• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 594
  • 185
  • 85
  • 47
  • 31
  • 26
  • 19
  • 19
  • 19
  • 19
  • 19
  • 19
  • 16
  • 15
  • 8
  • Tagged with
  • 1167
  • 342
  • 208
  • 188
  • 185
  • 118
  • 97
  • 90
  • 78
  • 73
  • 66
  • 63
  • 61
  • 60
  • 58
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Identification and characterization of ligand-dependent estrogen receptor-associated proteins as modulators of receptor action /

Loria, Paula M. January 1999 (has links)
Thesis (Ph. D.)--University of Chicago, Dept. of Biochemistry and Molecular Biology, August 1999. / Includes bibliographical references. Also available on the Internet.
22

The chemical behavior of estrone and 17beta-estradiol in the environment

Ullman, Jeffrey Layton 17 September 2007 (has links)
The endogenous hormones estrone and 17β-estradiol support vertebrate growth and development, but slight increases above ambient concentrations may paradoxically induce endocrine disruption, leading to increased frequencies of reproductive disorders and cancer in humans and wildlife. Livestock excrete estrogenic compounds which can lead to surface and groundwater contamination. Limited information exists concerning estrogen fate and transport, as exposure concerns have recently arisen. This study examined the chemical behavior of estrone and 17β-estradiol with the goal of elucidating manure management principles applicable to animal feeding operations (AFOs). Both compounds indicated that they are susceptible to physicochemical and biological decomposition. Photolysis yielded 27- and 35-day half-lives for estrone and 17β-estradiol at pH 7, respectively, based on test conditions. 17β-estradiol photolysis exhibited a slight pH-dependent behavior. Mineralization produced half-lives ranging from 7 to 15 days for estrone and 3 to 7 days for 17β-estradiol. Indigenous microbial populations did not demonstrate a lag phase and therefore appeared to have been well acclimated to degrading these compounds. Anaerobic lagoon supplements did not affect mineralization rates. The compounds had partition coefficients ranging from 2 to 4.4 mL g-1, depending on soil characteristics. Estrone and 17β-estradiol had a higher absorptivity to soils with greater clay content and organic matter. Once sorbed, binding appeared largely irreversible with minimal desorption. Column experiments detected no estrone in the leachate for the finer textured soils, while estrone had completely migrated through the loamy fine sand after 7 pore volumes. Hypothetical scenarios, simulated using HYDRUS-1D, evaluated the combined effects of soil texture and the values obtained for sorption and mineralization on leaching. Model results indicated rapid leaching in loamy sand, while sandy clay loam and clay yielded significantly slower estrone and 17β-estradiol movement with concentrations 1 to 3 orders of magnitude lower. Data suggest that estrogens applied to sandy soil may leach and contaminate groundwater, especially in the presence of shallow water tables. Sandy clay loam and clay likely present minimal risk for subsurface mobility, but simulated accumulation near the soil surface may promote transport via overland flow. Sound manure management practices will likely reduce off-site transport of estrogens originating from AFOs.
23

Mechanisms of transcriptional activation of estrogen responsive genes in breast cancer cells

Chen, Chien-Cheng 02 June 2009 (has links)
Estrogen receptor (ER) acts as a ligand-activated transcription factor that regulates the expression of genes. The genomic mechanisms of ER action include ligand-induced dimerization of ER which binds estrogen responsive elements (EREs) in the promoters of target genes. There are also nongenomic mechanisms of ER action which are associated with membrane bound or cytosol ER-dependent activation of various protein-kinase cascades which also influence expression of target genes. Egr-1 is an immediate-early gene induced by 17β-estradiol (E2) in the rodent uterus and breast cancer cells. Deletion analysis of the Egr-1 promoter identified a minimal E2-responsive region that contained serum response element (SRE3) which bound Elk-1 and serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a MAPKK inhibitor, but not by LY294002, an inhibitor of PI3-K. These results contrasted with the hormone-dependent activation of the SRE in the c-fos promoter, which was inhibited by both PD98059 and LY294002, suggesting that Egr-1, like c-fos, is activated through non-genomic pathways of estrogen action but through activation of different kinases. COUP-TFs are orphan nuclear receptors expressed in a variety of tissues where they regulate biological functions and organogenesis. In this study, we investigated coactivation of ERα by COUP-TF1 in cell lines transiently cotransfected with the pERE3 construct. COUP-TFI coactivated ERα-mediated transactivation, but unlike many other coactivators, COUP-TFI also enhanced transactivation of ERα when cells were cotransfected with the TAF1-ERα mutant or the 19c-ERα mutant. These data indicate that helix 12 of ERα is not required for coactivation by COUP-TFI when AF-1 of ERα is intact. However, when the AF-1 of ERα is deleted, the intact AF-2 function is required for coactivation by COUP-TFI. Analysis of multiple COUP-TFI deletion mutants showed that the DNA-binding domain and C-terminal region of COUP-TFI were important for coactivation of ERα. Point mutations of the DNA-binding domain of COUP-TFI resulted in loss of interactions with ERα, suggesting that the DNA-binding domain of COUP-TFI is important for its coactivation activity facilitating interactions with ERα. These results demonstrate that COUP-TFI coactivated ERα through a non-classical LXXLL-independent pathway.
24

The role of estrogen receptors in the contribution of constrictor prostanoids to aortic coarctation-induced hypertension

Sellers, Minga Miown 15 May 2009 (has links)
This study investigated the effects of selective estrogen receptor (ER) agonists on constrictor prostanoid (CP) function and on the development of mean arterial pressure (MAP) in aortic coarctation-induced hypertension (ACIH). Female Sprague-Dawley rats were divided randomly into four groups: intact (INT), ovariectomized (OVX), OVX + ERα selective agonist (4, 4’, 4”-(4-Propyl-[1H]-pyrazole-1, 3, 5-triyl)trisphenol; OVX+PPT), or OVX + ERβ selective agonist (2,3-bis(4-Hydroxyphenyl)-propionitrile; OVX+DPN). Rats were then subjected to abdominal aortic coarctation (hypertensive, HT) or sham surgery (normotensive, NT). PPT, DPN or vehicle treatments were given daily as a subcutaneous injection. MAP was measured every other day at 2-14 days after coarctation. Mesenteric arterioles were harvested 12-14 days after coarctation for isometric tension studies to examine concentration-responses to VP. Basal and VP-stimulated prostanoid release and mRNA and protein levels of ERα and ERβ (using real time RT-PCR and immunoblotting) were measured in separate groups of arterioles. MAP was higher in INT-HT, OVX+PPT-HT and OVX+DPN-HT than in OVX-HT after 12 days. Vascular reactivity to VP was greater in OVX+PPT-NT rats than in other groups. There were no significant differences in vascular reactivity to VP in HT groups. Blockade of thromboxane receptor (TP) with SQ 29,548 (TP receptor antagonist) did not have a significant effect in any groups. Inhibition of intracellular calcium release with simvastatin (blocker of IP3 mediated calcium release) was greater in NT than in HT groups, and greater in OVX- and DPN-treated groups than in INT and PPT-treated groups. VP-stimulated release of thromboxane (TXA2) and prostacyclin (PGI2) were highest in INT-HT and OVX+PPT-HT rats. Neither mRNA nor protein expression of ERs changed significantly in response to selective ER agonist treatment or during hypertension. Selective ERα stimulation with PPT during development of ACIH resulted in similar effects to those seen in INT rats for CP release, VP reactivity of mesenteric arterioles and MAP, while selective stimulation of ERβ only increased MAP. While ERα is capable of modulating most of the effects of estrogen on the vasculature, ERβ has stimulatory effects on MAP during the development of ACIH that merit further investigation. Further studies of the vascular actions of ERα and ERβ may lead to better hormonal therapies that successfully prevent and/or treat cardiovascular disease in post-menopausal women.
25

The role of estrogen receptors in the contribution of constrictor prostanoids to aortic coarctation-induced hypertension

Sellers, Minga Miown 15 May 2009 (has links)
This study investigated the effects of selective estrogen receptor (ER) agonists on constrictor prostanoid (CP) function and on the development of mean arterial pressure (MAP) in aortic coarctation-induced hypertension (ACIH). Female Sprague-Dawley rats were divided randomly into four groups: intact (INT), ovariectomized (OVX), OVX + ERα selective agonist (4, 4’, 4”-(4-Propyl-[1H]-pyrazole-1, 3, 5-triyl)trisphenol; OVX+PPT), or OVX + ERβ selective agonist (2,3-bis(4-Hydroxyphenyl)-propionitrile; OVX+DPN). Rats were then subjected to abdominal aortic coarctation (hypertensive, HT) or sham surgery (normotensive, NT). PPT, DPN or vehicle treatments were given daily as a subcutaneous injection. MAP was measured every other day at 2-14 days after coarctation. Mesenteric arterioles were harvested 12-14 days after coarctation for isometric tension studies to examine concentration-responses to VP. Basal and VP-stimulated prostanoid release and mRNA and protein levels of ERα and ERβ (using real time RT-PCR and immunoblotting) were measured in separate groups of arterioles. MAP was higher in INT-HT, OVX+PPT-HT and OVX+DPN-HT than in OVX-HT after 12 days. Vascular reactivity to VP was greater in OVX+PPT-NT rats than in other groups. There were no significant differences in vascular reactivity to VP in HT groups. Blockade of thromboxane receptor (TP) with SQ 29,548 (TP receptor antagonist) did not have a significant effect in any groups. Inhibition of intracellular calcium release with simvastatin (blocker of IP3 mediated calcium release) was greater in NT than in HT groups, and greater in OVX- and DPN-treated groups than in INT and PPT-treated groups. VP-stimulated release of thromboxane (TXA2) and prostacyclin (PGI2) were highest in INT-HT and OVX+PPT-HT rats. Neither mRNA nor protein expression of ERs changed significantly in response to selective ER agonist treatment or during hypertension. Selective ERα stimulation with PPT during development of ACIH resulted in similar effects to those seen in INT rats for CP release, VP reactivity of mesenteric arterioles and MAP, while selective stimulation of ERβ only increased MAP. While ERα is capable of modulating most of the effects of estrogen on the vasculature, ERβ has stimulatory effects on MAP during the development of ACIH that merit further investigation. Further studies of the vascular actions of ERα and ERβ may lead to better hormonal therapies that successfully prevent and/or treat cardiovascular disease in post-menopausal women.
26

Mechanisms of transcriptional activation of estrogen responsive genes in breast cancer cells

Chen, Chien-Cheng 02 June 2009 (has links)
Estrogen receptor (ER) acts as a ligand-activated transcription factor that regulates the expression of genes. The genomic mechanisms of ER action include ligand-induced dimerization of ER which binds estrogen responsive elements (EREs) in the promoters of target genes. There are also nongenomic mechanisms of ER action which are associated with membrane bound or cytosol ER-dependent activation of various protein-kinase cascades which also influence expression of target genes. Egr-1 is an immediate-early gene induced by 17β-estradiol (E2) in the rodent uterus and breast cancer cells. Deletion analysis of the Egr-1 promoter identified a minimal E2-responsive region that contained serum response element (SRE3) which bound Elk-1 and serum response factor (SRF) in gel mobility shift assays. Hormone-responsiveness of Egr-1 in MCF-7 cells was specifically inhibited by PD98059, a MAPKK inhibitor, but not by LY294002, an inhibitor of PI3-K. These results contrasted with the hormone-dependent activation of the SRE in the c-fos promoter, which was inhibited by both PD98059 and LY294002, suggesting that Egr-1, like c-fos, is activated through non-genomic pathways of estrogen action but through activation of different kinases. COUP-TFs are orphan nuclear receptors expressed in a variety of tissues where they regulate biological functions and organogenesis. In this study, we investigated coactivation of ERα by COUP-TF1 in cell lines transiently cotransfected with the pERE3 construct. COUP-TFI coactivated ERα-mediated transactivation, but unlike many other coactivators, COUP-TFI also enhanced transactivation of ERα when cells were cotransfected with the TAF1-ERα mutant or the 19c-ERα mutant. These data indicate that helix 12 of ERα is not required for coactivation by COUP-TFI when AF-1 of ERα is intact. However, when the AF-1 of ERα is deleted, the intact AF-2 function is required for coactivation by COUP-TFI. Analysis of multiple COUP-TFI deletion mutants showed that the DNA-binding domain and C-terminal region of COUP-TFI were important for coactivation of ERα. Point mutations of the DNA-binding domain of COUP-TFI resulted in loss of interactions with ERα, suggesting that the DNA-binding domain of COUP-TFI is important for its coactivation activity facilitating interactions with ERα. These results demonstrate that COUP-TFI coactivated ERα through a non-classical LXXLL-independent pathway.
27

The chemical behavior of estrone and 17beta-estradiol in the environment

Ullman, Jeffrey Layton 17 September 2007 (has links)
The endogenous hormones estrone and 17β-estradiol support vertebrate growth and development, but slight increases above ambient concentrations may paradoxically induce endocrine disruption, leading to increased frequencies of reproductive disorders and cancer in humans and wildlife. Livestock excrete estrogenic compounds which can lead to surface and groundwater contamination. Limited information exists concerning estrogen fate and transport, as exposure concerns have recently arisen. This study examined the chemical behavior of estrone and 17β-estradiol with the goal of elucidating manure management principles applicable to animal feeding operations (AFOs). Both compounds indicated that they are susceptible to physicochemical and biological decomposition. Photolysis yielded 27- and 35-day half-lives for estrone and 17β-estradiol at pH 7, respectively, based on test conditions. 17β-estradiol photolysis exhibited a slight pH-dependent behavior. Mineralization produced half-lives ranging from 7 to 15 days for estrone and 3 to 7 days for 17β-estradiol. Indigenous microbial populations did not demonstrate a lag phase and therefore appeared to have been well acclimated to degrading these compounds. Anaerobic lagoon supplements did not affect mineralization rates. The compounds had partition coefficients ranging from 2 to 4.4 mL g-1, depending on soil characteristics. Estrone and 17β-estradiol had a higher absorptivity to soils with greater clay content and organic matter. Once sorbed, binding appeared largely irreversible with minimal desorption. Column experiments detected no estrone in the leachate for the finer textured soils, while estrone had completely migrated through the loamy fine sand after 7 pore volumes. Hypothetical scenarios, simulated using HYDRUS-1D, evaluated the combined effects of soil texture and the values obtained for sorption and mineralization on leaching. Model results indicated rapid leaching in loamy sand, while sandy clay loam and clay yielded significantly slower estrone and 17β-estradiol movement with concentrations 1 to 3 orders of magnitude lower. Data suggest that estrogens applied to sandy soil may leach and contaminate groundwater, especially in the presence of shallow water tables. Sandy clay loam and clay likely present minimal risk for subsurface mobility, but simulated accumulation near the soil surface may promote transport via overland flow. Sound manure management practices will likely reduce off-site transport of estrogens originating from AFOs.
28

Effect of GPR30 agonists on the release of prostaglandins in vascular cells

Wong, Cheong, Ida. January 2009 (has links)
Thesis (M.Med.Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 44-53).
29

Estrogen in ovarian cancer cell metastasis

Park, Se Hyung 11 1900 (has links)
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.
30

The relative estrogenic activity of toxaphene and isolated T2 and T12 congeners /

Stelzer, Andreas. January 1998 (has links)
Toxaphene is the most abundant persistent organic pollutant in the Arctic and in the Great Lakes. Toxaphene technical mixture (Tox) applied as a pesticide consists of over 800 congeners. Through processes of environmental degradation, selected metabolism, and bioaccumulation, 2 congeners are prominent in humans; 2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane (T2) and 2-exo,3-endo,5-exo,6-endo,8,8,9,10,10-nonachlorocamphene (T12). The MCF7-E3 human breast cancer cell model was used to screen for the estrogenic activities of Tox, T2, and T12. A concentration of 10muM was required by all 3 compounds to elicit an estrogenic response (a proliferative effect (PE) upon the cells). The congeners however, showed slightly different PEs from Tox. Both T2 and T12 had a lower PE than Tox, and T2 had a higher PE than T12. Results from binary combination studies showed that effects of Tox, T2, and T12 were additive. Tox, T2, and T12 had no significant effects on estrogen receptor and progesterone receptor levels. It was shown that the environmental prevalent congeners had lower estrogenic activities than Tox and there is no synergistic effect.

Page generated in 0.0698 seconds