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Sample records for hydrocarbon receptor-dependent estrogen

  1. Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methylcholanthrene.

    PubMed

    Shipley, Jonathan M; Waxman, David J

    2006-06-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that stimulates transcription directed by xenobiotic response elements upstream of target genes. Recently, AhR ligands were reported to induce formation of an AhR-estrogen receptor (ER) complex, which can bind to estrogen response elements (EREs) and stimulate transcription of ER target genes. Presently, we investigate the effect of the AhR ligands 3-methylcholanthrene (3MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3,3',4,4',5-pentachlorobiphenyl (BZ126) on ERE-regulated luciferase reporter activity and endogenous ER target gene expression. In MCF-7 human breast cancer cells, 3MC induced transcription of ER reporter genes containing native promoter sequences of the ER-responsive genes complement 3 and pS2 and heterologous promoters regulated by isolated EREs. Dose-response studies revealed that the concentration of 3MC required to half-maximally activate transcription (EC(50)) was >100-fold higher for an ER reporter (27-57 muM) than for an AhR reporter (86-250 nM) in both MCF-7 cells and in human endometrial cancer Ishikawa cells. 3MC also stimulated expression of the endogenous ER target genes amphiregulin, cathepsin D and progesterone receptor, albeit to a much lower extent than was achieved following stimulation with 17beta-estradiol. In Ishikawa cells, 3MC, but not BZ126 or TCDD, stimulated ERalpha-dependent reporter activity but did not induce expression of endogenous ER target genes. Finally, studies carried out in the AhR-positive rat hepatoma cell line 5L and the AhR-deficient variant BP8 demonstrated that ER reporter activity could be induced by 3MC in a manner that was independent of AhR and thus distinct from the AhR-ER 'hijacking' mechanism described recently. 3MC may thus elicit estrogenic activity by multiple mechanisms.

  2. Aryl hydrocarbon receptor-independent activation of estrogen receptor-dependent transcription by 3-methycholanthrene

    SciTech Connect

    Shipley, Jonathan M.; Waxman, David J. . E-mail: djw@bu.edu

    2006-06-01

    Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that stimulates transcription directed by xenobiotic response elements upstream of target genes. Recently, AhR ligands were reported to induce formation of an AhR-estrogen receptor (ER) complex, which can bind to estrogen response elements (EREs) and stimulate transcription of ER target genes. Presently, we investigate the effect of the AhR ligands 3-methylcholanthrene (3MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3,3',4,4',5-pentachlorobiphenyl (BZ126) on ERE-regulated luciferase reporter activity and endogenous ER target gene expression. In MCF-7 human breast cancer cells, 3MC induced transcription of ER reporter genes containing native promoter sequences of the ER-responsive genes complement 3 and pS2 and heterologous promoters regulated by isolated EREs. Dose-response studies revealed that the concentration of 3MC required to half-maximally activate transcription (EC{sub 5}) was >100-fold higher for an ER reporter (27-57 {mu}M) than for an AhR reporter (86-250 nM) in both MCF-7 cells and in human endometrial cancer Ishikawa cells. 3MC also stimulated expression of the endogenous ER target genes amphiregulin, cathepsin D and progesterone receptor, albeit to a much lower extent than was achieved following stimulation with 17{beta}-estradiol. In Ishikawa cells, 3MC, but not BZ126 or TCDD, stimulated ER{alpha}-dependent reporter activity but did not induce expression of endogenous ER target genes. Finally, studies carried out in the AhR-positive rat hepatoma cell line 5L and the AhR-deficient variant BP8 demonstrated that ER reporter activity could be induced by 3MC in a manner that was independent of AhR and thus distinct from the AhR-ER 'hijacking' mechanism described recently. 3MC may thus elicit estrogenic activity by multiple mechanisms.

  3. Estrogen Receptor-Dependent Regulation of Dendritic Cell Development and Function

    PubMed Central

    Laffont, Sophie; Seillet, Cyril; Guéry, Jean-Charles

    2017-01-01

    Autoimmunity, infectious diseases and cancer affect women and men differently. Because they tend to develop more vigorous adaptive immune responses than men, women are less susceptible to some infectious diseases but also at higher risk of autoimmunity. The regulation of immune responses by sex-dependent factors probably involves several non-redundant mechanisms. A privileged area of study, however, concerns the role of sex steroid hormones in the biology of innate immune cells, especially dendritic cells (DCs). In recent years, our understanding of the lineage origin of DC populations has expanded, and the lineage-committing transcription factors shaping peripheral DC subsets have been identified. Both progenitor cells and mature DC subsets express estrogen receptors (ERs), which are ligand-dependent transcription factors. This suggests that estrogens may contribute to the reported sex differences in immunity by regulating DC biology. Here, we review the recent literature and highlight evidence that estrogen-dependent activation of ERα regulates the development or the functional responses of particular DC subsets. The in vitro model of GM-CSF-induced DC differentiation shows that CD11c+ CD11bint Ly6cneg cells depend on ERα activation by estrogen for their development, and for the acquisition of competence to activate naive CD4+ T lymphocytes and mount a robust pro-inflammatory cytokine response to CD40 stimulation. In this model, estrogen signaling in conjunction with GM-CSF is necessary to promote early interferon regulatory factor (Irf)-4 expression in macrophage-DC progenitors and their subsequent differentiation into IRF-4hi CD11c+ CD11bint Ly6cneg cells, closely related to the cDC2 subset. The Flt3L-induced model of DC differentiation in turn shows that ERα signaling promotes the development of conventional DC (cDC) and plasmacytoid DC (pDC) with higher capability of pro-inflammatory cytokine production in response to TLR stimulation. Likewise, cell

  4. Aryl hydrocarbon receptor-dependent liver development and hepatotoxicity are mediated by different cell types.

    PubMed

    Walisser, Jacqueline A; Glover, Edward; Pande, Kalyan; Liss, Adam L; Bradfield, Christopher A

    2005-12-06

    The aryl hydrocarbon receptor (AHR) plays a role in three areas of biology that include the adaptive metabolism of xenobiotics, the toxic responses associated with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), and vascular remodeling of the developing embryo. To test the hypothesis that receptor signaling in different cell types is responsible for these aspects of AHR biology, we generated a conditional Ahr allele where exon 2 is flanked by loxP sites. Through the use of Cre-lox technology, we then investigated the role of AHR signaling in hepatocytes or endothelial cells in mediating prototypical endpoints of adaptive, toxic, or developmental signaling. Using this model, we provide evidence that AHR signaling in endothelial/hematopoietic cells is necessary for developmental closure of the ductus venosus, whereas AHR signaling in hepatocytes is necessary to generate adaptive and toxic responses of the liver in response to dioxin exposure. Taken together, these data illustrate the importance of cell-specific receptor signaling for the generation of distinct AHR-dependent physiological outcomes.

  5. Functions of Danggui Buxue Tang, a Chinese Herbal Decoction Containing Astragali Radix and Angelicae Sinensis Radix, in Uterus and Liver are Both Estrogen Receptor-Dependent and -Independent

    PubMed Central

    Zierau, Oliver; Zheng, Ken Y. Z.; Dong, Tina T. X.; Tsim, Karl W. K.; Vollmer, Günter

    2014-01-01

    Danggui Buxue Tang (DBT), a herbal decoction containing Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), has been used in treating menopausal irregularity in women for more than 800 years in China. Pharmacological results showed that DBT exhibited significant estrogenic properties in vitro, which therefore suggested that DBT could activate the nuclear estrogen receptors. Here, we assessed the estrogenic properties of DBT in an ovariectomized in vivo rat model: DBT was applied to the ovariectomized rats for 3 days. The application of DBT did not alter the weight of uterus and liver, as well as the transcript expression of the proliferation markers including the estrogen receptors α and β. However, DBT stimulated the transcript expression of the estrogen responsive genes. In addition, the inductive role of DBT on the expression of members of the aryl hydrocarbon receptor family in uterus and liver of ovariectomized rats was confirmed. These responses of DBT however were clearly distinct from the response pattern detectable here for 17β-estradiol. Therefore, DBT exhibited weak, but significant, estrogenic properties in vivo; however, some of its activities were independent of the estrogen receptor. Thus, DBT could be an exciting Chinese herbal decoction for an alternative treatment of hormone replacement therapy for women in menopause without subsequent estrogenic side effects. PMID:25214874

  6. Molecular Mechanism of Action of Genistein and Related Phytoestrogens in Estrogen Receptor Dependent & Independent Growth of Breast Cancer Cells.

    DTIC Science & Technology

    1998-07-01

    of 900 nM (task 1). Quercetin and genistein also bind to the type-II estrogen binding sites, and exert cell growth inhibition in MCF-7 and MDA-MB-468...In addition, we show that cell growth inhibition by genistein and quercetin is associated with decreased polyamine levels. Our results provide

  7. Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites.

    PubMed

    Van de Wiele, Tom; Vanhaecke, Lynn; Boeckaert, Charlotte; Peru, Kerry; Headley, John; Verstraete, Willy; Siciliano, Steven

    2005-01-01

    Ingestion is an important exposure route for polycyclic aromatic hydrocarbons (PAHs) to enter the human body. Although the formation of hazardous PAH metabolites by human biotransformation enzymes is well documented, nothing is known about the PAH transformation potency of human intestinal microbiota. Using a gastrointestinal simulator, we show that human intestinal microbiota can also bioactivate PAHs, more in particular to estrogenic metabolites. PAH compounds are not estrogenic, and indeed, stomach and small intestine digestions of 62.5 nmol naphthalene, phenanthrene, pyrene, and benzo(a)pyrene showed no estrogenic effects in the human estrogen receptor bioassay. In contrast, colon digests of these PAH compounds displayed estrogenicity, equivalent to 0.31, 2.14, 2.70, and 1.48 nmol 17alpha-ethynylestradiol (EE2), respectively. Inactivating the colon microbiota eliminated these estrogenic effects. Liquid chromatography-mass spectrometry analysis confirmed the microbial PAH transformation by the detection of PAH metabolites 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene in colon digests of pyrene and benzo(a)pyrene. Furthermore, we show that colon digests of a PAH-contaminated soil (simulated ingestion dose of 5 g/day) displayed estrogenic activity equivalent to 0.58 nmol EE2, whereas stomach or small intestine digests did not. Although the matrix in which PAHs are ingested may result in lower exposure concentrations in the gut, our results imply that the PAH bioactivation potency of colon microbiota is not eliminated by the presence of soil. Moreover, because PAH toxicity is also linked to estrogenicity of the compounds, the PAH bioactivation potency of colon microbiota suggests that current risk assessment may underestimate the risk from ingested PAHs.

  8. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors.

    PubMed Central

    Henttu, P M; Kalkhoven, E; Parker, M G

    1997-01-01

    Hormone-dependent transcriptional activation by nuclear receptors depends on the presence of a conserved C-terminal amphipathic alpha-helix (helix 12) in the ligand-binding domain. Here we show that a lysine residue, which is conserved in most nuclear receptors in the predicted helix 3, is also required for estrogen-dependent transactivation. The replacement of lysine 366 with alanine appreciably reduced activation function 2 (AF-2) activity without affecting steroid- or DNA-binding activity in the mouse estrogen receptor. The mutation dramatically reduced the ability of the receptor to bind steroid receptor coactivator 1 (SRC-1) but had no effect on receptor-interacting protein 140 (RIP-140) binding, indicating that while their sites of interaction overlap, they are not entirely consistent and in keeping with the proposal that the recruitment of coactivators, such as SRC-1, is required for AF-2 activity. Although the function of RIP-140 remains to be established, RIP-140 appears to be capable of recruiting the basal transcription machinery, since overexpression of the protein markedly increased the transcriptional activity of the mutant receptor. Since the lysine residue is conserved, we propose that it is required, together with residues in helix 12, to form the surface by which members of the nuclear receptor family interact with coactivators. PMID:9121431

  9. Egr1 is rapidly and transiently induced by estrogen and bisphenol A via activation of nuclear estrogen receptor-dependent ERK1/2 pathway in the uterus.

    PubMed

    Kim, Hye-Ryun; Kim, Yeon Sun; Yoon, Jung Ah; Lyu, Sang Woo; Shin, Hyejin; Lim, Hyunjung J; Hong, Seok-Ho; Lee, Dong Ryul; Song, Haengseok

    2014-12-01

    Coordinate actions of ovarian estrogen (E2) and progesterone (P4) via their own receptors are critical for establishing uterine receptivity for embryo implantation in the uterus. E2 regulates expression of an array of genes to mediate its major actions on heterogeneous uterine cell types. Here we have investigated regulatory mechanism(s) of E2 and bisphenol A (BPA), an endocrine disruptor with potent estrogenic activity on expression of early growth response 1 (Egr1), a zinc finger transcription factor that regulates cell growth, differentiation and apoptosis in the uterus. Egr1 was rapidly and transiently induced by E2 and BPA mainly in stromal cells via nuclear estrogen receptor (ER)-ERK1/2 pathway. ICI 182,780, an ER antagonist, effectively inhibited their actions on EGR1 expression following ERK1/2 phosphorylation. Administration of pharmacological inhibitors for ERK1/2, but not AKT significantly blocked EGR1 expression induced by E2 and BPA. P4 effectively dampened action(s) of E2 and BPA on Egr1 expression via nuclear progesterone receptor. Its antagonistic effects were partially interfered with RU486 pretreatment. Interestingly, EGR1 is specifically induced in stromal cells surrounding implanting blastocyst. Collectively, our results show that through nuclear ER-dependent ERK1/2 phosphorylation, not only E2 but also endocrine disruptors with estrogenic activity such as BPA rapidly and transiently induce Egr1 which may be important for embryo implantation and decidualization in mouse uterus.

  10. Aryl hydrocarbon receptor-dependent regulation of miR-196a expression controls lung fibroblast apoptosis but not proliferation

    SciTech Connect

    Hecht, Emelia; Zago, Michela; Sarill, Miles; Rico de Souza, Angela; Gomez, Alvin; Matthews, Jason; Hamid, Qutayba; Eidelman, David H.; Baglole, Carolyn J.

    2014-11-01

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor implicated in the regulation of apoptosis and proliferation. Although activation of the AhR by xenobiotics such as dioxin inhibits the cell cycle and control apoptosis, paradoxically, AhR expression also promotes cell proliferation and survival independent of exogenous ligands. The microRNA (miRNA) miR-196a has also emerged as a regulator of proliferation and apoptosis but a relationship between the AhR and miR-196a is not known. Therefore, we hypothesized that AhR-dependent regulation of endogenous miR-196a expression would promote cell survival and proliferation. Utilizing lung fibroblasts from AhR deficient (AhR{sup −/−}) and wild-type (AhR{sup +/+}) mice, we show that there is ligand-independent regulation of miRNA, including low miR-196a in AhR{sup −/−} cells. Validation by qRT-PCR revealed a significant decrease in basal expression of miR-196a in AhR{sup −/−} compared to AhR{sup +/+} cells. Exposure to AhR agonists benzo[a]pyrene (B[a]P) and FICZ as well as AhR antagonist CH-223191 decreased miR-196a expression in AhR{sup +/+} fibroblasts concomitant with decreased AhR protein levels. There was increased proliferation only in AhR{sup +/+} lung fibroblasts in response to serum, corresponding to a decrease in p27{sup KIP1} protein, a cyclin-dependent kinase inhibitor. Increasing the cellular levels of miR-196a had no effect on proliferation or expression of p27{sup KIP1} in AhR{sup −/−} fibroblasts but attenuated cigarette smoke-induced apoptosis. This study provides the first evidence that AhR expression is essential for the physiological regulation of cellular miRNA levels- including miR-196a. Future experiments designed to elucidate the functional relationship between the AhR and miR-196a may delineate additional novel ligand-independent roles for the AhR. - Highlights: • The AhR controls proliferation and apoptosis in lung cells. • The AhR regulates the

  11. In vitro estrogenicity of ambient particulate matter: contribution of hydroxylated polycyclic aromatic hydrocarbons.

    PubMed

    Wenger, Daniela; Gerecke, Andreas C; Heeb, Norbert V; Schmid, Peter; Hueglin, Christoph; Naegeli, Hanspeter; Zenobi, Renato

    2009-04-01

    Atmospheric particulate matter (PM1) was collected at an urban and a rural site in Switzerland during a hibernal high air pollution episode and was investigated for estrogenicity using an estrogen-sensitive reporter gene assay (ER-CALUX). All samples that were tested induced estrogen receptor-mediated gene expression in T47D human breast adenocarcinoma cells. Observed estrogenic activities corresponded to 17beta-estradiol (E2) CALUX equivalent concentrations ranging from 2 to 23 ng E2-CEQ per gram of PM1 (particulate matter of < or = 1 microm aerodynamic diameter) and from 0.07 to 1.25 pg E2-CEQ per m(3) of sampled air. There was a strong correlation between the PM1 estrogenicity of the urban and rural sites (r = 0.92). Five hydroxylated polycyclic aromatic hydrocarbons (hydroxy-PAHs), which show structural similarities to E2, were assessed for their estrogenic activity. The following order of estrogenic potency was found: 2-hydroxychrysene > 2-hydroxyphenanthrene > 1-hydroxypyrene > 2-hydroxynaphthalene > 1-hydroxynaphthalene. Three of these hydroxy-PAHs, namely 2-hydroxyphenanthrene, 2-hydroxynaphthalene and 1-hydroxynaphthalene, were detected in all PM1 extracts. However, they contributed only 0.01-0.2% to the overall estrogenic activity. Hence, mainly other estrogenic compounds not yet identified by chemical analysis must be responsible for the observed activity. The temporal trend of PM1 estrogenicity at the urban and rural site, respectively, was compared with the time course of several air pollutants (NO2, NO, SO2, O3, CO) and meteorological parameters (temperature, humidity, air pressure, solar irradiation, wind velocity). However, specific emission sources and formation processes of atmospheric xenoestrogens could not be elucidated. This study showed that ambient particulate matter contains compounds that are able to interact with estrogen receptors in vitro and potentially also interfere with estrogen-regulated pathways in vivo.

  12. Estrogenic Activity of Mineral Oil Aromatic Hydrocarbons Used in Printing Inks

    PubMed Central

    Tarnow, Patrick; Hutzler, Christoph; Grabiger, Stefan; Schön, Karsten; Tralau, Tewes; Luch, Andreas

    2016-01-01

    The majority of printing inks are based on mineral oils (MOs) which contain complex mixtures of saturated and aromatic hydrocarbons. Consumer exposure to these oils occurs either through direct skin contacts or, more frequently, as a result of MO migration into the contents of food packaging that was made from recycled newspaper. Despite this ubiquitous and frequent exposure little is known about the potential toxicological effects, particularly with regard to the aromatic MO fractions. From a toxicological point of view the huge amount of alkylated and unsubstituted compounds therein is reason for concern as they can harbor genotoxicants as well as potential endocrine disruptors. The aim of this study was to assess both the genotoxic and estrogenic potential of MOs used in printing inks. Mineral oils with various aromatic hydrocarbon contents were tested using a battery of in vitro assays selected to address various endpoints such as estrogen-dependent cell proliferation, activation of estrogen receptor α or transcriptional induction of estrogenic target genes. In addition, the comet assay has been applied to test for genotoxicity. Out of 15 MOs tested, 10 were found to potentially act as xenoestrogens. For most of the oils the effects were clearly triggered by constituents of the aromatic hydrocarbon fraction. From 5 oils tested in the comet assay, 2 showed slight genotoxicity. Altogether it appears that MOs used in printing inks are potential endocrine disruptors and should thus be assessed carefully to what extent they might contribute to the total estrogenic burden in humans. PMID:26771904

  13. Estrogenic Activity of Mineral Oil Aromatic Hydrocarbons Used in Printing Inks.

    PubMed

    Tarnow, Patrick; Hutzler, Christoph; Grabiger, Stefan; Schön, Karsten; Tralau, Tewes; Luch, Andreas

    2016-01-01

    The majority of printing inks are based on mineral oils (MOs) which contain complex mixtures of saturated and aromatic hydrocarbons. Consumer exposure to these oils occurs either through direct skin contacts or, more frequently, as a result of MO migration into the contents of food packaging that was made from recycled newspaper. Despite this ubiquitous and frequent exposure little is known about the potential toxicological effects, particularly with regard to the aromatic MO fractions. From a toxicological point of view the huge amount of alkylated and unsubstituted compounds therein is reason for concern as they can harbor genotoxicants as well as potential endocrine disruptors. The aim of this study was to assess both the genotoxic and estrogenic potential of MOs used in printing inks. Mineral oils with various aromatic hydrocarbon contents were tested using a battery of in vitro assays selected to address various endpoints such as estrogen-dependent cell proliferation, activation of estrogen receptor α or transcriptional induction of estrogenic target genes. In addition, the comet assay has been applied to test for genotoxicity. Out of 15 MOs tested, 10 were found to potentially act as xenoestrogens. For most of the oils the effects were clearly triggered by constituents of the aromatic hydrocarbon fraction. From 5 oils tested in the comet assay, 2 showed slight genotoxicity. Altogether it appears that MOs used in printing inks are potential endocrine disruptors and should thus be assessed carefully to what extent they might contribute to the total estrogenic burden in humans.

  14. Estrogenic status modulates aryl hydrocarbon receptor - mediated hepatic gene expression and carcinogenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogenic status is thought to influence the cancer risk in women and has been reported to affect toxicity of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in animals. The objective of this study was to examine the influence of estradiol (E2) on hepatic gene expression changes mediated by 7,...

  15. Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

    SciTech Connect

    Hwang, Yong Pil; Kim, Hyung Gyun; Hien, Tran Thi; Jeong, Myung Ho; Jeong, Tae Cheon; Jeong, Hye Gwang

    2011-11-15

    The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-{alpha}-stimulated monocytes to endothelial cells and suppressed the TNF-{alpha} induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-{alpha}-induced nuclear factor-{kappa}B activation, which was attenuated by pretreatment with N{sup G}-nitro-L-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease. -- Highlights: Black-Right-Pointing-Pointer Puerarin induced the phosphorylation of eNOS and the production of NO. Black-Right-Pointing-Pointer Puerarin activated eNOS through ER-dependent PI3-kinase and Ca{sup 2+}-dependent AMPK. Black-Right-Pointing-Pointer Puerarin-induced NO was involved in the inhibition of NF-kB activation. Black-Right-Pointing-Pointer Puerarin may help for prevention of vascular dysfunction and diabetes.

  16. Mechanism of phytoestrogen puerarin-mediated cytoprotection following oxidative injury: Estrogen receptor-dependent up-regulation of PI3K/Akt and HO-1

    SciTech Connect

    Hwang, Yong Pil; Jeong, Hye Gwang

    2008-12-15

    Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. The phytoestrogen puerarin, the main isoflavone glycoside found in the root of Pueraria lobata, has been used for various medicinal purposes in traditional Chinese medicines for thousands of years. Recent studies have indicated that the estrogen receptor (ER), through interaction with p85, regulates phosphoinositide 3-kinase (PI3K) activity, revealing a physiologic, non-nuclear function of ER that may be relevant in cytoprotection. In this study, we demonstrate that the phytoestrogen puerarin inhibits tert-butyl hydroperoxide (t-BHP)-induced oxidative injury via an ER-dependent G{beta}1/PI3K/Akt and heme oxygenase-1 (HO-1) pathway. Pretreatment of Hepa1c1c7 and HepG2 cells with puerarin significantly reduced t-BHP-induced caspase-3 activation and subsequent cell death. Also, puerarin up-regulated HO-1 expression and this expression conferred cytoprotection against oxidative injury induced by t-BHP. Moreover, puerarin induced Nrf2 nuclear translocation, which is upstream of puerarin-induced HO-1 expression, and PI3K activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection. Puerarin-induced up-regulation of HO-1 and cytoprotection against t-BHP were abolished by silencing Nrf2 expression with specific siRNA. Also, puerarin-mediated increases in PI3K activation and HO-1 induction were reversed by co-treatment with ICI 182,780 and pertussis toxin. Taken together, these results suggest that puerarin augments cellular antioxidant defense capacity through ER-dependent HO-1 induction via the G{beta}1/PI3K/Akt-Nrf2 signaling pathway, thereby protecting cells from oxidative stress.

  17. Neuroprotective effects of R,R-tetrahydrochrysene against glutamate-induced cell death through anti-excitotoxic and antioxidant actions involving estrogen receptor-dependent and -independent pathways.

    PubMed

    Xia, Y; Xing, J Z; Krukoff, T L

    2009-08-18

    Glutamate-induced neural cell death is mediated by excitotoxicity and oxidative stress. Treatment of glutamate toxicity with estrogen and its related compounds for neuroprotection remains controversial. In this study, we examined the effects of selective estrogen receptor (ER) ligands on glutamate toxicity and found that R,R-tetrahydrochrysene (R,R-THC), an antagonist of ERbeta and agonist of ERalpha, has neuroprotective effects against glutamate-induced death in primary rat cortical cells and mouse N29/4 hypothalamic cells. The protective effect of R,R-THC was dose-dependent and was maintained even when added several hours after the initial glutamate exposure. R,R-THC blocked glutamate-induced depletion of intracellular glutathione, increased superoxide dismutase activity, and protected cells from hydrogen peroxide-induced death. R,R-THC also prevented glutamate-induced nuclear translocation of apoptotic inducing factor and release of mitochondrial cytochrome c. The protective effect of R,R-THC was blocked by methyl-piperidino-pyrazole (MPP; an ERalpha antagonist) in glutamate-treated cortical cells, and pretreatment with MK-801 (an NMDA receptor antagonist) but not CNQX (an AMPA/kainate receptor antagonist) increased cell survival. On the other hand, MPP did not block the protective effect of R,R-THC in glutamate-treated N29/4 cells, and neither MK-801 nor CNQX conferred protection. Activation of ERalpha and/or ERbeta with 17beta-estradiol (E2), propyl-pyrazole-triol or diarylpropionitrile did not provide effective neuroprotection, and pretreatment with ICI 182,780 did not inhibit the protective effect of R,R-THC in either type of cell. These results suggest that the use of ER agonists (including E2) has limited beneficial effects when both excitotoxicity and oxidative stress occur. In contrast to agonists of ERs, R,R-THC, which possesses anti-excitotoxic and antioxidant actions via ER-dependent and -independent pathways, provides significant neuroprotection.

  18. MODELING THE BINDING OF THE METABOLITES OF SOME POLYCYCLIC AROMTIC HYDROCARBONS TO THE LIGAND BINDING DOMAIN OF THE ESTROGEN RECEPTOR

    EPA Science Inventory

    Modeling the binding of the metabolites of some Polycyclic Aromatic Hydrocarbons to the ligand binding domain of the estrogen receptor
    James Rabinowitz, Stephen Little, Katrina Brown, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC; Un...

  19. Bisphenol A depresses monosynaptic and polysynaptic reflexes in neonatal rat spinal cord in vitro involving estrogen receptor-dependent NO-mediated mechanisms.

    PubMed

    Pandey, A K; Deshpande, S B

    2015-03-19

    Bisphenol A (BPA), a toxic chemical from plastics, is known to produce locomotor abnormalities which may imply the alteration in synaptic activity at Ia-α motoneuron synapse also. However the effect of BPA on this synapse is not known. Therefore, this study was undertaken to examine the effect of BPA on reflexes originating at Ia-α motoneuron synapse in the spinal cord. The experiments were performed on isolated hemisected spinal cords from 4 to 6d rats. Stimulation of a dorsal root evoked segmental monosynaptic (MSR) and polysynaptic (PSR) reflex potentials in the corresponding ventral root. Nitrite content (indicator of NO activity) of cords was estimated in the presence of BPA with/without antagonists. Superfusion of BPA (3-100μM) depressed the reflexes in a concentration- and time-dependent manner. The depression was ∼20, ∼50 and ∼70% at 10, 30 and 100μM of BPA, respectively. The 50% depression occurred around 15min at 30μM of BPA. Pretreatment with estrogen receptor (ERα) antagonist, tamoxifen, blocked the BPA-induced depression of reflexes, whereas, 17β-estradiol, ER agonist, did not depress the reflexes even up to 10μM. Further, pretreatment with Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or hemoglobin (Hb) blocked the BPA-induced depression of spinal reflexes. Nitric oxide (NO) donor sodium-nitroprusside depressed the MSR and PSR in a concentration-dependent manner. The nitrite concentration of the cords exposed to BPA was 733μM/gm of tissue (three times the saline group). Pretreatment with tamoxifen/l-NAME/Hb blocked the BPA-induced increase of nitrite levels. The present observations indicate that BPA depressed spinal synaptic transmission through ERα-dependent NO-mediated mechanisms. The altered synaptic activity may implicate for neurobehavioral locomotor abnormalities after exposure to BPA.

  20. Fludioxonil induced the cancer growth and metastasis via altering epithelial-mesenchymal transition via an estrogen receptor-dependent pathway in cellular and xenografted breast cancer models.

    PubMed

    Go, Ryeo-Eun; Kim, Cho-Won; Jeon, So-Ye; Byun, Yong-Sub; Jeung, Eui-Bae; Nam, Ki-Hoan; Choi, Kyung-Chul

    2017-04-01

    Fludioxonil is an antifungal agent used in agricultural applications that is present at measurable amounts in fruits and vegetables. In this study, the effects of fludioxonil on cancer cell viability, epithelial-mesenchymal transition (EMT), and metastasis were examined in MCF-7 clonal variant breast cancer cell (MCF-7 CV cells) with estrogen receptors (ERs). MCF-7 CV cells were cultured with 0.1% DMSO (control), 17β-estradiol (E2; 1 ×10(-9) M, positive control), or fludioxonil (10(-5) -10(-8) M). MTT assay revealed that fludioxonil increased MCF-7 CV cell proliferation 1.2 to 1.5 times compared to the control, while E2 markedly increased the cell proliferation by about 3.5 times. When the samples were co-treated with ICI 182,780 (10(-8) M), an ER antagonist, fludioxonil-induced cell proliferation was reversed to the level of the control. Protein levels of cyclin E1, cyclin D1, Snail, and N-cadherin increased in response to fludioxonil as the reaction to E2, but these increases were not observed when fludioxonil was administered with ICI 182,780. Moreover, the protein level of p21 and E-cadherin decreased in response to treatment with fludioxonil, but remained at the control level when co-treated with ICI 182,780. In xenografted mouse models transplanted with MCF-7 CV cells, fludioxonil significantly increased the tumor mass formation by about 2.5 times as E2 did when compared to vehicle (0.1% DMSO) during the experimental period (80 days). Immunohistochemistry revealed that the protein level of proliferating cell nuclear antigen (PCNA), Snail, and cathepsin D increased in response to fludioxonil as the reaction to E2. These results imply that fludioxonil may have a potential to induce growth or metastatic behaviors of breast cancer by regulation of the expression of cell cycle-, EMT-, and metastasis-related genes via the ER-dependent pathway. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1439-1454, 2017.

  1. 3-Methylcholanthrene and other aryl hydrocarbon receptor agonists directly activate estrogen receptor alpha.

    PubMed

    Abdelrahim, Maen; Ariazi, Eric; Kim, Kyounghyun; Khan, Shaheen; Barhoumi, Rola; Burghardt, Robert; Liu, Shengxi; Hill, Denise; Finnell, Richard; Wlodarczyk, Bogdan; Jordan, V Craig; Safe, Stephen

    2006-02-15

    3-Methylcholanthrene (3MC) is an aryl hydrocarbon receptor (AhR) agonist, and it has been reported that 3MC induces estrogenic activity through AhR-estrogen receptor alpha (ER alpha) interactions. In this study, we used 3MC and 3,3',4,4',5-pentachlorobiphenyl (PCB) as prototypical AhR ligands, and both compounds activated estrogen-responsive reporter genes/gene products (cathepsin D) in MCF-7 breast cancer cells. The estrogenic responses induced by these AhR ligands were inhibited by the antiestrogen ICI 182780 and by the transfection of a small inhibitory RNA for ER alpha but were not affected by the small inhibitory RNA for AhR. These results suggest that 3MC and PCB directly activate ER alpha, and this was confirmed in a competitive ER alpha binding assay and in a fluorescence resonance energy transfer experiment in which PCB and 3MC induced CFP-ER alpha/YFP-ER alpha interactions. In a chromatin immunoprecipitation assay, PCB and 3MC enhanced ER alpha (but not AhR) association with the estrogen-responsive region of the pS2 gene promoter. Moreover, in AhR knockout mice, 3MC increased uterine weights and induced expression of cyclin D1 mRNA levels. These results show that PCB and 3MC directly activate ER alpha-dependent transactivation and extend the number of ligands that activate both AhR and ER alpha.

  2. Attenuation of Aβ{sub 25–35}-induced parallel autophagic and apoptotic cell death by gypenoside XVII through the estrogen receptor-dependent activation of Nrf2/ARE pathways

    SciTech Connect

    Meng, Xiangbao; Wang, Min; Sun, Guibo; Ye, Jingxue; Zhou, Yanhui; Dong, Xi; Wang, Tingting; Lu, Shan; Sun, Xiaobo

    2014-08-15

    Amyloid-beta (Aβ) has a pivotal function in the pathogenesis of Alzheimer's disease. To investigate Aβ neurotoxicity, we used an in vitro model that involves Aβ{sub 25–35}-induced cell death in the nerve growth factor-induced differentiation of PC12 cells. Aβ{sub 25–35} (20 μM) treatment for 24 h caused apoptotic cell death, as evidenced by significant cell viability reduction, LDH release, phosphatidylserine externalization, mitochondrial membrane potential disruption, cytochrome c release, caspase-3 activation, PARP cleavage, and DNA fragmentation in PC12 cells. Aβ{sub 25–35} treatment led to autophagic cell death, as evidenced by augmented GFP-LC3 puncta, conversion of LC3-I to LC3-II, and increased LC3-II/LC3-I ratio. Aβ{sub 25–35} treatment induced oxidative stress, as evidenced by intracellular ROS accumulation and increased production of mitochondrial superoxide, malondialdehyde, protein carbonyl, and 8-OHdG. Phytoestrogens have been proved to be protective against Aβ-induced neurotoxicity and regarded as relatively safe targets for AD drug development. Gypenoside XVII (GP-17) is a novel phytoestrogen isolated from Gynostemma pentaphyllum or Panax notoginseng. Pretreatment with GP-17 (10 μM) for 12 h increased estrogen response element reporter activity, activated PI3K/Akt pathways, inhibited GSK-3β, induced Nrf2 nuclear translocation, augmented antioxidant responsive element enhancer activity, upregulated heme oxygenase 1 (HO-1) expression and activity, and provided protective effects against Aβ{sub 25–35}-induced neurotoxicity, including oxidative stress, apoptosis, and autophagic cell death. In conclusion, GP-17 conferred protection against Aβ{sub 25–35}-induced neurotoxicity through estrogen receptor-dependent activation of PI3K/Akt pathways, inactivation of GSK-3β and activation of Nrf2/ARE/HO-1 pathways. This finding might provide novel insights into understanding the mechanism for neuroprotective effects of phytoestrogens or

  3. Heterocyclic aromatic hydrocarbons show estrogenic activity upon metabolization in a recombinant transactivation assay.

    PubMed

    Brinkmann, Markus; Maletz, Sibylle; Krauss, Martin; Bluhm, Kerstin; Schiwy, Sabrina; Kuckelkorn, Jochen; Tiehm, Andreas; Brack, Werner; Hollert, Henner

    2014-05-20

    Heterocyclic aromatic hydrocarbons (hetero-PAHs) are increasingly studied at contaminated sites; especially at former industrial facilities where coal tar-oil was handled, e.g., wood treatment plants, high concentrations of hetero-PAHs are frequently detected in groundwater plumes. In previous studies, fractions of groundwater with high estrogenic activity contained hetero-PAHs and their hydroxylated metabolites. To evaluate this preliminary evidence, selected hetero-PAHs were screened for their estrogenic activity in lyticase yeast estrogen screen (LYES) and ER CALUX. All tested substances were inactive in the LYES. Hetero-PAHs such as acridine, xanthene, indole, 2-methylbenzofuran, 2,3-dimethylbenzofuran, dibenzofuran, dibenzothiophene, quinoline, and 6-methylquinoline were positive in the ER CALUX, with estradiol equivalence factors (EEFs) from 2.85 × 10(-7) to 3.18 × 10(-5). The EEF values of these substances were comparable to those of other xenoestrogens (e.g., alkylphenols or bisphenol A) that are sometimes found in surface water. Chemical analyses revealed that T47Dluc cells could metabolize most of the substances. Among the metabolites (tentatively) identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were hydroxides and their keto tautomers, sulfates, sulfoxides, and N-oxides. Because of their high concentrations measured in groundwater, we conclude that hetero-PAHs and metabolites may be a potential risk and should be the subject of further research.

  4. Aryl-hydrocarbon receptor-dependent alteration of FAK/RhoA in the inhibition of HUVEC motility by 3-methylcholanthrene.

    PubMed

    Chang, Chih-Cheng; Tsai, Shih-Ying; Lin, Heng; Li, Hsiao-Fen; Lee, Yi-Hsuan; Chou, Ying; Jen, Chih-Yu; Juan, Shu-Hui

    2009-10-01

    We previously demonstrated the antiproliferative and antiangiogenic effects of 3-methylcholanthrene (3MC), an aryl-hydrocarbon receptor (AhR) agonist, in human umbilical vascular endothelial cells (HUVECs). Herein, we unraveled its molecular mechanisms in inhibiting HUVEC motility. 3MC down-regulated FAK, but up-regulated RhoA, which was rescued by AhR knockdown. It led us to identify novel AhR binding sites in the FAK/RhoA promoters. Additionally, 3MC increased RhoA activity via suppression of a negative feedback pathway of FAK/p190RhoGAP. With an increase in membrane-bound RhoA, subsequent stress fiber and focal adhesion complex formation was observed in 3MC-treated cells, and this was reversed by a RhoA inhibitor and AhR antagonists. Notably, these compounds significantly reversed 3MC-mediated anti-migration in a transwell assay. The in vitro findings were further confirmed using an animal model of Matrigel formation in Balb/c mice. Collectively, AhR's genomic regulation of FAK/RhoA, together with RhoA activation, is ascribable to the anti-migration effect of 3MC in HUVECs.

  5. Diversified expression of aryl hydrocarbon receptor dependent genes in human laryngeal squamous cell carcinoma cell lines treated with β-naphthoflavone.

    PubMed

    Brauze, Damian; Fijalkiewicz, Katarzyna; Szaumkessel, Marcin; Kiwerska, Katarzyna; Bednarek, Kinga; Rydzanicz, Malgorzata; Richter, Julia; Grenman, Reidar; Jarmuz-Szymczak, Malgorzata

    2014-11-18

    The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. In this study the effect of administration of β-naphthoflavone (BNF), potent AhR ligand, on the expression of AhR, AhRR, CYP1A1, CYP1A2, CYP1B1, NQO1, GSTA1, ALDH3A1 and UGT1A genes encoding the enzymes controlled by AhR were examined in thirteen laryngeal tumor cell lines and in HepaRG cell line. The analyzed cell lines were derived from patients with squamous laryngeal cancer, with history of cigarette smoking and without signs of human papillomavirus types 16 and 18 infection in investigated cells. Quantitative real-time RT-PCR analysis revealed huge interindividual differences in expression of genes from AhR regulatory network. Our results strongly suggest predominant effect of DNA methylation on induction of CYP1A1 expression by AhR ligands as well. Our results indicate that differentiated HepaRG cell line appeared to be very good substitute for human liver in studies on xenobiotic metabolism by AhR regulated enzymes.

  6. The Mitochondria-Targeted Antioxidant SkQ1 Downregulates Aryl Hydrocarbon Receptor-Dependent Genes in the Retina of OXYS Rats with AMD-Like Retinopathy

    PubMed Central

    Perepechaeva, M. L.; Grishanova, A. Yu.; Rudnitskaya, E. A.; Kolosova, N. G.

    2014-01-01

    The mitochondria-targeted antioxidant SkQ1 is a novel drug thought to retard development of age-related diseases. It has been shown that SkQ1 reduces clinical signs of retinopathy in senescence-accelerated OXYS rats, which are a known animal model of human age-related macular degeneration (AMD). The aim of this work was to test whether SkQ1 affects transcriptional activity of AhR (aryl hydrocarbon receptor) and Nrf2 (nuclear factor erythroid 2-related factor 2), which are considered as AMD-associated genes in the retina of OXYS and Wistar rats. Our results showed that only AhR and AhR-dependent genes were sensitive to SkQ1. Dietary supplementation with SkQ1 decreased the AhR mRNA level in both OXYS and Wistar rats. At baseline, the retinal Cyp1a1 mRNA level was lower in OXYS rats. SkQ1 supplementation decreased the Cyp1a1 mRNA level in Wistar rats, but this level remained unchanged in OXYS rats. Baseline Cyp1a2 and Cyp1b1 mRNA expression was stronger in OXYS than in Wistar rats. In the OXYS strain, Cyp1a2 and Cyp1b1 mRNA levels decreased as a result of SkQ1 supplementation. These data suggest that the Cyp1a2 and Cyp1b1 enzymes are involved in the pathogenesis of AMD-like retinopathy of OXYS rats and are possible therapeutic targets of SkQ1. PMID:25132985

  7. Norisoboldine, an Anti-Arthritis Alkaloid Isolated from Radix Linderae, Attenuates Osteoclast Differentiation and Inflammatory Bone Erosion in an Aryl Hydrocarbon Receptor-Dependent Manner.

    PubMed

    Wei, Zhi-feng; Lv, Qi; Xia, Ying; Yue, Meng-fan; Shi, Can; Xia, Yu-feng; Chou, Gui-xin; Wang, Zheng-tao; Dai, Yue

    2015-01-01

    Norisoboldine (NOR), the primary isoquinoline alkaloid constituent of the root of Lindera aggregata, has previously been demonstrated to attenuate osteoclast (OC) differentiation. Accumulative evidence has shown that aryl hydrocarbon receptor (AhR) plays an important role in regulating the differentiation of various cells, and multiple isoquinoline alkaloids can modulate AhR. In the present study, we explored the role of NOR in the AhR signaling pathway. These data showed that the combination of AhR antagonist resveratrol (Res) or α-naphthoflavone (α-NF) nearly reversed the inhibition of OC differentiation through NOR. NOR could stably bind to AhR, up-regulate the nuclear translocation of AhR, and enhance the accumulation of the AhR-ARNT complex, AhR-mediated reporter gene activity and CYP1A1 expression in RAW 264.7 cells, suggesting that NOR might be an agonist of AhR. Moreover, NOR inhibited the nuclear translocation of NF-κB-p65, resulting in the evident accumulation of the AhR-NF-κB-p65 complex, which could be markedly inhibited through either Res or α-NF. Although NOR only slightly affected the expression of HIF-1α, NOR markedly reduced VEGF mRNA expression and ARNT-HIF-1α complex accumulation. In vivo studies indicated that NOR decreased the number of OCs and ameliorated the bone erosion in the joints of rats with collagen-induced arthritis, accompanied by the up-regulation of CYP1A1 and the down-regulation of VEGF mRNA expression in the synovium of rats. A combination of α-NF nearly completely reversed the effects of NOR. In conclusion, NOR attenuated OC differentiation and bone erosion through the activation of AhR and the subsequent inhibition of both NF-κB and HIF pathways.

  8. A COMPUTER DOCKING STUDY OF THE BINDING OF POLYCYCLIC AROMATIC HYDROCARBONS AND THEIR METABOLITES TO THE LIGARD-BINDING DOMAIN OF THE ESTROGEN RECEPTOR

    EPA Science Inventory

    Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous, anthropogenic chemicals found in the environment. In the present study, computational methods are used to evaluate their potential estrogenicity and the contribution chemicals in this class make to environmental e...

  9. Aryl hydrocarbon receptor-mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments.

    PubMed

    Machala, M; Ciganek, M; Bláha, L; Minksová, K; Vondráck, J

    2001-12-01

    Reproductive dysfunction in wildlife populations can be a result of environmental contaminants binding to aryl hydrocarbon receptor (AhR) or estrogenic receptors. Signaling by both types of receptors can be affected by polycyclic aromatic hydrocarbons (PAHs), which are potential endocrine disruptors. However, our knowledge regarding the effects of oxygenated (oxy)-PAHs and azaarenes on AhR-mediated and estrogenic activities is incomplete. In the present study, we have identified 9-fluorenone, anthrone, anthraquinone, benzanthrone, benz[a]anthracene-7,12-dione, benz[c]acridine, and dibenz[a,h]acridine as prevalent oxy-PAHs and azaarenes found in river sediments. Their concentrations in sediment samples ranged from 2.1 to 165.2 ng g(-1) for oxy-PAHs and up to 27.3 ng g(-1) for azaarenes. Their relative AhR-inducing and estrogenic potencies were quantified in vitro using two cell lines that were stably transfected with a luciferase reporter gene system and expressed as induction equivalency factors (IEFs). The only oxy-PAHs with detectable levels of in vitro AhR-mediated activity were benzanthrone and benz[a]anthracene-7,12-dione. However, their IEFs were approximately three to four orders of magnitude lower than those of benzo[a]pyrene. On the other hand, azaarenes showed a strong AhR-mediated activity, with dibenzo[a,h]acridine being a far more potent inducer of activity than benzo[a]pyrene. Benzanthrone, benz[a]anthracene-7,12-dione, anthraquinone, and benz[a]acridine were weak inducers of in vitro estrogenic activity, with IEFs similar to that of benzo[a]pyrene. Based on concentrations and relative potencies, our results suggest that dibenzo[a,h]acridine can significantly contribute to the overall AhR-mediated activity in river sediments, whereas the remaining compounds do not. No studied compound was found to contribute significantly to estrogen receptor-mediated activity in vitro.

  10. Genome Sequence of Pseudomonas citronellolis SJTE-3, an Estrogen- and Polycyclic Aromatic Hydrocarbon-Degrading Bacterium

    PubMed Central

    Zheng, Daning; Wang, Xiuli; Wang, Pingping; Peng, Wanli; Ji, Nannan

    2016-01-01

    Pseudomonas citronellolis SJTE-3, isolated from the active sludge of a wastewater treatment plant in China, can utilize a series of environmental estrogens and estrogen-like toxicants. Here, we report its whole-genome sequence, containing one circular chromosome and one circular plasmid. Genes involved in estrogen biodegradation in this bacterium were predicted. PMID:27932659

  11. Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

  12. Relative potencies of individual polycyclic aromatic hydrocarbons to induce dioxinlike and estrogenic responses in three cell lines.

    PubMed

    Villeneuve, D L; Khim, J S; Kannan, K; Giesy, J P

    2002-01-01

    The dioxinlike and estrogenic relative potencies (REPs) of 16 priority polycyclic aromatic hydrocarbons (PAHs), seven methylated PAHs, and two hydroxylated PAHs were examined using three in vitro cell bioassays. An in vitro ethoxyresorufin-O-deethylase assay with PLHC-1 fish hepatoma cells and in vitro luciferase assay with H4IIE-luc recombinant rat hepatoma cells were used to evaluate dioxinlike potency. An in vitro luciferase assay with MVLN, recombinant human breast carcinoma cells, was used to evaluate estrogenic potency. Seven of the 16 priority PAHs tested induced significant dioxinlike responses. Excluding outliers with large ranges of uncertainty, the dioxinlike REPs for the PAHs ranged from 10(-6) to 10(-3). This is similar to the REPs reported for other xenobiotics of concern including polychlorinated naphthalenes (PCNs) and some polychlorinated biphenyls (PCBs). In general, REP estimates generated in this study were similar to those reported previously. However, a comparison of the estimates of total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents derived using assay-specific REPs with REPs reported in other studies indicated that the use of nonspecific REPs could lead to significant error in mass-balance (potency-balance) analyses. A 10-h acid treatment completely destroyed the dioxinlike activity of a PAH mixture. Among the compounds tested, only benzo[a]anthracene and dibenz[a,h]anthracene induced significant responses in the MVLN bioassay. Relative estrogenic potencies were estimated to be approximately 10(-7). Overall, this research contributes to the growing consensus regarding the dioxinlike potency of priority PAHs and PAH derivatives and provides some additional evidence about potentially estrogenic PAHs.

  13. Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling

    PubMed Central

    Helle, Janina; Bader, Manuela I.; Keiler, Annekathrin M.; Zierau, Oliver; Vollmer, Günter; Chittur, Sridar V.; Tenniswood, Martin; Kretzschmar, Georg

    2015-01-01

    Background: Cross-talk between the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) plays a major role in signaling processes in female reproductive organs. Objectives: We investigated the influence of the AHR ligand 3-methylcholanthrene (3-MC) on ER-mediated signaling in mammary gland tissue of ovariectomized (ovx) rats. Methods: After 14 days of hormonal decline, ovx rats were treated for 3 days with 4 μg/kg 17β-estradiol (E2), 15 mg/kg 8-prenylnaringenin (8-PN), 15 mg/kg 3-MC, or a combination of these compounds (E2 + 3-MC, 8-PN + 3-MC). Whole-mount preparations of the mammary gland were used to count terminal end buds (TEBs). Protein expression studies (immunohistochemistry, immunofluorescence), a cDNA microarray, pathway analyses, and quantitative real-time polymerase chain reaction (qPCR) were performed to evaluate the interaction between AHR- and ER-mediated signaling pathways. Results: E2 treatment increased the number of TEBs and the levels of Ki-67 protein and progesterone receptor (PR); this treatment also changed the expression of 325 genes by more than 1.5-fold. Although 3-MC treatment alone had marginal impact on gene or protein expression, when rats were co-treated with 3-MC and E2, 3-MC strongly inhibited E2-induced TEB development, protein synthesis, and the expression of nearly half of E2-induced genes. This inhibitory effect of 3-MC was partially mirrored when 8-PN was used as an ER ligand. The anti-estrogenicity of ligand-activated AHR was at least partly due to decreased protein levels of ERα in ductal epithelial cells. Conclusion: Our data show transcriptome-wide anti-estrogenic properties of ligand-activated AHR on ER-mediated processes in the mammary gland, thereby contributing an explanation for the chemopreventive and endocrine-disrupting potential of AHR ligands. Citation: Helle J, Bader MI, Keiler AM, Zierau O, Vollmer G, Chittur SV, Tenniswood M, Kretzschmar G. 2016. Cross-talk in the female rat mammary gland: influence

  14. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: Essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase

    SciTech Connect

    Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj; Oh, Seok Jeong; Lee, Moo Yeol; Kang, Keon Wook

    2010-08-01

    We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10 {mu}g/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase were enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.

  15. Ginsenoside Rg3 increases nitric oxide production via increases in phosphorylation and expression of endothelial nitric oxide synthase: essential roles of estrogen receptor-dependent PI3-kinase and AMP-activated protein kinase.

    PubMed

    Hien, Tran Thi; Kim, Nak Doo; Pokharel, Yuba Raj; Oh, Seok Jeong; Lee, Moo Yeol; Kang, Keon Wook

    2010-08-01

    We previously showed that ginsenosides increase nitric oxide (NO) production in vascular endothelium and that ginsenoside Rg3 (Rg3) is the most active one among ginseng saponins. However, the mechanism for Rg3-mediated nitric oxide production is still uncertain. In this study, we determined whether Rg3 affects phosphorylation and expression of endothelial nitric oxide synthase (eNOS) in ECV 304 human endothelial cells. Rg3 increased both the phosphorylation and the expression of eNOS in a concentration-dependent manner and a maximal effect was found at 10μg/ml of Rg3. The enzyme activities of phosphatidylinositol 3-kinase (PI3-kinase), c-Jun N-terminal kinase (JNK), and p38 kinase were enhanced as were estrogen receptor (ER)- and glucocorticoid receptor (GR)-dependent reporter gene transcriptions in Rg3-treated endothelial cells. Rg3-induced eNOS phosphorylation required the ER-mediated PI3-kinase/Akt pathway. Moreover, Rg3 activates AMP-activated protein kinase (AMPK) through up-regulation of CaM kinase II and Rg3-stimulated eNOS phosphorylation was reversed by AMPK inhibition. The present results provide a mechanism for Rg3-stimulated endothelial NO production.

  16. COMPARATIVE DOCKING STUDIES OF THE BINDING OF POLYCYCLIC AROMATIC HYDROCARBONS TO THE ESTROGEN RECEPTOR

    EPA Science Inventory

    The interactions of several PAHs, and some of their possible metabolites, with the ligand binding domain of the estrogen receptor have been examined using molecular docking and quantum mechanical methods. The geometries of the PAHs were optimized at the Hartree-Fock level and the...

  17. Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans.

    PubMed

    Vondrácek, Jan; Chramostová, Katerina; Plísková, Martina; Bláha, Ludek; Brack, Werner; Kozubík, Alois; Machala, Miroslav

    2004-09-01

    A group of heterocyclic aromatic compounds, dinaphthofurans (DNFs), recently have been identified as potentially significant contaminants in freshwater sediments. In the present study, a battery of in vitro assays was used for detection of toxic effects of DNFs that are potentially associated with endocrine disruption and tumor promotion. Dinaphthofurans were found to act as relatively potent inducers of aryl hydrocarbon receptor (AhR)-mediated activity in the chemical-activated luciferase reporter gene expression DR-CALUX assay. The relative AhR-inducing potencies of DNFs were similar or even higher than relative potencies of unsubstituted polycyclic aromatic hydrocarbons (PAHs), with dinaphtho[1,2-b;2'3'-d]furan being the most potent AhR agonist. Two compounds, dinaphtho[2,1-b;2'3'-d]furan and dinaphtho[1,2-b;1'2'-d]furan, induced estrogen receptor (ER)-mediated activity in the estrogen receptor-mediated CALUX (the ER-CALUX) assay. Two types of potential tumor-promoting effects of DNFs were investigated, using in vitro bioassays for detection of inhibition of gap-junctional intercellular communication and detection of a release from contact inhibition. Although the acute inhibition of gap-junctional intercellular communication was not observed, all six tested DNFs were able to release rat liver epithelial WB-F344 cells from contact inhibition at concentrations as low as 100 nM. In summary, the present study indicated that DNFs can exert multiple biological effects in vitro, including induction of the AhR-mediated activity, release of cells from contact inhibition, and induction of ER-mediated activity.

  18. Stapled Peptides with γ-Methylated Hydrocarbon Chains for the Estrogen Receptor/Coactivator Interaction.

    PubMed

    Speltz, Thomas E; Fanning, Sean W; Mayne, Christopher G; Fowler, Colin; Tajkhorshid, Emad; Greene, Geoffrey L; Moore, Terry W

    2016-03-18

    "Stapled" peptides are typically designed to replace two non-interacting residues with a constraining, olefinic staple. To mimic interacting leucine and isoleucine residues, we have created new amino acids that incorporate a methyl group in the γ-position of the stapling amino acid S5. We have incorporated them into a sequence derived from steroid receptor coactivator 2, which interacts with estrogen receptor α. The best peptide (IC50 =89 nm) replaces isoleucine 689 with an S-γ-methyl stapled amino acid, and has significantly higher affinity than unsubstituted peptides (390 and 760 nm). Through X-ray crystallography and molecular dynamics studies, we show that the conformation taken up by the S-γ-methyl peptide minimizes the syn-pentane interactions between the α- and γ-methyl groups.

  19. Xenoestrogens down-regulate aryl-hydrocarbon receptor nuclear translocator 2 mRNA expression in human breast cancer cells via an estrogen receptor alpha-dependent mechanism.

    PubMed

    Qin, Xian-Yang; Zaha, Hiroko; Nagano, Reiko; Yoshinaga, Jun; Yonemoto, Junzo; Sone, Hideko

    2011-10-10

    Environmental chemicals with estrogenic activity, known as xenoestrogens, may cause impaired reproductive development and endocrine-related cancers in humans by disrupting endocrine functions. Aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) is believed to play important roles in a variety of physiological processes, including estrogen signaling pathways, that may be involved in the pathogenesis and therapeutic responses of endocrine-related cancers. However, much of the underlying mechanism remains unknown. In this study, we investigated whether ARNT2 expression is regulated by a range of representative xenoestrogens in human cancer cell lines. Bisphenol A (BPA), benzyl butyl phthalate (BBP), and 1,1,1-trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) were found to be estrogenic toward BG1Luc4E2 cells by an E-CALUX bioassay. ARNT2 expression was downregulated by BPA, BBP, and o,p'-DDT in a dose-dependent manner in estrogen receptor 1 (ESR1)-positive MCF-7 and BG1Luc4E2 cells, but not in estrogen receptor-negative LNCaP cells. The reduction in ARNT2 expression in cells treated with the xenoestrogens was fully recovered by the addition of a specific ESR1 antagonist, MPP. In conclusion, we have shown for the first time that ARNT2 expression is modulated by xenoestrogens by an ESR1-dependent mechanism in MCF-7 breast cancer cells.

  20. Effect of nonpersistent pesticides on estrogen receptor, androgen receptor, and aryl hydrocarbon receptor.

    PubMed

    Medjakovic, Svjetlana; Zoechling, Alfred; Gerster, Petra; Ivanova, Margarita M; Teng, Yun; Klinge, Carolyn M; Schildberger, Barbara; Gartner, Michael; Jungbauer, Alois

    2014-10-01

    Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors.

  1. T-2 toxin is a cytochrome P450 1A1 inducer and leads to MAPK/p38- but not aryl hydrocarbon receptor-dependent interleukin-8 secretion in the human intestinal epithelial cell line Caco-2.

    PubMed

    Kruber, Pierre; Trump, Saskia; Behrens, Johann; Lehmann, Irina

    2011-06-18

    T-2 toxin (T-2) is a secondary metabolite produced by various mould species of the genus Fusarium and a common contaminant detectable in staple foods of cereal origin. In the present study the impact of this mycotoxin on the inflammatory response of the intestinal epithelial cell line Caco-2 was examined by measuring interleukin (IL)-8 secretion. A T-2 concentration dependent IL-8 up-regulation was detected in IL-1β stimulated and unstimulated Caco-2 cells. To elucidate the possible underlying molecular mechanism of this conditional T-2-provoked IL-8 induction, a possible involvement of the aryl hydrocarbon receptor (AHR) and the mitogen-activated protein kinase (MAPK) pathway was investigated. Like benzo-[a]-pyrene (B[a]P), a well known AHR ligand, T-2 led to cytochrome P450 1A1 (CYP1A1) mRNA expression in Caco-2 cells, which could be inhibited by the AHR antagonist resveratrol. However, resveratrol did not influence T-2-dependent IL-8 induction. Since T-2 did not lead to AHR-translocation in stably GFP-AHR-transfected cells, an AHR dependency of T-2-triggered IL-8 induction could be excluded. But finally, up to a total inhibition of T-2-induced IL-8 was obtained using p38 inhibitors. Therefore, we conclude that p38 MAPK is responsible for mediating the inflammatory properties of the type A trichothecene T-2.

  2. The aryl hydrocarbon receptor mediates raloxifene-induced apoptosis in estrogen receptor-negative hepatoma and breast cancer cells

    PubMed Central

    O'Donnell, E F; Koch, D C; Bisson, W H; Jang, H S; Kolluri, S K

    2014-01-01

    Identification of new molecular targets for the treatment of breast cancer is an important clinical goal, especially for triple-negative breast cancer, which is refractory to existing targeted treatments. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known primarily as the mediator of dioxin toxicity. However, the AhR can also inhibit cellular proliferation in a ligand-dependent manner and act as a tumor suppressor in mice, and thus may be a potential anticancer target. To investigate the AhR as an anticancer target, we conducted a small molecule screen to discover novel AhR ligands with anticancer properties. We identified raloxifene, a selective estrogen receptor (ER) modulator currently used in the clinic for prevention of ER-positive breast cancer and osteoporosis in post-menopausal women, as an AhR activator. Raloxifene directly bound the AhR and induced apoptosis in ER-negative mouse and human hepatoma cells in an AhR-dependent manner, indicating that the AhR is a molecular target of raloxifene and mediates raloxifene-induced apoptosis in the absence of ER. Raloxifene selectively induced apoptosis of triple-negative MDA-MB-231 breast cancer cells compared with non-transformed mammary epithelial cells via the AhR. Combined with recent data showing that raloxifene inhibits triple-negative breast cancer xenografts in vivo (Int J Oncol. 43(3):785-92, 2013), our results support the possibility of repurposing of raloxifene as an AhR-targeted therapeutic for triple-negative breast cancer patients. To this end, we also evaluated the role of AhR expression on survival of patients diagnosed with breast cancer. We found that higher expression of the AhR is significantly associated with increased overall survival and distant metastasis-free survival in both hormone-dependent (ER-positive) and hormone-independent (ER and progesterone receptor (PR)-negative) breast cancers. Together, our data strongly support the possibility of using the Ah

  3. The aryl hydrocarbon receptor mediates raloxifene-induced apoptosis in estrogen receptor-negative hepatoma and breast cancer cells.

    PubMed

    O'Donnell, E F; Koch, D C; Bisson, W H; Jang, H S; Kolluri, S K

    2014-01-30

    Identification of new molecular targets for the treatment of breast cancer is an important clinical goal, especially for triple-negative breast cancer, which is refractory to existing targeted treatments. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known primarily as the mediator of dioxin toxicity. However, the AhR can also inhibit cellular proliferation in a ligand-dependent manner and act as a tumor suppressor in mice, and thus may be a potential anticancer target. To investigate the AhR as an anticancer target, we conducted a small molecule screen to discover novel AhR ligands with anticancer properties. We identified raloxifene, a selective estrogen receptor (ER) modulator currently used in the clinic for prevention of ER-positive breast cancer and osteoporosis in post-menopausal women, as an AhR activator. Raloxifene directly bound the AhR and induced apoptosis in ER-negative mouse and human hepatoma cells in an AhR-dependent manner, indicating that the AhR is a molecular target of raloxifene and mediates raloxifene-induced apoptosis in the absence of ER. Raloxifene selectively induced apoptosis of triple-negative MDA-MB-231 breast cancer cells compared with non-transformed mammary epithelial cells via the AhR. Combined with recent data showing that raloxifene inhibits triple-negative breast cancer xenografts in vivo (Int J Oncol. 43(3):785-92, 2013), our results support the possibility of repurposing of raloxifene as an AhR-targeted therapeutic for triple-negative breast cancer patients. To this end, we also evaluated the role of AhR expression on survival of patients diagnosed with breast cancer. We found that higher expression of the AhR is significantly associated with increased overall survival and distant metastasis-free survival in both hormone-dependent (ER-positive) and hormone-independent (ER and progesterone receptor (PR)-negative) breast cancers. Together, our data strongly support the possibility of using the Ah

  4. Estrogen-, androgen- and aryl hydrocarbon receptor mediated activities in passive and composite samples from municipal waste and surface waters.

    PubMed

    Jálová, V; Jarošová, B; Bláha, L; Giesy, J P; Ocelka, T; Grabic, R; Jurčíková, J; Vrana, B; Hilscherová, K

    2013-09-01

    Passive and composite sampling in combination with in vitro bioassays and identification and quantification of individual chemicals were applied to characterize pollution by compounds with several specific modes of action in urban area in the basin of two rivers, with 400,000 inhabitants and a variety of industrial activities. Two types of passive samplers, semipermeable membrane devices (SPMD) for hydrophobic contaminants and polar organic chemical integrative samplers (POCIS) for polar compounds such as pesticides and pharmaceuticals, were used to sample wastewater treatment plant (WWTP) influent and effluent as well as rivers upstream and downstream of the urban complex and the WWTP. Compounds with endocrine disruptive potency were detected in river water and WWTP influent and effluent. Year-round, monthly assessment of waste waters by bioassays documented estrogenic, androgenic and dioxin-like potency as well as cytotoxicity in influent waters of the WWTP and allowed characterization of seasonal variability of these biological potentials in waste waters. The WWTP effectively removed cytotoxic compounds, xenoestrogens and xenoandrogens. There was significant variability in treatment efficiency of dioxin-like potency. The study indicates that the WWTP, despite its up-to-date technology, can contribute endocrine disrupting compounds to the river. Riverine samples exhibited dioxin-like, antiestrogenic and antiandrogenic potencies. The study design enabled characterization of effects of the urban complex and the WWTP on the river. Concentrations of PAHs and contaminants and specific biological potencies sampled by POCIS decreased as a function of distance from the city.

  5. The aryl hydrocarbon receptor and estrogen receptor alpha differentially modulate nuclear factor erythroid-2-related factor 2 transactivation in MCF-7 breast cancer cells

    SciTech Connect

    Lo, Raymond; Matthews, Jason

    2013-07-15

    Nuclear factor erythroid-2-related factor 2 (NRF2; NFE2L2) plays an important role in mediating cellular protection against reactive oxygen species. NRF2 signaling is positively modulated by the aryl hydrocarbon receptor (AHR) but inhibited by estrogen receptor alpha (ERα). In this study we investigated the crosstalk among NRF2, AHR and ERα in MCF-7 breast cancer cells treated with the NRF2 activator sulforaphane (SFN), a dual AHR and ERα activator, 3,3′-diindolylmethane (DIM), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 17β-estradiol (E2). SFN-dependent increases in NADPH-dependent oxidoreductase 1 (NQO1) and heme oxygenase I (HMOX1) mRNA levels were significantly reduced after co-treatment with E2. E2-dependent repression of NQO1 and HMOX1 was associated with increased ERα but reduced p300 recruitment and reduced histone H3 acetylation at both genes. In contrast, DIM + SFN or TCDD + SFN induced NQO1 and HMOX1 mRNA expression to levels higher than SFN alone, which was prevented by RNAi-mediated knockdown of AHR. DIM + SFN but not TCDD + SFN also induced recruitment of ERα to NQO1 and HMOX1. However, the presence of AHR at NQO1 and HMOX1 restored p300 recruitment and histone H3 acetylation, thereby reversing the ERα-dependent repression of NRF2. Taken together, our study provides further evidence of functional interplay among NRF2, AHR and ERα signaling pathways through altered p300 recruitment to NRF2-regulated target genes. - Highlights: • We examined crosstalk among ERα, AHR, and NRF2 in MCF-7 breast cancer cells. • AHR enhanced the mRNA expression levels of two NRF2 target genes – HMOX1 and NQO1. • ERα repressed HMOX1 and NQO1 expression via decreased histone acetylation. • AHR prevented ERα-dependent repression of HMOX1 and NQO1.

  6. Commonly occurring plant flavonoids have estrogenic activity.

    PubMed

    Miksicek, R J

    1993-07-01

    A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta-[3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta-estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet.

  7. Estrogen Injection

    MedlinePlus

    ... forms of estrogen injection are used to treat hot flushes (hot flashes; sudden strong feelings of heat and sweating) ... If you are using estrogen injection to treat hot flushes, your symptoms should improve within 1 to ...

  8. Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells.

    PubMed Central

    Sehgal, I; Bailey, J; Hitzemann, K; Pittelkow, M R; Maihle, N J

    1994-01-01

    Amphiregulin is a heparin-binding epidermal growth factor (EGF)-related peptide that binds to the EGF receptor (EGF-R) with high affinity. In this study, we report a role for amphiregulin in androgen-stimulated regulation of prostate cancer cell growth. Androgen is known to enhance EGF-R expression in the androgen-sensitive LNCaP human prostate carcinoma cell line, and it has been suggested that androgenic stimuli may regulate proliferation, in part, through autocrine mechanisms involving the EGF-R. In this study, we demonstrate that LNCaP cells express amphiregulin mRNA and peptide and that this expression is elevated by androgenic stimulation. We also show that ligand-dependent EGF-R stimulation induces amphiregulin expression and that androgenic effects on amphiregulin synthesis are mediated through this EGF-R pathway. Parallel studies using the estrogen-responsive breast carcinoma cell line, MCF-7, suggest that regulation of amphiregulin by estrogen may also be mediated via an EGF-R pathway. In addition, heparin treatment of LNCaP cells inhibits androgen-stimulated cell growth further suggesting that amphiregulin can mediate androgen-stimulated LNCaP proliferation. Together, these results implicate an androgen-regulated autocrine loop composed of amphiregulin and its receptor in prostate cancer cell growth and suggest that the mechanism of steroid hormone regulation of amphiregulin synthesis may occur through androgen upregulation of the EGF-R and subsequent receptor-dependent pathways. Images PMID:8049525

  9. Hydrocarbon pneumonia

    MedlinePlus

    Pneumonia - hydrocarbon ... Coughing Fever Shortness of breath Smell of a hydrocarbon product on the breath Stupor (decreased level of ... Most children who drink or inhale hydrocarbon products and develop ... hydrocarbons may lead to rapid respiratory failure and death.

  10. The Immune System Is a Natural Target for Estrogen Action: Opposing Effects of Estrogen in Two Prototypical Autoimmune Diseases

    PubMed Central

    Khan, Deena; Ansar Ahmed, S.

    2016-01-01

    Analogous to other physiological systems, the immune system also demonstrates remarkable sex differences. Although the reasons for sex differences in immune responses are not precisely understood, it potentially involves differences in sex hormones (estrogens, androgens, and differential sex hormone receptor-mediated events), X-chromosomes, microbiome, epigenetics among others. Overall, females tend to have more responsive and robust immune system compared to their male counterparts. It is therefore not surprising that females respond more aggressively to self-antigens and are more susceptible to autoimmune diseases. Female hormone (estrogen or 17β-estradiol) can potentially act on all cellular subsets of the immune system through estrogen receptor-dependent and -independent mechanisms. This minireview highlights differential expression of estrogen receptors on immune cells, major estrogen-mediated signaling pathways, and their effect on immune cells. Since estrogen has varied effects in female-predominant autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, we will mechanistically postulate the potential differential role of estrogen in these chronic debilitating diseases. PMID:26779182

  11. Estrogens and aging skin

    PubMed Central

    Thornton, M. Julie

    2013-01-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.   Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies. PMID:24194966

  12. Different modes of hippocampal plasticity in response to estrogen in young and aged female rats

    PubMed Central

    Adams, Michelle M.; Shah, Ravi A.; Janssen, William G. M.; Morrison, John H.

    2001-01-01

    Estrogen regulates hippocampal dendritic spine density and synapse number in an N-methyl-d-aspartate (NMDA) receptor-dependent manner, and these effects may be of particular importance in the context of age-related changes in endocrine status. We investigated estrogen's effects on axospinous synapse density and the synaptic distribution of the NMDA receptor subunit, NR1, within the context of aging. Although estrogen induced an increase in axospinous synapse density in young animals, it did not alter the synaptic representation of NR1, in that the amount of NR1 per synapse was equivalent across groups. Estrogen replacement in aged female rats failed to increase axospinous synapse density; however, estrogen up-regulated synaptic NR1 compared with aged animals with no estrogen. Therefore, the young and aged hippocampi react differently to estrogen replacement, with the aged animals unable to mount a plasticity response generating additional synapses, yet responsive to estrogen with respect to additional NMDA receptor content per synapse. These findings have important implications for estrogen replacement therapy in the context of aging. PMID:11427724

  13. Estrogen and Osteoporosis.

    ERIC Educational Resources Information Center

    Lindsay, Robert

    1987-01-01

    This article reviews the use of estrogen in the prevention and treatment of osteoporosis. Dosage levels, interactions with other factors, side effects, and the mechanism of estrogen action are discussed. (Author/MT)

  14. Estrogen and Bazedoxifene

    MedlinePlus

    ... estrogen that controls your symptoms and only taking estrogen as long as needed can help reduce these risks. Talk to your doctor from time to time to decide if you should take a lower dose of estrogen or should stop taking the medication.Talk to ...

  15. Postmenopausal skin and estrogen.

    PubMed

    Archer, David F

    2012-10-01

    The aging global population continues to drive increasing demand for cosmaceuticals and cosmetic surgery among older men and women. Since the discovery in the 1990s that estrogen receptors are present in skin cells and decline in number from the onset of menopause in women, researchers have explored a number of ways in which estrogen can improve skin condition. Skin is estrogen responsive, and several studies now exist to support the antiaging properties of estrogen replacement therapies in postmenopausal women. Both systemic and topical estrogens appear to have positive effects on hormonal aging, increasing skin collagen content, thickness, elasticity and hydration. Estrogen therapies may also improve wound healing and reduce the incidence of wound complications. This review explores the potential for targeted estrogen replacement as a therapeutic option for long-term skin management in postmenopausal women.

  16. A calcineurin/AKAP complex is required for NMDA receptor-dependent long-term depression.

    PubMed

    Jurado, Sandra; Biou, Virginie; Malenka, Robert C

    2010-09-01

    AKAP79/150 is a protein scaffold that is thought to position specific kinases (protein kinase A and C) and phosphatases (calcineurin) in appropriate synaptic domains so that their activities can regulate excitatory synaptic strength. Using a viral-mediated molecular replacement strategy in rat hippocampal slices, we found that AKAP is required for NMDA receptor-dependent long-term depression solely because of its interaction with calcineurin.

  17. ESTROGENIC STATUS MODULATES DMBA-MEDIATED HEPATIC GENE EXPRESSION: MICROARRAY-BASED ANALYSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogenic status in women influences the metabolism and toxicity of polycyclic aromatic hydrocarbons (PAH). The objective of this study was to examine the influence of estradiol (E2) on 7,12 dimethylbenz(a)anthracene (DMBA), a ligand for aryl hydrocarbon receptor, mediated changes on gene expressio...

  18. The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus.

    PubMed

    Ninan, Ipe; Bath, Kevin G; Dagar, Karishma; Perez-Castro, Rosalia; Plummer, Mark R; Lee, Francis S; Chao, Moses V

    2010-06-30

    The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene results in a defect in regulated release of BDNF and affects episodic memory and affective behaviors. However, the precise role of the BDNF Val66Met polymorphism in hippocampal synaptic transmission and plasticity has not yet been studied. Therefore, we examined synaptic properties in the hippocampal CA3-CA1 synapses of BDNF(Met/Met) mice and matched wild-type mice. Although basal glutamatergic neurotransmission was normal, both young and adult mice showed a significant reduction in NMDA receptor-dependent long-term potentiation. We also found that NMDA receptor-dependent long-term depression was decreased in BDNF(Met/Met) mice. However, mGluR-dependent long-term depression was not affected by the BDNF Val66Met polymorphism. Consistent with the NMDA receptor-dependent synaptic plasticity impairment, we observed a significant decrease in NMDA receptor neurotransmission in the CA1 pyramidal neurons of BDNF(Met/Met) mice. Thus, these results show that the BDNF Val66Met polymorphism has a direct effect on NMDA receptor transmission, which may account for changes in synaptic plasticity in the hippocampus.

  19. Assessing in-vitro estrogenic effects of currently-used flame retardants.

    PubMed

    Krivoshiev, Boris V; Dardenne, Freddy; Covaci, Adrian; Blust, Ronny; Husson, Steven J

    2016-06-01

    Flame retardants are chemicals that are added to nearly all manufactured materials. Additionally, there has been a steady increase in diseases resulting from endocrine-disruption with an aligned increase in use of chemicals. Given the persistence, potential bioaccumulation, limited toxicological understanding, and vast use of flame retardants, there is a need to investigate potential endocrine-disruptive activity associated with these compounds in an effort for better risk assessment. We therefore used the MCF-7 flow-cytometric proliferation assay in an effort to establish potential estrogen-disrupting effects of twelve currently-used flame retardants. Triphenyl phosphate, tris(1,3-dichloro-2-propyl) phosphate, tris(butyl) phosphate, hexabromocyclododecane, and tetrabromobisphenol A showed statistically significant estrogenic activity, with hexabromocyclododecane being the most potent of the five (EC20 of 5.5 μM). Tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, tri(2-chloroethyl) phosphate, tris(butyl) phosphate, hexabromocyclododecane, tetrabromobisphenol A, and tris(2,3,-dibromopropyl) isocyanurate harboured anti-estrogenic activity when co-treating with 17β-estradiol, with hexabromocyclododecane showing the highest potency (IC20 of 17.6 μM). Interestingly, some compounds showed both estrogenic and anti-estrogenic effects, indicating both receptor-dependant and -independent mechanisms attributed to some of these compounds, in line with other studies. Multiple currently-used flame retardants may therefore act as xenoestrogens and anti-estrogens, or alter estrogen homeostasis, which could affect endocrine function.

  20. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    PubMed Central

    2011-01-01

    Background Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments. Results We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7. Conclusions These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. PMID:22182308

  1. The Measurement of Estrogens

    NASA Astrophysics Data System (ADS)

    Holder, Geoff; Makin, Hugh L. J.; Bradlow, H. Leon

    Biologists use the word ‘estrogen' when referring to molecules which have the ability to induce uterine growth or vaginal cornification in the immature or ovariectomized rodent. The word estrogen was derived from two Greek words - oistros meaning frenzy and gennein - to beget. Chemists and biochemists, however, often restrict their use of this term to molecules that contain a characteristic 18-carbon steroid nucleus with an aromatic (phenolic) A-ring, both those that are biologically active estrogens and those without biologic activity but which are of intrinsic interest, such as the estrogen conjugates. This chapter is concerned only with these steroid compounds. The structure and inter-relationship of some common estrogens are given in Fig. 8.1. In addition to the biological estrogens, there are a wide variety of both natural and synthetic compounds which have estrogenic activity when measured by one or another parameter. While many of the assay procedures described in this review are applicable to these compounds, their application to non C18-steroids will not be discussed here. Methodology for these non-steroidal compounds can be found in reviews by Wang et al. (2002), Wu et al. (2004), Muir (2006), and Delmonte and Rader (2006). While not wishing to downgrade the importance of previous work in the estrogen field, the authors have taken a deliberate decision to exclude most publications prior to 1975, not because these do not have value but simply because space is not unlimited and readers of the present chapter might be expected to be seeking information about methodology which is less than 30 years old. Readers seeking pre-1975 information in this area can find it in Oakey and Holder (1995).

  2. Molecular cloning and characterization of ligand- and species-specificity of amphibian estrogen receptors.

    PubMed

    Katsu, Yoshinao; Taniguchi, Ena; Urushitani, Hiroshi; Miyagawa, Shinichi; Takase, Minoru; Kubokawa, Kaoru; Tooi, Osamu; Oka, Tomohiro; Santo, Noriaki; Myburgh, Jan; Matsuno, Akira; Iguchi, Taisen

    2010-09-01

    Estrogens are essential for normal reproductive activity in both males and females as well as for ovarian differentiation during a critical developmental stage in most vertebrates. To understand the molecular mechanisms of estrogen action and to evaluate estrogen receptor ligand interactions in amphibians, we isolated cDNAs encoding the estrogen receptors (ERalpha and ERbeta) from the Japanese firebelly newt (Cynops pyrrhogaster), Tokyo salamander (Hynobius tokyoensis), axolotl (Ambystoma mexicanum), and Raucous toad (Bufo rangeri). Full-length amphibian ER cDNAs were obtained using 5' and 3' rapid amplification of cDNA ends. The predicted amino acid sequences of these amphibian ERs showed a high degree of amino acid sequence identity (over 70%) to each other. We analyzed the relationships of these amphibian ER sequences to other vertebrate ER sequences by constructing a phylogenetic tree. We verified that these were bona fide estrogen receptors using receptor dependent reporter gene assays. We analyzed the effects of natural estrogens, ethinylestradiol, and DDT and its metabolites on the transactivation of the four amphibian species listed above, and Xenopus tropicalis ERs and found that there were species-specific differences in the sensitivity of these ERs to hormones and environmental chemicals. These findings will expand our knowledge of endocrine-disrupting events in amphibians.

  3. Estrogenic followed by anti-estrogenic effects of PCBs exposure in juvenil fish (Spaurus aurata).

    PubMed

    Calò, M; Alberghina, D; Bitto, A; Lauriano, E R; Lo Cascio, P

    2010-01-01

    Vitellogenin (Vtg) is a phospho-lipo-glycoprotein produced by oviparous animals in response to estrogen receptor (ER) binding. The presence of Vtg in juvenile and male fish liver and plasma has been used as biomarker to evaluate levels of environmental contaminants as dioxin and PCBs. Interaction of dioxins and PCBs with aryl hydrocarbon receptor (AhR) may affect reproduction by recruitment of estrogen receptor alpha (ERalpha). The aim of this study was to investigate the effects of PCB-126, a co-planar PCB prototypical AhR agonist, and of PCB-153, a non-coplanar PCB lacking dioxine-like activity, on Vtg expression in young fish (Spaurus aurata) after a 12 or 24h exposure to PCBs as well as 48h following PCBs removal. Vtg expression was evaluated by immunohistochemistry and by Western-blot analysis. Our results showed an increased Vtg expression following PCBs administration, with a maximum level after 12h of exposure to either PCB-126, PCB-153 or a mixture of both PCBs. Following this estrogenic activity, an anti-estrogenic activity was detected after 24h of incubation with PCB-126 (alone or mixed with PCB-153), suggested by a decrease in Vtg expression likely through AhR, as a consequence of a hypothetic defence mechanism to endogenous or exogenous ligands.

  4. IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity.

    PubMed

    Zhu, Li X; Sharma, Sherven; Gardner, Brian; Escuadro, Brian; Atianzar, Kimberly; Tashkin, Donald P; Dubinett, Steven M

    2003-04-01

    Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.

  5. Estrogen and the cardiovascular system.

    PubMed

    Knowlton, A A; Lee, A R

    2012-07-01

    Estrogen is a potent steroid with pleiotropic effects, which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription factor, both activating and repressing gene expression. Several different ERs regulate the specificity of response to estrogen, and appear to have specific effects in cardiac remodeling and the response to injury. However, much remains to be understood about the selectivity of these receptors and their specific effects on gene expression. Basic studies have demonstrated that estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and not shown the clear-cut benefit of more basic investigations. This can be explained in part by differences in study design: in basic studies estrogen treatment was used immediately or shortly after ovariectomy, while in some key clinical trials, estrogen was given years after menopause. Further basic research into the underlying molecular mechanisms of estrogen's actions is essential to provide a better comprehension of the many properties of this powerful hormone.

  6. Removal of Estrogens and Estrogenicity through Drinking Water Treatment

    EPA Science Inventory

    Estrogenic compounds have been shown to be present in surface waters, leading to concerns over their possible presence in finished drining waters. In this work, two in vitro human cell line bioassays for estrogenicity were used to evaluate the removal of estrogens through conven...

  7. Estrogen supplements in menopause.

    PubMed

    Booher, D L

    1990-01-01

    The number of women aged 65 and older is expected to double by the year 2000, increasing the need for effective management of symptoms related to menopause. Contemporary management of menopause addresses the continuum of events associated with the effects of estrogen deprivation on quality and duration of life, including neuroendocrine changes, urogenital atrophy, sexual dysfunction, skin and hair changes, osteoporosis, and cardiovascular disease. The risks and benefits of management strategies, including hormone replacement therapy, must be weighted carefully by both physician and patient. The use of estrogens and progestins, alterative compounds, dosages, routes of administration, and their advantages and disadvantages must be analyzed.

  8. HES1 Is a Master Regulator of Glucocorticoid Receptor-Dependent Gene Expression

    PubMed Central

    Revollo, Javier R.; Oakley, Robert H.; Lu, Nick Z.; Kadmiel, Mahita; Gandhavadi, Maheer; Cidlowski, John A.

    2014-01-01

    Hairy and enhancer of split-1 (HES1) is a basic helix-loop-helix transcription factor that is a key regulator of development and organogenesis. However, little is known about the role of HES1 after birth. Glucocorticoids, primary stress hormones that are essential for life, regulate numerous homeostatic processes that permit vertebrates to cope with physiological challenges. The molecular actions of glucocorticoids are mediated by glucocorticoid receptor-dependent regulation of nearly 25% of the genome. We now establish a genome wide molecular link between HES1 and glucocorticoid receptors that controls the ability of cells and animals to respond to stress. Glucocorticoid signaling rapidly and robustly silenced HES1 expression. This glucocorticoid-dependent repression of HES1 was necessary for the glucocorticoid receptor to regulate many of its target genes. Mice with conditional knockout of HES1 in the liver exhibited an expanded glucocorticoid receptor signaling profile and aberrant metabolic phenotype. Our results indicate that HES1 acts as a master repressor, the silencing of which is required for proper glucocorticoid signaling. PMID:24300895

  9. Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation

    SciTech Connect

    Suits, A.G.; Chait, A.; Aviram, M.; Heinecke, J.W. )

    1989-04-01

    Low density lipoprotein (LDL) modified by incubation with phospholipase C (PLC-LDL) aggregates in solution and is rapidly taken up and degraded by human and mouse macrophages, producing foam cells in vitro. Human, mouse, and rabbit macrophages degraded {sup 125}I-labeled PLC-LDL ({sup 125}I-PLC-LDL) more rapidly than native {sup 125}I-labeled LDL ({sup 125}I-LDL), while nonphagocytic cells such as human fibroblasts and bovine aortic endothelial cells degraded {sup 125}I-PLC-LDL more slowly than {sup 125}I-LDL. This suggested the mechanism for internalization of PLC-LDL was phagocytosis. When examined by electron microscopy, mouse peritoneal macrophages appeared to be phagocytosing PLC-LDL. The uptake and degradation of {sup 125}I-PLC-LDL by human macrophages was inhibited >80% by the monoclonal antibody C7 (IgG2b) produced by hybridoma C7, which blocks the ligand binding domain of the LDL receptor. Similarly, methylation of {sup 125}I-LDL ({sup 125}I-MeLDL) prior to treatment with phospholipase C decreased its subsequent uptake and degradation by human macrophages by >90%. The uptake and degradation of phospholipase C-modified {sup 125}I-MeLDL by macrophages could be restored by incubation of the methylated lipoprotein with apoprotein E, a ligand recognized by the LDL receptor. These results indicate that macrophages internalize PLC-LDL by LDL receptor-dependent phagocytosis.

  10. The receptor-dependent LQTA-QSAR: application to a set of trypanothione reductase inhibitors

    NASA Astrophysics Data System (ADS)

    Barbosa, Euzébio G.; Pasqualoto, Kerly Fernanda M.; Ferreira, Márcia M. C.

    2012-09-01

    A new Receptor- Dependent LQTA- QSAR approach, RD- LQTA- QSAR, is proposed as a new 4D-QSAR method. It is an evolution of receptor independent LQTA-QSAR. This approach uses the free GROMACS package to carry out molecular dynamics simulations and generates a conformational ensemble profile for each compound. Such an ensemble is used to build molecular interaction field-based QSAR models, as in CoMFA. To show the potential of this methodology, a set of 38 phenothiazine derivatives that are specific competitive T. cruzi trypanothione reductase inhibitors, was chosen. Using a combination of molecular docking and molecular dynamics simulations, the binding mode of the phenotiazine derivatives was evaluated in a simulated induced fit approach. The ligands alignments were performed using both ligand and binding site atoms, enabling unbiased alignment. The models obtained were extensively validated by leave- N-out cross-validation and y-randomization techniques to test for their robustness and absence of chance correlation. The final model presented Q 2 LOO of 0.87 and R² of 0.92 and a suitable external prediction of Q_{ext}2 = 0.78. The adapted binding site obtained is useful to perform virtual screening and ligand structure-based design and the descriptors in the final model can aid in the design new inhibitors.

  11. β-caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner

    PubMed Central

    Horváth, Béla; Mukhopadhyay, Partha; Kechrid, Malek; Patel, Vivek; Tanashian, Galin; Wink, David A.; Gertsch, Jürg; Pacher, Pál

    2012-01-01

    (E)-β-caryophyllene (BCP) is a natural sequiterpene found in many essential oils of spice (best known for contributing to the spiciness of black pepper) and food plants with recognized anti-inflammatory properties. Recently it was shown that BCP is a natural agonist of endogenous cannabinoid 2 (CB2) receptors, which are expressed in immune cells and mediate anti-inflammatory effects. In this study we aimed to test the effects of BCP in a clinically relevant murine model of nephropathy (induced by the widely used antineoplastic drug cisplatin) in which the tubular injury is largely dependent on inflammation and oxidative/nitrative stress. β-caryophyllene dose-dependently ameliorated cisplatin-induced kidney dysfunction, morphological damage, and renal inflammatory response (chemokines MCP-1 and MIP-2, cytokines TNF-α and IL-1β, adhesion molecule ICAM-1, and neutrophil and macrophage infiltration). It also markedly mitigated oxidative/nitrative stress (NOX-2, NOX-4 expression, 4-HNE and 3-NT content) and cell death. The protective effects of BCP against biochemical and histological markers of nephropathy were absent in CB2 knockout mice. Thus, BCP may be an excellent therapeutic agent to prevent cisplatin-induced nephrotoxicity through a CB2 receptor dependent pathway. Given the excellent safety profile of BCP in humans it has tremendous therapeutic potential in multitude of diseases associated with inflammation and oxidative stress. PMID:22326488

  12. β-Caryophyllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependent manner.

    PubMed

    Horváth, Béla; Mukhopadhyay, Partha; Kechrid, Malek; Patel, Vivek; Tanchian, Galin; Wink, David A; Gertsch, Jürg; Pacher, Pál

    2012-04-15

    (E)-β-caryophyllene (BCP) is a natural sesquiterpene found in many essential oils of spice (best known for contributing to the spiciness of black pepper) and food plants with recognized anti-inflammatory properties. Recently it was shown that BCP is a natural agonist of endogenous cannabinoid 2 (CB(2)) receptors, which are expressed in immune cells and mediate anti-inflammatory effects. In this study we aimed to test the effects of BCP in a clinically relevant murine model of nephropathy (induced by the widely used antineoplastic drug cisplatin) in which the tubular injury is largely dependent on inflammation and oxidative/nitrative stress. β-caryophyllene dose-dependently ameliorated cisplatin-induced kidney dysfunction, morphological damage, and renal inflammatory response (chemokines MCP-1 and MIP-2, cytokines TNF-α and IL-1β, adhesion molecule ICAM-1, and neutrophil and macrophage infiltration). It also markedly mitigated oxidative/nitrative stress (NOX-2 and NOX-4 expression, 4-HNE and 3-NT content) and cell death. The protective effects of BCP against biochemical and histological markers of nephropathy were absent in CB(2) knockout mice. Thus, BCP may be an excellent therapeutic agent to prevent cisplatin-induced nephrotoxicity through a CB(2) receptor-dependent pathway. Given the excellent safety profile of BCP in humans it has tremendous therapeutic potential in a multitude of diseases associated with inflammation and oxidative stress.

  13. Apparatus for hydrocarbon extraction

    DOEpatents

    Bohnert, George W.; Verhulst, Galen G.

    2013-03-19

    Systems and methods for hydrocarbon extraction from hydrocarbon-containing material. Such systems and methods relate to extracting hydrocarbon from hydrocarbon-containing material employing a non-aqueous extractant. Additionally, such systems and methods relate to recovering and reusing non-aqueous extractant employed for extracting hydrocarbon from hydrocarbon-containing material.

  14. Formation of estrogenic metabolites of benzo[a]pyrene and chrysene by cytochrome P450 activity and their combined and supra-maximal estrogenic activity.

    PubMed

    van Lipzig, Marola M H; Vermeulen, Nico P E; Gusinu, Renato; Legler, Juliette; Frank, Heinz; Seidel, Albrecht; Meerman, John H N

    2005-01-01

    Metabolism of polycyclic aromatic hydrocarbons (PAHs) has been studied intensively, and potential metabolites with estrogenic activity have been identified previously. However, little attention has been paid to the metabolic pathways in mammalians and to the combined effect of individual metabolites. Several hydroxylated metabolites of benzo[a]pyrene (BaP) and chrysene (CHN) were formed by rat liver microsomal cytochrome P450 (CYP) activity, some of which possess estrogenic activity. All mono- and several dihydroxylated metabolites of BaP and CHN were tested for ER affinity and estrogenic activity in a proliferation assay (E-screen) and in a reporter-gene assay (ER-CALUX). Twelve estrogenic metabolites were identified with EC50 values ranging from 40nM to 0.15mM. The combined effect of a mixture of seven PAH-metabolites was also studied in the ER binding assay. At concentrations that show little activity themselves, their joint action clearly exhibited significant estrogenic activity. BaP itself exhibited estrogenicity in the ER-CALUX assay due to bio-activation into estrogenic metabolites, probably via aryl hydrocarbon receptor (AhR) induced CYP activity. Furthermore, 2-hydroxy-CHN (2-OHCHN) induced supra-maximal (400%) estrogenic effects in the ER-CALUX assay. This effect was entirely ER-mediated, since the response was completely blocked with the ER-antagonist ICI182,780. We showed that 2-OHCHN increased ER-concentration, using ELISA techniques, which may explain the observed supra-maximal effects. Co-treatment with the AhR-antagonist 3',4'-dimethoxyflavone (DMF) enhanced ER-signaling, possibly via blockage of AhR-ER inhibitory cross-talk.

  15. Cannabidiol potentiates pharmacological effects of Delta(9)-tetrahydrocannabinol via CB(1) receptor-dependent mechanism.

    PubMed

    Hayakawa, Kazuhide; Mishima, Kenichi; Hazekawa, Mai; Sano, Kazunori; Irie, Keiichi; Orito, Kensuke; Egawa, Takashi; Kitamura, Yoshihisa; Uchida, Naoki; Nishimura, Ryoji; Egashira, Nobuaki; Iwasaki, Katsunori; Fujiwara, Michihiro

    2008-01-10

    Cannabidiol, a non-psychoactive component of cannabis, has been reported to have interactions with Delta(9)-tetrahydrocannabinol (Delta(9)-THC). However, such interactions have not sufficiently been clear and may have important implications for understanding the pharmacological effects of marijuana. In the present study, we investigated whether cannabidiol modulates the pharmacological effects of Delta(9)-THC on locomotor activity, catalepsy-like immobilisation, rectal temperature and spatial memory in the eight-arm radial maze task in mice. In addition, we measured expression level of cannabinoid CB(1) receptor at striatum, cortex, hippocampus and hypothalamus. Delta(9)-THC (1, 3, 6 and 10 mg/kg) induced hypoactivity, catalepsy-like immobilisation and hypothermia in a dose-dependent manner. In addition, Delta(9)-THC (1, 3 and 6 mg/kg) dose-dependently impaired spatial memory in eight-arm radial maze. On the other hand, cannabidiol (1, 3, 10, 25 and 50 mg/kg) did not affect locomotor activity, catalepsy-like immobilisation, rectal temperature and spatial memory on its own. However, higher dose of cannabidiol (10 or 50 mg/kg) exacerbated pharmacological effects of lower dose of Delta(9)-THC, such as hypoactivity, hypothermia and impairment of spatial memory. Moreover, cannabidiol (50 mg/kg) with Delta(9)-THC (1 mg/kg) enhanced the expression level of CB(1) receptor expression in hippocampus and hypothalamus. Cannabidiol potentiated pharmacological effects of Delta(9)-THC via CB(1) receptor-dependent mechanism. These findings may contribute in setting the basis for interaction of cannabinoids and to find a cannabinoid mechanism in central nervous system.

  16. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP

    PubMed Central

    Bickford, Paula C.; Browning, Michael D.

    2008-01-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4 months old) and aged rats (24 months old) given either a control diet or a diet supplemented with blueberry extract for 6–8 weeks. NMDAR-dependent LTP was evoked by high-frequency stimulation (HFS) in the presence of nifedipine, to eliminate voltage-gated calcium channel LTP. Field excitatory postsynaptic potentials (fEPSPs) were increased by 57% 1 h after HFS in young animals, but this potentiation was reduced to 31% in aged animals. Supplementation of the diet with blueberry extract elevated LTP (63%) in aged animals to levels seen in young. The normalization of LTP may be due to the blueberry diet preventing a decline in synaptic strength, as measured by the slope of the fEPSP for a given fiber potential. The blueberry diet did not prevent age-related declines in NMDAR protein expression. However, phosphorylation of a key tyrosine residue on the NR2B subunit, important for increasing NMDAR function, was enhanced by the diet, suggesting that an increase in NMDAR function might overcome the loss in protein. This report provides evidence that dietary alterations later in life may prevent or postpone the cognitive declines associated with aging. PMID:19424850

  17. Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

    PubMed

    Oviedo, Pilar J; Sobrino, Agua; Laguna-Fernandez, Andrés; Novella, Susana; Tarín, Juan J; García-Pérez, Miguel-Angel; Sanchís, Juan; Cano, Antonio; Hermenegildo, Carlos

    2011-03-30

    Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells.

  18. RNA Regulation of Estrogen

    DTIC Science & Technology

    2010-08-01

    contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position, policy or decision...Estrogen 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-09-1-0353 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) J. Andrew...ORGANIZATION NAME( S ) AND ADDRESS(ES) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER University of Oregon Eugene OR 97403-5295

  19. Molecular Mechanism of Action of Genistein and Related Phytoestrogens in Estrogen-Receptor Dependent and Independent Growth of Breast Cancer Cells

    DTIC Science & Technology

    1999-07-01

    quercetin inhibited ER-negative MDA-MB-468 breast cancer cell growth with 1050 values of 8.8 and 18.1 Micronmeter, respectively. The other compounds...were less effective. The mechanism of growth inhibition by genistein and quercetin involved G2/M cell cycle arrest, changes in cyclin B1 levels and...apoptosis. Our results indicate that genistein and quercetin may be useful in the treatment of ER-negative tumors. Results of our studies on MDA-MB-468 cells have been documented and submitted for publication.

  20. Methoxychlor and triclosan stimulates ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an estrogen receptor-dependent pathway.

    PubMed

    Kim, Joo-Young; Yi, Bo-Rim; Go, Ryeo-Eun; Hwang, Kyung-A; Nam, Ki-Hoan; Choi, Kyung-Chul

    2014-05-01

    Methoxychlor and triclosan are emergent or suspected endocrine-disrupting chemicals (EDCs). Methoxychlor [MXC; 1,1,1-trichlor-2,2-bis (4-methoxyphenyl) ethane] is an organochlorine pesticide that has been primarily used since dichlorodiphenyltrichloroethane (DDT) was banned. In addition, triclosan (TCS) is used as a common component of soaps, deodorants, toothpastes, and other hygiene products at concentrations up to 0.3%. In the present study, the potential impact of MXC and TCS on ovarian cancer cell growth and underlying mechanism(s) was examined following their treatments in BG-1 ovarian cancer cells. As results, MXC and TCS induced BG-1 cell growth via regulating cyclin D1, p21 and Bax genes related with cell cycle and apoptosis. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay confirmed that the proliferation of BG-1 ovarian cancer cells was stimulated by MXC (10(-6), 10(-7), 10(-8), and 10(-9)M) or TCS (10(-6), 10(-7), 10(-8), and 10(-9)M). Treatment of BG-1 cells with MXC or TCS resulted in the upregulation of cyclin D1 and downregulation of p21 and Bax transcriptions. In addition, the protein level of cyclin D1 was increased by MXC or TCS while p21 and Bax protein levels appeared to be reduced in these cells. Furthermore, MXC- or TCS-induced alterations of these genes were reversed in the presence of ICI 182,780 (10(-7)M), suggesting that the changes in these gene expressions may be regulated by an ER-dependent signaling pathway. In conclusion, the results of our investigation indicate that two potential EDCs, MXC and TCS, may stimulate ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an ER-dependent pathway.

  1. Estrogenic effects from household stoves.

    PubMed

    Wu, W Z; Chen, J; Rehmann, K; Schramm, K W; Kettrup

    2002-09-01

    With the application of a genetically modified yeast, estrogen receptor-activating compounds were detected in the soot and emission gas of a wood-burning household stove. The EC50 value of 17beta-estradiol was divided by the EC50 value of soot, and the obtained relative estrogenic value for raw soot was 2.37E-5, indicating that soot was about 100,000 times less estrogenic than 17beta-estradiol. Chemical analysis revealed that alkyl phenol, benzonic acid, and PAHs represented the major constituents in the most potent fractions of the soot. Along with PAHs, other constituents might also contribute to the estrogenicity of soot.

  2. Exercise, Eating, Estrogen, and Osteoporosis.

    ERIC Educational Resources Information Center

    Brown, Jim

    1986-01-01

    Osteoporosis affects millions of people, especially women. Three methods for preventing or managing osteoporosis are recommended: (1) exercise; (2) increased calcium intake; and (3) estrogen replacement therapy. (CB)

  3. Estrogen receptors in breast carcinoma.

    PubMed

    Huaman, A

    1979-11-01

    On the basis of estrogen receptor assays, breast carcinomas are presently classified as estrogen-dependent tumors, which respond to endocrine therapy, and autonomous tumors, for which endocrine therapy is useless. This paper presents a short review of the biochemical principles of estrogen dependence, the procedures used to determine estrogen receptors, and the clinical applications of the findings of these assay procedures. Biobhemically, the estroogen dependence of normal breast cells is explained as a biochemical reaction occurring between the circulating estradiol and the breast cell, which occurs in 3 steps: 1) circulating estradiol penetrates the cellular membrane by passive diffusion, followed by 2) combining of estradiol with the estrogen-binding protein (estrophilin) and formation of an estrogen receptor complex which undergoes activation and translocation into the nucleus, to result in 3) the activated steroid receptor which combines with the nuclear charomatin and stimulates ribonucleic acid synthesis for the formation of estradiol binding proteins or estradiol receptors. The cytosol method of Wittliff et al. is described in brief and entails radioactive competitive analysis; the other available laboratory procedure is immunofluorescence of tumor sections. Quantification of estrogen receptor content can be used clinically to decide on ablative endocrine therapy, to determine the effectiveness of anti-estrogen administration, to determine the primary site of metastatic carcinoma, and as a screenng device.

  4. Estrogen therapy for postmenopausal osteoporosis.

    PubMed

    Fitzpatrick, Lorraine A

    2006-08-01

    Osteoporosis is a worldwide problem that results in fractures that lead to disability and high costs to society. Estrogen therapy is frequently utilized for postmenopausal symptoms, but also has proven protective effects on the skeleton. The main action of estrogen at the cellular level is to inhibit the osteoclast by increasing levels of osteoprotegerin (OPG). OPG binds to the receptor activator of NFkB and prevents osteoclast differentiation, activity and survival. Numerous trials have demonstrated the positive effect estrogen has on the improvement of bone mineral density, and lower doses have also proven efficacious with fewer side effects. Both observational and randomized clinical trials have demonstrated the ability of estrogen treatment to prevent fractures. Topics that remain controversial include the appropriate length of estrogen treatment for postmenopausal women and the appropriate follow-up after treatment discontinuation.

  5. Risks of estrogens and progestogens.

    PubMed

    L'Hermite, M

    1990-09-01

    The risks and benefits of specific types of postmenopausal estrogens and progestogens are explored: those affecting serum lipids, clotting elements, hepatic proteins synthesis, blood pressure, glucose tolerance, endometrial, breast and cervical cancer. Ethinyl estradiol taken orally is the only estrogen likely to cause gall bladder disease. It also induces liver protein synthesis when taken orally or vaginally. Natural estrogens do not heighten coagulation factors, and may shift towards fibrinolysis. Both ethinyl estradiol and equine estrogens may increase blood pressure, while natural estrogens may decrease it. Similarly natural estrogens induce prostacyclin synthesis, while ethinyl estradiol activates both prostacyclin and thromboxanes. Progestagens, especially so the norprogestins, disturb carbohydrate metabolism and tend to reverse the beneficial effects of estrogens on serum lipids, a 40-70% reduction in risk of mortality from coronary heart disease. A meta- analysis of 23 studies concluded that menopausal estrogens do not increase the risk of breast cancer by a measurable degree, except in high doses and in those predisposed by family history. There is an increased risk of endometrial carcinoma for those taking unopposed estrogens for more than 3-6 years. This can be attenuated by taking combined estrogen-progestins, which will eventually result in absence of bleeding, or a 12-day progestogen course every 4-6 cycles. Oral micronized progesterone decreases blood pressure. The relative androgenic effects of progestins other than the norprogesterone derivatives are less significant. As an alternative to taking a progestogen, a woman could have regular endometrial sampling or abdominal or vaginal sonograms to detect endometrial cancer.

  6. Selective Estrogen Receptor Modulators

    PubMed Central

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are now being used as a treatment for breast cancer, osteoporosis and postmenopausal symptoms, as these drugs have features that can act as an estrogen agonist and an antagonist, depending on the target tissue. After tamoxifen, raloxifene, lasofoxifene and bazedoxifene SERMs have been developed and used for treatment. The clinically decisive difference among these drugs (i.e., the key difference) is their endometrial safety. Compared to bisphosphonate drug formulations for osteoporosis, SERMs are to be used primarily in postmenopausal women of younger age and are particularly recommended if there is a family history of invasive breast cancer, as their use greatly reduces the incidence of this type of cancer in women. Among the above mentioned SERMs, raloxifene has been widely used in prevention and treatment of postmenopausal osteoporosis and vertebral compression fractures, and clinical studies are now underway to test the comparative advantages of raloxifene with those of bazedoxifene, a more recently developed SERM. Research on a number of adverse side effects of SERM agents is being performed to determine the long-term safety of this class of compouds for treatment of osteoporosis. PMID:27559463

  7. Estrogen receptor signaling during vertebrate development

    PubMed Central

    Bondesson, Maria; Hao, Ruixin; Lin, Chin-Yo; Williams, Cecilia; Gustafsson, Jan-Åke

    2014-01-01

    Estrogen receptors are expressed and their cognate ligands produced in all vertebrates, indicative of important and conserved functions. Through evolution estrogen has been involved in controlling reproduction, affecting both the development of reproductive organs and reproductive behavior. This review broadly describes the synthesis of estrogens and the expression patterns of aromatase and the estrogen receptors, in relation to estrogen functions in the developing fetus and child. We focus on the role of estrogens for development of reproductive tissues, as well as non-reproductive effects on the developing brain. We collate data from human, rodent, bird and fish studies and highlight common and species-specific effects of estrogen signaling on fetal development. Morphological malformations originating from perturbed estrogen signaling in estrogen receptor and aromatase knockout mice are discussed, as well as the clinical manifestations of rare estrogen receptor alpha and aromatase gene mutations in humans. PMID:24954179

  8. Design and structure of stapled peptides binding to estrogen receptors.

    PubMed

    Phillips, Chris; Roberts, Lee R; Schade, Markus; Bazin, Richard; Bent, Andrew; Davies, Nichola L; Moore, Rob; Pannifer, Andrew D; Pickford, Andrew R; Prior, Stephen H; Read, Christopher M; Scott, Andrew; Brown, David G; Xu, Bin; Irving, Stephen L

    2011-06-29

    Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor-stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.

  9. Estrogenicity and acute toxicity of selected anilines using a recombinant yeast assay.

    PubMed

    Hamblen, Elizabeth L; Cronin, Mark T D; Schultz, T Wayne

    2003-08-01

    Suspected estrogen modulators include industrial organic chemicals (i.e., xenoestrogens), and have been shown to consist of alkylphenols, bisphenols, biphenylols, and some hydroxy-substituted polycyclic aromatic hydrocarbons. The most prominent structural feature identified to be important for estrogenic activity is a polar group capable of donating hydrogen bonds (i.e., hydroxyl) on an aromatic system. The present study was undertaken to explore the estrogenic activity and acute toxicity of chemicals containing a weaker hydrogen bond donor group on aromatic systems, i.e., the amino substituent. There is a great deal of chemical similarity between aromatic amines (anilines) and aromatic alcohols (phenols). The chemicals chosen for the current study contained an amino-substituted benzene ring with hydrophobic constituents varying in size and shape. Thus, 37 substituted aromatic amines were assayed for estrogenic activity EC50 and acute toxicity LC50 using the Saccharomyces cerevisiae recombinant yeast assay. While the EC50 of 17-beta-estradiol occurs at the 10(-10) range, the aniline with the greatest activity had an EC50 of 10(-6) M. Thus, anilines, in general, are capable only of very weak estrogenic activity in this assay. A comparison of estrogenic potency between the present group of anilines and a set of previously tested analogous phenols indicated that anilines are consistently less estrogenic than phenols. A comparison of hazard indices (EC50/LC50) of these chemicals revealed that, for the vast majority of anilines, the EC50 and LC50 were in the same order of magnitude. More specifically, estrogenic activity of para-substituted alkylanilines increases with alkyl group size up to 5 carbons in length, after which the acute toxicity of the larger alkyl-substituents precluded the ability of the compound to induce the estrogenic response.

  10. Genetic Demonstration of a Role for Stathmin in Adult Hippocampal Neurogenesis, Spinogenesis, and NMDA Receptor-Dependent Memory

    PubMed Central

    Martel, Guillaume; Uchida, Shusaku; Hevi, Charles; Chévere-Torres, Itzamarie; Fuentes, Ileana; Park, Young Jin; Hafeez, Hannah; Yamagata, Hirotaka; Watanabe, Yoshifumi

    2016-01-01

    Neurogenesis and memory formation are essential features of the dentate gyrus (DG) area of the hippocampus, but to what extent the mechanisms responsible for both processes overlap remains poorly understood. Stathmin protein, whose tubulin-binding and microtubule-destabilizing activity is negatively regulated by its phosphorylation, is prominently expressed in the DG. We show here that stathmin is involved in neurogenesis, spinogenesis, and memory formation in the DG. tTA/tetO-regulated bitransgenic mice, expressing the unphosphorylatable constitutively active Stathmin4A mutant (Stat4A), exhibit impaired adult hippocampal neurogenesis and reduced spine density in the DG granule neurons. Although Stat4A mice display deficient NMDA receptor-dependent memory in contextual discrimination learning, which is dependent on hippocampal neurogenesis, their NMDA receptor-independent memory is normal. Confirming NMDA receptor involvement in the memory deficits, Stat4A mutant mice have a decrease in the level of synaptic NMDA receptors and a reduction in learning-dependent CREB-mediated gene transcription. The deficits in neurogenesis, spinogenesis, and memory in Stat4A mice are not present in mice in which tTA/tetO-dependent transgene transcription is blocked by doxycycline through their life. The memory deficits are also rescued within 3 d by intrahippocampal infusion of doxycycline, further indicating a role for stathmin expressed in the DG in contextual memory. Our findings therefore point to stathmin and microtubules as a mechanistic link between neurogenesis, spinogenesis, and NMDA receptor-dependent memory formation in the DG. SIGNIFICANCE STATEMENT In the present study, we aimed to clarify the role of stathmin in neuronal and behavioral functions. We characterized the neurogenic, behavioral, and molecular consequences of the gain-of-function stathmin mutation using a bitransgenic mouse expressing a constitutively active form of stathmin. We found that stathmin plays an

  11. The epigenetics of estrogen

    PubMed Central

    Zhao, Zaorui; Fan, Lu

    2011-01-01

    Epigenetic processes have been implicated in everything from cell proliferation to maternal behavior. Epigenetic alterations, including histone alterations and DNA methylation, have also been shown to play critical roles in the formation of some types of memory, and in the modulatory effects that factors, such as stress, drugs of abuse and environmental stimulation, have on the brain and memory function. Recently, we demonstrated that the ability of the sex-steroid hormone 17β-estradiol (E2) to enhance memory formation is dependent on histone acetylation and DNA methylation, a finding that has important implications for understanding how hormones influence cognition in adulthood and aging. In this article, we provide an overview of the literature demonstrating that epigenetic processes and E2 influence memory, describe our findings indicating that epigenetic alterations regulate E2-induced memory enhancement, and discuss directions for future work on the epigenetics of estrogen. PMID:21593594

  12. Influence of estrogenic pesticides on membrane integrity and membrane transfer of monosaccharide into the human red cell

    SciTech Connect

    Ingermann, R.L. )

    1989-09-01

    Some natural and synthetic estrogens inhibit carrier-mediated transport of glucose into human red blood cells and membrane vesicles from the placenta. The inhibitory action of these estrogens on transport appears to be a direct effect at the membrane and does not involve receptor binding and protein synthesis. It is not clear, however, whether such inhibition is a common feature among estrogenic agents. Several chlorinated hydrocarbon pesticides have been shown to possess estrogenic activity. These pesticides could have inhibitory effects on the human sodium-independent glucose transporter. Owing to the apparent importance of this membrane transporter in human tissues, direct interaction of hormones and xenobiotics with the glucose transporter is of fundamental significance. Some pesticides have been shown to alter membrane structure directly and alter the passive permeability of membranes. Whether the estrogenic pesticides influence passive diffusion of sugars across membranes has not been established. Finally, preliminary observations have suggested that some estrogens and pesticides have lytic effects on intact cells. Consequently, this study focuses on the ability of several estrogens and estrogenic pesticides to disrupt the cell membrane, influence the monosaccharide transporter, and alter the rate of monosaccharide permeation through the membrane by simple diffusion.

  13. [Uterine estrogen sulfotransferase and estrogen sulfatase in embryo implantation].

    PubMed

    Loza Arredondo, M C; González Juarez, N A

    1994-11-01

    The relation conjugated/unconjugated estrogens associated with reproductive processes has brought about the interest to study the biological role and regulation of the estrogen sulfotransferase and estrogen sulfatase which participate in the formation and hydrolysis of estrogen 3-sulfates, respectively. In this paper, both activities were measured through the reciprocal conversion of 3H-estrone sulfate and 3H-unconjugated estrogen during in vitro incubation with implantation sites (SI) and non-implanted sites (SNI) from the rat uterus, during the process of embryo implantation. Contrasting enzyme activities were found in these tissues. While sulfotransferase activity was higher in SI than in SNI (0.205 vs 0.144 pmol of E1S formed/mg protein/h, the inverse was found for the sulfatase (1.470 vs 1.977 pmol of E1 formed/mg protein/h). These results indicate the presence of both enzymes in the rat uterus and suggest the existence of a mechanism in SI that locally regulate the concentration of free and sulfoconjugated estrogens in which these enzymes participate.

  14. Fish populations surviving estrogen pollution.

    PubMed

    Wedekind, Claus

    2014-02-10

    Among the most common pollutants that enter the environment after passing municipal wastewater treatment are estrogens, especially the synthetic 17α-ethinylestradiol that is used in oral contraceptives. Estrogens are potent endocrine disruptors at concentrations frequently observed in surface waters. However, new genetic analyses suggest that some fish populations can be self-sustaining even in heavily polluted waters. We now need to understand the basis of this tolerance.

  15. Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxybiphenyls

    SciTech Connect

    Waller, C.L.; Minor, D.L.; McKinney, J.D.

    1995-07-01

    Certain phenyl-substituted hydrocarbons of environmental concern have the potential to disrupt the endocrine system of animals, apparently in association with their estrogenic properties. Competition with natural estrogens for the estrogen receptor is a possible mechanism by which such effects could occur. We used comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (QSAR) paradigm, to examine the underlying structural properties of ortho-chlorinated hydroxybiphenyl analogs known to bind to the estrogen receptor. The cross-validated and conventional statistical results indicate a high degree of internal predictability for the molecules included in the training data set. In addition to the phenolic (A) ring system, conformational restriction of the overall structure appears to play an important role in estrogen receptor binding affinity. Hydrophobic character as assessed using hydropathic interaction fields also contributes in a positive way to binding affinity. The CoMFA-derived QSARs may be useful in examining the estrogenic activity of a wider range of phenyl-substituted hydrocarbons of environmental concern. 37 refs., 2 figs., 2 tabs.

  16. INTERACTION OF PAH-RELATED COMPOUNDS WITH THE ALPHA AND BETA ISOFORMS OF ESTROGEN RECEPTOR. (R826192)

    EPA Science Inventory

    The ability of several 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs), heterocyclic PAHs, and their monohydroxy derivatives to interact with the estrogen receptor (ER) alpha and beta isoforms was examined. Only compounds possessing a hydroxyl group were able to compete wit...

  17. Estrogenic flavonoids: structural requirements for biological activity.

    PubMed

    Miksicek, R J

    1995-01-01

    A systematic survey of polycyclic phenols has been performed to identify members of this chemical group with estrogenic activity. Twelve compounds were found to be able to stimulate the transcriptional activity of the human estrogen receptor expressed in cultured cells by transient transfection. These natural estrogens belong to several distinct, but chemically related classes including chalcones, flavanones, flavones, flavonols, and isoflavones. Selected examples of estrogenic flavonoids were further analyzed to determine their biological potencies and their relative affinities for binding to the estrogen receptor. These data are interpreted with respect to the molecular structure of polycyclic phenols required for hormonal activity as nonsteroidal estrogens.

  18. VASCULAR ACTIONS OF ESTROGENS: FUNCTIONAL IMPLICATIONS

    PubMed Central

    Miller, Virginia M.; Duckles, Sue P.

    2009-01-01

    The impact of estrogen exposure in preventing or treating cardiovascular disease is controversial. But it is clear that estrogen has important effects on vascular physiology and pathophysiology, with potential therapeutic implications. Therefore, it is the goal of this review to summarize, using an integrated approach, current knowledge of the vascular effects of estrogen, both in humans and in experimental animals. Aspects of estrogen synthesis and receptors, as well as general mechanisms of estrogenic action are reviewed with an emphasis on issues particularly relevant to the vascular system. Recent understanding of the impact of estrogen on mitochondrial function suggests that the longer lifespan of women compared to men may depend in part on the ability of estrogen to decrease production of reactive oxygen species in mitochondria. Mechanisms by which estrogen increases endothelial vasodilator function, promotes angiogenesis and modulates autonomic function are summarized. Key aspects of the relevant pathophysiology of inflammation, atherosclerosis, stroke, migraine and thrombosis are reviewed concerning current knowledge of estrogenic effects. A number of emerging concepts are addressed throughout. These include the importance of estrogenic formulation and route of administration and the impact of genetic polymorphisms, either in estrogen receptors or in enzymes responsible for estrogen metabolism, on responsiveness to hormone treatment. The importance of local metabolism of estrogenic precursors and the impact of timing for initiation of treatment and its duration are also considered. While consensus opinions are emphasized, controversial views are presented in order to stimulate future research. PMID:18579753

  19. Xenoestrogenic gene expression: structural features of active polycyclic aromatic hydrocarbons.

    PubMed

    Schultz, T Wayne; Sinks, Glendon D

    2002-04-01

    Estrogenicity was assessed using the Saccharomyces cerevisiae-based Lac-Z reporter assay and was reported as the logarithm of the inverse of the 50% molar beta-galactosidase activity (log[EC50(-1)]). In an effort to quantify the relationship between molecular structure of polycyclic aromatic hydrocarbons (PAHs) and estrogenic gene expression, a series of PAHs were evaluated. With noted exceptions, the results of these studies indicate that the initial two-dimensional structural warning for estrogenicity, the superpositioning of a hydroxylated aromatic system on the phenolic A-ring of 17-beta-estradiol, can be extended to the PAHs. This two-dimensional-alignment criterion correctly identified estrogenicity of 22 of the 29 PAHs evaluated. Moreover, the estrogenic potency of these compounds was directly related to the size of the hydrophobic backbone. The seven compounds classified incorrectly by this structural feature were either dihydroxylated naphthalenes or aromatic nitrogen-heterocyclic compounds; all such compounds were false positives. Results with dihydroxylated naphthalenes reveal derivatives that were nonestrogenic when superimposed on the phenolic A-ring of 17-beta-estradiol had the second hydroxyl group in the position of the C-ring or were catechol-like in structure. Structural alerts for nitrogen-heterocyclic compounds must take into account the position of the hydroxyl group and the in-ring nitrogen atom; compounds with the hydroxyl group and nitrogen atom involved with the same ring were observed to be nonactive.

  20. Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans.

    PubMed

    Hoiland, Ryan L; Bain, Anthony R; Tymko, Michael M; Rieger, Mathew G; Howe, Connor A; Willie, Christopher K; Hansen, Alex B; Flück, Daniela; Wildfong, Kevin W; Stembridge, Mike; Subedi, Prajan; Anholm, James; Ainslie, Philip N

    2017-04-01

    Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]), ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), CBF (duplex ultrasound), and intracranial blood velocities (transcranial Doppler ultrasound) were measured during 5-min stages of isocapnic hypoxia at sea level (98, 90, 80, and 70% [Formula: see text]). Ventilation, [Formula: see text] and [Formula: see text], blood pressure, heart rate, and CBF were also measured upon exposure (128 ± 31 min following arrival) to high altitude (3,800 m) and 6 h following theophylline administration. At sea level, although the CBF response to hypoxia was unaltered pre- and postplacebo, it was reduced following theophylline (P < 0.01), a finding explained by a lower [Formula: see text] (P < 0.01). Upon mathematical correction for [Formula: see text], the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of [Formula: see text] At high altitude, theophylline (n = 6) had no effect on CBF compared with placebo (n = 6) when end-tidal gases were comparable (P > 0.05). We conclude that adenosine receptor-dependent signaling is not obligatory for cerebral hypoxic vasodilation in humans.NEW & NOTEWORTHY The signaling pathways that regulate human cerebral blood flow in hypoxia remain poorly understood. Using a randomized, double-blinded, and placebo-controlled study design, we determined that adenosine receptor-dependent signaling is not obligatory for the

  1. Mixture interactions of xenoestrogens with endogenous estrogens.

    EPA Science Inventory

    There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. These environmental estrogens originate from various sources including concentrated animal feedlot operations (CAFO), m...

  2. Estrogen actions in the cardiovascular system.

    PubMed

    Mendelsohn, M E

    2009-01-01

    This brief review summarizes the current state of the field for estrogen receptor actions in the cardiovascular system and the cardiovascular effects of hormone replacement therapy (HRT). It is organized into three parts: a short Introduction and overview of the current view of how estrogen works on blood vessels; a summary of the current status of clinical information regarding HRT and cardiovascular effects; and an update on state-of-the-art mouse models of estrogen action using estrogen receptor knockout mice.

  3. Fish populations surviving estrogen pollution

    PubMed Central

    2014-01-01

    Among the most common pollutants that enter the environment after passing municipal wastewater treatment are estrogens, especially the synthetic 17α-ethinylestradiol that is used in oral contraceptives. Estrogens are potent endocrine disruptors at concentrations frequently observed in surface waters. However, new genetic analyses suggest that some fish populations can be self-sustaining even in heavily polluted waters. We now need to understand the basis of this tolerance. See research article: http://www.biomedcentral.com/1741-7007/12/1 PMID:24512617

  4. Melasma Associated with Topical Estrogen Cream

    PubMed Central

    Schiechert, Rachel A.; Zaiac, Martin N.

    2017-01-01

    A 47-year-old woman presented with hyperpigmented patches on her upper extremities. The patient had begun using a topical estrogen cream in the affected areas prior to noticing the hyperpigmentation. A diagnosis of melasma secondary to topical estrogen cream was made. While systemic hormones are a well-documented trigger for the development of melasma, this case represents the first report of melasma associated with topical estrogens. Topical estrogens are frequently prescribed to postmenopausal women for skin rejuvenation. Melasma should be discussed as a potential side effect of systemic as well as topical estrogen preparations. PMID:28367263

  5. P450 enzymes of estrogen metabolism.

    PubMed

    Martucci, C P; Fishman, J

    1993-01-01

    Endogenous and exogenous estrogens undergo extensive oxidative metabolism by specific cytochrome P450 enzymes. Certain drugs and xenobiotics have been found to be potent inducers of estrogen hydroxylating enzymes with C-2 hydroxylase induction being greater than that of C-16 hydroxylase. Oxygenated estrogen metabolites have different biological activities, with C-2 metabolites having limited or no activity and C-4 and C-16 metabolites having similar potency to estradiol. Pathophysiological roles for some of the oxygenated estrogen metabolites have been proposed, e.g. 16 alpha-hydroxyestrone and 4-hydroxyestrone. These reactive estrogens are capable of damaging cellular proteins and DNA and may be carcinogenic in specific cells.

  6. Estrogens and Male Lower Urinary Tract Dysfunction

    PubMed Central

    Wynder, Jalissa L.; Nicholson, Tristan M.; DeFranco, Donald B.

    2016-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology and affect the majority of men at some time during their lives. The development of BPH/LUTS is associated with an increased ratio of estrogen to androgen levels, and this ratio, when mimicked in a variety of animals, induces BPH and lower urinary tract dysfunction (LUTD). While the precise molecular etiology remains unclear, estrogens have been implicated in the development and maintenance of BPH. Numerous endogenous and exogenous estrogens exist in humans. These estrogens act via multiple estrogen receptors to promote or inhibit prostatic hyperplasia and other BPH-associated processes. The prostate is an estrogen target tissue, and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of estrogen action directly affecting prostate growth and differentiation in the context of BPH is an understudied area and remains to be elucidated. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation illustrating their potential roles in the development of BPH as therapy. More work will be required to identify estrogen signaling pathways associated with LUTD in order to develop more efficacious drugs for BPH treatment and prevention. PMID:26156791

  7. NMDA-receptor-dependent plasticity in the bed nucleus of the stria terminalis triggers long-term anxiolysis

    PubMed Central

    Glangetas, Christelle; Massi, Léma; Fois, Giulia R.; Jalabert, Marion; Girard, Delphine; Diana, Marco; Yonehara, Keisuke; Roska, Botond; Xu, Chun; Lüthi, Andreas; Caille, Stéphanie; Georges, François

    2017-01-01

    Anxiety is controlled by multiple neuronal circuits that share robust and reciprocal connections with the bed nucleus of the stria terminalis (BNST), a key structure controlling negative emotional states. However, it remains unknown how the BNST integrates diverse inputs to modulate anxiety. In this study, we evaluated the contribution of infralimbic cortex (ILCx) and ventral subiculum/CA1 (vSUB/CA1) inputs in regulating BNST activity at the single-cell level. Using trans-synaptic tracing from single-electroporated neurons and in vivo recordings, we show that vSUB/CA1 stimulation promotes opposite forms of in vivo plasticity at the single-cell level in the anteromedial part of the BNST (amBNST). We find that an NMDA-receptor-dependent homosynaptic long-term potentiation is instrumental for anxiolysis. These findings suggest that the vSUB/CA1-driven LTP in the amBNST is involved in eliciting an appropriate response to anxiogenic context and dysfunction of this compensatory mechanism may underlie pathologic anxiety states. PMID:28218243

  8. The role of environmental estrogens and autoimmunity.

    PubMed

    Chighizola, Cecilia; Meroni, Pier Luigi

    2012-05-01

    The prevalence of autoimmune diseases has significantly increased over the recent years. It has been proposed that this epidemiological evidence could be in part attributable to environmental estrogens, compounds that display estrogen-like activity and are ubiquitously present in the environment. Environmental estrogens can be found in a wide variety of foods: phytoestrogens occur in plants such as clover and soy, while mycoestrogens are food contaminants produced by fungi. Meat, eggs and dairy products from animals given exogenous hormones contain relatively high concentration of estrogens. Among xenoestrogens, industrial estrogens are synthetic chemicals produced for specific purposes (pesticides, plastics, surfactants and detergents) while metalloestrogens are found in heavy metals. Estrogens can be also administered through medications (contraceptive pill, hormone replacement therapy, genistein, cimetidine, creams). There is a considerable burden of evidence in vitro and in animal models that these compounds may exert immunotoxic effects. However, to date there is no convincing data that exposure to environmental estrogens can be regarded as a risk for human health. In particular, there is no consensus whether prolonged exposure to relatively low concentrations of different estrogenic chemicals can affect the human immune system and induce clinically evident diseases in real-life scenario. Moreover, the effects on human health of the synergistic interactions between natural, medical, dietary and environmental estrogens have not been fully elucidated yet. Here we provide an extensive review of the in vivo and in vitro effects of environmental estrogens on the immune system, focusing on the evidences of association between exposure and autoimmune disorders.

  9. Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-13-1-0400 TITLE: Targeting Epigenetics Therapy for Estrogen Receptor...2014 4. TITLE AND SUBTITLE Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers 5a. CONTRACT NUMBER 5b...estrogen- receptor positive breast cancer, estrogen receptor negative breast cancer, epigenetics , nuclear hormone receptor, estrogen Overall

  10. Targeted Radiotherapy of Estrogen Receptor Positive Tumors

    SciTech Connect

    Raghavan Rajagopalan

    2006-08-31

    The overall objectives of the proposal were to develop estrogen receptor (ER) binding small molecule radiopharmaceuticals for targeted radiotherapy of ER positive (ER+) tumors. In particular, this proposal focused on embedding a {sup 186,188}Re or a {sup 32}P radionuclide into an estrogen steroidal framework by isosteric substitution such that the resulting structure is topologically similar to the estrogen (estrogen mimic). The estrogen mimic molecules expected to bind to the ER and exhibit biodistribution akin to that of native estrogen due to structural mimicry. It is anticipated that the {sup 186,188}Re- or a {sup 32}P-containing estrogen mimics will be useful for targeted molecular radiotherapy of ER+ tumors. It is well established that the in vivo target tissue uptake of estrogen like steroidal molecules is related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG is important in the uptake of estrogens and testosterone in target tissues by SHBG receptors on the cell surface. However, hitherto the design of estrogen like small molecule radiopharmaceuticals was focused on optimizing ER binding characteristics without emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity in vitro, performed poorly in biodistribution studies. Based on molecular modeling studies the proposal focused on developing estrogen mimics 1-3 which were topologically similar to native estrogens, and form hydrogen bonds in ER and SHBG in the same manner as those of native estrogens. To this end the technical objectives of the proposal focused on synthesizing the rhenium-estrone and estradiol mimics 1 and 2 respectively, and phosphorous estradiol mimic 3 and to assess their stability and in vitro binding characteristics to ER and SHBG.

  11. ANALYSIS OF LAGOON SAMPLES FROM DIFFERENT CONCENTRATED ANIMAL FEEDING OPERATIONS FOR ESTROGENS AND ESTROGEN CONJUGATES

    EPA Science Inventory

    Although Concentrated Animal Feeding Operations CAFOs) have been identified as potentially important sources for the release of estrogens into the environment, information is lacking on the concentrations of estrogens in whole lagoon effluents (including suspended solids)which ar...

  12. [Transdermal estrogenic therapy in menopause].

    PubMed

    Nencioni, T; Polvani, F; Penotti, M; Porcaro, E; Barbieri Carones, M

    1989-01-01

    The availability of percutaneous estrogenic preparations capable of directly entering the bloodstream, avoiding the liver, has opened new prospects in the treatment of the climacteric syndrome. The purpose of our work has been to compare the effectiveness and tolerability of a percutaneous 17-beta-estradiol-oral progestin association with an all oral association of conjugated estrogens and progestins and to evaluate the ability to control menopausal symptoms and biohumoral characteristics. 42 (1 to 7 years postmenopausal) heavily symptomatic patients were selected at the "Centro per lo studio e la terapia del climaterio" in Milan and divided in two equally sized groups. One group was treated using the percutaneous therapy, the other with the all-oral one. The results show that percutaneous administration leads to a quicker control of vasomotor symptomatology and metabolic effects similar to oral administration.

  13. The Estrogen Hypothesis of Obesity

    PubMed Central

    Grantham, James P.; Henneberg, Maciej

    2014-01-01

    The explanation of obesity as a simple result of positive energy balance fails to account for the scope of variable responses to diets and lifestyles. It is postulated that individual physiological and anatomical variation may be responsible for developing obesity. Girls in poor families develop greater adiposity than their male siblings, a trend not present in richer environments. This indicates strong influence of estrogen on fat accumulation irrespective of poor socioeconomic conditions. Obesity rates in males and females of developed nations are similar, while in poorer nations obesity is much more prevalent in females. Female to male ratio of obesity correlates inversely with gross domestic product. Therefore, the parity of male and female obesity in developed countries may result from male exposure to environmental estrogen-like substances associated with affluence. These hormonally driven mechanisms may be equally active within both sexes in more developed areas, thereby increasing overall obesity. PMID:24915457

  14. Estrogen turns down "the AIRE".

    PubMed

    Bakhru, Pearl; Su, Maureen A

    2016-04-01

    Genetic alterations are known drivers of autoimmune disease; however, there is a much higher incidence of autoimmunity in women, implicating sex-specific factors in disease development. The autoimmune regulator (AIRE) gene contributes to the maintenance of central tolerance, and complete loss of AIRE function results in the development of autoimmune polyendocrinopathy syndrome type 1. In this issue of the JCI, Dragin and colleagues demonstrate that AIRE expression is downregulated in females as the result of estrogen-mediated alterations at the AIRE promoter. The association between estrogen and reduction of AIRE may at least partially account for the elevated incidence of autoimmune disease in women and has potential implications for sex hormone therapy.

  15. Distinct Effects of Estrogen on Mouse Maternal Behavior: The Contribution of Estrogen Synthesis in the Brain

    PubMed Central

    Murakami, Gen

    2016-01-01

    Estrogen surge following progesterone withdrawal at parturition plays an important role in initiating maternal behavior in various rodent species. Systemic estrogen treatment shortens the latency to onset of maternal behavior in nulliparous female rats that have not experienced parturition. In contrast, nulliparous laboratory mice show rapid onset of maternal behavior without estrogen treatment, and the role of estrogen still remains unclear. Here the effect of systemic estrogen treatment (for 2 h, 1 day, 3 days, and 7 days) after progesterone withdrawal was examined on maternal behavior of C57BL/6 mice. This estrogen regimen led to different effects on nursing, pup retrieval, and nest building behaviors. Latency to nursing was shortened by estrogen treatment within 2 h. Moreover, pup retrieval and nest building were decreased. mRNA expression was also investigated for estrogen receptor α (ERα) and for genes involved in regulating maternal behavior, specifically, the oxytocin receptor (OTR) and vasopressin receptor in the medial amygdala (MeA) and medial preoptic area (MPOA). Estrogen treatment led to decreased ERα mRNA in both regions. Although OTR mRNA was increased in the MeA, OTR and vasopressin receptor mRNA were reduced in the MPOA, showing region-dependent transcription regulation. To determine the mechanisms for the actions of estrogen treatment, the contribution of estrogen synthesis in the brain was examined. Blockade of estrogen synthesis in the brain by systemic letrozole treatment in ovariectomized mice interfered with pup retrieval and nest building but not nursing behavior, indicating different contributions of estrogen synthesis to maternal behavior. Furthermore, letrozole treatment led to an increase in ERα mRNA in the MeA but not in the MPOA, suggesting that involvement of estrogen synthesis is brain region dependent. Altogether, these results suggest that region-dependent estrogen synthesis leads to differential transcriptional activation due

  16. Distinct Effects of Estrogen on Mouse Maternal Behavior: The Contribution of Estrogen Synthesis in the Brain.

    PubMed

    Murakami, Gen

    2016-01-01

    Estrogen surge following progesterone withdrawal at parturition plays an important role in initiating maternal behavior in various rodent species. Systemic estrogen treatment shortens the latency to onset of maternal behavior in nulliparous female rats that have not experienced parturition. In contrast, nulliparous laboratory mice show rapid onset of maternal behavior without estrogen treatment, and the role of estrogen still remains unclear. Here the effect of systemic estrogen treatment (for 2 h, 1 day, 3 days, and 7 days) after progesterone withdrawal was examined on maternal behavior of C57BL/6 mice. This estrogen regimen led to different effects on nursing, pup retrieval, and nest building behaviors. Latency to nursing was shortened by estrogen treatment within 2 h. Moreover, pup retrieval and nest building were decreased. mRNA expression was also investigated for estrogen receptor α (ERα) and for genes involved in regulating maternal behavior, specifically, the oxytocin receptor (OTR) and vasopressin receptor in the medial amygdala (MeA) and medial preoptic area (MPOA). Estrogen treatment led to decreased ERα mRNA in both regions. Although OTR mRNA was increased in the MeA, OTR and vasopressin receptor mRNA were reduced in the MPOA, showing region-dependent transcription regulation. To determine the mechanisms for the actions of estrogen treatment, the contribution of estrogen synthesis in the brain was examined. Blockade of estrogen synthesis in the brain by systemic letrozole treatment in ovariectomized mice interfered with pup retrieval and nest building but not nursing behavior, indicating different contributions of estrogen synthesis to maternal behavior. Furthermore, letrozole treatment led to an increase in ERα mRNA in the MeA but not in the MPOA, suggesting that involvement of estrogen synthesis is brain region dependent. Altogether, these results suggest that region-dependent estrogen synthesis leads to differential transcriptional activation due

  17. Opioid Receptor-Dependent Sex Differences in Synaptic Plasticity in the Hippocampal Mossy Fiber Pathway of the Adult Rat

    PubMed Central

    Harte-Hargrove, Lauren C.; Varga-Wesson, Ada; Duffy, Aine M.; Milner, Teresa A.

    2015-01-01

    The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus. PMID:25632146

  18. Hydrocarbon Spectral Database

    National Institute of Standards and Technology Data Gateway

    SRD 115 Hydrocarbon Spectral Database (Web, free access)   All of the rotational spectral lines observed and reported in the open literature for 91 hydrocarbon molecules have been tabulated. The isotopic molecular species, assigned quantum numbers, observed frequency, estimated measurement uncertainty and reference are given for each transition reported.

  19. Oxygenated Derivatives of Hydrocarbons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    For the book entitled “Insect Hydrocarbons: Biology, Biochemistry and Chemical Ecology”, this chapter presents a comprehensive review of the occurrence, structure and function of oxygenated derivatives of hydrocarbons. The book chapter focuses on the occurrence, structural identification and functi...

  20. Recovering hydrocarbons from hydrocarbon-containing vapors

    DOEpatents

    Mirza, Zia I.; Knell, Everett W.; Winter, Bruce L.

    1980-09-30

    Values are recovered from a hydrocarbon-containing vapor by contacting the vapor with quench liquid consisting essentially of hydrocarbons to form a condensate and a vapor residue, the condensate and quench fluid forming a combined liquid stream. The combined liquid stream is mixed with a viscosity-lowering liquid to form a mixed liquid having a viscosity lower than the viscosity of the combined liquid stream to permit easy handling of the combined liquid stream. The quench liquid is a cooled portion of the mixed liquid. Viscosity-lowering liquid is separated from a portion of the mixed liquid and cycled to form additional mixed liquid.

  1. Unbalanced Estrogen Metabolism in Ovarian Cancer

    PubMed Central

    Zahid, Muhammad; Beseler, Cheryl L.; Hall, James B.; LeVan, Tricia; Cavalieri, Ercole L.; Rogan, Eleanor G.

    2013-01-01

    Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples by using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p<0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer. PMID:24170413

  2. Estrogens and Cognition: Friends or Foes?

    PubMed Central

    Korol, Donna L.; Pisani, Samantha L.

    2015-01-01

    Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings that show the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. PMID:26149525

  3. SETD6 controls the expression of estrogen-responsive genes and proliferation of breast carcinoma cells

    PubMed Central

    O'Neill, Daniel J; Williamson, Stuart Charles; Alkharaif, Dhuha; Monteiro, Isabella Christina Mazzaro; Goudreault, Marilyn; Gaughan, Luke; Robson, Craig N; Gingras, Anne-Claude; Binda, Olivier

    2014-01-01

    The lysine methyltransferase SETD6 modifies the histone variant H2AZ, a key component of nuclear receptor-dependent transcription. Herein, we report the identification of several factors that associate with SETD6 and are implicated in nuclear hormone receptor signaling. Specifically, SETD6 associates with the estrogen receptor α (ERα), histone deacetylase HDAC1, metastasis protein MTA2, and the transcriptional co-activator TRRAP. Luciferase reporter assays identify SETD6 as a transcriptional repressor, in agreement with its association with HDAC1 and MTA2. However, SETD6 behaves as a co-activator of several estrogen-responsive genes, such as PGR and TFF1. Consistent with these results, silencing of SETD6 in several breast carcinoma cell lines induced cellular proliferation defects accompanied by enhanced expression of the cell cycle inhibitor CDKN1A and induction of apoptosis. Herein, we have identified several chromatin proteins that associate with SETD6 and described SETD6 as an essential factor for nuclear receptor signaling and cellular proliferation. PMID:24751716

  4. Plant hydrocarbon recovery process

    SciTech Connect

    Dzadzic, P.M.; Price, M.C.; Shih, C.J.; Weil, T.A.

    1982-01-26

    A process for production and recovery of hydrocarbons from hydrocarbon-containing whole plants in a form suitable for use as chemical feedstocks or as hydrocarbon energy sources which process comprises: (A) pulverizing by grinding or chopping hydrocarbon-containing whole plants selected from the group consisting of euphorbiaceae, apocynaceae, asclepiadaceae, compositae, cactaceae and pinaceae families to a suitable particle size, (B) drying and preheating said particles in a reducing atmosphere under positive pressure (C) passing said particles through a thermal conversion zone containing a reducing atmosphere and with a residence time of 1 second to about 30 minutes at a temperature within the range of from about 200* C. To about 1000* C., (D) separately recovering the condensable vapors as liquids and the noncondensable gases in a condition suitable for use as chemical feedstocks or as hydrocarbon fuels.

  5. Subsea hydrocarbon sensor system

    SciTech Connect

    Marosko, R.J.; Warren, W.B.

    1981-08-04

    A hydrocarbon detection system is provided for use in a subsea hydrocarbon production installation which includes production tree assemblies, an electro-hydraulic control module located on the sea floor and remote from the production trees, cable assemblies interconnecting the control module with the production trees through magnetic coupling devices. A pair of inductive elements are electrically coupled by the surrounding sea water. Displacement of the conductive sea water by escaping hydrocarbons affects the coupling between the inductive elements to produce a hydrocarbon-presence-responsive output signal. The inductive elements are resonated within a selected frequency range by capacitors coupled with a primary inductor coil by auxiliary windings on a common core element. An excitation signal sweeps over the selected frequency range at a rate effective to produce a peak detected signal at the resonant frequency. The peak output signal is then monitored to form a control signal functionally related to the presence or absence of hydrocarbons in the sea water.

  6. Endocrine disrupting chemicals targeting estrogen receptor signaling: Identification and mechanisms of action

    PubMed Central

    Shanle, Erin K.; Xu, Wei

    2011-01-01

    Many endocrine disrupting chemicals (EDCs) adversely impact estrogen signaling by interacting with two estrogen receptors (ERs): ERα and ERβ. Though the receptors have similar ligand binding and DNA binding domains, ERα and ERβ have some unique properties in terms of ligand selectivity and target gene regulation. EDCs that target ER signaling can modify genomic and non-genomic ER activity through direct interactions with ERs, indirectly through transcription factors like the aryl hydrocarbon receptor (AhR), or through modulation of metabolic enzymes that are critical for normal estrogen synthesis and metabolism. Many EDCs act through multiple mechanisms as exemplified by chemicals that bind both AhR and ER, such as 3-methylcholanthrene. Other EDCs that target ER signaling include phytoestrogens, bisphenolics, and organochlorine pesticides and many alter normal ER signaling through multiple mechanisms. EDCs can also display tissue-selective ER agonist and antagonist activities similar to selective estrogen receptor modulators (SERMs) designed for pharmaceutical use. Thus, biological effects of EDCs need to be carefully interpreted because EDCs can act through complex tissue-selective modulation of ERs and other signaling pathways in vivo. Current requirements by the U.S. Environmental Protection Agency require some in vitro and cell-based assays to identify EDCs that target ER signaling through direct and metabolic mechanisms. Additional assays may be useful screens for identifying EDCs that act through alternative mechanisms prior to further in vivo study. PMID:21053929

  7. Parabens inhibit human skin estrogen sulfotransferase activity: possible link to paraben estrogenic effects.

    PubMed

    Prusakiewicz, Jeffery J; Harville, Heather M; Zhang, Yanhua; Ackermann, Chrisita; Voorman, Richard L

    2007-04-11

    Parabens (p-hydroxybenzoate esters) are a group of widely used preservatives in topically applied cosmetic and pharmaceutical products. Parabens display weak associations with the estrogen receptors in vitro or in cell based models, but do exhibit estrogenic effects in animal models. It is our hypothesis that parabens exert their estrogenic effects, in part, by elevating levels of estrogens through inhibition of estrogen sulfotransferases (SULTs) in skin. We report here the results of a structure-activity-relationship of parabens as inhibitors of estrogen sulfation in human skin cytosolic fractions and normal human epidermal keratinocytes. Similar to reports of paraben estrogenicity and estrogen receptor affinity, the potency of SULT inhibition increased as the paraben ester chain length increased. Butylparaben was found to be the most potent of the parabens in skin cytosol, yielding an IC(50) value of 37+/-5 microM. Butylparaben blocked the skin cytosol sulfation of estradiol and estrone, but not the androgen dehydroepiandrosterone. The parabens were also tested as inhibitors of SULT activity in a cellular system, with normal human epidermal keratinocytes. The potency of butylparaben increased three-fold in these cells relative to the IC(50) value from skin cytosol. Overall, these results suggest chronic topical application of parabens may lead to prolonged estrogenic effects in skin as a result of inhibition of estrogen sulfotransferase activity. Accordingly, the skin anti-aging benefits of many topical cosmetics and pharmaceuticals could be derived, in part, from the estrogenicity of parabens.

  8. Estrogen Promotes Luteolysis by Redistributing Prostaglandin F2α Receptors Within Primate Luteal Cells*

    PubMed Central

    Kim, Soon Ok; Markosyan, Nune; Pepe, Gerald J.; Duffy, Diane M.

    2015-01-01

    Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFR) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized to the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production by luteal cells obtained at mid-late and late luteal phases but did not decrease progesterone production by granulosa or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates. PMID:25687410

  9. Plasma Processing Of Hydrocarbon

    SciTech Connect

    Grandy, Jon D; Peter C. Kong; Brent A. Detering; Larry D. Zuck

    2007-05-01

    The Idaho National Laboratory (INL) developed several patented plasma technologies for hydrocarbon processing. The INL patents include nonthermal and thermal plasma technologies for direct natural gas to liquid conversion, upgrading low value heavy oil to synthetic light crude, and to convert refinery bottom heavy streams directly to transportation fuel products. Proof of concepts has been demonstrated with bench scale plasma processes and systems to convert heavy and light hydrocarbons to higher market value products. This paper provides an overview of three selected INL patented plasma technologies for hydrocarbon conversion or upgrade.

  10. Estrogen potency of oral contraceptive pills.

    PubMed

    Chihal, H J; Peppler, R D; Dickey, R P

    1975-01-01

    The estrogen potencies of 9 oral contraceptive pills, Enovid-E, Enovid-5, Ovulen, Demulen, Norinyl+80, Norinyl+50, Ovral, Norlestrin 1 mg. and Norlestrin 2.5 mg., were determined by bioassay. Relative estrogen potency was determined by analysis of variance. Enovid-5, the most estrogenic compound, had a potency of 4.88 compared to ethinyl estradiol, 50 mcg. equal 1.00; Ovral, the least estrogenic compound, had a potency of 0.81, a sixfold difference. Estrogen potencies at a fractional dose of 0.00155 correlate with reports of the incidence of minor side effects and thromboembolic disease. The effect of progestins on estrogen potency was purely additive (norgestrel and norethynodrel), purely antagonistic, or additive at low concentrations and antagonistic at high concentrations (norethindrone, norethindrone acetate, and ethynodiol diacetate). These results suggest that pills with a greater margin of safety might be developed by utilizing greater ratios of progestin to estrogen. In addition, differences in relative estrogen potency of oral contraceptive pills may be used as a basis for better clinical selection.

  11. Quantum chemical studies of estrogenic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Quantum chemical methods are potent tools to provide information on the chemical structure and electronic properties of organic molecules. Modern computational chemistry methods have provided a great deal of insight into the binding of estrogenic compounds to estrogenic receptors (ER), an important ...

  12. EADB: An Estrogenic Activity Database for Assessing ...

    EPA Pesticide Factsheets

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/ BioinformaticsTools/EstrogenicActivityDatabaseEADB/default. htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of

  13. Androgen, Estrogen and the Bone Marrow Microenvironment

    DTIC Science & Technology

    2009-12-01

    SUPPLEMENTARY NOTES 14. ABSTRACT We have accomplished the following: 1) Characterized androgen responsive genes in mouse bone marrow (BM) via...castration (androgen ablation) and estrogen stimulation. 2) Measurements of testosterone, dihydrotestosterone and of genes that regulate the local... gene expression in the bone marrow. In males, the main source of estrogen is through conversion of androgen by aromatase. We postulate that gene

  14. Estrogenic activity of naturally occurring anthocyanidins.

    PubMed

    Schmitt, E; Stopper, H

    2001-01-01

    Anthocyanins, which are natural plant pigments from the flavonoid family, represent substantial constituents of the human diet. Because some other bioflavonoids are known to have estrogenic activity, the aim of this study was to determine the estrogenic activity of the anthocyanine aglycones. Binding affinity to the estrogen receptor-alpha was 10,000- to 20,000-fold lower than that of the endogenous estrogen estradiol. In the estrogen receptor-positive cell line MCF-7, the anthocyanidins induced expression of a reporter gene. The tested anthocyanidins showed estrogen-inducible cell proliferation in two cell lines (MCF-7 and BG-1), but not in the receptor-negative human breast cancer cell line MDA-MB-231. The phytoestrogen-induced cell proliferation could be blocked by addition of the receptor antagonist 4-hydroxytamoxifen. Combination treatments with the endogenous estrogen estradiol resulted in a reduction of estradiol-induced cell proliferation. Overall, the tested anthocyanidins exert estrogenic activity, which might play a role in altering the development of hormone-dependent adverse effects.

  15. [Estrogen receptors and the mammary gland].

    PubMed

    Barrón, A; Bermejo, L; Castro, I

    1997-01-01

    For several decades it has been known that steroid hormones, estrogen and progesterone, regulate some genes involved in the growth, proliferation and differentiation of the mammary-gland in animals and humans. In the last years, the presence or absence of the nuclear estrogen receptor has been used by clinicians as a marker for tumor malignancy, as a prognostic index or as an important parameter for hormonal therapy with anti-estrogenic compounds of some hormone-dependent breast cancers. This review shows some advances in the knowledge of the structure, function, molecular mechanisms of estrogenic activity, and interaction with proteins like protooncogenes and growth factors. Also, we refer to the role of the estrogen receptor in the physiophatology of breast cancer.

  16. Process for preparing hydrocarbons

    SciTech Connect

    Breuker, J.H.; De H.H.; Kwant, P.B.

    1980-01-15

    A process for preparing light distillate fractions and medicinal oil from heavy hydrocarbon oils comprises two-stage hydrocracking, fractionation distillation and catalytic hydrotreatment of at least part of the fractionation residue.

  17. Membrane separation of hydrocarbons

    DOEpatents

    Funk, Edward W.; Kulkarni, Sudhir S.; Chang, Y. Alice

    1986-01-01

    Mixtures of heavy oils and light hydrocarbons may be separated by passing the mixture over a polymeric membrane which comprises a polymer capable of maintaining its integrity in the presence of hydrocarbon compounds at temperature ranging from about ambient to about 100.degree. C. and pressures ranging from about 50 to about 1000 psi. The membranes which possess pore sizes ranging from about 10 to about 500 Angstroms are cast from a solvent solution and recovered.

  18. Vascular Effects of Estrogenic Menopausal Hormone Therapy

    PubMed Central

    Reslan, Ossama M.; Khalil, Raouf A.

    2011-01-01

    Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post-MW) than premenopausal women (Pre-MW). Despite recent advances in preventive measures, the incidence of CVD in women has shown a rise that matched the increase in the Post-MW population. The increased incidence of CVD in Post-MW has been related to the decline in estrogen levels, and hence suggested vascular benefits of endogenous estrogen. Experimental studies have identified estrogen receptor ERα, ERβ and a novel estrogen binding membrane protein GPR30 (GPER) in blood vessels of humans and experimental animals. The interaction of estrogen with vascular ERs mediates both genomic and non-genomic effects. Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide, prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton, extracellular matrix, lipid profile and the vascular inflammatory response have been reported. In addition to the experimental evidence in animal models and vascular cells, initial observational studies in women using menopausal hormonal therapy (MHT) have suggested that estrogen may protect against CVD. However, randomized clinical trials (RCTs) such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), which examined the effects of conjugated equine estrogens (CEE) in older women with established CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular effects of estrogen treatment. Despite the initial set-back from the results of MHT RCTs, growing evidence now supports the ‘timing hypothesis’, which suggests that MHT could increase the risk of CVD if started late after menopause, but may produce beneficial cardiovascular effects in younger women during the perimenopausal period. The choice of

  19. Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

    PubMed

    Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

    2013-06-21

    We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

  20. Criteria for successful estrogen therapy in osteoporosis.

    PubMed

    Lindsay, R

    1993-01-01

    Estrogens are well established as agents that stabilize the skeleton and reduce the risk of osteoporotic fractures among postmenopausal women. For maximum benefit, preventive therapy should begin as early as possible after ovarian failure begins to occur. Efforts to prevent bone loss are likely to achieve the best results when initiated prior to significant loss of bone tissue and trabecular penetration. An effect on skeletal bone mass can be obtained by any route of administration and transdermal estrogen use is an alternative to oral estrogen. Long-term therapy may reduce the risk of hip fracture by 50% and of vertebral fracture by a greater amount. The minimum effective dose is probably that which achieves circulating estrogen levels in the mid-follicular range. For women with a uterus in place, a progestin usually is provided to protect the endometrium; it is given cyclically in younger women but may be given continuously in women several years past menopause. Progestins do not interfere with the effects of estrogen on the skeleton, and it is possible that some progestins enhance the skeletal effects of estrogen. For patients with osteoporosis, estrogens can be used as first-line therapy since in these patients they have the same skeletal stabilizing effect and reduce the risk of recurrent fracture.

  1. Estrogen

    MedlinePlus

    ... vaginal dryness, itching, or burning, or to prevent osteoporosis (a condition in which the bones become thin ... to treat vaginal dryness or only to prevent osteoporosis should consider a different treatment. Some brands of ...

  2. Vaginal Estrogen for Genitourinary Syndrome of Menopause

    PubMed Central

    Rahn, David D.; Carberry, Cassandra; Sanses, Tatiana V.; Mamik, Mamta M.; Ward, Renée M.; Meriwether, Kate V.; Olivera, Cedric K.; Abed, Husam; Balk, Ethan M.; Murphy, Miles

    2016-01-01

    OBJECTIVE To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. DATA SOURCES MEDLINE and Cochrane databases were searched from inception to April 2013. We included randomized controlled trials and prospective comparative studies. Interventions and comparators included all commercially available vaginal estrogen products. Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators. METHODS OF STUDY SELECTION We double-screened 1,805 abstracts, identifying 44 eligible studies. Discrepancies were adjudicated by a third reviewer. Studies were individually and collectively assessed for methodologic quality and strength of evidence. TABULATION, INTEGRATION, AND RESULTS Studies were extracted for participant, intervention, comparator, and outcomes data, including patient-reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen. Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar

  3. Associations of the Fecal Microbiome With Urinary Estrogens and Estrogen Metabolites in Postmenopausal Women

    PubMed Central

    Fuhrman, Barbara J.; Feigelson, Heather Spencer; Flores, Roberto; Gail, Mitchell H.; Xu, Xia; Ravel, Jacques

    2014-01-01

    Context: The gut microbiota may influence the risk of breast cancer through effects on endogenous estrogens. Objective: The objective of the study was to investigate whether urinary estrogens and estrogen metabolites are associated with the diversity and composition of the fecal microbiome. Design and Setting: This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado. Participants: A total of 60 women drawn from a random sample of healthy postmenopausal women (aged 55–69 y), without current or recent use of antibiotics or hormone therapy and no history of cancer or gastrointestinal disease participated in the study. Outcome Measures and Methods: Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal microbiome with parent estrogen (estrone + estradiol), total estrogens, and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer risk in previous studies. Results: The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P = .01). Relative abundances of the order Clostridiales (R = 0.32, P = .02) and the genus Bacteroides (R = −0.30, P = .03) were also correlated with the ratio of metabolites to parents. Associations were independent of age, body mass index, and study design factors. Conclusions: Our data suggest that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen. Further research is warranted to confirm and relate these findings to clinical disease. PMID:25211668

  4. Raloxifene. Not better than estrogen.

    PubMed Central

    2000-01-01

    Raloxifene is marketed in France for prevention of nontraumatic vertebral fracture in postmenopausal women. In animal pharmacology studies, it was found to both agonize and antagonize estrogen. The assessment file is methodologically sound but fails to answer many practical questions. A placebo-controlled trial showed that raloxifene reduced the risk of vertebral collapse after 2 years of treatment, in both primary and secondary prevention, but demonstrated no effect on nonvertebral fractures. In this trial, raloxifene also reduced the risk of breast cancer. Two trials versus combined hormone replacement therapy (HRT) showed HRT had a more favourable effect on surrogate end points reflecting the risk of fracture and cardiovascular risk (changes in bone mineral density and lipid profile). Compared with combined HRT, raloxifene reduced the incidence of menorrhagia and mastodynia, but did not relieve symptoms linked to menopause. Results of animal studies call for close clinical monitoring to detect a possible increase in the incidence of ovarian cancer. PMID:10955178

  5. In Vivo Imaging of Activated Estrogen Receptors in Utero by Estrogens and Bisphenol A

    PubMed Central

    Lemmen, Josephine G.; Arends, Roel J.; van der Saag, Paul T.; van der Burg, Bart

    2004-01-01

    Environmental estrogens are of particular concern when exposure occurs during embryonic development. Although there are good models to study estrogenic activity of chemicals in adult animals, developmental exposure is much more difficult to test. The weak estrogenic activity of the environmental estrogen bisphenol A (BPA) in embryos is controversial. We have recently generated transgenic mice that carry a reporter construct with estrogen-responsive elements coupled to luciferase. We show that, using this in vivo model in combination with the IVIS imaging system, activation of estrogen receptors (ERs) by maternally applied BPA and other estrogens can be detected in living embryos in utero. Eight hours after exposure to 1 mg/kg BPA, ER transactivation could be significantly induced in the embryos. This was more potent than would be estimated from in vitro assays, although its intrinsic activity is still lower than that of diethylstilbestrol and 17β-estradiol dipropionate. On the basis of these results, we conclude that the estrogenic potency of BPA estimated using in vitro assays might underestimate its estrogenic potential in embryos. PMID:15531440

  6. In vivo imaging of activated estrogen receptors in utero by estrogens and bisphenol A.

    PubMed

    Lemmen, Josephine G; Arends, Roel J; van der Saag, Paul T; van der Burg, Bart

    2004-11-01

    Environmental estrogens are of particular concern when exposure occurs during embryonic development. Although there are good models to study estrogenic activity of chemicals in adult animals, developmental exposure is much more difficult to test. The weak estrogenic activity of the environmental estrogen bisphenol A (BPA) in embryos is controversial. We have recently generated transgenic mice that carry a reporter construct with estrogen-responsive elements coupled to luciferase. We show that, using this in vivo model in combination with the IVIS imaging system, activation of estrogen receptors (ERs) by maternally applied BPA and other estrogens can be detected in living embryos in utero. Eight hours after exposure to 1 mg/kg BPA, ER transactivation could be significantly induced in the embryos. This was more potent than would be estimated from in vitro assays, although its intrinsic activity is still lower than that of diethylstilbestrol and 17beta-estradiol dipropionate. On the basis of these results, we conclude that the estrogenic potency of BPA estimated using in vitro assays might underestimate its estrogenic potential in embryos.

  7. Comparison of estrogens and estrogen metabolites in human breast tissue and urine

    PubMed Central

    2010-01-01

    Background An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens. Methods This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method. Results The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16-hydroxylation pathway levels in breast tissue in comparison to women carrying the wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary metabolites. Conclusions The urinary 2/16 ratio seems a good approximation of the ratio observed in breast tissue. Metabolic genes may have an important role in the estrogen metabolism locally in tissues where the gene is expressed, a role that is not readily observable when urinary measurements are performed. PMID:20678202

  8. Concentration of endogenous estrogens and estrogen metabolites in the NCI-60 human tumor cell lines

    PubMed Central

    2012-01-01

    Background Endogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence also supports their involvement in the development of certain lung, colon and prostate cancers. Methods In this study we systemically surveyed endogenous estrogen and estrogen metabolite levels in each of the NCI-60 human tumor cell lines, which include human breast, central nerve system, colon, ovarian, prostate, kidney and non-small cell lung cancers, as well as melanomas and leukemia. The absolute abundances of these metabolites were measured using a liquid chromatography-tandem mass spectrometry method that has been previously utilized for biological fluids such as serum and urine. Results Endogenous estrogens and estrogen metabolites were found in all NCI-60 human tumor cell lines and some were substantially elevated and exceeded the levels found in well known estrogen-dependent and estrogen receptor-positive tumor cells such as MCF-7 and T-47D. While estrogens were expected to be present at high levels in cell lines representing the female reproductive system (that is, breast and ovarian), other cell lines, such as leukemia and colon, also contained very high levels of these steroid hormones. The leukemia cell line RMPI-8226 contained the highest levels of estrone (182.06 pg/106 cells) and 17β-estradiol (753.45 pg/106 cells). In comparison, the ovarian cancer cell line with the highest levels of these estrogens contained only 19.79 and 139.32 pg/106 cells of estrone and 17β-estradiol, respectively. The highest levels of estrone and 17β-estradiol in breast cancer cell lines were only 8.45 and 87.37 pg/106 cells in BT-549 and T-47D cells, respectively. Conclusions The data provided evidence for the presence of significant amounts of endogenous estrogens and estrogen metabolites in cell lines not commonly associated with these steroid hormones. This broad discovery of

  9. Breast Cancer and Estrogen-Alone Update

    MedlinePlus

    ... Current Issue Past Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 ... hormone therapy does not increase the risk of breast cancer in postmenopausal women, according to an updated analysis ...

  10. Superconductivity in aromatic hydrocarbons

    NASA Astrophysics Data System (ADS)

    Kubozono, Yoshihiro; Goto, Hidenori; Jabuchi, Taihei; Yokoya, Takayoshi; Kambe, Takashi; Sakai, Yusuke; Izumi, Masanari; Zheng, Lu; Hamao, Shino; Nguyen, Huyen L. T.; Sakata, Masafumi; Kagayama, Tomoko; Shimizu, Katsuya

    2015-07-01

    'Aromatic hydrocarbon' implies an organic molecule that satisfies the (4n + 2) π-electron rule and consists of benzene rings. Doping solid aromatic hydrocarbons with metals provides the superconductivity. The first discovery of such superconductivity was made for K-doped picene (Kxpicene, five benzene rings). Its superconducting transition temperatures (Tc's) were 7 and 18 K. Recently, we found a new superconducting Kxpicene phase with a Tc as high as 14 K, so we now know that Kxpicene possesses multiple superconducting phases. Besides Kxpicene, we discovered new superconductors such as Rbxpicene and Caxpicene. A most serious problem is that the shielding fraction is ⩽15% for Kxpicene and Rbxpicene, and it is often ∼1% for other superconductors. Such low shielding fractions have made it difficult to determine the crystal structures of superconducting phases. Nevertheless, many research groups have expended a great deal of effort to make high quality hydrocarbon superconductors in the five years since the discovery of hydrocarbon superconductivity. At the present stage, superconductivity is observed in certain metal-doped aromatic hydrocarbons (picene, phenanthrene and dibenzopentacene), but the shielding fraction remains stubbornly low. The highest priority research area is to prepare aromatic superconductors with a high superconducting volume-fraction. Despite these difficulties, aromatic superconductivity is still a core research target and presents interesting and potentially breakthrough challenges, such as the positive pressure dependence of Tc that is clearly observed in some phases of aromatic hydrocarbon superconductors, suggesting behavior not explained by the standard BCS picture of superconductivity. In this article, we describe the present status of this research field, and discuss its future prospects.

  11. Pyrolysis of wastewater biosolids significantly reduces estrogenicity.

    PubMed

    Hoffman, T C; Zitomer, D H; McNamara, P J

    2016-11-05

    Most wastewater treatment processes are not specifically designed to remove micropollutants. Many micropollutants are hydrophobic so they remain in the biosolids and are discharged to the environment through land-application of biosolids. Micropollutants encompass a broad range of organic chemicals, including estrogenic compounds (natural and synthetic) that reside in the environment, a.k.a. environmental estrogens. Public concern over land application of biosolids stemming from the occurrence of micropollutants hampers the value of biosolids which are important to wastewater treatment plants as a valuable by-product. This research evaluated pyrolysis, the partial decomposition of organic material in an oxygen-deprived system under high temperatures, as a biosolids treatment process that could remove estrogenic compounds from solids while producing a less hormonally active biochar for soil amendment. The estrogenicity, measured in estradiol equivalents (EEQ) by the yeast estrogen screen (YES) assay, of pyrolyzed biosolids was compared to primary and anaerobically digested biosolids. The estrogenic responses from primary solids and anaerobically digested solids were not statistically significantly different, but pyrolysis of anaerobically digested solids resulted in a significant reduction in EEQ; increasing pyrolysis temperature from 100°C to 500°C increased the removal of EEQ with greater than 95% removal occurring at or above 400°C. This research demonstrates that biosolids treatment with pyrolysis would substantially decrease (removal>95%) the estrogens associated with this biosolids product. Thus, pyrolysis of biosolids can be used to produce a valuable soil amendment product, biochar, that minimizes discharge of estrogens to the environment.

  12. Function of Estrogen Receptor Tryosine Phosphorylation

    DTIC Science & Technology

    1998-07-01

    6219 TITLE: Function of Estrogen Receptor Tryosine Phosphorylation PRINCIPAL INVESTIGATOR: Matthew R. Yudt CONTRACTING ORGANIZATION: University of...Estrogen Receptor Tryosine Phosphorylation ~DAMD17-96-1-6219 6. AUTHOR(S) Matthew R. Yudt 7. PERFORMING ORGANIZATION NAME11S) AND AODRESS(ES...this model, tyrosine 537 (Y537) phosphorylation of one monomer interacts with another tyrosine phosphorylated monomer to constitute an hER dimer

  13. Estrogenic activity in Finnish municipal wastewater effluents.

    PubMed

    Välitalo, Pia; Perkola, Noora; Seiler, Thomas-Benjamin; Sillanpää, Markus; Kuckelkorn, Jochen; Mikola, Anna; Hollert, Henner; Schultz, Eija

    2016-01-01

    Effluents from wastewater treatment plants (WWTPs) are a major source of estrogenic compounds to the aquatic environment. In the present work, estrogenic activities of effluents from eight municipal WWTPs in Finland were studied. The main objectives of the study were to quantify the concentrations of selected estrogenic compounds, to evaluate their contribution to estrogenic potency and to test the feasibility of the commercial bioassays for wastewater analysis. The effluent samples were analyzed by two in vitro tests, i.e. ERα-CALUX(®) and ELISA-E2, and by liquid chromatography mass spectrometry for six estrogenic compounds: estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), 17α-estradiol and bisphenol A (BPA). Estrogenic effects were found in all of the effluent samples with both of the bioassays. The concentrations measured with ELISA-E2 (8.6-61.6 ng/L) were clearly higher but exhibited a similar pattern than those with chemical analysis (E2 estrogenic potency was possible only for E1 and BPA, which contributed less than 10% to the observed effects, except in one sample with a high BPA contribution (17%). The contribution of E2 was significant in two samples where it was detected (28% and 67%). The results demonstrated that more comprehensive information on potential estrogenic activity of wastewater effluents can be achieved by using in vitro biotests in addition to chemical analysis and their use would be beneficial in monitoring and screening purposes.

  14. Quantitative Hydrocarbon Surface Analysis

    NASA Technical Reports Server (NTRS)

    Douglas, Vonnie M.

    2000-01-01

    The elimination of ozone depleting substances, such as carbon tetrachloride, has resulted in the use of new analytical techniques for cleanliness verification and contamination sampling. The last remaining application at Rocketdyne which required a replacement technique was the quantitative analysis of hydrocarbons by infrared spectrometry. This application, which previously utilized carbon tetrachloride, was successfully modified using the SOC-400, a compact portable FTIR manufactured by Surface Optics Corporation. This instrument can quantitatively measure and identify hydrocarbons from solvent flush of hardware as well as directly analyze the surface of metallic components without the use of ozone depleting chemicals. Several sampling accessories are utilized to perform analysis for various applications.

  15. Hydrocarbon fuel detergent

    SciTech Connect

    Meyer, G.R.; Lyons, W.R.

    1990-01-23

    This patent describes a hydrocarbon fuel composition comprising: a hydrocarbon fuel; and a detergent amount of a detergent comprising an alkenylsuccinimide prepared by reacting an alkenylsuccinic acid or anhydride with a mixture of amines, wherein at least 90 weight percent of the alkenyl substituent is derived from an olefin having a carbon chain of from 10 to 30 carbons or mixtures thereof, and wherein the alkenylsuccinic acid or anhydride is reacted with the mixture of amines at a mole ratio of 0.8 to 1.5 moles of the amines per mole of the alkenylsuccinic acid or anhydride.

  16. Reduction of vitellogenin synthesis by an aryl hydrocarbon receptor agonist in the white sturgeon (Acipenser transmontamus).

    PubMed

    Palumbo, Amanda J; Denison, Michael S; Doroshov, Serge I; Tjeerdema, Ronald S

    2009-08-01

    Migrating white sturgeon (Acipenser transmontamus) may be subject to agricultural, municipal, and industrial wastewater effluents that likely contain different classes of endocrine-disrupting contaminants. Concern is mounting about the negative effects of environmental estrogens on fish reproduction; however, in environmental mixtures, the affects from estrogenic compounds may be suppressed by aryl hydrocarbon receptor (AhR) ligands. Indeed, reductions in 17beta-estradiol-induced (0.01 and 1 mg/kg) vitellogenin (VTG) levels were observed in white sturgeon coinjected with beta-naphthoflavone (BNF; 50 mg/kg), a model for contaminants that activate the AhR. Variation in the time of injection was used to attempt to correlate VTG inhibition to ethoxyresorufin-O-deethylase activity. No evidence was found to suggest that the inhibition of VTG is a direct result of enhanced estrogen metabolism by BNF-induced enzymes. Results of the present study are relevant for monitoring programs that measure VTG, because these results show that AhR-active environmental contaminants can repress VTG synthesis, which commonly is used as an indicator of estrogen-mimicking contaminants. Furthermore, suppression of natural estrogen signaling by AhR agonists may have significant effects on fish reproduction.

  17. The Molecular, Cellular and Clinical Consequences of Targeting the Estrogen Receptor Following Estrogen Deprivation Therapy

    PubMed Central

    Fan, Ping; Maximov, Philipp Y.; Curpan, Ramona F.; Abderrahman, Balkees; Jordan, V. Craig

    2015-01-01

    During the past twenty years our understanding of the control of breast tumor development, growth and survival has changed dramatically. The once long forgotten application of high dose synthetic estrogen therapy as the first chemical therapy to treat any cancer has been resurrected, refined and reinvented as the new biology of estrogen-induced apoptosis. High dose estrogen therapy was cast aside once tamoxifen, from its origins as a failed “morning after pill”, was reinvented as the first targeted therapy to treat any cancer. The current understanding of the mechanism of estrogen-induced apoptosis is described as a consequence of acquired resistance to long term antihormone therapy in estrogen receptor (ER) positive breast cancer. The ER signal transduction pathway remains a target for therapy in breast cancer despite “antiestrogen” resistance, but becomes a regulator of resistance. Multiple mechanisms of resistance come into play: Selective ER Modulator (SERM) stimulated growth, growth factor/ER crosstalk, estrogen-induced apoptosis and mutations of ER. But it is with the science of estrogen-induced apoptosis that the next innovation in women’s health will be developed. Recent evidence suggests that the glucocorticoid properties of medroxyprogesterone acetate blunt estrogen-induced apoptosis in estrogen deprived breast cancer cell populations. As a result breast cancer develops during long-term Hormone Replacement Therapy (HRT). A new synthetic progestin with estrogen-like properties, such as the 19 nortestosterone derivatives used in oral contraceptives, will continue to protect the uterus from unopposed estrogen stimulation but at the same time, reinforce apoptosis in vulnerable populations of nascent breast cancer cells. PMID:26052034

  18. Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrogen receptor beta - regulation by selective estrogen receptor modulators and importance in breast cancer

    PubMed Central

    S Katzenellenbogen, Benita; A Katzenellenbogen, John

    2000-01-01

    Estrogens display intriguing tissue-selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer, for menopausal hormone replacement, and for fertility regulation. Certain compounds that act through the estrogen receptor (ER), now referred to as selective estrogen receptor modulators (SERMs), can demonstrate remarkable differences in activity in the various estrogen target tissues, functioning as agonists in some tissues but as antagonists in others. Recent advances elucidating the tripartite nature of the biochemical and molecular actions of estrogens provide a good basis for understanding these tissue-selective actions. As discussed in this thematic review, the development of optimal SERMs should now be viewed in the context of two estrogen receptor subtypes, ERα and ERβ, that have differing affinities and responsiveness to various SERMs, and differing tissue distribution and effectiveness at various gene regulatory sites. Cellular, biochemical, and structural approaches have also shown that the nature of the ligand affects the conformation assumed by the ER-ligand complex, thereby regulating its state of phosphorylation and the recruitment of different coregulator proteins. Growth factors and protein kinases that control the phosphorylation state of the complex also regulate the bioactivity of the ER. These interactions and changes determine the magnitude of the transcriptional response and the potency of different SERMs. As these critical components are becoming increasingly well defined, they provide a sound basis for the development of novel SERMs with optimal profiles of tissue selectivity as medical therapeutic agents. PMID:11250726

  19. Assessment of estrogen receptor--histone interactions.

    PubMed Central

    Kallos, J; Fasy, T M; Hollander, V P

    1981-01-01

    Several different in vitro binding assays show that the estrogen receptor from rabbit uterus interacts selectively with purified histones from calf thymus. The estrogen receptor binds strongly to histones H2B and H2A, moderately to histones H3 and H4, and poorly to histone H1. In the presence of histones H2B or H2A, the position at which the estrogen receptor focuses in an isoelectric gradient is shifted to a more basic zone. Kinetic experiments show that, if histone H2B is bound to a DNA, the estrogen receptor dissociates more slowly from that DNA. The portion of the estrogen receptor molecule required for binding to histone H2B is relatively stable to tryptic digestion; in contrast, the portion of the receptor molecule responsible for DNA binding is promptly lost during limited tryptic digestion. These in vitro findings suggest that the mechanism by which the estrogen receptor selectively alters gene expression may involve specific contacts with histone molecules. PMID:6942408

  20. Prenatal ethanol exposure persistently impairs N-methyl-D-aspartate receptor-dependent activation of extracellular signal-regulated kinase in the mouse dentate gyrus

    PubMed Central

    Samudio-Ruiz, Sabrina L.; Allan, Andrea M.; Valenzuela, C. Fernando; Perrone-Bizzozero, Nora I.; Caldwell, Kevin K.

    2009-01-01

    The dentate gyrus (DG) is the central input region to the hippocampus and is known to play an important role in learning and memory. Previous studies have shown that prenatal alcohol is associated with hippocampal-dependent learning deficits and a decreased ability to elicit long term potentiation (LTP) in the DG in adult animals. Given that activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade by N-methyl-D-aspartate (NMDA) receptors is required for various forms of learning and memory, as well as LTP, in hippocampal regions, including the DG, we hypothesized that fetal alcohol-exposed (FAE) adult animals would have deficits in hippocampal NMDA receptor-dependent ERK1/2 activation. We used immunoblotting and immunohistochemistry techniques to detect NMDA-stimulated ERK1/2 activation in acute hippocampal slices prepared from adult FAE mice. We present the first evidence linking prenatal alcohol exposure to deficits in NMDA receptor-dependent ERK1/2 activation specifically in the DG of adult offspring. This deficit may account for the LTP deficits previously observed in the DG, as well as the life-long cognitive deficits, associated with prenatal alcohol exposure. PMID:19317851

  1. Zeroing in on hydrocarbons

    SciTech Connect

    Roest, I.P.B. van der; Brasser, D.J.S.; Wagebaert, A.P.J.; Stam, P.H.

    1997-05-01

    The increasing costs of remediating contaminated sites has stimulated research for cost-reducing techniques in soil investigation and cleanup techniques. MAP Environmental Research has developed a technology using ground penetrating radar in combination with in house developed software to locate and define the extent of hydrocarbon contamination. This article discusses the new technology. 2 figs.

  2. Hydrocarbon options emerge

    SciTech Connect

    Fairley, P.

    1995-11-01

    Europe stole the scene at last week`s International Chlorofluorocarbon (CFC) and Halon Alternatives Conference in Washington as attendees learned more about an accelerating shift to low-cost hydrocarbon refrigerants by European equipment manufacturers. Udo Wenning, representing German refrigerator market leader Bosch-Siemens, told the conference that hydrocarbons-isobutane as refrigerant and cyclopentane to blow the insulating foam-are now used in 90% of German production. Wenning says that in all performance parameters, hydrocarbons match the hydrochlorofluorocarbon (HCFC) and hydrofluorocarbon (HFC) replacements favored in the U.S. and Japan and that, unlike HCFCs and HFCs they have low global warming potential. Their Achille`s heel is flammability, Wenning says. American equipment manufacturers aiming to sell a new generation of equipment designed for the new HFC refrigerants sought to amplify concern over flammability at the conference. {open_quotes}In a society as litigious as ours, we do not see a future for flammable refrigerants,{close_quotes} says a representative of air conditioner manufacturer Carrier. Hydrocarbon supporters such as Greenpeace say the risks are mananageable.

  3. Optrode for sensing hydrocarbons

    DOEpatents

    Miller, Holly; Milanovich, Fred P.; Hirschfeld, Tomas B.; Miller, Fred S.

    1988-01-01

    A two-phase system employing the Fujiwara reaction is provided for the fluorometric detection of halogenated hydrocarbons. A fiber optic is utilized to illuminate a column of pyridine trapped in a capillary tube coaxially attached at one end to the illuminating end of the fiber optic. A strongly alkaline condition necessary for the reaction is maintained by providing a reservoir of alkali in contact with the column of pyridine, the surface of contact being adjacent to the illuminating end of the fiber optic. A semipermeable membrane caps the other end of the capillary tube, the membrane being preferentially permeable to the halogenated hydrocarbon and but preferentially impermeable to water and pyridine. As the halogenated hydrocarbon diffuses through the membrane and into the column of pyridine, fluorescent reaction products are formed. Light propagated by the fiber optic from a light source, excites the fluorescent products. Light from the fluorescence emission is also collected by the same fiber optic and transmitted to a detector. The intensity of the fluorescence gives a measure of the concentration of the halogenated hydrocarbons.

  4. Optrode for sensing hydrocarbons

    DOEpatents

    Miller, Holly; Milanovich, Fred P.; Hirschfeld, Tomas B.; Miller, Fred S.

    1987-01-01

    A two-phase system employing the Fujiwara reaction is provided for the fluorometric detection of halogenated hydrocarbons. A fiber optic is utilized to illuminate a column of pyridine trapped in a capillary tube coaxially attached at one end to the illuminating end of the fiber optic. A strongly alkaline condition necessary for the reaction is maintained by providing a reservoir of alkali in contact with the column of pyridine, the surface of contact being adjacent to the illuminating end of the fiber optic. A semipermeable membrane caps the other end of the capillary tube, the membrane being preferentially permeable to the halogenated hydrocarbon and but preferentially impermeable to water and pyridine. As the halogenated hydrocarbon diffuses through the membrane and into the column of pyridine, fluorescent reaction products are formed. Light propagated by the fiber optic from a light source, excites the fluorescent products. Light from the fluorescence emission is also collected by the same fiber optic and transmitted to a detector. The intensity of the fluorescence gives a measure of the concentration of the halogenated hydrocarbons.

  5. Optrode for sensing hydrocarbons

    DOEpatents

    Miller, H.; Milanovich, F.P.; Hirschfeld, T.B.; Miller, F.S.

    1987-05-19

    A two-phase system employing the Fujiwara reaction is provided for the fluorometric detection of halogenated hydrocarbons. A fiber optic is utilized to illuminate a column of pyridine trapped in a capillary tube coaxially attached at one end to the illuminating end of the fiber optic. A strongly alkaline condition necessary for the reaction is maintained by providing a reservoir of alkali in contact with the column of pyridine, the surface of contact being adjacent to the illuminating end of the fiber optic. A semipermeable membrane caps the other end of the capillary tube, the membrane being preferentially permeable to the halogenated hydrocarbon but preferentially impermeable to water and pyridine. As the halogenated hydrocarbon diffuses through the membrane and into the column of pyridine, fluorescent reaction products are formed. Light propagated by the fiber optic from a light source, excites the fluorescent products. Light from the fluorescence emission is also collected by the same fiber optic and transmitted to a detector. The intensity of the fluorescence gives a measure of the concentration of the halogenated hydrocarbons. 6 figs.

  6. Optrode for sensing hydrocarbons

    DOEpatents

    Miller, H.; Milanovich, F.P.; Hirschfeld, T.B.; Miller, F.S.

    1988-09-13

    A two-phase system employing the Fujiwara reaction is provided for the fluorometric detection of halogenated hydrocarbons. A fiber optic is utilized to illuminate a column of pyridine trapped in a capillary tube coaxially attached at one end to the illuminating end of the fiber optic. A strongly alkaline condition necessary for the reaction is maintained by providing a reservoir of alkali in contact with the column of pyridine, the surface of contact being adjacent to the illuminating end of the fiber optic. A semipermeable membrane caps the other end of the capillary tube, the membrane being preferentially permeable to the halogenated hydrocarbon and but preferentially impermeable to water and pyridine. As the halogenated hydrocarbon diffuses through the membrane and into the column of pyridine, fluorescent reaction products are formed. Light propagated by the fiber optic from a light source, excites the fluorescent products. Light from the fluorescence emission is also collected by the same fiber optic and transmitted to a detector. The intensity of the fluorescence gives a measure of the concentration of the halogenated hydrocarbons. 5 figs.

  7. Polycyclic hydrocarbons and cancer

    SciTech Connect

    Gelboin, H.V.P; Ts'o, P.O.P.

    1981-01-01

    This book is Volume 3 of a three-volume series. It discusses polynuclear aromatic hydrocarbons (PAHs) in the marine environment, various PAH dihydrodiols, certain enzyme reactions, carcinogenesis modifications, and tumor promotion. PAH epidemiology for quantifying cigarette smoking and air pollution risks is also covered. (JMT)

  8. Effects of Estrogens and Estrogenic Disrupting Compounds on Fish Mineralized Tissues

    PubMed Central

    Pinto, Patricia I. S.; Estêvão, Maria D.; Power, Deborah M.

    2014-01-01

    Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities. PMID:25196834

  9. MODELING THE EFFECTS OF FLEXIBILITY ON THE BINDING OF ENVIRONMENTAL ESTROGENS TO THE ESTROGEN RECEPTOR

    EPA Science Inventory

    Modeling the effects of flexibility on the binding of environmental estrogens to the estrogen receptor
    There are many reports of environmental endocrine disruption in the literature, yet it has been difficult to identify the specific chemicals responsible for these effects. ...

  10. Aromatase inhibiting and combined estrogenic effects of parabens and estrogenic effects of other additives in cosmetics

    SciTech Connect

    Meeuwen, J.A. van Son, O. van; Piersma, A.H.; Jong, P.C. de; Berg, M. van den

    2008-08-01

    There is concern widely on the increase in human exposure to exogenous (anti)estrogenic compounds. Typical are certain ingredients in cosmetic consumer products such as musks, phthalates and parabens. Monitoring a variety of human samples revealed that these ingredients, including the ones that generally are considered to undergo rapid metabolism, are present at low levels. In this in vitro research individual compounds and combinations of parabens and endogenous estradiol (E{sub 2}) were investigated in the MCF-7 cell proliferation assay. The experimental design applied a concentration addition model (CA). Data were analyzed with the estrogen equivalency (EEQ) and method of isoboles approach. In addition, the catalytic inhibitory properties of parabens on an enzyme involved in a rate limiting step in steroid genesis (aromatase) were studied in human placental microsomes. Our results point to an additive estrogenic effect in a CA model for parabens. In addition, it was found that parabens inhibit aromatase. Noticeably, the effective levels in both our in vitro systems were far higher than the levels detected in human samples. However, estrogenic compounds may contribute in a cumulative way to the circulating estrogen burden. Our calculation for the extra estrogen burden due to exposure to parabens, phthalates and polycyclic musks indicates an insignificant estrogenic load relative to the endogenous or therapeutic estrogen burden.

  11. Effects of estrogens and estrogenic disrupting compounds on fish mineralized tissues.

    PubMed

    Pinto, Patricia I S; Estêvão, Maria D; Power, Deborah M

    2014-08-15

    Estrogens play well-recognized roles in reproduction across vertebrates, but also intervene in a wide range of other physiological processes, including mineral homeostasis. Classical actions are triggered when estrogens bind and activate intracellular estrogen receptors (ERs), regulating the transcription of responsive genes, but rapid non-genomic actions initiated by binding to plasma membrane receptors were recently described. A wide range of structurally diverse compounds from natural and anthropogenic sources have been shown to interact with and disrupt the normal functions of the estrogen system, and fish are particularly vulnerable to endocrine disruption, as these compounds are frequently discharged or run-off into waterways. The effect of estrogen disruptors in fish has mainly been assessed in relation to reproductive endpoints, and relatively little attention has been given to other disruptive actions. This review will overview the actions of estrogens in fish, including ER isoforms, their expression, structure and mechanisms of action. The estrogen functions will be considered in relation to mineral homeostasis and actions on mineralized tissues. The impact of estrogenic endocrine disrupting compounds on fish mineralized tissues will be reviewed, and the potential adverse outcomes of exposure to such compounds will be discussed. Current lacunae in knowledge are highlighted along with future research priorities.

  12. Apparatus and methods for hydrocarbon extraction

    DOEpatents

    Bohnert, George W.; Verhulst, Galen G.

    2016-04-26

    Systems and methods for hydrocarbon extraction from hydrocarbon-containing material. Such systems and methods relate to extracting hydrocarbon from hydrocarbon-containing material employing a non-aqueous extractant. Additionally, such systems and methods relate to recovering and reusing non-aqueous extractant employed for extracting hydrocarbon from hydrocarbon-containing material.

  13. Hydrocarbonization research: completion report

    SciTech Connect

    Youngblood, E.L.; Cochran, H.D. Jr.; Westmoreland, P.R.; Brown, C.H. Jr.; Oswald, G.E.; Barker, R.E.

    1981-01-01

    Hydrocarbonization is a relatively simple process used for producing oil, substitute natural gas, and char by heating coal under a hydrogen-rich atmosphere. This report describes studies that were performed in a bench-scale hydrocarbonization system at Oak Ridge National Laboratory (ORNL) during the period 1975 to 1978. The results of mock-up studies, coal metering valve and flowmeter development, and supporting work in an atmospheric hydrocarbonization system are also described. Oil, gas, and char yields were determined by hydrocarbonization of coal in a 0.1-m-diam fluidized-bed reactor operated at a pressure of 2170 kPa and at temperatures ranging from 694 to 854 K. The nominal coal feed rate was 4.5 kg/h. Wyodak subbituminous coal was used for most of the experiments. A maximum oil yield of approx. 21% based on moisture- and ash-free (maf) coal was achieved in the temperature range of 810 to 840 K. Recirculating fluidized-bed, uniformly fluidized-bed, and rapid hydropyrolysis reactors were used. A series of operability tests was made with Illinois No. 6 coal to determine whether caking coal could be processed in the recirculating fluidized-bed reactor. These tests were generally unsuccessful because of agglomeration and caking problems; however, these problems were eliminated by the use of chemically pretreated coal. Hydrocarbonization experiments were carried out with Illinois No. 6 coal that had been pretreated with CaO-NaOH, Na/sub 2/CO/sub 3/, and CaO-Na/sub 2/CO/sub 3/. Oil yields of 14, 24, and 21%, respectively, were obtained from the runs with treated coal. Gas and char yield data and the composition of the oil, gas, and char products are presented.

  14. Mantle hydrocarbons: Abiotic or biotic?

    SciTech Connect

    Sugisaki, Ryuichi; Mimura, Koichi

    1994-06-01

    Analyses of 227 rocks from fifty localities throughout the world showed that mantle derived rocks such as tectonized peridotites in ophiolite sequences (tectonites) and peridotite xenoliths in alkali basalts contain heavier hydrocarbons (n-alkanes), whereas igneous rocks produced by magmas such as gabbro and granite lack them. The occurrence of hydrocarbons indicates that they were not derived either from laboratory contamination or from field contamination; these compounds found in the mantle-derived rocks are called here {open_quotes}mantle hydrocarbons.{close_quotes} The existence of hydrocarbons correlates with petrogenesis. For example, peridotite cumulates produced by magmatic differentiation lack hydrocarbons whereas peridotite xenoliths derived from the mantle contain them. Gas chromatographic-mass spectrometric records of the mantle hydrocarbons resemble those of aliphatics in meteorites and in petroleum. Features of the hydrocarbons are that (a) the mantle hydrocarbons reside mainly along grain boundaries and in fluid inclusions of minerals; (b) heavier isoprenoids such as pristane and phytane are present; and (c) {delta}{sup 13}C of the mantle hydrocarbons is uniform (about {minus}27{per_thousand}). Possible origins for the mantle hydrocarbons are as follows. (1) They were inorganically synthesized by Fischer-Tropsch type reaction in the mantle. (2) They were delivered by meteorites and comets to the early Earth. (3) They were recycled by subduction. The mantle hydrocarbons in the cases of (1) and (2) are abiogenic and those in (3) are mainly biogenic. It appears that hydrocarbons may survive high pressures and temperatures in the mantle, but they are decomposed into lighter hydrocarbon gases such as CH{sub 4} at lower pressures when magmas intrude into the crust; consequently, peridotite cumulates do not contain heavier hydrocarbons but possess hydrocarbon gases up to C{sub 4}H{sub 10}. 76 refs., 5 figs., 3 tabs.

  15. Mantle hydrocarbons: abiotic or biotic?

    PubMed

    Sugisaki, R; Mimura, K

    1994-06-01

    Analyses of 227 rocks from fifty localities throughout the world showed that mantle derived rocks such as tectonized peridotites in ophiolite sequences (tectonites) arid peridotite xenoliths in alkali basalts contain heavier hydrocarbons (n-alkanes), whereas igneous rocks produced by magmas such as gabbro arid granite lack them. The occurrence of hydrocarbons indicates that they were not derived either from laboratory contamination or from held contamination; these compounds found in the mantle-derived rocks are called here "mantle hydrocarbons." The existence of hydrocarbons correlates with petrogenesis. For example, peridotite cumulates produced by magmatic differentiation lack hydrocarbons whereas peridotite xenoliths derived from the mantle contain them. Gas chromatographic-mass spectrometric records of the mantle hydrocarbons resemble those of aliphatics in meteorites and in petroleum. Features of the hydrocarbons are that (a) the mantle hydrocarbons reside mainly along grain boundaries and in fluid inclusions of minerals; (b) heavier isoprenoids such as pristane and phytane are present; and (c) delta 13C of the mantle hydrocarbons is uniform (about -27%). Possible origins for the mantle hydrocarbons are as follows. (1) They were in organically synthesized by Fischer-Tropsch type reaction in the mantle. (2) They were delivered by meteorites and comets to the early Earth. (3) They were recycled by subduction. The mantle hydrocarbons in the cases of (1) and (2) are abiogenic and those in (3) are mainly biogenic. It appears that hydrocarbons may survive high pressures and temperatures in the mantle, but they are decomposed into lighter hydrocarbon gases such as CH4 at lower pressures when magmas intrude into the crust; consequently, peridotite cumulates do not contain heavier hydrocarbons but possess hydrocarbon gases up to C4H10.

  16. SCREENING CHEMICALS FOR ESTROGEN RECEPTOR ...

    EPA Pesticide Factsheets

    The U.S. Environmental Protection Agency (EPA) is considering the use high-throughput and computational methods for regulatory applications in the Endocrine Disruptor Screening Program (EDSP). To use these new tools for regulatory decision making, computational methods must be appropriately validated. Traditional validations of toxicity tests are time intensive, evaluate a relatively small number of chemicals, and are not well-suited to high-throughput methods. Here we describe a multi-step, performance-based validation establishing scientific confidence in new computational methods and demonstrating these tools are sufficiently robust to be used in a regulatory context. Results from 18 estrogen receptor (ER) ToxCast high-throughput screening assays, measuring different points along the signaling pathway with different assay technologies, were integrated into a computational model. The resulting ToxCast ER model scores range from 0 (no activity) to 1 (bioactivity of the native ligand, 17β-estradiol) and can discriminate ER bioactivity from assay-specific interference and cytotoxicity. ToxCast ER model performance was evaluated for 40 in vitro and 43 in vivo reference chemicals. ToxCast ER model results were also compared to EDSP Tier 1 screening assays in current regulatory practice for a diverse set of more than 100 chemicals. ToxCast ER model accuracy was 95% when compared to the large set of in vitro and in vivo reference chemicals. In addition, the T

  17. Estrogenic Compounds, Estrogen Receptors and Vascular Cell Signaling in the Aging Blood Vessels

    PubMed Central

    Smiley, Dia A.; Khalil, Raouf A.

    2010-01-01

    The cardiovascular benefits of menopausal hormone therapy (MHT) remain controversial. The earlier clinical observations that cardiovascular disease (CVD) was less common in MHT users compared to non-users suggested cardiovascular benefits of MHT. Also, experimental studies have identified estrogen receptors ERα, ERβ and GPR30, which mediate genomic or non-genomic effects in vascular endothelium, smooth muscle, and extracellular matrix (ECM). However, data from randomized clinical trials (RCTs), most notably the Women's Health Initiative (WHI) study, have challenged the cardiovascular benefits and highlighted adverse cardiovascular events with MHT. The discrepancies have been attributed to the design of RCTs, the subjects' advanced age and preexisting CVD, and the form of estrogen used. The discrepancies may also stem from age-related changes in vascular ER amount, distribution, integrity, and post-receptor signaling pathways as well as structural changes in the vasculature. Age-related changes in other sex hormones such as testosterone may also alter the hormonal environment and influence the cardiovascular effects of estrogen. Investigating the chemical properties, structure-activity relationship and pharmacology of natural and synthetic estrogens should improve the effectiveness of conventional MHT. Further characterization of phytoestrogens, selective estrogen-receptor modulators (SERMs), and specific ER agonists may provide substitutes to conventional MHT. Conditions with excess or low estrogen levels such as polycystic ovary syndrome (PCOS) and Turner syndrome may provide insight into the development and regulation of ER and the mechanisms of aberrant estrogen-ER interactions. The lessons learned from previous RCTs have led to more directed studies such as the Kronos Early Estrogen Prevention Study (KEEPS). Careful design of experimental models and RCTs, coupled with the development of specific ER modulators, hold the promise of improving the actions of

  18. Effect of vaginal estrogen on pessary use

    PubMed Central

    Dessie, Sybil G.; Armstrong, Katherine; Modest, Anna M.; Hacker, Michele R.

    2016-01-01

    Introduction and hypothesis Many providers recommend concurrent estrogen therapy with pessary use to limit complications; however, limited data exist to support this practice. We hypothesized that vaginal estrogen supplementation decreases incidence of pessary-related complications and discontinuation. Methods We performed a retrospective cohort study of women who underwent a pessary fitting from 1 January 2007 through 1 September 2013 at one institution; participants were identified by billing code and were eligible if they were post-menopausal and had at least 3 months of pessary use and 6 months of follow-up. All tests were two sided, and P values < 0.05 were considered statistically significant. Results Data from 199 women were included; 134 used vaginal estrogen and 65 did not. Women who used vaginal estrogen had a longer median follow-up time (29.5 months) compared with women who did not (15.4 months) and were more likely to have at least one pessary check (98.5 % vs 86.2 %, P < 0.001). Those in the estrogen group were less likely to discontinue using their pessary (30.6 % vs 58.5 %, P < 0.001) and less likely to develop increased vaginal discharge than women who did not [hazard ratio (HR) 0.31, 95 % confidence interval (CI) 0.17–0.58]. Vaginal estrogen was not protective against erosions (HR 0.93, 95 % CI 0.54–1.6) or vaginal bleeding (HR 0.78, 95 % CI 0.36–1.7). Conclusions Women who used vaginal estrogen exhibited a higher incidence of continued pessary use and lower incidence of increased vaginal discharge than women who did not. PMID:26992727

  19. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.

    PubMed

    Klinge, Carolyn M; Blankenship, Kristy A; Risinger, Kelly E; Bhatnagar, Shephali; Noisin, Edouard L; Sumanasekera, Wasana K; Zhao, Lei; Brey, Darren M; Keynton, Robert S

    2005-03-04

    Vascular endothelial cells (EC) are an important target of estrogen action through both the classical genomic (i.e. nuclear-initiated) activities of estrogen receptors alpha and beta (ERalpha and ERbeta) and the rapid "non-genomic" (i.e. membrane-initiated) activation of ER that stimulates intracellular phosphorylation pathways. We tested the hypothesis that the red wine polyphenol trans-resveratrol activates MAPK signaling via rapid ER activation in bovine aortic EC, human umbilical vein EC, and human microvascular EC. We report that bovine aortic EC, human umbilical vein EC, and human microvascular EC express ERalpha and ERbeta. We demonstrate that resveratrol and estradiol (E(2)) rapidly activated MAPK in a MEK-1, Src, matrix metalloproteinase, and epidermal growth factor receptor-dependent manner. Importantly, resveratrol activated MAPK and endothelial nitric-oxide synthase (eNOS) at nm concentrations (i.e. an order of magnitude less than that required for ER genomic activity) and concentrations possibly achieved transiently in serum following oral red wine consumption. Co-treatment with ER antagonists ICI 182,780 or 4-hydroxytamoxifen blocked resveratrol- or E(2)-induced MAPK and eNOS activation, indicating ER dependence. We demonstrate for the first time that ERalpha-and ERbeta-selective agonists propylpyrazole triol and diarylpropionitrile, respectively, stimulate MAPK and eNOS activity. A red but not a white wine extract also activated MAPK, and activity was directly correlated with the resveratrol concentration. These data suggest that ER may play a role in the rapid effects of resveratrol in EC and that some of the atheroprotective effects of resveratrol may be mediated through rapid activation of ER signaling in EC.

  20. Microbial degradation of petroleum hydrocarbons.

    PubMed

    Varjani, Sunita J

    2017-01-01

    Petroleum hydrocarbon pollutants are recalcitrant compounds and are classified as priority pollutants. Cleaning up of these pollutants from environment is a real world problem. Bioremediation has become a major method employed in restoration of petroleum hydrocarbon polluted environments that makes use of natural microbial biodegradation activity. Petroleum hydrocarbons utilizing microorganisms are ubiquitously distributed in environment. They naturally biodegrade pollutants and thereby remove them from the environment. Removal of petroleum hydrocarbon pollutants from environment by applying oleophilic microorganisms (individual isolate/consortium of microorganisms) is ecofriendly and economic. Microbial biodegradation of petroleum hydrocarbon pollutants employs the enzyme catalytic activities of microorganisms to enhance the rate of pollutants degradation. This article provides an overview about bioremediation for petroleum hydrocarbon pollutants. It also includes explanation about hydrocarbon metabolism in microorganisms with a special focus on new insights obtained during past couple of years.

  1. Is Estrogen a Therapeutic Target for Glaucoma?

    PubMed Central

    Dewundara, Samantha; Wiggs, Janey; Sullivan, David A.; Pasquale, Louis R.

    2016-01-01

    Objective To provide an overview of the association between estrogen and glaucoma. Methods A literature synthesis of articles published in peer review journals screened through May 05, 2015 using the PubMed database. Key words used were “estrogen and glaucoma,” “reproductive factors and glaucoma,” “estrogen, nitric oxide and eye.” Forty three journal articles were included. Results Markers for lifetime estrogen exposure have been measured by several studies and show that the age of menarche onset, oral contraceptive (OC) use, bilateral oophorectomy, age of menopause onset and duration between menarche to menopause are associated with primary open angle (POAG) risk. The Blue Mountain Eye Study found a significantly increased POAG risk with later (>13 years) compared with earlier (≤12 years) age of menarche. Nurses’ Health Study (NHS) investigators found that OC use of greater than 5 years was associated with a 25% increased risk of POAG. The Mayo Clinic Cohort Study of Oophorectomy and Aging found that women who underwent bilateral oophorectomy before age 43 had an increased risk of glaucoma. The Rotterdam Study found that women who went through menopause before reaching the age of 45 years had a higher risk of open-angle glaucoma (2.6-fold increased risk) while the NHS showed a reduced risk of POAG among women older than 65 who entered menopause after age ≥ 54 years. Increased estrogen states may confer a reduced risk of glaucoma or glaucoma related traits such as reduced intraocular pressure (IOP). Pregnancy, a hyperestrogenemic state, is associated with decreased IOP during the third trimester. Though the role of post-menopausal hormone (PMH) use in the reduction of IOP is not fully conclusive, PMH use may reduce the risk of POAG. From a genetic epidemiologic perspective, estrogen metabolic pathway single nucleotide polymorphisms (SNPs) were associated with POAG in women and polymorphisms in endothelial nitric oxide synthase, a gene receptive to

  2. Estrogenicity of Glabridin in Ishikawa Cells

    PubMed Central

    Su Wei Poh, Melissa; Viseswaran, Navaratnam

    2015-01-01

    Glabridin is an isoflavan from licorice root, which is a common component of herbal remedies used for treatment of menopausal symptoms. Past studies have shown that glabridin resulted in favorable outcome similar to 17β-estradiol (17β-E2), suggesting a possible role as an estrogen replacement therapy (ERT). This study aims to evaluate the estrogenic effect of glabridin in an in-vitro endometrial cell line -Ishikawa cells via alkaline phosphatase (ALP) assay and ER-α-SRC-1-co-activator assay. Its effect on cell proliferation was also evaluated using Thiazoyl blue tetrazolium bromide (MTT) assay. The results showed that glabridin activated the ER-α-SRC-1-co-activator complex and displayed a dose-dependent increase in estrogenic activity supporting its use as an ERT. However, glabridin also induced an increase in cell proliferation. When glabridin was treated together with 17β-E2, synergistic estrogenic effect was observed with a slight decrease in cell proliferation as compared to treatment by 17β-E2 alone. This suggest that the combination might be better suited for providing high estrogenic effects with lower incidences of endometrial cancer that is associated with 17β-E2. PMID:25816349

  3. Estrogen therapy in systemic lupus erythematosus.

    PubMed

    Askanase, Anca D

    2004-01-01

    Given the female preponderance of systemic lupus erythematosus (SLE) in humans, the adverse effects of female gender and sex hormones in murine lupus, and numerous reports (retrospective, often anecdotal and uncontrolled) that describe a temporal association between estrogen exposure and development or exacerbation of SLE, it is tempting to accept that estrogens and SLE simply do not mix. While there are valid concerns regarding the use of exogenous estrogens in women with SLE, there are also potential health benefits to be considered. Oral contraceptives (OCs) offer effective birth control and may be bone protective in corticosteroid-treated patients. Recent studies, albeit retrospective, suggest that OCs are well tolerated in patients with SLE. Several salutary effects of postmenopausal estrogens assume particular importance in SLE where the risks of osteoporosis, exaggerated by menopause (natural or cyclophosphamide-induced) and corticosteroids, are substantial. However, the results of the Women's Health Initiative trial significantly limit the use of hormone replacement therapy in the general population, and raise particular concern for SLE patients. Other exogenous hormones (clomifene, gonadotropins, gonadotropin-releasing hormones) may be used to elevate levels of endogenous estrogen and to stimulate ovulation in patients with diminished fertility. Patients with inactive or stable/moderate disease and at low risk for thrombosis may benefit from OCs and other hormonal therapies without a change in lupus activity. Large prospective, double-blind, placebo-controlled studies inclusive of all ethnic groups should provide the basis for more definitive recommendations.

  4. ANALYSIS OF SWINE LAGOONS AND GROUND WATER FOR ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    A method was developed for analysis of low levels of natural (estradiol, estrone, estriol) and synthetic (ethinyl estradiol) estrogens in ground water and swine waste lagoon effluent. The method includes solid phase extraction of the estrogens, preparation of pentafluorobenzyl de...

  5. Synergistic activation of estrogen receptor with combinations of environmental chemicals

    SciTech Connect

    Arnold, S.F.; Klotz, D.M.; Collins, B.M.

    1996-06-07

    Certain chemicals in the environment are estrogenic. The low potencies of the compounds, when studied singly, suggest that they may have little effect on biological systems. The estrogenic potencies of combinations of such chemicals were screened in a simple yeast estrogen potencies of combination of such chemicals were screened in a simple yeast estrogen systems (YES) containing human estrogen receptor (hER). Combinations of two weak environmental estrogens, such as dieldrin, endosulfan, or toxaphene, were 100 times as potent in hER-mediated transactivation as any chemical alone. Hydroxylated polychlorinated biphenyls shown previously to synergistically alter sexual development in turtles also synergized in the YES. The synergistic interaction of chemical mixtures with the estrogen receptor may have profound environmental implications. These results may represent a previously uncharacterized level of regulation of estrogen-associated responses. 32 refs., 3 figs., 3 tabs.

  6. ANALYSIS OF SWINE LAGOONS AND GROUND WATER FOR ENVIRONMENTAL ESTROGENS

    EPA Science Inventory

    A method was developed for analysis of low levels of natural (estradiol, estrone, estriol) and synthetic (ethynylestradiol) estrogens in ground water and swine waste lagoon effluent. The method includes solid phase extraction of the estrogens, preparation of pentafluorobenzyl der...

  7. Membrane separation of hydrocarbons

    DOEpatents

    Chang, Y. Alice; Kulkarni, Sudhir S.; Funk, Edward W.

    1986-01-01

    Mixtures of heavy oils and light hydrocarbons may be separated by passing the mixture through a polymeric membrane. The membrane which is utilized to effect the separation comprises a polymer which is capable of maintaining its integrity in the presence of hydrocarbon compounds and which has been modified by being subjected to the action of a sulfonating agent. Sulfonating agents which may be employed will include fuming sulfuric acid, chlorosulfonic acid, sulfur trioxide, etc., the surface or bulk modified polymer will contain a degree of sulfonation ranging from about 15 to about 50%. The separation process is effected at temperatures ranging from about ambient to about 100.degree. C. and pressures ranging from about 50 to about 1000 psig.

  8. Hydrocarbon bioremediation -- An overview

    SciTech Connect

    Reisinger, H.J.

    1995-12-31

    Bioremediation is the process that transforms xenobiotics introduced into the environment to a less toxic or innocuous form, or mineralizes them to inorganic species. The processes can be carried out through either aerobic or anaerobic pathways by indigenous heterotrophs or by specially engineered organisms. For some xenobiotics, the process can also be carried out by cometabolic processes, which use another compound as the carbon and energy source. This technique can be applied either in situ or ex situ. An overview is presented of real-world applications of a variety of hydrocarbon bioremediation approaches, including biopiling, bioventing, bioslurping, landfarming, electrobioreclamation, and biovertical circulation wells. Problems in translating laboratory and field-scale pilot test data to full-scale operating systems are discussed. Such issues include biodegradation enhancement, nutrient and electron acceptor delivery, alternative electron acceptors, and integration of biological, chemical, and physical approaches to hydrocarbon remediation.

  9. Direct hydrocarbon fuel cells

    DOEpatents

    Barnett, Scott A.; Lai, Tammy; Liu, Jiang

    2010-05-04

    The direct electrochemical oxidation of hydrocarbons in solid oxide fuel cells, to generate greater power densities at lower temperatures without carbon deposition. The performance obtained is comparable to that of fuel cells used for hydrogen, and is achieved by using novel anode composites at low operating temperatures. Such solid oxide fuel cells, regardless of fuel source or operation, can be configured advantageously using the structural geometries of this invention.

  10. Novel Promising Estrogenic Receptor Modulators: Cytotoxic and Estrogenic Activity of Benzanilides and Dithiobenzanilides.

    PubMed

    Kucinska, Malgorzata; Giron, Maria-Dolores; Piotrowska, Hanna; Lisiak, Natalia; Granig, Walter H; Lopez-Jaramillo, Francisco-Javier; Salto, Rafael; Murias, Marek; Erker, Thomas

    2016-01-01

    The cytotoxicity of 27 benzanilides and dithiobenzanilides built on a stilbene scaffold and possessing various functional groups in aromatic rings previously described for their spasmolytic properties was assayed on three human cancer cell lines (A549 -lung adenocarcinoma, MCF-7 estrogen dependent breast adenocarcinoma and MDA-MB-231 estrogen independent breast adenocarcinoma) and 2 non-tumorigenic cell lines (CCD39Lu-lung fibroblasts, MCF-12A - breast epithelial). Three compounds (6, 15 and 18) showed selective antiproliferative activity against estrogen dependent MCF-7 cancer cells and their estrogenic activity was further confirmed in MCF-7 transfected with an estrogen receptor reporter plasmid and in HEK239 cells over-expressing the estrogen receptor alpha (ERα). Compound 18 is especially interesting as a potential candidate for therapy since it is highly toxic and selective towards estrogen dependent MCF7 cell lines (IC50 = 5.07 μM versus more than 100 μM for MDA-MB-231) and almost innocuous for normal breast cells (IC50 = 91.46 μM for MCF-12A). Docking studies have shown that compound 18 interacts with the receptor in the same cavity as estradiol although the extra aromatic ring is involved in additional binding interactions with residue W383. The role of W383 and the extended binding mode were confirmed by site-directed mutagenesis.

  11. Novel Promising Estrogenic Receptor Modulators: Cytotoxic and Estrogenic Activity of Benzanilides and Dithiobenzanilides

    PubMed Central

    Kucinska, Malgorzata; Giron, Maria-Dolores; Piotrowska, Hanna; Lisiak, Natalia; Granig, Walter H.; Lopez-Jaramillo, Francisco-Javier; Salto, Rafael; Murias, Marek; Erker, Thomas

    2016-01-01

    The cytotoxicity of 27 benzanilides and dithiobenzanilides built on a stilbene scaffold and possessing various functional groups in aromatic rings previously described for their spasmolytic properties was assayed on three human cancer cell lines (A549 –lung adenocarcinoma, MCF-7 estrogen dependent breast adenocarcinoma and MDA-MB-231 estrogen independent breast adenocarcinoma) and 2 non-tumorigenic cell lines (CCD39Lu–lung fibroblasts, MCF-12A - breast epithelial). Three compounds (6, 15 and 18) showed selective antiproliferative activity against estrogen dependent MCF-7 cancer cells and their estrogenic activity was further confirmed in MCF-7 transfected with an estrogen receptor reporter plasmid and in HEK239 cells over-expressing the estrogen receptor alpha (ERα). Compound 18 is especially interesting as a potential candidate for therapy since it is highly toxic and selective towards estrogen dependent MCF7 cell lines (IC50 = 5.07 μM versus more than 100 μM for MDA-MB-231) and almost innocuous for normal breast cells (IC50 = 91.46 μM for MCF-12A). Docking studies have shown that compound 18 interacts with the receptor in the same cavity as estradiol although the extra aromatic ring is involved in additional binding interactions with residue W383. The role of W383 and the extended binding mode were confirmed by site-directed mutagenesis. PMID:26730945

  12. Functional associations between two estrogen receptors, environmental estrogens, and sexual disruption in the roach (Rutilus rutilus).

    PubMed

    Katsu, Yoshinao; Lange, Anke; Urushitani, Hiroshi; Ichikawa, Rie; Paull, Gregory C; Cahill, Laura L; Jobling, Susan; Tyler, Charles R; Iguchi, Taisen

    2007-05-01

    Wild male roach (Rutilus rutilus) living in U.K. rivers contaminated with estrogenic effluents from wastewater treatment works show feminized responses and have a reduced reproductive capability, but the chemical causation of sexual disruption in the roach has not been established. Feminized responses were induced in male roach exposed to environmentally relevant concentrations of the pharmaceutical estrogen 17alpha-ethinylestradiol, EE2 (up to 4 ng/ L), during early life (from fertilization to 84 days posthatch, dph), and these effects were signaled by altered patterns of expression of two cloned roach estrogen receptor (ER) subtypes, ERalpha. and ERbeta, in the brain and gonad/ liver. Transactivation assays were developed for both roach ER subtypes and the estrogenic potencies of steroidal estrogens differed markedly at the different ER subtypes. EE2 was by far the most potent chemical, and estrone (E1, the most prevalent environmental steroid in wastewater discharges) was equipotent with estradiol (E2) in activating the ERs. Comparison of the EC50 values for the compounds tested showed that ERbeta was 3-21-fold more sensitive to natural steroidal estrogens and 54-fold more sensitive to EE2 as compared to ERalpha. These findings add substantial support to the hypothesis that steroidal estrogens play a significant role in the induction of intersex in roach populations in U.K. rivers and that the molecular approach described could be usefully applied to understand interspecies sensitivity to xenoestrogens.

  13. Survey of estrogenic activity in fish feed by yeast estrogen-screen assay.

    PubMed

    Matsumoto, Takeru; Kobayashi, Makito; Moriwaki, Toshihisa; Kawai, Shin'ichiro; Watabe, Shugo

    2004-10-01

    Fishes have been used as laboratory animal for research of estrogenic endocrine disrupters by many researchers. However, much less attention was paid to the possibility that compounds with estrogenic activity are present in fish diets. In order to examine this possibility, we measured the estrogenic activity in commercial fish feed by in vitro yeast estrogen-screen (YES) assay based on the binding ability of tested compounds to estrogen receptors. Estrogenic activity was detected in all the commercial fish feed examined (0.2-6.2 ng estradiol equivalent/g fish feed), some phytoestrogens (genistein, formononetin, equol and coumestrol; relative activity to estradiol, 8.6 x 10(-6)-1.1 x 10(-4) by giving a value of 1.0 to estradiol) and some androgens (testosterone, 11-ketotestosterone and 5 alpha-dihydrotestosterone; relative activity to estradiol, 3.0 x 10(-6)-1.2 x 10(-4)). Therefore, it is possible that these compounds could affect the results of in vivo estrogen assay, such as vitellogenin production in male fish, especially when fish are fed commercial feed.

  14. Effect of Estrogen on Mutagenesis in Human Mammary Epithelial Cells

    DTIC Science & Technology

    2005-06-01

    estrogen signaling through the estrogen receptor alpha (ERa) may induce a mutator phenotype by suppressing DNA repair activity in ERa positive mammary...measure DNA MMR activity in live cells. We have also developed a method to measure mutation rate as a function of estrogen/ER signaling . Our goals were to...whether 1713-estradiol signaling through ER inhibits DNA MMR activity, we developed a method that can quantitatively assess MMR efficiency in live

  15. THERMOCHEMISTRY OF HYDROCARBON RADICALS

    SciTech Connect

    Kent M. Ervin, Principal Investigator

    2004-08-17

    Gas phase negative ion chemistry methods are employed to determine enthalpies of formation of hydrocarbon radicals that are important in combustion processes and to investigate the dynamics of ion-molecule reactions. Using guided ion beam tandem mass spectrometry, we measure collisional threshold energies of endoergic proton transfer and hydrogen atom transfer reactions of hydrocarbon molecules with negative reagent ions. The measured reaction threshold energies for proton transfer yield the relative gas phase acidities. In an alternative methodology, competitive collision-induced dissociation of proton-bound ion-molecule complexes provides accurate gas phase acidities relative to a reference acid. Combined with the electron affinity of the R {center_dot} radical, the gas phase acidity yields the RH bond dissociation energy of the corresponding neutral molecule, or equivalently the enthalpy of formation of the R{center_dot} organic radical, using equation: D(R-H) = {Delta}{sub acid}H(RH) + EA(R) - IE(H). The threshold energy for hydrogen abstraction from a hydrocarbon molecule yields its hydrogen atom affinity relative to the reagent anion, providing the RH bond dissociation energy directly. Electronic structure calculations are used to evaluate the possibility of potential energy barriers or dynamical constrictions along the reaction path, and as input for RRKM and phase space theory calculations. In newer experiments, we have measured the product velocity distributions to obtain additional information on the energetics and dynamics of the reactions.

  16. MEMBRANE ESTROGEN RECEPTOR REGULATION OF HYPOTHALAMIC FUNCTION

    PubMed Central

    Micevych, Paul E.; Kelly, Martin J.

    2012-01-01

    Over the decades, our understanding of estrogen receptor (ER) function has evolved. Today we are confronted by at least two nuclear ERs: ERα and ERβ; and a number of putative membrane ERs, including ERα, ERβ, ER-X, GPR30 and Gq-mER. These receptors all bind estrogens or at least estrogenic compounds and activate intracellular signaling pathways. In some cases, a well-defined pharmacology, and physiology has been discovered. In other cases, the identity or the function remains to be elucidated. This mini-review attempts to synthesize our understanding of 17β-estradiol membrane signaling within hypothalamic circuits involved in homeostatic functions focusing on reproduction and energy balance. PMID:22538318

  17. Radical scavengers from heavy hydrocarbons

    SciTech Connect

    Kubo, Junichi

    1996-10-01

    The hydrogen-donating properties of some hydrocarbons form the basis for processes such as coal liquefaction and heavy oil upgrading. However, these hydrocarbons have seldom been used for other purposes, because their potential applications have not been well recognized. Research has indicated that these hydrogen-donating hydrocarbons can be used in important reactions as radical scavengers and have properties particular to those of pure hydrocarbons without functional groups containing heteroatoms. Over years of study researchers have found that pure hydrocarbons with radical-scavenging effects nearly as high as those in conventional hindered phenolic antioxidants can be produced from petroleum, and these hydrogen-donating hydrocarbons exhibit such effects even in oxidative atmospheres (i.e., they function as antioxidants). He has also shown that these mixtures have some properties particular to pure hydrocarbons without functional groups containing heteroatoms, and they`ve seen that a mechanism based on the steric effects appears when these hydrocarbons are used in heavy oil hydroprocessing. Hydrogen-donating hydrocarbons should be a viable resource in many applications. In this article, he presents radical-scavenging abilities, characteristics as pure hydrocarbons, and applications on the basis of the studies.

  18. ANALYSIS OF LAGOON SAMPLES FROM DIFFERENT CONCENTRATED ANIMAL FEEDING OPERATIONS (CAFOS) FOR ESTROGENS AND ESTROGEN CONJUGATES (PRESENTATION)

    EPA Science Inventory

    Although Concentrated Animal Feeding Operations (CAFOs) have been identified as potentially important sources for the release of estrogens into the environment, information is lacking on the concentrations of estrogens in whole lagoon effluents (including suspended solids) which ...

  19. Cumulative Estrogen Exposure and Prospective Memory in Older Women

    ERIC Educational Resources Information Center

    Hesson, Jacqueline

    2012-01-01

    This study looked at cumulative lifetime estrogen exposure, as estimated with a mathematical index (Index of Cumulative Estrogen Exposure (ICEE)) that included variables (length of time on estrogen therapy, age at menarche and menopause, postmenopausal body mass index, time since menopause, nulliparity and duration of breastfeeding) known to…

  20. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    ERIC Educational Resources Information Center

    Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.

    2008-01-01

    Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or…

  1. The Immunophilin-Like Protein XAP2 Is a Negative Regulator of Estrogen Signaling through Interaction with Estrogen Receptor α

    PubMed Central

    Berg, Petra; Korbonits, Marta; Pongratz, Ingemar

    2011-01-01

    XAP2 (also known as aryl hydrocarbon receptor interacting protein, AIP) is originally identified as a negative regulator of the hepatitis B virus X-associated protein. Recent studies have expanded the range of XAP2 client proteins to include the nuclear receptor family of transcription factors. In this study, we show that XAP2 is recruited to the promoter of ERα regulated genes like the breast cancer marker gene pS2 or GREB1 and negatively regulate the expression of these genes in MCF-7 cells. Interestingly, we show that XAP2 downregulates the E2-dependent transcriptional activation in an estrogen receptor (ER) isoform-specific manner: XAP2 inhibits ERα but not ERβ-mediated transcription. Thus, knockdown of intracellular XAP2 levels leads to increased ERα activity. XAP2 proteins, carrying mutations in their primary structures, loose the ability of interacting with ERα and can no longer regulate ER target gene transcription. Taken together, this study shows that XAP2 exerts a negative effect on ERα transcriptional activity and may thus prevent ERα-dependent events. PMID:21984905

  2. Differential action of chlorinated polycyclic aromatic hydrocarbons on aryl hydrocarbon receptor-mediated signaling in breast cancer cells.

    PubMed

    Ohura, Takeshi; Morita, Maki; Kuruto-Niwa, Ryoko; Amagai, Takashi; Sakakibara, Hiroyuki; Shimoi, Kayoko

    2010-04-01

    Chlorinated polycyclic aromatic hydrocarbons (ClPAHs), which are a series of halogenated aromatic hydrocarbons, have been found in the environment. The primary step in their metabolic activation seems to be associated with aryl hydrocarbon receptor (AhR)-mediated induction of the cytochrome P450 (CYP) 1 family, although the evidence remains unclear. In this study, we first investigated the effects of five ClPAHs with three to five rings and the corresponding parent PAHs on the expression of CYP1A1 and 1B1 in human breast cancer MCF-7 cells. For the targeted ClPAHs, Western blot analysis of ClPAH-induced CYP1A1 and 1B1 showed an enhancement in activities in comparison with induction by the corresponding parent PAHs, and the effects of chlorination were especially prominent in phenanthrene. In a further study, using 6-chlorobenzo[a]pyrene (6-ClBaP), cotreatment with 17beta-estradiol showed an increase in the expression of CYP1B1 mRNA but not CYP1A1 mRNA. Since the AhR ligand has been reported to induce formation of an AhR-estrogen receptor (ER) complex, which stimulates transcription of ER target genes, the effects of ClPAHs in MCF-7 cells transfected with estrogen response elements-regulated green fluorescent protein (GFP) reporter genes were also investigated in this study. 6-ClBaP induced a dose-dependent increase in GFP expression related to ER signaling through AhR activation in the cells, but 3,9,10-trichlorophenanthrene (3,9,10-Cl(3)ClPhe) did not, despite its ability to activate AhR. Furthermore, we investigated the effect of ClPAHs on the expression of the endogenous ER-responsive genes, cathepsin D, in MCF-7 cells. 6-ClBaP stimulated expression of the ER-responsive genes but 3,9,10-Cl(3)ClPhe did not, as in the GFP expression system. These results suggest that estrogenic action mediated ER signaling through AhR activation does not necessarily occur for every ligand that can activate AhR.

  3. Estrogens in the daily diet: in vitro analysis indicates that estrogenic activity is omnipresent in foodstuff and infant formula.

    PubMed

    Behr, Maximilian; Oehlmann, Jörg; Wagner, Martin

    2011-10-01

    Food is a main source of exposure to endocrine active compounds, many of which have been linked to adverse health effects. Phytoestrogens, especially from soy, are the major dietary source of estrogenicity. However, foodstuff contains a variety of estrogen-like compounds that might not be detected analytically. To assess the total estrogenic activity of foodstuff, we employed the Yeast Estrogen Screen (YES). We analyzed 18 food samples and five milk-based infant formulas. Soy-based products contained potent estrogenicity of 100-1500ng estradiol equivalents per kilogram (EEQ/kg). The estrogenicity in soy-free products was far lower (10-40ng EEQ/kg). We also detected significant estrogenic activity in three infant formulas (14-22ng EEQ/kg). Furthermore, we found soy lecithin to be strongly estrogenic. It might, therefore, be a major contributor to total estrogenicity. We conclude that dietary estrogens are omnipresent and not limited to soy-based food. In an exposure assessment we calculated a total dietary intake of 27.5 and 34.0ng EEQ/d for adults and 1.46ng EEQ/d for infants. While the dietary exposure to estrogenic activity is lower than previously estimated, our results demonstrate that many food types are a source of unidentified estrogen-like compounds still awaiting toxicological evaluation.

  4. Delayed puberty and estrogen resistance in a woman with estrogen receptor α variant.

    PubMed

    Quaynor, Samuel D; Stradtman, Earl W; Kim, Hyung-Goo; Shen, Yiping; Chorich, Lynn P; Schreihofer, Derek A; Layman, Lawrence C

    2013-07-11

    Although androgen resistance has been characterized in men with a normal chromosome complement and mutations in the androgen-receptor gene, a mutation in the gene encoding estrogen receptor α (ESR1) was previously described only in one man and not, to our knowledge, in a woman. We now describe an 18-year-old woman without breast development and with markedly elevated serum levels of estrogens and bilateral multicystic ovaries. She was found to have a homozygous loss-of-function ESR1 mutation in a completely conserved residue that interferes with estrogen signaling. Her clinical presentation was similar to that in the mouse orthologue knockout. This case shows that disruption of ESR1 causes profound estrogen resistance in women. (Funded by the National Institutes of Health.).

  5. Estrogenic and dioxin-like compounds in sediment from Zierikzee harbour identified with CALUX assay-directed fractionation combined with one and two dimensional gas chromatography analyses.

    PubMed

    Houtman, Corine J; Booij, Petra; Jover, Eric; Pascual del Rio, David; Swart, Kees; van Velzen, Martin; Vreuls, Rene; Legler, Juliette; Brouwer, Abraham; Lamoree, Marja H

    2006-12-01

    The identity of compounds responsible for estrogenic and dioxin-like activities in sediment from the harbour of the small town Zierikzee in Zeeland, The Netherlands, was investigated using a bioassay directed fractionation approach with the in vitro estrogen and dioxin responsive reporter gene assays ER- and DR-CALUX. For identification of compounds exhibiting activity in the bioassays, either one or two-dimensional GC in combination with quadrupole (MSD), ion trap (ITD) or time-of-flight mass spectrometric detection (ToF-MS) was used, depending on the biological and chemical characteristics and the complexity of the fractions. The natural estrogenic hormone 17-beta-estradiol and its metabolite estrone were identified with GC-ITD as the main contributors to the estrogenic activity. After successive rounds of fractionation, the dioxin-like activity could be explained by the presence of various polycyclic aromatic hydrocarbons identified with GC-MSD and two-dimensional comprehensive GC x GC-ToF-MS. Some estrogenic activity of a relatively non-polar nature remained unidentified.

  6. Gas-Phase Ambient Air Contaminants Exhibit Significant Dioxin-like and Estrogen-like Activity in Vitro

    PubMed Central

    Klein, Gail P.; Hodge, Erin M.; Diamond, Miriam L.; Yip, Amelia; Dann, Tom; Stern, Gary; Denison, Michael S.; Harper, Patricia A.

    2006-01-01

    Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR)–based and estrogen receptor (ER)–based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum (∑) of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10–100 times more abundant than that of ∑polychlorinated biphenyls, ∑nitro-polycyclic aromatic hydrocarbons, and ∑organochlorine pesticides, and 103 to 104 times more abundant than ∑polychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways. PMID:16675423

  7. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD.

  8. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  9. Hydrocarbon Fuels Optimization

    DTIC Science & Technology

    2007-11-02

    P.A.A 󈧄r𔃺 Masters, "High Density Propellants for Single Stage to Orbit Vehicles," Technical Memorandum, No. NASA/TM X -73503, Lewis Research Center...by interpolation. Optimum Hydrocarbon IP vs. LOX Sea-Level Expansion (14.7 psi, Pc’- 1000 psi) Z X .(299.6 sec) ---- 330 see. 310 see. 0...alkenes all lie along a vertical hne reflective of their common C.H2n molecular. formula. The positions of specific molecules are denoted by an X along with

  10. Identification of an estrogenic hormone receptor in Caenorhabditis elegans

    SciTech Connect

    Mimoto, Ai; Fujii, Madoka; Usami, Makoto; Shimamura, Maki; Hirabayashi, Naoko; Kaneko, Takako; Sasagawa, Noboru; Ishiura, Shoichi

    2007-12-28

    Changes in both behavior and gene expression occur in Caenorhabditis elegans following exposure to sex hormones such as estrogen and progesterone, and to bisphenol A (BPA), an estrogenic endocrine-disrupting compound. However, only one steroid hormone receptor has been identified. Of the 284 known nuclear hormone receptors (NHRs) in C. elegans, we selected nhr-14, nhr-69, and nhr-121 for analysis as potential estrogenic hormone receptors, because they share sequence similarity with the human estrogen receptor. First, the genes were cloned and expressed in Escherichia coli, and then the affinity of each protein for estrogen was determined using a surface plasmon resonance (SPR) biosensor. All three NHRs bound estrogen in a dose-dependent fashion. To evaluate the specificity of the binding, we performed a solution competition assay using an SPR biosensor. According to our results, only NHR-14 was able to interact with estrogen. Therefore, we next examined whether nhr-14 regulates estrogen signaling in vivo. To investigate whether these interactions actually control the response of C. elegans to hormones, we investigated the expression of vitellogenin, an estrogen responsive gene, in an nhr-14 mutant. Semi-quantitative RT-PCR showed that vitellogenin expression was significantly reduced in the mutant. This suggests that NHR-14 is a C. elegans estrogenic hormone receptor and that it controls gene expression in response to estrogen.

  11. Selectively targeting estrogen receptors for cancer treatment

    PubMed Central

    Shanle, Erin K.; Xu, Wei

    2010-01-01

    Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ERα and ERβ, which mediate proliferation and differentiation of cells. For decades, ERα mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most notably with the selective estrogen receptor modulator (SERM) tamoxifen. Selectively targeting ERs occurs at two levels: tissue selectivity and receptor subtype selectivity. SERMs have been developed with emphasis on tissue selectivity to target ER signaling for breast cancer treatment. Additionally, new approaches to selectively target the action of ERα going beyond ligand-dependent activity are under current investigation. As evidence of the anti-proliferative role of ERβ accumulates, selectively targeting ERβ is an attractive approach for designing new cancer therapies with the emphasis shifted to designing ligands with subtype selectivity. This review will present the mechanistic and structural features of ERs that determine tissue and subtype selectivity with an emphasis on current approaches to selectively target ERα and ERβ for cancer treatment. PMID:20708050

  12. Function of Estrogen Receptor Tryosine Phosphorylation

    DTIC Science & Technology

    1999-07-01

    phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor. Proceedings of the National Academy of Sciences of the United States of America... Vivat , V., Chambon, P., Moras, D., and Gronemeyer, H. (1996) Nat. Struct. Biol. 3, 87-94 8. Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L

  13. Estrogen receptor expert system overview and examples

    EPA Science Inventory

    The estrogen receptor expert system (ERES) is a rule-based system developed to prioritize chemicals based upon their potential for binding to the ER. The ERES was initially developed to predict ER affinity of chemicals from two specific EPA chemical inventories, antimicrobial pe...

  14. Characterizing the Estrogenic Potential of 1060 Environmental ...

    EPA Pesticide Factsheets

    In order to detect environmental chemicals that pose a risk of endocrine disruption, high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals are needed. Alteration of estrogen signaling has been implicated in a variety of adverse health effects including cancer promotion, reproductive deficits, and vascular effects. Here we investigate the estrogenic potential of 1060 chemicals of environmental relevance using a real-time measure of growth kinetics by electrode impedance in the estrogen-responsive human ductal carcinoma, T47D cell line. Cells were treated in concentration response and measurements of cellular impedance were recorded every hour for six days. Progestens, androgens, and mineralocortocoids (progesterone, dihydrotestosterone, aldosterone) invoked a biphasic impedance signature that contrasted with the anticipated exponential impedance observed in response to known estrogen receptor agonists (17β-estradiol, genestein, bisphenol-A, nonylphenol, 4-tert-octylphenol). Several compounds, including bisphenol-A, and genestein caused impedance comparable to that of 17β-estradiol, although at much higher concentrations. Additionally, trenbolone and cyproterone acetate invoked the characteristic biphasic signature observed with other endogenous steroid hormones. The continuous real-time nature of this assay allows for the rapid detection of differential growth characteristics not easily detected by traditional cell prol

  15. Function of Estrogen Receptor Tryosine Phosphorylation

    DTIC Science & Technology

    1997-07-01

    localization of the receptors, ligand binding, DNA binding, transcriptional activation, and receptor turnover ( LeGoff et al. 1994; Lahooti et al. 1994...1040-1049 (1995). LeGoff P., M.M. Montano, D.J. Schodin, and B. Katzenellenbogen. Phosphorylation of the Human Estrogen Receptor. J. Biol. Chem

  16. Estrogens and Antiestrogens in Prostate Cancer

    DTIC Science & Technology

    2003-01-01

    vitamin E, and lycopene protect against prostate cancer. The project will determine the magnitude of the protective activity of these antioxidants...in particular estrogen- induced animal model, the efficacies of three dietary antioxidants (vitamin E, selenium and lycopene ), singularly or in

  17. HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS

    EPA Science Inventory

    HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS.

    Robert J. Kavlock, Reproductive Toxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC USA.

    Over the past several decades a hypothesis has been put forth that a numb...

  18. Histopathologic Effects of Estrogens on Marine Fishes

    EPA Science Inventory

    Endocrine-disrupting chemicals (EDCs), such as estrogens estradiol (E2) and ethinylestradiol (EE2) have been reported to affect fish reproduction. This study histologically compared and evaluated effects of EDCs in two species of treated fish. Juvenile male summer flounder (Paral...

  19. In vitro estrogenicity of polybrominated flame retardants.

    PubMed

    Nakari, Tarja; Pessala, Piia

    2005-09-10

    Estrogenicity of five brominated flame retardants (BFRs), namely BDE-47, BDE-99, BDE-205, PBB-153 and technical Firemaster BP-6, were assessed by in vitro assays developed to detect chemicals with estrogenic properties. Recombinant yeast cells containing a human estrogen receptor gene failed to give any response to the chemicals tested. However, the positive control compound, estradiol-17beta, showed that the yeast cell assays had worked properly. The freshly separated fish hepatocyte assay based on the synthesis and secretion of vitellogenin from the isolated liver cells produced a clear dose-response curve in the presence of all tested flame retardants except Firemaster BP-6. The toxicity of the BFRs was detected by determining the cell ethoxyresorufin-O-deethylase activity (EROD). The BFRs tested induced hepatic EROD activity at low test concentrations, but started to inhibit activity at higher concentrations. The decreased detoxification capacity of the hepatocytes resulted in a decrease in the vitellogenin production of the cells. The capability of in vitro assays to detect estrogenic properties of chemicals seems to vary. Thus, further work is needed to understand the mechanisms responsible for these reactions.

  20. Estrogen increases renal oxytocin receptor gene expression.

    PubMed

    Ostrowski, N L; Young, W S; Lolait, S J

    1995-04-01

    Estrogens have been implicated in the sodium and fluid imbalances associated with the menstrual cycle and late pregnancy. An estrogen-dependent role for renal oxytocin receptors in fluid homeostasis is suggested by the present findings which demonstrate that estradiol benzoate treatment increases the expression of the oxytocin receptor messenger ribonucleic acid and 125I-OTA binding to oxytocin receptors in the renal cortex and medullary collecting ducts of ovariectomized female rats. Moreover, estradiol induced high levels of oxytocin receptor expression in outer stripe proximal tubules of ovariectomized female and adrenalectomized male rats. Proximal tubule induction was inhibited in a dose-dependent manner by the antiestrogen tamoxifen, but cortical expression of oxytocin receptors in macula densa cells was unaffected by tamoxifen. These data demonstrate cell-specific regulation of oxytocin receptor expression in macula densa and proximal tubule cells, and suggest a important role for these receptors in mediating estrogen-induced alterations in renal fluid dynamics by possibly affecting glomerular filtration and water and solute reabsorption during high estrogen states.

  1. Breast cancer survivors who use estrogenic botanical supplements have lower serum estrogen levels than non users

    PubMed Central

    Wayne, Sharon J; Neuhouser, Marian L; Koprowski, Carol; Ulrich, Cornelia M; Wiggins, Charles; Gilliland, Frank; Baumgartner, Kathy B; Baumgartner, Richard N; McTiernan, Anne; Bernstein, Leslie; Ballard-Barbash, Rachel

    2014-01-01

    Objective To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors. Methods 502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements. Results Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 v 23.6 pg/mL), estradiol (12.8 v 14.7 pg/mL), free estradiol (0.29 v 0.35 pg/mL), and DHEAS (47.7 v 56.2 ug/dL) compared to women reporting no use. Conclusion Data from this cross-sectional study suggest the use of estrogenic botanical supplements may be associated with sex hormone concentrations in breast cancer survivors. Considering the high use of these supplements among breast cancer patients, further research is needed to clarify the relative estrogenicity/antiestrogenicity of these compounds and their relation with prognosis. PMID:18931907

  2. [Equine estrogens vs. esterified estrogens in the climacteric and menopause. The controversy arrives in Mexico].

    PubMed

    Velasco-Murillo, V

    2001-01-01

    It exists controversies about if the effects and benefits of the esterified estrogens could be similar to those informed for equines, because its chemical composition and bioavailability are different. Esterified estrogens has not delta 8,9 dehydroestrone, and its absorption and level of maximum plasmatic concentrations are reached very fast. In United States of America and another countries, esterified estrogens has been marketed and using for treatment of climacteric syndrome and prevention of postmenopausal osteoporosis, based on the pharmacopoiea of that country, but the Food and Drug administration (FDA) has not yet authorized up today, a generic version of conjugated estrogens. In Instituto Mexicano del Seguro Social (IMSS) and another institutions of health sector in Mexico, starting in year 2000, it has been used esterified estrogens for medical treatment of climacteric and menopausal conditions. For this reason, in this paper we revised the most recent information about pharmacology, chemical composition, clinical use and costs of the conjugated estrogens with the purpose to guide the decisions to purchase this kind of drugs in Mexican heath institutions.

  3. Brain sex matters: estrogen in cognition and Alzheimer's disease.

    PubMed

    Li, Rena; Cui, Jie; Shen, Yong

    2014-05-25

    Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer's disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function.

  4. Estrogen signaling crosstalk: implications for endocrine resistance in ovarian cancer

    PubMed Central

    Ribeiro, Jennifer R.; Freiman, Richard N.

    2014-01-01

    Resistance to anti-estrogen therapies is a prominent challenge in the treatment of ovarian cancer. Tumors develop endocrine resistance by acquiring adaptations that help them rely on alternative oncogenic signaling cascades, which crosstalk with estrogen signaling pathways. An understanding of estrogen signaling crosstalk with these growth promoting cascades is essential in order to maximize efficacy of anti-estrogen treatments in ovarian cancer. Herein, we provide an overview of estrogen signaling in ovarian cancer and discuss the major challenges associated with anti-estrogen therapies. We also review what is currently known about how genomic and non-genomic estrogen signaling pathways crosstalk with several major oncogenic signaling cascades. The insights provided here illustrate existing strategies for targeting endocrine resistant ovarian tumors and may help identify new strategies to improve the treatment of this disease. PMID:24565562

  5. Estrogen receptor-alpha mediates estrogen facilitation of baroreflex heart rate responses in conscious mice.

    PubMed

    Pamidimukkala, Jaya; Xue, Baojian; Newton, Leslie G; Lubahn, Dennis B; Hay, Meredith

    2005-03-01

    Estrogen facilitates baroreflex heart rate responses evoked by intravenous infusion of ANG II and phenylephrine (PE) in ovariectomized female mice. The present study aims to identify the estrogen receptor subtype involved in mediating these effects of estrogen. Baroreflex responses to PE, ANG II, and sodium nitroprusside (SNP) were tested in intact and ovariectomized estrogen receptor-alpha knockout (ERalphaKO) with (OvxE+) or without (OvxE-) estrogen replacement. Wild-type (WT) females homozygous for the ERalpha(+/+) were used as controls. Basal mean arterial pressures (MAP) and heart rates were comparable in all the groups except the ERalphaKO-OvxE+ mice. This group had significantly smaller resting MAP, suggesting an effect of estrogen on resting vascular tone possibly mediated by the ERbeta subtype. Unlike the WT females, estrogen did not facilitate baroreflex heart rate responses to either PE or ANG II in the ERalphaKO-OvxE+ mice. The slope of the line relating baroreflex heart rate decreases with increases in MAP evoked by PE was comparable in ERalphaKO-OvxE- (-6.97 +/- 1.4 beats.min(-1).mmHg(-1)) and ERalphaKO-OvxE+ (-6.18 +/- 1.3) mice. Likewise, the slope of the baroreflex bradycardic responses to ANG II was similar in ERalphaKO-OvxE- (-3.87 +/- 0.5) and ERalphaKO-OvxE+(-2.60 +/- 0.5) females. Data suggest that estrogen facilitation of baroreflex responses to PE and ANG II is predominantly mediated by ERalpha subtype. A second important observation in the present study is that the slope of ANG II-induced baroreflex bradycardia is significantly blunted compared with PE in the intact as well as the ERalphaKO-OvxE+ females. We have previously reported that this ANG II-mediated blunting of cardiac baroreflexes is observed only in WT males and not in ovariectomized WT females independent of their estrogen replacement status. The present data suggest that in females lacking ERalpha, ANG II causes blunting of cardiac baroreflexes similar to males and may be

  6. Volatile Hydrocarbon Pheromones from Beetles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter reviews literature about hydrocarbons from beetles that serve as long-range pheromones. The most thoroughly studied beetles that use volatile hydrocarbon pheromones belong to the family Nitidulidae in the genera Carpophilus and Colopterus. Published pheromone research deals with behav...

  7. Enhanced liquid hydrocarbon recovery process

    SciTech Connect

    Sydansk, R.D.

    1992-07-14

    This patent describes a process for recovering liquid hydrocarbons. It comprises: injecting into a fractured subterranean formation a polymer enhanced foam comprising a polymer selected from a synthetic polymer or a biopolymer, a surfactant, an aqueous solvent and a gas, recovering liquid hydrocarbons from the formation.

  8. Thermophysical Properties of Hydrocarbon Mixtures

    National Institute of Standards and Technology Data Gateway

    SRD 4 NIST Thermophysical Properties of Hydrocarbon Mixtures (PC database for purchase)   Interactive computer program for predicting thermodynamic and transport properties of pure fluids and fluid mixtures containing up to 20 components. The components are selected from a database of 196 components, mostly hydrocarbons.

  9. Hydrocarbon sensors and materials therefor

    DOEpatents

    Pham, Ai Quoc; Glass, Robert S.

    2000-01-01

    An electrochemical hydrocarbon sensor and materials for use in sensors. A suitable proton conducting electrolyte and catalytic materials have been found for specific application in the detection and measurement of non-methane hydrocarbons. The sensor comprises a proton conducting electrolyte sandwiched between two electrodes. At least one of the electrodes is covered with a hydrocarbon decomposition catalyst. Two different modes of operation for the hydrocarbon sensors can be used: equilibrium versus non-equilibrium measurements and differential catalytic. The sensor has particular application for on-board monitoring of automobile exhaust gases to evaluate the performance of catalytic converters. In addition, the sensor can be utilized in monitoring any process where hydrocarbons are exhausted, for instance, industrial power plants. The sensor is low cost, rugged, sensitive, simple to fabricate, miniature, and does not suffer cross sensitivities.

  10. Rapid signaling mechanisms of estrogens in the developing cerebellum.

    PubMed

    Belcher, Scott M

    2008-03-01

    The steroid hormone 17beta-estradiol regulates the normal function and development of the mammalian nervous system. Many of estradiol's effects are mediated via the nuclear hormone estrogen receptors ERalpha and ERbeta. In addition to regulating estrogen-responsive gene expression, estradiol also acts in an immediate and cell-specific fashion to regulate various intracellular signal transduction pathways. The goal of this review is to develop a contextual framework to understand the generalized function of estrogen during development of brain regions not known to be sexually specialized. However, it is first important to build this framework on the more well-developed foundation of estrogen's gonad-driven sex-specific actions. As a result, a discussion of known and proposed mechanisms of estrogen actions in reproductive and other tissues will be presented. Building upon this information, a review of our research group's recent in vitro and in vivo studies that have focused on elucidating the mechanisms of estrogen actions in neurons of the non-sexually specialized cerebellum will be presented. While the full spectrum of estrogen action during normal cerebellar development remains unresolved, results of recent studies have revealed a pathologic role for estrogen and estrogen receptors in medulloblastoma, common pediatric brain tumors that arise from cerebellar granule cell-like precursors. The potential use of anti-estrogen signaling agents as adjuvant therapy for medulloblastoma is proposed based on those finding.

  11. Estrogen Deficiency and the Origin of Obesity during Menopause

    PubMed Central

    Lizcano, Fernando; Guzmán, Guillermo

    2014-01-01

    Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the importance of estrogens in the development of metabolic diseases during menopause is disputed. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances of this metabolic signal lead to the development of metabolic syndrome and a higher cardiovascular risk in women. The absence of estrogens is a clue factor in the onset of cardiovascular disease during the menopausal period, which is characterized by lipid profile variations and predominant abdominal fat accumulation. However, influence of the absence of these hormones and its relationship to higher obesity in women during menopause are not clear. This systematic review discusses of the role of estrogens and estrogen receptors in adipocyte differentiation, and its control by the central nervous systemn and the possible role of estrogen-like compounds and endocrine disruptors chemicals are discussed. Finally, the interaction between the decrease in estrogen secretion and the prevalence of obesity in menopausal women is examined. We will consider if the absence of estrogens have a significant effect of obesity in menopausal women. PMID:24734243

  12. The Interplay between Estrogen and Fetal Adrenal Cortex

    PubMed Central

    Kaludjerovic, Jovana; Ward, Wendy E.

    2012-01-01

    Estrogen is a steroid hormone that regulates embryogenesis, cell proliferation and differentiation, organogenesis, the timing of parturition, and fetal imprinting by carrying chemical messages from glands to cells within tissues or organs in the body. During development, placenta is the primary source of estrogen production but estrogen can only be produced if the fetus or the mother supplies dehydroepiandrosterone (DHEA), the estrogen prohormone. Studies show that the fetal zone of the fetal adrenal cortex supplies 60% of DHEA for placental estrogen production, and that placental estrogen in turn modulates the morphological and functional development of the fetal adrenal cortex. As such, in developed countries where humans are exposed daily to environmental estrogens, there is concern that the development of fetal adrenal cortex, and in turn, placental estrogen production may be disrupted. This paper discusses fetal adrenal gland development, how endogenous estrogen regulates the structure and function of the fetal adrenal cortex, and highlights the potential role that early life exposure to environmental estrogens may have on the development and endocrinology of the fetal adrenal cortex. PMID:22536492

  13. Extra-gonadal sites of estrogen biosynthesis and function

    PubMed Central

    Barakat, Radwa; Oakley, Oliver; Kim, Heehyen; Jin, Jooyoung; Ko, CheMyong Jay

    2016-01-01

    Estrogens are the key hormones regulating the development and function of reproductive organs in all vertebrates. Recent evidence indicates that estrogens play important roles in the immune system, cancer development, and other critical biological processes related to human well-being. Obviously, the gonads (ovary and testis) are the primary sites of estrogen synthesis, but estrogens synthesized in extra- gonadal sites play an equally important role in controlling biological activities. Understanding non-gonadal sites of estrogen synthesis and function is crucial and will lead to therapeutic interventions targeting estrogen signaling in disease prevention and treatment. Developing a rationale targeting strategy remains challenging because knowledge of extra-gonadal biosynthesis of estrogens, and the mechanism by which estrogen activity is exerted, is very limited. In this review, we will summarize recent discoveries of extra-gonadal sites of estrogen biosynthesis and their local functions and discuss the significance of the most recent novel discovery of intestinal estrogen biosynthesis. [BMB Reports 2016; 49(9): 488-496] PMID:27530684

  14. Estrogen modulates cognitive and cholinergic processes in surgically menopausal monkeys.

    PubMed

    Tinkler, Gregory Paul; Voytko, Mary Lou

    2005-03-01

    Estrogen deficiency in postmenopausal women is associated with changes in physiological processes. The extent to which estrogen loss is associated with cognitive changes noted by postmenopausal women has been more difficult to determine for a variety of reasons. Primate models of menopause are now being used to determine the effects of estrogen loss and replacement on cognitive abilities and to investigate the neural mechanisms by which estrogen may influence cognitive function. The present report presents data from cognitive and neurobiological studies in surgically menopausal monkeys that have examined how estrogen loss and replacement may be affecting cognitive abilities and the cholinergic system; a neural system that is known to influence memory and attention function. These studies are indicating that visuospatial attention function is especially sensitive to estrogen states in young monkeys, but that multiple cognitive domains are sensitive to estrogen states in middle-aged monkeys. In addition, anatomical and functional imaging studies indicate that the primate cholinergic system is modulated by estrogen, and pharmacological studies demonstrate that estrogen uses cholinergic muscarinic receptors to influence visuospatial attention. These studies demonstrate that estrogen influences cognitive abilities in monkey models of menopause and the cholinergic system may be one of the mechanisms by which estrogen modulates cognitive function. Given the current unknowns and concerns regarding the use of hormone replacement therapy in postmenopausal women, continued studies in monkey models of menopause are especially needed to further elucidate the effects of estrogen on cognitive and neurobiological processes, with particular emphasis on studies in middle-aged monkeys, determining the optimal aspects of ERT regimens, and identifying the relationships between estrogen effects on cognitive and neurobiological function.

  15. Estrogen therapy in gynecological cancer survivors.

    PubMed

    Guidozzi, F

    2013-12-01

    Treatment of gynecological cancer has significant impact on a woman's quality of life because it commonly includes removal of the uterus and ovaries, both being the core of a woman's femininity, whilst irradiation and chemotherapy, be they as primary therapy or when indicated as postoperative adjuvant therapy, will lead to ablation of ovarian function if the ovaries had not been removed. This will lead to an acute onset of menopausal symptoms, which may be more debilitating than those occurring as a result of natural aging, and of which hot flushes, night sweats, insomnia, mood swings, vaginal dryness, decreased libido, malaise and a general feeling of apathy are the most common. About 25% of gynecological cancers will occur in pre- and perimenopausal women, a large percentage of whom will become menopausal as a result of their treatment. There are also the gynecological cancer survivors who are not rendered menopausal as a result of the treatment strategy but who will become menopausal because of natural aging. Concern among the medical attendants of these women is whether use of estrogen therapy or estrogen and progestogens for their menopausal symptoms will reactivate tumor deposits and therefore increase the rate of recurrence and, as a result, decrease overall survival among these women. Yet the data that are available do not support this concern. There are eight retrospective studies and only one randomized study that have analyzed outcome in endometrial cancer survivors who used hormone therapy after their surgery, whilst, among ovarian cancer survivors, there are four retrospective studies and one randomized study. The studies do suffer from small numbers and, although the studies pertaining to endometrial cancer analyze mostly women with early-stage disease, a number of the studies in both the endometrial and ovarian cancer survivors do have a sizeable follow-up. These studies seem to support that estrogen therapy after the treatment for gynecological

  16. Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels.

    PubMed

    Coussens, C M; Kerr, D S; Abraham, W C

    1997-07-01

    The effects of the glucocorticoid receptor agonist RU-28362 on homosynaptic long-term depression (LTD) were examined in hippocampal slices obtained from adrenal-intact adult male rats. Field excitatory postsynaptic potentials were evoked by stimulation of the Schaffer collateral/commissural pathway and recorded in stratum radiatum of area CA1. Low-frequency stimulation (LFS) was delivered at LTD threshold (2 bouts of 600 pulses, 1 Hz, at baseline stimulation intensity). LFS of the Schaffer collaterals did not produce significant homosynaptic LTD in control slices. However, identical conditioning in the presence of the glucocorticoid receptor agonist RU-28362 (10 microM) produced a robust LTD, which was blocked by the selective glucocorticoid antagonist RU-38486. The LTD induced by glucocorticoid receptor activation was dependent on N-methyl-D-aspartate (NMDA) receptor activity, because the specific NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) blocked the facilitation. However, the facilitation of LTD was not due to a potentiation of the isolated NMDA receptor potential by RU-28362. The facilitation of LTD by RU-28362 was also blocked by coincubation of the L-type voltage-dependent calcium channel (VDCC) antagonist nimodipine. Selective activation of the L-type VDCCs by the agonist Bay K 8644 also facilitated LTD induction. Both nimodipine and D-AP5 were effective in blocking the facilitation of LTD by Bay K 8644. These results indicate that L-type VDCCs can contribute to NMDA-receptor-dependent LTD induction.

  17. Endothelin-1 induces proliferation of human lung fibroblasts and IL-11 secretion through an ET(A) receptor-dependent activation of MAP kinases.

    PubMed

    Gallelli, Luca; Pelaia, Girolamo; D'Agostino, Bruno; Cuda, Giovanni; Vatrella, Alessandro; Fratto, Donatella; Gioffrè, Vincenza; Galderisi, Umberto; De Nardo, Marilisa; Mastruzzo, Claudio; Salinaro, Elisa Trovato; Maniscalco, Mauro; Sofia, Matteo; Crimi, Nunzio; Rossi, Francesco; Caputi, Mario; Costanzo, Francesco S; Maselli, Rosario; Marsico, Serafino A; Vancheri, Carlo

    2005-11-01

    Endothelin-1 (ET-1) is implicated in the fibrotic responses characterizing interstitial lung diseases, as well as in the airway remodeling process occurring in asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal human lung fibroblasts (NHLFs), the ET-1 receptor subtypes, and the intracellular signal transduction pathways involved in the proliferative effects of this peptide. Therefore, cells were exposed to ET-1 in the presence or absence of an overnight pre-treatment with either ET(A) or ET(B) selective receptor antagonists. After cell lysis, immunoblotting was performed using monoclonal antibodies against the phosphorylated, active forms of mitogen-activated protein kinases (MAPK). ET-1 induced a significant increase in MAPK phosphorylation pattern, and also stimulated fibroblast proliferation and IL-6/IL-11 release into cell culture supernatants. All these effects were inhibited by the selective ET(A) antagonist BQ-123, but not by the specific ET(B) antagonist BQ-788. The stimulatory influence of ET-1 on IL-11, but not on IL-6 secretion, was prevented by MAPK inhibitors. Therefore, such results suggest that in human lung fibroblasts ET-1 exerts a profibrogenic action via an ET(A) receptor-dependent, MAPK-mediated induction of IL-11 release and cell proliferation.

  18. EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathway.

    PubMed

    Li, Ko-Jen; Siao, Sue-Cien; Wu, Cheng-Han; Shen, Chieh-Yu; Wu, Tsai-Hung; Tsai, Chang-Youh; Hsieh, Song-Chou; Yu, Chia-Li

    2014-01-21

    Our previous studies showed that urinary Tamm-Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase.

  19. Catalytic cracking of hydrocarbons

    SciTech Connect

    Absil, R.P.L.; Bowes, E.; Green, G.J.; Marler, D.O.; Shihabi, D.S.; Socha, R.F.

    1992-02-04

    This patent describes an improvement in a catalytic cracking process in which a hydrocarbon feed is cracked in a cracking zone in the absence of added hydrogen and in the presence of a circulating inventory of solid acidic cracking a catalyst which acquires a deposit of coke that contains chemically bound nitrogen while the cracking catalyst is in the cracking zone, the coke catalyst being circulated to t regeneration zone to convert the coke catalyst to a regenerated catalyst with the formation of a flue gas comprising nitrogen oxides: the improvement comprises incorporating into the circulating catalyst inventory an amount of additive particles comprising a synthetic porous crystalline material containing copper metal or cations, to reduce the content of nitrogen oxides in the flue gas.

  20. Carbon neutral hydrocarbons.

    PubMed

    Zeman, Frank S; Keith, David W

    2008-11-13

    Reducing greenhouse gas emissions from the transportation sector may be the most difficult aspect of climate change mitigation. We suggest that carbon neutral hydrocarbons (CNHCs) offer an alternative pathway for deep emission cuts that complement the use of decarbonized energy carriers. Such fuels are synthesized from atmospheric carbon dioxide (CO2) and carbon neutral hydrogen. The result is a liquid fuel compatible with the existing transportation infrastructure and therefore capable of a gradual deployment with minimum supply disruption. Capturing the atmospheric CO2 can be accomplished using biomass or industrial methods referred to as air capture. The viability of biomass fuels is strongly dependent on the environmental impacts of biomass production. Strong constraints on land use may favour the use of air capture. We conclude that CNHCs may be a viable alternative to hydrogen or conventional biofuels and warrant a comparable level of research effort and support.

  1. Process for recovering hydrocarbons from a hydrocarbon-bearing formation

    SciTech Connect

    Alston, R.B.; Braden, W.B.; Flournoy, K.H.

    1980-03-11

    A method is described for transporting heavy crude oil through a pipeline which involves introducing into a pipeline or well-bore with the viscous hydrocarbons an aqueous solution containing (1) a sulfonate surfactant, (2) a rosin soap or a naphthenic acid soap and, optionally (3) coupling agent whereby there is spontaneously formed a low viscosity, salt tolerant, oil-in-water emulsion. Also disclosed is a method of recovery of hydrocarbons from a hydrocarbon bearing formation employing an aqueous solution containing (1) a sulfonate surfactant, (2) a rosin soap or a naphthenic acid soap and, optionally (3) a coupling agent.

  2. Estrogen Accelerates Cell Proliferation through Estrogen Receptor α during Rat Liver Regeneration after Partial Hepatectomy

    PubMed Central

    Batmunkh, Baatarsuren; Choijookhuu, Narantsog; Srisowanna, Naparee; Byambatsogt, Uugantsetseg; Synn Oo, Phyu; Noor Ali, Mohmand; Yamaguchi, Yuya; Hishikawa, Yoshitaka

    2017-01-01

    Although estrogen is implicated in the regulation of cell growth and differentiation in many organs, the exact mechanism for liver regeneration is not completely understood. We investigated the effect of estrogen on liver regeneration in male and female Wistar rats after 70% partial hepatectomy (PHx) and performed immunohistochemistry, western blotting and Southwestern histochemistry. 17β-estradiol (E2) and ICI 182,780 were injected into male rats on the day before PHx. The proliferating cell nuclear antigen (PCNA) labeling index reached a maximum at 48 hr after PHx in males, and at 36 hr in females and E2-treated male rats. Estrogen receptor α (ERα) was expressed in zones 1 and 2 in male rats, but was found in all zones in female rats. Interestingly, ERα was not detected at 6–12 hr after PHx but was found at 24–168 hr in male rats. However, ERα expression was found at all sampling time-points in female and E2-treated male rats. The activity of estrogen responsive element binding proteins was detected from 12 hr after PHx in male rats but was found from 6 hr in female and E2-treated male rats. ERα was co-expressed with PCNA during liver regeneration. These results indicate that estrogen may play an important role in liver regeneration through ERα. PMID:28386149

  3. Construction of a Bacterial Assay for Estrogen Detection Based on an Estrogen-Sensitive Intein ▿ †

    PubMed Central

    Liang, Rubing; Zhou, Jing; Liu, Jianhua

    2011-01-01

    Escherichia coli strain DIER was constructed for estrogen detection by inserting an estrogen-sensitive intein (VMAER intein) into the specific site of the constitutively expressed chromosomal lacZ gene. This VMAER intein was generated by replacing the endonuclease region of the Saccharomyces cerevisiae VMA intein with the estrogen binding region of the human estrogen receptor α (hERα). When there were estrogens or analogs, the splicing of the VMAER intein was induced to produce the mature LacZ protein, which was detected through a β-galactosidase colorimetric assay. Eight typical chemicals (17-β-estradiol, bisphenol A, chrysene, 6-OH-chrysene, benz[a]anthracene, pyrene, progesterone, and testosterone) were detected using this DIER strain, and the whole detection procedure was accomplished in 2 h. Their 50% effective concentrations (EC50), relative estrogenic activities, and estradiol equivalency factors were calculated and were quite consistent with those detected with the yeast estrogen screening (YES) system. Furthermore, the estrogenic activities of the synthetic musk samples extracted from the wastewater and waste sludge of a sewage treatment plant of Shanghai (China) were detected, and their results were comparable to those obtained from the YES system and gas chromatography-mass spectrometry (GC-MS). In conclusion, the DIER bioassay could fill a niche for the efficient, rapid, high-throughput screening of estrogenic compounds and has potential for the remote, near-real-time monitoring of environmental estrogens. PMID:21317264

  4. Delay in post-ovariectomy estrogen replacement negates estrogen-induced augmentation of post-exercise muscle satellite cell proliferation.

    PubMed

    Mangan, Gary; Iqbal, Sobia; Hubbard, Andrew; Hamilton, Victoria; Bombardier, Eric; Tiidus, Peter M

    2015-11-01

    This study examined the effects of a delay in post-ovariectomy replacement of 17β-estradiol (estrogen) on the post-exercise proliferation of muscle satellite cells. Nine-week-old, ovariectomized, female Sprague-Dawley rats (n = 64) were distributed among 8 groups based on estrogen status (0.25 mg estrogen pellet or sham), exercise status (90 min run at 17 m·min(-1) and a grade of -13.5° or unexercised), and estrogen replacement ("proximal", estrogen replacement within 2 weeks; or "delayed", estrogen replacement at 11 weeks following ovariectomy). Significant increases in satellite cells were found in the soleus and white gastrocnemius muscle (immunofluorescent colocalization of nuclei with Pax7) 72 h following eccentric exercise (p < 0.05) in all exercised groups. Proximal E2 replacement resulted in a further augmentation of muscle satellite cells in exercised rats (p < 0.05) relative to the delayed estrogen replacement group. Expression of PI3K was unaltered and phosphorylation of Akt relative to total Akt increased following estrogen supplementation and exercise. Exercise alone did not alter the expression levels of Akt. An 11 week delay in post-ovariectomy estrogen replacement negated the augmenting influence seen with proximal (2 week delay) post-ovariectomy estrogen replacement on post-exercise muscle satellite cell proliferation. This effect appears to be independent of the PI3K-Akt signaling pathway.

  5. Sensing Estrogen with Electrochemical Impedance Spectroscopy

    PubMed Central

    Li, Jing; Kim, Byung Kun; Im, Ji-Eun; Choi, Han Nim; Kim, Dong-Hwan; Cho, Seong In

    2016-01-01

    This study demonstrates the application feasibility of electrochemical impedance spectroscopy (EIS) in measuring estrogen (17β-estradiol) in gas phase. The present biosensor gives a linear response (R2 = 0.999) for 17β-estradiol vapor concentration from 3.7 ng/L to 3.7 × 10−4 ng/L with a limit of detection (3.7 × 10−4 ng/L). The results show that the fabricated biosensor demonstrates better detection limit of 17β-estradiol in gas phase than the previous report with GC-MS method. This estrogen biosensor has many potential applications for on-site detection of a variety of endocrine disrupting compounds (EDCs) in the gas phase. PMID:27803838

  6. Estrogen binding by leukocytes during phagocytosis,

    PubMed Central

    1977-01-01

    Estradiol binds covalently to normal leukocytes during phagocytosis. The binding involves three cell types, neutrophils, eosinophils, and monocytes and at least two reaction mechanisms, one involving the peroxidase of neutrophils and monocytes (myeloperoxidase [MPO]) and possibly the eosinophil peroxidase, and the second involving catalase. Binding is markedly reduced when leukocytes from patients with chronic granulomatous disease (CGD), severe leukocytic glucose 6-phosphate dehydrogenase deficiency, and familial lipochrome histiocytosis are employed and two populations of neutrophils, one which binds estradiol and one which does not, can be demonstrated in the blood of a CGD carrier. Leukocytes from patients with hereditary MPO deficiency also bind estradiol poorly although the defect is not as severe as in CGD. These findings are discussed in relation to the inactivation of estrogens during infection and the possible role of estrogens in neutrophil function. PMID:858996

  7. Estrogens as Antioxidant Modulators in Human Fertility

    PubMed Central

    Mancini, A.; Raimondo, S.; Persano, M.; Di Segni, C.; Cammarano, M.; Gadotti, G.; Silvestrini, A.; Pontecorvi, A.; Meucci, E.

    2013-01-01

    Among treatments proposed for idiopathic male infertility, antiestrogens, like tamoxifen, play a possible role. On the other hand, oxidative stress is a mechanism well recognized for deleterious effects on spermatozoa function. After reviewing the literature on the effects of estrogens in modulation of antioxidant systems, in both sexes, and in different in vivo and in vitro models, we suggest, also on the basis of personal data, that a tamoxifen treatment could be active via an increase in seminal antioxidants. PMID:24363671

  8. Immunosuppression Following Exposure to Exogenous Estrogens

    DTIC Science & Technology

    1983-08-01

    by severe depletion of cortical lymphocytes in DES or estradiol treated mice. Tnterestingly, this atrophy is histologically reversible since a normal...al., 1982). 91 ?Pf TABLE 1. THYMIC ATROPHY AND PROLIFERATIVE RESPONSES OF SPLENIC LYMPHOCYTES IN HORMONE TREATED MICE TREATMENTa THYMIC ATROPHY 3 H...1980). As summarized in Table 3, administration of either Tamoxiphen or Nafox- idine had a significant effect on estrogen-induced thymic atrophy . However

  9. Local Effects of Vaginally Administered Estrogen Therapy: A Review

    PubMed Central

    Krause, Megan; Wheeler, Thomas L.; Snyder, Thomas E.; Richter, Holly E.

    2011-01-01

    The results of the Women’s Health Initiative (WHI) led to a distinct decline in the routine use of estrogen as preventive therapy for vasomotor symptoms, osteoporosis, and cardiovascular disease in postmenopausal women. Without estrogen replacement, one third of women experience symptoms of atrophic vaginitis including dryness, irritation, itching and or dyspareunia. Local application of estrogen has been shown to relieve these symptoms and improve quality of life for these women. In addition, local estrogen therapy may have a favorable effect on sexuality, urinary tract infections, vaginal surgery, and incontinence. This review examines the effects of vaginally applied estrogen on the vaginal epithelium, urethra and endometrium. An accompanying review examines the systemic effects of vaginally applied estrogen. PMID:22229022

  10. Brain estrogen production and the encoding of recent experience

    PubMed Central

    Vahaba, Daniel M.; Remage-Healey, Luke

    2015-01-01

    The vertebrate central nervous system integrates cognition and behavior, and it also acts as both a source and target for steroid hormones like estrogens. Recent exploration of brain estrogen production in the context of learning and memory has revealed several common themes. First, across vertebrates, the enzyme that synthesizes estrogens is expressed in brain regions that are characterized by elevated neural plasticity and is also integral to the acquisition, consolidation, and retrieval of recent experiences. Second, measurement and manipulation of estrogens reveal that the period following recent sensory experience is linked to estrogenic signaling in brain circuits underlying both spatial and vocal learning. Local brain estrogen production within cognitive circuits may therefore be important for the acquisition and/or consolidation of memories, and new directions testing these ideas will be discussed. PMID:27453921

  11. Estrogenic activity of isoflavonoids from Onobrychis ebenoides.

    PubMed

    Halabalaki, Maria; Alexi, Xanthippi; Aligiannis, Nektarios; Lambrinidis, George; Pratsinis, Harris; Florentin, Ida; Mitakou, Sofia; Mikros, Emmanuel; Skaltsounis, Alexios-Leandros; Alexis, Michael N

    2006-05-01

    Fractionation of the neutral extract of Onobrychis ebenoides (Leguminosae) yielded a new isoflavone, named ebenosin (1), in addition to the known ones, afrormosin (2), formononetin (3) and daidzein (4). Although the relative binding affinities of 1 - 4 for estrogen receptor alpha (ERalpha) were nearly comparable and matched those of 1-3 for ERbeta, that of 4 for the latter receptor was significantly higher than any of the other. Compounds 1 - 4 induced cell proliferation and gene expression in breast and endometrial cancer cells in an ER-dependent manner. Nonetheless, the rank order of induction potencies ( 4 > 3 >or= 2 >or= 1) matched better that of affinities for ERbeta ( 4 > 3 >or= 2 >or= 1) rather than ERalpha ( 4 >or= 3 >or= 2 >or= 1). While the antiestrogen ICI 182,780 could inhibit the induction of proliferation of ER-positive breast cancer cells by 1-4, it could not prevent 1 from exhibiting significant ER-independent cytotoxicity at 10 microM. By contrast, 1 was much less cytotoxic and only weakly estrogenic for ER-positive endometrial adenocarcinoma cells. In conclusion, our data suggest that the C-8 isoprenyl substituent of 1 renders it cytotoxic and/or estrogenic in a cell-dependent manner.

  12. Estrogens sensitize anterior pituitary gland to apoptosis.

    PubMed

    Pisera, D; Candolfi, M; Navarra, S; Ferraris, J; Zaldivar, V; Jaita, G; Castro, M G; Seilicovich, A

    2004-10-01

    Tissue homeostasis results from a balance between cell proliferation and cell death by apoptosis. Estradiol affects proliferation as well as apoptosis in hormone-dependent tissues. In the present study, we investigated the apoptotic response of the anterior pituitary gland to lipopolysaccharide (LPS) in cycling female rats, and the influence of estradiol in this response in ovariectomized (OVX) rats. The OVX rats were chronically estrogenized with implanted Silastic capsules containing 1 mg of 17beta-estradiol (E2). Cycling or OVX and E2-treated rats were injected with LPS (250 microg/rat ip). Apoptosis was determined by the terminal deoxynucleotidyl-mediated dUTP nick-end labeling (TUNEL) method in sections of the anterior pituitary gland and spleen. Chronic estrogenization induced apoptosis in the anterior pituitary gland. Acute endotoxemia triggered apoptosis of cells in the anterior pituitary gland of E2-treated rats but not of OVX rats. No differences were observed in the apoptotic response to LPS in spleen between OVX and E2-treated rats. The apoptotic response of the anterior pituitary to LPS was variable along the estrous cycle, being higher at proestrus than at estrus or diestrus I. Approximately 75% of the apoptotic cells were identified as lactotropes by immunofluorescence. In conclusion, our results indicate that estradiol induces apoptosis and enables the proapoptotic action of LPS in the anterior pituitary gland. Also, our study suggests that estrogens may be involved in anterior pituitary cell renewal during the estrous cycle, sensitizing lactotropes to proapoptotic stimuli.

  13. Estrogen Regulation of Apoptosis in Osteoblasts

    PubMed Central

    Bradford, Peter G; Gerace, Ken V; Roland, Renée L; Chrzan, Brian G

    2010-01-01

    Dysregulated apoptosis is a critical failure associated with prominent degenerative diseases including osteoporosis. In bone, estrogen deficiency has been associated with accelerated osteoblast apoptosis and susceptibility to osteoporotic fractures. Hormone therapy continues to be an effective option for preventing osteoporosis and bone fractures. Induction of apoptosis in G-292 human osteoblastic cells by exposure to etoposide or the inflammatory cytokine TNFα promoted acute caspase-3/7 activity and this increased activity was inhibited by pretreatment with estradiol. Etoposide also increased the expression of a battery of apoptosis-promoting genes and this expression was also inhibited by estradiol. Among the apoptotic genes whose expression was inhibited by estradiol was ITPR1, which encodes the type 1 InsP3R. InsP3Rs are intracellular calcium channels and key proapoptotic mediators. Estradiol via estrogen receptor β1 suppresses ITPR1 gene transcription in G-292 cells. These analyses suggest that an underlying basis of the beneficial activity of estrogens in combating osteoporosis may involve the prevention of apoptosis in osteoblasts and that a key event in this process is the repression of apoptotic gene expression and inhibition of caspase-3/7. PMID:19426747

  14. Characterizing the Growth Kinetics in Estrogen Responsive ...

    EPA Pesticide Factsheets

    There is a need to develop high-throughput screening (HTS) tests capable of testing thousands of environmental chemicals for endocrine disrupting potential. The estrogen signaling pathway is a known xenobiotic target that has been implicated in a variety of adverse health effects including reproductive deficits and cancer promotion. Using real-time measurements of growth kinetics by electrode impedance, the estrogen-responsive human ductal carcinoma cell line, T47D, was treated with 2000 chemicals of environmental relevance. Cells were treated in concentration response and measurements of cellular impedance were recorded every hour for six days. Exponential impedance, signifying increased proliferation, was observed by prototypical estrogen receptor agonists (17β-estradiol, genestein, bisphenol-A, nonylphenol, 4-tert-octylphenol). Several compounds, including bisphenol-A and genestein, induced cell proliferation at comparable levels to 17β-estradiol, although at much higher concentrations. Progestins, and mineralocortocoids (progesterone, dihydrotestosterone, aldosterone) invoked a biphasic impedance signature. In conclusion, the real-time nature of this assay allows for rapid detection of differential growth characteristics shows potential, in combination with other ToxCast HTS assays, to detect environmental chemicals with potential endocrine activity. [This abstract does not necessarily reflect Agency policy]. Several compounds, including bisphenol-A and

  15. Radiobrominated triphenylethylenes as estrogen receptor binding radiopharmaceuticals

    SciTech Connect

    Seevers, R.H.; Meese, R.C.; Friedman, A.M.; DeSombre, E.R.

    1985-05-01

    Estrogen receptor binding radiopharmaceuticals have potential for use in the diagnosis and treatment of cancers of the female reproductive system. Tamoxifen is an antiestrogen derived from the triphenylethylene skeleton which is used in the treatment of mammary carcinoma. Hydroxytamoxifen is a metabolite of tamoxifen which binds tightly to the estrogen receptor. Two triphenylethylene derivatives based on the structure of hydroxytamoxifen have been prepared: 1-bromo-1-phenyl-2- (2-dimethylamino)-4-ethoxyphenyl -2-(4-hydroxyphenyl) ethene (1) where the ethyl group of hydroxytamoxifen has been replaced by a bromine, and 1-bromo-1-phenyl-2,2-(4-hydroxyphenyl) ethene (2) with a similar substitution and also lacking the aminoethoxy side chain believed to confer antiestrogenicity. Both 1 and 2 bind strongly to the estrogen receptor. 2 has been labeled with the Auger electron emitting nuclide Br-80m in moderate yields in high specific activity using either N-bromosuccinimide or N-bromophthalimide and shows promise as a potential radiotherapy agent.

  16. Steroid binding domain of porcine estrogen receptor

    SciTech Connect

    Koike, S.; Nii, A.; Sakai, M.; Muramatsu, M.

    1987-05-05

    For the purpose of characterizing the estrogen binding domain of porcine estrogen receptor (ER), the authors have made use of affinity labeling of partially purified ER with (/sup 3/H)tamoxifen aziridine. The labeling is very efficient and selective particularly after partial purification of ER. A 65,000-dalton (65-kDa) band was detected on the fluorogram of a sodium dodecyl sulfate-polyacrylamide gel, together with a 50-kDa band and a few more smaller bands. The 50-kDa protein appears to be a degradation product of the 65-kDa protein in view of the similar peptide map. ER was affinity labeled before or after controlled limited proteolysis with either trypsin, papain, or ..cap alpha..-chymotrypsin. The labeling patterns of limited digests indicate that a fragment of about 30 kDa is relatively resistant to proteases and has a full and specific binding activity to estrogen, whereas smaller fragments have lost much of the binding activity. This fragment is very hydrophobic and probably corresponds to the carboxy half of ER.

  17. The role of estrogen in intrusive memories.

    PubMed

    Cheung, Jessica; Chervonsky, Liza; Felmingham, Kim L; Bryant, Richard A

    2013-11-01

    Intrusive memories are highly vivid, emotional and involuntary recollections which cause significant distress across psychological disorders including posttraumatic disorder (PTSD). Recent evidence has potentially extended our understanding of the development of intrusive memories by identifying biological factors which significantly impact on memories for emotionally arousing stimuli. This study investigated the role of stress on the development of intrusions for negative and neutral images, and indexed the potential contributions of sex (estrogen and progesterone) and stress (noradrenaline and cortisol) hormones. Whilst viewing the images, half the participants underwent a cold pressor stress (CPS) procedure to induce stress while the control participants immersed their hands in warm water. Saliva samples were collected to index estrogen, progesterone and noradrenergic and cortisol response. Participants (55 university students, 26 men, 29 women) viewed a series of negatively arousing and neutral images. Participants completed recall and intrusions measures 2 days later. Negative images resulted in greater recall and more intrusions than neutral images. In the cold water condition females recalled fewer neutral memories than males. Cortisol increase predicted decreased recall of negative memories in males, and estrogen predicted increased intrusions of negative images in women. These findings are consistent with evidence that circulating levels of ovarian hormones influence memory for emotionally arousing events, and provides the first evidence of the influence of sex hormones on intrusive memories. These results provide one possible explanation for the higher incidence of anxiety disorders in women.

  18. Cell Cycle Regulation of Estrogen and Androgen Receptor

    DTIC Science & Technology

    2002-07-01

    Estrogen and Androgen Receptor PRINCIPAL INVESTIGATOR: Elisabeth D. Martinez CONTRACTING ORGANIZATION: Georgetown University Medical Center...Cycle Regulation of Estrogen and Androgen DAMD17-99-1-9199 Receptor 6. AUTHOR(S) Elisabeth D. Martinez 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...with androgens. 14. SUBJECT TERMS 15. NUMBER OF PAGES breast cancer, cell cycle, androgen receptor, estrogen receptor, non- 66 steroidal activators, L

  19. Cell Cycle Regulation of Estrogen and Androgen Receptor

    DTIC Science & Technology

    2001-07-01

    EC50 . "* It has been established that the estrogen receptor shows highest activity when the cells are treated by serum starvation and are mainly in GO...of Estrogen and Androgen Receptor PRINCIPAL INVESTIGATOR: Elisabeth D. Martinez CONTRACTING ORGANIZATION: Georgetown University Medical Center... Estrogen and Androgen Receptor DAMD 17-99-1- 9199 6. AUTHOR(S) Elisabeth D. Martinez 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING

  20. Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

    PubMed Central

    Woolfrey, Kevin M.; Penzes, Peter

    2013-01-01

    Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits

  1. Estrogen Receptor Alpha G525L Knock-In Mice

    DTIC Science & Technology

    2007-03-01

    response to endogenous estrogens. These female estrogen non-responsive ERα knock-in (ENERKI) mice had immature and hypoplastic uterine and vaginal ...developing mice as well as in adult animals with genetically induced mammary cancers through PPT administration or withdrawal. 15. SUBJECT TERMS estrogen...is a crucial therapeutic target for hormone dependent breast cancers . More effective treatment and prevention strategies are likely to emerge from

  2. Estrogens and Prostate Cancer: Etiology, Mediators, Prevention, and Management

    PubMed Central

    Ho, Shuk-Mei; Lee, Ming-tsung; Lam, Hung-Ming; Leung, Yuet-Kin

    2011-01-01

    The relationship between hormones and the pathogenesis of prostate cancer (PCa) has been studied extensively. All the mainstay targets for hormonal PCa therapies are based on negating androgen action. Recent epidemiologic and experimental data have clearly pinpointed the key roles of estrogens in PCa development and progression. Racial and geographical differences, as well as age-associated changes, in estrogen synthesis and metabolism contribute significantly to the etiology by increasing the ratio of circulating estrogen to androgen, sex hormone binding globulin synthesis, and aromatase activity and reducing androgen glucuronidation and tissue bioactivation. Promotion of aberrant cell growth, evasion of apoptosis, increased oxidative stress and inflammation, and gains in adiposity and bioactivation to genotoxic carcinogens during adulthood are probable mechanisms of estrogen carcinogenicity, while “estrogen imprinting” via epigenetics in early-life also determines PCa risk. Although the effects of estrogens are known to be mediated by genomic actions of the two estrogen receptor (ER) subtypes (ERα and ERβ), other non-canonical mediators, including the different ERβ isoforms, membrane and mitochondrial ERs, and G protein-coupled receptor 30, may have major actions diverging from classical ER actions. These new discoveries have led to renewed interest among the public and the medicinal field in estrogens and antiestrogens as singular and adjuvant PCa treatment and prevention regimens. This review summarizes current knowledge on how different estrogens/antiestrogens/estrogen mimics contribute to prostate carcinogenesis, the roles of the different mediators of estrogen in the process, and the potentials of new estrogenic/antiestrogenic compounds as targeted therapies for prevention and treatment of PCa. PMID:21889723

  3. Estrogen Receptor Alpha G525L Knock-In-Mice

    DTIC Science & Technology

    2006-03-01

    Padilla-Banks E, Clark G, Newbold RR. Assessing estrogenic activity of phytochemicals using transcriptional activation and immature mouse...AD_________________ Award Number: W81XWH-04-1-0347 TITLE: Estrogen Receptor Alpha G525L...TITLE AND SUBTITLE Estrogen Receptor Alpha G525L Knock-In Mice 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-04-1-0347 5c. PROGRAM ELEMENT

  4. Genetic Susceptibility to Estrogen-Induced Mammary Cancers

    DTIC Science & Technology

    2001-11-01

    Susceptibility to Estrogen -Induced Mammary Cancers PRINCIPAL INVESTIGATOR: Dr. James D. Shull CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha...DATES COVERED blank) November 2001 Final (01 Oct 98 - 01 Oct 01) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Genetic Susceptibility to Estrogen -Induced...Street, Fort Detrick, Maryland 21702-5012. 13. ABSTRACT (Maximum 200 Words) Estrogens are important in the etiology of breast cancer. We have developed

  5. Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens

    SciTech Connect

    Shyu, Conrad; Cavileer, Timothy D.; Nagler, James J.; Ytreberg, F. Marty

    2011-02-01

    Environmental estrogens have been the subject of intense research due to their documented detrimental effects on the health of fish and wildlife and their potential to negatively impact humans. A complete understanding of how these compounds affect health is complicated because environmental estrogens are a structurally heterogeneous group of compounds. In this work, computational molecular dynamics simulations were utilized to predict the binding affinity of different compounds using rainbow trout (Oncorhynchus mykiss) estrogen receptors (ERs) as a model. Specifically, this study presents a comparison of the binding affinity of the natural ligand estradiol-17{beta} to the four rainbow trout ER isoforms with that of three known environmental estrogens 17{alpha}-ethinylestradiol, bisphenol A, and raloxifene. Two additional compounds, atrazine and testosterone, that are known to be very weak or non-binders to ERs were tested. The binding affinity of these compounds to the human ER{alpha} subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17{beta}, bisphenol A binds less strongly to all four receptors, 17{alpha}-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the {alpha} subtype only. The results also show that atrazine and testosterone are weak or non-binders to the ERs. All of the results are in excellent qualitative agreement with the known in vivo estrogenicity of these compounds in the rainbow trout and other fishes. Computational estimation of binding affinities could be a valuable tool for predicting the impact of environmental estrogens in fish and other animals.

  6. Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element.

    PubMed

    Qian, Yi; Yin, Chunyang; Chen, Yue; Zhang, Shuping; Jiang, Li; Wang, Fudi; Zhao, Meirong; Liu, Sijin

    2015-05-01

    Ferroportin (FPN) is the only known iron exporter in mammalian cells, and is universally expressed in most types of cells. FPN signaling plays a crucial role in maintaining iron homeostasis through governing the level of intracellular iron. Serum iron storage is conversely related with the estrogen level in the female bodies, and women in post-menopause are possibly subjected to iron retention. However, the potential effects of estrogen on iron metabolism are not clearly understood. Here, FPN mRNA transcription in all selected estrogen receptor positive (ER+) cells was significantly reduced upon 17β-estradiol (E2) treatment; and this inhibitory effect could be attenuated by ER antagonist tamoxifen. Likewise, in murine bone marrow-derived macrophages (BMDMs), FPN reduction with elevated intracellular iron (reflected by increased ferritin) was observed in response to E2; however, ferritin level barely responded to E2 in FPN-null BMDMs. The observation of inhibition of FPN mRNA expression was not replicated in ER(-) cells upon E2. A functional estrogen response element (ERE) was identified within the promoter of FPN, and this ERE was responsible for the suppressive effect of E2 on FPN expression. Moreover, ovariectomized (OVX) and sham-operated (SHAM) mice were used to further confirm the in vitro finding. The expression of hepatic FPN was induced in OVX mice, compared to that in the SHAM mice. Taken together, our results demonstrated that estrogen is involved in regulating FPN expression through a functional ERE on its promoter, providing additional insights into a vital role of estrogen in iron metabolism.

  7. Neonatal oxytocin alters subsequent estrogen receptor alpha protein expression and estrogen sensitivity in the female rat.

    PubMed

    Perry, Adam N; Paramadilok, Auratip; Cushing, Bruce S

    2009-12-14

    In most species, the effects of oxytocin (OT) on female reproductive behavior are dependent upon estrogen, which increases both OT and OT receptor expression. It is also becoming apparent that OT neurotransmission can influence estrogen signaling, especially during development, as neonatal OT manipulations in prairie voles alter ERalpha expression and estrogen-dependent behaviors. We tested the hypothesis that OT developmentally programs ERalpha expression and estrogen sensitivity in female Sprague-Dawley rats, a species previously used to establish the estrogen-dependence of OT signaling in adulthood. OT treatment for the first postnatal week significantly increased ERalpha-immunoreactivity in the ventromedial nucleus of the hypothalamus (VMH), but not in the medial preoptic area (MPOA). Conversely, neonatal OT antagonist (OTA) treatment significantly reduced ERalpha-immunoreactivity in the MPOA, but not in the VMH. Both treatments increased OT-immunoreactivity in the paraventricular nucleus of the hypothalamus (PVN) and reduced estrogen sensitivity, indicated by reduced sexual receptivity following chronic estradiol benzoate (EB) administration. Behavioral deficits in OTA-treated females were apparent during both paced and non-paced tests with 0.5 microg EB (but not 5.0 or 10.0 microg EB), whereas deficits in OT-treated females were only observed during the initial paced test with 0.5 and 5.0 microg EB (but not 10.0 microg EB). The current results demonstrate that OT can positively regulate ERalpha expression within the MPOA and VMH during development; however, endogenous OT selectively programs ERalpha expression within the MPOA. Thus, exogenous OT or OTA exposure during development may have long-term consequences on behavior through stable changes in ERalpha and OT expression.

  8. Melatonin affects the dynamic steady-state equilibrium of estrogen sulfates in human umbilical vein endothelial cells by regulating the balance between estrogen sulfatase and sulfotransferase.

    PubMed

    González, Alicia; Martínez-Campa, Carlos; Alonso-González, Carolina; Cos, Samuel

    2015-12-01

    Melatonin is known to reduce the growth of endocrine-responsive breast cancers by interacting with estrogen signaling pathways. Estrogens play an important role in breast cancer, but also in various types of tissues, including vascular tissue. Estrogen sulfatase (STS) converts inactive estrogen sulfates into active estrogens, whereas estrogen sulfotransferase (EST) sulfonates estrogens to estrogen sulfates. Therefore, STS and EST are considered to be involved in the regulation of local estrogen levels in hormone‑dependent tumors and in non-pathologic tissues, such as those of the vascular system. Estrogens have a major impact on the vasculature, influencing vascular function, the expression of adhesion proteins, angiogenesis and the inflammatory state. In this study, we investigated the status of STS and EST in human umbilical vein endothelial cells (HUVECs) and the modulatory effects of melatonin. Both STS and EST were highly expressed in the HUVECs. The enzymatic activity correlated with the expression levels in these cells. Our findings also demonstrated that melatonin, at physiological concentrations, modulated the synthesis and transformation of biologically active estrogens in HUVECs through the inhibition of STS activity and expression, and the stimulation of EST activity and expression. Since melatonin decreased the STS levels and increased the EST levels, it modified the dynamic steady‑state equilibrium of estrogen sulfates by increasing the inactive estrogen levels and decreasing the active estrogen levels. Therefore, melatonin may modulate the known different biological actions of estrogens in endothelial cells, as well as in estrogen-dependent tumors and non-pathologic tissues.

  9. Transformation of the rat uterine estrogen receptor after partial purification.

    PubMed

    Nielsen, S; Notides, A C

    1975-02-13

    Warming crude ratuterine cytosol after the addition of [3H] estradiol accelerates the association of the 4-S estrogen-binding protein with a second macromolecule, resulting in the formation of the 5-S estrogen-binding protein. To determine whether the 5-S estrogen-binding protein consists of two similar or dissimilar subunits, uterine cytosol was subjected to a number of fractionation procedures that separate macromolecules by solubility, molecular gel sieving, sedimentation rate, ionic charge, and heat lability. Following each of these methods, the fraction containing the 4-S estrogen-binding protein was incubated at 28 degrees C; each of the these 4-S estrogen-binding protein-containing fractions retained its capacity to completely transform to the 5-S estrogen-binding protein. In samples subjected to partial purification procedures, it was necessary that the buffer contain 40 mM Tris, 60 mM Tris, 60 mM KC1, 1-10 MM dithiothreitol, and 1 M urea at pH 7.4, in order to accomplish the 4-S to 5-S estrogen-binding protein transformation at 25 degrees C. Formation of the 5-S estrogen-binding protein requires association of the 4-Estrogen-binding protein with a molecule identical to or very similar to itself.

  10. Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice.

    PubMed

    Massaro, Donald; Massaro, Gloria Decarlo

    2004-12-01

    Lung tissue elastic recoil and the dimension and number of pulmonary gas-exchange units (alveoli) are major determinants of gas-exchange function. Loss of gas-exchange function accelerates after menopause in the healthy aged and is progressively lost in individuals with chronic obstructive pulmonary disease (COPD). The latter, a disease of midlife and later, though more common in men than in women, is a disease to which women smokers and never smokers may be more susceptible than men; it is characterized by diminished lung tissue elastic recoil and presently irremediable alveolar loss. Ovariectomy in sexually immature rats diminishes the formation of alveoli, and estrogen prevents the diminution. In the present work, we found that estrogen receptor-alpha and estrogen receptor-beta, the only recognized mammalian estrogen receptors, are required for the formation of a full complement of alveoli in female mice. However, only the absence of estrogen receptor-beta diminishes lung elastic tissue recoil. Furthermore, ovariectomy in adult mice results, within 3 wk, in loss of alveoli and of alveolar surface area without a change of lung volume. Estrogen replacement, after alveolar loss, induces alveolar regeneration, reversing the architectural effects of ovariectomy. These studies 1) reveal estrogen receptors regulate alveolar size and number in a nonredundant manner, 2) show estrogen is required for maintenance of already formed alveoli and induces alveolar regeneration after their loss in adult ovariectomized mice, and 3) offer the possibility estrogen can slow alveolar loss and induce alveolar regeneration in women with COPD.

  11. Structure and estrogenic activity of new lignans from Iryanthera lancifolia.

    PubMed

    Mesa-Siverio, Dulce; Machín, Rubén P; Estévez-Braun, Ana; Ravelo, Angel G; Lock, Olga

    2008-03-15

    Five new dibenzylbutane type lignans (1-5) were isolated from the stem bark of Iryanthera lancifolia. Their structures were determined by extensive 1D and 2D NMR spectroscopic studies and chemical evidence. Seventeen of the isolated compounds were tested for their estrogenic activities in the estrogen responsive human breast cancer cell line MCF-7 BUS using the E-Screen proliferation assay. Cell proliferation was evaluated by the SRB assay to calculate the estrogenic parameters. The majority of the compounds induced a mitogenic response. This effect, given as Relative Proliferative Effect (RPE) to reference estrogen 17beta-estradiol (E(2)), ranged between 14% and 84%.

  12. Insights from the Study of Animals Lacking Functional Estrogen Receptor

    NASA Astrophysics Data System (ADS)

    Korach, Kenneth S.

    1994-12-01

    Estrogen hormones produce physiological actions within a variety of target sites in the body and during development by activating a specific receptor protein. Hormone responsiveness for the estrogen receptor protein was investigated at different stages of development with the use of gene knockout techniques because no natural genetic mutants have been described. A mutant mouse line without a functional estrogen receptor was created and is being used to assess estrogen responsiveness. Both sexes of these mutant animals are infertile and show a variety of phenotypic changes, some of which are associated with the gonads, mammary glands, reproductive tracts, and skeletal tissues.

  13. Visualization of Estrogen Receptor Transcriptional Activation in Zebrafish

    PubMed Central

    Halpern, Marnie E.

    2011-01-01

    Estrogens regulate a diverse range of physiological processes and affect multiple tissues. Estrogen receptors (ERs) regulate transcription by binding to DNA at conserved estrogen response elements, and such elements have been used to report ER activity in cultured cells and in transgenic mice. We generated stable, transgenic zebrafish containing five consecutive elements upstream of a c-fos minimal promoter and green fluorescent protein (GFP) to visualize and quantify transcriptional activation in live larvae. Transgenic larvae show robust, dose-dependent estrogen-dependent fluorescent labeling in the liver, consistent with er gene expression, whereas ER antagonists inhibit GFP expression. The nonestrogenic steroids dexamethasone and progesterone fail to activate GFP, confirming ER selectivity. Natural and synthetic estrogens activated the transgene with varying potency, and two chemicals, genistein and bisphenol A, preferentially induce GFP expression in the heart. In adult fish, fluorescence was observed in estrogenic tissues such as the liver, ovary, pituitary gland, and brain. Individual estrogen-responsive neurons and their projections were visualized in the adult brain, and GFP-positive neurons increased in number after 17β-estradiol exposure. The transgenic estrogen-responsive zebrafish allow ER signaling to be monitored visually and serve as in vivo sentinels for detection of estrogenic compounds. PMID:21540282

  14. Molecular biology of beta-estradiol-estrogen receptor complex binding to estrogen response element and the effect on cell proliferation.

    PubMed

    Heger, Zbynek; Zitka, Ondrej; Krizkova, Sona; Beklova, Miroslava; Kizek, Rene; Adam, Vojtech

    2013-01-01

    Group of estrogen pollutants, where the highest estrogen activity is reported at estradiol, is characterized by the fact that even at very low concentrations have potential to cause xenoestrogenic effects. During exposure of excessive amounts of estradiols may be produced undesirable effects resulting in the feminization of males of water organisms. The presence of estradiols in drinking water implies also a risk for the human population in the form of cancers of endocrine systems, abnormalities in reproduction or dysfunctions of neuronal and immune system. Currently, the research is focused mainly to uncover the relationship between the estrogen receptors binding affinity with an estrogen response element and estradiol. In this review we summarized facts about molecular biological principles of β estradiol-estrogen receptor complex binding with estrogen response element and its successive effect on cancer genes expression.

  15. Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors

    SciTech Connect

    Pinto, Caroline; Grimaldi, Marina; Boulahtouf, Abdelhay; Pakdel, Farzad; Brion, François; Aït-Aïssa, Sélim; Cavaillès, Vincent; Bourguet, William; Gustafsson, Jan-Ake; and others

    2014-10-01

    Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28 °C as compared to 37 °C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology. - Highlights: • Zebrafish is increasingly used to study the effects of estrogens. • We assessed the activity of pharmaceutical and environmental estrogens on zfERs. • Environmental estrogens displayed greater potency for zfERα compared to zfERβs. • hERβ selective agonists displayed greater potency for zf

  16. Expression profiles of estrogen-regulated microRNAs in breast cancer cells

    PubMed Central

    Katchy, Anne; Williams, Cecilia

    2016-01-01

    Summary Molecular signaling through both estrogen and microRNAs are critical for breast cancer development and growth. The activity of estrogen is mediated by transcription factors, the estrogen receptors. Here we describe a method for robust characterization of estrogen-regulated microRNA profiles. The method details how to prepare cells for optimal estrogen response, directions for estrogen treatment, RNA extraction, microRNA large-scale profiling and subsequent confirmations. PMID:26585151

  17. Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus.

    PubMed

    Mango, D; Braksator, E; Battaglia, G; Marcelli, S; Mercuri, N B; Feligioni, M; Nicoletti, F; Bashir, Z I; Nisticò, R

    2017-01-27

    Acid-sensing ion channels (ASICs), members of the degenerin/epithelial Na(+) channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca(2+) and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

  18. Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer proteins in the hippocampus of Ube3A hemizygous mice modeling angelman syndrome.

    PubMed

    Pignatelli, Marco; Piccinin, Sonia; Molinaro, Gemma; Di Menna, Luisa; Riozzi, Barbara; Cannella, Milena; Motolese, Marta; Vetere, Gisella; Catania, Maria Vincenza; Battaglia, Giuseppe; Nicoletti, Ferdinando; Nisticò, Robert; Bruno, Valeria

    2014-03-26

    Angelman syndrome (AS) is caused by the loss of Ube3A, an ubiquitin ligase that commits specific proteins to proteasomal degradation. How this defect causes autism and other pathological phenotypes associated with AS is unknown. Long-term depression (LTD) of excitatory synaptic transmission mediated by type 5 metabotropic glutamate (mGlu5) receptors was enhanced in hippocampal slices of Ube3A(m-/p+) mice, which model AS. No changes were found in NMDA-dependent LTD induced by low-frequency stimulation. mGlu5 receptor-dependent LTD in AS mice was sensitive to the protein synthesis inhibitor anisomycin, and relied on the same signaling pathways as in wild-type mice, e.g., the mitogen-activated protein kinase (MAPK) pathway, the phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycine pathway, and protein tyrosine phosphatase. Neither the stimulation of MAPK and PI3K nor the increase in Arc (activity-regulated cytoskeleton-associated protein) levels in response to mGlu5 receptor activation were abnormal in hippocampal slices from AS mice compared with wild-type mice. mGlu5 receptor expression and mGlu1/5 receptor-mediated polyphosphoinositide hydrolysis were also unchanged in the hippocampus of AS mice. In contrast, AS mice showed a reduced expression of the short Homer protein isoform Homer 1a, and an increased coupling of mGlu5 receptors to Homer 1b/c proteins in the hippocampus. These findings support the link between Homer proteins and monogenic autism, and lay the groundwork for the use of mGlu5 receptor antagonists in AS.

  19. Latent inhibition of cued fear conditioning: an NMDA receptor-dependent process that can be established in the presence of anisomycin.

    PubMed

    Lewis, Michael C; Gould, Thomas J

    2004-08-01

    Much of the research examining the biological basis for long-term memories has focused on mechanisms that support the formation of conditioned associations. Less information is available on biological mechanisms which underlie processes that modify the strength of conditioned associations. Latent inhibition is a phenomenon by which pre-exposure to a to-be-conditioned stimulus (CS) weakens subsequent conditioning of that CS to an unconditioned stimulus (US). Here we report that latent inhibition of cued fear conditioning is dependent on NMDA receptor activation. MK-801 (1 mg/kg), an NMDA receptor antagonist, abolished latent inhibition of cued fear conditioning. This dose of MK-801 administered before training did not disrupt cued fear conditioning. Conversely, anisomycin (150 mg/kg), a protein synthesis inhibitor, had no effect on latent inhibition of cued fear conditioning when administered 20 min before, immediately after, or 2, 4, 6, or 8 h after CS pre-exposure. Furthermore, continuous anisomycin administration (50 mg/kg, administered every 2 h for 6 h starting 20 min prior to pre-exposure) did not disrupt latent inhibition of cued fear conditioning. In addition, anisomycin had no effect on a long-lasting version of latent inhibition of cued fear conditioning that was maintained over a 7-day interval. Anisomycin administered before training, however, disrupted learning of the CS-US association. These findings suggest that latent inhibition of cued fear conditioning is a long-lasting NMDA receptor-dependent process that can develop during the inhibition of protein synthesis.

  20. Electroacupuncture pretreatment attenuates spinal cord ischemia-reperfusion injury via inhibition of high-mobility group box 1 production in a LXA4 receptor-dependent manner.

    PubMed

    Zhu, Xiao-Ling; Chen, Xin; Wang, Wei; Li, Xu; Huo, Jia; Wang, Yu; Min, Yu-Yuan; Su, Bin-Xiao; Pei, Jian-Ming

    2017-03-15

    Paraplegia caused by spinal cord ischemia is a severe complication following surgeries in the thoracic aneurysm. HMGB1 has been recognized as a key mediator in spinal inflammatory response after spinal cord injury. Electroacupuncture (EA) pretreatment could provide neuroprotection against cerebral ischemic injury through inhibition of HMGB1 release. Therefore, the present study aims to test the hypothesis that EA pretreatment protects against spinal cord ischemia-reperfusion (I/R) injury via inhibition of HMGB1 release. Animals were pre-treated with EA stimulations 30min daily for 4 successive days, followed by 20-min spinal cord ischemia induced by using a balloon catheter placed into the aorta. We found that spinal I/R significantly increased mRNA and cytosolic protein levels of HMGB1 after reperfusion in the spinal cord. The EA-pretreated animals displayed better motor performance after reperfusion along with the decrease of apoptosis, HMGB1, TNF-α and IL-1β expressions in the spinal cord, whereas these effects by EA pretreatment was reversed by rHMGB1 administration. Furthermore, EA pretreatment attenuated the down-regulation of LXA4 receptor (ALX) expression induced by I/R injury, while the decrease of HMGB1 release in EA-pretreated rats was reversed by the combined BOC-2 (an inhibitor of LXA4 receptor) treatment. In conclusion, EA pretreatment may promote spinal I/R injury through the inhibition of HMGB1 release in a LXA4 receptor-dependent manner. Our data may represent a new therapeutic technique for treating spinal cord ischemia-reperfusion injury.

  1. Chronic intermittent alcohol disrupts the GluN2B-associated proteome and specifically regulates group I mGlu receptor-dependent long-term depression.

    PubMed

    Wills, Tiffany A; Baucum, Anthony J; Holleran, Katherine M; Chen, Yaoyi; Pasek, Johanna G; Delpire, Eric; Tabb, David L; Colbran, Roger J; Winder, Danny G

    2017-03-01

    N-Methyl-d-aspartate receptors (NMDARs) are major targets of both acute and chronic alcohol, as well as regulators of plasticity in a number of brain regions. Aberrant plasticity may contribute to the treatment resistance and high relapse rates observed in alcoholics. Recent work suggests that chronic alcohol treatment preferentially modulates both the expression and subcellular localization of NMDARs containing the GluN2B subunit. Signaling through synaptic and extrasynaptic GluN2B-NMDARs has already been implicated in the pathophysiology of various other neurological disorders. NMDARs interact with a large number of proteins at the glutamate synapse, and a better understanding of how alcohol modulates this proteome is needed. We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes. Protein enrichment analyses revealed changes in the association of post-synaptic proteins, including scaffolding, glutamate receptor and PDZ-domain binding proteins with GluN2B. In particular, GluN2B interaction with metabotropic glutamate (mGlu)1/5 receptor-dependent long-term depression (LTD)-associated proteins such as Arc and Homer 1 was increased, while GluA2 was decreased. Accordingly, we found a lack of mGlu1/5 -induced LTD while α1 -adrenergic receptor-induced LTD remained intact in hippocampal CA1 following CIE. These data suggest that CIE specifically disrupts mGlu1/5 -LTD, representing a possible connection between NMDAR and mGlu receptor signaling. These studies not only demonstrate a new way in which alcohol can modulate plasticity in the hippocampus but also emphasize the utility of this discovery-based proteomic approach to generate new hypotheses regarding alcohol-related mechanisms.

  2. LIQUID HYDROCARBON FUEL CELL DEVELOPMENT.

    DTIC Science & Technology

    A compound anode consists of a reforming catalyst bed in direct contact with a palladium-silver fuel cell anode. The objective of this study was to...prove the feasibility of operating a compound anode fuel cell on a liquid hydrocarbon and to define the important parameters that influence cell...performance. Both reformer and fuel cell tests were conducted with various liquid hydrocarbon fuels. Included in this report is a description of the

  3. Bioassay of polycyclic aromatic hydrocarbons

    SciTech Connect

    Van Kirk, E.A.

    1980-08-01

    A positive relationship was found between the photodynamic activity of 24 polycyclic aromatic hydrocarbons versus published results on the mutagenicity, carcinogenicity, and initiation of unscheduled DNA synthesis. Metabolic activation of benzo(a)pyrene resulted in detection of increased mutagenesis in Paramecium tetraurelia as found also in the Ames Salmonella assay. The utility of P. tetraurelia as a biological detector of hazardous polycyclic aromatic hydrocarbons is discussed.

  4. Aliphatic hydrocarbons of the fungi.

    NASA Technical Reports Server (NTRS)

    Weete, J. D.

    1972-01-01

    Review of studies of aliphatic hydrocarbons which have been recently detected in the spores of phytopathogenic fungi, and are found to be structurally very similar to the alkanes of higher plants. It appears that the hydrocarbon components of the few mycelial and yeast forms reported resemble the distribution found in bacteria. The occurence and distribution of these compounds in the fungi is discussed. Suggested functional roles of fungal spore alkanes are presented.

  5. Hydrocarbon potential of Morocco

    SciTech Connect

    Achnin, H.; Nairn, A.E.M.

    1988-08-01

    Morocco lies at the junction of the African and Eurasian plates and carries a record of their movements since the end of the Precambrian. Four structural regions with basins and troughs can be identified: Saharan (Tarfaya-Ayoun and Tindouf basins); Anti-Atlas (Souss and Ouarzazate troughs and Boudnib basin); the Essaouria, Doukkala, Tadla, Missour, High Plateau, and Guercif basins; and Meseta and Rif (Rharb and Pre-Rif basins). The targets in the Tindouf basin are Paleozoic, Cambrian, Ordovician (clastics), Devonian (limestones), and Carboniferous reservoirs sourced primarily by Silurian shales. In the remaining basins, excluding the Rharb, the reservoirs are Triassic detritals, limestones at the base of the Lias and Dogger, Malm detritals, and sandy horizons in the Cretaceous. In addition to the Silurian, potential source rocks include the Carboniferous and Permo-Carboniferous shales and clays; Jurassic shales, marls, and carbonates; and Cretaceous clays. In the Rharb basin, the objectives are sand lenses within the Miocene marls. The maturation level of the organic matter generally corresponds to oil and gas. The traps are stratigraphic (lenses and reefs) and structural (horsts and folds). The seals in the pre-Jurassic rocks are shales and evaporites; in the younger rocks, shales and marl. Hydrocarbon accumulations have been found in Paleozoic, Triassic, Liassic, Malm, and Miocene rocks.

  6. Evaluation of hydrocarbon potential

    SciTech Connect

    Cashman, P.H.; Trexler, J.H. Jr.

    1992-09-30

    Task 8 is responsible for assessing the hydrocarbon potential of the Yucca Mountain vincinity. Our main focus is source rock stratigraphy in the NTS area in southern Nevada. (In addition, Trexler continues to work on a parallel study of source rock stratigraphy in the oil-producing region of east central Nevada, but this work is not funded by Task 8.) As a supplement to the stratigraphic studies, we are studying the geometry and kinematics of deformation at NTS, particularly as these pertain to reconstructing Paleozoic stratigraphy and to predicting the nature of the Late Paleozoic rocks under Yucca Mountain. Our stratigraphic studies continue to support the interpretation that rocks mapped as the {open_quotes}Eleana Formation{close_quotes} are in fact parts of two different Mississippian units. We have made significant progress in determining the basin histories of both units. These place important constraints on regional paleogeographic and tectonic reconstructions. In addition to continued work on the Eleana, we plan to look at the overlying Tippipah Limestone. Preliminary TOC and maturation data indicate that this may be another potential source rock.

  7. Illite and hydrocarbon exploration

    PubMed Central

    Pevear, David R.

    1999-01-01

    Illite is a general term for the dioctahedral mica-like clay mineral common in sedimentary rocks, especially shales. Illite is of interest to the petroleum industry because it can provide a K-Ar isotope date that constrains the timing of basin heating events. It is critical to establish that hydrocarbon formation and migration occurred after the formation of the trap (anticline, etc.) that is to hold the oil. Illite also may precipitate in the pores of sandstone reservoirs, impeding fluid flow. Illite in shales is a mixture of detrital mica and its weathering products with diagenetic illite formed by reaction with pore fluids during burial. K-Ar ages are apparent ages of mixtures of detrital and diagenetic end members, and what we need are the ages of the end members themselves. This paper describes a methodology, based on mineralogy and crystallography, for interpreting the K-Ar ages from illites in sedimentary rocks and for estimating the ages of the end members. PMID:10097055

  8. Bioluminescent yeast estrogen assay (BLYES) as a sensitive tool to monitor surface and drinking water for estrogenicity.

    PubMed

    Bergamasco, Ana Marcela Di Dea; Eldridge, Melanie; Sanseverino, John; Sodré, Fernando Fabriz; Montagner, Cassiana Carolina; Pescara, Igor Cardoso; Jardim, Wilson Figueiredo; Umbuzeiro, Gisela de Aragão

    2011-11-01

    Estrogenic Endocrine Disrupting Chemicals (EDCs) are a concern due to their ubiquity and recognized adverse effects to humans and wildlife. Methods to assess exposure to and associated risks of their presence in aquatic environment are still under development. The aim of this work is to assess estrogenicity of raw and treated waters with different degrees of pollution. Chemical analyses of selected EDCs were performed by liquid chromatography-tandem mass spectrometry, and estrogenic activity was evaluated using in vitro bioluminescent yeast estrogen assay (BLYES). Most raw water samples (18/20) presented at least one EDC and 16 rendered positive in BLYES. When EDCs were detected, the bioassay usually provided a positive response, except when only bisphenol A was detected at low concentrations. The highest values of estrogenic activity were detected in the most polluted sites. The maximum estrogenic activity observed was 8.7 ng equiv. of E2 L(-1). We compared potencies observed in the bioassay to the relative potency of target compounds and their concentrations failed to fully explain the biological response. This indicates that bioassay is more sensitive than the chemical approach either detecting estrogenic target compounds at lower concentrations, other non-target compounds or even synergistic effects, which should be considered on further investigations. We have not detected either estrogenic activity or estrogenic compounds in drinking water. BLYES showed good sensitivity with a detection limit of 0.1 ng equiv. E2 L(-1) and it seems to be a suitable tool for water monitoring.

  9. Estrogens and cognition: Friends or foes?: An evaluation of the opposing effects of estrogens on learning and memory.

    PubMed

    Korol, Donna L; Pisani, Samantha L

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions.

  10. Comparative analysis of the interaction of various estrogens with the estrogen-receptor system of the uterus

    SciTech Connect

    Fanchenko, N.D.; Alekseeva, M.L.; Minina, L.S.; Novikov, E.A.; Khel'mun, D.K.

    1986-05-20

    The binding of various labeled estrogens under conditions of equilibrium in the cytosol of the uterus of sexually immature Wistar rats was studied. An analysis of the data obtained, as well as the kinetics of the dissociation of the complexes of the ligands used with specific high-affinity estrogen-binding sites of the cytosol, suggested that the population of estrogen receptors in the rat uterus is homogeneous. The possibility of intracellular regulation of the action of estrogens in the target cell in the presence of a homogeneous population of receptors, both at the receptor and at the post-receptor stages, is suggested.

  11. Effect of estrogens on boar sperm capacitation in vitro

    PubMed Central

    2010-01-01

    Background Mammalian sperm must undergo a series of controlled molecular processes in the female reproductive tract called capacitation before they are capable of penetrating and fertilizing the egg. Capacitation, as a complex biological process, is influenced by many molecular factors, among which steroidal hormone estrogens play their role. Estrogens, present in a high concentration in the female reproductive tract are generally considered as primarily female hormones. However, there is increasing evidence of their important impact on male reproductive parameters. The purpose of this study is to investigate the effect of three natural estrogens such as estrone (E1), 17beta-estradiol (E2) and estriol (E3) as well as the synthetical one, 17alpha-ethynylestradiol (EE2) on boar sperm capacitation in vitro. Methods Boar sperm were capacitated in vitro in presence of estrogens. Capacitation progress in control and experimental samples was analyzed by flow cytometry with the anti-acrosin monoclonal antibody (ACR.2) at selected times of incubation. Sperm samples were analyzed at 120 min of capacitation by CTC (chlortetracycline) assay, immunocytochemistry and flow cytometry with anti-acrosin ACR.2 antibody. Furthermore, sperm samples and capacitating media were analyzed by immunocytochemistry, ELISA with the ACR.2 antibody, and the acrosin activity assay after induced acrosomal reaction (AR). Results Estrogens stimulate sperm capacitation of boar sperm collected from different individuals. The stimulatory effect depends on capacitation time and is highly influenced by differences in the response to estrogens such as E2 by individual animals. Individual estrogens have relatively same effect on capacitation progress. In the boar samples with high estrogen responsiveness, estrogens stimulate the capacitation progress in a concentration-dependent manner. Furthermore, estrogens significantly increase the number of acrosome-reacted sperm after zona pellucida- induced acrosomal

  12. Estrogen Receptor Ligands: A Review (2013–2015)

    PubMed Central

    Farzaneh, Shabnam; Zarghi, Afshin

    2016-01-01

    Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintenance to reproduction. Their action is mediated through ER nuclear receptors. Two subtypes of the estrogen receptor, ERα and ERβ, exist and exhibit distinct cellular and tissue distribution patterns. In humans, both receptor subtypes are expressed in many cells and tissues, and they control key physiological functions in various organ systems. Estrogens attract great attention due to their wide applications in female reproductive functions and treatment of some estrogen-dependent cancers and osteoporosis. This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015. The broad physiological profile of estrogens has attracted the attention of many researchers to develop new estrogen ligands as therapeutic molecules for various clinical purposes. After the discovery of the ERβ receptor, subtype-selective ligands could be used to elicit beneficial estrogen-like activities and reduce adverse side effects, based on the different distributions and relative levels of the two ER subtypes in different estrogen target tissues. Therefore, recent literature has focused on selective estrogen ligands as highly promising agents for the treatment of some types of cancer, as well as for cardiovascular, inflammatory, and neurodegenerative diseases. Estrogen receptors are nuclear transcription factors that are involved in the regulation of many complex physiological functions in humans. Selective estrogen ligands are highly promising targets for treatment of some types of cancer, as well as for cardiovascular, inflammatory and neurodegenerative diseases. Extensive structure-activity relationship studies of ER ligands based on small molecules indicate that many different structural scaffolds may provide high

  13. Association of Active and Sedentary Behaviors with Postmenopausal Estrogen Metabolism

    PubMed Central

    Dallal, Cher M.; Brinton, Louise A.; Matthews, Charles E.; Pfeiffer, Ruth M.; Hartman, Terryl J.; Lissowska, Jolanta; Falk, Roni T.; Garcia-Closas, Montserrat; Xu, Xia; Veenstra, Timothy D.; Gierach, Gretchen L.

    2015-01-01

    Purpose Physical activity may reduce endogenous estrogens but few studies have assessed effects on estrogen metabolism and none have evaluated sedentary behavior in relation to estrogen metabolism. We assessed relationships between accelerometer-measured physical activity and sedentary behavior and 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal controls from a population-based breast cancer case-control study conducted in Poland (2000-2003). Methods Postmenopausal women (N=542) were ages 40 to 72 years and not currently using hormone therapy. Accelerometers, worn for seven days, were used to derive measures of average activity (counts/day) and sedentary behavior (<100 counts/min/day). EM were measured in 12-hour urine samples using liquid chromatography-tandem mass spectrometry. EM were analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to parent estrogens. Geometric means of EM by tertiles of accelerometer-measures, adjusted for age and body mass, were computed using linear models. Results High activity was associated with lower levels of estrone and estradiol (p-trend=0.01) while increased sedentary time was positively associated with these parent estrogens (p-trend=0.04). Inverse associations were observed between high activity and 2-methoxyestradiol, 4-methoxyestradiol, 17-epiestriol and 16-epiestriol (p-trend=0.03). Sedentary time was positively associated with methylated catechols in the 2- and 4-hydroxylation pathways (p-trend≤0.04). Women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites relative to parent estrogens (p-trend≤0.02) while increased sedentary time was associated with a lower 16-pathway:parent estrogen ratio (p-trend=0.01). Conclusions Higher activity was associated with lower urinary estrogens, possibly through increased estrogen hydroxylation and subsequent metabolism, while sedentary behavior may reduce metabolism. PMID:26460631

  14. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin.

    PubMed

    Brander, Susanne M; He, Guochun; Smalling, Kelly L; Denison, Michael S; Cherr, Gary N

    2012-12-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. The authors evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid-contaminated aquatic habitats. The authors then compared the in vivo response with an in vitro assay--chemical activated luciferase gene expression (CALUX). Juvenile M. beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. Though Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. Whereas the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. The results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells.

  15. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin

    PubMed Central

    Brander, Susanne M.; He, Guochun; Smalling, Kelly L.; Denison, Michael S.; Cherr, Gary N.

    2012-01-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. We evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid contaminated aquatic habitats. We then compared the in vivo response to an in vitro assay: CALUX (Chemical Activated Luciferase Gene Expression). Juvenile Menidia beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. While Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration-response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. While the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. Our results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, and/or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells. PMID:23007834

  16. Estrogen receptor genes in gastropods: phylogenetic divergence and gene expression responses to a synthetic estrogen.

    PubMed

    Hultin, Cecilia L; Hallgren, Per; Hansson, Maria C

    2016-11-01

    Endocrine disrupting chemicals (EDCs) have the potential to affect development and reproduction in gastropods. However, one is today lacking basic understanding of the Molluscan endocrine system and one can therefore not fully explain these EDC-induced affects. Furthermore, only a few genes that potentially may be connected to the endocrine system have been sequenced in gastropods. An example is the estrogen receptor gene (er) that have been identified in a restricted number of freshwater and marine gastropods. Here, we have identified a new partial coding sequence of an estrogen receptor gene (er) in the European common heterobranch Radix balthica. The following phylogenetic analysis divided the ers of heterobranchs and ceanogastropods in two branches. Furthermore, exposure to the synthetic estrogen 17α-ethinylestradiol (EE2) showed that exposure could significantly affect er expression level in the heterobranch R. balthica. This paper is the first that phylogenetically compares gastropods' er, basal er expression profiles, and transcriptional estrogenic responses in gastropods from two different evolutionary groups.

  17. Is Soy Estrogenic? Hepatic Gene Expression in the Presence or Absence of Endogenous Estrogen

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to address the question of soy's estrogenicity by studying the hepatic gene expression (HGE) signature of diets made with soy protein isolate (SPI) fed in the presence or absence of estradiol (E2). Sprague-Dawley rats were ovariectomized (OVX) at PND50, infused with E...

  18. Sex Hormones and Cardiometabolic Health: Role of Estrogen and Estrogen Receptors.

    PubMed

    Clegg, Deborah; Hevener, Andrea L; Moreau, Kerrie L; Morselli, Eugenia; Criollo, Alfredo; Van Pelt, Rachael E; Vieira-Potter, Victoria J

    2017-02-17

    With increased life expectancy, women will spend over three decades of life post-menopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics. In this brief review, we provide a detailed overview of the literature, from basic science findings to human clinical trial evidence, supporting a protective role of estrogens and their receptors, specifically ERα, in maintenance of cardiometabolic health. In so doing, we provide a concise mechanistic discussion of some of the major tissue-specific roles of estrogens signaling through ERα. Taken together, evidence suggests that targeted, perhaps receptor-specific, hormonal therapies can and should be used to optimize the health of women as they transition through menopause, while reducing the undesired complications that have limited the efficacy and use of traditional hormone replacement interventions.

  19. Polycyclic Aromatic Hydrocarbons

    NASA Technical Reports Server (NTRS)

    Salama, Farid

    2010-01-01

    Carbonaceous materials play an important role in space. Polycyclic Aromatic Hydrocarbons (PAHs) are a ubiquitous component of the carbonaceous materials. PAHs are the best-known candidates to account for the IR emission bands. They are also thought to be among the carriers of the diffuse interstellar absorption bands (DIBs). PAH ionization states reflect the ionization balance of the medium while PAH size, composition, and structure reflect the energetic and chemical history of the medium. A major challenge is to reproduce in the laboratory the physical conditions that exist in the emission and absorption interstellar zones. The harsh physical conditions of the ISM -low temperature, collisionless, strong UV radiation fields- are simulated in the laboratory by associating a molecular beam with an ionizing discharge to generate a cold plasma expansion. PAH ions and radicals are formed from the neutral precursors in an isolated environment at low temperature and probed with high-sensitivity cavity ringdown spectroscopy in the NUV-NIR range. Carbon nanoparticles are also formed during the short residence time of the precursors in the plasma and are characterized with time-offlight mass spectrometry. These experiments provide unique information on the spectra of large carbonaceous molecules and ions in the gas phase that can now be directly compared to interstellar and circumstellar observations (IR emission bands, DIBs, extinction curve). These findings also hold great potential for understanding the formation process of interstellar carbonaceous grains. We will review recent progress in the experimental and theoretical studies of PAHs, compare the laboratory data with astronomical observations and discuss the global implications.

  20. Comparative responses of molluscs and fish to environmental estrogens and an estrogenic effluent.

    PubMed

    Jobling, S; Casey, D; Rodgers-Gray, T; Oehlmann, J; Schulte-Oehlmann, U; Pawlowski, S; Baunbeck, T; Turner, A P; Tyler, C R

    2003-10-29

    It is now well established that there is a diverse array of chemicals discharged into the environment that can mimic or antagonise the action of hormones. These endocrine-disrupting chemicals (EDCs) can thus interact with physiological systems and cause alterations in development, growth and reproduction in wildlife that are exposed to them. As yet, however, there is little information on the relative sensitivities of different wildlife groups to these chemicals and/or mixtures of them (e.g. estrogenic effluents) and hence, there are fundamental shortfalls in our knowledge of the ecological importance of endocrine disruption in wildlife. In this study, the effects of exposure to individual estrogenic chemicals (17alpha-ethinylestradiol; EE2, bisphenol-A, and 4-tert octylphenol) and a mixture containing these chemicals (treated sewage effluent) on embryo production in the prosobranch mollusc, Potamopyrgus antipodarum, were studied and compared with the effects of EE2 and the same estrogenic effluent on vitellogenin induction and/or egg production in various species of freshwater fish (fathead minnow; Pimaphales promelas, rainbow trout (Oncorhynchus mykiss); Cyprinus carpio, carp; Cyprinus carpio). The lab-based studies demonstrated that all of the tested chemicals (known to be estrogenic and to cause reproductive effects in fish) also affected embryo production in P. antipodarum. Furthermore, exposure to EE2 induced similar reproductive responses in the snails as in the fathead minnow (Pimephales promelas), stimulating egg/embryo production at low doses (up to 1 ng/l in the minnow and 25 ng/l in the snail) and causing inhibitory effects at higher doses. A similar pattern of embryo production occurred in P. antipodarum when it was exposed to a graded concentration of treated sewage effluent containing mixtures of estrogenic EDCs and hence, the total number of new embryos produced by the snails increased steadily over the 9 weeks exposure period in treated snails

  1. Dietary Estrogens Act through Estrogen Receptor-Mediated Processes and Show No Antiestrogenicity in Cultured Breast Cancer Cells.

    PubMed Central

    Makela, S; Davis, VL; Tally, WC; Korkman, J; Salo, L; Vihko, R; Santti, R; Korach, KS

    1994-01-01

    Dietary estrogens are believed to exert their estrogenic or antiestrogenic (chemopreventive) action in estrogen responsive cells by interacting with the estrogen receptor (ER). The present study was undertaken to evaluate a direct role of ER in estrogenic or antiestrogenic activities of three dietary estrogens (coumestrol, genistein and zearalenone). HeLa cells were transiently co-transfected with an expression vector for ER and an estrogen-responsive reporter gene construct. Coumestrol, genistein, and zearalenone all increased the activity of the reporter gene, only in the presence of the ER, and the activation was blocked with the ER antagonist ICI 164,384, demonstrating an ER-specific, agonist response. In addition, in MCF-7 cells, coumestrol and zearalenone increased the expression of the estrogen-responsive pS2 gene. Coumestrol and genistein inhibited the purified estrogen-specific 17ß-hydroxysteroid oxidoreductase enzyme and the conversion of estrone to 17ß-estradiol in T-47D cells, which contain this enzyme. However, they did not inhibit the estrone-induced proliferation of T-47D cells. In conclusion, coumestrol, genistein, and zearalenone are all potent estrogens in vitro, and they act through ER mediated mechanism. Our findings give no evidence to support the idea that these compounds act as antiestrogens through competition for the binding sites of ER or by inhibition of the conversion of estrone to 17ß-estradiol in breast cancer cells, since this effect was nullified by their agonist action on cell proliferation. Therefore, their suggested chemopreventive action in estrogen-related cancers must be mediated through other mechanisms. Images Figure 2. A Figure 2. B Figure 2. C Figure 2. D Figure 2. E Figure 3. A Figure 3. B Figure 4. A Figure 4. B Figure 4. C Figure 4. D Figure 4. E Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. A Figure 9. B Figure 9. C PMID:9679118

  2. Estrogenic activity of UV filter mixtures.

    PubMed

    Kunz, Petra Y; Fent, Karl

    2006-11-15

    UV-absorbing chemicals (UV filters) are widely used for protection against UV radiation in sunscreens and in a variety of cosmetic products and materials. Depending on the breadth and factor of UV protection, they are added as single compounds or as a combination thereof. Some UV filters have estrogenic activity, but their activity and interactions in mixtures are largely unknown. In this work, we analyzed 8 commonly used UV filters, which are pure or partial hERalpha agonists, for their estrogenic activity in equieffective mixtures in a recombinant yeast assay carrying the human estrogen receptor alpha (hERalpha). Mixtures of two, four and eight UV filters alone, or in combination with 17 beta estradiol (E2), were assessed at different effect levels and no-observed-effect-concentrations (NOEC). Predictions of the joint effects of these mixtures were calculated by employing the concentration addition (CA) and independent action (IA) model. Most binary mixtures comprising of pure hERalpha agonists showed a synergistic activity at all mixture combinations. Only in combination with benzophenone-1, antagonistic activity was observed at some effect levels. All mixtures of four or eight, pure or pure and partial hERalpha agonists, alone or including E2, showed synergistic activity at concentrations giving an increase of 10% of basal activity (BC10). This occurred even at concentrations that were at the NOEC level of each single compound. Hence, there were substantial mixture effects even though each UV filter was present at its NOEC level. These results show that significant interactions occur in UV filter mixtures, which is important for the hazard and risk assessments of these personal care products.

  3. Estrogenic activity of UV filter mixtures

    SciTech Connect

    Kunz, Petra Y. . E-mail: petra.kunz@fhnw.ch; Fent, Karl . E-mail: karl.fent@bluewin.ch

    2006-11-15

    UV-absorbing chemicals (UV filters) are widely used for protection against UV radiation in sunscreens and in a variety of cosmetic products and materials. Depending on the breadth and factor of UV protection, they are added as single compounds or as a combination thereof. Some UV filters have estrogenic activity, but their activity and interactions in mixtures are largely unknown. In this work, we analyzed 8 commonly used UV filters, which are pure or partial hER{alpha} agonists, for their estrogenic activity in equieffective mixtures in a recombinant yeast assay carrying the human estrogen receptor alpha (hER{alpha}). Mixtures of two, four and eight UV filters alone, or in combination with 17 {beta} estradiol (E2), were assessed at different effect levels and no-observed-effect-concentrations (NOEC). Predictions of the joint effects of these mixtures were calculated by employing the concentration addition (Canada) and independent action (IA) model. Most binary mixtures comprising of pure hER{alpha} agonists showed a synergistic activity at all mixture combinations. Only in combination with benzophenone-1, antagonistic activity was observed at some effect levels. All mixtures of four or eight, pure or pure and partial hER{alpha} agonists, alone or including E2, showed synergistic activity at concentrations giving an increase of 10% of basal activity (BC10). This occurred even at concentrations that were at the NOEC level of each single compound. Hence, there were substantial mixture effects even though each UV filter was present at its NOEC level. These results show that significant interactions occur in UV filter mixtures, which is important for the hazard and risk assessments of these personal care products.

  4. Isoflavones: estrogenic activity, biological effect and bioavailability.

    PubMed

    Vitale, Daniela Cristina; Piazza, Cateno; Melilli, Barbara; Drago, Filippo; Salomone, Salvatore

    2013-03-01

    Isoflavones are phytoestrogens with potent estrogenic activity; genistein, daidzein and glycitein are the most active isoflavones found in soy beans. Phytoestrogens have similarity in structure with the human female hormone 17-β-estradiol, which can bind to both alpha and beta estrogen receptors, and mimic the action of estrogens on target organs, thereby exerting many health benefits when used in some hormone-dependent diseases. Numerous clinical studies claim benefits of genistein and daidzein in chemoprevention of breast and prostate cancer, cardiovascular disease and osteoporosis as well as in relieving postmenopausal symptoms. The ability of isoflavones to prevent cancer and other chronic diseases largely depends on pharmacokinetic properties of these compounds, in particular absorption and distribution to the target tissue. The chemical form in which isoflavones occur is important because it influences their bioavailability and, therefore, their biological activity. Glucose-conjugated isoflavones are highly polar, water-soluble compounds. They are hardly absorbed by the intestinal epithelium and have weaker biological activities than the corresponding aglycone. Different microbial families of colon can transform glycosylated isoflavones into aglycones. Clinical studies show important differences between the aglycone and conjugated forms of genistein and daidzein. The evaluation of isoflavone metabolism and bioavailability is crucial to understanding their biological effects. Lipid-based formulations such as drug incorporation into oils, emulsions and self-microemulsifying formulations have been introduced to increase bioavailability. Complexation with cyclodextrin also represent a valid method to improve the physicochemical characteristics of these substances in order to be absorbed and distributed to target tissues. We review and discuss pharmacokinetic issues that critically influence the biological activity of isoflavones.

  5. Estrogen synthesis and signaling pathways during ageing: from periphery to brain

    PubMed Central

    Cui, Jie; Shen, Yong; Li, Rena

    2012-01-01

    Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases. PMID:23348042

  6. Bioluminescent bioreporter integrated circuit devices and methods for detecting estrogen

    DOEpatents

    Simpson, Michael L.; Paulus, Michael J.; Sayler, Gary S.; Applegate, Bruce M.; Ripp, Steven A.

    2006-08-15

    Bioelectronic devices for the detection of estrogen include a collection of eukaryotic cells which harbor a recombinant lux gene from a high temperature microorganism wherein the gene is operably linked with a heterologous promoter gene. A detectable light-emitting lux gene product is expressed in the presence of the estrogen and detected by the device.

  7. Estrogen receptor polymorphisms: significance to human physiology, disease and therapy.

    PubMed

    Figtree, Gemma A; Noonan, Jonathon E; Bhindi, Ravinay; Collins, Peter

    2009-01-01

    Other than its well-recognized effects on reproductive physiology, estrogen has important actions in a wide variety of other body systems with important examples including bone, blood vessels and the heart. These effects are seen in both females and males. Investigators have hypothesized those genetic variants in the genes coding for estrogen signaling proteins may cause variable sensitivity to the hormone and influence an individual's estrogen-sensitive phenotypes. The most obvious candidate genes are the estrogen receptors alpha and (ERalpha and beta). However, the regulation of these genes is complex and not well understood. Furthermore, their coding exons, and regulatory sequences are dispersed across large segments of the genome. A number of common polymorphisms have been identified in both ERalpha and ERbeta, with variable degrees of evidence of their direct biological significance and their association with human disease. The identification of genetic variations associated with altered estrogen response is of potential public health importance. Insights may be gained into the pathogenesis of estrogen sensitive diseases such as osteoporosis, breast cancer and cardiovascular disease contributing to the development and application of newer therapies for these disorders. Furthermore, genetic variants that alter sensitivity to estrogen may affect both therapeutic and harmful responses to exogenous estrogen administered in the form of the oral contraceptive pill or hormone replacement therapy. This clinical significance has led to the publication of a number of patents which will be reviewed.

  8. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Patient package inserts for estrogens. 310.515 Section 310.515 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS Requirements for Specific New Drugs or Devices § 310.515 Patient package inserts for estrogens....

  9. Modulation of estrogenic effects by environmental temperature and food availability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endocrine-disrupting chemicals (EDCs), in combination with environmental influences, interfere with endocrine function in humans and wildlife. Estrogens are a type of EDC that may alter the hypothalamic-pituitary-gonadal axis in male fathead minnows, Pimephales promelas. The impact of estrogens on P...

  10. EADB: an estrogenic activity database for assessing potential endocrine activity.

    PubMed

    Shen, Jie; Xu, Lei; Fang, Hong; Richard, Ann M; Bray, Jeffrey D; Judson, Richard S; Zhou, Guangxu; Colatsky, Thomas J; Aungst, Jason L; Teng, Christina; Harris, Steve C; Ge, Weigong; Dai, Susie Y; Su, Zhenqiang; Jacobs, Abigail C; Harrouk, Wafa; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2013-10-01

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.

  11. Bioassay- versus analytically-derived estrogen equivalents: Ramifications for monitoring

    EPA Science Inventory

    Due to concern for possible endocrine-related effects on aquatic vertebrates, environmental estrogens (EEs) are a growing focus of surface water contaminant monitoring programs. Some efforts utilize measurement of a targeted set of chemicals known to act as estrogen receptor (ER)...

  12. Anti-estrogenic activity of lignans from Acanthopanax chiisanensis root.

    PubMed

    Lee, Sanghyun; Yoo, Hye Hyun; Piao, Xiang Lan; Kim, Ju Sun; Kang, Sam Sik; Shin, Kuk Hyun

    2005-02-01

    Anti-estrogenic activity of (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), and 3-(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl)butyrolactone (5) isolated from the root of Acanthopanax chiisanensis was tested using Ishikawa cells. Among them, compound 3 exhibited anti-estrogenic activity (IC50 = 4.86 microM).

  13. Evaluation of the estrogenic activity of Leguminosae plants.

    PubMed

    Yoo, Hye Hyun; Kim, Taehyeong; Ahn, Soyun; Kim, Yoon Jung; Kim, Hyun Young; Piao, Xiang Lan; Park, Jeong Hill

    2005-03-01

    The plant extracts of the Leguminosae family were screened for their estrogenic activity with the Ishikawa cell system. Of the tested plants, Desmodium oxyphyllum, Dunbaria villosa, Kummerowia striata, Lespedeza bicolor, Maackia amurensis, Maackia fauriei, Pueraria thunbergiana, and Sophora flavescens were highly estrogenic with EC50 values of less than 10 microg/ml.

  14. The emerging role of estrogen in B cell malignancies.

    PubMed

    Ladikou, Eleni-Eirini; Kassi, Eva

    2017-03-01

    Increasing evidence implicates a role of estrogens in hematological malignancies. We reviewed current knowledge on the emerging role of estrogens and estrogen receptors in normal B-cell function, chronic lymphocytic leukemia, and B-cell lymphoma. Data support that (1) normal human peripheral blood cells (mononuclear cells, total lymphocytes, T as well as B lymphocytes, and NK cells) express both estrogen receptor subtypes (ERα and ERβ), (2) B-cell malignancies express mainly ERβ while selective ERβ agonists inhibit cell growth and induce apoptosis, (3) estrogens regulate, via an ER-mediated pathway, gene expression of cyclins, kinases, bcl-2 proto-oncogene, activation-induced deaminase (AID), and transcription factors, associated with changes in BCR signaling and B cell tumorigenesis. In conclusion, estrogen receptors play an important role in normal B-cell function and B-cell tumorigenesis; however, further investigations are required to delineate the role of estrogens and estrogen receptors in the etiopathogenesis and therapy of B-cell malignancies.

  15. Vascular Aging in Women: is Estrogen the Fountain of Youth?

    PubMed Central

    Novella, Susana; Dantas, Ana Paula; Segarra, Gloria; Medina, Pascual; Hermenegildo, Carlos

    2012-01-01

    Aging is associated with structural and functional changes in the vasculature, including endothelial dysfunction, arterial stiffening and remodeling, impaired angiogenesis, and defective vascular repair, and with increased prevalence of atherosclerosis. Cardiovascular risk is similar for older men and women, but lower in women during their fertile years. This age- and sex-related difference points to estrogen as a protective factor because menopause is marked by the loss of endogenous estrogen production. Experimental and some clinical studies have attributed most of the protective effects of estrogen to its modulatory action on vascular endothelium. Estrogen promotes endothelial-derived NO production through increased expression and activity of endothelial nitric oxide synthase, and modulates prostacyclin and thromboxane A2 release. The thromboxane A2 pathway is key to regulating vascular tone in females. Despite all the experimental evidence, some clinical trials have reported no cardiovascular benefit from estrogen replacement therapy in older postmenopausal women. The “Timing Hypothesis,” which states that estrogen-mediated vascular benefits occur only before the detrimental effects of aging are established in the vasculature, offers a possible explanation for these discrepancies. Nevertheless, a gap remains in current knowledge of cardiovascular aging mechanisms in women. This review comprises clinical and experimental data on the effects of aging, estrogens, and hormone replacement therapy on vascular function of females. We aim to clarify how menopause and aging contribute jointly to vascular aging and how estrogen modulates vascular response at different ages. PMID:22685434

  16. Tamoxifen inhibits estrogen-induced hepatic injury in hamsters.

    PubMed

    Coe, J E; Ross, M J

    1988-01-01

    Estrogens have an unusual toxic effect on the liver of two hamster species, the Armenian and the Chinese hamster. The hepatotoxicity was detectable clinically by hyperbilirubinemia and confirmed histologically by the presence of hepatic degenerative-regenerative changes. Administration of tamoxifen with estrogen [either ethynyl estradiol or diethylstilbestrol (DES)] completely abrogated the hepatotoxic effects, suggesting that estrogen receptor (ER) was necessary for estrogen to damage liver. In Armenian hamsters, estrogens decreased hepatic synthesis of female protein (FP); tamoxifen also abolished this DES effect and resulted in a net increase in serum FP levels. DES administration produced higher serum bilirubin levels and lower serum FP levels in females than in males. Paradoxically, tamoxifen blocked these DES effects more effectively and efficiently in females than in males. Estrogens did not injure uteri of Armenian and Chinese hamsters and were nontoxic to livers of other hamsters species, such as Syrian and Turkish. This model provides another perspective of the acute cellular derangement that can be effected by estrogen-ER complex and may indicate a yet unknown mode of ER action.

  17. Assaying estrogenicity by quantitating the expression levels of endogenous estrogen-regulated genes.

    PubMed

    Jørgensen, M; Vendelbo, B; Skakkebaek, N E; Leffers, H

    2000-05-01

    Scientific evidence suggests that humans and wildlife species may experience adverse health consequences from exposure to environmental chemicals that interact with the endocrine system. Reliable short-term assays are needed to identify hormone-disrupting chemicals. In this study we demonstrate that the estrogenic activity of a chemical can be evaluated by assaying induction or repression of endogenous estrogen-regulated "marker genes" in human breast cancer MCF-7 cells. We included four marker genes in the assay--pS2, transforming growth factor beta3 (TGFbeta3), monoamine oxidase A, and [alpha]1-antichymotrypsin--and we evaluated estrogenic activity for 17beta-estradiol (E(2)), diethylstilbestrol, [alpha]-zearalanol, nonylphenol, genistein, methoxychlor, endosulphan, o,p-DDE, bisphenol A, dibutylphthalate, 4-hydroxy tamoxifen, and ICI 182.780. All four marker genes responded strongly to the three high-potency estrogens (E(2), diethylstilbestrol, and [alpha]-zearalanol), whereas the potency of the other chemicals was 10(3)- to 10(6)-fold lower than that of E(2). There were some marker gene-dependent differences in the relative potencies of the tested chemicals. TGFbeta3 was equally sensitive to the three high-potency estrogens, whereas the sensitivity to [alpha]-zearalanol was approximately 10-fold lower than the sensitivity to E(2) and diethylstilbestrol when assayed with the other three marker genes. The potency of nonylphenol was equal to that of genistein when assayed with pS2 and TGFbeta3, but 10- to 100-fold higher/lower with monoamine oxidase A and [alpha]1-antichymotrypsin, respectively. The results are in agreement with results obtained by other methods and suggest that an assay based on endogenous gene expression may offer an attractive alternative to other E-SCREEN methods.

  18. Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors.

    PubMed

    Pinto, Caroline; Grimaldi, Marina; Boulahtouf, Abdelhay; Pakdel, Farzad; Brion, François; Aït-Aïssa, Sélim; Cavaillès, Vincent; Bourguet, William; Gustafsson, Jan-Ake; Bondesson, Maria; Balaguer, Patrick

    2014-10-01

    Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28°C as compared to 37°C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.

  19. Alcohol Consumption and Urinary Estrogens and Estrogen Metabolites in Premenopausal Women

    PubMed Central

    Sisti, Julia S.; Hankinson, Susan E.; Xu, Xia; Eliassen, A. Heather; Ziegler, Regina

    2016-01-01

    In a cross-sectional analysis, we evaluated the associations of usual total alcohol and wine intake with a comprehensive profile of mid-luteal phase urinary estrogens and estrogen metabolites (referred to jointly as EM) in a sample of 603 premenopausal women participating in the Nurses' Health Study II (NHSII). A total of 15 individual EM (pmol/mg creatinine) were measured by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method with high accuracy and reproducibility. We used linear mixed models to calculate the adjusted geometric means of individual EM, EM grouped by metabolic pathways, and pathway ratios by category of alcohol intake with non-drinkers of alcohol as the referent. Total alcohol intake was not associated with total EM but was positively associated with estradiol (26 % higher among women consuming >15 g/day vs. non-drinkers; P trend=0.03). Wine consumption was positively associated with a number of EM measures including estradiol (22 % higher among women consuming ≥5 drinks/week vs. non-drinkers, P trend < 0.0001). In conclusion, the total alcohol intake was positively and significantly associated with urinary estradiol levels. Some differences in urinary estrogen metabolites were observed with wine drinking, when compared with non-drinkers. This study strengthens the evidence that alcohol consumption might play a role in breast cancer and other estrogen-related conditions. Additional studies of premenopausal women are needed to further explore the association of alcohol, particularly the specific types of alcohol, on patterns of estrogen metabolism in blood, urine, and tissue. PMID:26728472

  20. Alcohol Consumption and Urinary Estrogens and Estrogen Metabolites in Premenopausal Women.

    PubMed

    Hartman, Terryl J; Sisti, Julia S; Hankinson, Susan E; Xu, Xia; Eliassen, A Heather; Ziegler, Regina

    2016-02-01

    In a cross-sectional analysis, we evaluated the associations of usual total alcohol and wine intake with a comprehensive profile of mid-luteal phase urinary estrogens and estrogen metabolites (referred to jointly as EM) in a sample of 603 premenopausal women participating in the Nurses' Health Study II (NHSII). A total of 15 individual EM (pmol/mg creatinine) were measured by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method with high accuracy and reproducibility. We used linear mixed models to calculate the adjusted geometric means of individual EM, EM grouped by metabolic pathways, and pathway ratios by category of alcohol intake with non-drinkers of alcohol as the referent. Total alcohol intake was not associated with total EM but was positively associated with estradiol (26% higher among women consuming >15 g/day vs. non-drinkers; P trend = 0.03). Wine consumption was positively associated with a number of EM measures including estradiol (22% higher among women consuming ≥ 5 drinks/week vs. non-drinkers, P trend < 0.0001). In conclusion, the total alcohol intake was positively and significantly associated with urinary estradiol levels. Some differences in urinary estrogen metabolites were observed with wine drinking, when compared with non-drinkers. This study strengthens the evidence that alcohol consumption might play a role in breast cancer and other estrogen-related conditions. Additional studies of premenopausal women are needed to further explore the association of alcohol, particularly the specific types of alcohol, on patterns of estrogen metabolism in blood, urine, and tissue.

  1. Evolution of estrogen receptors in ray-finned fish and their comparative responses to estrogenic substances.

    PubMed

    Tohyama, Saki; Miyagawa, Shinichi; Lange, Anke; Ogino, Yukiko; Mizutani, Takeshi; Ihara, Masaru; Tanaka, Hiroaki; Tatarazako, Norihisa; Kobayashi, Tohru; Tyler, Charles R; Iguchi, Taisen

    2016-04-01

    In vertebrates, estrogens play fundamental roles in regulating reproductive activities through estrogen receptors (ESRs), and disruption of estrogen signaling is now of global concern for both wildlife and human health. To date, ESRs of only a limited number of species have been characterized. We investigated the functional diversity and molecular basis or ligand sensitivity of ESRs among ray-finned fish species (Actinopterygii), the most variable group within vertebrates. We cloned and characterized ESRs from several key species in the evolution of ray-finned fish including bichir (Polypteriformes, ESR1 and ESR2) at the basal lineage of ray-finned fish, and arowana (Osteoglossiformes, ESR1 and ESR2b) and eel (Anguilliformes, ESR1, ESR2a and ESR2b) both belonging to ancient early-branching lineages of teleosts, and suggest that ESR2a and ESR2b emerged through teleost-specific whole genome duplication, but an ESR1 paralogue has been lost in the early lineage of euteleost fish species. All cloned ESR isoforms showed similar responses to endogenous and synthetic steroidal estrogens, but they responded differently to non-steroidal estrogenic endocrine disrupting chemicals (EDCs) (e.g., ESR2a exhibits a weaker reporter activity compared with ESR2b). We show that variation in ligand sensitivity of ESRs can be attributed to phylogeny among species of different taxonomic groups in ray-finned fish. The molecular information provided contributes both to understanding of the comparative role of ESRs in the reproductive biology of fish and their comparative responses to EDCs.

  2. Effect of estrogenic binary mixtures in the yeast estrogen screen (YES).

    PubMed

    Ramirez, Tzutzuy; Buechse, Andreas; Dammann, Martina; Melching-Kollmuß, Stephanie; Woitkowiak, Claudia; van Ravenzwaay, Bennard

    2014-10-01

    Endocrine disrupting compounds (EDCs) of natural or synthetic origin can interfere with the balance of the hormonal system, either by altering hormone production, secretion, transport, or their binding and consequently lead to an adverse outcome in intact animals. An important aspect is the prediction of effects of combined exposure to two or more EDCs at the same time. The yeast estrogen assay (YES) is a broadly used method to assess estrogenic potential of chemicals. Besides exhibiting good predictivity to identify compounds which interfere with the estrogen receptor, it is easy to handle, rapid and therefore allows screening of a large number of single compounds and varying mixtures. Herein, we applied the YES assay to determine the potential combination effects of binary mixtures of two estrogenic compounds, bisphenol A and genistein, as well as one classical androgen that in vitro also exhibits estrogenic activity, trenbolone. In addition to generating data from combined exposure, we fitted these to a four-parametric logistic dose-response model. As all compounds tested share the same mode of action dose additivity was expected. To assess this, the Loewe model was utilized. Deviations between the Loewe additivity model and the observed responses were always small and global tests based on the whole dose-response data set indicated in general a good fit of the Loewe additivity model. At low concentrations concentration additivity was observed, while at high concentrations, the observed effect was lower than additivity, most likely reflecting receptor saturation. In conclusion, our results suggest that binary combinations of genistein, bisphenol A and trenbolone in the YES assay do not deviate from expected additivity.

  3. Science Signaling podcast for 24 May 2016: Designer estrogens.

    PubMed

    Katzenellenbogen, Benita S; Katzenellenbogen, John A; Madak-Erdogan, Zeynep; VanHook, Annalisa M

    2016-05-24

    This Podcast features an interview with Zeynep Madak-Erdogan, Benita Katzenellenbogen, and John Katzenellenbogen, authors of a Research Article that appears in the 24 May 2016 issue of Science Signaling, about designer estrogens that have the therapeutic benefits of natural estrogens, but less cancer risk. In addition to controlling female reproduction and secondary sex characteristics, estrogen is also an important regulator of metabolism, the vasculature, and bone. Estrogen production decreases as women enter menopause, leading to changes in metabolism, a reduced ability to repair blood vessels, and decreased bone density. Although hormone replacement therapy can alleviate these symptoms, it can also promote the growth of uterine and breast cancers. Madak-Erdogan et al engineered synthetic forms of estrogen that activate the cytosolic signaling pathways that are associated with the beneficial effects of this hormone without also activating the nuclear signaling events associated with cancer growth.Listen to Podcast.

  4. Of mice and men: the many guises of estrogens.

    PubMed

    Simpson, E R; Jones, M E

    2006-01-01

    Models of estrogen insufficiency have revealed new and unexpected roles for estrogens in males as well as females. These models include natural mutations in the aromatase gene in humans, as well as mouse knock-outs of aromatase and the estrogen receptors, and one man with a mutation in the ERa gene. These mutations, both natural and experimental, have revealed that estrogen deficiency results in a spectrum of symptoms. These include loss of fertility and libido in both males and females; loss of bone in both males and females; a cardiovascular and cerebrovascular phenotype; development of a metabolic syndrome in both males and females, with truncal adiposity and male-specific hepatic steatosis. Most of these symptoms can be reversed or attenuated by estradiol therapy. Thus estrogen is involved in the maintenance of general physiological homeostasis in both sexes.

  5. The Antidepressant-like Effects of Estrogen-mediated Ghrelin

    PubMed Central

    Wang, Pu; Liu, Changhong; Liu, Lei; Zhang, Xingyi; Ren, Bingzhong; Li, Bingjin

    2015-01-01

    Ghrelin, one of the brain-gut peptides, stimulates food-intake. Recently, ghrelin has also shown to play an important role in depression treatment. However, the mechanism of ghrelin’s antidepressant-like actions is unknown. On the other hand, sex differences in depression, and the fluctuation of estrogens secretion have been proved to play a key role in depression. It has been reported that women have higher level of ghrelin expression, and ghrelin can stimulate estrogen secretion while estrogen acts as a positive feedback mechanism to up-regulate ghrelin level. Ghrelin may be a potential regulator of reproductive function, and estrogen may have additional effect in ghrelin’s antidepressantlike actions. In this review, we summarize antidepressant-like effects of ghrelin and estrogen in basic and clinical studies, and provide new insight on ghrelin’s effect in depression. PMID:26412072

  6. Prediction of Estrogenic Bioactivity of Environmental Chemical Metabolites.

    PubMed

    Pinto, Caroline L; Mansouri, Kamel; Judson, Richard; Browne, Patience

    2016-09-19

    The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high-throughput screening assays to assess the endocrine activity of environmental chemicals. Considering that in vitro assays may have limited metabolic capacity, inactive chemicals that are biotransformed into metabolites with endocrine bioactivity may be missed for further screening and testing. Therefore, there is a value in developing novel approaches to account for metabolism and endocrine activity of both parent chemicals and their associated metabolites. We used commercially available software to predict metabolites of 50 parent compounds, out of which 38 chemicals are known to have estrogenic metabolites, and 12 compounds and their metabolites are negative for estrogenic activity. Three ER QSAR models were used to determine potential estrogen bioactivity of the parent compounds and predicted metabolites, the outputs of the models were averaged, and the chemicals were then ranked based on the total estrogenicity of the parent chemical and metabolites. The metabolite prediction software correctly identified known estrogenic metabolites for 26 out of 27 parent chemicals with associated metabolite data, and 39 out of 46 estrogenic metabolites were predicted as potential biotransformation products derived from the parent chemical. The QSAR models estimated stronger estrogenic activity for the majority of the known estrogenic metabolites compared to their parent chemicals. Finally, the three models identified a similar set of parent compounds as top ranked chemicals based on the estrogenicity of putative metabolites. This proposed in silico approach is an inexpensive and rapid strategy for the detection of chemicals with estrogenic metabolites and may reduce potential false negative results from in vitro assays.

  7. Window Of Opportunity: Estrogen As A Treatment For Ischemic Stroke✰

    PubMed Central

    Liu, Ran; Yang, Shao-Hua

    2013-01-01

    The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the “critical period” and newly emerged “biomarkers window” hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. PMID:23340160

  8. Gender and cataract--the role of estrogen.

    PubMed

    Zetterberg, Madeleine; Celojevic, Dragana

    2015-02-01

    There is evidence from epidemiologic data that cataract is more common in women than men. This is not solely due to a higher rate of cataract extraction in women, as is the case in the western world, but several population-based studies show that females have a higher prevalence of lens opacities, especially cortical. There is no firm evidence that lifestyle-related factors are the cause of this gender discrepancy. Focus has therefore been directed towards the role of estrogen in cataract formation. Although data on endogenous and exogenous estrogen involvement in cataractogenesis are conflicting, some studies have indicated that hormone therapy may decrease the risk of cataract and thus be protective. It has been hypothesized that the decrease in estrogen at menopause cause increased risk of cataract in women, i.e. not strictly the concentration of estrogen, but more the withdrawal effect. Estrogens are known to exert several anti-aging effects that may explain the longer lifespan in women, including metabolically beneficial effects, neuroprotection, preservation of telomeres and anti-oxidative properties. Since oxidative stress is considered important in cataractogenesis, studies have investigated the effects of estrogens on lens epithelial cells in culture or in animal models. Several investigators have found protection by physiological concentrations of 17β-estradiol against oxidative stress induced by H2O2 in cultured lens epithelial cells. Although both main types of estrogen receptors, ERα and ERβ, have been demonstrated in lens epithelium, most studies so far indicate that the estrogen-mediated protection in the lens is exerted through non-genomic, i.e. receptor-independent mechanisms, possibly through phosphorylation of extracellular signal-regulated kinase (ERK1/ERK2), a member of the mitogen-activated protein kinase (MAPK)-signaling pathway. Further studies are needed, both epidemiologic as to the role of hormone therapies, and laboratory studies

  9. Alkylphenols, polycyclic aromatic hydrocarbons, and organochlorines in sediment from Lake Shihwa, Korea: Instrumental and bioanalytical characterization

    SciTech Connect

    Khim, J.S.; Villeneuve, D.L.; Kannan, K.; Lee, K.T.; Snyder, S.A.; Koh, C.H.; Giesy, J.P.

    1999-11-01

    Lake Shihwa is an artificial lake, located on the west coast of Korea, that has experienced environmental deterioration since 1994, when it was formed by construction of a sea dike. This study used instrumental analysis and in vitro bioassays to characterize organic contaminants in sediment collected from 11 stations on Lake Shihwa. Alkylphenol (AP) concentrations in Lake Shihwa sediment ranged from 20.2 to 1,820 ng/g nonylphenol and from 4.69 to 50.5 ng/g octylphenol, on a dry weight basis. Maximum concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) were 30.8, 2.26, and 12.3 ng/g (dry weight), respectively. Significant estrogenic activity was associated with fractions containing APs. Mass-balance analysis suggested that reported concentrations of APs account for less than 20% of the estrogenic activity observed. No significant dioxin like activity was associated with fractions containing classic aryl hydrocarbon receptor agonists, such as PCBs, but the mid-polarity fractions containing PAHs and most polar fractions yielded significant dioxin like activity. Overall, most of the in vitro bioassay responses appear to have been caused by unidentified and/or undetectable compounds associated with Lake Shihwa sediment.

  10. Licorice Root Components in Dietary Supplements are Selective Estrogen Receptor Modulators with a Spectrum of Estrogenic and Anti-Estrogenic Activities

    PubMed Central

    Boonmuen, Nittaya; Gong, Ping; Ali, Zulfiqar; Chittiboyina, Amar G.; Khan, Ikhlas; Doerge, Daniel R.; Helferich, William G.; Carlson, Kathryn E.; Martin, Teresa; Piyachaturawat, Pawinee; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

    2016-01-01

    Licorice root extracts are often consumed as botanical dietary supplements by menopausal women as a natural alternative to pharmaceutical hormone replacement therapy. In addition to their components liquiritigenin (Liq) and isoliquiritigenin (Iso-Liq), known to have estrogenic activity, licorice root extracts also contain a number of other flavonoids, isoflavonoids, and chalcones. We have investigated the estrogenic activity of 7 of these components, obtained from an extract of Glycyrrhiza glabra powder, namely Glabridin (L1), Calycosin (L2), Methoxychalcone (L3), Vestitol (L4), Glyasperin C (L5), Glycycoumarin (L6), and Glicoricone (L7), and compared them with Liq, Iso-Liq, and estradiol (E2). All components, including Liq and Iso-Liq, have low binding affinity for estrogen receptors (ERs). Their potency and efficacy in stimulating the expression of estrogen-regulated genes reveal that Liq and Iso-Liq and L2, L3, L4, and L6 are estrogen agonists. Interestingly, L3 and L4 have an efficacy nearly equivalent to E2 but with a potency ca. 10,000-fold less. The other components, L1, L5 and L7, acted as partial estrogen antagonists. All agonist activities were reversed by the antiestrogen, ICI 182,780, or by knockdown of ERα with siRNA, indicating that they are ER dependent. In HepG2 hepatoma cells stably expressing ERα, only Liq, Iso-Liq, and L3 stimulated estrogen-regulated gene expression, and in all cases gene stimulation did not occur in HepG2 cells lacking ERα. Collectively, these findings classify the components of licorice root extracts as low potency, mixed ER agonists and antagonists, having a character akin to that of selective estrogen receptor modulators or SERMs. PMID:26631549

  11. Bioassays for estrogenic activity: development and validation of estrogen receptor (ERalpha/ERbeta) and breast cancer proliferation bioassays to measure serum estrogenic activity in clinical studies.

    PubMed

    Li, J; Lee, L; Gong, Y; Shen, P; Wong, S P; Wise, Stephen D; Yong, E L

    2009-02-01

    Standard estrogenic prodrugs such as estradiol valerate (E2V) and increasingly popular phytoestrogen formulations are commonly prescribed to improve menopausal health. These drugs are metabolized to numerous bioactive compounds, known or unknown, which may exert combinatorial estrogenic effects in vivo. The aim of this study is to develop and validate estrogen receptor (ER) alpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays to quantify serum estrogenic activities in a clinical trial setting. We measured changes in serum estrogenicity following ingestion of E2V and compared this to mass spectrometric measurements of its bioactive metabolites, estrone and 17beta-stradiol. ERalpha bioactivity of the 192 serum samples correlated well (R = 79%) with 17beta-estradiol levels, and adding estrone improved R to 0.83 (likelihood ratio test, P < 0.0001), suggesting that the ERalpha assay reflects summated activity of compounds in serum. ERbeta correlated moderately (R = 0.52) with estrone and 17beta-estradiol, with an estrone/17beta-estradiol coefficient ratio that was twice that of ERalpha, indicating estrone was more active on a molar basis in the ERbeta assay. Unlike the ERalpha and ERbeta bioassays, MCF-7 cell proliferation was driven by 17beta-estradiol, and addition of estrone did not increase the predictive value of the model, suggesting that the driver or drivers for breast cancer cell proliferation were not the same as for ERalpha and ERbeta transactivation. In contrast, a decoction of the traditional Chinese medicinal herb Epimedium pubescens did not induce significant changes in estrogenic bioactivity over baseline. These data indicate that ERalpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays reflect different aspects of estrogenic activity and that these assays suggest that the Epimedium formulation tested is unlikely to exert significant estrogenic effects in humans.

  12. Contemporary Alternatives to Plant Estrogens for Menopause

    PubMed Central

    Geller, Stacie E.; Studee, Laura

    2006-01-01

    Objectives Every year, millions of women begin the peri-menopause and may experience a number of symptoms related to this transition. Many women are reluctant to use exogenous hormone therapy for treatment of menopausal symptoms and are turning to botanical and dietary supplements (BDS) for relief. This paper reviews the literature on alternatives to plant estrogens for relief of menopausal symptoms. Methods The MEDLINE database was searched for clinical trials of non-estrogenic plant extracts for menopausal symptoms. To be included, studies had to include peri- or postmenopausal women as subjects. All clinical trials (randomized-controlled trials, open trials, and comparison group studies) were included for this review. Results Black Cohosh appears to be one of the most effective botanicals for relief of vasomotor symptoms, while St. John’s wort can improve mood disorders related to the menopausal transition. Many other botanicals have limited evidence to demonstrate safety and efficacy for relief of symptoms related to menopause. Conclusions A growing body of evidence suggests that some botanicals and dietary supplements could result in improved clinical outcomes. Health care providers should discuss these issues with their patients so they can assist them in managing these alternative therapies through an evidence-based approach. PMID:16884867

  13. Estrogen Signaling in Hypothalamic Circuits Controling Reproduction

    PubMed Central

    Kelly, Martin J.; Qiu, Jian

    2010-01-01

    It is well known that many of the actions of 17β-estradiol (E2) in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there is compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. Yet, it is not well understood how estrogen signals via membrane receptors, and how these signals impact not only membrane excitability but also gene transcription in neurons that modulate GnRH neuronal excitability. Indeed, it has been known for sometime that E2 can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, E2 can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review will consider our current knowledge of rapid membrane-initiated and intracellular signaling by E2 in hypothalamic neurons critical for reproductive function. PMID:20807512

  14. Epigenetic regulation of estrogen-dependent memory

    PubMed Central

    Fortress, Ashley M.; Frick, Karyn M.

    2014-01-01

    Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement. PMID:24878494

  15. Epigenetic regulation of estrogen-dependent memory.

    PubMed

    Fortress, Ashley M; Frick, Karyn M

    2014-10-01

    Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement.

  16. The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes.

    PubMed

    Botelho, Mónica C; Alves, Helena; Barros, Alberto; Rinaldi, Gabriel; Brindley, Paul J; Sousa, Mário

    2015-06-01

    Schistosoma haematobium, a parasitic flatworm that infects more than 100 million people, mostly in the developing world, is the causative agent of urogenital schistosomiasis, and is associated with a high incidence of squamous cell carcinoma (SCC) of the bladder. Schistosomiasis haematobia also appears to negatively influence fertility, and is particularly associated with female infertility. Given that estrogens and estrogen receptors are key players in human reproduction, we speculate that schistosome estrogen-like molecules may contribute to infertility through hormonal imbalances. Here, we review recent findings on the role of estrogens and estrogen receptors on both carcinogenesis and infertility associated with urogenital schistosomiasis and discuss the basic hormonal mechanisms that might be common in cancer and infertility.

  17. Enrichment of light hydrocarbon mixture

    SciTech Connect

    Yang; Dali; Devlin, David; Barbero, Robert S.; Carrera, Martin E.; Colling, Craig W.

    2010-08-10

    Light hydrocarbon enrichment is accomplished using a vertically oriented distillation column having a plurality of vertically oriented, nonselective micro/mesoporous hollow fibers. Vapor having, for example, both propylene and propane is sent upward through the distillation column in between the hollow fibers. Vapor exits neat the top of the column and is condensed to form a liquid phase that is directed back downward through the lumen of the hollow fibers. As vapor continues to ascend and liquid continues to countercurrently descend, the liquid at the bottom of the column becomes enriched in a higher boiling point, light hydrocarbon (propane, for example) and the vapor at the top becomes enriched in a lower boiling point light hydrocarbon (propylene, for example). The hollow fiber becomes wetted with liquid during the process.

  18. Enrichment of light hydrocarbon mixture

    SciTech Connect

    Yang, Dali; Devlin, David; Barbero, Robert S; Carrera, Martin E; Colling, Craig W

    2011-11-29

    Light hydrocarbon enrichment is accomplished using a vertically oriented distillation column having a plurality of vertically oriented, nonselective micro/mesoporous hollow fibers. Vapor having, for example, both propylene and propane is sent upward through the distillation column in between the hollow fibers. Vapor exits neat the top of the column and is condensed to form a liquid phase that is directed back downward through the lumen of the hollow fibers. As vapor continues to ascend and liquid continues to countercurrently descend, the liquid at the bottom of the column becomes enriched in a higher boiling point, light hydrocarbon (propane, for example) and the vapor at the top becomes enriched in a lower boiling point light hydrocarbon (propylene, for example). The hollow fiber becomes wetted with liquid during the process.

  19. Saturated hydrocarbons in bovine liver

    PubMed Central

    Nagy, Bartholomew; Modzeleski, Vincent E.; Scott, Ward M.

    1969-01-01

    A homologous series of n-alkanes (C14–C33) and two isoprenoid hydrocarbons, 2,6,10,14-tetramethylhexadecane (phytane) and 2,6,10,14-tetramethylpentadecane (pristane) have been identified in bovine liver. Another branched but non-isoprenoid alkane and three isomers of molecular formula C20H40 were partially identified. Phytane and the C18–C22 and C29–C33 n-alkanes were found to be the major components in liver, suggesting that at least the main hydrocarbon components were derived from various plants in the diet. The hydrocarbons were separated and identified by a series of steps involving solvent extraction, saponification, elution chromatography on alumina and silica gel columns, molecular sieving and by infrared and ultraviolet spectroscopy, followed by combined capillary gas chromatography–mass spectrometry. PMID:5820649

  20. Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-{alpha} with BCAR1 and Traf6

    SciTech Connect

    Robinson, Lisa J.; Yaroslavskiy, Beatrice B.; Griswold, Reed D.; Zadorozny, Eva V.; Guo, Lida; Tourkova, Irina L.; Blair, Harry C.

    2009-04-15

    The effects of estrogen on osteoclast survival and differentiation were studied using CD14-selected mononuclear osteoclast precursors from peripheral blood. Estradiol at {approx} 1 nM reduced RANKL-dependent osteoclast differentiation by 40-50%. Osteoclast differentiation was suppressed 14 days after addition of RANKL even when estradiol was withdrawn after 18 h. In CD14+ cells apoptosis was rare and was not augmented by RANKL or by 17-{beta}-estradiol. Estrogen receptor-{alpha} (ER{alpha}) expression was strongly down-regulated by RANKL, whether or not estradiol was present. Mature human osteoclasts thus cannot respond to estrogen via ER{alpha}. However, ER{alpha} was present in CD14+ osteoclast progenitors, and a scaffolding protein, BCAR1, which binds ER{alpha} in the presence of estrogen, was abundant. Immunoprecipitation showed rapid ({approx} 5 min) estrogen-dependent formation of ER{alpha}-BCAR1 complexes, which were increased by RANKL co-treatment. The RANKL-signaling intermediate Traf6, which regulates NF-{kappa}B activity, precipitated with this complex. Reduction of NF-{kappa}B nuclear localization occurred within 30 min of RANKL stimulation, and estradiol inhibited the phosphorylation of I{kappa}B in response to RANKL. Inhibition by estradiol was abolished by siRNA knockdown of BCAR1. We conclude that estrogen directly, but only partially, curtails human osteoclast formation. This effect requires BCAR1 and involves a non-genomic interaction with ER{alpha}.

  1. Cloning, expression and functional characterization of carp, Cyprinus carpio, estrogen receptors and their differential activations by estrogens.

    PubMed

    Katsu, Yoshinao; Lange, Anke; Miyagawa, Shinichi; Urushitani, Hiroshi; Tatarazako, Norishisa; Kawashima, Yukio; Tyler, Charles R; Iguchi, Taisen

    2013-01-01

    Sex-steroid hormones are essential for normal reproductive activity in both sexes. Estrogens are necessary for ovarian differentiation during a critical developmental stage in vertebrates and promote the growth and differentiation of the female reproductive system. Importantly, environmental estrogens can influence the reproductive system and have been shown to disrupt gametogenesis in males. To understand the molecular mechanisms of estrogen actions and to evaluate estrogen receptor ligand interactions in the carp, Cyprinus carpio, a species used widely for both field- and laboratory-based studies, we cloned all three carp estrogen receptors (ER; ERα, ERβ1 and ERβ2) and applied an estrogen-responsive (ERE)-luciferase reporter assay system to characterize the interactions of these receptors with steroidal and synthetic estrogens. DNA fragments encoding all three ERs in carp, ERα, ERβ1 and ERβ2, were obtained from the ovary using degenerate primer sets and PCR techniques, and full-length carp ER (cER) cDNAs were then obtained using RACE (rapid amplification of the cDNA end) techniques. Amino acid sequences of cERs showed overall homology of 46% (α vs β1), 49% (α vs β2) and 53% (β1 vs β2). In the transient transfection ERE-luciferase reporter assay system (using mammalian cells) the cER proteins displayed estrogen-dependent activation of transcription and cERβ2 showed a higher sensitivity to the natural steroid oestrogen, 17β-estradiol, than cERα. The assay system developed is a powerful assay for toxicology and provides a tool for future studies examining the receptor-environmental chemical interactions and estrogen-disrupting mechanisms in carp. The data presented also expand our knowledge of estrogen receptor evolution.

  2. Assessment of methods of detection of water estrogenicity for their use as monitoring tools in a process of estrogenicity removal.

    PubMed

    Blavier, J; Songulashvili, G; Simon, C; Penninckx, M; Flahaut, S; Scippo, M L; Debaste, F

    2016-12-01

    Methods of monitoring of estrogenicity in water were gathered, compared, and tested within the context of their practical use as measurement and design tools, in the development of a process of degradation of estrogenic endocrine disruptors. In this work, the focus was put on in vitro assays, with the use of analytical techniques as additional analysis when possible. Practically, from a literature review, four methods that seemed most suitable to practical use required in a process development were tested: the Yeast Estrogen Screen assay, the Lyticase-assisted Yeast Estrogen Screen assay (LYES), the MMV-LUC assay and the HPLC-UV analytical method. Dose-response curves in response to estrogenic standard 17β-estradiol were compared. Bisphenol A estrogenicity was measured by the methods as well. The model for the calculation of estradiol equivalents as measurements units was adapted. The methods were assessed in terms of ranges of detection, time of experiment, cost, ease of the experiment, reproducibility, etc. Based on that assessment, the LYES assay was selected and successfully applied to the monitoring of estrogenicity removal from 17β-estradiol and bisphenol A. More precisely, the bioassay allowed the acquisition of kinetic curves for a laboratory-scaled process of estrogenicity removal by immobilized enzymes in a continuous packed-bed reactor. The LYES assay was found to have a real methodological potential for scale-up and design of a treatment process. The HPLC-UV method showed good complementarity with the LYES assay for the monitoring of bisphenol A concentrations in parallel with estrogenicity, reporting no significant estrogenicity from degradation byproducts, among others.

  3. Method for producing viscous hydrocarbons

    DOEpatents

    Poston, Robert S.

    1982-01-01

    A method for recovering viscous hydrocarbons and synthetic fuels from a subterranean formation by drilling a well bore through the formation and completing the well by cementing a casing means in the upper part of the pay zone. The well is completed as an open hole completion and a superheated thermal vapor stream comprised of steam and combustion gases is injected into the lower part of the pay zone. The combustion gases migrate to the top of the pay zone and form a gas cap which provides formation pressure to produce the viscous hydrocarbons and synthetic fuels.

  4. Biological enhancement of hydrocarbon extraction

    DOEpatents

    Brigmon, Robin L.; Berry, Christopher J.

    2009-01-06

    A method of microbial enhanced oil recovery for recovering oil from an oil-bearing rock formation is provided. The methodology uses a consortium of bacteria including a mixture of surfactant producing bacteria and non-surfactant enzyme producing bacteria which may release hydrocarbons from bitumen containing sands. The described bioprocess can work with existing petroleum recovery protocols. The consortium microorganisms are also useful for treatment of above oil sands, ground waste tailings, subsurface oil recovery, and similar materials to enhance remediation and/or recovery of additional hydrocarbons from the materials.

  5. 21 CFR 862.1270 - Estrogens (total, in pregnancy) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Estrogens (total, in pregnancy) test system. 862... Test Systems § 862.1270 Estrogens (total, in pregnancy) test system. (a) Identification. As estrogens (total, in pregnancy) test system is a device intended to measure total estrogens in plasma, serum,...

  6. Hydrocarbon and chlorinated hydrocarbon-soluble magnesium dialkoxides

    SciTech Connect

    Kamienski, C.W.

    1988-05-31

    This patent describes a process for the preparation of hydrocarbon or chlorinated hydrocarbon solvent solutions of magnesium dialkoxides, which comprises reacting a suspension of magnesium metal or magnesium amide, or a solution of a dialkyimagnesium compound, in a volatile hydrocarbon or chlorinated hydrocarbon solvent with an alcohol selected from the group of (a) aliphatic, cycloaliphatic and acyclic C/sub 5/-C/sub 18/ beta- and gamma-alkyl-substituted secondary and tertiary monohydric alcohols; or (b) mixtures of the (a) alcohols with C/sub 3/-C/sub 18/ aliphatic or cycloaliphatic beta- and gamma-alkyl-unsubstituted secondary or tertiary alcohols; or (c) mixtures of the (a) alcohols with C/sub 1/-C/sub 18/ aliphatic primary unsubstituted and 2-alkyl-substituted alcohols; the mole ratios of the (a) to the (b), and the (a) to the (c), alcohols being 1 of the (a) alcohols to 0.1 to 2 of the (b) and/or the (c) alcohols.

  7. THE PHOTOTOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) continues to be interested in developing methods for the detection of polycyclic aromatic hydrocarbons (PAHS) in the environment. Polycyclic aromatic hydrocarbons (PAHS) are common contaminants in our environment. Being major product...

  8. Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A.

    PubMed

    Zsarnovszky, Attila; Le, Hoa H; Wang, Hong-Sheng; Belcher, Scott M

    2005-12-01

    In addition to regulating estrogen receptor-dependent gene expression, 17beta-estradiol (E(2)) can directly influence intracellular signaling. In primary cultured cerebellar neurons, E(2) was previously shown to regulate growth and oncotic cell death via rapid stimulation of ERK1/2 signaling. Here we show that ERK1/2 signaling in the cerebellum of neonatal and mature rats was rapidly responsive to E(2) and during development to the environmental estrogen bisphenol A (BPA). In vivo dose-response analysis for each estrogenic compound was performed by brief (6-min) intracerebellar injection, followed by rapid fixation and phosphorylation-state-specific immunohistochemistry to quantitatively characterize changes in activated ERK1/2 (pERK) immunopositive cell numbers. Beginning on postnatal d 8, E(2) significantly influenced the number of pERK-positive cells in a cell-specific manner that was dependent on concentration and age but not sex. In cerebellar granule cells on postnatal d 10, E(2) or BPA increased pERK-positive cell numbers at low doses (10(-12) to 10(-10) M) and at higher (10(-7) to 10(-6) M) concentrations. Intermediate concentrations of either estrogenic compound did not modify basal ERK signaling. Rapid E(2)-induced increases in pERK immunoreactivity were specific to the ERK1/2 pathway as demonstrated by coinjection of the mitogen-activated, ERK-activating kinase (MEK)1/2 inhibitor U0126. Coadministration of BPA (10(-12) to 10(-10) M) with 10(-10) M E(2) dose-dependently inhibited rapid E(2)-induced ERK1/2 activation in developing cerebellar neurons. The ability of BPA to act as a highly potent E(2) mimetic and to also disrupt the rapid actions of E(2) at very low concentrations during cerebellar development highlights the potential low-dose impact of xenoestrogens on the developing brain.

  9. Estrogenic/antiestrogenic activity of selected selective serotonin reuptake inhibitors

    PubMed Central

    POP, ANCA; LUPU, DIANA IOANA; CHERFAN, JULIEN; KISS, BELA; LOGHIN, FELICIA

    2015-01-01

    Background and aims Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed classes of psychotropics. Even though the SSRI class consists of 6 molecules (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), only fluoxetine was intensively studied for endocrine disruptive effects, while the other SSRIs received less attention. This study was designed to evaluate the estrogenic/antiestrogenic effect of fluoxetine, sertraline and paroxetine. Methods The in vitro (anti)estrogenic activity was assessed using a firefly luciferase reporter construct in the T47D-KBluc breast cancer cell line. These cells express nuclear estrogen receptors that can activate the transcription of the luciferase reporter gene upon binding of estrogen receptor agonists. Results All three compounds were found to interact with the estrogen receptor. Fluoxetine had dual properties, weak estrogenic at lower concentrations and antiestrogenic effect at higher concentrations. Sertraline shared the same properties with fluoxetine, but also increased the estradiol-mediated transcriptional activity. Paroxetine presented only one type of effect, the ability to increase the estradiol-mediated transcriptional activity. Conclusions Overall, our results indicate a possible interaction of SSRIs with the estrogen receptor. As SSRIs are being used by all categories of population, including pregnant women or children, establishing whether they can affect the endocrine mediated mechanisms should be a priority. PMID:26609273

  10. Estrogen Receptors and Their Implications in Colorectal Carcinogenesis

    PubMed Central

    Caiazza, Francesco; Ryan, Elizabeth J.; Doherty, Glen; Winter, Desmond C.; Sheahan, Kieran

    2015-01-01

    Upon binding their cognate receptors, ERα (ESR1) and ERβ (ESR2), estrogens activate intracellular signaling cascades that have important consequences for cellular behavior. Historically linked to carcinogenesis in reproductive organs, estrogens have also been implicated in the pathogenesis of different cancer types of non-reproductive tissues including the colon. ERβ is the predominant estrogen receptor expressed in both normal and malignant colonic epithelium. However, during colon cancer progression, ERβ expression is lost, suggesting that estrogen signaling may play a role in disease progression. Estrogens may in fact exert an anti-tumor effect through selective activation of pro-apoptotic signaling mediated by ERβ, inhibition of inflammatory signals and modulation of the tumor microenvironment. In this review, we analyze the estrogen pathway as a possible therapeutic avenue in colorectal cancer, we report the most recent experimental evidence to explain the cellular and molecular mechanisms of estrogen-mediated protection against colorectal tumorigenesis, and we discuss future challenges and potential avenues for targeted therapy. PMID:25699240

  11. Determination of estrogenic potential in waste water without sample extraction.

    PubMed

    Avberšek, Miha; Žegura, Bojana; Filipič, Metka; Uranjek-Ževart, Nataša; Heath, Ester

    2013-09-15

    This study describes the modification of the ER-Calux assay for testing water samples without sample extraction (NE-(ER-Calux) assay). The results are compared to those obtained with ER-Calux assay and a theoretical estrogenic potential obtained by GC-MSD. For spiked tap and waste water samples there was no statistical difference between estrogenic potentials obtained by the three methods. Application of NE-(ER-Calux) to "real" influent and effluents from municipal waste water treatment plants and receiving surface waters found that the NE-(ER-Calux) assay gave higher values compared to ER-Calux assay and GC-MSD. This is explained by the presence of water soluble endocrine agonists that are usually removed during extraction. Intraday dynamics of the estrogenic potential of a WWTP influent and effluent revealed an increase in the estrogenic potential of the influent from 12.9 ng(EEQ)/L in the morning to a peak value of 40.0 ng(EEQ)/L in the afternoon. The estrogenic potential of the effluent was estrogenic potential was 92-98%. Daytime estrogenic potential values varied significantly.

  12. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

    SciTech Connect

    Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck . E-mail: khchung@skku.edu

    2006-08-01

    Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect.

  13. Estrogen patient package insert: medication acceptance despite negative attitudes

    SciTech Connect

    Weintraub, M.; Glickstein, S.; Lasagna, L.

    1981-08-01

    We surveyed 100 women receiving short courses of estrogen post partum to suppress lactation. Thirty six had significant apprehension about estrogens, but took them. These women were significantly older and better educated and 92% of them were married. In contrast, only one third of the ''nonapprehensive'' women were married and they had significantly lower family incomes. More of the apprehensive women read the estrogen patient package insert (PPI) and almost 30% developed negative attitudes toward estrogens. The major concerns of these women reflected information in the PPI about cancer and thromboembolism. The reasons given for taking estrogens despite apprehension included the lower risk of short courses, assurance from physicians, nurses, or family members, and the desired therapeutic effect. These women should not be given the current estrogen PPI, which was designed to warn women of the risks of long-term estrogen use; a PPI should be written specifically for patients receiving short courses. Similar problems will arise with the PPIs for other medications that have different risks for different therapeutic indications.

  14. Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis

    PubMed Central

    Li, Chenggang; Li, Na; Liu, Xiaolei; Zhang, Erik Y.; Sun, Yang; Masuda, Kouhei; Li, Jing; Sun, Julia; Morrison, Tasha; Li, Xiangke; Chen, Yuanguang; Wang, Jiang; Karim, Nagla A.; Zhang, Yi; Blenis, John; Reginato, Mauricio J.; Henske, Elizabeth P.; Yu, Jane J.

    2016-01-01

    Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient–derived cells’ resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis. The resistance to anoikis was reversed by the proteasome inhibitor, bortezomib. Treatment of LAM patient–derived cells with estrogen plus bortezomib promoted anoikis compared with estrogen alone. Depletion of Bim by siRNA in TSC2-deficient cells resulted in anoikis resistance. Treatment of mice with bortezomib reduced estrogen-promoted lung colonization of TSC2-deficient cells. Importantly, molecular depletion of Bim by siRNA in Tsc2-deficient cells increased lung colonization in a mouse model. Collectively, these data indicate that Bim plays a key role in estrogen-enhanced survival of LAM patient–derived cells under detached conditions that occur with dissemination. Thus, targeting Bim may be a plausible future treatment strategy in patients with LAM. PMID:27882343

  15. Synthesis and Functional Analysis of Novel Bivalent Estrogens

    PubMed Central

    Wendlandt, Alison E.; Yelton, Sharon M.; Lou, Dingyuan; Watt, David S.; Noonan, Daniel J.

    2010-01-01

    The steroid hormone estrogen plays a critical role in female development and homeostasis. Estrogen mediates its effects through binding and activation of specific estrogen receptors alpha (ERα) and beta (ERβ), members of the steroid/nuclear receptor family of ligand-induced transcription factors. Due to their intimate roles in genomic and nongenomic signaling pathways, these hormones and their receptors have been also implicated in the pathologies of a variety of cancers and metabolic disorders, and have been the target of large therapeutic development efforts. The binding of estrogen to its respective receptors initiates a cascade of events that include receptor dimerization, nuclear localization, DNA binding and recruitment of co-regulatory protein complexes. In this manuscript, we investigate the potential for manipulating steroid receptor gene expression activity through the development of bivalent steroid hormones that are predicted to facilitate hormone receptor dimerization events. Data are presented for the development and testing of novel estrogen dimers, linked through their C-17 moiety, that can activate estrogen receptor alpha (ERα)-mediated transcription events with efficacy and potency equal to or greater than that of ERα’s cognate ligand, 17β-estradiol. These bivalent estrogen structures open the door to the development of a variety of steroid therapeutics that could dramatically impact future drug development in this area. PMID:20685325

  16. Tissue-selective estrogen complexes for postmenopausal women.

    PubMed

    Mirkin, Sebastian; Komm, Barry S

    2013-11-01

    Although hormone therapy using estrogens plus progestogens (EPT) is effective for the management of menopausal symptoms (e.g., vasomotor symptoms and vulvar/vaginal atrophy) and prevention/treatment of postmenopausal osteoporosis, EPT is associated with safety and tolerability concerns. A new alternative to EPT is the tissue selective estrogen complex (TSEC), which partners a selective estrogen receptor modulator (SERM) with one or more estrogens and is designed to treat menopausal symptoms and prevent postmenopausal osteoporosis without the tolerability concerns associated with EPT. The first TSEC to reach advanced clinical development is a combination of the SERM bazedoxifene (BZA) with conjugated estrogens (CE). BZA has been shown to inhibit the stimulatory activity of CE on uterine tissue and breast in vitro and in vivo. In clinical studies, BZA/CE treatment has been associated with significant improvements in menopausal symptoms including hot flushes and vulvar/vaginal atrophy and significant increases in bone mineral density, coupled with reductions in bone turnover marker levels and improvements in sleep and health-related quality of life. Additionally, BZA/CE has been shown to have a neutral effect on endometrial and breast tissue because BZA inhibits the stimulatory effects of estrogens in tissue-selective fashion in these 2 organs. Taken together, results of these preclinical and clinical studies indicate that the benefits of estrogens for treating menopausal symptoms are maintained with BZA/CE without endometrial or breast stimulation, resulting in a safe and effective treatment for symptomatic postmenopausal women.

  17. Developmental synergism of steroidal estrogens in sex determination.

    PubMed

    Bergeron, J M; Willingham, E; Osborn, C T; Rhen, T; Crews, D

    1999-02-01

    Gonadal sex in the red-eared slider turtle, Trachemys scripta, is determined by incubation temperature during embryonic development. Evidence suggests that temperature determines sex by influencing steroid hormone metabolism and/or sensitivity: steroidogenic enzyme inhibitors or exogenous sex steroid hormones and their man-made analogs override (or enhance) temperature effects on sex determination. Specifically, nonaromatizable androgens and aromatase inhibitors induce testis differentiation at female-producing temperatures, whereas aromatizable androgens and estrogens induce ovary differentiation at male-producing temperatures. Moreover, natural estrogens and temperature synergize to produce more females than would be expected if estrogens and temperature had purely additive effects on sex determination. In this study, we use sex reversal of turtle embryos incubated at a male-producing temperature to examine synergism among steroidal estrogens: estrone, 17ss-estradiol, and estriol. A low dose of 17ss-estradiol (200 ng) showed significant synergism when administered with a single low dose of estriol (10 ng). Likewise, a single low dose of estrone (250 ng) had a synergistic effect when combined with the same low dose of estriol (10 ng). We conclude that the weak natural estrogens estrone and 17ss-estradiol synergize with a low dose of the more potent estriol to reverse gonadal sex during the critical period of sexual differentiation. These results suggest that weak environmental estrogens may also synergize with stronger natural estrogens.

  18. INTERACTION OF ESTROGEN AND PROGESTERONE IN CHICK OVIDUCT DEVELOPMENT

    PubMed Central

    Oka, Takami; Schimke, Robert T.

    1969-01-01

    Daily administration of estrogen to immature female chicks results in marked oviduct growth and appearance of characteristic tubular gland cells which contain lysozyme. Although a rapid increase in total DNA and RNA content begins within 24 hr, cell specific protein, lysozyme, is first detectable after 3 days of estrogen. Progesterone administered concomitantly with estrogen antagonizes the estrogen-induced tissue growth as well as appearance of tubular gland cells and their specific products, lysozyme and ovalbumin. When the initiation of progesterone administration is delayed for progressively longer periods (days) during estrogen treatment, proportionally greater growth occurs with more lysozyme and tubular gland cells after 5 days of total treatment. Progesterone does not inhibit the estrogen-stimulated increase in uptake of α-aminoisobutyric acid and water by oviduct occurring within 24 hr or the estrogen-induced increase in total lipid, phospholipid, and phosphoprotein content of serum. The above results of progesterone antagonism can best be explained by the hypothesis that progesterone inhibits the initial proliferation of cells which become tubular gland cells but does not antagonize the subsequent cytodifferentiation leading to the synthesis of lysozyme and ovalbumin once such cell proliferation has occurred. PMID:5814004

  19. Glyphosate induces human breast cancer cells growth via estrogen receptors.

    PubMed

    Thongprakaisang, Siriporn; Thiantanawat, Apinya; Rangkadilok, Nuchanart; Suriyo, Tawit; Satayavivad, Jutamaad

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study.

  20. In vitro estrogenic activity of Achillea millefolium L.

    PubMed

    Innocenti, G; Vegeto, E; Dall'Acqua, S; Ciana, P; Giorgetti, M; Agradi, E; Sozzi, A; Fico, G; Tomè, F

    2007-02-01

    Isolation and biological characterization of pure compounds was used to identify and characterize estrogenic activity and estrogen receptors (ER) preference in chemical components of Achillea millefolium. This medicinal plant is used in folk medicine as an emmenagogue. In vitro assay, based on recombinant MCF-7 cells, showed estrogenic activity in a crude extract of the aerial parts of A. millefolium. After fractionation of the crude extract with increasing polar solvents, estrogenic activity was found in the methanol/water fraction. Nine compounds were isolated and characterized by HR-MS spectra and 1D- and 2D-NMR techniques. In particular, dihydrodehydrodiconiferyl alcohol 9-O-beta-D-glucopyranoside - a glycosyl-neolignan - was isolated for the first time from the genus Achillea in addition to six flavone derivatives, apigenin, apigenin-7-O-beta-D-glucopyranoside, luteolin, luteolin-7-O-beta-D-glucopyranoside, luteolin-4'-O-beta-D-glucopyranoside, rutin, and two caffeic acid derivatives, 3,5-dicaffeoylquinic acid and chlorogenic acid. Apigenin and luteolin, the most important estrogenic compounds among those tested, were studied for their ability to activate alpha or beta estrogen receptors (ERalpha, ERbeta) using transiently transfected cells. Our results suggest that isolation and biological characterization of estrogenic compounds in traditionally used medicinal plants could be a first step in better assessing further (e.g. in vivo) tests of nutraceutical and pharmacological strategies based on phytoestrogens.

  1. Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis.

    PubMed

    Li, Chenggang; Li, Na; Liu, Xiaolei; Zhang, Erik Y; Sun, Yang; Masuda, Kouhei; Li, Jing; Sun, Julia; Morrison, Tasha; Li, Xiangke; Chen, Yuanguang; Wang, Jiang; Karim, Nagla A; Zhang, Yi; Blenis, John; Reginato, Mauricio J; Henske, Elizabeth P; Yu, Jane J

    2016-11-17

    Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily affects young women. Genetic evidence suggests that LAM cells bearing TSC2 mutations migrate to the lungs, proliferate, and cause cystic remodeling. The female predominance indicates that estrogen plays a critical role in LAM pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by inhibition of anoikis. We report here that estrogen increased LAM patient-derived cells' resistance to anoikis in vitro, accompanied by decreased accumulation of the proapoptotic protein Bim, an activator of anoikis. The resistance to anoikis was reversed by the proteasome inhibitor, bortezomib. Treatment of LAM patient-derived cells with estrogen plus bortezomib promoted anoikis compared with estrogen alone. Depletion of Bim by siRNA in TSC2-deficient cells resulted in anoikis resistance. Treatment of mice with bortezomib reduced estrogen-promoted lung colonization of TSC2-deficient cells. Importantly, molecular depletion of Bim by siRNA in Tsc2-deficient cells increased lung colonization in a mouse model. Collectively, these data indicate that Bim plays a key role in estrogen-enhanced survival of LAM patient-derived cells under detached conditions that occur with dissemination. Thus, targeting Bim may be a plausible future treatment strategy in patients with LAM.

  2. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds.

    PubMed

    Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

    2006-08-01

    Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect.

  3. p150/Glued Modifies Nuclear Estrogen Receptor Function

    PubMed Central

    Lee, Soo Jung; Chae, Christina; Wang, Michael M.

    2009-01-01

    Estrogen modulates gene expression through interactions with estrogen receptors (ERs) that bind chromosomal target genes. Recent studies have suggested an interaction between the cytoskeletal system and estrogen signaling; these have implicated a role of cytoplasmic microtubules in scaffolding ERα and enhancing nongenomic function; in addition, other experiments demonstrate that dynein light chain 1 may chaperone ERα to the nucleus, indirectly increasing transcriptional potency. Actin/myosin and dynein light chain 1 are also required for estrogen-mediated chromosomal movement that is required for transcriptional up-regulation of ERα targets. We present evidence that the dynactin component, p150/glued, directly influences the potency of nuclear ER function. Increasing the stoichiometric ratio of p150/glued and ERα by overexpression enhances estrogen responses. ERα enhancement by p150/glued does not appear to be influenced by shifts in subcellular localization because microtubule disruption fails to increase nuclear ERα. Rather, we find that modest amounts of p150/glued reside in the nucleus of cells, suggesting that it plays a direct role in nuclear transcription. Notably, p150/glued is recruited to the pS2 promoter in the presence of hormone, and, in MCF-7 cells, knockdown of p150/glued levels reduces estrogen-dependent transcription. Our results suggest that p150/glued modulates estrogen sensitivity in cells through nuclear mechanisms. PMID:19228793

  4. Estrogen binding and estrogen receptor activity in the human prostate: a preliminary report.

    PubMed

    Fondo, E Y; Menendez-Botet, C J; Schwartz, M K; Whitmore, W F

    1981-03-01

    Assay of estrogen receptor activity in prostates from patients who ranged in age from 22 to 78 years and had not received any previous hormonal therapy was carried out by incubation of cytosols with (3)H-estradiol in the presence and absence of excess, nonradioactive estradiol. Hyperplastic prostatic tissues were used in the study. The kinetics of each reaction were studied and analysis of the data revealed 3.4 to 35.7 femtomoles of receptor protein per mg of cytosol protein; the dissociation constants obtained from a Scatchard plot ranged from 1.1 × 10(-10) to 1.2 × 10(-8)M.The small number of patients prevents realistic quantitative assessment of the apparent estrogen binding activity demonstrated in these preliminary studies, but the qualitative identification of such activity provides possible grounds for further insight into the hormonal mechanisms in the pathophysiology of prostatic diseases and of their responses to endocrine therapy.

  5. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    PubMed Central

    Mansouri, Kamel; Abdelaziz, Ahmed; Rybacka, Aleksandra; Roncaglioni, Alessandra; Tropsha, Alexander; Varnek, Alexandre; Zakharov, Alexey; Worth, Andrew; Richard, Ann M.; Grulke, Christopher M.; Trisciuzzi, Daniela; Fourches, Denis; Horvath, Dragos; Benfenati, Emilio; Muratov, Eugene; Wedebye, Eva Bay; Grisoni, Francesca; Mangiatordi, Giuseppe F.; Incisivo, Giuseppina M.; Hong, Huixiao; Ng, Hui W.; Tetko, Igor V.; Balabin, Ilya; Kancherla, Jayaram; Shen, Jie; Burton, Julien; Nicklaus, Marc; Cassotti, Matteo; Nikolov, Nikolai G.; Nicolotti, Orazio; Andersson, Patrik L.; Zang, Qingda; Politi, Regina; Beger, Richard D.; Todeschini, Roberto; Huang, Ruili; Farag, Sherif; Rosenberg, Sine A.; Slavov, Svetoslav; Hu, Xin; Judson, Richard S.

    2016-01-01

    Background: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. Objectives: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. Methods: CERAPP combined multiple models developed in collaboration with 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure–activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. Results: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing. Conclusion: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other

  6. Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity

    DTIC Science & Technology

    2011-07-01

    Medical Research Manhasset, NY 11030 Systemic lupus erythematosus is an autoimmune disease that occurs preferentially in women. We have developed a...Introduction: There is abundant clinical data that estrogen can increase risk of developing systemic lupus erythematosus (SLE) and disease...crux of systemic lupus erythematosus (SLE). SLE is characterized by an array of antibodies against self-antigens (3,4). Anti–double-stranded (ds) DNA

  7. Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B Cell Autoreactivity

    DTIC Science & Technology

    2010-07-01

    14. ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE, it is... Systemic Lupus , Estrogen, BCR Signaling, B Cell Maturation, B Cell Selection 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...therefore, be important to test ERα antagonists in murine studies of B cell development and in murine models of lupus . This approach to therapy might

  8. Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B cell Autoreactivity. Addendum

    DTIC Science & Technology

    2012-07-01

    14. ABSTRACT Systemic lupus erythematosus is an autoimmune disease that occurs preferentially in women. We have developed a murine model...4 Introduction: There is abundant clinical data that estrogen can increase risk of developing systemic lupus erythematosus (SLE) and disease...Kawabata, D., Pinto-Rodriguez, D., Grimaldi, C. and Diamond B. Hormonal regulator of B cell function and systemic lupus erythematosus . Lupus 17:528

  9. Mixture Effects of Estrogenic Pesticides at the Human Estrogen Receptor α and β

    PubMed Central

    Seeger, Bettina; Klawonn, Frank; Nguema Bekale, Boris; Steinberg, Pablo

    2016-01-01

    Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor α (hERα) or β (hERβ). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human-relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17β-estradiol were tested experimentally at the hERα in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ERα chemical-activated luciferase gene expression (ERα CALUX) assay and at the hERβ in the ERβ CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hERβ showed that most test substances being active at the hERα could also elicit additive effects at the hERβ, but the hERβ was less sensitive. In conclusion, effects of the same ligands at the hERα and the hERβ could influence the estrogenic outcome under physiological conditions. PMID:26812056

  10. Measurement of Hydrocarbon Transport in Bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hydrocarbon uptake by bacteria has not been extensively studied, and strong evidence for active transport of hydrocarbons is lacking. The volatile nature of hydrocarbons, their hydrophobicity, and their relatively low aqueous solubilities can complicate transport assays. Here we present a detailed...

  11. 33 CFR 157.166 - Hydrocarbon emissions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Hydrocarbon emissions. 157.166... Crude Oil Washing (COW) System on Tank Vessels Cow Operations § 157.166 Hydrocarbon emissions. If the... ballasted in that port the hydrocarbon vapors in each tank are contained by a means under § 157.132....

  12. 33 CFR 157.166 - Hydrocarbon emissions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Hydrocarbon emissions. 157.166... Crude Oil Washing (COW) System on Tank Vessels Cow Operations § 157.166 Hydrocarbon emissions. If the... ballasted in that port the hydrocarbon vapors in each tank are contained by a means under § 157.132....

  13. 33 CFR 157.166 - Hydrocarbon emissions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Hydrocarbon emissions. 157.166... Crude Oil Washing (COW) System on Tank Vessels Cow Operations § 157.166 Hydrocarbon emissions. If the... ballasted in that port the hydrocarbon vapors in each tank are contained by a means under § 157.132....

  14. 33 CFR 157.166 - Hydrocarbon emissions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Hydrocarbon emissions. 157.166... Crude Oil Washing (COW) System on Tank Vessels Cow Operations § 157.166 Hydrocarbon emissions. If the... ballasted in that port the hydrocarbon vapors in each tank are contained by a means under § 157.132....

  15. 33 CFR 157.166 - Hydrocarbon emissions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Hydrocarbon emissions. 157.166... Crude Oil Washing (COW) System on Tank Vessels Cow Operations § 157.166 Hydrocarbon emissions. If the... ballasted in that port the hydrocarbon vapors in each tank are contained by a means under § 157.132....

  16. Hydrophobic encapsulation of hydrocarbon gases.

    PubMed

    Leontiev, Alexander V; Saleh, Anas W; Rudkevich, Dmitry M

    2007-04-26

    [reaction: see text] Encapsulation data for hydrophobic hydrocarbon gases within a water-soluble hemicarcerand in aqueous solution are reported. It is concluded that hydrophobic interactions serve as the primary driving force for the encapsulation, which can be used for the design of gas-separating polymers with intrinsic inner cavities.

  17. Steam Hydrocarbon Cracking and Reforming

    ERIC Educational Resources Information Center

    Golombok, Michael

    2004-01-01

    The interactive methods of steam hydrocarbon reforming and cracking of the oil and chemical industries are scrutinized, with special focus on their resemblance and variations. The two methods are illustrations of equilibrium-controlled and kinetically-controlled processes, the analysis of which involves theories, which overlap and balance each…

  18. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    SciTech Connect

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-11-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor alpha (ERalpha) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERalpha and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERalpha- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17beta-estradiol (E{sub 2}). With these LTEE cells and with parallel control cells cultured without E{sub 2} supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E{sub 2}-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E{sub 2}.

  19. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    PubMed Central

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-01-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E2). With these LTEE cells and with parallel control cells cultured without E2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E2-dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E2. PMID:19619570

  20. Neurobiology of estrogen status in deep craniofacial pain.

    PubMed

    Bereiter, David A; Okamoto, Keiichiro

    2011-01-01

    Pain in the temporomandibular joint (TMJ) region often occurs with no overt signs of injury or inflammation. Although the etiology of TMJ-related pain may involve multiple factors, one likely risk factor is female gender or estrogen status. Evidence is reviewed from human and animal studies, supporting the proposition that estrogen status acts peripherally or centrally to influence TMJ nociceptive processing. A new model termed the "TMJ pain matrix" is proposed as critical for the initial integration of TMJ-related sensory signals in the lower brainstem that is both modified by estrogen status, and closely linked to endogenous pain and autonomic control pathways.

  1. Systemic Effects of Vaginally Administered Estrogen Therapy: A Review

    PubMed Central

    Krause, Megan; Wheeler, Thomas L.; Richter, Holly E.; Snyder, Thomas E.

    2015-01-01

    Hormone Therapy (HT) was considered the standard of care prior to the publication of the Women’s Health Initiative (WHI). After the study was published, the use of systemic HT dramatically decreased resulting in an increased incidence of menopausal symptoms such as hot flashes, vaginal dryness and dyspareunia experienced by women. Use of vaginal estrogen offers women a unique alternative for relief of these symptoms. This article reviews the systemic effects of vaginally administered estrogen. Effects on serum hormone levels, vasomotor symptoms, lipid profiles and use in women with breast cancer are reviewed. An accompanying review examines the local effects of vaginally administered estrogen. PMID:22453284

  2. Estrogen-DNA Adducts as Novel Biomarkers for Ovarian Cancer Risk and for Use in Prevention

    DTIC Science & Technology

    2013-03-01

    the association between ovarian cancer and (1) imbalances in estrogen metabolism that lead to higher levels of estrogen-DNA adducts in urine and/or (2...provides a measure of the imbalance 6 of estrogen metabolism in a person. A high ratio indicates that the person’s estrogen metabolism is...polymorphisms and risk of hormonal cancers. The estrogen quinone resulting from CYP1B1 activity may proceed to adduct formation in the presence of

  3. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products

    PubMed Central

    Myers, Sharon L.; Yang, Chun Z.; Bittner, George D.; Witt, Kristine L.; Tice, Raymond R.; Baird, Donna D.

    2014-01-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products. PMID:24849798

  4. Effect of combining in vitro estrogenicity data with kinetic characteristics of estrogenic compounds on the in vivo predictive value.

    PubMed

    Punt, Ans; Brand, Walter; Murk, Albertinka J; van Wezel, Annemarie P; Schriks, Merijn; Heringa, Minne B

    2013-02-01

    With the ultimate aim of increasing the utility of in vitro assays for toxicological risk assessment, a method was developed to calculate in vivo estrogenic potencies from in vitro estrogenic potencies of compounds by taking into account systemic availability. In vitro estrogenic potencies of three model compounds (bisphenol A, genistein, and 4-nonylphenol) relative to ethinylestradiol (EE2), determined with the estrogen receptor alpha (ERα) transcriptional activation assay using hER-HeLa-9903 cells, were taken from literature and used to calculate the EE2 equivalent (EE2EQ) effect doses in the predominantly ERα-dependent rat uterotrophic assay. Compound-specific differences in hepatic clearance relative to the reference compound EE2 were determined in vitro to examine whether in vivo estrogenic potencies reported in literature could be more accurately estimated. The EE2EQ doses allowed to predict in vivo uterotrophic responses within a factor of 6-25 and the inclusion of the hepatic clearance further improved the prediction with a factor 1.6-2.1 for especially genistein and bisphenol A. Yet, the model compounds still were less potent in vivo than predicted based on their EE2 equivalent estrogenic potency and hepatic clearance. For further improvement of the in vitro to in vivo predictive value of in vitro assays, the relevance of other kinetic characteristics should be studied, including binding to carrier proteins, oral bioavailability and the formation of estrogenic metabolites.

  5. The removal of estrogenic activity with UV/chlorine technology and identification of novel estrogenic disinfection by-products.

    PubMed

    Li, Man; Xu, Bi; Liungai, Zhiqi; Hu, Hong-Ying; Chen, Chao; Qiao, Juan; Lu, Yun

    2016-04-15

    As a recently developed disinfection technology, ultraviolet (UV)/chlorine treatment has received much attention. Many studies have evaluated its effects on pathogen inactivation, contaminant removal, and formation of disinfection by-products (DBPs), but its potential for environmental estrogen removal and estrogenic DBP generation, which can also be a risk to both ecosystem and human health, have not been evaluated. In this study, UV/chlorine treatment resulted in a greater removal of estrogenic activity in synthetic effluent samples containing 17β-estradiol (E2) than did UV or chlorine treatment alone regardless of the water quality. For both the UV/chlorine and chlorine treatments, there was significant interference from NH3-N, although the UV/chlorine treatment was less affected. Estrogen receptor based affinity chromatography was used to isolate the specific estrogenic DBPs, and a novel product, with high estrogenic activity compared to E2, Δ9(11)-dehydro-estradiol, was identified. It was generated by all three treatments, and might be previously mistakenly recognized as estrone (E1). This study demonstrated that UV/chlorine is a better treatment for the removal of 17β-estradiol than chlorine and UV alone. The new identified estrogenic DBP, Δ9(11)-dehydro-estradiol, which can be isolated by affinity chromatography, could be an emerging concern in the future.

  6. Channel catfish (Ictalurus punctatus) leukocytes express estrogen receptor isoforms ERα and ERβ2 and are functionally modulated by estrogens

    USGS Publications Warehouse

    Iwanowicz, Luke R.; Stafford, James L.; Patiño, Reynaldo; Bengten, Eva; Miller, Norman W.; Blazer, Vicki

    2014-01-01

    Estrogens are recognized as modulators of immune responses in mammals and teleosts. While it is known that the effects of estrogens are mediated via leukocyte-specific estrogen receptors (ERs) in humans and mice, leucocyte-specific estrogen receptor expression and the effects of estrogens on this cell population is less explored and poorly understood in teleosts. Here in, we verify that channel catfish (Ictalurus punctaus) leukocytes express ERα and ERβ2. Transcripts of these isoforms were detected in tissue-associated leukocyte populations by PCR, but ERβ2 was rarely detected in PBLs. Expression of these receptors was temporally regulated in PBLs following polyclonal activation by concanavalin A, lipopolysaccharide or alloantigen based on evaluation by quantitative and end-point PCR. Examination of long-term leukocyte cell lines demonstrated that these receptors are differentially expressed depending on leukocyte lineage and phenotype. Expression of ERs was also temporally dynamic in some leukocyte lineages and may reflect stage of cell maturity. Estrogens affect the responsiveness of channel catfish peripheral blood leukocytes (PBLs) to mitogens in vitro. Similarly, bactericidal activity and phorbol 12-myristate 13-acetate induced respiratory burst was modulated by 17β-estradiol. These actions were blocked by the pure ER antagonist ICI 182780 indicating that response is, in part, mediated via ERα. In summary, estrogen receptors are expressed in channel catfish leukocytes and participate in the regulation of the immune response. This is the first time leukocyte lineage expression has been reported in teleost cell lines.

  7. Validation and application of a robust yeast estrogen bioassay for the screening of estrogenic activity in animal feed.

    PubMed

    Bovee, Toine F H; Bor, Gerrit; Heskamp, Henri H; Hoogenboom, Ron L A P; Nielen, Michel W F

    2006-06-01

    Previously we described the construction and properties of a rapid yeast bioassay stably expressing human estrogen receptor alpha (hERalpha) and yeast enhanced green fluorescent protein (yEGFP), the latter in response to estrogens. In the present study this yeast estrogen assay was validated as a qualitative screening method for the determination of estrogenic activity in animal feed. This validation was performed according to EC Decision 2002/657. Twenty blank animal feed samples, including milk replacers and wet and dry feed samples, were spiked with 17beta-estradiol (E2beta) at 5 ng g(-1), 17alpha-ethynylestradiol (EE2) at 5 ng g(-1), diethylstilbestrol (DES) at 10 ng g(-1), zearalenone at 1.25 microg g(-1) or equal at 200 microg g(-1). All of these blank and low estrogen spiked feed samples fulfilled the CCalpha and CCbeta criterions, meaning that all 20 blank feed samples gave a signal below the determined decision limit CCalpha and were thus classified as compliant, and at least 19 out of the 20 spiked samples gave a signal above this CCalpha (beta = 5%) and were thus classified as suspect. The method was specific and estrogens in feed were stable for up to 98 days. In this study we also present long-term performance data and several examples of estrogens found in the routine screening of animal feed. This is the first successful example of a developed, validated and applied bioassay for the screening of hormonal substances in feed.

  8. Maternal Regulation of Estrogen Receptor α Methylation

    PubMed Central

    Champagne, Frances A.; Curley, James P.

    2008-01-01

    Summary Advances in molecular biology have provided tools for studying the epigenetic factors which modulate gene expression. DNA methylation is an epigenetic modification which can have sustained effects on transcription and is associated with long-term gene silencing. In this review, we focus on the regulation of estrogen receptor alpha (ERα) expression by hormonal and environmental cues, the consequences of these cues for female maternal and sexual behavior and recent studies which explore the role of DNA methylation in mediating these developmental effects, with particular focus on the mediating role of maternal care. The methylation status of ERα has implications for reproductive behavior, cancer susceptibility and recovery from ischemic injury suggesting an epigenetic basis for risk and resilience across the life span. PMID:18644464

  9. [Estrogen receptor alpha in obesity and diabetes].

    PubMed

    Cahua-Pablo, José Ángel; Flores-Alfaro, Eugenia; Cruz, Miguel

    2016-01-01

    Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein-coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D).

  10. Bioassay of estrogenicity and chemical analyses of estrogens in streams across the United States associated with livestock operations

    USGS Publications Warehouse

    Alvarez, David A.; Shappell, Nancy W.; Billey, L.O.; Bermudez, Dietrich S.; Wilson, Vickie S.; Kolpin, Dana W.; Perkins, Stephanie D.; Evans, Nicola; Foreman, William T.; Gray, James L.; Shipitalo, J.M.; Meyer, Michael T.

    2013-01-01

    Animal manures, used as a nitrogen source for crop production, are often associated with negative impacts on nutrient levels in surface water. The concentrations of estrogens in streams from these manures also are of concern due to potential endocrine disruption in aquatic species. Streams associated with livestock operations were sampled by discrete samples (n = 38) or by time-integrated polar organic chemical integrative samplers (POCIS,n = 19). Samples were analyzed for estrogens by gas chromatography-tandem mass spectrometry (GC-MSM2) and estrogenic activity was assessed by three bioassays: Yeast Estrogen Screen (YES), T47D-KBluc Assay, MCF-7 Estrogenicity Screen (E-Screen). Samples were collected from 19 streams within small (∼1-30 km2) watersheds in 12 U.S. states representing a range of hydrogeologic conditions, dominated by: dairy (3), grazing beef (3), feedlot cattle (1); swine (5); poultry (3); and 4 areas where no livestock were raised or manure was applied. Water samples were consistently below the United Kingdom proposed Lowest Observable Effect Concentration for 17b-estradiol in fish (10 ng/L) in all watersheds, regardless of land use. Estrogenic activity was often higher in samples during runoff conditions following a period of manure application. Estrone was the most commonly detected estrogen (13 of 38 water samples, mean 1.9, maximum 8.3 ng/L). Because of the T47D-KBluc assay’s sensitivity towards estrone (1.4 times 17β-estradiol) it was the most sensitive method for detecting estrogens, followed by the E-Screen, GC-MS2, and YES. POCIS resulted in more frequent detections of estrogens than discrete water samples across all sites, even when applying the less-sensitive YES bioassay to the POCIS extracts.

  11. Estrogens Can Disrupt Amphibian Mating Behavior

    PubMed Central

    Hoffmann, Frauke; Kloas, Werner

    2012-01-01

    The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline. PMID:22355410

  12. Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc).

    EPA Science Inventory

    There is growing concern of exposure to fish, wildlife, and humans to water sources contaminated with estrogens and the potential impact on reproductive health. Environmental estrogens can come from various sources including concentrated animal feedlot operations (CAFO), municipa...

  13. BIOCHEMICAL AND ANALYTICAL CHARACTERIZATION OF ESTROGENICALLY ACTIVE WASTEWATER: COMPARISON OF FIELD EXTRAPOLATIONS TO THE MEASURED CONCENTRATION OF ESTROGENS IN SEWAGE EFFLUENT

    EPA Science Inventory

    Estrogenically active wastewater was observed at two municipal wastewater treatment plants (WWTPs) utilizing caged male channel catfish in a previous study. The focus of this investigation was to identify and characterize the compound(s) responsible for this estrogenic response. ...

  14. Estrogen regulation of chicken riboflavin carrier protein gene is mediated by ERE half sites without direct binding of estrogen receptor.

    PubMed

    Bahadur, Urvashi; Ganjam, Goutham K; Vasudevan, Nandini; Kondaiah, Paturu

    2005-02-28

    Estrogen is an important steroid hormone that mediates most of its effects on regulation of gene expression by binding to intracellular receptors. The consensus estrogen response element (ERE) is a 13bp palindromic inverted repeat with a three nucleotide spacer. However, several reports suggest that many estrogen target genes are regulated by diverse elements, such as imperfect EREs and ERE half sites (ERE 1/2), which are either the proximal or the distal half of the palindrome. To gain more insight into ERE half site-mediated gene regulation, we used a region from the estrogen-regulated chicken riboflavin carrier protein (RCP) gene promoter that contains ERE half sites. Using moxestrol, an analogue of estrogen and transient transfection of deletion and mutation containing RCP promoter/reporter constructs in chicken hepatoma (LMH2A) cells, we identified an estrogen response unit (ERU) composed of two consensus ERE 1/2 sites and one non-consensus ERE 1/2 site. Mutation of any of these sites within this ERU abolishes moxestrol response. Further, the ERU is able to confer moxestrol responsiveness to a heterologous promoter. Interestingly, RCP promoter is regulated by moxestrol in estrogen responsive human MCF-7 cells, but not in other cell lines such as NIH3T3 and HepG2 despite estrogen receptor-alpha (ER-alpha) co transfection. Electrophoretic mobility shift assays (EMSAs) with promoter regions encompassing the half sites and nuclear extracts from LMH2A cells show the presence of a moxestrol-induced complex that is abolished by a polyclonal anti-ERalpha antibody. Surprisingly, estrogen receptor cannot bind to these promoter elements in isolation. Thus, there appears to be a definite requirement for some other factor(s) in addition to estrogen receptor, for the generation of a suitable response of this promoter to estrogen. Our studies therefore suggest a novel mechanism of gene regulation by estrogen, involving ERE half sites without direct binding of ER to the

  15. Syngas Upgrading to Hydrocarbon Fuels Technology Pathway

    SciTech Connect

    Talmadge, M.; Biddy, M.; Dutta, A.; Jones, S.; Meyer, A.

    2013-03-01

    This technology pathway case investigates the upgrading of woody biomass derived synthesis gas (syngas) to hydrocarbon biofuels. While this specific discussion focuses on the conversion of syngas via a methanol intermediate to hydrocarbon blendstocks, there are a number of alternative conversion routes for production of hydrocarbons through a wide array of intermediates from syngas. Future work will also consider the variations to this pathway to determine the most economically viable and lowest risk conversion route. Technical barriers and key research needs have been identified that should be pursued for the syngas-to-hydrocarbon pathway to be competitive with petroleum-derived gasoline-, diesel- and jet-range hydrocarbon blendstocks.

  16. Biodegradation of petroleum hydrocarbons in hypersaline environments

    PubMed Central

    Martins, Luiz Fernando; Peixoto, Raquel Silva

    2012-01-01

    Literature on hydrocarbon degradation in extreme hypersaline media presents studies that point to a negative effect of salinity increase on hydrocarbonoclastic activity, while several others report an opposite tendency. Based on information available in the literature, we present a discussion on the reasons that justify these contrary results. Despite the fact that microbial ability to metabolize hydrocarbons is found in extreme hypersaline media, indeed some factors are critical for the occurrence of hydrocarbon degradation in such environments. How these factors affect hydrocarbon degradation and their implications for the assessment of hydrocarbon biodegradation in hypersaline environments are presented in this review. PMID:24031900

  17. Biodegradation of petroleum hydrocarbons in hypersaline environments.

    PubMed

    Martins, Luiz Fernando; Peixoto, Raquel Silva

    2012-07-01

    Literature on hydrocarbon degradation in extreme hypersaline media presents studies that point to a negative effect of salinity increase on hydrocarbonoclastic activity, while several others report an opposite tendency. Based on information available in the literature, we present a discussion on the reasons that justify these contrary results. Despite the fact that microbial ability to metabolize hydrocarbons is found in extreme hypersaline media, indeed some factors are critical for the occurrence of hydrocarbon degradation in such environments. How these factors affect hydrocarbon degradation and their implications for the assessment of hydrocarbon biodegradation in hypersaline environments are presented in this review.

  18. A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings

    PubMed Central

    Gogos, Andrea; Sbisa, Alyssa M.; Sun, Jeehae; Gibbons, Andrew; Udawela, Madhara; Dean, Brian

    2015-01-01

    Gender differences in schizophrenia have been extensively researched and it is being increasingly accepted that gonadal steroids are strongly attributed to this phenomenon. Of the various hormones implicated, the estrogen hypothesis has been the most widely researched one and it postulates that estrogen exerts a protective effect by buffering females against the development and severity of the illness. In this review, we comprehensively analyse studies that have investigated the effects of estrogen, in particular 17β-estradiol, in clinical, animal, and molecular research with relevance to schizophrenia. Specifically, we discuss the current evidence on estrogen dysfunction in schizophrenia patients and review the clinical findings on the use of estradiol as an adjunctive treatment in schizophrenia patients. Preclinical research that has used animal models and molecular probes to investigate estradiol's underlying protective mechanisms is also substantially discussed, with particular focus on estradiol's impact on the major neurotransmitter systems implicated in schizophrenia, namely, the dopamine, serotonin, and glutamate systems. PMID:26491441

  19. Modeling environmental loading rates of municipal wastewater contaminants: steroidal estrogens

    EPA Science Inventory

    Estrogenic compounds in municipal wastewater are of substantial interest because of suspicion that they may cause reproductive disruption in aquatic invertebrates, and because of their potential to contaminate human drinking water sources. Previous work suggests the primary contr...

  20. Comparison of estrogen mixtures in vitro vs. in vivo

    EPA Science Inventory

    Numerous sources contribute to widespread contamination of drinking water sources with both natural and synthetic estrogens, which isa concern for potential ecological and human health effects. In vitro screening assays are valuable tools for identifying mechanisms of toxicity bu...

  1. ROLE OF ESTROGEN RECEPTOR-α ON FOOD DEMAND ELASTICITY

    PubMed Central

    Minervini, Vanessa; Rowland, Neil E.; Robertson, Kimberly L.; Foster, Thomas C.

    2016-01-01

    Estrogens have been shown to have an inhibitory effect on food intake under free-feeding conditions, yet the effects of estrogens on food-maintained operant responding have been studied to a much lesser extent and, thus, are not well understood. Therefore, the purpose of the present experiment was to use a behavioral economics paradigm to assess differences in demand elasticity between mice with knockout of the estrogen receptor subtype α, knockout of subtype β, and their wild type controls. The mice responded in a closed economy, and the price of food was increased by increasing the fixed-ratio response requirement every four sessions. Overall, we found that mice with the knockout of receptor subtype α had the most elastic demand functions. Therefore, under these conditions, estrogens increased food seeking via activation of the receptor subtype α. The results were inconsistent with those reported by previous studies that employed free-feeding conditions. PMID:25869426

  2. Role of estrogen receptor-α on food demand elasticity.

    PubMed

    Minervini, Vanessa; Rowland, Neil E; Robertson, Kimberly L; Foster, Thomas C

    2015-05-01

    Estrogens have been shown to have an inhibitory effect on food intake under free-feeding conditions, yet the effects of estrogens on food-maintained operant responding have been studied to a much lesser extent and, thus, are not well understood. Therefore, the purpose of the present experiment was to use a behavioral economics paradigm to assess differences in demand elasticity between mice with knockout of the estrogen receptor subtype α, knockout of subtype β, and their wild type controls. The mice responded in a closed economy, and the price of food was increased by increasing the fixed-ratio response requirement every four sessions. Overall, we found that mice with the knockout of receptor subtype α had the most elastic demand functions. Therefore, under these conditions, estrogens increased food seeking via activation of the receptor subtype α. The results were inconsistent with those reported by previous studies that employed free-feeding conditions.

  3. Estrogen Intake and Copper Depositions: Implications for Alzheimer's Disease?

    PubMed Central

    Amtage, Florian; Birnbaum, Dzelila; Reinhard, Thomas; Niesen, Wolf-Dirk; Weiller, Cornelius; Mader, Irina; Meyer, Philipp T.; Rijntjes, Michel

    2014-01-01

    We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease. PMID:25076894

  4. Estrogenic involvement in social learning, social recognition and pathogen avoidance.

    PubMed

    Choleris, Elena; Clipperton-Allen, Amy E; Phan, Anna; Valsecchi, Paola; Kavaliers, Martin

    2012-04-01

    Sociality comes with specific cognitive skills that allow the proper processing of information about others (social recognition), as well as of information originating from others (social learning). Because sociality and social interactions can also facilitate the spread of infection among individuals the ability to recognize and avoid pathogen threat is also essential. We review here various studies primarily from the rodent literature supporting estrogenic involvement in the regulation of social recognition, social learning (socially acquired food preferences and mate choice copying) and the recognition and avoidance of infected and potentially infected individuals. We consider both genomic and rapid estrogenic effects involving estrogen receptors α and β, and G-protein coupled estrogen receptor 1, along with their interactions with neuropeptide systems in the processing of social stimuli and the regulation and expression of these various socially relevant behaviors.

  5. SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE

    EPA Science Inventory

    Rationale: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans. Objectives: To examine the role of estrogen receptors in modulat...

  6. The estrogenic activity of phthalate esters in vitro.

    PubMed

    Harris, C A; Henttu, P; Parker, M G; Sumpter, J P

    1997-08-01

    A large number of phthalate esters were screened for estrogenic activity using a recombinant yeast screen. a selection of these was also tested for mitogenic effect on estrogen-responsive human breast cancer cells. A small number of the commercially available phthalates tested showed extremely weak estrogenic activity. The relative potencies of these descended in the order butyl benzyl phthalate (BBP) > dibutyl phthalate (DBP) > diisobutyl phthalate (DIBP) > diethyl phthalate (DEP) > diisiononyl phthalate (DINP). Potencies ranged from approximately 1 x 10(6) to 5 x 10(7) times less than 17beta-estradiol. The phthalates that were estrogenic in the yeast screen were also mitogenic on the human breast cancer cells. Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity in these in vitro assays. A number of metabolites were tested, including mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mon-n-octyl phthalate; all were wound to be inactive. One of the phthalates, ditridecyl phthalate (DTDP), produced inconsistent results; one sample was weakly estrogenic, whereas another, obtained from a different source, was inactive. analysis by gel chromatography-mass spectometry showed that the preparation exhibiting estrogenic activity contained 0.5% of the ortho-isomer of bisphenol A. It is likely that the presence of this antioxidant in the phthalate standard was responsible for the generation of a dose-response curve--which was not observed with an alternative sample that had not been supplemented with o,p'-bisphenol A--in the yeast screen; hence, DTDP is probably not weakly estrogenic. The activities of simple mixtures of BBP, DBP, and 17beta-estradiol were assessed in the yeast screen. No synergism was observed, although the activities of the mixtures were approximately additive. In summary, a small number of phthalates are weakly estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vitro. No data has

  7. Characterization and Consequences of Estrogen Receptor Exon Five Deletion.

    DTIC Science & Technology

    1998-08-01

    adhesion belt (whose 127 contraction has been implicated in lumen formation during gland development) (17), and tight junctions (necessary for...G.G.J.M. Kuiper , J.-A. Gustafsson, and O.-K. Park-Sarge, Estrogen receptor-fl mRNA expression in rat ovary: down regulation by gonadotropins...Molecular Endocrinology, 1997. 11: p. 172-182. 87. Kuiper , G., E. Enmark, M. Pelto-Huikko, S. Nilsson, and J.-A. Gustafsson, Cloning of a novel estrogen

  8. Characterization and Consequences of Estrogen Receptor Exon Five Deletion.

    DTIC Science & Technology

    1997-08-01

    the assembly of an adhesion belt (whose contraction has been implicated in lumen formation during gland development) [17], and tight junctions...down regulation by gonadotropins. Molecular Endocrinology, 1997. 11: p. 172-182. 87. Kuiper , G., et al., Cloning of a novel estrogen receptor...and K. Korach, Editorial: A new actor in the estrogen receptor drama - enter ER-B3. Endocrinology, 1997. 138(3): p. 861-862. 90. Kuiper , G.G.J.M., et

  9. Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone

    DTIC Science & Technology

    2007-03-01

    and white. 14. ABSTRACT Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or...metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors are tracked in living mice by whole-body imaging, and...macrometastases or micrometastases are detected by intravital imaging or fluorescence microscopy. Tumor growth is estrogen dependent and required for

  10. Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra).

    PubMed

    Simons, Rudy; Vincken, Jean-Paul; Mol, Loes A M; The, Susan A M; Bovee, Toine F H; Luijendijk, Teus J C; Verbruggen, Marian A; Gruppen, Harry

    2011-07-01

    The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography-mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17β-estradiol (E(2)). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20-60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERα or ERβ subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E(2), not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E(2) by approximately 80% at 6 × 10(-6) M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.

  11. Antiestrogenicity and estrogenicity in leachates from solid waste deposits.

    PubMed

    Svenson, Anders; Sjöholm, Sofia; Allard, Ann-Sofie; Kaj, Lennart

    2011-06-01

    A great deal of effort has been devoted to developing new in vitro and in vivo methods to identify and classify endocrine disrupting chemicals that have been identified in environmental samples. In this study an in vitro test based on recombinant yeast strains transfected with genes for the human estrogen receptor α was adapted to examine the presence of estrogenic and antiestrogenic substances in six Swedish landfill leachates. Antiestrogenic effects were measured as inhibition of the estradiol induced response with the human estrogen receptor α, and quantified by comparison with the corresponding inhibitory effects of a known antiestrogen, hydroxytamoxifen. The estrogenicity was within the range of that determined in domestic sewage effluents, from below the limit of detection to 29 ng estradiol units L(-1). Antiestrogenicity was detected in some of the investigated landfill leachates, ranging between <38 and 3800 μg hydroxytamoxifen equivalents L(-1). There was no apparent relation between the type of waste deposited on the landfills and the antiestrogenic effect. Fractionation of a landfill leachate showed that estrogenic compounds were located in two dominant fractions. Three estrogenic compounds were found that accounted for the estrogenic activity in extracts of leachates: bisphenol A, estradiol, and ethinylestradiol. The bisphenol may have been released from decomposing plastic waste and the estrogenic steroids from earlier deposits of municipal sewage sludge and pharmaceutical waste. Fractionation of leachates from three parts of a landfill showed that the antiestrogenic activity was distributed in at least four fractions and somewhat different in different flows of leachate. This indicated a heterogeneous mixture of antiestrogenic substances.

  12. Circulatory Estrogen Level Protects Against Breast Cancer in Obese Women

    PubMed Central

    Suba, Zsuzsanna

    2013-01-01

    Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass. Obesity is associated with dysmetabolism and endangers the healthy equilibrium of sexual hormone-production and regular menstrual cycles in women, which are the prerequisites not only for reproductive capacity but also for somatic health. At the same time, literary data support that anovulatory infertility is a very strong risk for breast cancer in young women either with or without obesity. In the majority of premenopausal women, obesity associated insulin resistance is moderate and may be counteracted by their preserved circulatory estrogen level. Consequently, it is not obesity but rather the still sufficient estrogen-level, which may be protective against breast cancer in young adult females. In obese older women, never using hormone replacement therapy (HRT) the breast cancer risk is high, which is associated with their continuous estrogen loss and increasing insulin-resistance. By contrast, obese postmenopausal women using HRT, have a decreased risk for breast cancer as the protective effect of estrogen-substitution may counteract to their obesity associated systemic alterations. The revealed inverse correlation between circulatory estrogen-level and breast cancer risk in obese women should advance our understanding of breast cancer etiology and promotes primary prevention measures. New patents recommend various methods for the prevention and treatment of obesity

  13. Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse

    PubMed Central

    Hara, Yuko; Waters, Elizabeth M.; McEwen, Bruce S.; Morrison, John H.

    2015-01-01

    Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction. PMID:26109339

  14. Caffeine as an indicator of estrogenic activity in source water.

    PubMed

    Montagner, C C; Umbuzeiro, G A; Pasquini, C; Jardim, W F

    2014-08-01

    Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. In this work, the presence of caffeine has been correlated with the estrogenic activity of water samples measured using the BLYES assay. After testing 96 surface water samples, it was concluded that caffeine can be used to prioritize samples to be tested for estrogenic activity in water quality programs evaluating emerging contaminants with endocrine disruptor activity.

  15. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc)

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  16. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc).

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  17. Fate and removal of estrogens in municipal wastewater.

    PubMed

    Racz, LeeAnn; Goel, Ramesh K

    2010-01-01

    Natural and synthetic estrogens are some of the most potent endocrine disrupting compounds found in municipal wastewater. Much research has been conducted on the source and fate of estrogens in wastewater treatment plants. Sorption and biodegradation are the primary removal mechanisms for estrogens in activated sludge systems, which are widely used biological treatment techniques for municipal wastewater treatment. However, when removal of estrogens in a wastewater treatment plant is incomplete, these compounds enter the environment through wastewater discharges or waste activated sludge at concentrations that can cause endocrine-reproductive system alterations in birds, reptiles and mammals. Therefore, studies have also focused on potential advanced treatment technologies with the aim of removing the compounds before discharging wastewater effluent or disposing waste sludge. This review discusses the physiological effects of these estrogens and the degree of problems estrogens pose as they enter the wastewater stream. Thereafter, this review also analyzes their fate in wastewater treatment systems and how they may reach drinking water sources. Furthermore, this review includes a discussion on various treatment technologies being investigated and future research trends for this pressing environmental issue.

  18. Effects of estrogen on growth plate senescence and epiphyseal fusion.

    PubMed

    Weise, M; De-Levi, S; Barnes, K M; Gafni, R I; Abad, V; Baron, J

    2001-06-05

    Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 microg/kg estradiol cypionate or vehicle i.m. once a week. Growth plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial growth rate, rate of chondrocyte proliferation, growth plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent growth plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of growth plate chondrocytes is exhausted; and (ii) estrogen does not induce growth plate ossification directly; instead, estrogen accelerates the programmed senescence of the growth plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.

  19. A novel mechanism of non-feminizing estrogens in neuroprotection.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Covey, Douglas F; Simpkins, James W

    2016-11-03

    Estrogens are potent and efficacious neuroprotectants both in vitro and in vivo in a variety of models of neurotoxicity. We determined the structural requirements for neuroprotection in an in vitro assay using a panel of >70 novel estratrienes, synthesized to reduce or eliminate estrogen receptor (ER) binding. We observed that neuroprotection could be enhanced by as much as 200-fold through modifications that positioned a large bulky group at the C2 or C4 position of the phenolic A ring of the estratriene. Further, substitutions on the B, C or D rings either reduced or did not markedly change neuroprotection. Collectively, there was a negative correlation between binding to ERs and neuroprotection with the more potent compounds showing no ER binding. In an in vivo model for neuroprotection, transient cerebral ischemia, efficacious compounds were active in protection of brain tissue from this pro-oxidant insult. We demonstrated that these non-feminizing estrogens engage in a redox cycle with glutathione, using the hexose monophosphate shunt to apply cytosolic reducing potential to cellular membranes. Together, these results demonstrate that non-feminizing estrogens are neuroprotective and protect brain from the induction of ischemic- and Alzheimer's disease (AD)-like neuropathology in an animal model. These features of non-feminizing estrogens make them attractive compounds for assessment of efficacy in AD and stroke, as they are not expected to show the side effects of chronic estrogen therapy that are mediated by ER actions in the liver, uterus and breast.

  20. Molecular Cloning, Characterization, and Chromosome Mapping of Reptilian Estrogen Receptors

    PubMed Central

    Katsu, Yoshinao; Matsubara, Kazumi; Kohno, Satomi; Matsuda, Yoichi; Toriba, Michihisa; Oka, Kaori; Guillette, Louis J.; Ohta, Yasuhiko; Iguchi, Taisen

    2010-01-01

    In many vertebrates, steroid hormones are essential for ovarian differentiation during a critical developmental stage as well as promoting the growth and differentiation of the adult female reproductive system. Although studies have been extensively conducted in mammals and a few fish, amphibians, and bird species, the molecular mechanisms of sex steroid hormone (estrogens) action have been poorly examined in reptiles. Here, we evaluate hormone receptor and ligand interactions in two species of snake, the Okinawa habu (Protobothrops flavoviridis, Viperidae) and the Japanese four-striped rat snake (Elaphe quadrivirgata, Colubridae) after the isolation of cDNAs encoding estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Using a transient transfection assay with mammalian cells, the transcriptional activity of reptilian (Okinawa habu, Japanese four-striped rat snake, American alligator, and Florida red-belly freshwater turtle) ESR1 and ESR2 was examined. All ESR proteins displayed estrogen-dependent activation of transcription via an estrogen-response element-containing promoter; however, the responsiveness to various estrogens was different. Further, we determined the chromosomal locations of the snake steroid hormone receptor genes. ESR1 and ESR2 genes were localized to the short and long arms of chromosome 1, respectively, whereas androgen receptor was localized to a pair of microchromosomes in the two snake species examined. These data provide basic tools that allow future studies examining receptor-ligand interactions and steroid endocrinology in snakes and also expands our knowledge of sex steroid hormone receptor evolution. PMID:20926589

  1. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens.

    PubMed

    Boué, Stephen M; Wiese, Thomas E; Nehls, Suzanne; Burow, Matthew E; Elliott, Steven; Carter-Wientjes, Carol H; Shih, Betty Y; McLachlan, John A; Cleveland, Thomas E

    2003-04-09

    Seven legume extracts containing phytoestrogens were analyzed for estrogenic activity. Methanol extracts were prepared from soybean (Glycine max L.), green bean (Phaseolus vulgaris L.), alfalfa sprout (Medicago sativa L.), mung bean sprout (Vigna radiata L.), kudzu root (Pueraria lobata L.), and red clover blossom and red clover sprout (Trifolium pratense L.). Extracts of kudzu root and red clover blossom showed significant competitive binding to estrogen receptor beta (ERbeta). Estrogenic activity was determined using an estrogen-dependent MCF-7 breast cancer cell proliferation assay. Kudzu root, red clover blossom and sprout, mung bean sprout, and alfalfa sprout extracts displayed increased cell proliferation above levels observed with estradiol. The pure estrogen antagonist, ICI 182,780, suppressed cell proliferation induced by the extracts, suggesting an ER-related signaling pathway was involved. The ER subtype-selective activities of legume extracts were examined using transiently transfected human embryonic kidney (HEK 293) cells. All seven of the extracts exhibited preferential agonist activity toward ERbeta. Using HPLC to collect fractions and MCF-7 cell proliferation, the active components in kudzu root extract were determined to be the isoflavones puerarin, daidzin, genistin, daidzein, and genistein. These results show that several legumes are a source of phytoestrogens with high levels of estrogenic activity.

  2. Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

    PubMed

    Xin, D; Wang, H; Yang, J; Su, Y-F; Fan, G-W; Wang, Y-F; Zhu, Y; Gao, X-M

    2010-02-01

    The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

  3. Estrogen Biology: New Insights into GPER Function and Clinical Opportunities

    PubMed Central

    Prossnitz, Eric R.; Barton, Matthias

    2014-01-01

    Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen’s rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and certain drugs such as SERMs and SERDs in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine. PMID:24530924

  4. Free and conjugated estrogens and androgens in stallion semen.

    PubMed

    Lemazurier, Emmanuel; Moslemi, Safa; Sourdaine, Pascal; Desjardins, Isabelle; Plainfosse, Bruno; Seralini, Gilles-Eric

    2002-02-01

    The steroid content of semen from a total of 11 mature fertile stallions was studied during two breeding seasons and one winter. The levels of free and conjugated substrates (testosterone and androstenedione), and products (estradiol and estrone), of aromatase were measured by radioimmunoassay with a validated method. The results were seasonally and monthly highly variable with characteristic peaks. The concentrations of free and conjugated estrogens were always higher in the gel-free ejaculate than in the gel except in one subfertile stallion used as comparison. Furthermore, the steroid production and the maximal resulting aromatase activity, estimated by the estrogens/androgens ratio, peaked in April-May and June. The breeding season (spring and summer) presents a clear estrogenic profile with estrogens/androgens ratios higher in contrast to the nonbreeding period (autumn and winter). The involvement of estrogens in the regulation of reproduction and equine spermatogenesis is discussed, and estrogens production and thus equine aromatase is proposed as a strong marker of testicular endocrine function.

  5. Evaluation of estrogenic activity in diets for experimental animals using in vitro assay.

    PubMed

    Kato, Hideo; Iwata, Toshio; Katsu, Yoshinao; Watanabe, Hajime; Ohta, Yasuhiko; Iguchi, Taisen

    2004-03-10

    We used a modified yeast-based human estrogen receptor alpha (ER alpha) bioassay to determine the estrogenic activity in 22 kinds of diets for experimental animals. The estrogenic activity of each diet was reevaluated by comparison with a calibration curve of 17 beta-estradiol. Almost all of the diets had estrogenic activity. The diets for rabbits and guinea pigs had the highest estrogenic activity compared to any other diets, including those for rats and mice. Estrogenic activity was found in dried skim milk, fishmeal, soybean meal, and alfalfa meal. In the NIH-07 diet opened for the ingredients, estrogenic activity was nearly all derived from the alfalfa meal. Multiple assays were performed to evaluate potential seasonal variations in the estrogenic potency in the raw materials of the rat and mouse diets. We found that the estrogenic activity in these raw materials changed throughout the year.

  6. Histone methylase MLL1 and MLL3 coordinate with estrogen receptors in estrogen-mediated HOXB9 expression

    PubMed Central

    Ansari, Khairul I.; Shrestha, Bishakha; Hussain, Imran; Kasiri, Sahba; Mandal, Subhrangsu S.

    2011-01-01

    Homeobox gene HOXB9 is a critical player in development of mammary gland and sternum and in regulation of Renin which is closely linked with blood pressure control. Our studies demonstrated that HOXB9 gene is transcriptionally regulated by estrogen (E2). HOXB9 promoter contains several estrogen-response elements (ERE). Reporter assay based experiments demonstrated that HOXB9 promoter EREs are estrogen-responsive. Estrogen receptors ERα and ERβ are essential for E2-mediated transcriptional activation of HOXB9. Chromatin immuno-precipitation assay demonstrated that ERs bind to HOXB9 EREs as a function of E2. Similarly, histone methylases MLL1 and MLL3 also bind to HOXB9 EREs and play critical role in E2-mediated transcriptional activation of HOXB9. Overall, our studies demonstrated that HOXB9 is an E2-responsive gene and ERs coordinate with MLL1 and MLL3 in E2-mediated transcriptional regulation of HOXB9. PMID:21428455

  7. Hydrocarbon Rocket Technology Impact Forecasting

    NASA Technical Reports Server (NTRS)

    Stuber, Eric; Prasadh, Nishant; Edwards, Stephen; Mavris, Dimitri N.

    2012-01-01

    Ever since the Apollo program ended, the development of launch propulsion systems in the US has fallen drastically, with only two new booster engine developments, the SSME and the RS-68, occurring in the past few decades.1 In recent years, however, there has been an increased interest in pursuing more effective launch propulsion technologies in the U.S., exemplified by the NASA Office of the Chief Technologist s inclusion of Launch Propulsion Systems as the first technological area in the Space Technology Roadmaps2. One area of particular interest to both government agencies and commercial entities has been the development of hydrocarbon engines; NASA and the Air Force Research Lab3 have expressed interest in the use of hydrocarbon fuels for their respective SLS Booster and Reusable Booster System concepts, and two major commercially-developed launch vehicles SpaceX s Falcon 9 and Orbital Sciences Antares feature engines that use RP-1 kerosene fuel. Compared to engines powered by liquid hydrogen, hydrocarbon-fueled engines have a greater propellant density (usually resulting in a lighter overall engine), produce greater propulsive force, possess easier fuel handling and loading, and for reusable vehicle concepts can provide a shorter turnaround time between launches. These benefits suggest that a hydrocarbon-fueled launch vehicle would allow for a cheap and frequent means of access to space.1 However, the time and money required for the development of a new engine still presents a major challenge. Long and costly design, development, testing and evaluation (DDT&E) programs underscore the importance of identifying critical technologies and prioritizing investment efforts. Trade studies must be performed on engine concepts examining the affordability, operability, and reliability of each concept, and quantifying the impacts of proposed technologies. These studies can be performed through use of the Technology Impact Forecasting (TIF) method. The Technology Impact

  8. Passive secondary biological treatment systems reduce estrogens in dairy shed effluent.

    PubMed

    Gadd, Jennifer B; Northcott, Grant L; Tremblay, Louis A

    2010-10-01

    Steroid estrogens are found at high concentrations in untreated dairy shed effluents. Reduction of estrogenic activity and steroid estrogen concentrations was assessed in two systems used to treat dairy shed effluents: the two-pond system and the advanced pond system. Both include anaerobic and aerobic treatment stages. Samples of effluent were collected from the systems and analyzed for free estrogens, conjugated estrogens and total estrogenic activity using E-Screen assay. Both systems showed increases of up to 8000% in aqueous free estrogens and estrogenic activity after anaerobic treatment, followed by decreases after aerobic treatment (36-83%). The complete systems decreased total steroid estrogen concentrations by 50-100% and estrogen activity by 62-100%, with little difference between systems. Removal rates were lower in winter for both systems. Final effluents from the advanced pond system contained total estrogens at <15-1400 ng/L and estrogenic activity at 3.2-43 ng/L. Final effluent from the two-pond system contained total estrogens at <15-300 ng/L and estrogenic activity at 3.3-25 ng/L. At times the final effluent EEQs exceeded guideline values for protection of freshwater fish and suggest further treatment may be required.

  9. Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats.

    PubMed

    Mazzucco, C A; Lieblich, S E; Bingham, B I; Williamson, M A; Viau, V; Galea, L A M

    2006-09-15

    This study investigated the involvement of estrogen receptors alpha and beta in estradiol-induced enhancement of hippocampal neurogenesis in the adult female rat. Subtype selective estrogen receptor agonists, propyl-pyrazole triol (estrogen receptor alpha agonist) and diarylpropionitrile (estrogen receptor beta agonist) were examined for each receptor's contribution, individual and cooperative, for estradiol-enhanced hippocampal cell proliferation. Estradiol increases hippocampal cell proliferation within 4 h [Ormerod BK, Lee TT, Galea LA (2003) Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats. J Neurobiol 55:247-260]. Therefore, animals received s.c. injections of estradiol (10 microg), propyl-pyrazole triol and diarylpropionitrile alone (1.25, 2.5, 5.0 mg/0.1 ml dimethylsulfoxide) or in combination (2.5 mg propyl-pyrazole triol+2.5 mg diarylpropionitrile/0.1 ml dimethylsulfoxide) and 4 h later received an i.p. injection of the cell synthesis marker, bromodeoxyuridine (200 mg/kg). Diarylpropionitrile enhanced cell proliferation at all three administered doses (1.25 mg, P<0.008; 2.5 mg, P<0.003; 5 mg, P<0.005), whereas propyl-pyrazole triol significantly increased cell proliferation (P<0.0002) only at the dose of 2.5 mg. Our results demonstrate both estrogen receptor alpha and estrogen receptor beta are individually involved in estradiol-enhanced cell proliferation. Furthermore both estrogen receptor alpha and estrogen receptor beta mRNA was found co-localized with Ki-67 expression in the hippocampus albeit at low levels, indicating a potential direct influence of each receptor subtype on progenitor cells and their progeny. Dual receptor activation resulted in reduced levels of cell proliferation, supporting previous studies suggesting that estrogen receptor alpha and estrogen receptor beta may modulate each other's activity. Our results also suggest that a component

  10. Deep desulfurization of hydrocarbon fuels

    DOEpatents

    Song, Chunshan [State College, PA; Ma, Xiaoliang [State College, PA; Sprague, Michael J [Calgary, CA; Subramani, Velu [State College, PA

    2012-04-17

    The invention relates to processes for reducing the sulfur content in hydrocarbon fuels such as gasoline, diesel fuel and jet fuel. The invention provides a method and materials for producing ultra low sulfur content transportation fuels for motor vehicles as well as for applications such as fuel cells. The materials and method of the invention may be used at ambient or elevated temperatures and at ambient or elevated pressures without the need for hydrogen.

  11. Catalytic method for synthesizing hydrocarbons

    DOEpatents

    Sapienza, R.S.; Sansone, M.J.; Slegeir, W.A.R.

    A method for synthesizing hydrocarbons from carbon monoxide and hydrogen by contacting said gases with a slurry of a catalyst composed of palladium or platinum and cobalt supported on a solid phase is disclosed. The catalyst is prepared by heating a heterogeneous component of the palladium or platinum deposited on the solid support in a solution of cobalt carbonyl or precursors thereof. The catalyst exhibits excellent activity, stability in air, and produces highly desirable product fractions even with dilute gaseous reactants.

  12. Catalytic method for synthesizing hydrocarbons

    DOEpatents

    Sapienza, Richard S.; Sansone, Michael J.; Slegeir, William A. R.

    1984-01-01

    A method for synthesizing hydrocarbons from carbon monoxide and hydrogen by contacting said gases with a slurry of a catalyst composed of palladium or platinum and cobalt supported on a solid phase is disclosed. The catalyst is prepared by heating a heterogeneous component of the palladium or platinum deposited on the solid support in a solution of cobalt carbonyl or precursors thereof. The catalyst exhibits excellent activity, stability in air, and produces highly desirable product fractions even with dilute gaseous reactants.

  13. Occurrence of selected estrogenic compounds and estrogenic activity in surface water and sediment of Langat River (Malaysia).

    PubMed

    Praveena, Sarva Mangala; Lui, Tang Seok; Hamin, Nur'Aqilah; Razak, Siti Quistina Noorain Abdul; Aris, Ahmad Zaharin

    2016-07-01

    The occurrence and estrogenic activities of steroid estrogens, such as the natural estrone (E1), 17β estradiol (E2), and estriol (E3), as well as the synthetic 17α-ethynylestradiol (EE2), were investigated in eight sampling points along the Langat River (Malaysia). Surface water samples were collected at 0.5 m and surface sediment 0-5 cm from the river surface. Instrument analysis of steroid estrogens was determined by UPLC-ESI-MS with an ultra-performance liquid chromatograph (Perkin Elmer FX15) coupled to a Q Trap function mass spectrophotometer (model 3200: AB Sciex). Steroid estrogen concentrations were higher in the Langat River sediments than those in its surface water. In surface water, E1 was not detected in any sampling point, E2 was only detected in two midstream sampling points (range 0-0.004 ng/L), E3 in three sampling points (range 0-0.002 ng/L), and EE2 in four sampling points (range 0-0.02 ng/L). E1 and E2 were detected in sediments from all sampling points, E3 in five sampling points, while EE2 only in one midstream sample (3.29E-4 ng/g). Sewage treatment plants, farming waste, and agricultural activities particularly present midstream and downstream were identified as potential sources of estrogens. Estrogenic activity expressed as estradiol equivalents (EEQs) was below 1 ng/L in all samples for both surface water and sediment, indicating therefore a low potential estrogenic risk to the aquatic environment. Although the health risks are still uncertain for drinking water consumers exposed to low levels of steroid estrogen concentrations, Langat River water is unacceptable for direct drinking purposes without treatment. Further studies of endocrine disruptors in Malaysian waters are highly recommended.

  14. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  15. Molecular Characterization of a B-ring Unsaturated Estrogen: Implications for Conjugated Equine Estrogen Components of Premarin

    PubMed Central

    Hsieh, Robert W.; Rajan, Shyamala S.; Sharma, Sanjay K.; Greene, Geoffrey L.

    2008-01-01

    Conjugated equine estrogens (CEEs) are routinely used for hormone replacement therapy (HRT), making it important to understand the activities of individual estrogenic components. Although 17β-estradiol (17β-E2), the most potent estrogen in CEE, has been extensively characterized, the actions of nine additional less potent estrogens are not well understood. Structural differences between CEEs and 17β-E2 result in altered interactions with the two estrogen receptors (ERα and ERβ) and different biological activities. To better understand these interactions, we have determined the crystal structure of the CEE analog, 17β-methyl-17α-dihydroequilenin (NCI 122), in complex with the ERα ligand-binding domain and a peptide from the glucocorticoid receptor-interacting protein 1 (GRIP1) coactivator. NCI 122 has chemical properties, including an unsaturated B-ring and 17α-hydroxyl group, which are shared with some of the estrogens found in CEEs. Structural analysis of the NCI 122-ERα LBD-GRIP1 complex, combined with biochemical and cell-based comparisons of CEE components, suggests that factors such as decreased ligand flexibility, decreased ligand hydrophobicity and loss of a hydrogen bond between the 17-hydroxyl group and His524, contribute significantly to the reduced potency of CEEs on ERα. PMID:17949766

  16. Effects of gamma irradiation on the DNA-protein complex between the estrogen response element and the estrogen receptor

    NASA Astrophysics Data System (ADS)

    Štísová, Viktorie; Goffinont, Stephane; Spotheim-Maurizot, Melanie; Davídková, Marie

    2010-08-01

    Signaling by estrogens, risk factors in breast cancer, is mediated through their binding to the estrogen receptor protein (ER), followed by the formation of a complex between ER and a DNA sequence, called estrogen response element (ERE). Anti-estrogens act as competitive inhibitors by blocking the signal transduction. We have studied in vitro the radiosensitivity of the complex between ERα, a subtype of this receptor, and a DNA fragment bearing ERE, as well as the influence of an estrogen (estradiol) or an anti-estrogen (tamoxifen) on this radiosensitivity. We observe that the complex is destabilized upon irradiation with γ rays in aerated aqueous solution. The analysis of the decrease of binding abilities of the two partners shows that destabilization is mainly due to the damage to the protein. The destabilization is reduced when irradiating in presence of tamoxifen and is increased in presence of estradiol. These effects are due to opposite influences of the ligands on the loss of binding ability of ER. The mechanism that can account for our results is: binding of estradiol or tamoxifen induces distinct structural changes of the ER ligand-binding domain that can trigger (by allostery) distinct structural changes of the ER DNA-binding domains and thus, can differently affect ER-ERE interaction.

  17. Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor: predictions across species.

    PubMed Central

    Tong, W; Perkins, R; Strelitz, R; Collantes, E R; Keenan, S; Welsh, W J; Branham, W S; Sheehan, D M

    1997-01-01

    The recognition of adverse effects due to environmental endocrine disruptors in humans and wildlife has focused attention on the need for predictive tools to select the most likely estrogenic chemicals from a very large number of chemicals for subsequent screening and/or testing for potential environmental toxicity. A three-dimensional quantitative structure-activity relationship (QSAR) model using comparative molecular field analysis (CoMFA) was constructed based on relative binding affinity (RBA) data from an estrogen receptor (ER) binding assay using calf uterine cytosol. The model demonstrated significant correlation of the calculated steric and electrostatic fields with RBA and yielded predictions that agreed well with experimental values over the entire range of RBA values. Analysis of the CoMFA three-dimensional contour plots revealed a consistent picture of the structural features that are largely responsible for the observed variations in RBA. Importantly, we established a correlation between the predicted RBA values for calf ER and their actual RBA values for human ER. These findings suggest a means to begin to construct a more comprehensive estrogen knowledge base by combining RBA assay data from multiple species in 3D-QSAR based predictive models, which could then be used to screen untested chemicals for their potential to bind to the ER. Another QSAR model was developed based on classical physicochemical descriptors generated using the CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) program. The predictive ability of the CoMFA model was superior to the corresponding CODESSA model. Images Figure 2. Figure 3. Figure 4. Figure 5. PMID:9353176

  18. No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals☆☆☆

    PubMed Central

    Bannister, Richard; Beresford, Nicola; Granger, David W.; Pounds, Nadine A.; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J.

    2013-01-01

    Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of

  19. Evolutionary origins of the estrogen signaling system: insights from amphioxus.

    PubMed

    Callard, G V; Tarrant, A M; Novillo, A; Yacci, P; Ciaccia, L; Vajda, S; Chuang, G-Y; Kozakov, D; Greytak, S R; Sawyer, S; Hoover, C; Cotter, K A

    2011-11-01

    Classically, the estrogen signaling system has two core components: cytochrome P450 aromatase (CYP19), the enzyme complex that catalyzes the rate limiting step in estrogen biosynthesis; and estrogen receptors (ERs), ligand activated transcription factors that interact with the regulatory region of target genes to mediate the biological effects of estrogen. While the importance of estrogens for regulation of reproduction, development and physiology has been well-documented in gnathostome vertebrates, the evolutionary origins of estrogen as a hormone are still unclear. As invertebrates within the phylum Chordata, cephalochordates (e.g., the amphioxus of the genus Branchiostoma) are among the closest invertebrate relatives of the vertebrates and can provide critical insight into the evolution of vertebrate-specific molecules and pathways. To address this question, this paper briefly reviews relevant earlier studies that help to illuminate the history of the aromatase and ER genes, with a particular emphasis on insights from amphioxus and other invertebrates. We then present new analyses of amphioxus aromatase and ER sequence and function, including an in silico model of the amphioxus aromatase protein, and CYP19 gene analysis. CYP19 shares a conserved gene structure with vertebrates (9 coding exons) and moderate sequence conservation (40% amino acid identity with human CYP19). Modeling of the amphioxus aromatase substrate binding site and simulated docking of androstenedione in comparison to the human aromatase shows that the substrate binding site is conserved and predicts that androstenedione could be a substrate for amphioxus CYP19. The amphioxus ER is structurally similar to vertebrate ERs, but differs in sequence and key residues of the ligand binding domain. Consistent with results from other laboratories, amphioxus ER did not bind radiolabeled estradiol, nor did it modulate gene expression on an estrogen-responsive element (ERE) in the presence of estradiol, 4

  20. Competitive product inhibition of aromatase by natural estrogens.

    PubMed

    Shimizu, Y; Yarborough, C; Osawa, Y

    1993-03-01

    In order to better understand the function of aromatase, we carried out kinetic analyses to assess the ability of natural estrogens, estrone (E1), estradiol (E2), 16 alpha-OHE1, and estriol (E3), to inhibit aromatization. Human placental microsomes (50 micrograms protein) were incubated for 5 min at 37 degrees C with [1 beta-3H]testosterone (1.24 x 10(3) dpm 3H/ng, 35-150 nM) or [1 beta-3H,4-14C]androstenedione (3.05 x 10(3) dpm 3H/ng, 3H/14C = 19.3, 7-65 nM) as substrate in the presence of NADPH, with and without natural estrogens as putative inhibitors. Aromatase activity was assessed by tritium released to water from the 1 beta-position of the substrates. Natural estrogens showed competitive product inhibition against androgen aromatization. The Ki of E1, E2, 16 alpha-OHE1, and E3 for testosterone aromatization was 1.5, 2.2, 95, and 162 microM, respectively, where the Km of aromatase was 61.8 +/- 2.0 nM (n = 5) for testosterone. The Ki of E1, E2, 16 alpha-OHE1, and E3 for androstenedione aromatization was 10.6, 5.5, 252, and 1182 microM, respectively, where the Km of aromatase was 35.4 +/- 4.1 nM (n = 4) for androstenedione. These results show that estrogen inhibit the process of androgen aromatization and indicate that natural estrogens regulate their own synthesis by the product inhibition mechanism in vivo. Since natural estrogen binds to the active site of human placental aromatase P-450 complex as competitive inhibitors, natural estrogens might be further metabolized by aromatase. This suggests that human placental estrogen 2-hydroxylase activity is catalyzed by the active site of aromatase cytochrome P-450 and also agrees with the fact that the level of catecholestrogens in maternal plasma increases during pregnancy. The relative affinities and concentration of androgens and estrogens would control estrogen and catecholestrogen biosynthesis by aromatase.

  1. Fulvestrant, a selective estrogen receptor down-regulator, sensitizes estrogen receptor negative breast tumors to chemotherapy.

    PubMed

    Jiang, Donghai; Huang, Yuan; Han, Ning; Xu, Mingjie; Xu, Liang; Zhou, Lin; Wang, Shu; Fan, Weimin

    2014-05-01

    Drug resistance frequently results in poor prognosis and high 5-year recurrence rate in estrogen receptor-negative (ER-) breast cancer patients. Herein, we examined the reversal effects of fulvestrant on multidrug resistance (MDR) in ER- breast cancer cells. Co-administration of fulvestrant significantly sensitized ER- MDR tumors to paclitaxel both in vitro and in vivo. Further analyses indicated that fulvestrant did not affect P-gp expression, but could inhibit P-gp function and subsequently reverse P-gp mediated drug resistance in ER- breast cancer cells. These results showed that combination of fulvestrant and chemotherapeutic agents might provide an effective treatment for ER- MDR breast cancers.

  2. Estrogen receptor-related receptors in the killifish Fundulus heteroclitus: diversity, expression, and estrogen responsiveness.

    PubMed

    Tarrant, A M; Greytak, S R; Callard, G V; Hahn, M E

    2006-08-01

    The estrogen receptor-related receptors (ERRs) are a group of nuclear receptors that were originally identified on the basis of sequence similarity to the estrogen receptors. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, but the diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In this study, we report the cloning of four ERR cDNAs from the Atlantic killifish, Fundulus heteroclitus, along with adult tissue expression and estrogen responsiveness. Phylogenetic analysis indicates that F. heteroclitus (Fh)ERRalpha is an ortholog of the single ERRalpha identified in mammals, pufferfish, and zebrafish. FhERRbetaa and FhERRbetab are co-orthologs of the mammalian ERRbeta. Phylogenetic placement of the fourth killifish ERR gene, tentatively identified as FhERRgammab, is less clear. The four ERRs showed distinct, partially overlapping mRNA expression patterns in adult tissues. FhERRalpha was broadly expressed. FhERRbetaa was expressed at apparently low levels in eye, brain, and ovary. FhERRbetab was expressed more broadly in liver, gonad, eye, brain, and kidney. FhERRgammab was expressed in multiple tissues including gill, heart, kidney, and eye. Distinct expression patterns of FhERRbetaa and FhERRbetab are consistent with subfunctionalization of the ERRbeta paralogs. Induction of ERRalpha mRNA by exogenous estrogen exposure has been reported in some mammalian tissues. In adult male killifish, ERR expression did not significantly change following estradiol injection, but showed a trend toward a slight induction (three- to five-fold) of ERRalpha expression in heart. In a second, more targeted experiment, expression of ERRalpha in adult female killifish was downregulated 2.5-fold in the heart following estradiol injection. In summary, our results indicate that killifish contain additional ERR genes relative to mammals, including

  3. A gene expression biomarker accurately predicts estrogen ...

    EPA Pesticide Factsheets

    The EPA’s vision for the Endocrine Disruptor Screening Program (EDSP) in the 21st Century (EDSP21) includes utilization of high-throughput screening (HTS) assays coupled with computational modeling to prioritize chemicals with the goal of eventually replacing current Tier 1 screening tests. The ToxCast program currently includes 18 HTS in vitro assays that evaluate the ability of chemicals to modulate estrogen receptor α (ERα), an important endocrine target. We propose microarray-based gene expression profiling as a complementary approach to predict ERα modulation and have developed computational methods to identify ERα modulators in an existing database of whole-genome microarray data. The ERα biomarker consisted of 46 ERα-regulated genes with consistent expression patterns across 7 known ER agonists and 3 known ER antagonists. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm by comparison to annotated gene expression data sets from experiments in MCF-7 cells. Using 141 comparisons from chemical- and hormone-treated cells, the biomarker gave a balanced accuracy for prediction of ERα activation or suppression of 94% or 93%, respectively. The biomarker was able to correctly classify 18 out of 21 (86%) OECD ER reference chemicals including “very weak” agonists and replicated predictions based on 18 in vitro ER-associated HTS assays. For 114 chemicals present in both the HTS data and the MCF-7 c

  4. Cystic fibrosis and estrogens: a perfect storm

    PubMed Central

    Zeitlin, Pamela L.

    2008-01-01

    Irreversible destruction and widening of the airways due to acquired infections or genetic mutations as well as those of unknown cause are more severe in females. Differences between male and female anatomy, behavior, and hormonal state have been proposed to explain the increased incidence and severity in females with airway disease such as cystic fibrosis (CF); however, a mechanism to explain a sex-related difference has remained elusive. In this issue of the JCI, Coakley et al. report that elevations in the major estrogen hormone in humans — 17β-estradiol — reduce Ca2+-activated Cl– secretion by airway epithelial cells in culture, thereby disrupting ion and water balance (see the related article beginning on page 4025). They measure a similar diminution of nasal epithelial Ca2+-activated Cl– secretion in women with CF during the menstrual cycle phase at which 17β-estradiol level is at its highest. These data suggest that for about one week of a four-week menstrual cycle, women with CF will have a reduced ability to efficiently clear airway secretions, the buildup of which is a hallmark of CF. The authors suggest that these data warrant the testing of antiestrogen therapy in females with CF and propose an alternative avenue for CF therapeutic development. PMID:19033654

  5. The Polybrominated Diphenyl Ether Mixture DE-71 Is Mildly Estrogenic

    PubMed Central

    Mercado-Feliciano, Minerva; Bigsby, Robert M.

    2008-01-01

    Background Polybrominated diphenyl ethers (PBDEs) are widely found in the environment, and they may act as endocrine disruptors. Objective Our goal in this study was to test the PBDE mixture DE-71 for estrogenic activity. Methods We used proliferation of cultured breast cancer cells (MCF-7) and trophic effects in the reproductive tracts of ovariectomized mice as estrogen bioassays. DE-71 was administered to mice by subcutaneous injection (sc) or oral gavage (po), alone or in combination with estradiol, for 3 or 34 days. Liver weights and cytochrome P450 enzyme activities were also measured. Results DE-71 increased MCF-7 cell proliferation, and this was prevented by antiestrogen. DE-71 cotreatment reduced the effect of estradiol in MCF-7 cells. In the mouse 3-day assay, DE-71 administered alone had no effect on uterine weight, uterine epithelial height (UEH), or vaginal epithelial thickness (VET); however, when DE-71 was administered as a cotreatment, it potentiated estradiol’s effect on uterine weight. DE-71 administered sc to BALB/c mice for 34 days slightly increased UEH and VET, and attenuated the estradiol-induced increase in UEH; these effects were not seen in BALB/c mice treated po or in C57BL/6 mice treated sc. DE-71 increased liver weight in BALB/c, C57BL/6, and estrogen receptor-α knockout mice. We also found an increase in liver cytochrome P450 1A (CYP1A) and CYP2B activities when DE-71 was administered po, but only CYP2B increased after sc treatment. Conclusion DE-71 behaves as a weak estrogen. In mice, the treatment route and duration determined if DE-71 was estrogenic. BALB/c mice are more susceptible to DE-71 effects in estrogen target tissues than C57BL/6 mice. DE-71 increased liver weight independently of estrogen receptor-α. PMID:18470304

  6. Can zero-valent iron nanoparticles remove waterborne estrogens?

    PubMed

    Jarošová, Barbora; Filip, Jan; Hilscherová, Klára; Tuček, Jiří; Šimek, Zdeněk; Giesy, John P; Zbořil, Radek; Bláha, Luděk

    2015-03-01

    Steroidal estrogens are one of the most challenging classes of hazardous contaminants as they can cause adverse effects to biota in extremely low concentrations. They emerge in both waste waters and surface waters serving as a source of drinking water. Environmental Quality Standards for 17β-estradiol (E2) and 17α-ethinylestradiol (EE2), promulgated within the EU Water Framework Directive, are 0.4 and 0.035 ng L(-1), respectively. Because nanoscale zero-valent iron (nZVI) particles have been previously used in numerous remediation technologies and have the advantage of possible magnetic separation, interaction of nZVI with E2 and EE2 in water was investigated to assess the potential role of nZVI in removing steroidal estrogens. A mixture of E2 and EE2 dissolved in water was shaken with varying doses of nZVI for 1-5 h. Concentration-dependent removal of the estrogens was observed but removal did not increase significantly with time. Concentrations of the estrogens were determined by HPLC/MS/MS and a biodetection reporter gene assay. Sorption and nonspecific oxygen-mediated oxidation of estrogens were identified as the most probable removal mechanisms. Two independent experiments confirmed that significant decrease of estrogens concentration is achieved when at least 2 g L(-1) of nZVI is applied. The presented study provides insights into the mechanisms of nZVI interaction with steroidal estrogens under aerobic conditions prevailing in currently applied water treatment technologies.

  7. Pilot Studies of Estrogen-Related Physical Findings in Infants

    PubMed Central

    Bernbaum, Judy C.; Umbach, David M.; Ragan, N. Beth; Ballard, Jeanne L.; Archer, Janet I.; Schmidt-Davis, Holly; Rogan, Walter J.

    2008-01-01

    Background Soy formula containing estrogenic isoflavones is widely used in the United States. Infants consuming soy formula exclusively have high isoflavone exposures. We wanted to study whether soy formula prolonged the physiologic estrogenization of newborns, but available quantitative descriptions of the natural history of breast and genital development are inadequate for study design. Objective We piloted techniques for assessing infants’ responses to the withdrawal from maternal estrogen and gathered data on breast and genital development in infants at different ages. Methods We studied 37 boys and 35 girls, from term pregnancies with normal birth weights, who were < 48 hr to 6 months of age, and residents of Philadelphia, Pennsylvania, during 2004–2005. One-third of the children of each sex and age interval were exclusively fed breast milk, soy formula, or cow-milk formula. Our cross-sectional study measured breast adipose tissue, breast buds, and testicular volume; observed breast and genital development; and collected vaginal wall cells and information on vaginal discharge. We assessed reliability of the measures. Results Breast tissue was maximal at birth and disappeared in older children, consistent with waning maternal estrogen. Genital development did not change by age. Breast-milk secretion and withdrawal bleeding were unusual. Vaginal wall cells showed maximal estrogen effect at birth and then reverted; girls on soy appeared to show reestrogenization at 6 months. Conclusions Examination of infants for plausible effects of estrogens is valid and repeatable. Measurement of breast tissue and characterization of vaginal wall cells could be used to evaluate exposures with estrogen-like effects. PMID:18335112

  8. Assessment of aryl hydrocarbon receptor complex interactions using pBEVY plasmids: expressionvectors with bi-directional promoters for use in Saccharomyces cerevisiae.

    PubMed

    Miller, C A; Martinat, M A; Hyman, L E

    1998-08-01

    The pBEVY (bi-directional expression vectors for yeast) plasmids were designed with constitutive and galactose-induced bi-directional promoters to direct the expression of multiple proteins in Saccharomyces cerevisiae . Using human estrogen receptor as a test gene, relatively balanced expression levels from each side of a bi-directional promoter were observed. Expression of a functional heterodimeric transcription factor composed of human aryl hydrocarbon receptor (Ahr) and aryl hydrocarbon receptor nuclear translocator (Arnt) proteins was accomplished using a single pBEVY plasmid. Previous studies suggest that inhibitory cross-talk between the estrogen receptor and the Ahr/Arnt complex may occur and that Hsp90-Ahr complex formation is important for Ahr-mediated signal transduction. Evidence for functional interaction among these proteins was investigated using pBEVY plasmids in a yeast system. No inhibitory cross-talk was observed in signaling assays performed with yeast that co-expressed Ahr, Arnt and estrogen receptor. In contrast, Ahr/Arnt-mediated signal transduction was reduced by 80% in a temperature-sensitive Hsp90 strain grown under non-permissive conditions. We conclude that pBEVY plasmids facilitate the examination of multiple protein interactions in yeast model systems.

  9. Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells.

    PubMed

    Teng, Yun; Radde, Brandie N; Litchfield, Lacey M; Ivanova, Margarita M; Prough, Russell A; Clark, Barbara J; Doll, Mark A; Hein, David W; Klinge, Carolyn M

    2015-06-19

    Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3-12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction.

  10. Dehydroepiandrosterone Activation of G-protein-coupled Estrogen Receptor Rapidly Stimulates MicroRNA-21 Transcription in Human Hepatocellular Carcinoma Cells*

    PubMed Central

    Teng, Yun; Radde, Brandie N.; Litchfield, Lacey M.; Ivanova, Margarita M.; Prough, Russell A.; Clark, Barbara J.; Doll, Mark A.; Hein, David W.; Klinge, Carolyn M.

    2015-01-01

    Little is known about the regulation of the oncomiR miR-21 in liver. Dehydroepiandrosterone (DHEA) regulates gene expression as a ligand for a G-protein-coupled receptor and as a precursor for steroids that activate nuclear receptor signaling. We report that 10 nm DHEA increases primary miR-21 (pri-miR-21) transcription and mature miR-21 expression in HepG2 cells in a biphasic manner with an initial peak at 1 h followed by a second, sustained response from 3–12 h. DHEA also increased miR-21 in primary human hepatocytes and Hep3B cells. siRNA, antibody, and inhibitor studies suggest that the rapid DHEA-mediated increase in miR-21 involves a G-protein-coupled estrogen receptor (GPER/GPR30), estrogen receptor α-36 (ERα36), epidermal growth factor receptor-dependent, pertussis toxin-sensitive pathway requiring activation of c-Src, ERK1/2, and PI3K. GPER antagonist G-15 attenuated DHEA- and BSA-conjugated DHEA-stimulated pri-miR-21 transcription. Like DHEA, GPER agonists G-1 and fulvestrant increased pri-miR-21 in a GPER- and ERα36-dependent manner. DHEA, like G-1, increased GPER and ERα36 mRNA and protein levels. DHEA increased ERK1/2 and c-Src phosphorylation in a GPER-responsive manner. DHEA increased c-Jun, but not c-Fos, protein expression after 2 h. DHEA increased androgen receptor, c-Fos, and c-Jun recruitment to the miR-21 promoter. These results suggest that physiological concentrations of DHEA activate a GPER intracellular signaling cascade that increases pri-miR-21 transcription mediated at least in part by AP-1 and androgen receptor miR-21 promoter interaction. PMID:25969534

  11. Nitric Oxide Plays a Key Role in Ovariectomy-Induced Apoptosis in Anterior Pituitary: Interplay between Nitric Oxide Pathway and Estrogen

    PubMed Central

    Quinteros, Fernanda A.; Duvilanski, Beatriz H.; Cabilla, Jimena P.

    2016-01-01

    Changes in the estrogenic status produce deep changes in pituitary physiology, mainly because estrogens (E2) are one of the main regulators of pituitary cell population. Also, E2 negatively regulate pituitary neuronal nitric oxide synthase (nNOS) activity and expression and may thereby modulate the production of nitric oxide (NO), an important regulator of cell death and survival. Little is known about how ovary ablation affects anterior pituitary cell remodelling and molecular mechanisms that regulate this process have not yet been elucidated. In this work we used freshly dispersed anterior pituitaries as well as cell cultures from ovariectomized female rats in order to study whether E2 deficiency induces apoptosis in the anterior pituitary cells, the role of NO in this process and effects of E2 on the NO pathway. Our results showed that cell activity gradually decreases after ovariectomy (OVX) as a consequence of cell death, which is completely prevented by a pan-caspase inhibitor. Furthermore, there is an increase of fragmented nuclei and DNA cleavage thereby presenting the first direct evidence of the existence of apoptosis in the anterior pituitary gland after OVX. NO production and soluble guanylyl cyclase (sGC) expression in anterior pituitary cells increased concomitantly to the apoptosis. Inhibition of both, NO synthase (NOS) and sGC activities prevented the drop of cell viability after OVX, showing for the first time that increased NO levels and sGC activity observed post-OVX play a key role in the induction of apoptosis. Conversely, E2 and prolactin treatments decreased nNOS expression and activity in pituitary cells from OVX rats in a time- and E2 receptor-dependent manner, thus suggesting interplay between NO and E2 pathways in anterior pituitary. PMID:27611913

  12. Comparing hydrogen and hydrocarbon booster fuels

    NASA Technical Reports Server (NTRS)

    Martin, James A.

    1988-01-01

    The present evaluation of the consequences of hydrogen and hydrocarbon fuels as the basis of launch vehicle booster rocket-stage performance notes that hydrocarbon fuels lead to lower vehicle dry mass, for low-velocity requirements, while hydrogen fuel furnishes lower dry mass. Vehicles employing both types of fuel attempt to take advantage of the low intercept and slope of hydrocarbon fuel at low velocity, and subsequently, of the slope of the hydrogen curves at higher velocities.

  13. HYDROCARBON AND SULFUR SENSORS FOR SOFC SYSTEMS

    SciTech Connect

    A.M. Azad; Chris Holt; Todd Lesousky; Scott Swartz

    2003-11-01

    The following report summarizes work conducted during the Phase I program Hydrocarbon and Sulfur Sensors for SOFC Systems under contract No. DE-FC26-02NT41576. For the SOFC application, sensors are required to monitor hydrocarbons and sulfur in order to increase the operation life of SOFC components. This report discusses the development of two such sensors, one based on thick film approach for sulfur monitoring and the second galvanic based for hydrocarbon monitoring.

  14. Photoperiod affects estrogen receptor α, estrogen receptor β and aggressive behavior

    PubMed Central

    Trainor, Brian C.; Rowland, Michael R.; Nelson, Randy J.

    2007-01-01

    Estrogens have important effects on male and female social behavior. Despite growing knowledge of the anatomy and behavioral effects of the two predominant estrogen receptor subtypes in mammals (ERα and ERβ), relatively little is known about how these receptors respond to salient environmental stimuli. Many seasonally breeding species respond to changing photoperiods that predict seasonal changes in resource availability. We characterized the effects of photoperiod on aggressive behavior in two species of Peromyscus that exhibit gonadal regression in short days. P. polionotus (old field mice) were more aggressive than P. maniculatus (deer mice) and both species were more aggressive in short days. We used immunocytochemistry and real-time polymerase chain reaction to characterize the effects of photoperiod on ERα and ERβ expression. In both species ERα-immunoreactive staining in the posterior bed nucleus of the stria terminalis (BNST) was increased in short vs. long days. Both species had reduced ERβ-immunoreactive expression in the posterior BNST in short days. In the medial amygdala ERβ immunoreactivity was increased in long days for both species. Using real-time polymerase chain reaction on punch samples that included the BNST, we observed that ERα mRNA was increased and ERβ mRNA was decreased in short days. These data suggest that the effects of photoperiod on ERα and ERβ expression may thus have important behavioral consequences. PMID:17614949

  15. 40 CFR 91.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Hydrocarbon analyzer calibration. 91....316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon analyzer as described... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  16. 40 CFR 91.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Hydrocarbon analyzer calibration. 91....316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon analyzer as described... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  17. 40 CFR 89.319 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Hydrocarbon analyzer calibration. 89... Equipment Provisions § 89.319 Hydrocarbon analyzer calibration. (a) The FID hydrocarbon analyzer shall... and at least annually thereafter, adjust the FID hydrocarbon analyzer for optimum hydrocarbon...

  18. 40 CFR 91.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Hydrocarbon analyzer calibration. 91....316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon analyzer as described... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  19. 40 CFR 89.319 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Hydrocarbon analyzer calibration. 89... Equipment Provisions § 89.319 Hydrocarbon analyzer calibration. (a) The FID hydrocarbon analyzer shall... and at least annually thereafter, adjust the FID hydrocarbon analyzer for optimum hydrocarbon...

  20. 40 CFR 89.319 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Hydrocarbon analyzer calibration. 89... Equipment Provisions § 89.319 Hydrocarbon analyzer calibration. (a) The FID hydrocarbon analyzer shall... and at least annually thereafter, adjust the FID hydrocarbon analyzer for optimum hydrocarbon...

  1. 40 CFR 86.121-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Hydrocarbon analyzer calibration. 86... Complete Heavy-Duty Vehicles; Test Procedures § 86.121-90 Hydrocarbon analyzer calibration. The hydrocarbon... FID and HFID hydrocarbon analyzers shall be adjusted for optimum hydrocarbon response....

  2. 40 CFR 86.121-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Hydrocarbon analyzer calibration. 86... Complete Heavy-Duty Vehicles; Test Procedures § 86.121-90 Hydrocarbon analyzer calibration. The hydrocarbon... FID and HFID hydrocarbon analyzers shall be adjusted for optimum hydrocarbon response....

  3. 40 CFR 91.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Hydrocarbon analyzer calibration. 91....316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon analyzer as described... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  4. 40 CFR 90.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Hydrocarbon analyzer calibration. 90... Equipment Provisions § 90.316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  5. 40 CFR 86.121-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Hydrocarbon analyzer calibration. 86... Complete Heavy-Duty Vehicles; Test Procedures § 86.121-90 Hydrocarbon analyzer calibration. The hydrocarbon... FID and HFID hydrocarbon analyzers shall be adjusted for optimum hydrocarbon response....

  6. 40 CFR 90.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Hydrocarbon analyzer calibration. 90... Equipment Provisions § 90.316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  7. 40 CFR 86.121-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Hydrocarbon analyzer calibration. 86... Complete Heavy-Duty Vehicles; Test Procedures § 86.121-90 Hydrocarbon analyzer calibration. The hydrocarbon... FID and HFID hydrocarbon analyzers shall be adjusted for optimum hydrocarbon response....

  8. 40 CFR 89.319 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Hydrocarbon analyzer calibration. 89... Equipment Provisions § 89.319 Hydrocarbon analyzer calibration. (a) The FID hydrocarbon analyzer shall... and at least annually thereafter, adjust the FID hydrocarbon analyzer for optimum hydrocarbon...

  9. 40 CFR 90.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Hydrocarbon analyzer calibration. 90... Equipment Provisions § 90.316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  10. 40 CFR 89.319 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Hydrocarbon analyzer calibration. 89... Equipment Provisions § 89.319 Hydrocarbon analyzer calibration. (a) The FID hydrocarbon analyzer shall... and at least annually thereafter, adjust the FID hydrocarbon analyzer for optimum hydrocarbon...

  11. 40 CFR 86.121-90 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 19 2013-07-01 2013-07-01 false Hydrocarbon analyzer calibration. 86... Complete Heavy-Duty Vehicles; Test Procedures § 86.121-90 Hydrocarbon analyzer calibration. The hydrocarbon... FID and HFID hydrocarbon analyzers shall be adjusted for optimum hydrocarbon response....

  12. 40 CFR 91.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Hydrocarbon analyzer calibration. 91....316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon analyzer as described... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  13. 40 CFR 90.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Hydrocarbon analyzer calibration. 90... Equipment Provisions § 90.316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  14. 40 CFR 90.316 - Hydrocarbon analyzer calibration.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Hydrocarbon analyzer calibration. 90... Equipment Provisions § 90.316 Hydrocarbon analyzer calibration. (a) Calibrate the FID and HFID hydrocarbon... thereafter, adjust the FID and HFID hydrocarbon analyzer for optimum hydrocarbon response as specified...

  15. Hydrocarbon exposure, pancreatitis, and bile acids.

    PubMed Central

    Hotz, P; Pilliod, J; Bourgeois, R; Boillat, M A

    1990-01-01

    The data on hydrocarbon induced pancreatitis are conflicting. This question was therefore studied in a non-selected population exposed to hydrocarbons and in "formerly" exposed workers. Neither the past clinical history nor the pancreatic tests provided any evidence for a causal relation between exposure and pancreatitis. No signs of hydrocarbon induced liver damage were seen either. As a healthy worker effect cannot be totally excluded, however, a case-control study in a group of patients suffering from non-alcohol induced pancreatitis could give useful indications for finally excluding the possibility of pancreatitis being induced by hydrocarbons. PMID:2271391

  16. Nox reduction system utilizing pulsed hydrocarbon injection

    DOEpatents

    Brusasco, Raymond M.; Penetrante, Bernardino M.; Vogtlin, George E.; Merritt, Bernard T.

    2001-01-01

    Hydrocarbon co-reductants, such as diesel fuel, are added by pulsed injection to internal combustion engine exhaust to reduce exhaust NO.sub.x to N.sub.2 in the presence of a catalyst. Exhaust NO.sub.x reduction of at least 50% in the emissions is achieved with the addition of less than 5% fuel as a source of the hydrocarbon co-reductants. By means of pulsing the hydrocarbon flow, the amount of pulsed hydrocarbon vapor (itself a pollutant) can be minimized relative to the amount of NO.sub.x species removed.

  17. Membrane separation of hydrocarbons using cycloparaffinic solvents

    DOEpatents

    Kulkarni, Sudhir S.; Chang, Y. Alice; Gatsis, John G.; Funk, Edward W.

    1988-01-01

    Heavy crude oils which contain metal contaminants such as nickel, vanadium and iron may be separated from light hydrocarbon oils by passing a solution of the crude oil dissolved in a cycloparaffinic hydrocarbon solvent containing from about 5 to about 8 carbon atoms by passing through a polymeric membrane which is capable of maintaining its integrity in the presence of hydrocarbon compounds. The light hydrocarbon oils which possess relatively low molecular weights will be recovered as the permeate while the heavy oils which possess relatively high molecular weights as well as the metal contaminants will be recovered as the retentate.

  18. New technique for calibrating hydrocarbon gas flowmeters

    NASA Technical Reports Server (NTRS)

    Singh, J. J.; Puster, R. L.

    1984-01-01

    A technique for measuring calibration correction factors for hydrocarbon mass flowmeters is described. It is based on the Nernst theorem for matching the partial pressure of oxygen in the combustion products of the test hydrocarbon, burned in oxygen-enriched air, with that in normal air. It is applied to a widely used type of commercial thermal mass flowmeter for a number of hydrocarbons. The calibration correction factors measured using this technique are in good agreement with the values obtained by other independent procedures. The technique is successfully applied to the measurement of differences as low as one percent of the effective hydrocarbon content of the natural gas test samples.

  19. Membrane separation of hydrocarbons using cycloparaffinic solvents

    DOEpatents

    Kulkarni, S.S.; Chang, Y.A.; Gatsis, J.G.; Funk, E.W.

    1988-06-14

    Heavy crude oils which contain metal contaminants such as nickel, vanadium and iron may be separated from light hydrocarbon oils by passing a solution of the crude oil dissolved in a cycloparaffinic hydrocarbon solvent containing from about 5 to about 8 carbon atoms by passing through a polymeric membrane which is capable of maintaining its integrity in the presence of hydrocarbon compounds. The light hydrocarbon oils which possess relatively low molecular weights will be recovered as the permeate while the heavy oils which possess relatively high molecular weights as well as the metal contaminants will be recovered as the retentate.

  20. Spreading coefficients of aliphatic hydrocarbons on water

    SciTech Connect

    Takii, Taichi; Mori, Y.H. . Dept. of Mechanical Engineering)

    1993-11-01

    Experiments have been performed to determine the equilibrium spreading coefficients of some aliphatic hydrocarbons (C[sub 6]C[sub 10]) on water. The thickness of a discrete lens of each hydrocarbon sample floating on a stagnant water pool was measured interferometrically and used to calculate the spreading coefficient of the hydrocarbon with the aid of Langmuir's capillarity theory. The dependences of the spreading coefficient, thus observed, on temperature (0--50 C) and on the number of carbon atoms in the hydrocarbon molecule are in qualitative agreement with the predictions based on the Lifshitz theory of van der Waals forces.

  1. Evolutionary origins of the estrogen signaling system: insights from amphioxus

    PubMed Central

    Tarrant, AM; Novillo, A; Yacci, P; Ciaccia, L; Vajda, S; Chuang, G-Y; Kozakov, D; Greytak, SR; Sawyer, S; Hoover, C; Cotter, K

    2011-01-01

    Classically, the estrogen signaling system has two core components: cytochrome P450 aromatase (CYP19), the enzyme complex that catalyzes the rate limiting step in estrogen biosynthesis; and estrogen receptors (ERs), ligand activated transcription factors that interact with the regulatory region of target genes to mediate the biological effects of estrogen. While the importance of estrogens for regulation of reproduction, development and physiology has been well-documented in gnathostome vertebrates, the evolutionary origins of estrogen as a hormone are still unclear. As invertebrates within the phylum Chordata, cephalochordates (e.g. the amphioxus of the genus Branchiostoma) are among the closest invertebrate relatives of the vertebrates and can provide critical insight into the evolution of vertebrate-specific molecules and pathways. To address this question, this paper briefly reviews relevant earlier studies that help to illuminate the history of the aromatase and ER genes, with a particular emphasis on insights from amphioxus and other invertebrates. We then present new analyses of amphioxus aromatase and ER sequence and function, including an in silico model of the amphioxus aromatase protein, and CYP19 gene analysis. CYP19 shares a conserved gene structure with vertebrates (9 coding exons) and moderate sequence conservation (40% amino acid identity with human CYP19). Modeling of the amphioxus aromatase substrate binding site and simulated docking of androstenedione in comparison to the human aromatase shows that the substrate binding site is conserved and predicts that androstenedione could be a substrate for amphioxus CYP19. The amphioxus ER is structurally similar to vertebrate ERs, but differs in sequence and key residues of the ligand binding domain. Consistent with results from other laboratories, amphioxus ER did not bind radiolabeled estradiol, nor did it modulate gene expression on anestrogen-responsive element (ERE) in the presence of estradiol, 4

  2. Effects of reciprocal treatment with estrogen and estrogen plus parathyroid hormone on bone structure and strength in ovariectomized rats.

    PubMed Central

    Shen, V; Birchman, R; Xu, R; Otter, M; Wu, D; Lindsay, R; Dempster, D W

    1995-01-01

    Intermittent administration of PTH has been found to be an effective anabolic agent in cancellous bone. We have reported previously that combined treatment with PTH and estrogen in estrogen-deficient rats was beneficial in correcting established osteopenia. To determine if the beneficial effects of PTH therapy can be preserved by estrogen alone and whether PTH therapy can be effective in treating osteopenic subjects stabilized with estrogen, we have undertaken a "crossover" study in the rat model of estrogen-deficiency induced osteopenia. Six-month-old female rats were ovariectomized and after 5 wk treated for 8 wk with vehicle, 30 micrograms/kg per day of rPTH(1-34) plus 15 micrograms/kg per day of 17 beta-estradiol or 17 beta-estradiol alone. One group from each treatment regimen was then sacrificed and for an additional 8 weeks the remaining rats were (a) maintained on their previous treatment; (b) "crossed over" to their reciprocal treatment; or (c) administered vehicle only. At the end of this second 8-wk treatment period all rats were sacrificed. Bone mineral density of the distal femur, histomorphometric measurements of the proximal tibia and mechanical testing of the distal femur and selected vertebral bodies were performed. Our results demonstrated that (a) the gains in bone mass, trabecular connectivity and mechanical strength induced by PTH can be maintained by estrogen alone, but are reversed when both agents are withdrawn; and (b) rats with established osteopenia, maintained on estrogen treatment alone, can derive the full beneficial effects from the addition of PTH to the treatment at a later date. These data indicate that combined and/or sequential use of antiresorptive and anabolic agents may be a promising approach to the treatment of osteoporosis. Images PMID:7593620

  3. Estrogenicity of food-associated estrogenic compounds in the fetuses of female transgenic mice upon oral and IP maternal exposure.

    PubMed

    Ter Veld, Marcel G R; Zawadzka, E; Rietjens, Ivonne M C M; Murk, Albertinka J

    2009-04-01

    The present study investigated to what extent seven food-associated in vitro estrogenic compounds can induce estrogenic effects in the fetuses of pregnant female mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc-induction was determined either 8h after maternal dosing with a single intraperitoneal (IP) dose or 24h after the last of a series of 8 daily oral dosages. Three known estrogens, 17beta-estradiol (E(2)), 17 alpha-ethynylestradiol (EE) and 17beta-estradiol 3,17-dipropionate (EP) were used as positive controls at 1mg/kgbw and DMSO as solvent control. The food-associated estrogenic compounds tested were: bisphenol A (BPA), nonylphenol (NP) both at 50mg/kgbw, dichlorodiphenyldichloroethylene (p,p'-DDE) at 50mg/kgbw, quercetin at 16.6 mg/kgbw, and di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 100mg/kgbw. Exposure to E(2), EE and EP resulted in significant luc inductions upon both oral and/or IP dosing in a variety of tissues including liver, tibia and femurs, and upon IP dosing also in fetuses. BPA, NP, DEHA, DEHP, DIHP, DDE and quercetin were unable to significantly induce luc activity in fetuses. However, after maternal oral exposure during gestation to NP, BPA and DIHP placental luc activity was significantly lowered. The results indicate that at the current levels of exposure to food-associated estrogenic compounds, estrogenic effects to the fetus are not expected. The significant luc reduction in the placenta, should be further studied for its significance for fetal development and relevance for the human situation.

  4. Activation of the G protein-coupled estrogen receptor, but not estrogen receptor α or β, rapidly enhances social learning.

    PubMed

    Ervin, Kelsy Sharice Jean; Mulvale, Erin; Gallagher, Nicola; Roussel, Véronique; Choleris, Elena

    2015-08-01

    Social learning is a highly adaptive process by which an animal acquires information from a conspecific. While estrogens are known to modulate learning and memory, much of this research focuses on individual learning. Estrogens have been shown to enhance social learning on a long-term time scale, likely via genomic mechanisms. Estrogens have also been shown to affect individual learning on a rapid time scale through cell-signaling cascades, rather than via genomic effects, suggesting they may also rapidly influence social learning. We therefore investigated the effects of 17β-estradiol and involvement of the estrogen receptors (ERs) using the ERα agonist propyl pyrazole triol, the ERβ agonist diarylpropionitrile, and the G protein-coupled ER 1 (GPER1) agonist G1 on the social transmission of food preferences (STFP) task, within a time scale that focused on the rapid effects of estrogens. General ER activation with 17β-estradiol resulted in a modest facilitation of social learning, with mice showing a preference up to 30min of testing. Specific activation of the GPER1 also rapidly enhanced social learning, with mice showing a socially learned preference up to 2h of testing. ERα activation instead shortened the expression of a socially learned food preference, while ERβ activation had little to no effects. Thus, rapid estrogenic modulation of social learning in the STFP may be the outcome of competing action at the three main receptors. Hence, estrogens' rapid effects on social learning likely depend on the specific ERs present in brain regions recruited during social learning.

  5. Establishment of a transgenic yeast screening system for estrogenicity and identification of the anti-estrogenic activity of malachite green.

    PubMed

    Jiao, Baowei; Yeung, Eric K C; Chan, Chi Bun; Cheng, Christopher H K

    2008-12-15

    Endocrine disruptors refer to chemical compounds in the environment which interfere with the endocrine systems of organisms. Among them, environmental estrogens pose serious problems to aquatic organisms, in particular fish. It is therefore important and necessary to have a fast and low-cost system to screen the large number of different chemical compounds in the aquatic environment for their potential endocrine disrupting actions. In this study, a screening platform was developed to detect xenoestrogens in the aquatic environment using the fission yeast Schizosaccharomyces pombe, and applied for compound screening. The aim was to demonstrate any significant potential differences between the fish screening system and the human screening system. To this end, a yeast expression vector harboring a fish estrogen receptor alpha and a reporter vector containing the estrogen responsive element fused with the Escherichia coli LacZ gene were constructed. After transformation with these two vectors, the transformed yeast clones were confirmed by Western blotting and selected on the basis of the beta-galactosidase activity. In this transgenic yeast system, the natural estrogen (estradiol) and other known xenoestrogens such as diethylstilbestrol, bisphenol A, genistein and dichloro-diphenyl-trichloroethane exhibited dose-dependent activities. Using this system, more than 40 putative endocrine disruptors including phytoestrogens, pesticides, herbicides, industrial dyes and other industrial chemicals were screened. Ten of them were demonstrated to exhibit estrogenic actions. Industrial dyes such as malachite green (MG) that disrupt thyroid hormone synthesis are extensively used and are widely distributed in the aquatic environment. Using this system, MG did not show any estrogenic action, but was demonstrated to exhibit anti-estrogenic activity.

  6. Disturbed estrogen and progesterone action in ovarian endometriosis.

    PubMed

    Smuc, Tina; Hevir, Neli; Ribic-Pucelj, Martina; Husen, Bettina; Thole, Hubert; Rizner, Tea Lanisnik

    2009-03-25

    Endometriosis is a very common disease in pre-menopausal women, where defective metabolism of steroid hormones plays an important role in its development and promotion. In the present study, we have examined the expression of 11 estrogen and progesterone metabolizing enzymes and their corresponding receptors in samples of ovarian endometriomas and control endometrium. Expression analysis revealed significant up-regulation of enzymes involved in estradiol formation (aromatase, sulfatase and all reductive 17beta-hydroxysteroid dehydrogenases) and in progesterone inactivation (AKR1C1 and AKR1C3). Among the estrogen and progesterone receptors, ERalpha was down-regulated, ERbeta was up-regulated, and there was no significant difference in expression of progesterone receptors A and B (PRAB). Our data indicate that several enzymes of estrogen and progesterone metabolism are aberrantly expressed in endometriosis, which can lead to increased local levels of mitogenic estradiol and decreased levels of protective progesterone. Changes in estrogen receptor expression suggest that estradiol may also act via non-estrogen receptor-mediated pathways, while expression of progesterone receptors still needs further investigation.

  7. Effect of estrogen and testosterone replacement therapy on cognitive fatigue.

    PubMed

    Möller, Marika Christina; Rådestad, Angelique Flöter; von Schoultz, Bo; Bartfai, Aniko

    2013-02-01

    Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue. However, hormonal replacement studies on fatigue are rare. Therefore, we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women. Fifty women with surgically induced menopause (mean age: 54.0 ± 2.9 years) were randomly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study. Neuropsychological tests and questionnaires were used to assess cognitive fatigue and psychological well-being. Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels. Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels. The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se. We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue.

  8. Screening of estrogenic and antiestrogenic activities from medicinal plants.

    PubMed

    Kim, In Gyu; Kang, Se Chan; Kim, Kug Chan; Choung, Eui Su; Zee, Ok Pyo

    2008-01-01

    The medicinal plant extracts commercially used in Asia were screened for their estrogenic and antiestrogenic activities in a recombinant yeast system featuring both a human estrogen receptor (ER) expression plasmid and a reporter plasmid. Pueraria lobata (flower) had the highest estrogenic relative potency (RP, 7.75×10(-3); RP of 17β-estradiol=1), followed by Amomum xanthioides (1.25×10(-3)). Next potent were a group consisting of Glycyrrhiza uralensis, Zingiber officinale, Rheum undulatum, Curcuma aromatica, Eriobotrya japonica, Sophora flavescens, Anemarrhena asphodeloides, Polygonum multiflorum, and Pueraria lobata (root) (ranging from 9.5×10(-4) to 1.0×10(-4)). Least potent were Prunus persica, Lycoppus lucidus, and Adenophora stricta (ranging from 9.0×10(-5) to 8.0×10(-5)). The extracts exerting antiestrogenic effects, Cinnamomum cassia and Prunus persica, had relative potencies of 1.14×10(-3) and 7.4×10(-4), respectively (RP of tamoxifen=1). The solvent fractions from selected estrogenic or antiestrogenic herbs had higher estrogenic relative potencies, with their RP ranging from 9.3×10(-1) to 2.7×10(-4) and from 8.2×10(-1) to 9.1×10(-3), respectively. These results support previous reports on the efficacy of Oriental medicinal plants used or not used as phytoestrogens for hormone replacement therapy.

  9. Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

    PubMed Central

    Talaber, Gergely; Yakimchuk, Konstantin; Guan, Jiyu; Inzunza, Jose; Okret, Sam

    2016-01-01

    Most lymphomas show higher incidence and poorer prognosis in males compared to females. However, the endocrine contribution to this gender difference is not entirely known. Here we show that castration accelerates lymphoma growth in C57BL6 male mice grafted with murine EG7 T cell lymphoma cells. However, the androgen receptor antagonist Bicalutamide did not affect lymphoma growth, suggesting no impact of androgen receptor signaling on lymphoma progression. In contrast, inhibition of androgen-to-estrogen conversion by the aromatase inhibitor (AI) Letrozole induced faster lymphoma growth in mice, suggesting that androgens impact lymphoma growth through its conversion to estrogens. This was supported by the inability of dihydrotestosterone, which is not converted to estrogens by aromatase, to influence lymphoma growth in castrated male mice. Lymphoma growth was also stimulated in immunocompromised mice grafted with human B cell lymphoma (Granta-519) and treated with either reversible or irreversible AIs, showing that the blockage of estrogen synthesis caused enhanced growth of both murine T and human B cell lymphomas and with different AIs. Additionally, AI-treated EG7 lymphomas showed accelerated growth not only in male but also in intact female mice. Altogether, our results demonstrate that aromatase inhibition accelerates lymphoma growth but not androgens per se, highlighting a protective role of estrogens in lymphoma pathogenesis. These results also raise concern that the use of AIs in women with breast cancer might enhance lymphoma progression. PMID:26943574

  10. VUV Photoionisation of hydrocarbon radicals

    NASA Astrophysics Data System (ADS)

    Alcaraz, C.; Noller, Bastian; Hemberger, Patrick; Fischer, Ingo; Gans, Bérenger; Boyé-Peronne, Séverine; Douin, Stéphane; Gauyacq, Dolorès; Soldi-Lose, Héloïse; Garcia, Gustavo

    2008-09-01

    Hydrocarbon radicals CxHy are constituents of various planetary atmospheres, in particular Titan, as a result of the methane photochemistry induced by the solar radiation. They contribute to the neutral chemistry, but are also important for the ionosphere through their photoionisation leading to their cations CxHy +. These cations are also produced by ion-molecule reactions starting from the reaction of the primary ions CH4 + and CH3 + which are created in the non-dissociative and dissociative photoionisation of CH4. This work aims at caracterizing the VUV photoionisation of small hydrocarbon radicals as a function of photon energy. The objective is to provide laboratory data for modelers on the spectroscopy, the thermochemistry, and the reactivity of the radicals and their cations. The hydrocarbon radicals are much less caracterized than stable molecules since they have to be produced in situ in the laboratory experiment. We have adapted at Orsay [1-3] a pyrolysis source (Figure 1) well suited to produce cold beams of hydrocarbon radicals to our experimental setups. Available now at Orsay, we have two new sources of VUV radiation, complementary in terms of tunability and resolution, that can be used for these studies. The first one is the DESIRS beamline [4] at the new french synchrotron, SOLEIL. The second one is the VUV laser developped at the Centre Laser de l'Université Paris-Sud (CLUPS) [5]. At SOLEIL, a photoelectron-photoion coincidence spectrometer is used to monitor the photoionisation on a large photon energy range. At the CLUPS, a pulsedfield ionisation (PFI-ZEKE) spectrometer allows studies at higher resolution on selected photon energies. The first results obtained with these new setups will be presented. References [1] Fischer, I., Schussler, T., Deyerl, H.J., Elhanine, M. & Alcaraz, C., Photoionization and dissociative photoionization of the allyl radical, C3H5. Int. J. Mass Spectrom., 261 (2-3), 227-233 (2007) [2] Schüßler, T., Roth, W., Gerber

  11. Hydrocarbon release investigations in Missouri

    SciTech Connect

    Fels, J.B.

    1996-09-01

    Hydrocarbon releases are among the most common environmental problems in Missouri, as well as across the country. Old, unprotected underground storage tanks and buried piping from the tanks to pumps are notorious sources of petroleum contamination at LUST (leaking underground storage tank) sites. Missouri has an estimated 5000 LUST sites across the state with the majority being simple spills into clay-rich soils or into a shallow perched water system. However, in the southern half of the state, where residual soils and karst bedrock are not conducive to trapping such releases, significant groundwater supplies are at risk. This article discusses the process used to identify the source of contamination.

  12. Hydrocarbon bioremediation 2(2)

    SciTech Connect

    Hinchee, R.E.; Alleman, B.C.; Hoeppel, R.E.; Miller, R.N.

    1993-12-31

    Hydrocarbon contamination of soil and groundwater, although less visible, is even more widespread than oil spills and is the background for a number of studies presented in this book, in addition to those devoted to shoreline spills. Chapters address a wide variety of theory and practice and cover important subjects such as biofiltration, natural attenuation, surfactants, and the use of in situ bioventing compared to soil venting. This book represents the collective experience of practitioners and researchers in North America, Europe, Africa, and Asia.

  13. ESTROGEN INDUCED VITELLOGENIN MRNA AND PROTEIN IN SHEEPSHEAD MINNOW (CYPRINODON VARIEGATUS)

    EPA Science Inventory

    Many environmentally persistent xenobiotic chemicals appear to disrupt normal endocrine function by acting as ligands for endogenous steroid receptors, including the estrogen receptor. Xenobiotics that bind to the estrogen receptor may elicit several effects, one of which is acti...

  14. COLLAPSE OF A FISH POPULATION FOLLOWING EXPOSURE TO A SYNTHETIC ESTROGEN

    EPA Science Inventory

    Municipal wastewaters are a complex mixture containing estrogens and estrogen mimics that are known to affect the reproductive health of wild fishes. Male fishes downstream of some wastewater outfalls produce vitellogenin (VTG) (a protein normally synthesized by females during oo...

  15. Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

    PubMed Central

    Wend, Korinna; Wend, Peter; Krum, Susan A.

    2012-01-01

    The roles of estrogens have been best studied in the breast, breast cancers, and in the female reproductive tract. However, estrogens have important functions in almost every tissue in the body. Recent clinical trials such as the Women’s Health Initiative have highlighted both the importance of estrogens and how little we know about the molecular mechanism of estrogens in these other tissues. In this review, we illustrate the diverse functions of estrogens in the bone, adipose tissue, skin, hair, brain, skeletal muscle and cardiovascular system, and how the loss of estrogens during aging affects these tissues. Early transcriptional targets of estrogen are reviewed in each tissue. We also describe the tissue-specific effects of selective estrogen receptor modulators (SERMs) used for the treatment of breast cancers and postmenopausal symptoms. PMID:22654856

  16. Estrogenic Activity of Perfluoroalkyl Acids in Juvenile Rainbow Trout (Oncorhynchus Mykiss)

    EPA Science Inventory

    The potential estrogenic activity of perfluoroalkyl acids (PFAAs) was determined using separate screening and dose response studies with juvenile rainbow trout (Oncorhynchus mykiss). Results of this study indicate that some PFAAs may act as estrogens in fish.

  17. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

    EPA Science Inventory

    Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

  18. Adaptive Significance of ERα Splice Variants in Killifish (Fundulus heteroclitus) Resident in an Estrogenic Environment

    EPA Science Inventory

    The possibility that chronic, multigenerational exposure to environmental estrogens selects for adaptive hormone response phenotypes is a critical unanswered question. Embryos/larvae of killifish from an estrogenic polluted environment (New Bedford Harbor, NBH), as compared to th...

  19. Function of G-Protein-Coupled Estrogen Receptor-1 in Reproductive System Tumors

    PubMed Central

    Qian, Hongyan; Xuan, Jingxiu; Liu, Yuan; Shi, Guixiu

    2016-01-01

    The G-protein-coupled estrogen receptor-1 (GPER-1), also known as GPR30, is a novel estrogen receptor mediating estrogen receptor signaling in multiple cell types. The progress of estrogen-related cancer is promoted by GPER-1 activation through mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), and phospholipase C (PLC) signaling pathways. However, this promoting effect of GPER-1 is nonclassic estrogen receptor (ER) dependent manner. In addition, clinical evidences revealed that GPER-1 is associated with estrogen resistance in estrogen-related cancer patients. These give a hint that GPER-1 may be a novel therapeutic target for the estrogen-related cancers. However, preclinical studies also found that GPER-1 activation of its special agonist G-1 inhibits cancer cell proliferation. This review aims to summarize the characteristics and complex functions of GPER-1 in cancers. PMID:27314054

  20. COMPARISON OF FATHEAD MINNOW AND HUMAN ESTROGEN RECEPTOR BINDING TO ENDOCRINE DISRUPTING COMPOUNDS

    EPA Science Inventory

    Environmental estrogens have the potential to disrupt endocrine function in a myriad of species. However, in vitro assays designed to detect and characterize endocrine disrupting chemicals (EDCs) typically utilize mammalian estrogen receptors. Our overall objective is to charac...