscle cells (hPASMCs) and this was inhibited by a scavenger of reactive oxygen species (ROS) and an inhibitor of extracellular regulated kinase 1/2 (ERK 1/2). 4-hydroxylation is the predominant metabolic pathway activated by CYP1B1 activity and we therefore investigated the effects of the 4-hydroxylated metabolite of 17β-E2 in vivo. 4-hydroxyestradiol (4-OHE2) had no effects on PAH parameters in mice (1.5mg/kg/day by intra-peritoneal injection for 28 days). However, serotonin-induced vasoconstriction of the intra-pulmonary arteries was dramatically reduced in arteries harvested from mice dosed with 4-OHE2. More recent studies have identified that 4-hydroxyestrone (4-OHE1) is the predominant CYP1B1 metabolite in the lungs of mice. Interestingly, despite evidence for a pathogenic function of CYP1B1 activity in vivo, 4-OHE1 inhibited cellular proliferation in hPASMCs as assessed by thymidine incorporation whilst no effects were reported on cell viability. We provide evidence for an altered estrogen metabolic axis in PAH, by in part, overexpression of the putatively pathological CYP1B1. Yet, the dynamic estrogen metabolic profile in pulmonary vascular cells remains undetermined. To address this, we developed a high fidelity HPLC method to quantitatively fate map estrogen metabolism in hPASMCs to determine the dynamic regulation of estrogen metabolism in PAH. We provide the first direct evidence that hPASMCs metabolize 17β-E2 and that estrogen metabolism is pathologically altered in PAH. Our metabolic screen revealed a prominent role for 17β-hydroxysteroid dehydrogenase enzymes in hPASMCs by rapid formation of E1 in all groups studied, increasing with time, with the highest activity in male control hPASMCs and the lowest activity in female control hPASMCs. In female control hPASMCs there was no evidence of CYP activity, whilst numerous metabolites were formed in the other groups studied. The formation of the pathogenic 16α-hydroxylated estrogens was only evident in PASMCs from both male and female PAH patients at 24 and 48 hours. Globally, this study introduces a platform to elucidate effects of PAH insults and potential therapies on the estrogen-metabolic profile in pulmonary vascular cells. Overall, we provide eminent evidence that the estrogen metabolic axis is pathologically altered in PAH and is influenced by gender. This provides a strong rationale for the application of estrogen-sensitive therapies in the management of this highly female discriminating disease.