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Sample records for affects estrogen sensitivity

  1. Developmental exposure to PBDE 99 and PCB affects estrogen sensitivity of target genes in rat brain regions and female sexual behavior

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    Lichtensteiger, W.; Faass, O.; Ceccatelli, R.; Schlumpf, M. [Zurich Univ. (Switzerland). Inst. of Pharmacology and Toxicology

    2004-09-15

    We recently reported effects of PBDE99 (2,2',4,4'5-pentabromoBDE) on sexual differentiation processes in rat reproductive organs and central nervous system. These studies were prompted by reports on an increase of PBDE levels in human milk, an indicator of the body burden of pregnant women and of potential exposure of the nursing infant, during the last decade. Even higher human adipose tissue and milk levels were reported for North America. PBDE99 is present in human and animal samples and exhibits developmental neurotoxicity in mice. The developing brain is subject to the organizing action of estradiol locally formed from circulating testosterone, and thus represents a target for endocrine active chemicals. One molecular mechanism by which chemicals may interfere with sexual brain differentiation, may be a change in the expression of sex hormone (estrogen)-regulated genes. Such effects may manifest themselves in mRNA expression levels, or in the sensitivity of the genes to estrogen. In order to detect alterations of the latter, more subtle parameter, we have conducted experiments in developmentally chemical-exposed rat offspring that were gonadectomized in adulthood and injected with a challenge dose of estradiol. Effects of PBDE99 were compared with those of a commercial PCB mixture, Aroclor 1254, which had previously been found to influence sexual brain differentiation. We analyzed the expression of estrogen-regulated genes in ventromedial hypothalamus (VMH) and medial preoptic area (MPO), two brain regions that are part of a network involved in the integration of environmental cues, sexual behavior and gonadal function. Since prominent changes were observed in VMH which is particularly important for female sexual behavior, the study was completed by a behavioral analysis.

  2. Estrogen

    Science.gov (United States)

    ... estrogen tablets. If you will be taking Estrace® brand tablets, tell your doctor and pharmacist if you are allergic to aspirin or tartrazine (a food color additive). Ask your pharmacist or check the manufacturer's ...

  3. Detecting estrogenic activity in water samples withestrogen-sensitive yeast cells using spectrophotometry and fluorescencemicroscopy

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    Wozei, E.; Holman, H-Y.N.; Hermanowicz, S.W.; Borglin S.

    2006-03-15

    Environmental estrogens are environmental contaminants that can mimic the biological activities of the female hormone estrogen in the endocrine system, i.e. they act as endocrine disrupters. Several substances are reported to have estrogen-like activity or estrogenic activity. These include steroid hormones, synthetic estrogens (xenoestrogens), environmental pollutants and phytoestrogens (plant estrogens). Using the chromogenic substrate ortho-nitrophenyl-{beta}-D-galactopyranoside (ONPG) we show that an estrogen-sensitive yeast strain RMY/ER-ERE, with human estrogen receptor (hER{alpha}) gene and the lacZ gene which encodes the enzyme {beta}-galactosidase, is able to detect estrogenic activity in water samples over a wide range of spiked concentrations of the hormonal estrogen 17{beta}-estradiol (E2). Ortho-nitrophenol (ONP), the yellow product of this assay can be detected using spectrophotometry but requires cell lysis to release the enzyme and allow product formation. We improved this aspect in a fluorogenic assay by using fluorescein di-{beta}-D-galactopyranoside (FDG) as a substrate. The product was visualized using fluorescence microscopy without the need to kill, fix or lyse the cells. We show that in live yeast cells, the uptake of E2 and the subsequent production of {beta}-galactosidase enzyme occur quite rapidly, with maximum enzyme-catalyzed fluorescent product formation evident after about 30 minutes of exposure to E2. The fluorogenic assay was applied to a selection of estrogenic compounds and the Synchrotron-based Fourier transform infrared (SR-FTIR) spectra of the cells obtained to better understand the yeast whole cell response to the compounds. The fluorogenic assay is most sensitive to E2, but the SR-FTIR spectra suggest that the cells respond to all the estrogenic compounds tested even when no fluorescent response was detected. These findings are promising and may shorten the duration of environmental water screening and monitoring regimes using

  4. Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

    International Nuclear Information System (INIS)

    Cell differentiation and response to hormonal signals were studied in a 3D environment on an in-house generated mouse fibroblast cell line expressing a reporter gene under the control of estrogen responsive sequences (EREs). 3D cell culture conditions were obtained in a Rotary Cell Culture System; (RCCS™), a microgravity based bioreactor that promotes the aggregation of cells into multicellular spheroids (MCS). In this bioreactor the cells maintained a better differentiated phenotype and more closely resembled in vivo tissue. The RCCS™ cultured fibroblasts showed higher expression of genes regulating cell assembly, differentiation and hormonal functions. Microarray analysis showed that genes related to cell cycle, proliferation, cytoskeleton, migration, adhesion and motility were all down-regulated in 3D as compared to 2D conditions, as well as oncogene expression and inflammatory cytokines. Controlled remodeling of ECM, which is an essential aspect of cell organization, homeostasis and tissue was affected by the culture method as assessed by immunolocalization of β-tubulin. Markers of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates. The fibroblasts cultured in the RCCS™ maintain a better responsiveness to estrogens, measured as expression of ERα and regulation of an ERE-dependent reporter and of the endogenous target genes CBP, Rarb, MMP1 and Dbp. Our data highlight the interest of this 3D culture model for its potential application in the field of cell response to hormonal signals and the pharmaco-toxicological analyses of chemicals and natural molecules endowed of estrogenic potential. - Highlights: • We here characterized the first cell line derived from an estrogen reporter mouse. • In the RCCS cells express an immortalized behavior but not a transformed phenotype. • The RCCS provides a system for

  5. Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens

    Energy Technology Data Exchange (ETDEWEB)

    Montani, Claudia [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Steimberg, Nathalie; Boniotti, Jennifer [Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia (Italy); Biasiotto, Giorgio; Zanella, Isabella [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Diafera, Giuseppe [Integrated Systems Engineering (ISE), Milan (Italy); Biunno, Ida [IRGB-CNR, Milan (Italy); IRCCS-Multimedica, Milan (Italy); Caimi, Luigi [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy); Department of Molecular and Translational Medicine, University of Brescia, Brescia (Italy); Mazzoleni, Giovanna [Laboratory of Tissue Engineering, Anatomy and Physiopathology Unit, Department of Clinical and Experimental Sciences, School of Medicine, University of Brescia (Italy); Di Lorenzo, Diego, E-mail: diego.dilorenzo@yahoo.it [Laboratory of Biotechnology, Department of Laboratory Medicine, Civic Hospital of Brescia (Italy)

    2014-11-01

    Cell differentiation and response to hormonal signals were studied in a 3D environment on an in-house generated mouse fibroblast cell line expressing a reporter gene under the control of estrogen responsive sequences (EREs). 3D cell culture conditions were obtained in a Rotary Cell Culture System; (RCCS™), a microgravity based bioreactor that promotes the aggregation of cells into multicellular spheroids (MCS). In this bioreactor the cells maintained a better differentiated phenotype and more closely resembled in vivo tissue. The RCCS™ cultured fibroblasts showed higher expression of genes regulating cell assembly, differentiation and hormonal functions. Microarray analysis showed that genes related to cell cycle, proliferation, cytoskeleton, migration, adhesion and motility were all down-regulated in 3D as compared to 2D conditions, as well as oncogene expression and inflammatory cytokines. Controlled remodeling of ECM, which is an essential aspect of cell organization, homeostasis and tissue was affected by the culture method as assessed by immunolocalization of β-tubulin. Markers of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates. The fibroblasts cultured in the RCCS™ maintain a better responsiveness to estrogens, measured as expression of ERα and regulation of an ERE-dependent reporter and of the endogenous target genes CBP, Rarb, MMP1 and Dbp. Our data highlight the interest of this 3D culture model for its potential application in the field of cell response to hormonal signals and the pharmaco-toxicological analyses of chemicals and natural molecules endowed of estrogenic potential. - Highlights: • We here characterized the first cell line derived from an estrogen reporter mouse. • In the RCCS cells express an immortalized behavior but not a transformed phenotype. • The RCCS provides a system for

  6. Sensitive and robust gene expression changes in fish exposed to estrogen – a microarray approach

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    Nerman Olle

    2007-06-01

    Full Text Available Abstract Background Vitellogenin is a well established biomarker for estrogenic exposure in fish. However, effects on gonadal differentiation at concentrations of estrogen not sufficient to give rise to a measurable vitellogenin response suggest that more sensitive biomarkers would be useful. Induction of zona pellucida genes may be more sensitive but their specificities are not as clear. The objective of this study was to find additional sensitive and robust candidate biomarkers of estrogenic exposure. Results Hepatic mRNA expression profiles were characterized in juvenile rainbow trout exposed to a measured concentration of 0.87 and 10 ng ethinylestradiol/L using a salmonid cDNA microarray. The higher concentration was used to guide the subsequent identification of generally more subtle responses at the low concentration not sufficient to induce vitellogenin. A meta-analysis was performed with data from the present study and three similar microarray studies using different fish species and platforms. Within the generated list of presumably robust responses, several well-known estrogen-regulated genes were identified. Two genes, confirmed by quantitative RT-PCR (qPCR, fulfilled both the criteria of high sensitivity and robustness; the induction of the genes encoding zona pellucida protein 3 and a nucleoside diphosphate kinase (nm23. Conclusion The cross-species, cross-platform meta-analysis correctly identified several robust responses. This adds confidence to our approach used for identifying candidate biomarkers. Specifically, we propose that analyses of an nm23 gene together with zona pellucida genes may increase the possibilities to detect an exposure to low levels of estrogenic compounds in fish.

  7. Effects of Estrogen Receptor Modulators on Morphine Induced Sensitization in Mice Memory

    OpenAIRE

    Mahdieh Anoush; Ali Jani; Moosa Sahebgharani; Mohammad Reza Jafari

    2015-01-01

     Objective: In this study, the effects of estradiol valerate and raloxifenea selective estrogen receptor modulator; (SERM) on morphine induced sensitization were examined in mice memory, according to the step-down passive avoidance task.  Method:The mice received morphine or estradiol and raloxifene for three days alone or in combination with morphine. After a drug free period of 5 days, the subjects received saline or morphine as pre- training treatments followed by a pre-test saline adminis...

  8. Intermittent exposure to ethanol vapor affects osteoblast behaviour more severely than estrogen deficiency does

    International Nuclear Information System (INIS)

    With rising rates of alcohol consumption acute and chronic damage from alcohol is expected to increase all over the world. Habitual excessive alcohol consumption is associated with pathological effects on bone. The aim of the present in vitro study was to investigate comparatively the proliferation and synthetic activity of osteoblasts (OB) isolated from the trabecular bone of rats previously exposed to 7-week intermittent exposure to ethanol vapor, sham-aged rats and long-term estrogen deficient rats. Cell proliferation (WST1) and synthesis of alkaline phosphatase (ALP), osteocalcin (OC), collagen I (CICP), transforming growth factor beta1 (TGF-β1), interleukin-6 (IL-6), tumor necrosis factor alfa (TNFα) were measured at 3, 7 and 14 days of culture. Osteoblast proliferation rate and TGF-β1, IL-6 and TNFα syntheses were significantly affected by alcohol exposure. Estrogen deficiency and alcohol consumption share many common pathophysiological mechanisms of damage to bone, but alcohol affects OB proliferation and TNFα synthesis significantly more than menopause does. Therefore, these in vitro data suggest that alcohol has even more deleterious effects on bone than estrogen deficiency does

  9. Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries.

    Science.gov (United States)

    Dikshit, Anushka; Gao, Chunqi; Small, Carrie; Hales, Karen; Hales, Dale Buchanan

    2016-05-01

    Flaxseed has been studied for decades for its health benefits that include anti-cancer, cardio-protective, anti-diabetic, anti-inflammatory properties. The biologically active components that mediate these effects are the omega-3 fatty acids and the lignan, secoisolariciresinol diglucoside. We have previously shown that whole flaxseed supplemented diet decreases the severity and incidence of ovarian cancer while a 15% dose of flaxseed is most protective against inflammation and estrogen-induced chemical and genotoxicity. The objective of this study was to dissect the independent effects of the two flaxseed components on estrogen signaling and metabolism. Two and half year old hens were fed either a control diet, 15% whole flaxseed diet, defatted flax meal diet or 5% flax oil diet for 3 months after which the animals were sacrificed and blood and tissues were harvested. Whole flaxseed diet caused a decrease in expression of ERα. ERα target gene expression was assessed using RT(2) profiler PCR array. Some targets involved in the IGF/insulin signaling pathway (IRS1, IGFBP4, IGFBP5) were downregulated by flaxseed and its components. Flaxseed diet also downregulated AKT expression. A number of targets related to NF-kB signaling were altered by flaxseed diet including a series of targets implicated in cancer. Whole flaxseed diet also affected E2 metabolism by increasing CYP1A1 expression with a corresponding increase in the onco-protective E2 metabolite, 2-methoxyestradiol. The weak anti-estrogens, enterolactone, enterodiol and 2-methoxyestradiol, might be working synergistically to generate a protective effect on the ovaries from hens on whole flaxseed diet by altering the estrogen signaling and metabolism. PMID:26925929

  10. Effects of Estrogen Receptor Modulators on Morphine Induced Sensitization in Mice Memory

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    Mahdieh Anoush

    2015-11-01

    Full Text Available  Objective: In this study, the effects of estradiol valerate and raloxifenea selective estrogen receptor modulator; (SERM on morphine induced sensitization were examined in mice memory, according to the step-down passive avoidance task.  Method:The mice received morphine or estradiol and raloxifene for three days alone or in combination with morphine. After a drug free period of 5 days, the subjects received saline or morphine as pre- training treatments followed by a pre-test saline administration. The memory retrieval was evaluated using step-down passive avoidance test both on the training and test day. Results:The results illustrated that the three- day administration of morphine induced sensitization through the enhancement of memory retrieval (morphine induced sensitization in mice memory. Both the three- day administration of estradiol valerate alone and with morphine (5 mg/kg restored memory. On the other hand, the three- day administration of raloxifene had no effect on memory retrieval alone, but declined morphine induced sensitization in mice memory. Conclusion:The results of the study indicated that there is an interaction between estrogen receptor modulators and morphine induced sensitization in mice memory.

  11. ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer.

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    Maria Kalyuga

    Full Text Available We have previously shown that during pregnancy the E-twenty-six (ETS transcription factor ELF5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (ER-negative and milk producing cell lineage, raising the possibility that ELF5 may suppress the estrogen sensitivity of breast cancers. To test this we constructed inducible models of ELF5 expression in ER positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of DNA followed by DNA sequencing (ChIP-Seq. ELF5 suppressed ER and FOXA1 expression and broadly suppressed ER-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. Direct transcriptional targets of ELF5, which included FOXA1, EGFR, and MYC, accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes, predicted ER status with high precision, and defined groups with differential prognosis. Knockdown of ELF5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. Luminal breast cancer cells that acquired resistance to the antiestrogen Tamoxifen showed greatly elevated levels of ELF5 and its transcriptional signature, and became dependent on ELF5 for proliferation, compared to the parental cells. Thus ELF5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells, an action that may be utilised to acquire antiestrogen resistance.

  12. Involvement of β-adrenergic receptor of nucleus tractus solitarius in changing of baroreflex sensitivity by estrogen in female rats

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    Ali Asghar Pourshanazari

    2014-01-01

    Full Text Available Background: Arterial baroreflex (ABR is an important factor in preventing of blood pressure fluctuations that determined by baroreflex sensitivity (BRS. Estrogen is an ovarian hormone that has influence on ABR. The mechanism of this effect of estrogen unknown and may be mediated by β-adrenergic receptor of nucleus tractus solitarius (NTS, an important area in regulation of baroreflex. Therefore, in this study changing of BRS by estrogen after blockade β-adrenergic receptor of NTS in ovariectomized rats (Ovx and Ovx treated with estrogen (Est was examined. Materials and Methods: After ovariectomy, all female rats divided to Ovx and Ovx + Est groups and two series of experiments were performed. In the first experiment, phenylephrine was [intravenously, IV] injected in both the Ovx and Ovx + Est groups, and mean arterial pressure (MAP, heart rate (HR, and BRS were evaluated (n = 8 for each group. In the second experiment, each of Ovx and Ovx + Est groups divided into saline and propranolol (pro groups, saline and pro stereotaxically were microinjected into NTS, respectively. Further, phenylephrine (IV was injected in all groups and BRS was evaluated. Results: BRS significantly increased in estrogen-treated groups (Ovx + Est compared to Ovx groups (P < 0.01. The blockade β-adrenergic receptor of NTS by pro did not significantly changed BRS in both Ovx and Ovx + Est groups. Conclusion: We concluded that there aren′t any intraction between estrogen and β-adrenergic receptor of NTS in BRS.

  13. Biochanin A affects steroidogenesis and estrogen receptor-β expression in porcine granulosa cells.

    Science.gov (United States)

    Nynca, Anna; Swigonska, Sylwia; Piasecka, Joanna; Kolomycka, Agnieszka; Kaminska, Barbara; Radziewicz-Pigiel, Marta; Gut-Nagel, Marta; Ciereszko, Renata E

    2013-10-15

    Biochanin A, similar to other isoflavones, is present in soy and soy-based food, but predominantly in red clover. Red clover extract and biochanin A were reported to affect reproductive processes as well as to demonstrate menopause relief and anticancerogenic properties. Because porcine granulosa cells provide a suitable in vitro model for studying the intracellular mechanism of phytoestrogen action in the ovary, the objective of the study was to evaluate the in vitro effects of biochanin A on the following: (1) progesterone (P4) and estradiol (E2) secretion by granulosa cells, (2) viability of the granulosa cells, and (3) mRNA and protein expression of estrogen receptors α (ERα) and β (ERβ) in the granulosa cells harvested from both medium (3-6 mm) and large (≥8 mm) porcine ovarian follicles. RIA, alamarBlue assay, reverse transcriptase-polymerase chain reaction, and immunocytochemistry were used in the study to address the objectives. Biochanin A significantly inhibited P4 and did not affect E2 secretion by porcine granulosa cells regardless of the size of follicles that served as the source of the cells. Cell viability was not affected by the treatment. Biochanin A did not alter ERα and ERβ mRNA levels in the cultured porcine granulosa cells. In contrast, this isoflavone increased (P < 0.05) the immunoexpression of ERβ in the cells from both follicle types. In summary, biochanin A, similar to genistein and daidzein, affects follicular steroidogenesis and ER expression. Its effect on ERβ protein was more intense compared with other previously examined phytoestrogens. PMID:23953692

  14. Estrogen receptor-α expression in neuronal cells affects bone mass

    OpenAIRE

    Ohlsson, Claes; Engdahl, Cecilia; Börjesson, Anna E; Sara H Windahl; Studer, Erik; Westberg, Lars; Eriksson, Elias; Koskela, Antti; Tuukkanen, Juha; Krust, Andree; Chambon, Pierre; Carlsten, Hans; Lagerquist, Marie K

    2012-01-01

    It has generally been assumed that bone mass is controlled by endocrine mechanisms and the local bone environment. Recent findings demonstrate that central pathways are involved in the regulation of bone mass. Estrogen is involved in the regulation of bone homeostasis and the CNS is also a target for estrogen actions. The aim of this study was to investigate in vivo the role of central estrogen receptor-α (ERα) expression for bone mass. Nestin-Cre mice were crossed with ERαflox mice to genera...

  15. High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

    Science.gov (United States)

    Madularu, Dan; Kulkarni, Praveen; Yee, Jason R; Kenkel, William M; Shams, Waqqas M; Ferris, Craig F; Brake, Wayne G

    2016-06-01

    The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17β-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17β-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17β-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders. PMID:27154458

  16. Ultra-high sensitivity analysis of estrogens for special populations in serum and plasma by liquid chromatography-mass spectrometry: Assay considerations and suggested practices.

    Science.gov (United States)

    Wang, Qingqing; Mesaros, Clementina; Blair, Ian A

    2016-09-01

    Estrogen measurements play an important role in the clinical evaluation of many endocrine disorders as well as in research on the role of hormones in human biology and disease. It remains an analytical challenge to quantify estrogens and their metabolites in specimens from special populations including older men, children, postmenopausal women and women receiving aromatase inhibitors. Historically, immunoassays have been used for measuring estrogens and their metabolites in biological samples for risk assessment. However, the lack of specificity and accuracy of immunoassay-based methods has caused significant problems when interpreting data generated from epidemiological studies and across different laboratories. Stable isotope dilution (SID) methodology coupled with liquid chromatography-selected reaction monitoring-mass spectrometry (LC-SRM/MS) is now accepted as the 'gold-standard' to quantify estrogens and their metabolites in serum and plasma due to improved specificity, high accuracy, and the ability to monitor multiple estrogens when compared with immunoassays. Ultra-high sensitivity can be obtained with pre-ionized derivatives when using triple quadruple mass spectrometers in the selected reaction monitoring (SRM) mode coupled with nanoflow LC. In this review, we have examined the special issues related to utilizing ultra-high sensitivity SID LC-SRM/MS-based methodology to accurately quantify estrogens and their metabolites in the serum and plasma from populations with low estrogen levels. The major issues that are discussed include: sample preparation for both unconjugated and conjugated estrogens, derivatization, chromatographic separation, matrix effects, and assay validation. PMID:26767303

  17. Derivatization of estrogens enhances specificity and sensitivity of analysis of human plasma and serum by liquid chromatography tandem mass spectrometry

    Science.gov (United States)

    Faqehi, Abdullah M.M.; Cobice, Diego F.; Naredo, Gregorio; Mak, Tracy C.S.; Upreti, Rita; Gibb, Fraser W.; Beckett, Geoffrey J.; Walker, Brian R.; Homer, Natalie Z.M.; Andrew, Ruth

    2016-01-01

    Estrogens circulate at concentrations less than 20 pg/mL in men and postmenopausal women, presenting analytical challenges. Quantitation by immunoassay is unreliable at these low concentrations. Liquid chromatography tandem mass spectrometry (LC–MS/MS) offers greater specificity and sometimes greater sensitivity, but ionization of estrogens is inefficient. Introduction of charged moieties may enhance ionization, but many such derivatives of estrogens generate non-specific product ions originating from the “reagent” group. Therefore an approach generating derivatives with product ions specific to individual estrogens was sought. Estrogens were extracted from human plasma and serum using solid phase extraction and derivatized using 2-fluoro-1-methylpyridinium-p-toluenesulfonate (FMP-TS). Electrospray in positive mode with multiple reaction monitoring using a QTrap 5500 mass spectrometer was used to quantify “FMP” derivatives of estrogens, following LC separation. Transitions for the FMP derivatives of estrone (E1) and estradiol (E2) were compound specific (m/z 362→238 and m/z 364→128, respectively). The limits of detection and quantitation were 0.2 pg on-column and the method was linear from 1–400 pg/sample. Measures of intra- and inter-assay variability, precision and accuracy were acceptable (<20%). The derivatives were stable over 24 h at 10 °C (7–9% degradation). Using this approach, E1 and E2, respectively were detected in human plasma and serum: pre-menopausal female serum (0.5 mL) 135–473, 193–722 pmol/L; male plasma (1 mL) 25–111, 60–180 pmol/L and post-menopausal female plasma (2 mL), 22–78, 29–50 pmol/L. Thus FMP derivatization, in conjunction with LC–MS/MS, is suitable for quantitative analysis of estrogens in low abundance in plasma and serum, offering advantages in specificity over immunoassay and existing MS techniques. PMID:26946022

  18. Developing a Biosensor for Estrogens in Water Samples: Study ofthe Real-time Response of Live Cells of the Estrogen-sensitive YeastStrain RMY/ER-ERE using Fluorescence Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wozei, E.; Hermanowicz, S.W.; Holman, H-Y.N.

    2005-07-13

    Using a fluorescein di-{beta}-D-galactopyranoside (FDG) substrate we show that in live cells of an estrogen-sensitive yeast strain RMY/ER-ERE with human estrogen receptor (ER{alpha}) gene and the lacZ gene which encodes {beta}-galactosidase, the uptake of 17 {beta}-estradiol (E2) and the subsequent production of {beta}-galactosidase enzyme occur quite rapidly, with maximal enzyme-catalyzed product formation evident after about 30 minutes of exposure to E2. This finding which agrees with the well-known rates of enzyme-catalyzed reactions could have implications for shortening the duration of environmental sample screening and monitoring regimes using yeast-based estrogen assays, and the development of biosensors for environmental estrogens to complement quantification methods.

  19. Developing a Biosensor for Estrogens in Water Samples: Study ofthe Real-time Response of Live Cells of the Estrogen-sensitive YeastStrain RMY/ER-ERE using Fluorescence Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wozei, E.; Hermanowicz, S.W.; Holman, H-Y.N.

    2006-01-01

    Using a fluorescein di-{beta}-d-galactopyranoside (FDG) substrate we show that in live cells of an estrogen-sensitive yeast strain RMY/ER-ERE with human estrogen receptor (ER{alpha}) gene and the lacZ gene which encodes {beta}-galactosidase, the uptake of 17{beta}-estradiol (E2) and the subsequent production of {beta}-galactosidase enzyme occur quite rapidly, with maximal enzyme-catalyzed product formation evident after about 30 min of exposure to E2. This finding which agrees with the well-known rates of enzyme-catalyzed reactions could have implications for shortening the duration of environmental sample screening and monitoring regimes using yeast-based estrogen assays, and the development of biosensors for environmental estrogens to complement quantification methods.

  20. Parental Sensitivity, Infant Affect, and Affect Regulation: Predictors of Later Attachment.

    Science.gov (United States)

    Braungart-Rieker, Julia M.; Garwood, Molly M.; Powers, Bruce P.; Wang, Xiaoyu

    2001-01-01

    Examined extent to which parent sensitivity, infant affect, and affect regulation at 4 months predicted mother- and father-infant attachment classifications at 1 year. Found that affect regulation and maternal sensitivity discriminated infant-mother attachment groups. The association between maternal sensitivity and infant-mother attachment was…

  1. Minocycline affects cocaine sensitization in mice

    OpenAIRE

    Chen, Hu; Uz, Tolga; Manev, Hari

    2009-01-01

    Growing evidence has pointed to an interaction between the tetracycline antibiotic minocycline and drugs with abuse liability such as opioids and amphetamines. In this work, we tested the hypothesis that similar to its effects on methamphetamine-induced locomotor sensitization, minocycline may influence the behavioral effects of cocaine. Experiments were performed in male C57BL/6J mice using an automated system to measure locomotor activity. We found that 80 mg/kg minocycline significantly re...

  2. Rapid and Sensitive Reporter Gene Assays for Detection of Antiandrogenic and Estrogenic Effects of Environmental Chemicals

    DEFF Research Database (Denmark)

    Vinggaard, Anne Marie; Bonefeld-Jørgensen, Eva Cecilie; Larsen, John Christian

    1999-01-01

    Reports on increasing incidences in developmental abnormalities of the human male reproductive tract and the recent identifications of environmental chemicals with antiandrogenic activity necessitate the screening of a larger number of compounds in order to get an overview of potential antiandrog......Reports on increasing incidences in developmental abnormalities of the human male reproductive tract and the recent identifications of environmental chemicals with antiandrogenic activity necessitate the screening of a larger number of compounds in order to get an overview of potential...... cancer cells with an estrogen response element–luciferase vector. Thus, FuGene may prove to be valuable in diverse reporter gene assays involving transient transfections for screening of potential endocrine disruptors for (anti)androgenic and (anti)estrogenic properties....

  3. Aging negatively affects estrogens-mediated effects on nitric oxide bioavailability by shifting ERα/ERβ balance in female mice.

    Directory of Open Access Journals (Sweden)

    Laura Novensà

    Full Text Available AIMS: Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2 during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO production in a mouse model of accelerated senescence (SAM. METHODS AND RESULTS: Although we found no differences on NO production in females SAM prone (SAMP, aged compared to SAM resistant (SAMR, young, by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3, in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR but not in SAMP. E2 is also known to increase NO by decreasing its catabolism by superoxide anion (O(2(-. Interestingly, E2 treatment decreased O(2(- production in young females, while increased O(2(- in aged ones. Furthermore, we observed that aging changed expression ratio of estrogen receptors (ERβ/ERα and levels of DNA methylation. Increased ratio ERβ/ERα in aged females is associated to a lack of estrogen modulation of NO production and with a reversal in its antioxidant effect to a pro-oxidant profile. CONCLUSIONS: Together, our data suggest that aging has detrimental effects on E2-mediated benefits on NO bioavailability, partially by affecting the ability of E2 to induce up regulation of eNOS and decrease of O(2(-. These modifications may be associated to aging-mediated modifications on global DNA methylation status, but not to a specific methylation at 5'flanking region of ERα gene.

  4. Epigenetic reactivation of estrogen receptor-α (ERα by genistein enhances hormonal therapy sensitivity in ERα-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Li Yuanyuan

    2013-02-01

    Full Text Available Abstract Background Estrogen receptor-α (ERα-negative breast cancer is clinically aggressive and normally does not respond to conventional estrogen target-directed therapies. The soybean isoflavone, genistein (GE, has been shown to prevent and inhibit breast cancer and recent studies have suggested that GE can enhance the anticancer capacity of an estrogen antagonist, tamoxifen (TAM, especially in ERα-positive breast cancer cells. However, the role of GE in ERα-negative breast cancer remains unknown. Methods We have evaluated the in vitro and in vivo epigenetic effects of GE on ERα reactivation by using MTT assay, real-time reverse transcription-polymerase chain reaction (RT-PCR assay, western-blot assay, immunoprecipitation (ChIP assay, immunohistochemistry and epigenetic enzymatic activity analysis. Preclinical mouse models including xenograft and spontaneous breast cancer mouse models were used to test the efficacy of GE in vivo. Results We found that GE can reactivate ERα expression and this effect was synergistically enhanced when combined with a histone deacetylase (HDAC inhibitor, trichostatin A (TSA, in ERα-negative MDA-MB-231 breast cancer cells. GE treatment also re-sensitized ERα-dependent cellular responses to activator 17β-estradiol (E2 and antagonist TAM. Further studies revealed that GE can lead to remodeling of the chromatin structure in the ERα promoter thereby contributing to ERα reactivation. Consistently, dietary GE significantly prevented cancer development and reduced the growth of ERα-negative mouse breast tumors. Dietary GE further enhanced TAM-induced anti-cancer efficacy due at least in part to epigenetic ERα reactivation. Conclusions Our studies suggest that soybean genistein can epigenetically restore ERα expression, which in turn increases TAM-dependent anti-estrogen therapeutic sensitivity in vitro and in vivo. The results from our studies reveal a novel therapeutic combination approach using bioactive

  5. Factors affecting estrogen receptor status in a multiracial Asian country: an analysis of 3557 cases.

    Science.gov (United States)

    Yip, C H; Pathy, N Bhoo; Uiterwaal, C S; Taib, N A; Tan, G H; Mun, K S; Choo, W Y; Rhodes, A

    2011-04-01

    Estrogen receptor (ER) positive rates in breast cancer may be influenced by grade, stage, age and race. This study reviews the ER positive rates over a 15-year period at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. Data on ER status of 3557 patients from 1994 to 2008 was analyzed. ER status was determined by immunohistochemistry with a cut-off point of 10%. ER positivity increased by about 2% for every 5-year cohort, from 54.5% in 1994-1998 to 58.4% in 2004-2008. Ethnicity and grade were significantly associated with ER positivity rates: Malay women were found to have a higher risk of ER negative tumors compared with Chinese women. Grade 1 cancers were nine times more likely to be ER positive compared with grade 3 cancers. In summary, the proportion of ER positive cancers increased with each time period, and ethnicity and grade were independent factors that influenced ER positive rates. PMID:21349715

  6. Clinically used selective estrogen receptor modulators affect different steps of macrophage-specific reverse cholesterol transport.

    Science.gov (United States)

    Fernández-Suárez, María E; Escolà-Gil, Joan C; Pastor, Oscar; Dávalos, Alberto; Blanco-Vaca, Francisco; Lasunción, Miguel A; Martínez-Botas, Javier; Gómez-Coronado, Diego

    2016-01-01

    Selective estrogen receptor modulators (SERMs) are widely prescribed drugs that alter cellular and whole-body cholesterol homeostasis. Here we evaluate the effect of SERMs on the macrophage-specific reverse cholesterol transport (M-RCT) pathway, which is mediated by HDL. Treatment of human and mouse macrophages with tamoxifen, raloxifene or toremifene induced the accumulation of cytoplasmic vesicles of acetyl-LDL-derived free cholesterol. The SERMs impaired cholesterol efflux to apolipoprotein A-I and HDL, and lowered ABCA1 and ABCG1 expression. These effects were not altered by the antiestrogen ICI 182,780 nor were they reproduced by 17β-estradiol. The treatment of mice with tamoxifen or raloxifene accelerated HDL-cholesteryl ester catabolism, thereby reducing HDL-cholesterol concentrations in serum. When [(3)H]cholesterol-loaded macrophages were injected into mice intraperitoneally, tamoxifen, but not raloxifene, decreased the [(3)H]cholesterol levels in serum, liver and feces. Both SERMs downregulated liver ABCG5 and ABCG8 protein expression, but tamoxifen reduced the capacity of HDL and plasma to promote macrophage cholesterol efflux to a greater extent than raloxifene. We conclude that SERMs interfere with intracellular cholesterol trafficking and efflux from macrophages. Tamoxifen, but not raloxifene, impair M-RCT in vivo. This effect is primarily attributable to the tamoxifen-mediated reduction of the capacity of HDL to promote cholesterol mobilization from macrophages. PMID:27601313

  7. How seasonality affects the flow of estrogens and their conjugates in one of Japan's most populous catchments

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Vimal, E-mail: vimalk.hatwal@gmail.com [Research Center for Environmental Quality Management, Kyoto University, 1-2 Yumihama, Otsu, Shiga 520-0811 (Japan); Nakada, Norihide; Yamashita, Naoyuki [Research Center for Environmental Quality Management, Kyoto University, 1-2 Yumihama, Otsu, Shiga 520-0811 (Japan); Johnson, Andrew C. [Centre for Ecology and Hydrology, Wallingford, Oxfordshire OX10 8BB (United Kingdom); Tanaka, Hiroaki [Research Center for Environmental Quality Management, Kyoto University, 1-2 Yumihama, Otsu, Shiga 520-0811 (Japan)

    2011-10-15

    A detailed study of the free and conjugated estrogen load discharged by the eight major sewage treatment plants into the Yodo River basin, Japan was carried out. Sampling campaigns were focused on the winter and autumn seasons from 2005 to 2008 and the free estrogens estrone(E1), 17{beta}-estradiol(E2), estriol(E3), 17{alpha}-ethynylestradiol(EE2) as well as their conjugated (sulfate and glucuronide) forms. For both sewage effluent and river water E2 and E1 concentrations were greatest during the winter period (December-March). This coincides with the period of lowest rainfall and lowest temperatures in Japan. E1 was the dominant estrogenic component in effluent (means of 10-50 ng/L) followed by E2 (means of 0.5-3 ng/L). The estrogen sulfate conjugates were found intermittently in the 0.5-1.7 ng/L concentration range in the sewage effluents. The greatest estrogen exposure was found to be in the Katsura River tributary which exceeded 1 ng/L E2-equivalents during the winter period. - Highlights: > Comprehensive survey of free and conjugated estrogens in Yodo River (Japan). > Season play an important role in estrogen concentrations both in river and STPs. > The main estrogen reduction mechanism was dilution in the Yodo River. - This manuscript provides a comprehensive survey of estrogen conjugates in a densely populated river catchment.

  8. Estrogen Receptor β Agonists Differentially Affect the Growth of Human Melanoma Cell Lines.

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    Full Text Available Cutaneous melanoma is an aggressive malignancy; its incidence is increasing worldwide and its prognosis remains poor. Clinical observations indicate that estrogen receptor β (ERβ is expressed in melanoma tissues and its expression decreases with tumor progression, suggesting its tumor suppressive function. These experiments were performed to investigate the effects of ERβ activation on melanoma cell growth.Protein expression was analyzed by Western blot and immunofluorescence assays. Cell proliferation was assessed by counting the cells by hemocytometer. ERβ transcriptional activity was evaluated by gene reporter assay. Global DNA methylation was analyzed by restriction enzyme assay and ERβ isoforms were identified by qRT-PCR. We demonstrated that ERβ is expressed in a panel of human melanoma cell lines (BLM, WM115, A375, WM1552. In BLM (NRAS-mutant cells, ERβ agonists significantly and specifically inhibited cell proliferation. ERβ activation triggered its cytoplasmic-to-nuclear translocation and transcriptional activity. Moreover, the antiproliferative activity of ERβ agonists was associated with an altered expression of G1-S transition-related proteins. In these cells, global DNA was found to be hypomethylated when compared to normal melanocytes; this DNA hypomethylation status was reverted by ERβ activation. ERβ agonists also decreased the proliferation of WM115 (BRAF V600D-mutant cells, while they failed to reduce the growth of A375 and WM1552 (BRAF V600E-mutant cells. Finally, we could observe that ERβ isoforms are expressed at different levels in the various cell lines. Specific oncogenic mutations or differential expression of receptor isoforms might be responsible for the different responses of cell lines to ERβ agonists.Our results demonstrate that ERβ is expressed in melanoma cell lines and that ERβ agonists differentially regulate the proliferation of these cells. These data confirm the notion that melanoma is a

  9. Estrogen overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002584.htm Estrogen overdose To use the sharing features on this page, please enable JavaScript. Estrogen is a female hormone. Estrogen overdose occurs when ...

  10. Rapid and sensitive reporter gene assays for detection of antiandrogenic and estrogenic effects of environmental chemicals

    DEFF Research Database (Denmark)

    Vinggaard, Anne; Jørgensen, E.C.B.; Larsen, John Christian

    1999-01-01

    antiandrogenic chemicals present in our environment. Thus, there is a great need for an effective in vitro screening method for (anti)androgenic chemicals. We have developed a rapid, sensitive, and reproducible reporter gene assay for detection of antiandrogenic chemicals. Chinese Hamster Ovary cells were...

  11. Maternal Glucose Tolerance in Pregnancy Affects Fetal Insulin Sensitivity

    OpenAIRE

    Luo, Zhong-Cheng; Delvin, Edgard; Fraser, William D.; Audibert, Francois; Deal, Cheri I.; Julien, Pierre; Girard, Isabelle; Shear, Roberta; Levy, Emile; Nuyt, Anne-Monique

    2010-01-01

    OBJECTIVE Offspring of mothers with impaired glucose tolerance are far more likely to develop type 2 diabetes. We tested the hypothesis that maternal glucose tolerance in pregnancy affects fetal insulin sensitivity or β-cell function. RESEARCH DESIGN AND METHODS In a prospective singleton pregnancy cohort study, we analyzed glucose, insulin, and proinsulin concentrations in maternal blood at the 50-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation and in venous cord blood (n = ...

  12. Factors Affecting Sensitivity of Variable Charge Soils to Acid Rain

    Institute of Scientific and Technical Information of China (English)

    WANGJING-HUA

    1995-01-01

    The sensitivity of a large number of variable charge soils to acid rain was evaluated through examining pH-H2SO4 input curves.Two derivative parameters,the consumption of hydrogen ions by the soil and the acidtolerant limit as defined as the quantity of sulfuric acid required to bring the soil to pH 3.5 in a 0.001mol L-1 Ca(NO3)2 solution,were used.The sensitivity of variable charge soils was higher than that of constant charge soils,due to the predominance of kaolinite in clay mineralogical composition.Among these soils the sensitivity was generally of the order lateritic red soil>red soil> latosol.For a given type of soil within the same region the sensitivity was affected by parent material,due to differences in clay minerals and texture.The sensitivity of surface soil may be lower or higher than that of subsiol,depending on whether organic matter or texture plays the dominant role in determining the buffering capacity.Paddy soils consumed more acid within lower range of acid input when compared with upland soils,due to the presence of more exchangeable bases,but consumed less acid within higher acid input range,caused by the decrease in clay content.

  13. The sensitivity of the child to sex steroids: possible impact of exogenous estrogens

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Juul, Anders; Leffers, Henrik;

    2006-01-01

    The current trends of increasing incidences of testis, breast and prostate cancers are poorly understood, although it is assumed that sex hormones play a role. Disrupted sex hormone action is also believed to be involved in the increased occurrence of genital abnormalities among newborn boys and...... precocious puberty in girls. In this article, recent literature on sex steroid levels and their physiological roles during childhood is reviewed. It is concluded that (i) circulating levels of estradiol in prepubertal children are lower than originally claimed; (ii) children are extremely sensitive to...... levels during fetal and prepubertal development may have severe effects in adult life and (v) the daily production rates of sex steroids in children estimated by the Food and Drug Administration in 1999 and still used in risk assessments are highly overestimated and should be revised. Because no lower...

  14. Estrogen Injection

    Science.gov (United States)

    The estradiol cypionate and estradiol valerate forms of estrogen injection are used to treat hot flushes (hot ... should consider a different treatment. These forms of estrogen injection are also sometimes used to treat the ...

  15. Estrogen Vaginal

    Science.gov (United States)

    Vaginal estrogen is used to treat vaginal dryness, itching, and burning; painful or difficult urination; and sudden need to ... in women or girls of any age). Vaginal estrogen is in a class of medications called hormones. ...

  16. Hunger state affects both olfactory abilities and gustatory sensitivity.

    Science.gov (United States)

    Hanci, Deniz; Altun, Huseyin

    2016-07-01

    Chemical senses such as odor, taste and appearance are directly related with appetite. Understanding the relation between appetite and flavor is getting more important due to increasing number of obese patients worldwide. The literature on the studies investigating the change in olfactory abilities and gustatory sensitivity mostly performed using food-related odors and tastes rather than standardized tests were developed to study olfaction and gustation. Therefore, results are inconsistent and the relationship between olfactory and gustatory sensitivity with respect to the actual state of human satiety is still not completely understood. Here, for the first time in literature, we investigated the change in both olfactory abilities and gustatory sensitivity in hunger and in satiety using 123 subjects (37 men, 86 women; mean age 31.4 years, age range 21-41 years). The standardized Sniffin' Sticks Extended Test and Taste Strips were used for olfactory testing and gustatory sensitivity, respectively. TDI score (range 1-48) was calculated as the collective scores of odor threshold (T), odor discrimination (D) and odor identification (I). The evaluation was performed in two successive days where the hunger state of test subjects was confirmed by blood glucose test strips (mean blood glucose level 90.0 ± 5.6 mg/dl in hunger and 131.4 ± 8.1 mg/dl in satiety). The results indicated statistically significant decrease in olfaction in satiety compared to hunger (mean TDI 39.3 ± 1.1 in hunger, 37.4 ± 1.1 in satiety, p < 0.001). The comparison of gustatory sensitivity indicated significantly higher sensitivity to sweet, sour and salty in hunger (p < 0.001), but significantly higher sensitivity to bitter tastant in satiety (p < 0.001). With this prospective study, we were able to show that both olfactory abilities and gustatory sensitivity were affected by hunger state. PMID:25744049

  17. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen

    OpenAIRE

    Mendes-Pereira, Ana M.; Sims, David; Dexter, Tim; Fenwick, Kerry; Assiotis, Ioannis; Kozarewa, Iwanka; Mitsopoulos, Costas; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J; Ashworth, Alan

    2011-01-01

    Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,4...

  18. [Selective estrogen receptor modulators (SERMs)].

    Science.gov (United States)

    Chaki, Osamu

    2015-10-01

    Selective estrogen receptor modulators (SERMs) have the potential to provide the skeletal benefits of estrogen without the increased risk of uterine and breast cancer. Raloxifene, second generation SERM has been approved for the prevention and treatment of post-menopausal osteoporosis. Bazedoxifene, third generation SERM acts as a tissue selective estrogen antagonist or agonist. These SERMs inhibited bone turnover and prevented bone loss caused estrogen deficiency. Furthermore, these SERMs did not affect the uterine endometrial thickness and reduced serum cholesterol. These data suggest that SERMs are potential drug for the prevention of osteoporosis in postmenopausal women. PMID:26529929

  19. Variations in Maternal 5-HTTLPR Affect Observed Sensitive Parenting

    Science.gov (United States)

    Cents, Rolieke A. M.; Kok, Rianne; Tiemeier, Henning; Lucassen, Nicole; Székely, Eszter; Bakermans-Kranenburg, Marian J.; Hofman, Albert; Jaddoe, Vincent W. V.; IJzendoorn, Marinus H.; Verhulst, Frank C.; Lambregtse-van den Berg, Mijke P.

    2014-01-01

    Background: Little is known about the genetic determinants of sensitive parenting. Two earlier studies examined the effect of the serotonin transporter polymorphism (5-HTTLPR) on sensitive parenting, but reported opposite results. In a large cohort we further examined whether 5-HTTLPR is a predictor of observed maternal sensitivity and whether…

  20. Calmodulin affects sensitization of Drosophila melanogaster odorant receptors

    Directory of Open Access Journals (Sweden)

    Latha eMukunda

    2016-02-01

    Full Text Available Flying insects have developed a remarkably sensitive olfactory system to detect faint and turbulent odor traces. This ability is linked to the olfactory receptors class of odorant receptors (ORs, occurring exclusively in winged insects. ORs form heteromeric complexes of an odorant specific receptor protein (OrX and a highly conserved co-receptor protein (Orco. The ORs form ligand gated ion channels that are tuned by intracellular signaling systems. Repetitive subthreshold odor stimulation of olfactory sensory neurons sensitizes insect ORs. This OR sensitization process requires Orco activity. In the present study we first asked whether OR sensitization can be monitored with heterologously expressed OR proteins. Using electrophysiological and calcium imaging methods we demonstrate that D. melanogaster OR proteins expressed in CHO cells show sensitization upon repeated weak stimulation. This was found for OR channels formed by Orco as well as by Or22a or Or56a and Orco. Moreover, we show that inhibition of calmodulin (CaM action on OR proteins, expressed in CHO cells, abolishes any sensitization. Finally, we investigated the sensitization phenomenon using an ex vivo preparation of olfactory sensory neurons (OSNs expressing Or22a inside the fly’s antenna. Using calcium imaging, we observed sensitization in the dendrites as well as in the soma. Inhibition of calmodulin with W7 disrupted the sensitization within the outer dendritic shaft, whereas the sensitization remained in the other OSN compartments. Taken together, our results suggest that CaM action is involved in sensitizing the OR complex and that this mechanisms accounts for the sensitization in the outer dendrites, whereas further mechanisms contribute to the sensitization observed in the other OSN compartments. The use of heterologously expressed OR proteins appears to be suitable for further investigations on the mechanistic basis of OR sensitization, while investigations on native

  1. Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

    International Nuclear Information System (INIS)

    We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE2) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRSPE and BRSSNP). Nicotine (100 μg/kg i.v.) reduced BRSSNP in OVX rats but not in proestrus or OVXE2 rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRSPE was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRSSNP interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRSSNP attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E2 against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

  2. Bu-Shen-Ning-Xin Decoction ameliorated the osteoporotic phenotype of ovariectomized mice without affecting the serum estrogen concentration or uterus

    Directory of Open Access Journals (Sweden)

    Wang L

    2015-08-01

    Full Text Available Ling Wang,1,2,* Xue-Min Qiu,1,2,* Yu-Yan Gui,1,2 Ying-Ping Xu,1,2 Hans-Jürgen Gober,3 Da-Jin Li1 1Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China; 3Department of Pharmacy, Wagner Jauregg Hospital and Children’s Hospital, Linz, Austria *These authors contributed equally to this work Introduction: Bu-Shen-Ning-Xin Decoction (BSNXD, a traditional Chinese medicinal composition, has been used as a remedy for postmenopausal osteoporosis, but its effects on bone metabolism and the uterus have not been reported.Purpose: We aimed to determine the respective effects of BSNXD on the bones and the uterus of ovariectomized (OVX mice to evaluate the efficacy and safety of this herbal formula.Materials and methods: Postmenopausal osteoporosis animal models that were generated by ovariectomy were treated with BSNXD. Dual-energy X-ray absorptiometry was performed to analyze the bone mineral density, and histomorphometric analysis was performed to measure the parameters related to bone metabolism. Calcein labeling was performed to detect bone formation. The uteruses from the mice were weighed, and the histomorphometry was analyzed. Drug-derived serum was prepared to assess the 17-β-estradiol concentration via enzyme immunoassay.Results: BSNXD administration ameliorated the osteoporotic phenotype of OVX mice, as evidenced by an increase in the bone mineral density and bone volume; these effects could not be abolished by the administration of the aromatase inhibitor letrozole. Moreover, BSNXD had no effect on the serum estrogen concentration or uterus.Conclusion: These results suggest that BSNXD has ameliorating effects on bone loss due to estrogen deprivation without affecting the peripheral blood estrogen concentration or the uterus in OVX mice. Keywords

  3. Importance and sensitivity of parameters affecting the Zion Seismic Risk

    Energy Technology Data Exchange (ETDEWEB)

    George, L.L.; O' Connell, W.J.

    1985-06-01

    This report presents the results of a study on the importance and sensitivity of structures, systems, equipment, components and design parameters used in the Zion Seismic Risk Calculations. This study is part of the Seismic Safety Margins Research Program (SSMRP) supported by the NRC Office of Nuclear Regulatory Research. The objective of this study is to provide the NRC with results on the importance and sensitivity of parameters used to evaluate seismic risk. These results can assist the NRC in making decisions dealing with the allocation of research resources on seismic issues. This study uses marginal analysis in addition to importance and sensitivity analysis to identify subject areas (input parameter areas) for improvements that reduce risk, estimate how much the improvement dfforts reduce risk, and rank the subject areas for improvements. Importance analysis identifies the systems, components, and parameters that are important to risk. Sensitivity analysis estimates the change in risk per unit improvement. Marginal analysis indicates the reduction in risk or uncertainty for improvement effort made in each subject area. The results described in this study were generated using the SEISIM (Systematic Evaluation of Important Safety Improvement Measures) and CHAIN computer codes. Part 1 of the SEISIM computer code generated the failure probabilities and risk values. Part 2 of SEISIM, along with the CHAIN computer code, generated the importance and sensitivity measures.

  4. Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility

    OpenAIRE

    Sinkevicius, Kerstin W; Laine, Muriel; Lotan, Tamara L.; Woloszyn, Karolina; Richburg, John H.; Greene, Geoffrey L.

    2009-01-01

    Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ER...

  5. Sensitivity analysis on parameters and processes affecting vapor intrusion risk

    KAUST Repository

    Picone, Sara

    2012-03-30

    A one-dimensional numerical model was developed and used to identify the key processes controlling vapor intrusion risks by means of a sensitivity analysis. The model simulates the fate of a dissolved volatile organic compound present below the ventilated crawl space of a house. In contrast to the vast majority of previous studies, this model accounts for vertical variation of soil water saturation and includes aerobic biodegradation. The attenuation factor (ratio between concentration in the crawl space and source concentration) and the characteristic time to approach maximum concentrations were calculated and compared for a variety of scenarios. These concepts allow an understanding of controlling mechanisms and aid in the identification of critical parameters to be collected for field situations. The relative distance of the source to the nearest gas-filled pores of the unsaturated zone is the most critical parameter because diffusive contaminant transport is significantly slower in water-filled pores than in gas-filled pores. Therefore, attenuation factors decrease and characteristic times increase with increasing relative distance of the contaminant dissolved source to the nearest gas diffusion front. Aerobic biodegradation may decrease the attenuation factor by up to three orders of magnitude. Moreover, the occurrence of water table oscillations is of importance. Dynamic processes leading to a retreating water table increase the attenuation factor by two orders of magnitude because of the enhanced gas phase diffusion. © 2012 SETAC.

  6. Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes

    OpenAIRE

    Scott, LM; Durant, P; Leone-Kabler, S; Wood, CE; Register, TC; Townsend, A.; Cline, JM

    2008-01-01

    Estrogen exposure and metabolism may play an important role in the development of estrogen-sensitive cancers in postmenopausal women. In this study we investigated whether past oral contraceptive (OC) administration or current dietary isoflavonoids (IF) affected expression and/or activity of steroid hormone-metabolizing cytochrome P450 (CYP) enzymes using complementary primate and cell culture models. One-hundred-eighty-one female cynomolgus macaques were randomized to receive OC or nothing f...

  7. Genome-wide functional screen identifies a compendium of genes affecting sensitivity to tamoxifen

    Science.gov (United States)

    Mendes-Pereira, Ana M.; Sims, David; Dexter, Tim; Fenwick, Kerry; Assiotis, Ioannis; Kozarewa, Iwanka; Mitsopoulos, Costas; Hakas, Jarle; Zvelebil, Marketa; Lord, Christopher J.; Ashworth, Alan

    2012-01-01

    Therapies that target estrogen signaling have made a very considerable contribution to reducing mortality from breast cancer. However, resistance to tamoxifen remains a major clinical problem. Here we have used a genome-wide functional profiling approach to identify multiple genes that confer resistance or sensitivity to tamoxifen. Combining whole-genome shRNA screening with massively parallel sequencing, we have profiled the impact of more than 56,670 RNA interference reagents targeting 16,487 genes on the cellular response to tamoxifen. This screen, along with subsequent validation experiments, identifies a compendium of genes whose silencing causes tamoxifen resistance (including BAP1, CLPP, GPRC5D, NAE1, NF1, NIPBL, NSD1, RAD21, RARG, SMC3, and UBA3) and also a set of genes whose silencing causes sensitivity to this endocrine agent (C10orf72, C15orf55/NUT, EDF1, ING5, KRAS, NOC3L, PPP1R15B, RRAS2, TMPRSS2, and TPM4). Multiple individual genes, including NF1, a regulator of RAS signaling, also correlate with clinical outcome after tamoxifen treatment. PMID:21482774

  8. Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action.

    Science.gov (United States)

    Curtis Hewitt, S; Couse, J F; Korach, K S

    2000-01-01

    Natural, synthetic and environmental estrogens have numerous effects on the development and physiology of mammals. Estrogen is primarily known for its role in the development and functioning of the female reproductive system. However, roles for estrogen in male fertility, bone, the circulatory system and immune system have been established by clinical observations regarding sex differences in pathologies, as well as observations following menopause or castration. The primary mechanism of estrogen action is via binding and modulation of activity of the estrogen receptors (ERs), which are ligand-dependent nuclear transcription factors. ERs are found in highest levels in female tissues critical to reproduction, including the ovaries, uterus, cervix, mammary glands and pituitary gland. Since other affected tissues have extremely low levels of ER, indirect effects of estrogen, for example induction of pituitary hormones that affect the bone, have been proposed. The development of transgenic mouse models that lack either estrogen or ER have proven to be valuable tools in defining the mechanisms by which estrogen exerts its effects in various systems. The aim of this article is to review the mouse models with disrupted estrogen signaling and describe the associated phenotypes. PMID:11250727

  9. Unbalanced estrogen metabolism in ovarian cancer.

    Science.gov (United States)

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

    2014-05-15

    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 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

  10. Estrogen Deficiency and the Origin of Obesity during Menopause

    OpenAIRE

    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 estro...

  11. Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bendtzen, Klaus; Beck-Nielsen, H

    1997-01-01

    flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups. There was no...

  12. Perfectionism, personality, and affective experiences: New insights from revised Reinforcement Sensitivity Theory

    OpenAIRE

    Stoeber, Joachim; Philip J. Corr

    2015-01-01

    Previous studies have linked perfectionism to differences in reinforcement sensitivity, but findings have been mixed. The present study explored the relationships between three forms of perfectionism (self-oriented, other-oriented, socially prescribed) and components of the revised Reinforcement Sensitivity Theory of personality in relation to the experience of positive and negative affect. In a sample of 388 university students, we found consistent evidence of significant bivariate and semip...

  13. Do calcium-mediated cellular signalling pathways, prostaglandin E2 (PGE2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro?

    Science.gov (United States)

    Weems, Y S; Randel, R D; Carstens, G E; Welsh, T H; Weems, C W

    2004-04-01

    The major objective of this experiment was to determine whether the bovine placenta could be stimulated to secrete progesterone, since the bovine placenta secretes little progesterone when the corpus luteum is functional. Secondly, we wanted to determine whether reported abortifacients or progesterone or estrogen receptor antagonists affected bovine placental prostaglandin secretion. The ovine placenta secretes half of the circulating progesterone at day 90 of pregnancy and PGE2 appears to regulate ovine placental progesterone secretion. Calcium has been reported to regulate placental progesterone secretion in cattle. Diced 186-245-day placental slice explants from six Brahman and six Angus cows were incubated in vitro at 39.5 degrees C under 95% air: 5% CO2 at pH 7.2 in 5 ml of M-199 for 1 h in the absence of treatments and for 4 and 8 h in the presence of treatments. Treatments were: vehicle; R24571; compound 48/80; IP3; PGE2; CaCl2; cyclosporin A; lipopolysaccharide (endotoxin) from Salmonella abortus equi., enteriditis, and typhimurium; monensin; ionomycin; arachidonic acid; mimosine; palmitic acid; progesterone, androstenedione; estradiol-17beta; A23187; RU-486; or MER-25. Jugular and uterine venous plasma and culture media were analyzed for progesterone, PGE2 and PGF2alpha by radioimmunoassay (RIA). Plasma hormone data were analyzed by a One-Way Analysis of Variance (ANOVA). Hormone data in culture media were analyzed for breed and treatment effects by a Factorial Design (2 breeds, 2-range of days, 21 treatments) for ANOVA (2 x 2 x 21). Since hormone data secreted by placental tissue in vitro did not differ (P > or = 0.05) by breed or range of days of pregnancy, data were pooled and analyzed by a One-Way ANOVA. Concentrations of PGE2 in uterine venous blood were two-fold greater (P Angus than Brahman cows. PGE2 and PGF2alpha in vehicle controls increased from 4 to 8h (P or = 0.05) Progesterone in culture media treated with RU-486 increased (P or = 0

  14. From Specificity to Sensitivity: Affective states modulate visual working memory for emotional expressive faces

    Directory of Open Access Journals (Sweden)

    Thomas eMaran

    2015-08-01

    Full Text Available Previous findings suggest that visual working memory preferentially remembers angry looking faces. However, the meaning of facial actions is construed in relation to context. To date, there are no studies investigating the role of perceiver-based context when processing emotional cues in visual working memory. To explore the influence of affective context on visual working memory for faces, we conducted two experiments using both a visual working memory task for emotionally expressive faces and a mood induction procedure. Affective context was manipulated by unpleasant (Experiment 1 and pleasant (Experiment 2 IAPS pictures in order to induce an affect high in motivational intensity (defensive or appetitive, respectively compared to a low arousal control condition. Results indicated specifically increased sensitivity of visual working memory for angry looking faces in the neutral condition. Enhanced visual working memory for angry faces was prevented by inducing affects of high motivational intensity. In both experiments, affective states led to a switch from specific enhancement of angry expressions in visual working memory to an equally sensitive representation of all emotional expressions. Our findings demonstrate that emotional expressions are of different behavioral relevance for the receiver depending on the affective context, supporting a functional organization of visual working memory along with flexible resource allocation. In visual working memory, stimulus processing adjusts to situational requirements and transitions from a specifically prioritizing default mode in predictable environments to a sensitive, hypervigilant mode in exposure to emotional events.

  15. Estrogen increases ENaC activity via PKCδ signaling in renal cortical collecting duct cells.

    Science.gov (United States)

    Yusef, Yamil R; Thomas, Warren; Harvey, Brian J

    2014-05-01

    The most active estrogen, 17β-estradiol (E2), has previously been shown to stimulate a female sex-specific antisecretory response in the intestine. This effect is thought to contribute to the increase in whole body extracellular fluid (ECF) volume which occurs in high estrogen states, such as in the implantation window during estrous cycle. The increased ECF volume may be short-circuited by a renal compensation unless estrogen exerts a proabsorptive effect in the nephron. Thus, the effect of E2 on ENaC in kidney cortical collecting duct (CCD) cells is of interest to understand estrogen regulation of ECF volume. Previous studies showed a rapid stimulatory effect of estrogen on ENaC in bronchial epithelium. In this study we examined if such a rapid effect on Na(+) absorption could occur in the kidney. Experiments were carried out on murine M1-CCD cell cultures. E2 (25 nmol/L) treatment caused a rapid-onset (<15 min) and sustained increase in the amiloride-sensitive Na(+) current (INa) in CCD monolayers mounted in Ussing chambers (control, 1.9 ± 0.2 μA/cm(2); E2, 4.7 ± 0.3 μA/cm(2); n = 43, P < 0.001), without affecting the ouabain-sensitive Na(+)/K(+) pump current. The INa response to E2 was inhibited by PKCδ activity antagonism with rottlerin (5 μmol/L), inhibition of matrix metalloproteinases activity with GM6001 (1 μmol/L), inhibition of EGFR activity with AG1478 (10 μmol/L), inhibition of PLC activity with U-73122 (10 μmol/L), and inhibition of estrogen receptors with the general ER antagonist ICI-182780 (100 nmol/L). The estrogen activation of INa could be mimicked by the ERα agonist PPT (1 nmol/L). The nuclear excluded estrogen dendrimer conjugate (EDC) induced similar stimulatory effects on INa comparable to free E2. The end target for E2 stimulation of PKCδ was shown to be an increased abundance of the γ-ENaC subunit in the apical plasma membrane of CCD cells. We have demonstrated a novel rapid "nongenomic" function of estrogen to stimulate ENa

  16. Factors affecting differential sweet corn sensitivity to HPPD-inhibiting herbicides

    Science.gov (United States)

    Mutation of a cytochrome P450 (CYP) allele on the short arm of chromosome five affects sensitivity in sweet corn to mesotrione and tembotrione+isoxadifen applied POST. Hybrids that are homozygous for the functional allele (i.e. CYPCYP) are tolerant of both herbicides and rarely injured at registered...

  17. Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

    Energy Technology Data Exchange (ETDEWEB)

    El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

    2012-02-01

    We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

  18. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties.

    Science.gov (United States)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus; Andersen, Klaus Ejner

    2011-06-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens in ethanolic liposomes have been reported to enhance allergenicity compared with the allergens in similar vehicles without liposomes. The present report includes data on more sensitization studies using the mouse local lymph node assay with three contact allergens encapsulated in different dermal drug-delivery systems: liposomes, ethosomes, and polycaprolactone particles. The results show that the drug-delivery systems are not sensitizers in themselves. Encapsulating the hydrophilic contact allergen potassium dichromate in all three drug-delivery systems did not affect the sensitizing capacity of potassium dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed for encapsulating isoeugenol in polycaprolactone (1100 ± 406) compared with a formulation in acetone:olive oil (4491 ± 819) and in liposomes (3668 ± 950). Further, the size of DNCB-loaded liposomes did not affect the sensitizing properties. These results suggest that modern dermal drug-delivery systems may in some cases magnify or decrease the sensitizing capacity of the encapsulated contact allergen. PMID:21198410

  19. Estrogen and Growth Hormone and their Roles in Reproductive Function

    Directory of Open Access Journals (Sweden)

    Hüseyin Baki ÇİFTCİ

    2013-02-01

    Full Text Available The aim of this study was to review the effect of estrogen on growth hormone secretion and the roles of estrogen and growth hormone in reproductive function. Estrogen is the main hormone affecting growth, development, maturation and functioning of reproductive tract as well as the sexual differentiation and the behavior. Growth hormone is also important factor in sexual maturation and attainment of puberty. The impact of estrogen on growth hormone secretion has been reported in rodents and primates. However, the precise mechanism for the alterations in growth hormone secretion is not clearly known. Estrogen may possibility have a direct affect on growth hormone secretion via the binding to estrogen receptor-α due to its co-expression in growth hormone neurons in the medial preoptic area and arcuate nucleus. Estrogen may also have an indirect effect via the reducing insulin-like growth factor-1 feedback inhibition resulting with increased growth hormone secretion.

  20. KBERG: KnowledgeBase for Estrogen Responsive Genes

    DEFF Research Database (Denmark)

    Tang, Suisheng; Zhang, Zhuo; Tan, Sin Lam;

    2007-01-01

    Estrogen has a profound impact on human physiology affecting transcription of numerous genes. To decipher functional characteristics of estrogen responsive genes, we developed KnowledgeBase for Estrogen Responsive Genes (KBERG). Genes in KBERG were derived from Estrogen Responsive Gene Database...... user-friendly system that provides links to other relevant resources such as ERGDB, UniGene, Entrez Gene, HomoloGene, GO, eVOC and GenBank, and thus offers a platform for functional exploration and potential annotation of genes responsive to estrogen. KBERG database can be accessed at http...

  1. Estrogen and Bazedoxifene

    Science.gov (United States)

    Estrogen and bazedoxifene tablets are used to treat hot flashes (sudden feelings of warmth, especially in the ... women may experience other symptoms and body changes). Estrogen and bazedoxifene tablets are also used to prevent ...

  2. p21-activated kinase group II small compound inhibitor GNE-2861 perturbs estrogen receptor alpha signaling and restores tamoxifen-sensitivity in breast cancer cells

    OpenAIRE

    Zhuang, Ting; Zhu, Jian; Li, Zhilun; Lorent, Julie; Zhao, Chunyan; Dahlman-Wright, Karin; Strömblad, Staffan

    2015-01-01

    Estrogen receptor alpha (ERα) is highly expressed in most breast cancers. Consequently, ERα modulators, such as tamoxifen, are successful in breast cancer treatment, although tamoxifen resistance is commonly observed. While tamoxifen resistance may be caused by altered ERα signaling, the molecular mechanisms regulating ERα signaling and tamoxifen resistance are not entirely clear. Here, we found that PAK4 expression was consistently correlated to poor patient outcome in endocrine treated and ...

  3. Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray.

    Science.gov (United States)

    Coser, Kathryn R; Chesnes, Jessica; Hur, Jingyung; Ray, Sandip; Isselbacher, Kurt J; Shioda, Toshi

    2003-11-25

    To obtain comprehensive information on 17beta-estradiol (E2) sensitivity of genes that are inducible or suppressible by this hormone, we designed a method that determines ligand sensitivities of large numbers of genes by using DNA microarray and a set of simple Perl computer scripts implementing the standard metric statistics. We used it to characterize effects of low (0-100 pM) concentrations of E2 on the transcriptome profile of MCF7/BUS human breast cancer cells, whose E2 dose-dependent growth curve saturated with 100 pM E2. Evaluation of changes in mRNA expression for all genes covered by the DNA microarray indicated that, at a very low concentration (10 pM), E2 suppressed approximately 3-5 times larger numbers of genes than it induced, whereas at higher concentrations (30-100 pM) it induced approximately 1.5-2 times more genes than it suppressed. Using clearly defined statistical criteria, E2-inducible genes were categorized into several classes based on their E2 sensitivities. This approach of hormone sensitivity analysis revealed that expression of two previously reported E2-inducible autocrine growth factors, transforming growth factor alpha and stromal cell-derived factor 1, was not affected by 100 pM and lower concentrations of E2 but strongly enhanced by 10 nM E2, which was far higher than the concentration that saturated the E2 dose-dependent growth curve of MCF7/BUS cells. These observations suggested that biological actions of E2 are derived from expression of multiple genes whose E2 sensitivities differ significantly and, hence, depend on the E2 concentration, especially when it is lower than the saturating level, emphasizing the importance of characterizing the ligand dose-dependent aspects of E2 actions. PMID:14610279

  4. Estrogens and aging skin

    OpenAIRE

    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...

  5. Estrogen Signaling and Cardiovascular Disease

    OpenAIRE

    Murphy, Elizabeth

    2011-01-01

    Estrogen has pleiotropic effects on the cardiovascular system. The mechanisms by which estrogen confers these pleiotropic effects on cardiovascular function is under active investigation. Until a decade ago, all estrogen signaling was thought to occur by estrogen binding to nuclear estrogen receptors (ERα and ERβ), which bind to DNA and function as ligand activated transcription factors. Estrogen binding to the receptor alters gene expression thereby altering cell function. In 2000 estrogen w...

  6. A peptide derived from α-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen

    OpenAIRE

    James A. Bennett; Mesfin, Fassil B.; Andersen, Thomas T.; Gierthy, John F.; Jacobson, Herbert I.

    2002-01-01

    An 8-mer peptide (EMTOVNOG) derived from α-fetoprotein was compared with tamoxifen for activity against growth of human breast cancer xenografts implanted in immune-deficient mice. Both peptide and tamoxifen prevented growth of estrogen-receptor-positive MCF-7 and T47D human breast cancer xenografts. A subline of MCF-7, made resistant to tamoxifen by a 6-month exposure to this drug in culture, was found to be resistant to tamoxifen in vivo. Peptide completely prevented the xenograft growth of...

  7. The multiple factors affecting the association between atopic dermatitis and contact sensitization

    DEFF Research Database (Denmark)

    Thyssen, J P; McFadden, J P; Kimber, I

    2014-01-01

    Atopic dermatitis and allergic contact dermatitis are both common skin diseases having an immune pathogenesis. There has been considerable interest about their inter-relationships with regard to altered susceptibility. Recent investigations have shed new light on this important question, and in...... this article, we explore whether there is evidence that atopic dermatitis affects the risk of contact sensitization and allergic contact dermatitis. The use of topical products to treat xerotic and inflamed skin in atopic dermatitis often results in a higher prevalence of sensitization to, for example......, fragrances and other ingredients in emollients. Moreover, the prevalence of metal allergy seems to be increased, probably due to compromised chelation of the metals in the stratum corneum of patients with atopic dermatitis. However, conversely, the T-helper cell 2 bias that characterizes immune responses in...

  8. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

    Science.gov (United States)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-12-15

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17alpha-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERalpha-selective agonist), diarylpropionitrile (DPN, an ERbeta-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERalpha-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERbeta-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats. PMID:17109907

  9. Influence of sex and estrogen on musculotendinous protein turnover at rest and after exercise

    DEFF Research Database (Denmark)

    Hansen, Mette; Kjaer, Michael

    2014-01-01

    Women differ from men with regard to muscle and tendon, most likely because of sex differences in estrogen. The present experimental findings suggest the hypothesis that estrogen has an anabolic effect on muscle primarily by lowering the protein turnover and enhancing sensitivity to resistance...... training. Furthermore, estrogen may reduce the stiffness of tendons, an effect that may be modified by physical training....

  10. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Flores Roberto

    2012-12-01

    functional activity of fecal β-glucuronidase (R=0.36, P=0.04. In contrast, fecal β-glucuronidase correlated inversely with fecal total estrogens, both conjugated and deconjugated (R≤-0.47, P≤0.01. Premenopausal female estrogen levels, which were collected across menstrual cycles and thus highly variable, were completely unrelated to fecal microbiome and enzyme parameters (P≥0.6. Conclusions Intestinal microbial richness and functions, including but not limited to β-glucuronidase, influence levels of non-ovarian estrogens via enterohepatic circulation. Thus, the gut microbial community likely affects the risk for estrogen-related conditions in older adults. Understanding how Clostridia taxa relate to systemic estrogens may identify targets for interventions. Trial registration Not applicable.

  11. Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, Ann-Sofie, E-mail: ann-sofie.gustafsson@bms.uu.se; Abramenkovs, Andris; Stenerlöw, Bo

    2014-11-15

    Highlights: • We reduced the level of DNA-PKcs with siRNA and examined cells after γ-irradiation. • Low DNA-PKcs levels lead to radiosensitivity but did not affect repair of DSB. • Low DNA-PKcs levels may block progression of mitosis. • DNA-PKcs role in mitotic progression is independent of its role in DSB repair. • We suggest different mechanisms by which loss of DNA-PKcs function sensitize cells. - Abstract: Efficient and correct repair of DNA double-strand break (DSB) is critical for cell survival. Defects in the DNA repair may lead to cell death, genomic instability and development of cancer. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an essential component of the non-homologous end joining (NHEJ) which is the major DSB repair pathway in mammalian cells. In the present study, by using siRNA against DNA-PKcs in four human cell lines, we examined how low levels of DNA-PKcs affected cellular response to ionizing radiation. Decrease of DNA-PKcs levels by 80–95%, induced by siRNA treatment, lead to extreme radiosensitivity, similar to that seen in cells completely lacking DNA-PKcs and low levels of DNA-PKcs promoted cell accumulation in G2/M phase after irradiation and blocked progression of mitosis. Surprisingly, low levels of DNA-PKcs did not affect the repair capacity and the removal of 53BP1 or γ-H2AX foci and rejoining of DSB appeared normal. This was in strong contrast to cells completely lacking DNA-PKcs and cells treated with the DNA-PKcs inhibitor NU7441, in which DSB repair were severely compromised. This suggests that there are different mechanisms by which loss of DNA-PKcs functions can sensitize cells to ionizing radiation. Further, foci of phosphorylated DNA-PKcs (T2609 and S2056) co-localized with DSB and this was independent of the amount of DNA-PKcs but foci of DNA-PKcs was only seen in siRNA-treated cells. Our study emphasizes on the critical role of DNA-PKcs for maintaining survival after radiation exposure

  12. Computational method for discovery of estrogen responsive genes

    DEFF Research Database (Denmark)

    Tang, Suisheng; Tan, Sin Lam; Ramadoss, Suresh Kumar;

    2004-01-01

    Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of...... human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames...... across different promoters in the human genome. Matching ERE frames of a test set of 60 known estrogen responsive genes to the collection of over 18,000 human promoters, we obtained 604 candidate genes. Evaluating our result by comparison with the published microarray data and literature, we found that...

  13. Enzymatic treatment of estrogens and estrogen glucuronide

    Institute of Scientific and Technical Information of China (English)

    Takaaki Tanaka; Toshiyuki Tamura; Yuuichi Ishizaki; Akito Kawasaki; Tomokazu Kawase; Masahiro Teraguchi; Masayuki Taniguchi

    2009-01-01

    Natural and synthetic estrogens from sewage treatment systems are suspected to influence the reproductive health of the animals in the rivers.In this article we investigated the enzymatic treatment of three estrogens (estrone,17β-estradiol,and 17α-ethynyletstradiol) by a fungal laccase which oxidize phenolic compounds with dissolved oxygen.The elimination of the estrogenic activities by enzymatic oxidation was demonstrated by medaka vitellogenin assay.In addition,we developed an enzymatic treatment system comprised of β-D-glucuronidase and the laccase for 17β-estradiol 3-(β-D-glucuronide) degradation.The two enzymes eliminated 17β-estradiol 3-(β-D-glucuronide) and the intermediate,17β-estradiol,efficiently.

  14. Short-Term Estrogen Replacement Effects on Insulin Sensitivity and Glucose Tolerance in At-Risk Cats for Feline Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Allison Wara

    Full Text Available Male domestic cats that are neutered and overweight are at an increased risk for developing a type-2-like diabetes mellitus. Beneficial effects of 17β-estradiol (E2 on glucose homeostasis may be lost with neutering and thereby account for increased diabetes risk. To evaluate this, adult male neutered overweight cats (n=6 were given daily E2 (1.0 μg/kg or vehicle (Vh; ethanol, 1.0 μL/kg in a single crossover trial of 14-day periods with a 7-day washout. The E2 and Vh were voluntarily ingested on food. The E2 dosage was determined in a pre-trial to significantly and transiently reduce food intake with no measurable change in plasma E2 concentration. During treatments, physical activity was assessed with collar-mounted accelerometers on days 9-11, and tests of intravenous insulin tolerance and intravenous glucose tolerance were conducted on days 13 and 14, respectively. Over the 14 days, E2 compared to Vh treatment reduced (p=0.03 food intake (- 22% but not enough to significantly reduce body weight; activity counts were not significantly changed. With E2 compared to Vh treatment, the late-phase plasma insulin response of the glucose tolerance test was less (p=0.03 by 31%, while glucose tolerance and insulin sensitivity indexes were not significantly changed. The results indicate that oral E2 at a dosage that moderately affects food intake may reduce insulin requirement for achieving glucose homeostasis in neutered male cats. Further investigation is needed to identify the mechanism underlying the E2 effect.

  15. Estrogen sulfotransferase regulates body fat and glucose homeostasis in female mice

    OpenAIRE

    Victor K Khor; Dhir, Ravindra; Yin, Xiaoyan; Ahima, Rexford S.; Song, Wen-Chao

    2010-01-01

    Estrogen regulates fat mass and distribution and glucose metabolism. We have previously found that estrogen sulfotransferase (EST), which inactivates estrogen through sulfoconjugation, was highly expressed in adipose tissue of male mice and induced by testosterone in female mice. To determine whether inhibition of estrogen in female adipose tissue affects adipose mass and metabolism, we generated transgenic mice expressing EST via the aP2 promoter. As expected, EST expression was increased in...

  16. Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women

    OpenAIRE

    Lim, Vanessa W; Li, Jun; Gong, Yinhan; Jin, Aizhen; Yuan, Jian-Min; Yong, Eu Leong; Koh, Woon-Puay

    2014-01-01

    The estrogen levels of Asian women are different from those of Western women, and this could affect estrogen receptor (ER) bioactivity and breast cancer risk. We conducted a case-control study of 169 postmenopausal breast cancer cases and 426 matched controls nested within a population-based prospective cohort, The Singapore Chinese Health Study, to evaluate serum levels of estrogens and their receptor (ERα and ERβ)-mediated estrogenic activities in relation to breast cancer risk. Breast canc...

  17. Infant Affect and Affect Regulation during the Still-Face Paradigm with Mothers and Fathers: The Role of Infant Characteristics and Parental Sensitivity.

    Science.gov (United States)

    Braungart-Rieker, Julia; Garwood, Molly Murphy; Powers, Bruce P.; Notaro, Paul C.

    1998-01-01

    Examined parents' and 4-month-old infants' behavior during face-to-face interactions. Results indicated that mothers and fathers were equally sensitive to their infants, and that infants' affect and regulatory behaviors were stable across mother-infant and father-infant situations in the still-face model. (BC)

  18. Prematurity does not markedly affect intestinal sensitivity to endotoxins and feeding in pigs.

    Science.gov (United States)

    Bering, Stine B; Bai, Shiping; Zhang, Keying; Sangild, Per T

    2012-08-01

    Preterm neonates show enhanced sensitivity to nutrient maldigestion and bacteria-mediated gut inflammatory disorders, such as necrotising enterocolitis (NEC). We hypothesised that preterm birth increases the sensitivity of intestinal nutrient absorption to endotoxins and that feeding after birth reduces this response. Hence, we investigated the postnatal development of nutrient digestive and absorptive capacity in the preterm and term pig intestine, and its responsiveness to endotoxins. Pigs were delivered by caesarean section at preterm (n 20) or term (n 17) gestation, and the small intestine was collected at birth or after 2 d of colostrum feeding, followed by ex vivo stimulation with lipopolysaccharide endotoxins and mixed gut contents collected from pigs with NEC. Brush border enzyme activities were reduced in newborn preterm v. term pigs (39-45 % reduction, P < 0.05), but normalised after 2 d of feeding. Ex vivo leucine and glucose uptake increased with prenatal age. Bacterial stimulation reduced the nutrient uptake similarly at birth and after 2 d in preterm and term pigs (23-41 % reduction, P < 0.05), whereas IL-6 and TNF-α expression was stimulated only at birth. Toll-like receptor-4 expression increased markedly at day 2 for preterm and term pigs (22-33-fold, P < 0.05) but with much lower expression levels in newborn preterm pigs (approximately 95 %, P < 0.01). In conclusion, digestive and absorptive functions mature in the prenatal period, but are similarly affected by postnatal feeding and bacterial exposure in both preterm and term pigs. Nutrient maldigestion may contribute to NEC development, while a prematurity-related hyper-responsiveness to endotoxins could be less important, at least in pigs. PMID:22136806

  19. Dihydropyridine-sensitive calcium channel activity related to prolactin, growth hormone, and luteinizing hormone release from anterior pituitary cells in culture: interactions with somatostatin, dopamine, and estrogens

    International Nuclear Information System (INIS)

    In the present work, we determined the activity of voltage-dependent dihydropyridine (DHP)-sensitive Ca2+ channels related to PRL, GH, and LH secretion in primary cultures of pituitary cells from male or female rats. We investigated their modulation by 17 beta-estradiol (E2) and their involvement in dopamine (DA) and somatostatin (SRIF) inhibition of PRL and GH release. BAY-K-8644 (BAYK), a DHP agonist which increases the opening time of already activated channels, stimulated PRL and GH secretion in a dose-dependent manner. The effect was more pronounced on PRL than on GH release. BAYK-evoked hormone secretion was further amplified by simultaneous application of K+ (30 or 56 mM) to the cell cultures; in parallel, BAYK-induced 45Ca uptake by the cells was potentiated in the presence of depolarizing stimuli. In contrast, BAYK was unable to stimulate LH secretion from male pituitary cells, but it potentiated LHRH- as well as K+-induced LH release; it had only a weak effect on LH secretion from female cell cultures. Basal and BAYK-induced pituitary hormone release were blocked by the Ca2+ channel antagonist nitrendipine. Under no condition did BAYK affect the hydrolysis of phosphoinositides or cAMP formation. Pretreatment of female pituitary cell cultures with E2 (10(-9) M) for 72 h enhanced LH and PRL responses to BAYK, but was ineffective on GH secretion. DA (10(-7) M) inhibited basal and BAYK-induced PRL release from male or female pituitary cells treated or not treated with E2 (10(-9) M). SRIF (10(-9) and 10(-8) M) reversed BAYK-evoked GH release to the same extent in cell cultures derived from male or female animals. It was ineffective on BAYK-induced PRL secretion in the absence of E2, but antagonized it after E2 pretreatment. The effect was dependent upon the time of steroid treatment and was specific, since 17 alpha-estradiol was inactive

  20. Estrogen intracrinology: therapy and chemoprevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Barbara Licznerska

    2010-05-01

    Full Text Available Breast cancer affects approximately 1 in 10 women and is the leading cause of death in females between the ages of 40 and 50 years in the Western world. The World Health Organization (WHO classified estrogens as carcinogenic in humans and one of the most important risk factors of breast cancer. One of the main arguments has been that estrogens can not only promote cancers but may also initiate mutations caused by certain estrogen metabolites. Therapeutics and chemopreventive agents (e.g. tamoxifen currently in use for breast cancer generally act through an estrogen receptor (ER mechanism and are thus inappropriate for estrogen-independent disease. In the last decade, numerous studies have searched for new therapeutic and preventive agents acting independently of ER status, hence suitable for cases of estrogen-independent breast cancer. In postmenopausal women, when gonads stop producing estrogens, active hormones are produced locally. These locally produced bioactive estrogens exert their actions in the cells of tissues that have not been considered classical hormone-producing sites (i.e. breast cancer tissue and where synthesis occurs without release into the circulation. This mechanism has been termed “intracrinology”, a phenomenon different from the classical concept of endocrinology. Interference in the local production of estrogens seems to be a good alternative to chemotherapy and chemoprevention of breast carcinoma. In this article, crucial enzymes in estrogen’s biosynthesis in the breast and their potential use in therapy and chemoprevention are discussed.

  1. Sucrose Sensitivity of Honey Bees Is Differently Affected by Dietary Protein and a Neonicotinoid Pesticide

    Science.gov (United States)

    Démares, Fabien J.; Crous, Kendall L.; Pirk, Christian W. W.; Nicolson, Susan W.; Human, Hannelie

    2016-01-01

    Over a decade, declines in honey bee colonies have raised worldwide concerns. Several potentially contributing factors have been investigated, e.g. parasites, diseases, and pesticides. Neonicotinoid pesticides have received much attention due to their intensive use in crop protection, and their adverse effects on many levels of honey bee physiology led the European Union to ban these compounds. Due to their neuronal target, a receptor expressed throughout the insect nervous system, studies have focused mainly on neuroscience and behaviour. Through the Geometric Framework of nutrition, we investigated effects of the neonicotinoid thiamethoxam on survival, food consumption and sucrose sensitivity of honey bees (Apis mellifera). Thiamethoxam did not affect protein and carbohydrate intake, but decreased responses to high concentrations of sucrose. Interestingly, when bees ate fixed unbalanced diets, dietary protein facilitated better sucrose detection. Both thiamethoxam and dietary protein influenced survival. These findings suggest that, in the presence of a pesticide and unbalanced food, honey bee health may be severely challenged. Consequences for foraging efficiency and colony activity, cornerstones of honey bee health, are also discussed. PMID:27272274

  2. Sucrose Sensitivity of Honey Bees Is Differently Affected by Dietary Protein and a Neonicotinoid Pesticide.

    Directory of Open Access Journals (Sweden)

    Fabien J Démares

    Full Text Available Over a decade, declines in honey bee colonies have raised worldwide concerns. Several potentially contributing factors have been investigated, e.g. parasites, diseases, and pesticides. Neonicotinoid pesticides have received much attention due to their intensive use in crop protection, and their adverse effects on many levels of honey bee physiology led the European Union to ban these compounds. Due to their neuronal target, a receptor expressed throughout the insect nervous system, studies have focused mainly on neuroscience and behaviour. Through the Geometric Framework of nutrition, we investigated effects of the neonicotinoid thiamethoxam on survival, food consumption and sucrose sensitivity of honey bees (Apis mellifera. Thiamethoxam did not affect protein and carbohydrate intake, but decreased responses to high concentrations of sucrose. Interestingly, when bees ate fixed unbalanced diets, dietary protein facilitated better sucrose detection. Both thiamethoxam and dietary protein influenced survival. These findings suggest that, in the presence of a pesticide and unbalanced food, honey bee health may be severely challenged. Consequences for foraging efficiency and colony activity, cornerstones of honey bee health, are also discussed.

  3. Tissue Specific Effects of Loss of Estrogen During Menopause and Aging

    Directory of Open Access Journals (Sweden)

    Korinna eWend

    2012-02-01

    Full Text Available 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 post-menopausal symptoms.

  4. Dual effects of daidzein on chicken hepatic vitellogenin II expression and estrogen receptor-mediated transactivation in vitro.

    Science.gov (United States)

    Ni, Ying-Dong; Hong, Wen-Jie; Zhou, Yu-Chuan; Grossmann, Roland; Zhao, Ru-Qian

    2010-03-01

    Two in vitro systems were employed to delineate the estrogenic activity of daidzein (Da), alone or in combination with high or low concentrations of estrogen in two cell types possessing different estrogen-receptor (ER) isoforms, ERalpha and/or ERbeta: (1) vitellogenin II (VTG), the egg yolk precursor protein and the endpoint biomarker for estrogenicity, in chicken primary hepatocytes, and (2) CHO-K1 cells transiently co-transfected with ERalpha or ERbeta and estrogen-response elements (ERE) linked to a luciferase reporter gene. Da (100 microM) alone induced VTG mRNA expression in chicken hepatocytes, albeit with much less potency compared to estradiol (E(2)). Da exhibited different effects in the presence of 1 microM and 10 microM E(2). At a concentration of 100 microM, Da enhanced 1 microM E(2)-induced VTG transcription by 2.4-fold, but significantly inhibited 10 microM E(2)-induced VTG mRNA expression in a dose-dependent fashion from 1 to 100 microM. Tamoxifen completely blocked the estrogenic effect of daidzein, alone or in combination with 1 microM of E(2), but did not influence its anti-estrogenic effect on 10 microM E(2)-induced VTG mRNA expression. Furthermore, neither E(2) nor daidzein, alone or in combination, affected ERalpha mRNA expression, yet all the treatments significantly up-regulated ERbeta mRNA expression in chicken hepatocytes. E(2) effectively triggered estrogen-response elements (ERE)-driven reporter gene transactivation in CHO-K1 cells expressing ERalpha or ERbeta and showed much greater potency with ERalpha than with ERbeta. In contrast, daidzein was 1000 times more powerful in stimulating ERbeta- over ERalpha-mediated transactivation. Daidzein, in concentrations ranging from 5 nM to 50 microM, did not affect ERbeta-mediated transactivation induced by 1 nM E(2), but it significantly inhibited ERbeta-mediated transactivation induced by 10 nM E(2) at 500 nM. Despite the tremendous difference in sensitivity between the two in vitro systems

  5. Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray

    OpenAIRE

    Coser, Kathryn R.; Chesnes, Jessica; Hur, Jingyung; Ray, Sandip; Isselbacher, Kurt J.; Shioda, Toshi

    2003-01-01

    To obtain comprehensive information on 17β-estradiol (E2) sensitivity of genes that are inducible or suppressible by this hormone, we designed a method that determines ligand sensitivities of large numbers of genes by using DNA microarray and a set of simple Perl computer scripts implementing the standard metric statistics. We used it to characterize effects of low (0–100 pM) concentrations of E2 on the transcriptome profile of MCF7/BUS human breast cancer cells, whose E2 dose-dependent growt...

  6. Steroid estrogens, conjugated estrogens and estrogenic activity in farm dairy shed effluents

    Energy Technology Data Exchange (ETDEWEB)

    Gadd, Jennifer B., E-mail: j.gadd@niwa.co.n [Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Tremblay, Louis A., E-mail: tremblayl@landcareresearch.co.n [Landcare Research, PO Box 40, Lincoln, 7640 (New Zealand); Northcott, Grant L., E-mail: grant.northcott@plantandfood.co.n [Plant and Food Research, Private Bag 3123, Waikato Mail Centre, Hamilton 3240 (New Zealand)

    2010-03-15

    Agricultural wastes are a source of steroid estrogens and, if present, conjugated estrogens may add to the estrogen load released to soil and aquatic environments. Dairy shed effluent samples were collected from 18 farms for analysis of steroid estrogens by GC-MS, conjugated estrogens by LC-MS-MS, and estrogenic activity by E-screen in vitro bioassay. 17alpha-estradiol was found at highest concentrations (median 730 ng l{sup -1}), followed by estrone (100 ng l{sup -1}) and 17beta-estradiol (24 ng l{sup -1}). Conjugated estrogens (estrone-3-sulfate, 17alpha-estradiol-3-sulfate and 17beta-estradiol-3,17-disulfate) were measured in most samples (12-320 ng l{sup -1}). Median estrogenic activity was 46 ng l{sup -1} 17beta-estradiol equivalents. Conjugated estrogens contributed up to 22% of the total estrogen load from dairy farming, demonstrating their significance. Steroid estrogens dominated overall estrogenic activity measured in the samples. Significantly, 17alpha-estradiol contributed 25% of overall activity, despite potency 2% that of 17beta-estradiol, highlighting the importance in environmental risk assessments of this previously neglected compound. - In rural ecosystems, 17alpha-estradiol and conjugated estrogens are significant sources of environmental estrogens from agricultural wastes.

  7. Steroid estrogens, conjugated estrogens and estrogenic activity in farm dairy shed effluents

    International Nuclear Information System (INIS)

    Agricultural wastes are a source of steroid estrogens and, if present, conjugated estrogens may add to the estrogen load released to soil and aquatic environments. Dairy shed effluent samples were collected from 18 farms for analysis of steroid estrogens by GC-MS, conjugated estrogens by LC-MS-MS, and estrogenic activity by E-screen in vitro bioassay. 17α-estradiol was found at highest concentrations (median 730 ng l-1), followed by estrone (100 ng l-1) and 17β-estradiol (24 ng l-1). Conjugated estrogens (estrone-3-sulfate, 17α-estradiol-3-sulfate and 17β-estradiol-3,17-disulfate) were measured in most samples (12-320 ng l-1). Median estrogenic activity was 46 ng l-1 17β-estradiol equivalents. Conjugated estrogens contributed up to 22% of the total estrogen load from dairy farming, demonstrating their significance. Steroid estrogens dominated overall estrogenic activity measured in the samples. Significantly, 17α-estradiol contributed 25% of overall activity, despite potency 2% that of 17β-estradiol, highlighting the importance in environmental risk assessments of this previously neglected compound. - In rural ecosystems, 17α-estradiol and conjugated estrogens are significant sources of environmental estrogens from agricultural wastes.

  8. Manure-borne estrogens as potential environmental contaminants: a review.

    Science.gov (United States)

    Hanselman, Travis A; Graetz, Donald A; Wilkie, Ann C

    2003-12-15

    Livestock wastes are potential sources of endocrine disrupting compounds to the environment. Steroidal estrogen hormones such as estradiol, estrone, and estriol are a particular concern because there is evidence that low nanogram per liter concentrations of estrogens in water can adversely affect the reproductive biology of fish and other aquatic vertebrate species. We performed a literature review to assess the current state of science regarding estrogen physicochemical properties, livestock excretion, and the fate of manure-borne estrogens in the environment. Unconjugated steroidal estrogens have low solubility in water (0.8-13.3 mg L(-1)) and are moderately hydrophobic (log Kow 2.6-4.0). Cattle excrete mostly 17alpha-estradiol, 17beta-estradiol, estrone, and respective sulfated and glucuronidated counterparts, whereas swine and poultry excrete mostly 17beta-estradiol, estrone, estriol, and respective sulfated and glucuronidated counterparts. The environmental fate of estrogens is not clearly known. Laboratory-based studies have found that the biological activity of these compounds is greatly reduced or eliminated within several hours to days due to degradation and sorption. On the other hand, field studies have demonstrated that estrogens are sufficiently mobile and persistent to impact surface and groundwater quality. Future research should use standardized methods for the analysis of manure, soil, and water. More information is needed about the types and amounts of estrogens that exist in livestock wastes and the fate of manure-borne estrogens applied to agricultural lands. Field and laboratory studies should work toward revealing the mechanisms of estrogen degradation, sorption, and transport so that the risk of estrogen contamination of waterways can be minimized. PMID:14717153

  9. Subinhibitory concentrations of antibiotics affect stress and virulence gene expression in Listeria monocytogenes and cause enhanced stress sensitivity but do not affect Caco‐2 cell invasion

    DEFF Research Database (Denmark)

    Knudsen, Gitte Maegaard; Holch, Anne; Gram, Lone

    2012-01-01

    Antibiotics can act as signal molecules and affect bacterial gene expression, physiology and virulence. The purpose of this study was to determine whether subinhibitory antibiotic concentrations alter gene expression and physiology of Listeria monocytogenes. Using an agar‐based screening assay with...... promoter fusions, 14 of 16 antibiotics induced or repressed expression of one or more stress and/or virulence genes. Despite ampicillin‐induced up‐regulation of PinlA‐lacZ expression, Caco‐2 cell invasion was not affected. Subinhibitory concentrations of ampicillin and tetracycline caused up‐ and down......‐regulation of stress response genes, respectively, but both antibiotics caused increased sensitivity to acid stress. Six combinations of gene‐antibiotic were quantified in broth cultures and five of the six resulted in the same expression pattern as the agar‐based assay. Antibiotics affect virulence and...

  10. Estrogen receptor transcription and transactivation: Basic aspects of estrogen action

    International Nuclear Information System (INIS)

    Estrogen signaling has turned out to be much more complex and exciting than previously thought; the paradigm shift in our understanding of estrogen action came in 1996, when the presence of a new estrogen receptor (ER), ERβ, was reported. An intricate interplay between the classical ERα and the novel ERβ is of paramount importance for the final biological effect of estrogen in different target cells

  11. Quantitative assessment of factors affecting the sensitivity of a competitive immunomicroarray for pesticide detection

    DEFF Research Database (Denmark)

    Belleville, Erik; Dufva, Hans Martin; Aamund, J.,; Bruun, L.; Christensen, Claus Bo Vöge

    2003-01-01

    Analytical protein microarrays offering highly parallel analysis can become an invaluable tool for a wide range of immunodiagnostic applications. Here we describe factors that influence the sensitivity of a competitive immunomicroarray that quantifies small molecules; in this case, the pesticides...

  12. Estrogen regulation of epithelial ion transport: Implications in health and disease.

    Science.gov (United States)

    Saint-Criq, Vinciane; Rapetti-Mauss, Raphael; Yusef, Yamil R; Harvey, Brian J

    2012-08-01

    Estrogen, 17β-estradiol (E2), has been shown to modulate the activity of ion channels in a diverse range of epithelial tissues. The channel activation or inhibition responses to E2 are often rapid, occurring in seconds to minutes, independent of protein synthesis and gene transcription ('non-genomic' response). These rapid effects of E2 require activation of specific protein kinases or changes in intracellular calcium and pH which in turn modulate the conductance, open probability or number of channels in the plasmamembrane. Estrogen has also been shown to affect the expression of ion transporters over days ('genotropic' response) causing long-term sustained changes in transepithelial ion transport. It is now accepted that so called non-genomic responses are not stand-alone events and are necessary to prime the latent genomic response and even be critical for the full latent response to occur. In a number of epithelia the non-genomic and genotropic responses to estrogen are sex-specific and variable in potency and sensitivity to E2 depending on the stage of the estrous cycle. Of increasing interest is the effect these rapid and latent actions of E2 on ion transporters have on the physiological functions of epithelia. For example, estrogen regulation of a class of voltage-gated K(+) channels (KCNQ1) can determine the rate of Cl(-) secretion in the intestine. In whole-body terms, the combined effects of estrogen on a variety of ion channels which control fluid and electrolyte transport in the kidney, intestine and lung may be necessary for endometrial expansion and implantation of the blastocyte. PMID:22410439

  13. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    Energy Technology Data Exchange (ETDEWEB)

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

  14. Estrogen Stimulates Homing of Endothelial Progenitor Cells to Endometriotic Lesions.

    Science.gov (United States)

    Rudzitis-Auth, Jeannette; Nenicu, Anca; Nickels, Ruth M; Menger, Michael D; Laschke, Matthias W

    2016-08-01

    The incorporation of endothelial progenitor cells (EPCs) into microvessels contributes to the vascularization of endometriotic lesions. Herein, we analyzed whether this vasculogenic process is regulated by estrogen. Estrogen- and vehicle-treated human EPCs were analyzed for migration and tube formation. Endometriotic lesions were induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN (Tie2/green fluorescent protein) 287 Sato mice. The animals were treated with 100 μg/kg β-estradiol 17-valerate or vehicle (control) over 7 and 28 days. Lesion growth, cyst formation, homing of green fluorescent protein(+)/Tie2(+) EPCs, vascularization, cell proliferation, and apoptosis were analyzed by high-resolution ultrasonography, caliper measurements, histology, and immunohistochemistry. Numbers of blood circulating EPCs were assessed by flow cytometry. In vitro, estrogen-treated EPCs exhibited a higher migratory and tube-forming capacity when compared with controls. In vivo, numbers of circulating EPCs were not affected by estrogen. However, estrogen significantly increased the number of EPCs incorporated into the lesions' microvasculature, resulting in an improved early vascularization. Estrogen further stimulated the growth of lesions, which exhibited massively dilated glands with a flattened layer of stroma. This was mainly because of an increased glandular secretory activity, whereas cell proliferation and apoptosis were not markedly affected. These findings indicate that vasculogenesis in endometriotic lesions is dependent on estrogen, which adds a novel hormonally regulated mechanism to the complex pathophysiology of endometriosis. PMID:27315780

  15. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus;

    2012-01-01

    tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses of...... ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction of...... of NODAT remains unclear. We sought to compare the impact of CsA and Tac on glucose metabolism in human subjects. METHODS: Ten healthy men underwent 5 h infusions of CsA, Tac and saline in a randomized, double-blind, crossover study. During infusion glucose metabolism was investigated using following...

  16. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Frank D Rinkevich

    Full Text Available The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (<1-fold, moderate differences in pyrethroid bioassays (1.5 to 3-fold, and dramatic differences in neonicotinoid bioassays (3.4 to 33.3-fold. Synergism bioassays with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin sensitivity in all stocks and also demonstrated further physiological differences between stocks. In addition, as bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the

  17. Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability

    DEFF Research Database (Denmark)

    Breinholt, Vibeke; Hossaini, A.; Svendsen, Gitte W.;

    2000-01-01

    The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, genistein and equol was investigated in immature female mice. Genistein and equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17-20, 100 mg/kg body weight], was found to significantly increase uterine...... weights and the overall uterine concentration of estrogen receptor alpha (ER alpha). In kaempferol- and equol-exposed mice the cytosolic ER alpha concentration was significantly increased as compared to the solvent control, which is speculated to result in an increased sensitivity of the uterus to...... subsequently encountered estrogens. Oral administration of equol, genistein, biochanin A and daidzein to 6-week-old female mice revealed a great variation in their systemic bioavailability. The urinary recovery of equol was thus over 90% of a single gavage administered dose, whereas the urinary recoveries of...

  18. Pharmacokinetic and Pharmacodynamic Factors That Can Affect Sensitivity to Neurotoxic Sequelae in Elderly Individuals

    OpenAIRE

    Ginsberg, Gary; Hattis, Dale; Russ, Abel; Sonawane, Babasaheb

    2005-01-01

    Early-life exposure to agents that modulate neurologic function can have long-lasting effects well into the geriatric period. Many other factors can affect neurologic function and susceptibility to neurotoxicants in elderly individuals. In this review we highlight pharmacokinetic and pharmacodynamic factors that may increase geriatric susceptibility to these agents. There is a decreasing trend in hepatic metabolizing capacity with advancing years that can affect the ability to clear therapeut...

  19. The distribution of attention in RSVP tasks and its sensitivity to affect, personality traits and estradiol

    OpenAIRE

    Dhinakaran, Janani

    2014-01-01

    In this thesis, the influences of positive and negative affect state, the personality trait neuroticism, and the hormone estradiol on selective attention are explored in three studies. In Study 1 a double-stream RSVP paradigm was used to explore if attention can be spatially diffused and focused by affect. A spatial interpretation of the diffuse mental state was not found. Study 2 studied the distribution of attention as influenced by neuroticism and cognitive control. Results confirmed that ...

  20. Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor

    DEFF Research Database (Denmark)

    Nellemann, Christine Lydia; Dalgaard, Majken; Holst, Bjørn;

    2005-01-01

    Several endpoints of different molecular complexity were studied in the Hershberger assay in order to evaluate the specificity and suitability of this test as a broad screening model. Androgen and estrogen receptors were activated or blocked, and expression of typical estrogen- or androgen...... anti-estrogen, ICI 182780, only affected ODC expression. Therefore, estrogenic or anti-estrogenic compounds would not be expected to seriously affect the outcome of a Hershberger test. However, EB given alone to castrated rats resulted in various effects. EB increased seminal vesicle weight, an effect...... reversed by ICI 182780, and affected TRPM-2, PBP C3, ODC, IGF-1, AR, and ERa mRNA levels. AR expression in the prostate seemed to be under regulation of both estrogens and androgens, as ICI 182780 inhibited the testosterone-induced AR expression, and flutamide inhibited the EB-induced AR expression. These...

  1. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, A.; Konings, E.; Goossens, G.H.; Bouwman, F.G.; Moors, C.C.; Boekschoten, M.V.; Afman, L.A.; Muller, M.R.; Mariman, E.C.; Blaak, E.E.

    2012-01-01

    Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial

  2. Anaerobic biotransformation of estrogens

    Energy Technology Data Exchange (ETDEWEB)

    Czajka, Cynthia P. [Department of Microbiology, University of Manitoba, Winnipeg, MB, R3T 2N2 (Canada); Londry, Kathleen L. [Department of Microbiology, University of Manitoba, Winnipeg, MB, R3T 2N2 (Canada)]. E-mail: londryk@cc.umanitoba.ca

    2006-08-31

    Estrogens are important environmental contaminants that disrupt endocrine systems and feminize male fish. We investigated the potential for anaerobic biodegradation of the estrogens 17-{alpha}-ethynylestradiol (EE2) and 17-{beta}-estradiol (E2) in order to understand their fate in aquatic and terrestrial environments. Cultures were established using lake water and sediment under methanogenic, sulfate-, iron-, and nitrate-reducing conditions. Anaerobic degradation of EE2 (added at 5 mg/L) was not observed in multiple trials over long incubation periods (over three years). E2 (added at 5 mg/L) was transformed to estrone (E1) under all four anaerobic conditions (99-176 {mu}g L{sup -1} day{sup -1}), but the extent of conversion was different for each electron acceptor. The oxidation of E2 to E1 was not inhibited by E1. Under some conditions, reversible inter-conversion of E2 and E1 was observed, and the final steady state concentration of E2 depended on the electron-accepting condition but was independent of the total amount of estrogens added. In addition, racemization occurred and E1 was also transformed to 17-{alpha}-estradiol under all but nitrate-reducing conditions. Although E2 could be readily transformed to E1 and in many cases 17-{alpha}-estradiol under anaerobic conditions, the complete degradation of estrogens under these conditions was minimal, suggesting that they would accumulate in anoxic environments.

  3. Sensitivity analysis of a global aerosol model to understand how parametric uncertainties affect model predictions

    Science.gov (United States)

    Lee, L. A.; Carslaw, K. S.; Pringle, K. J.

    2012-04-01

    Global aerosol contributions to radiative forcing (and hence climate change) are persistently subject to large uncertainty in successive Intergovernmental Panel on Climate Change (IPCC) reports (Schimel et al., 1996; Penner et al., 2001; Forster et al., 2007). As such more complex global aerosol models are being developed to simulate aerosol microphysics in the atmosphere. The uncertainty in global aerosol model estimates is currently estimated by measuring the diversity amongst different models (Textor et al., 2006, 2007; Meehl et al., 2007). The uncertainty at the process level due to the need to parameterise in such models is not yet understood and it is difficult to know whether the added model complexity comes at a cost of high model uncertainty. In this work the model uncertainty and its sources due to the uncertain parameters is quantified using variance-based sensitivity analysis. Due to the complexity of a global aerosol model we use Gaussian process emulation with a sufficient experimental design to make such as a sensitivity analysis possible. The global aerosol model used here is GLOMAP (Mann et al., 2010) and we quantify the sensitivity of numerous model outputs to 27 expertly elicited uncertain model parameters describing emissions and processes such as growth and removal of aerosol. Using the R package DiceKriging (Roustant et al., 2010) along with the package sensitivity (Pujol, 2008) it has been possible to produce monthly global maps of model sensitivity to the uncertain parameters over the year 2008. Global model outputs estimated by the emulator are shown to be consistent with previously published estimates (Spracklen et al. 2010, Mann et al. 2010) but now we have an associated measure of parameter uncertainty and its sources. It can be seen that globally some parameters have no effect on the model predictions and any further effort in their development may be unnecessary, although a structural error in the model might also be identified. The

  4. Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera.

    Science.gov (United States)

    Rinkevich, Frank D; Margotta, Joseph W; Pittman, Jean M; Danka, Robert G; Tarver, Matthew R; Ottea, James A; Healy, Kristen B

    2015-01-01

    The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature. PMID:26431171

  5. Estrogens and autoimmune diseases.

    Science.gov (United States)

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  6. Quantitative assessment of factors affecting the sensitivity of a competitive immunomicroarray for pesticide detection

    DEFF Research Database (Denmark)

    Belleville, Erik; Dufva, Hans Martin; Aamund, J.,;

    2003-01-01

    Analytical protein microarrays offering highly parallel analysis can become an invaluable tool for a wide range of immunodiagnostic applications. Here we describe factors that influence the sensitivity of a competitive immunomicroarray that quantifies small molecules; in this case, the pesticides...... dichlobenil metabolite 2,6-dichlorobenzamide (BAM) and atrazine. Free pesticide concentrations in solution are quantified by the competitive binding of fluorescence-conjugated monoclonal antibodies to either surface-immobilized pesticide hapten-protein conjugates or pesticides in solution. We investigated the...

  7. Factors affecting the ozone sensitivity of temperate European grasslands: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Bassin, S. [Agroscope FAL Reckenholz, Swiss Federal Research Station for Agroecology and Agriculture, Air Pollution/Climate Group, Reckenholzstrasse 191, CH-8046 Zurich (Switzerland)]. E-mail: seraina.bassin@fal.admin.ch; Volk, M. [Agroscope FAL Reckenholz, Swiss Federal Research Station for Agroecology and Agriculture, Air Pollution/Climate Group, Reckenholzstrasse 191, CH-8046 Zurich (Switzerland); Fuhrer, J. [Agroscope FAL Reckenholz, Swiss Federal Research Station for Agroecology and Agriculture, Air Pollution/Climate Group, Reckenholzstrasse 191, CH-8046 Zurich (Switzerland)

    2007-04-15

    This overview of experimentally induced effects of ozone aims to identify physiological and ecological principles, which can be used to classify the sensitivity to ozone of temperate grassland communities in Europe. The analysis of data from experiments with single plants, binary mixtures and multi-species communities illustrates the difficulties to relate individual responses to communities, and thus to identify grassland communities most at risk. Although there is increasing evidence that communities can be separated into broad classes of ozone sensitivity, the database from experiments under realistic conditions with representative systems is too small to draw firm conclusions. But it appears that risk assessments, based on results from individuals or immature mixtures exposed in chambers, are only applicable to intensively managed, productive grasslands, and that the risk of ozone damage for most of perennial grasslands with lower productivity tends to be less than previously expected. - An overview of experimentally induced ozone effects suggests that temperate grasslands could be separated into broad classes of ozone sensitivity based on physiological and ecological principles.

  8. Factors affecting the ozone sensitivity of temperate European grasslands: An overview

    International Nuclear Information System (INIS)

    This overview of experimentally induced effects of ozone aims to identify physiological and ecological principles, which can be used to classify the sensitivity to ozone of temperate grassland communities in Europe. The analysis of data from experiments with single plants, binary mixtures and multi-species communities illustrates the difficulties to relate individual responses to communities, and thus to identify grassland communities most at risk. Although there is increasing evidence that communities can be separated into broad classes of ozone sensitivity, the database from experiments under realistic conditions with representative systems is too small to draw firm conclusions. But it appears that risk assessments, based on results from individuals or immature mixtures exposed in chambers, are only applicable to intensively managed, productive grasslands, and that the risk of ozone damage for most of perennial grasslands with lower productivity tends to be less than previously expected. - An overview of experimentally induced ozone effects suggests that temperate grasslands could be separated into broad classes of ozone sensitivity based on physiological and ecological principles

  9. Fecal calprotectin is equally sensitive in Crohn's disease affecting the small bowel and colon

    DEFF Research Database (Denmark)

    Jensen, Michael Dam; Kjeldsen, Jens; Nathan, Torben

    2011-01-01

    The utility of fecal calprotectin (fCal) in small bowel Crohn's disease (CD) remains to be clarified. The primary aim of this study was to determine levels of fCal in CD restricted to the small bowel compared with CD affecting the colon, in patients undergoing their first diagnostic work-up. In...

  10. Factors Affecting Sensitivity to Frequency Change in School-Age Children and Adults

    Science.gov (United States)

    Buss, Emily; Taylor, Crystal N.; Leibold, Lori J.

    2014-01-01

    Purpose: The factors affecting frequency discrimination in school-age children are poorly understood. The goal of the present study was to evaluate developmental effects related to memory for pitch and the utilization of temporal fine structure. Method: Listeners were 5.1- to 13.6-year-olds and adults, all with normal hearing. A subgroup of…

  11. Reviewing the options for local estrogen treatment of vaginal atrophy

    Directory of Open Access Journals (Sweden)

    Lindahl SH

    2014-03-01

    Full Text Available Sarah H Lindahl Sutter East Bay Medical Foundation, SEBMF – Diablo Division, Castro Valley, CA, USA Background: Vaginal atrophy is a chronic condition with symptoms that include vaginal dryness, pain during sex, itching, irritation, burning, and discharge, as well as various urinary problems. Up to 45% of postmenopausal women may be affected, but it often remains underreported and undertreated. This article aims to review the current recommendations for treatment of vaginal atrophy, and current data on the effectiveness and safety of local vaginal estrogen therapies. Methods: Literature regarding vaginal atrophy (2007–2012 was retrieved from PubMed and summarized, with emphasis on data related to the treatment of vaginal atrophy with local vaginal estrogen therapy. Results: Published data support the effectiveness and endometrial safety of low-dose local estrogen therapies. These results further support the general recommendation by the North American Menopause Society that a progestogen is not needed for endometrial protection in patients using low-dose local vaginal estrogen. Benefits of long-term therapy for vaginal atrophy include sustained relief of symptoms as well as physiological improvements (eg, decreased vaginal pH and increased blood flow, epithelial thickness, secretions. Conclusion: Currently available local vaginal estrogen therapies are well tolerated and effective in relieving symptoms of vaginal atrophy. Recent data support the endometrial safety of low-dose regimens for up to 1 year. Keywords: menopause, estrogen, local estrogen therapy, vaginal atrophy

  12. Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes.

    Science.gov (United States)

    Scott, L M; Durant, P; Leone-Kabler, S; Wood, C E; Register, T C; Townsend, A; Cline, J M

    2008-12-01

    Estrogen exposure and metabolism may play an important role in the development of estrogen-sensitive cancers in postmenopausal women. In this study we investigated whether past oral contraceptive (OC) administration or current dietary isoflavonoids (IF) affected expression and/or activity of steroid hormone-metabolizing cytochrome P450 (CYP) enzymes using complementary primate and cell culture models. One-hundred-eighty-one female cynomolgus macaques were randomized to receive OC or nothing for 26 months premenopausally, then ovariectomized and randomized to one of three diets for 36 months: an IF-depleted soy protein isolate (Soy-) diet, a Soy diet with IF (Soy+), or a Soy- diet supplemented with conjugated equine estrogens (CEE). Prior OC-treatment significantly reduced CYP gene expression in the mammary gland (CYP expression, while CEE-treatment decreased CYP1A1 and increased CYP3A4 mRNA in a tissue-specific manner. For in vitro studies, we measured effects of the isoflavonoids genistein, daidzein and equol on CYP activity using intact V79 cells stably transfected to express CYP1A1, CYP1B1, or CYP3A4. All three IFs significantly altered CYP activity in a dose-dependent and isoform-specific manner (20-95% inhibition versus controls). These results suggest potential mechanisms for prior OC and dietary IF effects on cancer risk in estrogen-responsive tissues. PMID:18955142

  13. The Expression of Estrogen Receptor is Dependent on the Estrogen Level and Associated with Cholesterol-Rich Diet in Female Rat's Heart and Vascular Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    吴赛珠; 刘建国; 周可祥; 刘长青; 马瑞; 孙飞; 隗和明

    2003-01-01

    Objective To study the effects of estrogen level and cholesterol - rich diet on the ex-pression of estrogen receptor (ER) in cardiovasculartissues including vascular endothelial cells (VEC) offemale rats. Methods The receptor binding assay(RBA) was adopted to measure the estrogen receptorlevel in aortic wall, heart and vascular endothelialcells of female rats on a cholesterol- rich diet. A ra-dioimmunoassay was employed to measure the level ofserum estradiol. Results The number of ER signif-icantly decreased in hearts, aorta and vascular en-dothelial cells in the ovariectomized rats and the ratson a cholesterol- rich diet. In contrast, the adminis-tration of estrogen somewhat restored the expression ofER. Conclusions For female rats, the level of es-trogen affects the expression of ER in cardiovascularsystem. The number of ER decreases along with thedecrease in the level of estrogen. A cholesterol -richdiet also can decrease the expression of ER in cardio-vascular system of female rats.

  14. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus;

    2011-01-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens...... dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed...

  15. Encapsulating contact allergens in liposomes, ethosomes, and polycaprolactone may affect their sensitizing properties

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Vogel, Stefan; Johansen, Jeanne Duus;

    2011-01-01

    Attempts to improve formulation of topical products are a continuing process and the development of micro- and nanovesicular systems as well as polymeric microparticles has led to marketing of topical drugs and cosmetics using these technologies. Encapsulation of some well-known contact allergens...... dichromate compared with control solutions. However, encapsulating the lipophilic contact allergen dinitrochlorobenzene (DNCB) in polycaprolactone reduced the sensitizing capacity to 1211 ± 449 compared with liposomes (7602 ± 2658) and in acetone:olive oil (4:1) (5633 ± 666). The same trend was observed...

  16. Effects of phytoestrogens and environmental estrogens on osteoblastic differentiation in MC3T3-E1 cells

    International Nuclear Information System (INIS)

    Phytoestrogens and environmental estrogens, which have in part some structural similarity to 17β-estradiol, are reported to act as agonists/antagonists of estrogen in animals and humans. Estrogen is known to play an important role in maintaining bone mass, since the concentration of serum estrogen decreases after menopause and the estrogen deficiency results in bone loss. In this study, we report the effects of phytoestrogens (genistein, daidzein, and coumestrol) and environmental estrogens (bisphenol A (BPA), p-n-nonylphenol (NP) and bis(2-ethylhexyl)phthalate (DEHP)) on osteoblast differentiation using MC3T3-E1 cells, a mouse calvaria osteoblast-like cell line. Coumestrol (10-10 to 10-6 M) slightly enhanced cell proliferation, while neither the other phytoestrogens (daidzein, genistein) nor environmental estrogens increased cell proliferation. Alkaline phosphatase (ALP) activity and cellular calcium (Ca) and phosphorus (P) contents were increased by phytoestrogens and BPA; however, neither NP nor DEHP affected those osteoblastic indicators. The effects of estrogenic potency, using the cell proliferation of MCF-7 cells, an estrogen receptor (ER)-positive human breast cancer cell line, indicate that coumestrol has the highest estrogenic potency among those phytoestrogens and environmental estrogens. The estrogenic potency of NP and DEHP were lower than the others. In conclusion, phytoestrogens, such as coumestrol, genistein and daidzein, and BPA increased ALP activity and enhanced bone mineralization in MC3T3-E1 cells, suggesting that not only phytoestrogen but also BPA, an environmental estrogen, is implicated in bone metabolism

  17. Parameters affecting the electron beam sensitivity of poly(methyl methacrylate)

    International Nuclear Information System (INIS)

    Poly(methyl methacrylate), PMMA, is used as a model polymer to determine quantitatively the effect of molecular weight, molecular weight distribution, and tacticity on electron beam sensitivity. The heterotactic, syndiotactic, and isotactic stereoforms of PMMA were synthesized with molecular weights ranging from 104 to 107 and dispersivities from 1.2 to about 10. The G-values as determined by gamma radiation are about 1.3 and are independent of the three parameters. However, the solubility rate of PMMA is very dependent on the tacticity, and the relative solubility rates are in the order syndiotactic < heterotactic much less than isotactic. The weight-average molecular weight ratio was found to give a better correlation with solubility rate ratio than the number-average molecular weight ratio. The molecular size of the developer solvent was shown to have a much greater effect on the solubility rate than the molecular weight of the resist. An optimal developer solvent for PMMA can be systematically selected from a homologous series of n-alkyl acetates which enhance the resist sensitivity

  18. Broadband noise exposure does not affect hearing sensitivity in big brown bats (Eptesicus fuscus).

    Science.gov (United States)

    Simmons, Andrea Megela; Hom, Kelsey N; Warnecke, Michaela; Simmons, James A

    2016-04-01

    In many vertebrates, exposure to intense sounds under certain stimulus conditions can induce temporary threshold shifts that reduce hearing sensitivity. Susceptibility to these hearing losses may reflect the relatively quiet environments in which most of these species have evolved. Echolocating big brown bats (Eptesicus fuscus) live in extremely intense acoustic environments in which they navigate and forage successfully, both alone and in company with other bats. We hypothesized that bats may have evolved a mechanism to minimize noise-induced hearing losses that otherwise could impair natural echolocation behaviors. The hearing sensitivity of seven big brown bats was measured in active echolocation and passive hearing tasks, before and after exposure to broadband noise spanning their audiometric range (10-100 kHz, 116 dB SPL re. 20 µPa rms, 1 h duration; sound exposure level 152 dB). Detection thresholds measured 20 min, 2 h or 24 h after exposure did not vary significantly from pre-exposure thresholds or from thresholds in control (sham exposure) conditions. These results suggest that big brown bats may be less susceptible to temporary threshold shifts than are other terrestrial mammals after exposure to similarly intense broadband sounds. These experiments provide fertile ground for future research on possible mechanisms employed by echolocating bats to minimize hearing losses while orienting effectively in noisy biological soundscapes. PMID:27030779

  19. Estrogenic compounds -endocrine disruptors

    OpenAIRE

    Munteanu Constantin; Hoteteu Mihai

    2011-01-01

    Endocrine disruptors (polychlorinated biphenyls, dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inf...

  20. I feel you: the design and evaluation of a domotic affect-sensitive spoken conversational agent.

    Science.gov (United States)

    Lutfi, Syaheerah Lebai; Fernández-Martínez, Fernando; Lorenzo-Trueba, Jaime; Barra-Chicote, Roberto; Montero, Juan Manuel

    2013-01-01

    We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO). In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA). NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive) were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users' frustrations and, ultimately, improving their satisfaction. PMID:23945740

  1. I Feel You: The Design and Evaluation of a Domotic Affect-Sensitive Spoken Conversational Agent

    Directory of Open Access Journals (Sweden)

    Juan Manuel Montero

    2013-08-01

    Full Text Available We describe the work on infusion of emotion into a limited-task autonomous spoken conversational agent situated in the domestic environment, using a need-inspired task-independent emotion model (NEMO. In order to demonstrate the generation of affect through the use of the model, we describe the work of integrating it with a natural-language mixed-initiative HiFi-control spoken conversational agent (SCA. NEMO and the host system communicate externally, removing the need for the Dialog Manager to be modified, as is done in most existing dialog systems, in order to be adaptive. The first part of the paper concerns the integration between NEMO and the host agent. The second part summarizes the work on automatic affect prediction, namely, frustration and contentment, from dialog features, a non-conventional source, in the attempt of moving towards a more user-centric approach. The final part reports the evaluation results obtained from a user study, in which both versions of the agent (non-adaptive and emotionally-adaptive were compared. The results provide substantial evidences with respect to the benefits of adding emotion in a spoken conversational agent, especially in mitigating users’ frustrations and, ultimately, improving their satisfaction.

  2. NO EFFECT OF DIFFERENT ESTROGEN RECEPTOR LIGANDS ON COGNITION IN ADULT FEMALE MONKEYS

    OpenAIRE

    Lacreuse, Agnès; Wilson, Mark E.; Herndon, James G.

    2008-01-01

    Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, the mechanisms by which estrogens may impact cognition remain unclear. The goal of the present study was to assess the effects of different estrogen receptor (ER) ligands on cognitive function in adult ovariectomized female rhesus monkeys. The monkeys were tested for 6 weeks on a battery of memory and attentional tasks administered on a touchscreen: the object, face, and spatial versions of the Dela...

  3. An Assessment of Potential Exposure and Risk from Estrogens in Drinking Water

    OpenAIRE

    Caldwell, Daniel J.; Mastrocco, Frank; Nowak, Edward; Johnston, James; Yekel, Harry; Pfeiffer, Danielle; Hoyt, Marilyn; DuPlessie, Beth M.; Anderson, Paul D.

    2009-01-01

    Background Detection of estrogens in the environment has raised concerns in recent years because of their potential to affect both wildlife and humans. Objectives We compared exposures to prescribed and naturally occurring estrogens in drinking water to exposures to naturally occurring background levels of estrogens in the diet of children and adults and to four independently derived acceptable daily intakes (ADIs) to determine whether drinking water intakes are larger or smaller than dietary...

  4. Estrogen-mediated effects on depression and memory formation in females

    OpenAIRE

    Shors, Tracey J.; Leuner, Benedetta

    2003-01-01

    Women are twice as likely to suffer from depression as men. It has been proposed that the ovarian hormones estrogen and progesterone contribute to the higher incidence of this potentially debilitating disorder. Depression can also be accompanied by a loss of cognitive performance. Here we review estrogen-mediated effects on depression and memory formation in females. We propose that changes in levels of estrogen are associated with sex differences in learning as well as changes in affect prio...

  5. Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein

    OpenAIRE

    Yahata, Tetsuro; Shao, Wenlin; Endoh, Hideaki; Hur, Jingyung; Coser, Kathryn R.; Sun, Huiping; Ueda, Yoshitaka; Kato, Shigeaki; Isselbacher, Kurt J.; Brown, Myles; Shioda, Toshi

    2001-01-01

    CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is a transcriptional coregulator. Here, we show evidence that CITED1 functions as a selective coactivator for estrogen-dependent transcription. When transfected, CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of both estrogen receptor-α (ERα) and ERβ in an estrogen-dependent manner, but it affected transcriptional activities of other nuclear receptors only marginally. CITED1 bound direc...

  6. Impact of secondary treatment types and sludge handling processes on estrogen concentration in wastewater sludge.

    Science.gov (United States)

    Marti, Erica J; Batista, Jacimaria R

    2014-02-01

    Endocrine-disrupting compounds (EDCs), such as estrogen, are known to be present in the aquatic environment at concentrations that negatively affect fish and other wildlife. Wastewater treatment plants (WWTPs) are major contributors of EDCs into the environment. EDCs are released via effluent discharge and land application of biosolids. Estrogen removal in WWTPs has been studied in the aqueous phase; however, few researchers have determined estrogen concentration in sludge. This study focuses on estrogen concentration in wastewater sludge as a result of secondary treatment types and sludge handling processes. Grab samples were collected before and after multiple treatment steps at two WWTPs receiving wastewater from the same city. The samples were centrifuged into aqueous and solid phases and then processed using solid phase extraction. Combined natural estrogens (estrone, estradiol and estriol) were measured using an enzyme-linked immunosorbent assay (ELISA) purchased from a manufacturer. Results confirmed that activated sludge treatments demonstrate greater estrogen removal compared to trickling filters and mass concentration of estrogen was measured for the first time on trickling filter solids. Physical and mechanical sludge treatment processes, such as gravity thickeners and centrifuges, did not significantly affect estrogen removal based on mass balance calculations. Dissolved air flotation thickening demonstrated a slight decrease in estrogen concentration, while anaerobic digestion resulted in increased mass concentration of estrogen on the sludge and a high estrogen concentration in the supernatant. Although there are no state or federally mandated discharge effluent standards or sludge application standards for estrogen, implications from this study are that trickling filters would need to be exchanged for activated sludge treatment or followed by an aeration basin in order to improve estrogen removal. Also, anaerobic digestion may need to be replaced

  7. Estrogen and Progestin (Hormone Replacement Therapy)

    Science.gov (United States)

    Combinations of estrogen and progestin are used to treat certain symptoms of menopause. Estrogen and progestin are two female sex hormones. Hormone replacement therapy works by replacing estrogen hormone that is no longer being made by ...

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

    International Nuclear Information System (INIS)

    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-17β to the four rainbow trout ER isoforms with that of three known environmental estrogens 17α-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 ERα subtype is also included for comparison. The results of this study suggest that, when compared to estradiol-17β, bisphenol A binds less strongly to all four receptors, 17α-ethinylestradiol binds more strongly, and raloxifene has a high affinity for the α 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.

  9. Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues*

    OpenAIRE

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N.; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-01-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patters of brown and white adipose tissue from ATGL (−/−) and HSL (−/−) mice using differential activity-based gel electrophoresis. This method is based on activity-r...

  10. Parameter sensitivities affecting the flutter speed of a MW-sized blade.

    Energy Technology Data Exchange (ETDEWEB)

    Lobitz, Donald Wayne, Jr.

    2005-08-01

    With the current trend toward larger and larger horizontal axis wind turbines, classical flutter is becoming a more critical issue. Recent studies have indicated that for a single blade turning in still air the flutter speed for a modern 35 m blade occurs at approximately twice its operating speed (2 per rev), whereas for smaller blades (5-9 m), both modern and early designs, the flutter speeds are in the range of 3.5-6 per rev. Scaling studies demonstrate that the per rev flutter speed should not change with scale. Thus, design requirements that change with increasing blade size are producing the concurrent reduction in per rev flutter speeds. In comparison with an early small blade design (5 m blade), flutter computations indicate that the non rotating modes which combine to create the flutter mode change as the blade becomes larger (i.e., for the larger blade the second flapwise mode, as opposed to the first flapwise mode for the smaller blade, combines with the first torsional mode to produce the flutter mode). For the more modern smaller blade design (9 m blade), results show that the non rotating modes that couple are similar to those of the larger blade. For the wings of fixed-wing aircraft, it is common knowledge that judicious selection of certain design parameters can increase the airspeed associated with the onset of flutter. Two parameters, the chordwise location of the center of mass and the ratio of the flapwise natural frequency to the torsional natural frequency, are especially significant. In this paper studies are performed to determine the sensitivity of the per rev flutter speed to these parameters for a 35 m wind turbine blade. Additional studies are performed to determine which structural characteristics of the blade are most significant in explaining the previously mentioned per rev flutter speed differences. As a point of interest, flutter results are also reported for two recently designed 9 m twist/coupled blades.

  11. Parameter sensitivities affecting the flutter speed of a MW-sized blade.

    Energy Technology Data Exchange (ETDEWEB)

    Lobitz, Donald Wayne, Jr.

    2004-10-01

    With the current trend toward larger and larger horizontal axis wind turbines, classical flutter is becoming a more critical issue. Recent studies have indicated that for a single blade turning in still air the flutter speed for a modern 35 m blade occurs at approximately twice its operating speed (2 per rev), whereas for smaller blades (5-9 m), both modern and early designs, the flutter speeds are in the range of 3.5-6 per rev. Scaling studies demonstrate that the per rev flutter speed should not change with scale. Thus, design requirements that change with increasing blade size are producing the concurrent reduction in per rev flutter speeds. In comparison with an early small blade design (5 m blade), flutter computations indicate that the non rotating modes which combine to create the flutter mode change as the blade becomes larger (i.e., for the larger blade the second flapwise mode, as opposed to the first flapwise mode for the smaller blade, combines with the first torsional mode to produce the flutter mode). For the more modern smaller blade design (9 m blade), results show that the non rotating modes that couple are similar to those of the larger blade. For the wings of fixed-wing aircraft, it is common knowledge that judicious selection of certain design parameters can increase the airspeed associated with the onset of flutter. Two parameters, the chordwise location of the center of mass and the ratio of the flapwise natural frequency to the torsional natural frequency, are especially significant. In this paper studies are performed to determine the sensitivity of the per rev flutter speed to these parameters for a 35 m wind turbine blade. Additional studies are performed to determine which structural characteristics of the blade are most significant in explaining the previously mentioned per rev flutter speed differences. As a point of interest, flutter results are also reported for two recently designed 9 m twist/coupled blades.

  12. An olfactory-limbic model of multiple chemical sensitivity syndrome: Possible relationships to kindling and affective spectrum disorders

    Energy Technology Data Exchange (ETDEWEB)

    Bell, I.R.; Miller, C.S.; Schwartz, G.E. (Univ. of Arizona Health Sciences Center, Tucson (United States))

    1992-08-01

    This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. 170 refs.

  13. Behavioural responses to thermal conditions affect seasonal mass change in a heat-sensitive northern ungulate.

    Directory of Open Access Journals (Sweden)

    Floris M van Beest

    Full Text Available BACKGROUND: Empirical tests that link temperature-mediated changes in behaviour (activity and resource selection to individual fitness or condition are currently lacking for endotherms yet may be critical to understanding the effect of climate change on population dynamics. Moose (Alces alces are thought to suffer from heat stress in all seasons so provide a good biological model to test whether exposure to non-optimal ambient temperatures influence seasonal changes in body mass. Seasonal mass change is an important fitness correlate of large herbivores and affects reproductive success of female moose. METHODOLOGY/PRINCIPAL FINDINGS: Using GPS-collared adult female moose from two populations in southern Norway we quantified individual differences in seasonal activity budget and resource selection patterns as a function of seasonal temperatures thought to induce heat stress in moose. Individual body mass was recorded in early and late winter, and autumn to calculate seasonal mass changes (n = 52 over winter, n = 47 over summer. We found large individual differences in temperature-dependent resource selection patterns as well as within and between season variability in thermoregulatory strategies. As expected, individuals using an optimal strategy, selecting young successional forest (foraging habitat at low ambient temperatures and mature coniferous forest (thermal shelter during thermally stressful conditions, lost less mass in winter and gained more mass in summer. CONCLUSIONS/SIGNIFICANCE: This study provides evidence that behavioural responses to temperature have important consequences for seasonal mass change in moose living in the south of their distribution in Norway, and may be a contributing factor to recently observed declines in moose demographic performance. Although the mechanisms that underlie the observed temperature mediated habitat-fitness relationship remain to be tested, physiological state and individual variation in

  14. Estrogen signalling and the DNA damage response in hormone dependent breast cancers

    Directory of Open Access Journals (Sweden)

    C Elizabeth Caldon

    2014-05-01

    Full Text Available Estrogen is necessary for the normal growth and development of breast tissue, but high levels of estrogen are a major risk factor for breast cancer. One mechanism by which estrogen could contribute to breast cancer is via the induction of DNA damage. This perspective discusses the mechanisms by which estrogen alters the DNA damage response (DDR and DNA repair through the regulation of key effector proteins including ATM, ATR, CHK1, BRCA1 and p53 and the feedback on estrogen receptor signalling from these proteins. We put forward the hypothesis that estrogen receptor signalling converges to suppress effective DNA repair and apoptosis in favour of proliferation. This is important in hormone-dependent breast cancer as it will affect processing of estrogen-induced DNA damage, as well as other genotoxic insults. DDR and DNA repair proteins are frequently mutated or altered in estrogen responsive breast cancer which will further change the processing of DNA damage. Finally the action of estrogen signalling on DNA damage is also relevant to the therapeutic setting as the suppression of a DNA damage response by estrogen has the potential to alter the response of cancers to anti-hormone treatment or chemotherapy that induces DNA damage.

  15. Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves.

    Science.gov (United States)

    Pantophlet, A J; Gilbert, M S; van den Borne, J J G C; Gerrits, W J J; Roelofsen, H; Priebe, M G; Vonk, R J

    2016-04-01

    Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight=114±2.4kg; age=97±1.4 d) calves were fed an MR containing 462g of lactose/kg (CON), or an MR in which 150g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5g of [U-(13)C] substrates was added to their respective meals and plasma glucose, insulin, and (13)C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2±0.1 and 1.0±0.1 (mU/L)(-1) × min(-1)], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4±1.0g/d), but increased in CON and GLU calves (26.9±3.9 and 43.0±10.6g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU and GLY and similar

  16. Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts

    DEFF Research Database (Denmark)

    Sørensen, M G; Henriksen, K; Dziegiel, Morten Hanefeld;

    2006-01-01

    Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen......-receptor mediated effects on the bone-resorbing osteoclasts have also been proposed. Little information is available on whether estrogens modulate human osteoclastogenesis or merely inhibit the functional activity of osteoclasts. To clarify whether estrogens directly modulate osteoclastic activities human CD14...... not affect bone resorption or TRACP activity. We investigated expression of the estrogen receptors, using immunocytochemistry and Western blotting. We found that ER-alpha is expressed in osteoclast precursors, whereas ER- beta is expressed at all stages, indicating that the inhibitory effect of...

  17. Estrogen receptor scintigraphy.

    Science.gov (United States)

    Scheidhauer, K; Scharl, A; Schicha, H

    1998-03-01

    Radio-labeled estrogen receptor ligands are tracers that can be used for functional receptor diagnosis. Their specificity towards receptors, together with the fact that only 50-70% of mammary carcinomas are receptor positive, renders them unsuitable for detection of primary tumors or metastases, and this means that estrogen receptor scintigraphy can be used neither for tumor screening nor for staging. However, both 18F-labeled and 123I-labeled estradiol derivatives are suitable for in vivo imaging of estrogen receptors. Their high specificity, established in animal experiments and in vitro studies has been reproduced in in vivo applications in humans. Tracers with positron radiation emitters are, however, hardly suitable for broad application owing to the short half-life of 18F, which would mean that users would need to be situated close to a cyclotron and a correspondingly equipped radiochemical laboratory. The number of available PET scanners, on the other hand, has increased over the last few years, especially in Germany, so that this, at least, does not present a limiting factor. All the same, 123I-labeled estradiol derivatives will find more widespread application, since the number of gamma-cameras incorporating modern multi-head systems is several times greater. The results of studies with 123I-E2-scintigraphy published to date are very promising, even given the initial technical problems mentioned above. As a method of examination, it could be optimised by using improved tracers with a higher tumor contrast and less disturbance from overlapping in diagnostically relevant locations, for instance, by selecting tracers with higher activities whose excretion is more renal than hepatobiliary. The use of modern multi-head camera systems can also be expected to improve the photon yield. PMID:9646642

  18. ESTROGEN IN THE LIMBIC SYSTEM

    NARCIS (Netherlands)

    ter Horst, Gert J.; Litwack, G

    2010-01-01

    Estrogens are a group of steroid hormones that function as the primary female sex hormone. Estrogens not only have an important role in the regulation of the estrous or menstrual cycle but also control, for example, bone formation, the cardiovascular system, and cognitive functions. Estradiol (E2),

  19. Estrogenic compounds -endocrine disruptors

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-11-01

    Full Text Available Endocrine disruptors (polychlorinated biphenyls, dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions.

  20. Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

    KAUST Repository

    Essack, Magbubah

    2012-10-26

    Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first

  1. Anorexia nervosa and estrogen receptors.

    Science.gov (United States)

    Ramoz, Nicolas; Versini, Audrey; Gorwood, Philip

    2013-01-01

    Anorexia nervosa (AN) is a chronic psychiatric disorder with a high prevalence of 0.6% and the highest mortality rates among psychiatric diseases, around 10%, mostly due to undernutrition and suicide. AN is characterized by physiological features with a body mass index less than 17.5 kg/m(2), low bone mineral density and amenorrhea, psychological symptoms with a distortion of image body, and behavioral abnormalities. Estrogen molecules and estrogen biological pathway are clearly involved in food intake and body weight in animals and humans. Further, hypoestrogenism has been demonstrated in AN patients and convergent evidence involves the estrogen pathway in the development of AN. AN presents a high heritability and polymorphisms in genes coding the estrogen receptors alpha and beta have been found significantly associated with the disorder. This chapter shows the implication of estrogens in AN and suggests investigation to develop future pharmacological treatments for anorexia. PMID:23601424

  2. Effects of gamma irradiation on the DNA-protein complex between the estrogen response element and the estrogen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Stisova, Viktorie [Department of Radiation Dosimetry, Nuclear Physics Institute AS CR, Na Truhlarce 39/64, 18086 Praha 8 (Czech Republic); Goffinont, Stephane; Spotheim-Maurizot, Melanie [Centre de Biophysique Moleculaire CNRS, rue Charles Sadron, 45071 Orleans Cedex 2 (France); Davidkova, Marie, E-mail: davidkova@ujf.cas.c [Department of Radiation Dosimetry, Nuclear Physics Institute AS CR, Na Truhlarce 39/64, 18086 Praha 8 (Czech Republic)

    2010-08-15

    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 ERalpha, 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 gamma 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.

  3. The Effects of Phytoestrogen Genistein on Steroidogenesis and Estrogen Receptor Expression in Porcine Granulosa Cells of Large Follicles.

    Science.gov (United States)

    Nynca, Anna; Sadowska, Agnieszka; Orlowska, Karina; Jablonska, Monika; Ciereszko, Renata E

    2015-01-01

    Genistein is a biologically active isoflavone with estrogenic or antiestrogenic activity which can be found in a variety of soy products. Since in pigs' diet soy is the main source of protein, genistein may affect the reproductive/endocrine systems in these animals. Genistein has been shown to alter porcine ovarian and adrenal steroidogenesis but the mechanism of this action is still not clear. It is known that genistein binds to both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), although it has a higher affinity to ERβ. Moreover, this phytoestrogen was demonstrated to posses the activity of protein tyrosine kinase (PTK) inhibitor. The aim of the study was to examine the in vitro effects of genistein on: (1) progesterone (P4) and estradiol (E2) secretion by porcine luteinized granulosa cells harvested from large follicles, and (2) the mRNA and protein expression of ERa and ERβ in these cells. In addition, to verify the role of PTK-dependent mechanisms possibly involved in genistein biological action, we tested the effects of lavendustin C, the nonsteroidal PTK inhibitor, on granulosa cell steroidogenesis. Genistein significantly inhibited P4 and did not affect E2 secretion by porcine luteinized granulosa cells isolated from large follicles. Lavendustin C did not affect basal steroids secretion by examined cells. Genistein did not alter ERa but increased ERβ mRNA levels in the cultured porcine granulosa cells. In contrast to medium follicles, the expression of ERβ protein was unaffected by genistein in granulosa cells of large follicles. To conclude, the soy phytoestrogen genistein acts directly on the porcine ovary to decrease progesterone production and to increase the expression of ERβ mRNA. Moreover, genistein-induced changes in follicular steroidogenesis and granulosal sensitivity to estrogens in pigs may depend on maturity of the follicles. PMID:26255463

  4. From the Women's Health Initiative to the combination of estrogen and selective estrogen receptor modulators to avoid progestin addition.

    Science.gov (United States)

    Valera, Marie-Cécile; Gourdy, Pierre; Trémollières, Florence; Arnal, Jean-François

    2015-11-01

    The female life expectancy rose from an average of 48 years to over 80 years in a century. The decline in the endogenous production of estrogen (especially the main circulating physiological hormone, 17β-estradiol, E2) at menopause (51 years on average) often leads to functional disorders affecting the quality of life. Estrogen deficiency impacts different tissues and results in an increase of various diseases, such as osteoporosis or cardiovascular diseases. Hormone therapy (HT) for menopause is a rather new challenge which experienced vagaries following the women's health initiative (WHI) study conducted in largely post-menopausal women. In the first part of this review, we will try to summarize the main conclusions of the WHI trials, in particular the timing effect as well as the deleterious impact of the associated progestin, medroxyprogesterone acetate (MPA). Hormone therapy, particularly the conjugated equine estrogen (CEE) combined with the MPA favor the occurrence of breast cancer, whereas conversely selective estrogen receptor modulators (SERMs, such as tamoxifen or raloxifene) that block the activity of estrogen receptor alpha (ERa) prevent the risk of recurrence of ERa-positive breast cancers. A new strategy of ERa modulation called tissue selective estrogen complex (TSEC), combines (1) CEE to maintain the benefits of estrogen (climacteric symptoms and prevention of osteoporosis) and (2) bazedoxifene, which is not only a SERM, but which also induces a rapid degradation of ERa in the uterus and in the breast, thereby prevents the stimulatory effects of estrogens on epithelial proliferation of these two sex targets. In the second part of this review, we will summarize the recognized benefits of the TSEC approach, and our current knowledge of its potential benefits and risks. PMID:26261036

  5. The affection of neoadjuvant chemotherapy on estrogen and progesterone receptor expression in breast cancer patients and its clinical significance%新辅助化疗对乳腺癌患者雌激素、孕激素受体表达的影响及其临床意义

    Institute of Scientific and Technical Information of China (English)

    金雪瑛; 田欣

    2013-01-01

    Objective To observe the affection of neoadjuvant chemotherapy on estrogen and progesterone receptor expression in breast cancer patients and its clinical significance. Methods From October 2009 to October 2011, the expression of ER and PR were detected by immunohistochemical methods in 128 cases with breast cancer patients. Results In 128 cases with breast cancer, 14 were CR, accounting for 10.9% , 87 were PR, accounting for 68. 0% , 17 were SD, accounting for 13. 3% , 10 were CR, accounting for 7. 8%. The rate of CR + PR in negative group was significantly higher than that in positive(P 0. 05). The positive rates of ER and PR in CR + PR group before and after treatment were significantly lower than those in SD + PD group( P < 0. 05 ). Conclusion The breast cancer patients with negative expression of ER and PR are more sensitive to neoadjuvant chemotherapy, and the neoadjuvant chemotherapy also can change the expression status of ER and PR.%目的 观察新辅助化疗对乳腺癌患者雌激素受体(ER)、孕激素受体(PR)表达的影响及其临床意义.方法 2009年10月~2011年10月,采用免疫组织化学方法检测128例新辅助化疗的乳腺癌患者治理前后ER、PR.结果 128例乳腺癌患者CR 14例(10.9%),PR 87例(68.0%),SD 17例(13.3%),PD 10例(7.8%).阴性组CR+ PR率明显高于阳性组,差异有统计学意义(P<0.05).CR +PR组治疗后ER、PR阳性率明显下降(P<0.05),而SD+ PD组阳性率无明显变化(P>0.05).CR +PR组治疗前后ER、PR阳性率均明显低于SD+ PD组,差异有统计学意义(P<0.05).结论 治疗前ER、PR表达阴性者对新辅助化疗更为敏感,同时新辅助化疗能够改变CR+ PR患者ER、PR的表达状况.

  6. Partial inhibition of estrogen-induced mammary carcinogenesis in rats by tamoxifen: balance between oxidant stress and estrogen responsiveness.

    Directory of Open Access Journals (Sweden)

    Bhupendra Singh

    Full Text Available Epidemiological and experimental evidences strongly support the role of estrogens in breast tumor development. Both estrogen receptor (ER-dependent and ER-independent mechanisms are implicated in estrogen-induced breast carcinogenesis. Tamoxifen, a selective estrogen receptor modulator is widely used as chemoprotectant in human breast cancer. It binds to ERs and interferes with normal binding of estrogen to ERs. In the present study, we examined the effect of long-term tamoxifen treatment in the prevention of estrogen-induced breast cancer. Female ACI rats were treated with 17β-estradiol (E2, tamoxifen or with a combination of E2 and tamoxifen for eight months. Tissue levels of oxidative stress markers 8-iso-Prostane F(2α (8-isoPGF(2α, superoxide dismutase (SOD, glutathione peroxidase (GPx, catalase, and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG were quantified in the mammary tissues of all the treatment groups and compared with age-matched controls. Levels of tamoxifen metabolizing enzymes cytochrome P450s as well as estrogen responsive genes were also quantified. At necropsy, breast tumors were detected in 44% of rats co-treated with tamoxifen+E2. No tumors were detected in the sham or tamoxifen only treatment groups whereas in the E2 only treatment group, the tumor incidence was 82%. Co-treatment with tamoxifen decreased GPx and catalase levels; did not completely inhibit E2-mediated oxidative DNA damage and estrogen-responsive genes monoamine oxygenase B1 (MaoB1 and cell death inducing DFF45 like effector C (Cidec but differentially affected the levels of tamoxifen metabolizing enzymes. In summary, our studies suggest that although tamoxifen treatment inhibits estrogen-induced breast tumor development and increases the latency of tumor development, it does not completely abrogate breast tumor development in a rat model of estrogen-induced breast cancer. The inability of tamoxifen to completely inhibit E2-induced breast

  7. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

    International Nuclear Information System (INIS)

    Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-κB activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or γ-glutamyl transpeptidase activity. Radiation activated NF-κB was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-κB activity, without toxicity to bone marrow, liver, and kidney

  8. Evaluation of Factors Affecting the Value of Online Shopping Considering Price Sensitivity and Variety-Seeking of Buyers

    Directory of Open Access Journals (Sweden)

    Mahdi Alhoseini Almodarresi

    2015-09-01

    Full Text Available Ease of access to information, possibility to compare products quickly, and many other facilities that Internet provides for consumers, increase the power of consumers much higher. Internet sellers for the purpose of increasing their sales, often offer lower prices in compare to retailer's price. Nevertheless, the recent studies represent that even price-sensitive customers, avoid shopping from low price online stores. Rather value is considered as the key driver of costumers' decision-making in economic and marketing. Therefore, it is necessary to try to identify those factors affecting online shopping. This research is aimed to study the effective factors on customer's values using survey research method, descriptive-causal type. The research statistical population consists of people who have an experience of on-line shopping at lease for one time. Data were analyzed using structural equation modeling method via LISREL software and partial least squares method via SMART PLS software. The results showed that, although system quality is an effective factor on utilitarian shopping values, information quality have no effect on both utilitarian and hedonic values. Generally, utilitarian and hedonic values could cause to online consumers' satisfaction, and satisfaction significantly could improve repurchase intention. Moreover, the results show the moderating effect of price sensitivity in relation of system quality and information with utilitarian value and also moderating effect of variety-seeking in relation of information quality with hedonic value.

  9. Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint

    Directory of Open Access Journals (Sweden)

    Bellinger Larry L

    2009-12-01

    Full Text Available Abstract Background Estrogen is known to play role in temporomandibular joint (TMJ disorders and estrogen effects can be mediated by estrogen receptor (ER alpha present in the TMJ. Cells expressing the estrogen receptor ERalpha are present in the temporomandibular joint (TMJ but changes in expression due to estrogen and inflammation have not been characterized. In this study, ERalpha protein content and the number of cells expressing ERalpha was measured in 17 beta-estradiol-treated rats after inflammation was induced in the TMJ. Methods Sixteen ovariectomized female rats were divided into two groups such that one group received 17 beta estradiol (E2 and the other was given vehicle (VEH. Groups were then subdivided further, one received injections of saline and the other received Complete Freund's adjuvant (CFA within the superior joint space of the TMJ. Thus the four groups include no E2/saline, E2/saline, no E2/CFA and E2/CFA. After treatment, the rats were sacrificed, and the TMJ anterior, disc, retrodiscal and synovial tissues were analyzed by western blot and immunocytochemistry. Positive stained cells were counted using a Nikon epifluorescent microscope. Results The western blot showed that ERalpha protein significantly decreased with inflammation. The number of ERalpha-positive cells in the TMJ was not affected by inflammation or 17 beta-estradiol with exception of the retrodiscal tissue. In the retrodiscal tissue 17 beta-estradiol significantly decreased the number of ERalpha-positive cells but only in a non-inflamed joint. Conclusions In conclusion, inflammation and 17 beta-estradiol can modulate ERalpha expression in the TMJ but the effects are tissue specific.

  10. Estrogen and gastrointestinal malignancy.

    LENUS (Irish Health Repository)

    Hogan, A M

    2012-02-01

    The concept that E2 exerts an effect on the gastrointestinal tract is not new and its actions on intestinal mucosa have been investigated for at least three decades. An attempt to consolidate results of these investigations generates more questions than answers, thus suggesting that many unexplored avenues remain and that the full capabilities of this steroid hormone are far from understood. Evidence of its role in esophageal, gastric and gallbladder cancers is confusing and often equivocal. The most compelling evidence regards the protective role conferred by estrogen (or perhaps ERbeta) against the development and proliferation of colon cancer. Not only has the effect been described but also many mechanisms of action have been explored. It is likely that, along with surgery, chemotherapy and radiotherapy, hormonal manipulation will play an integral role in colon cancer management in the very near future.

  11. Mechanisms enforcing the estrogen receptor β selectivity of botanical estrogens

    OpenAIRE

    Jiang, Yan; Gong, Ping; Madak-Erdogan, Zeynep; Martin, Teresa; Jeyakumar, Muthu; Carlson, Kathryn; Khan, Ikhlas; Smillie, Troy J.; Amar G. Chittiboyina; Rotte, Sateesh C. K.; Helferich, William G.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

    2013-01-01

    Because little is known about the actions of botanical estrogens (BEs), widely consumed by menopausal women, we investigated the mechanistic and cellular activities of some major BEs. We examined the interactions of genistein, daidzein, equol, and liquiritigenin with estrogen receptors ERα and ERβ, with key coregulators (SRC3 and RIP140) and chromatin binding sites, and the regulation of gene expression and proliferation in MCF-7 breast cancer cells containing ERα and/or ERβ. Unlike the endog...

  12. Molecular conservation of estrogen-response associated with cell cycle regulation, hormonal carcinogenesis and cancer in zebrafish and human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Govindarajan Kunde R

    2011-05-01

    Full Text Available Abstract Background The zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are involved in estrogen-dependent carcinogenesis and human cancer are operating in zebrafish. In order to determine the potential of zebrafish model for estrogen-related cancer research, we investigated the molecular conservation of estrogen responses operating in both zebrafish and human cancer cell lines. Methods Microarray experiment was performed on zebrafish exposed to estrogen (17β-estradiol; a classified carcinogen and an anti-estrogen (ICI 182,780. Zebrafish estrogen-responsive genes sensitive to both estrogen and anti-estrogen were identified and validated using real-time PCR. Human homolog mapping and knowledge-based data mining were performed on zebrafish estrogen responsive genes followed by estrogen receptor binding site analysis and comparative transcriptome analysis with estrogen-responsive human cancer cell lines (MCF7, T47D and Ishikawa. Results Our transcriptome analysis captured multiple estrogen-responsive genes and signaling pathways that increased cell proliferation, promoted DNA damage and genome instability, and decreased tumor suppressing effects, suggesting a common mechanism for estrogen-induced carcinogenesis. Comparative analysis revealed a core set of conserved estrogen-responsive genes that demonstrate enrichment of estrogen receptor binding sites and cell cycle signaling pathways. Knowledge-based and network analysis led us to propose that the mechanism involving estrogen-activated estrogen receptor mediated down-regulation of human homolog HES1 followed by up-regulation cell cycle-related genes (human homologs E2F4, CDK2, CCNA, CCNB, CCNE, is highly conserved, and this mechanism may involve novel crosstalk with basal AHR. We also identified mitotic roles of polo-like kinase as a conserved signaling pathway with multiple entry

  13. Estrogen and Progestin (Oral Contraceptives)

    Science.gov (United States)

    ... your packet. Start a new packet the day after you take your 28th tablet. The tablets in most ... of estrogen. Start your new packet the day after you take your 91st tablet.Your doctor will tell ...

  14. Estrogen and Progestin (Oral Contraceptives)

    Science.gov (United States)

    Oral contraceptives (birth-control pills) are used to prevent pregnancy. Estrogen and progestin are two female sex hormones. ... to prevent sperm (male reproductive cells) from entering. Oral contraceptives are a very effective method of birth control, ...

  15. Temperature dependence of estrogen binding: importance of a subzone in the ligand binding domain of a novel piscine estrogen receptor.

    Science.gov (United States)

    Tan, N S; Frecer, V; Lam, T J; Ding, J L

    1999-11-11

    The full length estrogen receptor from Oreochromis aureus (OaER) was cloned and expressed in vitro and in vivo as a functional transcription factor. Amino acid residues involved in the thermal stability of the receptor are located at/near subzones beta1 and beta3, which are highly conserved in other non-piscine species but not in OaER. Hormone binding studies, however, indicate that OaER is thermally stable but exhibited a approximately 3-fold reduced affinity for estrogen at elevated temperatures. Transfection of OaER into various cell lines cultured at different temperatures displayed a significant estrogen dose-response shift compared with that of chicken ER (cER). At 37 degrees C, OaER requires approximately 80-fold more estrogen to achieve half-maximal stimulation of CAT. Lowering of the incubation temperature from 37 degrees C to 25 degrees C or 20 degrees C resulted in a 4-fold increase in its affinity for estrogen. The thermally deficient transactivation of OaER at temperatures above 25 degrees C was fully prevented by high levels of estrogen. Thus, compared to cER, the OaER exhibits reduced affinity for estrogen at elevated temperature as reflected in its deficient transactivation capability. Amino acid replacements of OaER beta3 subzones with corresponding amino acids from cER could partially rescue this temperature sensitivity. The three-dimensional structure of the OaER ligand binding domain (LBD) was modelled based on conformational similarity and sequence homology with human RXRalpha apo, RARgamma holo and ERalpha LBDs. Unliganded and 17beta-estradiol-liganded OaER LBD retained the overall folding pattern of the nuclear receptor LBDs. The residues at/near the subzone beta3 of the LBD constitute the central core of OaER structure. Thus, amino acid alteration at this region potentially alters the structure and consequently its temperature-dependent ligand binding properties. PMID:10559464

  16. Estrogen Sulfotransferase Inhibits Adipocyte Differentiation

    OpenAIRE

    Wada, Taira; Ihunnah, Chibueze A.; Gao, Jie; Chai, Xiaojuan; Zeng, Su; Philips, Brian J.; Rubin, J. Peter; Marra, Kacey G.; Xie, Wen

    2011-01-01

    The estrogen sulfotransferase (EST) is a phase II drug-metabolizing enzyme known to catalyze the sulfoconjugation of estrogens. EST is highly expressed in the white adipose tissue of male mice, but the role of EST in the development and function of adipocytes remains largely unknown. In this report, we showed that EST played an important role in adipocyte differentiation. EST was highly expressed in 3T3-L1 preadipocytes and primary mouse preadipocytes. The expression of EST was dramatically r...

  17. Immunohistochemical study of estrogen receptors and progesterone in breast cancer

    International Nuclear Information System (INIS)

    Presence of estrogen receptors in breast tumors allows to judge about sensitivity of cancer to hormone therapy and diseases prognosis. Objective of the study is to compare histological forms of patient's age and various estrogen receptors combination in breast cancer. 30 patients were undergone to immune-histo-chemical examination of breast tumors in the Semipalatinsk cancer clinic. According to expression of estrogen and testosteron receptors they were divided into 4 groups. The most wide-spread histologic type of cancer was dust-infiltrative. This type took place of 3.3 % for the first group, 9.9 % for the second group, 16-6 % for the third one, and 36.6 % for the fourth one. Histological type of cancer had not effects on expression of receptors estrogen and progesterone in tumor. Rare breast cancer types like medullary occurred only in the fourth group. Dividing breast cancer into positive and negative or with expression of one hormone depending on expression of estrogen, testosteron receptors may be regarded as a sensible way. More expanded examination on immune-histo-chemical markers allows extending topics regarding therapy of breast cancer. (author)

  18. METHOXYCHLOR REGULATES RAT UTERINE ESTROGEN-INDUCED PROTEIN

    Science.gov (United States)

    Methoxychlor (MXC), a pesticide, affects fertility and the uterus. o address the question of whether MXC acts like estradiol (E2) at the molecular level, we used immature rat uteri to compare the effects of MXC and E2 on the estrogen-induced protein (IP), also known as creatine k...

  19. Aboveground allometric models for freeze-affected black mangroves (Avicennia germinans: equations for a climate sensitive mangrove-marsh ecotone.

    Directory of Open Access Journals (Sweden)

    Michael J Osland

    Full Text Available Across the globe, species distributions are changing in response to climate change and land use change. In parts of the southeastern United States, climate change is expected to result in the poleward range expansion of black mangroves (Avicennia germinans at the expense of some salt marsh vegetation. The morphology of A. germinans at its northern range limit is more shrub-like than in tropical climes in part due to the aboveground structural damage and vigorous multi-stem regrowth triggered by extreme winter temperatures. In this study, we developed aboveground allometric equations for freeze-affected black mangroves which can be used to quantify: (1 total aboveground biomass; (2 leaf biomass; (3 stem plus branch biomass; and (4 leaf area. Plant volume (i.e., a combination of crown area and plant height was selected as the optimal predictor of the four response variables. We expect that our simple measurements and equations can be adapted for use in other mangrove ecosystems located in abiotic settings that result in mangrove individuals with dwarf or shrub-like morphologies including oligotrophic and arid environments. Many important ecological functions and services are affected by changes in coastal wetland plant community structure and productivity including carbon storage, nutrient cycling, coastal protection, recreation, fish and avian habitat, and ecosystem response to sea level rise and extreme climatic events. Coastal scientists in the southeastern United States can use the identified allometric equations, in combination with easily obtained and non-destructive plant volume measurements, to better quantify and monitor ecological change within the dynamic, climate sensitive, and highly-productive mangrove-marsh ecotone.

  20. Aboveground allometric models for freeze-affected black mangroves (Avicennia germinans): equations for a climate sensitive mangrove-marsh ecotone.

    Science.gov (United States)

    Osland, Michael J; Day, Richard H; Larriviere, Jack C; From, Andrew S

    2014-01-01

    Across the globe, species distributions are changing in response to climate change and land use change. In parts of the southeastern United States, climate change is expected to result in the poleward range expansion of black mangroves (Avicennia germinans) at the expense of some salt marsh vegetation. The morphology of A. germinans at its northern range limit is more shrub-like than in tropical climes in part due to the aboveground structural damage and vigorous multi-stem regrowth triggered by extreme winter temperatures. In this study, we developed aboveground allometric equations for freeze-affected black mangroves which can be used to quantify: (1) total aboveground biomass; (2) leaf biomass; (3) stem plus branch biomass; and (4) leaf area. Plant volume (i.e., a combination of crown area and plant height) was selected as the optimal predictor of the four response variables. We expect that our simple measurements and equations can be adapted for use in other mangrove ecosystems located in abiotic settings that result in mangrove individuals with dwarf or shrub-like morphologies including oligotrophic and arid environments. Many important ecological functions and services are affected by changes in coastal wetland plant community structure and productivity including carbon storage, nutrient cycling, coastal protection, recreation, fish and avian habitat, and ecosystem response to sea level rise and extreme climatic events. Coastal scientists in the southeastern United States can use the identified allometric equations, in combination with easily obtained and non-destructive plant volume measurements, to better quantify and monitor ecological change within the dynamic, climate sensitive, and highly-productive mangrove-marsh ecotone. PMID:24971938

  1. Aboveground allometric models for freeze-affected black mangroves (Avicennia germinans): equations for a climate sensitive mangrove-marsh ecotone

    Science.gov (United States)

    Osland, Michael J.; Day, Richard H.; Larriviere, Jack C.; From, Andrew S.

    2014-01-01

    Across the globe, species distributions are changing in response to climate change and land use change. In parts of the southeastern United States, climate change is expected to result in the poleward range expansion of black mangroves (Avicennia germinans) at the expense of some salt marsh vegetation. The morphology of A. germinans at its northern range limit is more shrub-like than in tropical climes in part due to the aboveground structural damage and vigorous multi-stem regrowth triggered by extreme winter temperatures. In this study, we developed aboveground allometric equations for freeze-affected black mangroves which can be used to quantify: (1) total aboveground biomass; (2) leaf biomass; (3) stem plus branch biomass; and (4) leaf area. Plant volume (i.e., a combination of crown area and plant height) was selected as the optimal predictor of the four response variables. We expect that our simple measurements and equations can be adapted for use in other mangrove ecosystems located in abiotic settings that result in mangrove individuals with dwarf or shrub-like morphologies including oligotrophic and arid environments. Many important ecological functions and services are affected by changes in coastal wetland plant community structure and productivity including carbon storage, nutrient cycling, coastal protection, recreation, fish and avian habitat, and ecosystem response to sea level rise and extreme climatic events. Coastal scientists in the southeastern United States can use the identified allometric equations, in combination with easily obtained and non-destructive plant volume measurements, to better quantify and monitor ecological change within the dynamic, climate sensitive, and highly-productive mangrove-marsh ecotone.

  2. The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer

    DEFF Research Database (Denmark)

    Brunner, N; Spang-Thomsen, M; Cullen, K

    1996-01-01

    Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen receptor...... in the study of the molecular mechanism of estrogen therapy in breast cancer, and suggest that in this system, modulation of a specific growth factor (IGF-II) by endocrine therapy can have profound effects on tumor growth....... positive tumor which was originally derived from a T1N0M0 invasive ductal cancer and has been carried as a serially transplanted xenograft in nude mice. T61 is a hormone sensitive tumor whose growth is suppressed by both estrogen and tamoxifen, in contrast to other estrogen receptor positive tumors such as...

  3. Interaction between ionizing radiation, estrogens and antiestrogens in the modification of tumor microenvironment in estrogen dependent multicellular spheroids

    International Nuclear Information System (INIS)

    MCF7 human breast cancer cells growing an multicellular spheroids were examined as a model of three-dimensional cellular organization. Estrogen-free medium inhibited spheroid formation. In medium containing estrogens, the antiestrogen hydroxytamoxifen decreased the spheroid growth rate. Analyses with the recursion formula after Gompertz fitting showed that the rate of exponential decrease in growth rate (α) was α = 0.099 ± 0.013 d-1, and the decrease in α' was 0.061 ± 0.015 d-1 for 0.1 μM hydroxytamoxifen and control spheroids respectively. MCF7 cells which had been growth arrested in an estrogen-free medium showed a significant decrease in radiosensitivity (surviving fraction at 2 Gy, SF2 = 63%) when compared with 0.1 nM 17β-estradiol-treated cells (SF2 = 38%). No differences in radiosensitivity were seen in MCF7 spheroids in estrogen-supplemented medium (radiation dose necessary to control 50% of spheroids (SCD50) was 5.51 Gy; derived α, β and SF2 were 0.301 ± 0.110 Gy-1, 0.018 ± 0.005 Gy-2, and 51% respectively) when compared with monolayer cultures in the same medium (α = 0.316 ± 0.059 Gy-1, β = 0.023 ± 0.006 Gy-2 and SF2 = 50%). In the spheroid model, manipulating the cellular environment, i.e., with estrogen treatment, modulates sensitivity to ionizing radiation. (orig.)

  4. Detection of estrogenic activity in sediment-associated compounds using in vitro reporter gene assays.

    Science.gov (United States)

    Legler, Juliette; Dennekamp, Martine; Vethaak, A Dick; Brouwer, Abraham; Koeman, Jan H; van der Burg, Bart; Murk, Albertinka J

    2002-07-01

    Sediments may be the ultimate sink for persistent (xeno-)estrogenic compounds released into the aquatic environment. Sediment-associated estrogenic potency was measured with an estrogen receptor-mediated luciferase reporter gene (ER-CALUX) assay and compared with a recombinant yeast screen. The ER-CALUX assay was more sensitive to 17beta-estradiol (E2) than the recombinant yeast screen, with an EC50 of 6 pM E2 compared to 100 pM in the yeast screen. Yeast cells were unable to distinguish the anti-estrogens ICI 182,780 and (4-hydroxy)tamoxifen, which were agonistic in the yeast. Acetone-soluble fractions of hexane/acetone extracts of sediments showed higher estrogenic potency than hexane-soluble extracts in the ER-CALUX assay. Sediments obtained from industrialized areas such as the Port of Rotterdam showed the highest estrogenic potency of the 12 marine sediments tested (up to 40 pmol estradiol equivalents per gram sediment). The estrogenic activity of individual chemicals that can be found in sediments including: alkylphenol ethoxylates and carboxylates; phthalates; and pesticides, was tested. Increasing sidechain length of various nonylphenol ethoxylates resulted in decreased estrogenic activity. Of the phthalates tested, butylbenzylphthalate was the most estrogenic, though with a potency approximately 100,000 times less than E2. The organochlorine herbicides atrazine and simazine failed to induce reporter gene activity. As metabolic activation may be required to induce estrogenic activity, a metabolic transformation step was added to the ER-CALUX assay using incubation of compounds with liver microsomes obtained from PCB-treated rats. Results indicate that metabolites of E2, NP and bisphenol A were less active than the parent compounds, while metabolites of methoxychlor were more estrogenic following microsomal incubations. PMID:12109482

  5. Myocardial performance index is sensitive to changes in cardiac contractility, but is also affected by vascular load condition.

    Science.gov (United States)

    Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Shishido, Toshiaki; Sugimachi, Masaru

    2013-01-01

    Myocardial performance index (MPI), or Tei index, is measured by Doppler echocardiography in clinical practice. MPI has been shown to be useful in evaluating left ventricular (LV) performance and predicting prognosis in cardiac patients. However, the effects of LV load and contractile states on MPI remain to be thoroughly investigated. In 14 anesthetized dogs, we obtained LV pressure-volume relationship with use of sonomicrometry and catheter-tip manometry. MPI was determined from the time derivative of LV volume and pressure. LV end-systolic pressure-volume ratio (Ees'), effective arterial elastance (Ea) and LV end-diastolic volume (Ved) were used as indices of LV contractility, afterload and preload, respectively. Hemodynamic conditions were varied over wide ranges [heart rate (HR), 66-192 bpm; mean arterial pressure, 71-177 mmHg] by infusing cardiovascular agents, by inducing ischemic heart failure and by electrical atrial pacing. Multiple linear regression analysis of pooled data (66 data sets) indicated that MPI (0.6-1.8) significantly correlated with Ees' [1.5-17.5 mmHg · ml(-1), pVed (11-100 ml, p0.1). Theoretical analysis also indicated that MPI decreases following the increases in LV contractility and in preload, while it increases in response to an increase in LV afterload. We conclude that MPI sensitively detects changes in LV contractility. However, MPI is also affected by changes in LV afterload and preload. PMID:24109782

  6. Differences in the sensitivity of fungi and bacteria to season and invertebrates affect leaf litter decomposition in a Mediterranean stream.

    Science.gov (United States)

    Mora-Gómez, Juanita; Elosegi, Arturo; Duarte, Sofia; Cássio, Fernanda; Pascoal, Cláudia; Romaní, Anna M

    2016-08-01

    Microorganisms are key drivers of leaf litter decomposition; however, the mechanisms underlying the dynamics of different microbial groups are poorly understood. We investigated the effects of seasonal variation and invertebrates on fungal and bacterial dynamics, and on leaf litter decomposition. We followed the decomposition of Populus nigra litter in a Mediterranean stream through an annual cycle, using fine and coarse mesh bags. Irrespective of the season, microbial decomposition followed two stages. Initially, bacterial contribution to total microbial biomass was higher compared to later stages, and it was related to disaccharide and lignin degradation; in a later stage, bacteria were less important and were associated with hemicellulose and cellulose degradation, while fungi were related to lignin decomposition. The relevance of microbial groups in decomposition differed among seasons: fungi were more important in spring, whereas in summer, water quality changes seemed to favour bacteria and slowed down lignin and hemicellulose degradation. Invertebrates influenced litter-associated microbial assemblages (especially bacteria), stimulated enzyme efficiencies and reduced fungal biomass. We conclude that bacterial and fungal assemblages play distinctive roles in microbial decomposition and differ in their sensitivity to environmental changes, ultimately affecting litter decomposition, which might be particularly relevant in highly seasonal ecosystems, such as intermittent streams. PMID:27288197

  7. Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

    Science.gov (United States)

    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

  8. Alike but not the same: Anatomic Heterogeneity of Estrogen Receptor-Mediated Vasodilation

    OpenAIRE

    Barton, Matthias; Meyer, Matthias R.; Prossnitz, Eric R.

    2013-01-01

    In view of recent findings on the anatomic heterogeneity of rapid vasodilation via estrogen receptor-dependent mechanisms it is obvious that with regard to human physiology and disease much of it is still unknown, and research in this area is urgently needed. This is also important since chronic drug therapy with estrogens in women systemically affects the circulation and may affect certain arterial beds but not others. It is conceivable that the presence of any vascular disease (as was the c...

  9. The Relationship between Periodontopathy and Estrogen

    Institute of Scientific and Technical Information of China (English)

    YAN Shiguang; LI Dexiang

    2002-01-01

    Objecitve To discuss the relationship between peridontopathy and estrogen. Method We discussed the relationship between periodontopathy and increasing of estrogen, the relationship between peridontopoathy and deficiency of estrogen and the relationship between osteoprotegerin in osteoblasts and estrogen. Results When estrogen increased or decreased abnormally, osteoporosis could occur, which induced alveolar ridge resorption and alveolar bone atrophy. Then the teeth exfoliated.Teeth uncleanness facilitated periodontopathy. Conclusion No matter how young or old, keeping the relative balance of estrogen can protect gingiva and alveolar bone. At the same time, keeping teeth clean is also essential to prevent periodontopathy.

  10. The Influence of Estrogens on the Biological and Therapeutic Actions of Growth Hormone in the Liver

    Directory of Open Access Journals (Sweden)

    Leandro Fernández-Pérez

    2012-07-01

    Full Text Available GH is main regulator of body growth and composition, somatic development, intermediate metabolism and gender-dependent dimorphism in mammals. The liver is a direct target of estrogens because it expresses estrogen receptors which are connected with development, lipid metabolism and insulin sensitivity, hepatic carcinogenesis, protection from drug-induced toxicity and fertility. In addition, estrogens can modulate GH actions in liver by acting centrally, regulating pituitary GH secretion, and, peripherally, by modulating GHR-JAK2-STAT5 signalling pathway. Therefore, the interactions of estrogens with GH actions in liver are biologically and clinically relevant because disruption of GH signaling may cause alterations of its endocrine, metabolic, and gender differentiated functions and it could be linked to dramatic impact in liver physiology during development as well as in adulthood. Finally, the interplay of estrogens with GH is relevant because physiological roles these hormones have in human, and the widespread exposition of estrogen or estrogen-related compounds in human. This review highlights the importance of these hormones in liver physiology as well as how estrogens modulate GH actions in liver which will help to improve the clinical use of these hormones.

  11. Estrogenic profile on a water-soluble estrogen, estrazinol hydrobromide.

    Science.gov (United States)

    Rassaert, C L; DiPasquale, G; Giannina, T; Manning, J P; Meli, A

    1973-01-01

    The estrogenic properties of estrazinol hydrobromide (EZ), a water-soluble estrogen, were compared with those of Premarin (PR), another water-soluble estrogen preparation consisting of conjugated equine estrogens. Estradiol-17beta, estra-1,3,5(10)-triene-3,17beta-diol (E), and ethinyl estradiol, 17alpha-ethinyl-1,3,5 (10)-estratriene-3,17beta-diol (EE) were used as reference standards. Subcutaneous progesterone (400 mcg) given to rabbits primed with comparable subcutaneous doses of either E or EE produced full secretory changes of the endometrium, while such a transformation could not be elicited in orally primed animals regardless of the estrogen used. The biological profile or orally administered EZ was very similar to that of oral EE and different from oral PR. Howerver, the oral EZ-induced morphological changes of the rabbit endometrium appeared somewhat different from those produced by oral EE. The findings indicated that following oral administration, EZ-induced endometrial transformation is more "normal" and/or adequate than the changes produced by either EE or PR. PMID:4368700

  12. Effects of pinostrobin on estrogen metabolism and estrogen receptor transactivation.

    Science.gov (United States)

    Le Bail, J C; Aubourg, L; Habrioux, G

    2000-08-01

    The interaction between the estrogen receptor and 5-hydroxy-7-methoxyflavanone (pinostrobin) was studied in the presence or absence of estradiol or dehydroepiandrosterone sulfate (DHEAS), respectively, using a stably transfected human breast cancer cell line (MVLN). We also evaluated its action on the proliferation in estrogen-dependent (MCF-7) human breast cancer cells in the same conditions than the estrogen receptor assay. On the other hand pinostrobin was evaluated for their effects on the human placental aromatase, 3beta-hydroxysteroid dehydrogenase Delta(4)/Delta(5) isomerase and 17beta-hydroxysteroid dehydrogenase activities. Pinostrobin did not possess antiestrogenic activity but presented anti-aromatase activity and decreased the growth of MCF-7 cells induced by DHEAS and E(2). This study provides particularly evidence of the potential biological interest of pinostrobin among the flavonoids. PMID:10840157

  13. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

    International Nuclear Information System (INIS)

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI

  14. Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell–matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yan; Li, Zheng; He, Yan; Shang, Dandan; Pan, Jigang; Wang, Hongmei; Chen, Huamei; Zhu, Zhuxia [Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China); Wan, Lei [Department of Pharmacology, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China); Wang, Xudong, E-mail: xdwang@gmc.edu.cn [Department of Physiology/Cancer Research Group, Guiyang Medical University School of Basic Medicine, 9 Beijing Road, Guiyang 550004, Guizhou (China)

    2014-03-01

    Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2), and suppression of ERK1/2 phosphorylation by U0126 profoundly impeded calpain activation triggered by estrogenic and antiestrogenic stimulations indicating implication of ERK1/2 in the GPR30-mediated action. Lastly, the E2- or ICI-induced cell adhesion was dramatically impaired by calpain-specific inhibitors, ALLN or calpeptin, suggesting requirement of calpain in the GPR30-associated action. These data show that enhanced cell adhesion by E2 and ICI occurs via a novel GPR30-ERK1/2-calpain pathway. Our results indicate that targeting the GPR30 signaling may be a potential strategy to reduce metastasis and improve the efficacy of antiestrogens in treatment of advanced breast cancer. - Highlights: • Estrogen and ICI augment adhesion to matrigel with calpain activation in MCF-7 cells. • GPR30 mediates cell–matrigel adhesion and calpain activation via ERK1/2. • Calpain is required in the cell–matrigel adhesion induced by E2 and ICI.

  15. Determination of steroidal estrogens in flushed dairy manure wastewater by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Hanselman, Travis A; Graetz, Donald A; Wilkie, Ann C; Szabo, Nancy J; Diaz, Carolyn S

    2006-01-01

    There is a critical need to accurately measure the concentrations of natural steroidal estrogens in flushed dairy manure wastewater (FDMW) to assess any potential risk of waterway contamination resulting from land application. Estrogens are a concern because low concentrations (10-100 ng L-1) in water can adversely affect aquatic vertebrate species such as fish, turtles, and frogs by disrupting the normal function of their endocrine systems. The objective of this study was to develop a sample preparation method that permits the quantification of four natural steroidal estrogens (17alpha-estradiol, 17beta-estradiol, estrone, and estriol) in FDMW by gas chromatography-mass spectrometry (GC-MS). Solid-phase extraction with graphitized carbon black was used for the bulk extraction of estrogens from FDMW and additional sample purification was accomplished with C-18. The sample preparation method allowed estrogens to be detected accurately by GC-MS in FDMW. Spiked recovery experiments indicated that the method is satisfactory for measuring the estrogens of interest in FDMW with average recovery of >90%. As expected in FDMW, characterization of the estrogen profile revealed a large abundance of 17alpha-estradiol relative to 17beta-estradiol and estrone. Estriol was not detected in FDMW. The methodology developed in this research helps provide an analytical foundation for the quantification of steroidal estrogens in FDMW by GC-MS. PMID:16585610

  16. Effects of estrogen on diverse stem cells and relevant intracellular mechanisms

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Sexual dimorphism definitely exists in the pathogenesis of a variety of cardiovascular,neurodegenerative and bone metabolism disorders.Estrogen affects the healing of ischemic myocardium partially through paracrine growth hormone production by bone marrow mesenchymal stem cells(MSCs) and facilitation on mobilization of endothelial progenitors cells(EPCs) to the ischemic myocardium.Estrogen can also inhibit the proliferation of the cardiac fibroblasts.Therefore,estrogen effectively enhances the neovascularization at the ischemic border zone and limits pathological myocardial remodeling.Moreover,estrogen increases proliferation of embryonic neural stem cells and accelerates differentiation of neurons during neurogenesis,suggesting a possible role of estrogen in transplantation of neural stem cells as a therapeutic approach for neurodegenerative diseases.Finally,estrogen can modulate osteogenic progenitors and osteoclasts,preventing the osteoporosis.In general,estrogen offers significant benefits on diverse stem/progenitor cell populations.A great understanding of estrogens on these cells and relevant intracellular mechanisms will allow modulation of the potent stem cells directly for the ultimate clinical applications.

  17. ERGDB: Estrogen Responsive Genes Database.

    Science.gov (United States)

    Tang, Suisheng; Han, Hao; Bajic, Vladimir B

    2004-01-01

    ERGDB is an integrated knowledge database dedicated to genes responsive to estrogen. Genes included in ERGDB are those whose expression levels are experimentally proven to be either up-regulated or down-regulated by estrogen. Genes included are identified based on publications from the PubMed database and each record has been manually examined, evaluated and selected for inclusion by biologists. ERGDB aims to be a unified gateway to store, search, retrieve and update information about estrogen responsive genes. Each record contains links to relevant databases, such as GenBank, LocusLink, Refseq, PubMed and ATCC. The unique feature of ERGDB is that it contains information on the dependence of gene reactions on experimental conditions. In addition to basic information about the genes, information for each record includes gene functional description, experimental methods used, tissue or cell type, gene reaction, estrogen exposure time and the summary of putative estrogen response elements if the gene's promoter sequence was available. Through a web interface at http://sdmc.i2r.a-star.edu.sg/ergdb/ cgi-bin/explore.pl users can either browse or query ERGDB. Access is free for academic and non-profit users. PMID:14681475

  18. Breast Cancer and Estrogen-Alone Update

    Science.gov (United States)

    ... Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 Table of ... version of this page please turn Javascript on. Estrogen-alone hormone therapy does not increase the risk ...

  19. Molecular mechanisms of alternative estrogen receptor signaling

    OpenAIRE

    Björnström, Linda

    2003-01-01

    Estrogen is a key regulator of growth, differentiation and function in a broad range of target tissues, including the male and female reproductive tracts, mammary gland, bone, brain and the cardiovascular system. The biological effects of estrogen are mediated through estrogen receptor a (ERalpha) and estrogen receptor beta (ERbeta), which belong to a large superfamily of nuclear receptors that act as ligand-activated transcription factors. The classical mechanism of ER acti...

  20. Selectively targeting estrogen receptors for cancer treatment

    NARCIS (Netherlands)

    Shanle, Erin K.; Xu, Wei

    2010-01-01

    Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ER alpha and ER beta, which mediate proliferation and differentiation of cells. For decades, ER alpha mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most nota

  1. Cloning and functional characterization of Chondrichthyes, cloudy catshark, Scyliorhinus torazame and whale shark, Rhincodon typus estrogen receptors.

    Science.gov (United States)

    Katsu, Yoshinao; Kohno, Satomi; Narita, Haruka; Urushitani, Hiroshi; Yamane, Koudai; Hara, Akihiko; Clauss, Tonya M; Walsh, Michael T; Miyagawa, Shinichi; Guillette, Louis J; Iguchi, Taisen

    2010-09-15

    Sex-steroid hormones are essential for normal reproductive activity in both sexes in all vertebrates. Estrogens are required for ovarian differentiation during a critical developmental stage and promote the growth and differentiation of the female reproductive system following puberty. Recent studies have shown that environmental estrogens influence the developing reproductive system as well as gametogenesis, especially in males. To understand the molecular mechanisms of estrogen actions and to evaluate estrogen receptor-ligand interactions in Elasmobranchii, we cloned a single estrogen receptor (ESR) from two shark species, the cloudy catshark (Scyliorhinus torazame) and whale shark (Rhincodon typus) and used an ERE-luciferase reporter assay system to characterize the interaction of these receptors with steroidal and other environmental estrogens. In the transient transfection ERE-luciferase reporter assay system, both shark ESR proteins displayed estrogen-dependent activation of transcription, and shark ESRs were more sensitive to 17beta-estradiol compared with other natural and synthetic estrogens. Further, the environmental chemicals, bisphenol A, nonylphenol, octylphenol and DDT could activate both shark ESRs. The assay system provides a tool for future studies examining the receptor-ligand interactions and estrogen disrupting mechanisms in Elasmobranchii. PMID:20600039

  2. Induction of hypospadias in a murine model by maternal exposure to synthetic estrogens

    International Nuclear Information System (INIS)

    We tested the hypothesis that maternal exposure to synthetic estrogen can cause hypospadias in male offspring and defined the morphological changes in the disrupted urethral seam. Timed pregnant C57/6 mice were exposed to synthetic estrogens. The genital tubercles were examined for the presence of hypospadias using histology, three-dimensional computer reconstruction, and plastic cast injection molds of the urethra. Microscopic serial analysis confirmed the presence of hypospadias, which occurred in ∼50% of the synthetic-estrogen-treated male fetuses. No effect was seen in the female embryos. Plastic cast injection showed that affected males had a shorter total urethral length and loss of male anatomic features such as the prostatic utricle. Exposure to synthetic estrogens during pregnancy affects the normal development of the urethra in the mouse. We conclude that endocrine disrupters play an important role in genital tubercle anomalies

  3. The role of local estrogen therapy in the management of pelvic floor disorders.

    Science.gov (United States)

    Tzur, T; Yohai, D; Weintraub, A Y

    2016-04-01

    Pelvic floor disorders are common and bothersome problems that include a variety of conditions. These conditions greatly affect the performance of daily activities and social function such as work, traveling, physical exercise, sleep and sexual function. Aging is a well-known factor affecting the pelvic floor and lower urinary tract anatomy and function. It is clear that the pelvic organs and their surrounding muscular and connective tissue support are estrogen-responsive. Treatment of pelvic floor disorders requires significant health-care resources and their impact is likely to increase in the near future. This literature review aims to provide an overview of both research and clinical aspects of the pathophysiology of urogenital estrogen deficiency and the role of local estrogen therapy as part of the management strategy of different pelvic floor disorders. The safety and risk concerns regarding the use of local estrogen therapy are addressed as well. PMID:26830033

  4. Compounds of Natural Origin and Acupuncture for the Treatment of Diseases Caused by Estrogen Deficiency.

    Science.gov (United States)

    Thakur, Abhishek; Mandal, Subhash C; Banerjee, Sugato

    2016-06-01

    A predominant number of diseases affecting women are related to female hormones. In most of the cases, these diseases are reported to be associated with menstrual problems. These diseases affect female reproductive organs such as the breast, uterus, and ovaries. Estrogen is the main hormone responsible for the menstrual cycle, so irregular menstruation is primarily due to a disturbance in estrogen levels. Estrogen imbalance leads to various pathological conditions in premenopausal women, such as endometriosis, breast cancer, colorectal cancer, prostate cancer, poly cysts, intrahepatic cholestasis of pregnancy, osteoporosis, cardiovascular diseases, obesity, etc. In this review, we discuss common drug targets and therapeutic strategies, including acupuncture and compounds of natural origin, for the treatment of diseases caused by estrogen deficiency. PMID:27342884

  5. A Genomewide Screen in Schizosaccharomyces pombe for Genes Affecting the Sensitivity of Antifungal Drugs That Target Ergosterol Biosynthesis

    OpenAIRE

    Fang, Yue; Hu, Lingling; Zhou, Xin; Jaiseng, Wurentuya; Zhang, Ben; Takami, Tomonori; Kuno, Takayoshi

    2012-01-01

    We performed a genomewide screen for altered sensitivity to antifungal drugs, including clotrimazole and terbinafine, that target ergosterol biosynthesis using a Schizosaccharomyces pombe gene deletion library consisting of 3,004 nonessential haploid deletion mutants. We identified 109 mutants that were hypersensitive and 11 mutants that were resistant to these antifungals. Proteins whose absence rendered cells sensitive to these antifungals were classified into various functional categories,...

  6. Estrogen-inducible neuropeptides in the rat brain: role in focal ischemic lesions

    OpenAIRE

    Theodorsson, Annette

    2005-01-01

    Sex steroids in general and estrogens in particular – in addition to their effects on the reproductive organs – affect a large number of crucial bodily functions, including “higher” brain functions. Neuropeptides constitute the phylogenetically oldest neurotransmitter system and are currently thought to act mainly during stress, disease or injury. The concentration of galanin is i.a. up-regulated by injury to the nervous system and by estrogen. The main focus of the present thesis was to inve...

  7. Effect of Prenatal Exposure to Lead on Estrogen Action in the Prepubertal Rat Uterus

    OpenAIRE

    Tchernitchin, Andrei N.; Leonardo Gaete; Rodrigo Bustamante; Aracelly Báez

    2012-01-01

    Lead is a widely spread environmental pollutant known to affect both male and female reproductive systems in humans and experimental animals and causes infertility and other adverse effects. The present paper investigated the effects of prenatal exposure to lead on different parameters of estrogen stimulation in the uterus of the prepubertal rat. In prenatally and perinatally exposed rats, estrogen-induced endometrial eosinophilia, endometrial stroma edema, and eosinophil migration towards th...

  8. Sex hormones modulate circulating antioxidant enzymes: Impact of estrogen therapy ☆

    OpenAIRE

    Francesco Bellanti; Maria Matteo; Tiziana Rollo; Filomena De Rosario; Pantaleo Greco; Gianluigi Vendemiale; Gaetano Serviddio

    2013-01-01

    Objective: Ovarian senescence affects many tissues and produces a variety of symptoms and signs. We hypothesized that estrogens may also influence circulating redox balance by regulating activity of the cellular antioxidative enzyme system. We aimed to explore the impact of surgical estrogen deprivation and replacement (ERT) on the glutathione balance and antioxidant enzymes expression in fertile women. Study design: Nineteen healthy premenopausal women who underwent total hysterectomy wit...

  9. PI3K in the ventromedial hypothalamic nucleus mediates estrogenic actions on energy expenditure in female mice.

    Science.gov (United States)

    Saito, Kenji; He, Yanlin; Yang, Yongjie; Zhu, Liangru; Wang, Chunmei; Xu, Pingwen; Hinton, Antentor Othrell; Yan, Xiaofeng; Zhao, Jean; Fukuda, Makoto; Tong, Qingchun; Clegg, Deborah J; Xu, Yong

    2016-01-01

    Estrogens act in the ventromedial hypothalamic nucleus (VMH) to regulate body weight homeostasis. However, the molecular mechanisms underlying these estrogenic effects are unknown. We show that activation of estrogen receptor-α (ERα) stimulates neural firing of VMH neurons expressing ERα, and these effects are blocked with intracellular application of a pharmacological inhibitor of the phosphatidyl inositol 3-kinase (PI3K). Further, we demonstrated that mice with genetic inhibition of PI3K activity in VMH neurons showed a sexual dimorphic obese phenotype, with only female mutants being affected. In addition, inhibition of VMH PI3K activity blocked effects of 17β-estradiol to stimulate energy expenditure, but did not affect estrogen-induced anorexia. Collectively, our results indicate that PI3K activity in VMH neurons plays a physiologically relevant role in mediating estrogenic actions on energy expenditure in females. PMID:26988598

  10. Role of estrogen and estrogen receptors in sperm physiology

    Czech Academy of Sciences Publication Activity Database

    Dostálová, Pavla; Děd, Lukáš; Kubátová, Alena; Žatecká, Eva; Pěknicová, Jana

    Praha : Biotechnologický ústav v. v. i. AV ČR, 2012 - (Pěknicová, J.). s. 45-46 [XVIII. symposium českých reprodukčních imunologů s mezinárodní účastí. 25.05.2012-26.05.2012, Žďár nad Sázavou] R&D Projects: GA ČR(CZ) GA523/09/1793; GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : estrogene * estrogene receptor * capacitation * monoclonal antibody Subject RIV: DN - Health Impact of the Environment Quality

  11. Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

    Science.gov (United States)

    Gorelick, Daniel A.; Iwanowicz, Luke R.; Hung, Alice L.; Blazer, Vicki; Halpern, Marnie E.

    2014-01-01

    Background: Environmental endocrine disruptors (EED) are exogenous chemicals that mimic endogenous hormones, such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ER) in the larval heart compared to the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit similar tissue-specific effects as BPA and genistein or why some compounds preferentially target receptors in the heart. Methods: We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue-specificity in ER activation is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

  12. Estrogen Therapy Rescues Advanced Heart Failure via Estrogen Receptor Beta

    OpenAIRE

    Iorga, Andrea

    2015-01-01

    Cardiac hypertrophy, defined as an enlargement of the ventricles, is often triggered when the heart is subjected to hemodynamic stress from physiological stimuli such as pregnancy, or from pathological stimuli such as pressure overload-induced left ventricular hypertrophy or pulmonary hypertension-induced right ventricular hypertrophy. Physiological hypertrophy is beneficial and adaptive, while pathological hypertrophy is maladaptive and detrimental. Estrogen treatment prior to the onset of p...

  13. Targeted Radiotherapy of Estrogen Receptor Positive Tumors

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Assessment of Relationship-Specific Incentive and Threat Sensitivities: Predicting Satisfaction and Affect in Adult Intimate Relationships

    Science.gov (United States)

    Laurenceau, Jean-Philippe; Kleinman, Brighid M.; Kaczynski, Karen J.; Carver, Charles S.

    2010-01-01

    Self-report scales assessing relationship-specific incentive and threat sensitivity were created. Initial tests of factor structure and associations with relationship quality were conducted in a sample of persons in intimate relationships (Study 1). Associations with conceptually related measures were examined to determine convergent and…

  15. Sex hormones modulate circulating antioxidant enzymes: Impact of estrogen therapy

    Directory of Open Access Journals (Sweden)

    Francesco Bellanti

    2013-01-01

    Conclusions: Menopause is associated with significant change in antioxidant gene expression that in turn affects circulating redox state. Estrogens replacement therapy is able to prevent and counteract such modifications by acting as regulators of key antioxidant gene expression. These findings suggest that antioxidant genes are, almost in part, under the control of sex hormones, and that pathophysiology of the difference in gender disease may depend on the redox biology.

  16. Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus.

    Science.gov (United States)

    Weiser, M J; Handa, R J

    2009-03-17

    Numerous studies have established a link between individuals with affective disorders and a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, most notably characterized by a reduced sensitivity to glucocorticoid negative (-) feedback. Furthermore there is a sex difference in the etiology of mood disorders with incidence in females being two to three times that of males, an association that may be a result of the influence of estradiol (E2) on HPA axis function. In these studies, we have examined the effect of E2 on glucocorticoid-mediated HPA axis (-) feedback during both the diurnal peak and the stress-induced rise in corticosterone (CORT). Young adult female Sprague-Dawley (SD) rats were ovariectomized (OVX) and 1 week later treated subcutaneous (s.c.) with oil or estradiol benzoate (EB) for 4 days. On the 4th day of treatment, animals were injected with a single dose of dexamethasone (DEX), or vehicle. EB treatment significantly increased the evening elevation in CORT and the stress-induced rise in CORT. In contrast, DEX treatment reduced the diurnal and stress induced rise in CORT and adrenocorticotropic hormone (ACTH), and this reduction was not apparent following co-treatment with EB. To determine a potential site of E2's action, female SD rats were OVX and 1 week later, wax pellets containing E2, the estrogen receptor beta (ERbeta) agonist diarylpropionitrile (DPN), or the estrogen receptor alpha (ERalpha) agonist propylpyrazoletriol (PPT), was implanted bilaterally and dorsal to the paraventricular nucleus of the hypothalamus (PVN). Seven days later, animals were injected s.c. with a single dose of DEX, or vehicle to test for glucocorticoid-dependent (-) feedback. Results show that E2 and PPT increased, while DPN decreased the diurnal peak and stress-induced CORT and ACTH levels as compared to controls. Furthermore, E2 and PPT impaired the ability of DEX to inhibit both the diurnal and the stress-induced rise in CORT and ACTH, whereas DPN had

  17. X-ray survival characteristics and genetic analysis for nineSaccharomyces deletion mutants that affect radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2006-07-21

    We examine ionizing radiation (IR) sensitivity and epistasisrelationships of several Saccharomyces mutants affectingpost-translational modifications of histones H2B and H3. Mutantsbre1delta, lge1delta, and rtf1delta, defective in histone H2B lysine 123ubiquitination, show IR sensitivity equivalent to that of the dot1deltamutant that we reported on earlier, consistent with published findingsthat Dot1p requires H2B K123 ubiquitination to fully methylate histone H3K79. This implicates progressive K79 methylation rather thanmono-methylation in IR resistance. The set2delta mutant, defective in H3K36 methylation, shows mild IR sensitivity whereas mutants that abolishH3 K4 methylation resemble wild type. The dot1delta, bre1delta, andlge1delta mutants show epistasis for IR sensitivity. The paf1deltamutant, also reportedly defective in H2B K123 ubiquitination, confers nosensitivity. The rad6delta, rad51null, rad50delta, and rad9deltamutations are epistatic to bre1? and dot1delta, but rad18delta andrad5delta show additivity with bre1delta, dot1delta, and each other. Thebre1delta rad18delta double mutant resembles rad6delta in sensitivity;thus the role of Rad6p in ubiquitinating H2B accounts for its extrasensitivity compared to rad18delta. We conclude that IR resistanceconferred by BRE1 and DOT1 is mediated through homologous recombinationalrepair, not postreplication repair, and confirm findings of a G1checkpoint role for the RAD6/BRE1/DOT1 pathway.

  18. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    OpenAIRE

    Erika eBorella; Barbara eCarretti; Massimo eGrassi; Massimo eNucci; Roberta eSciore

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we ...

  19. Estrogen receptor transcription and transactivation: Estrogen receptor knockout mice - what their phenotypes reveal about mechanisms of estrogen action

    OpenAIRE

    Curtis Hewitt, Sylvia; F Couse, John; S Korach, Kenneth

    2000-01-01

    Natural, synthetic and environmental estrogens have numerous effects on the development and physiology of mammals. Estrogen is primarily known for its role in the development and functioning of the female reproductive system. However, roles for estrogen in male fertility, bone, the circulatory system and immune system have been established by clinical observations regarding sex differences in pathologies, as well as observations following menopause or castration. The primary mechanism of estr...

  20. [Transdermal estrogenic therapy in menopause].

    Science.gov (United States)

    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. PMID:2543896

  1. Holographic QSAR of environmental estrogens

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaodong; XIAO Qianfen; CUI Shihai; LIU Shushen; YIN Daqiang; WANG Liansheng

    2005-01-01

    Experimental and epidemiological studies suggest that some man-made and naturally occurring chemicals related to the environment have the potential to interrupt normal functioning of the endocrine systems of humans and wildlife. These chemicals, termed EDCs (Endocrine disrupting Chemicals), pose serious threats to the reproductive capability of humans and wildlife. Because of the structural diversity and various types, development of structure-based rapid screening methodologies is important and necessary for the assessment of the environmental pollutants. In this paper molecular hologram based QSAR models were developed with the combinatory application of partial least square (PLS) regression for a large diverse set of 105 environmental estrogens. Quantitatively predictive models were developed based on only molecular structures, which can be used for the accurate prediction of estrogenicity to rapidly screen potential environmental endocrine disrupting chemicals.

  2. c-Src modulates estrogen-induced stress and apoptosis in estrogen-deprived breast cancer cells

    OpenAIRE

    Fan, Ping; Griffith, Obi L; Agboke, Fadeke; Anur, Pavana; Zou, Xiaojun; McDaniel, Russell E.; Creswell, Karen; Kim, Sung Hoon; Katzenellenbogen, John A.; Gray, Joe W; Jordan, V Craig

    2013-01-01

    The emergence of antiestrogen resistance in breast cancer is an important clinical phenomenon affecting long-term survival in this disease. Identifying factors that convey cell survival in this setting may guide improvements in treatment. Estrogen (E2) can induce apoptosis in breast cancer cells that have been selected for survival after E2 deprivation for long periods (MCF-7:5C cells), but the mechanisms underlying E2-induced stress in this setting have not been elucidated. Here, we report t...

  3. Mammary gland development--It's not just about estrogen.

    Science.gov (United States)

    Berryhill, Grace E; Trott, Josephine F; Hovey, Russell C

    2016-01-01

    The mammary gland (MG) is one of a few organs that undergoes most of its growth after birth. Much of this development occurs concurrently with specific reproductive states, such that the ultimate goal of milk synthesis and secretion is coordinated with the nutritional requirements of the neonate. Central to the reproductive-MG axis is its endocrine regulation, and pivotal to this regulation is the ovarian secretion of estrogen (E). Indeed, it is widely accepted that estrogens are essential for growth of the MG to occur, both for ductal elongation during puberty and for alveolar development during gestation. As the factors regulating MG development continually come to light from the fields of developmental biology, lactation physiology, and breast cancer research, a growing body of evidence serves as a reminder that the MG are not as exclusively dependent on estrogens as might have been thought. The objective of this review is to summarize the state of information regarding our understanding of how estrogen (E) has been implicated as the key regulator of MG development, and to highlight some of the alternative E-independent mechanisms that have been discovered. In particular, we review our findings that dietary trans-10,cis-12 conjugated linoleic acid promotes ductal elongation and that the combination of progesterone (P) and prolactin (PRL) can stimulate branching morphogenesis in the absence of E. Ultimately, these examples stand as a healthy challenge to the question of just how important estrogens are for MG development. Answers to this question, in turn, increase our understanding of MG development across all mammals and the ways in which it can affect milk production. PMID:26506542

  4. Evaluation of Factors Affecting the Value of Online Shopping Considering Price Sensitivity and Variety-Seeking of Buyers

    OpenAIRE

    Mahdi Alhoseini Almodarresi; Fatemeh Mohammadi

    2015-01-01

    Ease of access to information, possibility to compare products quickly, and many other facilities that Internet provides for consumers, increase the power of consumers much higher. Internet sellers for the purpose of increasing their sales, often offer lower prices in compare to retailer's price. Nevertheless, the recent studies represent that even price-sensitive customers, avoid shopping from low price online stores. Rather value is considered as the key driver of costumers' decision-making...

  5. Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

    OpenAIRE

    Nguyen, Holly M.; Nazanin Ruppender; Xiaotun Zhang; Lisha G. Brown; Gross, Ted S.; Colm Morrissey; Roman Gulati; Vessella, Robert L.; Frauke Schimmoller; Aftab, Dana T.; Eva Corey

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemis...

  6. Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer

    Directory of Open Access Journals (Sweden)

    Lundgren Steinar

    2010-06-01

    Full Text Available Abstract Background The cytochrome P450 (CYP enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM, tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam and 4-hydroxy-N-demethyltamoxifen (4OHNDtam, endoxifen. Inter-individual variations of the activity of these enzymes due to polymorphisms may be predictors of outcome of breast cancer patients during tamoxifen treatment. Since tamoxifen and estrogens are both partly metabolized by these enzymes we hypothesize that a correlation between serum tamoxifen and estrogen levels exists, which in turn may interact with tamoxifen on treatment outcome. Here we examined relationships between the serum levels of tamoxifen, estrogens, follicle-stimulating hormone (FSH, and also determined the genotypes of CYP2C19, 2D6, 3A5, and SULT1A1 in 90 postmenopausal breast cancer patients. Methods Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Estrogen and FSH levels were determined using a sensitive radio- and chemiluminescent immunoassay, respectively. Results We observed significant correlations between the serum concentrations of tamoxifen, N-dedimethyltamoxifen, and tamoxifen-N-oxide and estrogens (p Conclusions We have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted.

  7. Estrogen Free Contraception: Progestin-only-systems

    Directory of Open Access Journals (Sweden)

    Ahrendt HJ

    2010-01-01

    Full Text Available To reduce side effects of estrogen-progestin combination preparations, the dose of estrogen has continuously been reduced in the pill. As an alternative, estrogen-free preparations are increasingly used and are now available as oral, subdermal, intrauterine and intramuscular applications. The benefits of estrogen-free contraceptives are the prevention of estrogen-related side effects (nausea, edema, weight gain, mastodynia and of cycle-dependent side effects (dysmenorrhea, pelvic pain, premenstrual syndrome [PMS], hypermenorrhea, menstrual migraine. Furthermore, they can be used in women with risk factors, in whom estrogens are contraindicated. These include hypertension, thrombophilia, status post thrombosis, myocardial infarction, stroke, liver tumors, cholelithiasis and during lactation. In the following sections, the available preparations are being discussed.

  8. Estrogen formulations and beauty care practices in Japanese women

    Directory of Open Access Journals (Sweden)

    Takeda T

    2012-01-01

    range of “moderate” to “very good” and “sticky feeling” greatly affected the usability of the formulation.Conclusion: These results suggest that the level of attention to beauty care plays some role in the choice of estrogen formulations.Keywords: HRT, estrogen, transdermal gel, cosmetics, subjective impression

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

    Science.gov (United States)

    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

  10. Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women

    OpenAIRE

    Eliassen, A. Heather; Spiegelman, Donna; Xu, Xia; Keefer, Larry K; Veenstra, Timothy D.; Barbieri, Robert L.; Willett, Walter C; Hankinson, Susan E.; Ziegler, Regina G.

    2011-01-01

    Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites (EM) and breast cancer risk among premenopausal women in a case-control study nested within the Nurses’ Health Study II (NHSII). In 1996–1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N=247) diagnosed between collection and June 2005 were match...

  11. No effect of different estrogen receptor ligands on cognition in adult female monkeys.

    Science.gov (United States)

    Lacreuse, Agnès; Wilson, Mark E; Herndon, James G

    2009-03-01

    Many studies in women and animal models suggest that estrogens affect cognitive function. Yet, the mechanisms by which estrogens may impact cognition remain unclear. The goal of the present study was to assess the effects of different estrogen receptor (ER) ligands on cognitive function in adult ovariectomized female rhesus monkeys. The monkeys were tested for 6 weeks on a battery of memory and attentional tasks administered on a touchscreen: the object, face, and spatial versions of the Delayed Recognition Span Test (DRST) and a Visual Search task. Following a 2-week baseline period with oil vehicle treatment, monkeys were randomly assigned to one of 3 treatment groups: estradiol benzoate (EB), selective ERbeta agonist (diarylpropionitrile DPN) or selective ER modulator tamoxifen (TAM). In each treatment group, monkeys received oil vehicle for 2 weeks and the drug for 2 weeks, in a cross-over design. After a 4-week washout, a subset of monkeys was re-tested on the battery when treated with a selective ERalpha agonist (propyl-pyrazole-triol, PPT) or oil vehicle. Overall, drug treatments had no or negligible effects on cognitive performance. These results support the contention that exogenous estrogens and selective estrogen receptor modulators (SERMS) do not significantly affect cognition in young adult female macaques. Additional studies are needed to determine whether the cognitive effects of estrogens in monkeys of more advanced age are mediated by ERbeta, ERalpha or complex interactions between the two receptors. PMID:19101578

  12. Estrogen, Efferent Ductules, and the Epididymis1

    OpenAIRE

    Joseph, Avenel; Shur, Barry D.; Hess, Rex A.

    2010-01-01

    Estrogen's presence in the male reproductive system has been known for over 60 years, but its potential function in the epididymis remains an important area of investigation. Estrogen is synthesized by germ cells, producing a relatively high concentration in rete testis fluid. There are two estrogen receptors (ESR), the presence of which in the head of the epididymis is well documented and consistent between species; however, in other regions of the epididymis, their expression appears to be ...

  13. Oral Contraceptive Estrogen Content and Adverse Effects

    OpenAIRE

    Russell, Margaret; Ramcharan, Savitri

    1987-01-01

    The 1985 Health and Welfare Canada Report on Oral Contraceptives recommended oral contraceptives (OCs) containing 30-35 mcg of estrogen rather than 50 mcg as the preferred dosage for contraception. Many family physicians may regard these guidelines as mandatory when prescribing OCs, because of a presumption that pills of 50-mcg estrogen content carry a higher risk of disease. In this article, the epidemiologic evidence pertaining to a dose-response relationship between the estrogen dose of or...

  14. Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case–control study

    OpenAIRE

    Yao, Song; Till, Cathee; Kristal, Alan R.; Goodman, Phyllis J.; Hsing, Ann W.; Tangen, Catherine M.; Platz, Elizabeth A.; Stanczyk, Frank Z.; Reichardt, Juergen K. V.; Tang, Li; Neuhouser, Marian L; Santella, Regina M.; William D Figg; Price, Douglas K.; Parnes, Howard L.

    2011-01-01

    Objective Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. Methods These questions were investigated in a case–control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. Results Among men on placebo, no relationship of serum estroge...

  15. In absolute or relative terms? How framing prices affects the consumer price sensitivity of health plan choice

    OpenAIRE

    Schmitz, Hendrik; Ziebarth, Nicolas R.

    2011-01-01

    This paper provides field evidence on (a) how price framing affects consumers’ decision to switch health insurance plans and (b) how the price elasticity of demand for health insurance can be influenced by policymakers through simple regulatory efforts. In 2009, in order to foster competition among health insurance companies, German federal regulation required health insurance companies to express price differences between health plans in absolute Euro values rather than percentage point pa...

  16. Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice

    OpenAIRE

    Yu, Qinghui; Teixeira, Cátia M; Mahadevia, Darshini; Huang, Yung-yu; Balsam, Daniel; Mann, J. John; Gingrich, Jay A.; Ansorge, Mark S.

    2014-01-01

    Pharmacologic blockade of monoamine oxidase A (MAOA) or serotonin transporter (5-HTT) has antidepressant and anxiolytic efficacy in adulthood. Yet, genetically conferred MAOA or 5-HTT hypo-activity is associated with altered aggression and increased anxiety/depression. Here we test the hypothesis that increased monoamine signaling during development causes these paradoxical aggressive and affective phenotypes. We find that pharmacologic MAOA blockade during early postnatal development (P2-P21...

  17. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Science.gov (United States)

    Nguyen, Holly M; Ruppender, Nazanin; Zhang, Xiaotun; Brown, Lisha G; Gross, Ted S; Morrissey, Colm; Gulati, Roman; Vessella, Robert L; Schimmoller, Frauke; Aftab, Dana T; Corey, Eva

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. PMID:24205338

  18. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Directory of Open Access Journals (Sweden)

    Holly M Nguyen

    Full Text Available Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa, cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.

  19. Reduced near-UV sensitivity in Phycomyces mutants affected in the biosynthesis of 6,7-dimethyl-8-ribitylllumazine

    International Nuclear Information System (INIS)

    Riboflavin-requiring mutants of Phycomyces blakesleeanus with defects in the genes, ribA, ribB, ribC and ribD were analyzed with respect to their contents of flavins, 6,7-dimethyl-8-ribityllumazine (DMRL) and pterins as well as their phototropic sensitivity. Strains were grown on minimal medium enriched with 10-6 M riboflavin (RB), and the concentrations of the respective pigments in sporangiophores were determined by HPLC. In strains A607 ribC401 and A641 ribC402 madA7 a loss of DMRL correlated with a loss of near-UV sensitivity. In general terms, the results suggest the participation of DMRL in photoreception, which does not necessarily imply DMRL as a photoreceptor chromophore. In more specific terms, the result could be understood on the basis of a UV/blue-light photorecptor, which includes besides a flavin also a lumazine-like chromophore. Mutants C318 ribAl and C323 ribA4 accumulated DMRL, the immediate precursor of RB, as well as biopterin and neopterin. Mutant C322 ribB contained normal amounts of DMRL and pterins. Mutant C324 ribD5 had reduced amounts of neopterin and biopterin. The fact that some of the RB-requiring mutants displayed abnormal amounts of pterins indicates a common regulation for the flavin and the pterin pathway. (Author)

  20. Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only

    OpenAIRE

    Evans, D. G.; N. Bowers; Burkitt-Wright, E.; Miles, E.; S. Garg; Scott-Kitching, V.; Penman-Splitt, M.; Dobbie, A.; Howard, E.; Ealing, J.; Vassalo, G.; Wallace, A. J.; Newman, W.; ,; Huson, S M

    2016-01-01

    Background The detection rate for identifying the underlying mutation in neurocutaneous syndromes is affected by the sensitivity of the mutation test and the heterogeneity of the disease based on the diagnostic criteria. Neurofibromatosis type (NF1) has been defined for 29 years by the National Institutes for Health (NIH) criteria which include ≥ 6 Café au Lait macules (CAL) as a defining criterion. The discovery of SPRED1 as a cause of Legius syndrome which is manifested by CAL, freckling an...

  1. Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only

    OpenAIRE

    Evans, D. G.; N. Bowers; Burkitt-Wright, E.; Miles, E.; S. Garg; Scott-Kitching, V.; Penman-Splitt, M.; Dobbie, A.; Howard, E.; Ealing, J.; Vassalo, G.; Wallace, A. J.; Newman, W.; Huson, S M

    2016-01-01

    Background: The detection rate for identifying the underlying mutation in neurocutaneous syndromes is affected by the sensitivity of the mutation test and the heterogeneity of the disease based on the diagnostic criteria. Neurofibromatosis type (NF1) has been defined for 29 years by the National Institutes for Health (NIH) criteria which include ≥6 Café au Lait macules (CAL) as a defining criterion. The discovery of SPRED1 as a cause of Legius syndrome which is manifested by CAL, freckling an...

  2. Role of estrogen in avian osteoporosis.

    Science.gov (United States)

    Beck, M M; Hansen, K K

    2004-02-01

    One of the difficulties associated with commercial layer production is the development of osteoporosis in hens late in the production cycle. In light of this fact and because of hens' unique requirements for Ca, many studies have focused on the regulation of Ca and the role of estrogen in this process. The time course of estrogen synthesis over the productive life of hens has been well documented; increased circulating estrogen accompanies the onset of sexual maturity while decreases signal a decline in egg production prior to a molt. Numbers of estrogen receptors decrease with age in numerous tissues. The parallel changes in calcium-regulating proteins, primarily Calbindin D28K, and in the ability of duodenal cells to transport Ca, are thought to occur as a result of the changes in estrogen, and are also reversible by the molt process. In addition to the traditional model of estrogen action, evidence now exists for a possible nongenomic action of estrogen via membrane-bound receptors, demonstrated by extremely rapid surges of ionized Ca in chicken granulosa cells in response to 17beta-estradiol. Estrogen receptors have also been discovered in duodenal tissue, and tamoxifen, which binds to the estrogen receptor, has been shown to cause a rapid increase in Ca transport in the duodenum. In addition, recent evidence also suggests that mineralization of bone per se may not explain entirely the etiology of osteoporosis in the hen but that changes in the collagen matrix may contribute through decreases in bone elasticity. Taken together, these studies suggest that changes in estrogen synthesis and estrogen receptor populations may underlie the age-related changes in avian bone. As with postmenopausal women, dietary Ca and vitamin D are of limited benefit as remedies for osteoporosis in the hen. PMID:14979570

  3. Modulation of Root Signals in Relation to Stomatal Sensitivity to Root-sourced Abscisic Acid in Drought-affected Plants

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Stomatal sensitivity to root signals induced by soil drying may vary between environments and plant species. This is likely central role in root to shoot signaling. pH and hydraulic signals may interact with ABA signals and thus, jointly regulate stomatal responses to changed soil water status. pH itself can be modified by several factors, among which the chemical compositions In the xylem stream and the live cells surrounding the vessels play crucial roles. In addition to the xylem pH,more attention should be paid to the direct modulation of leaf apoplastic pH, because many chemical compositions might strongly modify the leaf apoplastlc pH while having no significant effect on the xylem pH. The direct modulation of the ABA signal intensity may be more important for the regulation of stomatal responses to soil drying than the ABA signal per se.The ABA signal is also regulated by the ABA catabolism and the supply of precursors to the roots If a sustained root to shoot communication of soil drying operates at the whole plant level. More importantly, ABA catabolism could play crucial roles In the determination of the fate of the ABA signal and thereby control the stomatal behavior of the root-sourced ABA signal.

  4. Ultra-sensitive detection of prion protein fibrils by flow cytometry in blood from cattle affected with bovine spongiform encephalopathy

    Directory of Open Access Journals (Sweden)

    Maas Elke

    2005-10-01

    Full Text Available Abstract Background The definite diagnosis of prion diseases such as Creutzfeldt-Jakob disease (CJD in humans or bovine spongiform encephalopathy (BSE in cattle currently relies on the post mortem detection of the pathological form of the prion protein (PrPSc in brain tissue. Infectivity studies indicate that PrPSc may also be present in body fluids, even at presymptomatic stages of the disease, albeit at concentrations well below the detection limits of currently available analytical methods. Results We developed a highly sensitive method for detecting prion protein aggregates that takes advantage of kinetic differences between seeded and unseeded polymerization of prion protein monomers. Detection of the aggregates was carried out by flow cytometry. In the presence of prion seeds, the association of labelled recombinant PrP monomers in plasma and serum proceeds much more efficiently than in the absence of seeds. In a diagnostic model system, synthetic PrP aggregates were detected down to a concentration of approximately 10-8 nM [0.24 fg/ml]. A specific signal was detected in six out of six available serum samples from BSE-positive cattle. Conclusion We have developed a method based on seed-dependent PrP fibril formation that shows promising results in differentiating a small number of BSE-positive serum samples from healthy controls. This method may provide the basis for an ante mortem diagnostic test for prion diseases.

  5. Quantum chemical studies of estrogenic compounds

    Science.gov (United States)

    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 ...

  6. Comparison of six different sewage treatment processes-Reduction of estrogenic substances and effects on gene expression in exposed male fish

    International Nuclear Information System (INIS)

    Treated sewage effluents often contain a mixture of estrogenic compounds in low concentrations. The total combined activity of these, however, may be sufficiently high to affect the reproduction of aquatic vertebrates. The introduction of advanced treatment technologies has been suggested as a way to remove micro-contaminants, including estrogenic substances. In this study, one municipal influent was treated with six different processes in parallel on a semi-large scale in order to assess their potential to reduce substances that could contribute to estrogenic effects in male fish. The effluent from a conventional, activated sludge treatment line was compared to a similarly treated effluent with a final sand-filtering step. The addition of ozonation (15 g O3/m3), a moving bed biofilm reactor (MBBR) or both in combination was also evaluated. There was also a separate treatment line that was based on a membrane bioreactor. A small battery of hepatic estrogen-responsive genes was measured in the exposed fish using quantitative PCR. Concentrations of steroid estrogens and estrogenic phenols in the effluents were measured by GC-ECNI-MS. The ozonated effluents were the only tested effluents for which all measured biological effects in exposed fish were removed. Chemical data suggested that the MBBR technology was equally effective in removing the analyzed estrogens; however, elevated expression of estrogen-responsive genes suggested that some estrogenic substances were still present in the effluent. The membrane bioreactor removed most of the measured estrogens and it reduced the induction of the estrogen-responsive genes. However, fish exposed to this effluent had significantly enlarged livers. Given that the same influent was treated in parallel with a broad set of technologies and that the chemical analyses were combined with an in vivo assessment of estrogenic responses, this study provides valuable input into the assessment of advanced treatment processes for

  7. Effects of estrogen on collagen gel contraction by human retinal glial cells

    Institute of Scientific and Technical Information of China (English)

    QIU Qing-hua; CHEN Zhi-Yi; YIN Li-li; ZHENG Zhi; WU Xing-wei

    2012-01-01

    Background There are definite gender differences in patients with macular holes.Menopausal women over 50 years are most affected.We aimed to observe the effect of estrogen on collagen gel contraction by cultured human retinal glial cells.It is speculated that estrogen could strengthen the tensile stress of the macula by maintaining the correct morphology and contraction.Methods Estrogen was used to determine its effects on collagen gel contraction,and its function was measured using morphological changes in cells.Human retinal glial cells were cultured in collagen solution.The cells were then exposed to collagen gels and the degree of contraction of the gel was determined.Results Estrogen at differing concentrations had no effect on the growth of human retinal glial cells.However,after exposed to collagen gel block,less contraction was noted in the estrogen-treated group than in the control group.Conclusions Estrogen can inhibit collagen gel contraction by glial cells.These results suggest a mechanism for macular hole formation,which is observed in menopausal females.

  8. Phorbol ester induced phosphorylation of the estrogen receptor in intact MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Recent studies with a variety of cellular receptors have shown that phorbol ester induced phosphorylation modulates ligand binding and function. In this study the authors present direct evidence that the estrogen receptor in MCF-7 human breast cancer cells is a phosphoprotein whose phosphorylation state can be enhanced specifically by phorbol-12-myristate-13-acetate (PMA). Cells were cultured to 6h in the presence of [32P]-orthophosphate. Whole cell extracts were immunoprecipitated with a monoclonal antibody (D58) against the estrogen receptor and subjected to SDS-polyacrylamide electrophoresis. Autoradiography showed a specific band in the region of 60-62 kDa which was significantly increased in preparations from PMA treated cells. Phospho-amino acid analysis demonstrated specific phosphorylation of serine and threonine residues. Cholera toxin or forskolin did not change the phosphorylation state of this protein. In a parallel binding analysis PMA led to a rapid decrease of estrogen binding sites. The estrogen induction of both progesterone receptors and growth in semisolid medium was blocked by PMA, whereas the estrogen induction of the 8kDa protein corresponding to the ps2 gene product and of the 52 kDa protein was not affected. In conclusion, phorbol esters can induce phosphorylation of the estrogen receptor. This process may be associated with the inactivation of certain receptor functions

  9. Performance of the flow cytometric E-screen assay in screening estrogenicity of pure compounds and environmental samples

    International Nuclear Information System (INIS)

    In vitro estrogenicity screens are believed to provide a first prioritization step in hazard characterization of endocrine disrupting chemicals. When applied to complex environmental matrices or mixture samples, they have been indicated valuable in estimating the overall estrogen-mimicking load. In this study, the performance of an adapted format of the classical E-screen or MCF-7 cell proliferation assay was profoundly evaluated to rank pure compounds as well as influents and effluents of sewage treatment plants (STPs) according to estrogenic activity. In this adapted format, flow cytometric cell cycle analysis was used to allow evaluation of the MCF-7 cell proliferative effects after only 24 h of exposure. With an average EC50 value of 2 pM and CV of 22%, this assay appears as a sensitive and reproducible system for evaluation of estrogenic activity. Moreover, estrogenic responses of 17 pure compounds corresponded well, qualitatively and quantitatively, with other in vitro and in vivo estrogenicity screens, such as the classical E-screen (R2 = 0.98), the estrogen receptor (ER) binding (R2 = 0.84) and the ER transcription activation assay (R2 = 0.87). To evaluate the applicability of this assay for complex samples, influents and effluents of 10 STPs covering different treatment processes, were compared and ranked according to estrogenic removal efficiencies. Activated sludge treatment with phosphorus and nitrogen removal appeared most effective in eliminating estrogenic activity, followed by activated sludge, lagoon and filter bed. This is well in agreement with previous findings based on chemical analysis or biological activity screens. Moreover, ER blocking experiments indicated that cell proliferative responses were mainly ER mediated, illustrating that the complexity of the end point, cell proliferation, compared to other ER screens, does not hamper the interpretation of the results. Therefore, this study, among other E-screen studies, supports the use of MCF

  10. Winter climate affects long-term trends in stream water nitrate in acid-sensitive catchments in southern Norway

    Directory of Open Access Journals (Sweden)

    H. A. de Wit

    2008-03-01

    Full Text Available Controls of stream water NO3 in mountainous and forested catchments are not thoroughly understood. Long-term trends in stream water NO3 are positive, neutral and negative, often apparently independent of trends in N deposition. Here, time series of NO3 in four small acid-sensitive catchments in southern Norway were analysed in order to identify likely drivers of long-term changes in NO3. In two sites, stream water NO3 export declined ca 50% over a period of 25 years while in the other sites NO3 export increased with roughly 20%. Discharge and N deposition alone were poor predictors of these trends. The most distinct trends in NO3 were found in winter and spring. Empirical models explained between 45% and 61% of the variation in weekly concentrations of NO3, and described both upward and downward seasonal trends tolerably well. Key explaining variables were snow depth, discharge, temperature and N deposition. All catchments showed reductions in snow depth and increases in winter discharge. In two inland catchments, located in moderate N deposition areas, these climatic changes appeared to drive the distinct decreases in winter and spring concentrations and fluxes of NO3. In a coast-near mountainous catchment in a low N deposition area, these climatic changes appeared to have the opposite effect, i.e. lead to increases in especially winter NO3. This suggests that the effect of a reduced snow pack may result in both decreased and increased catchment N leaching depending on interactions with N deposition, soil temperature regime and winter discharge.

  11. Winter climate affects long-term trends in stream water nitrate in acid-sensitive catchments in southern Norway

    Directory of Open Access Journals (Sweden)

    H. A. de Wit

    2007-09-01

    Full Text Available Controls of stream water NO3 in mountainous and forested catchments are not thoroughly understood. Long-term trends in stream water NO3 are positive, neutral and negative, often apparently independent of trends in N deposition. Here, time series of NO3 in four small acid-sensitive catchments in southern Norway were analysed in order to identify likely drivers of long-term changes in NO3. In two sites, stream water NO3 export declined ca 50% over a period of 25 years while in the other sites NO3 export increased with roughly 20%. Discharge and N deposition alone were poor predictors of these trends. The most distinct trends in NO3 were found in winter and spring. Empirical models explained between 45% and 61% of the variation in weekly concentrations of NO3, and described both upward and downward seasonal trends tolerably well. Key explaining variables were snow depth, discharge, temperature and N deposition. All catchments showed reductions in snow depth and increases in winter discharge. In two inland catchments, located in moderate N deposition areas, these climatic changes appeared to drive the distinct decreases in winter and spring concentrations and fluxes of NO3. In a coast-near mountainous catchment in a low N deposition area, these climatic changes appeared to have the opposite effect, i.e. lead to increases in especially winter NO3. This suggests that the effect of a reduced snow pack may result in both decreased and increased catchment N leaching depending on interactions with N deposition, soil temperature regime and winter discharge.

  12. Evaluation of possible factors affecting contrast sensitivity function in patients with primary Sjögren’s syndrome

    Directory of Open Access Journals (Sweden)

    Sedat Arikan

    2015-06-01

    Full Text Available ABSTRACT Purpose: The contrast sensitivity (CS function in patients with primary Sjögren’s syndrome (pSS may be impaired either frequently as a result of dry eye diseases or rarely as a result of optic neuropathy. In this study, we aimed to evaluate the CS function in pSS patients as well as to assess corneal aberrations and thickness of the peripapillary retinal nerve fiber layer (pRNFL. Methods: Fourteen eyes of 14 pSS patients (pSS group and 14 eyes of 14 healthy participants (control group were subjected to assessment of CS at the spatial frequencies of 1.5, 3.0, 6.0, 12, and 18 cycles/degree (cpd using a functional visual acuity contrast test (FACT; measurement of corneal high-order aberrations (HOAs in terms of coma-like, spherical-like, and total HOAs using Scheimpflug corneal topography; and measurement of the thickness of both the macular ganglion cell-inner plexiform layer (mGCIPL and pRNFL in all quadrants using optical coherence tomography. None of the participants were under treatment with artificial tears. Results: The results of the CS test did not differ between the 2 groups at all spatial frequencies (p>0.05. In addition, there were no statistically significant differences between the 2 groups in terms of corneal HOAs (p>0.05 and thickness of mGCIPL (p>0.05. However, among all quadrants, only the inferior quadrant of pRNFL in pSS patients was statistically significantly thinner than that in the healthy participants (p=0.04. Conclusions: The CS function in pSS patients can be maintained with normal thickness of both pRNFL and mGCIPL and with lack of increased corneal HOAs, which may be present even in the absence of artificial tear usage.

  13. Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause

    Directory of Open Access Journals (Sweden)

    Anikó Pósa

    2015-01-01

    Full Text Available Estrogen deficiency is one of the main causes of age-associated diseases in the cardiovascular system. Female Wistar rats were divided into four experimental groups: pharmacologically ovariectomized, surgically ovariectomized, and 24-month-old intact aging animals were compared with a control group. The activity and expression of heme oxygenases (HO in the cardiac left ventricle, the concentrations of cardiac interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α, the myeloperoxidase (MPO activity in the cardiac left ventricle, and the effects of heme oxygenase blockade (by 24-hour and 1-hour pretreatment with tin-protoporphyrin IX, SnPP on the epinephrine and phentolamine-induced electrocardiogram ST segment changes in vivo were investigated. The cardiac HO activity and the expression of HO-1 and HO-2 were significantly decreased in the aged rats and after ovariectomy. Estrogen depletion was accompanied by significant increases in the expression of IL-6 and TNF-α. The aged and ovariectomized animals exhibited a significantly elevated MPO activity and a significant ST segment depression. After pretreatment with SnPP augmented ST segment changes were determined. These findings demonstrate that the sensitivity to cardiac ischemia in estrogen depletion models is associated with suppression of the activity and expression of the HO system and increases in the secretion of proinflammatory cytokines and biomarkers.

  14. Amygdala subnuclei resting-state functional connectivity sex and estrogen differences.

    Science.gov (United States)

    Engman, Jonas; Linnman, Clas; Van Dijk, Koene R A; Milad, Mohammed R

    2016-01-01

    The amygdala is a hub in emotional processing, including that of negative affect. Healthy men and women have distinct differences in amygdala responses, potentially setting the stage for the observed sex differences in the prevalence of fear, anxiety, and pain disorders. Here, we examined how amygdala subnuclei resting-state functional connectivity is affected by sex, as well as explored how the functional connectivity is related to estrogen levels. Resting-state functional connectivity was measured using functional magnetic resonance imaging (fMRI) with seeds placed in the left and right laterobasal (LB) and centromedial (CM) amygdala. Sex differences were studied in 48 healthy men and 48 healthy women, matched for age, while the association with estrogen was analyzed in a subsample of 24 women, for whom hormone levels had been assessed. For the hormone analyses, the subsample was further divided into a lower and higher estrogen levels group based on a median split. We found distinct sex differences in the LB and CM amygdala resting-state functional connectivity, as well as preliminary evidence for an association between estrogen levels and connectivity patterns. These results are potentially valuable in explaining why women are more afflicted by conditions of negative affect than are men, and could imply a mechanistic role for estrogen in modulating emotion. PMID:26406106

  15. A rapid, sensitive two-site immunometric assay for TSH using monoclonal antibodies: investigation of factors affecting optimisation

    International Nuclear Information System (INIS)

    Twenty-three monoclonal antibodies specific for human thyrotropin (TSH) have been prepared and characterised. Four different epitopes have been identified, 3 of which are sufficiently distinct to allow simultaneous binding of the corresponding antibodies. Only 1 epitope is expressed on free TSH β-subunit. The best antibodies have affinities for TSH approaching 1011 M-1 and cross-reactions with lutropin and chorionic gonadotropin of 0.2% or less. A 2-site immunoradiometric assay for TSH was established using 2 monoclonal antibodies, one of which was adsorbed to plastic tubes and the other labelled with 125I. Several parameters affecting assay performance were investigated, including conditions for adsorption of antibodies to various plastics, selection of antibody combinations, concentration of labelled antibody and incubation protocol. The optimised assay covered a working range of 1-60 mU/l (0.17-10 ng/ml) TSH in a 4 h, single incubation protocol, with no significant interference from other glycoprotein hormones at their maximum physiological or pathological concentrations. (Auth.)

  16. Are Age-Related Differences Between Young and Older Adults in an Affective Working Memory Test Sensitive to the Music Effects?

    Directory of Open Access Journals (Sweden)

    Erika eBorella

    2014-11-01

    Full Text Available There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words, are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni, which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task were analyzed.Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni. However, as in previous studies, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences, in terms of accuracy in the processing phase of the Operation Span task, were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music.Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are less sensitive to music effects.

  17. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    Science.gov (United States)

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064

  18. Discovery of a sulfamate-based steroid sulfatase inhibitor with intrinsic selective estrogen receptor modulator properties.

    Science.gov (United States)

    Ouellet, Charles; Maltais, René; Ouellet, Étienne; Barbeau, Xavier; Lagüe, Patrick; Poirier, Donald

    2016-08-25

    Steroid sulfatase (STS), the enzyme which converts inactive sulfated steroid precursors into active hormones, is a promising therapeutic target for the treatment of estrogen-sensitive breast cancer. We report herein the synthesis and in vitro study of dual-action STS inhibitors with selective estrogen-receptor modulator (SERM) effects. A library of tetrahydroisoquinoline-N-substituted derivatives (phenolic compounds) was synthesized by solid-phase chemistry and tested on estrogen-sensitive breast cancer T-47D cells. Three phenolic compounds devoid of estrogenic activity and toxicity emerged from this screening. Their sulfamate analogs were then synthesized, tested in STS-transfected HEK-293 cells, and found to be potent inhibitors of the enzyme (IC50 of 3.9, 8.9, and 16.6 nM). When tested in T-47D cells they showed no estrogenic activity and produced a moderate antiestrogenic activity. The compounds were further tested on osteoblast-like Saos-2 cells and found to significantly stimulate their proliferation as well as their alkaline phosphatase activity, thus suggesting a SERM activity. These results are supported by molecular docking experiments. PMID:27155470

  19. Testing boron-containing estrogens on human breast cancer cells in a neutron beam

    International Nuclear Information System (INIS)

    Of the several boron-containing estrogen derivatives synthesized by the authors, they found that 17α-carboranyestradiol (Carbestrol) had estrogenic potency equal to natural estradiol both in female rats and also in human breast cancer cells (cell line MCF-7, estrogen sensitive). The therapy neutron beam from the MITR II nuclear reactor was trained on the MCF-7 cells which had been pre-incubated with various concentrations of Carbestrol. The background γ-radiation was 300 rads. Both the test cells and also the control cells were markedly damaged by the irradiation. Under similar experimental conditions, 300 rads of γ-radiation from a calibrated cesium source were found to produce about half of the cell damage observed in the neutron irradiation experiments. Experiments involving the treatment of estrogen-sensitive cancer cells with a boron-containing estrogen may be more productive when the non-selectively destructive γ-radiation is removed from the neutron beam and also by enriching Carbestrol with 10B

  20. Sensitivity analysis of the FEMA HAZUS-MH MR4 Earthquake Model using seismic events affecting King County Washington

    Science.gov (United States)

    Neighbors, C.; Noriega, G. R.; Caras, Y.; Cochran, E. S.

    2010-12-01

    HAZUS-MH MR4 (HAZards U. S. Multi-Hazard Maintenance Release 4) is a risk-estimation software developed by FEMA to calculate potential losses due to natural disasters. Federal, state, regional, and local government use the HAZUS-MH Earthquake Model for earthquake risk mitigation, preparedness, response, and recovery planning (FEMA, 2003). In this study, we examine several parameters used by the HAZUS-MH Earthquake Model methodology to understand how modifying the user-defined settings affect ground motion analysis, seismic risk assessment and earthquake loss estimates. This analysis focuses on both shallow crustal and deep intraslab events in the American Pacific Northwest. Specifically, the historic 1949 Mw 6.8 Olympia, 1965 Mw 6.6 Seattle-Tacoma and 2001 Mw 6.8 Nisqually normal fault intraslab events and scenario large-magnitude Seattle reverse fault crustal events are modeled. Inputs analyzed include variations of deterministic event scenarios combined with hazard maps and USGS ShakeMaps. This approach utilizes the capacity of the HAZUS-MH Earthquake Model to define landslide- and liquefaction- susceptibility hazards with local groundwater level and slope stability information. Where Shakemap inputs are not used, events are run in combination with NEHRP soil classifications to determine site amplification effects. The earthquake component of HAZUS-MH applies a series of empirical ground motion attenuation relationships developed from source parameters of both regional and global historical earthquakes to estimate strong ground motion. Ground motion and resulting ground failure due to earthquakes are then used to calculate, direct physical damage for general building stock, essential facilities, and lifelines, including transportation systems and utility systems. Earthquake losses are expressed in structural, economic and social terms. Where available, comparisons between recorded earthquake losses and HAZUS-MH earthquake losses are used to determine how region

  1. Ozonation of estrogenic chemicals in biologically treated sewage

    DEFF Research Database (Denmark)

    Hansen, Kamilla Marie Speht; Andersen, Henrik Rasmus; Ledin, Anna

    2010-01-01

    for removal of 17 estrogenic chemicals. The estrogenic compounds included parabens, industrial phenols, sunscreen chemicals, and steroid estrogens. The obtained values of Electrical Energy per Order (EEOs) for the treatment of the estrogens were in the range 0.14–1.1 kWh/m3 corresponding to 1.7–14 g O3/m3...

  2. Prepubertal tamoxifen treatment affects development of heifer reproductive tissues and related signaling pathways.

    Science.gov (United States)

    Al Naib, A; Tucker, H L M; Xie, G; Keisler, D H; Bartol, F F; Rhoads, R P; Akers, R M; Rhoads, M L

    2016-07-01

    Prepubertal exposure of the developing ovaries and reproductive tract (RT) to estrogen or xenoestrogens can have acute and long-term consequences that compromise the reproductive performance of cattle. This research examined effects of the selective estrogen receptor modulator tamoxifen (TAM) on gene and protein abundance in prepubertal ovaries and RT, with a particular focus on signaling pathways that affect morphology. Tamoxifen was administered to Holstein heifer calves (n=8) daily (0.3mg/kg subcutaneously) from 28 to 120 d of age, when tissues were collected. Control calves (n=7) received an equal volume of excipient. Weight, gross measurements, and samples of reproductive tissues were collected, and protein and mRNA were extracted from snap-frozen samples of vagina, cervix, uterus, oviduct, ovary, and liver. Neither estradiol nor insulin-like growth factor I (IGFI) concentrations in the serum were affected by TAM treatment. Tamoxifen treatment reduced ovarian weight independently from effects on antral follicle populations, as there was no difference in visible antral follicle numbers on the day of collection. Estrogen receptor α (ESR1) and β (ESR2) mRNA, ESR1 protein, IGFI, progesterone receptor, total growth hormone receptor, WNT4, WNT5A, and WNT7A mRNA, in addition to mitogen-activated protein kinase (MAPK) and phosphorylated MAPK proteins were affected differently depending on the tissue examined. However, neither IGFI receptor mRNA nor protein abundance were affected by TAM treatment. Results indicate that reproductive development in prepubertal Holstein heifer calves is TAM-sensitive, and that bovine RT and ovarian development are supported, in part, by estrogen receptor-dependent mechanisms during the period studied here. Potential long-term consequences of such developmental disruption remain to be defined. PMID:27085397

  3. Differential estrogen receptor binding of estrogenic substances: a species comparison.

    Science.gov (United States)

    Matthews, J; Celius, T; Halgren, R; Zacharewski, T

    2000-11-15

    The study investigated the ability of 34 natural and synthetic chemicals to compete with [3H]17beta-estradiol (E2) for binding to bacterially expressed glutathione-S-transferase (GST)-estrogen receptors (ER) fusion proteins from five different species. Fusion proteins consisted of the ER D, E and F domains of human alpha (GST-hERalphadef), mouse alpha (GST-mERalphadef), chicken (GST-cERdef), green anole (GST-aERdef) and rainbow trout ERs (GST-rtERdef). All five fusion proteins displayed high affinity for E2 with dissociation constants (K(d)) ranging from 0.3 to 0.9 nM. Although, the fusion proteins exhibited similar binding preferences and binding affinities for many of the chemicals, several differences were observed. For example, alpha-zearalenol bound with greater affinity to GST-rtERdef than E2, which was in contrast to other GST-ERdef fusion proteins examined. Coumestrol, genistein and naringenin bound with higher affinity to the GST-aERdef, than to the other GST-ERdef fusion proteins. Many of the industrial chemicals examined preferentially bound to GST-rtERdef. Bisphenol A, 4-t-octylphenol and o,p' DDT bound with approximately a ten-fold greater affinity to GST-rtERdef than to other GST-ERdefs. Methoxychlor, p,p'-DDT, o,p'-DDE, p,p'-DDE, alpha-endosulfan and dieldrin weakly bound to the ERs from the human, mouse, chicken and green anole. In contrast, these compounds completely displaced [3H]E2 from GST-rtERdef. These results demonstrate that ERs from different species exhibit differential ligand preferences and relative binding affinities for estrogenic compounds and that these differences may be due to the variability in the amino acid sequence within their respective ER ligand binding domains. PMID:11162928

  4. Estrogen deficiency in porcine cystic ovaries

    International Nuclear Information System (INIS)

    Estrone(E1) and estradiol-17β (E2) were measured in follicular cyst fluid obtained from swine ovaries by a simultaneous radioimmunoassay method. Follicular fluid from small (diameter, <3.9mm), medium (4-5.9mm) and large (6-10mm) normal follicles were similarly analyzed. The two hormones increased in concentration with increasing maturity of the normal follicles. Medium and large follicles, respectively, contained 2x and 8x the concentration of El as in small follicles. The concentration of E2 in medium and large follicles, respectively, was approximately 2x and 13x the concentration found in small follicles. The E2:E1 ratio also increased with size of the follicles. In contrast, cystic fluid contained virtually no estrogens. E2 was not detectable (assay sensitivity, 5.0 pg/tube for E2 and 10.0 pg/tube for E1) while E1 was present at 2-4ng/ml representing 1/25th of the E1 concentration found in large normal follicles

  5. Estrogen receptor beta treats Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Zhu Tian; Jia Fan; Yang Zhao; Sheng Bi; Lihui Si; Qun Liu

    2013-01-01

    In vitro studies have shown that estrogen receptor β can attenuate the cytotoxic effect of amyloid β protein on PC12 cells through the Akt pathway without estrogen stimulation. In this study, we aimed to observe the effect of estrogen receptor β in Alzheimer's disease rat models established by intraventricular injection of amyloid β protein. Estrogen receptor β lentiviral particles delivered via intraventricular injection increased Akt content in the hippocampus, decreased interleukin-1β mRNA, tumor necrosis factor α mRNA and amyloid β protein levels in the hippocampus, and improved the learning and memory capacities in Alzheimer's disease rats. Estrogen receptor β short hairpin RNA lentiviral particles delivered via intraventricular injection had none of the above impacts on Alzheimer's disease rats. These experimental findings indicate that estrogen receptor β, independent from estrogen, can reduce inflammatory reactions and amyloid β deposition in the hippocampus of Alzheimer's disease rats, and improve learning and memory capacities. This effect may be mediated through activation of the Akt pathway.

  6. Determination of estrogenic activity in the river Chienti (Marche Region, Italy) by using in vivo and in vitro bioassays.

    Science.gov (United States)

    Cocci, Paolo; Palermo, Francesco Alessandro; Quassinti, Luana; Bramucci, Massimo; Miano, Antonino; Mosconi, Gilberto

    2016-05-01

    Environmental estrogen-like compounds (i.e. xenoestrogens) are a variety of pollutants, ranging from synthetic to natural occurring molecules, that are found in surface and waste waters over a wide range of concentrations. In aquatic environment, the overall estrogenic activity is often due to the presence of a mixture of chemicals and their degraded products which can induce synergistic effects. Current strategies for monitoring estrogen-like chemicals are based on the use of a battery of in vivo and in vitro ecotoxicological tests. In this regard, the aim of the present work was to carry out a bio-monitoring study for testing estrogenicity of the Chienti river (Marche Region, Italy) by using both an E-screen and a vitellogenin (Vtg) induction assay in juvenile goldfish. Three sites were used for analysis, localized at the mouth (sampling point 1), in the middle (sampling point 2) and at the origin (sampling point 3) of Chienti river. For most of the water samples (i.e. samples collected at sampling points 2 and 3), clear estrogenic activity was detected in the E-screen assay suggesting different proliferation activities in function of the collecting site. In contrast, the Vtg ELISA demonstrated that water samples collected from each sampling point were estrogenic. Overall, we showed for the first time that the estrogenic activities in water samples from the Chienti river were significant in both in vivo and in vitro; we also observed a different sensitivity between bioassays. PMID:27155408

  7. Effects of triclocarban on the transcription of estrogen, androgen and aryl hydrocarbon receptor responsive genes in human breast cancer cells.

    Science.gov (United States)

    Tarnow, Patrick; Tralau, Tewes; Hunecke, Danele; Luch, Andreas

    2013-08-01

    Triclocarban (TCC) is an antimicrobial agent that is used in detergents, soaps and other personal hygiene products. Similarly to triclosan the widespread use of TCC has raised concerns about its endocrine potential. In luciferase-based reporter assays TCC has been shown to enhance estrogenic and androgenic activities following cellular coexposure with estrogen or dihydrotestosterone, respectively. The present study demonstrates that although coexposure with TCC enhances the estrogenic and androgenic readout of luciferase-based reporter cell lines such as HeLa9908 and MDA-kb2, it fails to act as a xenoandrogen on transcriptional level, nor does it induce cell proliferation in the estrogen sensitive E-screen. In addition TCC did not alter the expression of estrogen responsive genes in human mammary carcinoma MCF-7 cells exposed to 17β-estradiol, bisphenol A, butylparaben or genistein. However, TCC was shown to interfere with the regulon of the aryl hydrocarbon receptor (AhR) as TCC showed a costimulatory effect on transcription of CYP1A1 and CYP1B1, effectively lowering the transcriptional threshold for both genes in the presence of estrogens. It thus seems, that while the induction of the respective luciferase reporter assays by TCC is an unspecific false positive signal caused by luciferase stabilisation, TCC has the potential to interfere with the regulatory crosstalk of the estrogen receptor (ER) and the AhR regulon. PMID:23524099

  8. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

    Science.gov (United States)

    Stefano, G B; Prevot, V; Beauvillain, J C; Fimiani, C; Welters, I; Cadet, P; Breton, C; Pestel, J; Salzet, M; Bilfinger, T V

    1999-10-01

    We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase (cNOS) activity in human peripheral monocytes by acting on an estrogen surface receptor. NO release was measured in real time with an amperometric probe. 17beta-estradiol exposure to monocytes stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol had no effect. 17beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA, whereas ICI 182,780, a selective inhibitor of the nuclear estrogen receptor, had no effect. We further showed, using a dual emission microfluorometry in a calcium-free medium, that the 17beta-estradiol-stimulated release of monocyte NO was dependent on the initial stimulation of intracellular calcium transients in a tamoxifen-sensitive process. Leeching out the intracellular calcium stores abolished the effect of 17beta-estradiol on NO release. RT-PCR analysis of RNA obtained from the cells revealed a strong estrogen receptor-alpha amplification signal and a weak beta signal. Taken together, a physiological dose of estrogen acutely stimulates NO release from human monocytes via the activation of an estrogen surface receptor that is coupled to increases in intracellular calcium. PMID:10490972

  9. Factors affecting the effects of EDU on growth and yield of field-grown bush beans (Phaseolus vulgaris L.), with varying degrees of sensitivity to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Elagoez, Vahram [Plant Biology Graduate Program, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: velagoz@nsm.umass.edu; Manning, William J. [Department of Plant, Soil and Insect Sciences, University of Massachusetts, Amherst, MA 01003 (United States)

    2005-08-15

    The effects of foliar applications of ethylenediurea (EDU) on responses to ozone by field-grown bush bean (Phaseolus vulgaris L.) lines 'S156' (O{sub 3}-sensitive) and 'R123' (O{sub 3}-tolerant), and cultivars 'BBL 290' (O{sub 3}-sensitive) and 'BBL 274' (O{sub 3}-tolerant) were investigated during the 2001 and 2002 growing seasons. EDU was applied weekly to designated plants between primary leaf expansion and pod senescence. Results were compared with control plants at harvests made at pod maturation and pod senescence. In 2001, average hourly ambient O{sub 3} concentrations ranged between 41 and 59 ppb for a total of 303 h; in 2002, for 355 h. EDU applications prior to pod maturation significantly increased the number of marketable pods in 'R123', but not for the other cultivars. Harvests at pod senescence showed significant improvements in crop yield production in EDU-treated 'S156' plants, whereas for EDU-treated 'R123' plants significant reductions were determined in above-ground biomass and seed production. In contrast, results from 'BBL 290' and 'BBL 274' at both harvest points were inconclusive. Growth and reproductive responses of O{sub 3}-sensitive and O{sub 3}-tolerant bush bean plants to EDU applications varied, depending on developmental stages, duration of EDU applications, and fluctuations in ambient O{sub 3}. - Plant sensitivity to ozone, stage of plant development, number of applications of EDU and ambient ozone affect bean plant responses to EDU.

  10. Treatment of menopausal affective disorders with electroacupuncture combining selective estrogen receptor modulators%电针联合选择性雌激素受体调节剂治疗绝经期情感障碍的临床观察

    Institute of Scientific and Technical Information of China (English)

    刘桂玲; 柳霞; 张弘; 郭琳

    2011-01-01

    Objective To observe the curative effect of electroacupuncture combining with selective estrogen receptor modulators (Tibolone) on menopausal affective disorders. Methods The menopausal patients with affective disorders (n =40) were randomly divided into two groups (each n = 20) according to their visiting orders. The treatment group was treated with electroacupuncture (4 times a week) and Tibolone (2.5 mg/piece) one table every other day. The control group was treated with only Tibolone (2.5 mg/piece) one table every other day. The treatment cycle was 4 weeks. The degree of patients depression was reviewed by using Hamilton Depression Scale (HAMD) before and after the treatment. Results The observation showed that there was a significant difference in HAMD scores between two groups after the treatment (P<0.05), and the total effective rate was significantly different between two groups (P<0.05). Conclusion Electroacupuncture combining Tibolone has a better effect than only Tibolone on menopausal affective disorders.%目的 观察电针联合选择性雌激素受体调节剂(替勃龙)治疗绝经期情感障碍的疗效.方法 将已绝经并伴有情感障碍的患者40例按就诊顺序随机分为2组,每组20例.电针联合替勃龙治疗组:电针,4次/周,替勃龙(每片2.5 mg)1片/隔日.单纯替勃龙对照组:替勃龙(每片2.5mg)1片/隔日.治疗周期为4周.治疗前和治疗后各评价1次,应用汉密尔顿抑郁量表(HAMD)评价抑郁程度.结果 本组临床观察显示治疗组与对照组治疗后HAMD评分比较差异有显著性(P<0.05),2组之间总有效率差异有显著性(P<0.05).结论 电针联合替勃龙治疗绝经期情感障明显优于单纯替勃龙.

  11. Climatic and basin factors affecting the flood frequency curve: PART I – A simple sensitivity analysis based on the continuous simulation approach

    Directory of Open Access Journals (Sweden)

    A. M. Hashemi

    2000-01-01

    physical mechanism through which their influence is exercised. However, perturbations to the parameters of the linear routing component affect only the unstandardised ffc. In Franchini et al. (2000, the sensitivity analysis of the model parameters has been assessed through an analysis of variance (ANOVA of the results obtained from a formal experimental design, where all the parameters are allowed to vary simultaneously, thus providing deeper insight into the interactions between the different factors. This approach allows a wider range of climatic and basin conditions to be analysed and reinforces the results presented in this paper, which provide valuable new insight into the climatic and basin factors controlling the ffc. Keywords: stochastic rainfall model; rainfall runoff model; simulation; derived distribution; flood frequency; sensitivity analysis

  12. Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ERα-positive breast carcinomas

    OpenAIRE

    Muñoz-de-Toro, Mónica; Durando, Milena; Beldoménico, Pablo M; Beldoménico, Horacio R; Kass, Laura; García, Silvia R; Luque, Enrique H

    2006-01-01

    Introduction Breast cancer is the most frequent malignant disease in women. Exposure to estrogens throughout a woman's life is a risk factor for the development of breast cancer. Organochlorine compounds (OCCs), such as pesticides and polychlorinated biphenyls, are persistent lipophilic chemicals identified as endocrine disruptors, mainly with estrogenic effects. To test the hypothesis that the amount and quality of organochlorine residues in adipose tissue adjacent to breast carcinoma affect...

  13. Purified estrogen receptor enhances in vitro transcription.

    Science.gov (United States)

    Nigro, V; Molinari, A M; Armetta, I; de Falco, A; Abbondanza, C; Medici, N; Puca, G A

    1992-07-31

    An in vitro transcription system was developed to investigate the mechanisms of gene regulation by the estrogen receptor (ER). ER purified from calf uterus was highly active in enhancing RNA transcription from a template DNA containing estrogen response elements (EREs) upstream from a minimal promoter. Under the conditions employed, no addition of tissue specific factors was required and both estrogen or antiestrogens were ineffective. The stimulation of transcription correlated with the copy number of EREs in the template. The addition of competitor ERE oligonucleotides specifically inhibited the ER-induced transcription. We suggest that the ER may be involved in the formation of the stable initiation complex. PMID:1497666

  14. CITED2 modulates estrogen receptor transcriptional activity in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lau, Wen Min; Doucet, Michele; Huang, David; Weber, Kristy L.; Kominsky, Scott L., E-mail: kominsc@jhmi.edu

    2013-07-26

    Highlights: •The effects of elevated CITED2 on ER function in breast cancer cells are examined. •CITED2 enhances cell growth in the absence of estrogen and presence of tamoxifen. •CITED2 functions as a transcriptional co-activator of ER in breast cancer cells. -- Abstract: Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a member of the CITED family of non-DNA binding transcriptional co-activators of the p300/CBP-mediated transcription complex. Previously, we identified CITED2 as being overexpressed in human breast tumors relative to normal mammary epithelium. Upon further investigation within the estrogen receptor (ER)-positive subset of these breast tumor samples, we found that CITED2 mRNA expression was elevated in those associated with poor survival. In light of this observation, we investigated the effect of elevated CITED2 levels on ER function. While ectopic overexpression of CITED2 in three ER-positive breast cancer cell lines (MCF-7, T47D, and CAMA-1) did not alter cell proliferation in complete media, growth was markedly enhanced in the absence of exogenous estrogen. Correspondingly, cells overexpressing CITED2 demonstrated reduced sensitivity to the growth inhibitory effects of the selective estrogen receptor modulator, 4-hydroxytamoxifen. Subsequent studies revealed that basal ER transcriptional activity was elevated in CITED2-overexpressing cells and was further increased upon the addition of estrogen. Similarly, basal and estrogen-induced expression of the ER-regulated genes trefoil factor 1 (TFF1) and progesterone receptor (PGR) was higher in cells overexpressing CITED2. Concordant with this observation, ChIP analysis revealed higher basal levels of CITED2 localized to the TFF-1 and PGR promoters in cells with ectopic overexpression of CITED2, and these levels were elevated further in response to estrogen stimulation. Taken together, these data indicate that CITED2 functions as a transcriptional co

  15. CITED2 modulates estrogen receptor transcriptional activity in breast cancer cells

    International Nuclear Information System (INIS)

    Highlights: •The effects of elevated CITED2 on ER function in breast cancer cells are examined. •CITED2 enhances cell growth in the absence of estrogen and presence of tamoxifen. •CITED2 functions as a transcriptional co-activator of ER in breast cancer cells. -- Abstract: Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a member of the CITED family of non-DNA binding transcriptional co-activators of the p300/CBP-mediated transcription complex. Previously, we identified CITED2 as being overexpressed in human breast tumors relative to normal mammary epithelium. Upon further investigation within the estrogen receptor (ER)-positive subset of these breast tumor samples, we found that CITED2 mRNA expression was elevated in those associated with poor survival. In light of this observation, we investigated the effect of elevated CITED2 levels on ER function. While ectopic overexpression of CITED2 in three ER-positive breast cancer cell lines (MCF-7, T47D, and CAMA-1) did not alter cell proliferation in complete media, growth was markedly enhanced in the absence of exogenous estrogen. Correspondingly, cells overexpressing CITED2 demonstrated reduced sensitivity to the growth inhibitory effects of the selective estrogen receptor modulator, 4-hydroxytamoxifen. Subsequent studies revealed that basal ER transcriptional activity was elevated in CITED2-overexpressing cells and was further increased upon the addition of estrogen. Similarly, basal and estrogen-induced expression of the ER-regulated genes trefoil factor 1 (TFF1) and progesterone receptor (PGR) was higher in cells overexpressing CITED2. Concordant with this observation, ChIP analysis revealed higher basal levels of CITED2 localized to the TFF-1 and PGR promoters in cells with ectopic overexpression of CITED2, and these levels were elevated further in response to estrogen stimulation. Taken together, these data indicate that CITED2 functions as a transcriptional co

  16. Duration of estrogen deprivation, not chronological age, prevents estrogen's ability to enhance hippocampal synaptic physiology

    OpenAIRE

    Smith, Caroline C.; Vedder, Lindsey C.; Nelson, Amy R.; Bredemann, Teruko M.; McMahon, Lori L.

    2010-01-01

    Whether estrogen replacement is beneficial to cognitive health is controversial. Some studies have shown that estrogen replacement therapy (ERT) relieves memory impairment associated with menopause in women, whereas others suggest that estrogen not only is incapable of providing a benefit, but actually can be detrimental. One possible explanation for this discrepancy in study findings could be the varying time after menopause at which ERT is initiated. It has been proposed that a critical per...

  17. Effects of estrogen and tibolone on bladder histology and estrogen receptors in rats

    Institute of Scientific and Technical Information of China (English)

    YANG Xin; LI Ya-zhen; MAO Zhuo; GU Pei; SHANG Ming

    2009-01-01

    Background Estrogen deficiency causes atrophic changes within the urogenital tract, and is associated with urinary symptoms. The purpose of this study was to investigate the effects of estrogen and tibolone on bladder histology, and the changes of estrogen receptor α and β (ERα and β) protein expression in the detrusor muscle.Methods Forty female rats were separated into four groups of ten each. They received a sham operation (Sham), ovariectomy (Ovx), ovariectomy plus estrogen replacement (Ovx+E), or ovariectomy plus tibolone treatment (Ovx+T). After 12 weeks each rat was anesthetized and the bladders were removed. The bladders' ultra structure, collagen fiber (CF) to smooth muscle(SM) ratio and ER subtypes were studied. Statistical analyses were performed using the one-way analysis of variance test.Results Ovx resulted in significant degeneration in bladder ultra structure; however, estrogen and tibolone reversed those changes. Ovx increased the CF/SM ratio, estrogen and tibolone resulted in an increase. Two estrogen receptors (ERs) were expressed in the bladder detrusor, with ERβ the main subtype. Ovx resulted in up-regulation of ERα and down-regulation of ERβ. With estrogen and tibolone treatment, ERβ showed a significant increase but ERα showed no significant difference compared with Ovx.Conclusions Estrogen deficiency deteriorates bladder ultra structure and histology. Supplementary estrogen can improve bladder function which may be due to inhibition of collagen hyperplasia and increased SM density. ERβ has an important role in mediating estrogen function in the bladder. Tibolone has a mild estrogenic action and has an effect on bladder function and structure to some degree.

  18. Photochemical induced changes of in vitro estrogenic activity of steroid hormones.

    Science.gov (United States)

    Whidbey, Christopher M; Daumit, Kelly E; Nguyen, Thanh-Hoa; Ashworth, Danielle D; Davis, Jasmine C C; Latch, Douglas E

    2012-10-15

    Steroid estrogens are endocrine disrupting contaminants frequently detected in natural waters. Because these estrogens can elicit significant biological responses in aquatic organisms, it is important to study their rates and pathways of degradation in natural waters and to identify whether the transformation products retain biological activity. Photochemical kinetics experiments were conducted under simulated solar light for the hormones 17β-estradiol (E2), 17α-ethinylestradiol (EE2), estrone (E1), equilin (EQ), and equilenin (EQN) under direct and indirect photolysis conditions. All of these hormones were susceptible to direct photodegradation, with half-lives ranging from 40 min for E1 to about 8 h for E2 and EE2. Indirect photolysis experiments with added Suwannee River fulvic acid (SRFA) lead to faster degradation rates for E2, EE2, and EQ. Added SRFA caused slower photodegradation rates for E1 and EQN, indicating that it acts primarily as an inner filter for these analytes. The well-established yeast estrogen screen (YES) was used to measure the estrogenicity of the analytes and their photoproducts. Results of YES assay experiments show that only the direct photolysis of E1 gave estrogenic products. Lumiestrone, the major E1 direct photolysis product, was isolated and characterized. It formed in 53% yield and exhibited moderate estrogenic activity. When photolysed in the presence of perinaphthenone, a potent synthetic sensitizer, E1 degraded via an indirect photolysis pathway and did not produce lumiestrone or any other active products. These results suggest that under typical natural water conditions photochemical reactions of E2, EE2, EQ, and EQN are expected to produce inactive products while E1 will give the estrogenic product lumiestrone in moderate yield. PMID:22877877

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

    Directory of Open Access Journals (Sweden)

    Veenstra Timothy D

    2010-08-01

    Full Text Available Abstract 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.

  20. Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes

    Science.gov (United States)

    Ku, Ming-Chun; Fang, Chieh-Ming; Cheng, Juei-Tang; Liang, Huei-Chen; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Chiao-Chen; Tai, Jung-Hsiang; Chen, Shu-Hui

    2016-06-01

    Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.

  1. Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors.

    Science.gov (United States)

    Peretz, Jackye; Pekosz, Andrew; Lane, Andrew P; Klein, Sabra L

    2016-03-01

    Influenza causes an acute infection characterized by virus replication in respiratory epithelial cells. The severity of influenza and other respiratory diseases changes over the life course and during pregnancy in women, suggesting that sex steroid hormones, such as estrogens, may be involved. Using primary, differentiated human nasal epithelial cell (hNEC) cultures from adult male and female donors, we exposed cultures to the endogenous 17β-estradiol (E2) or select estrogen receptor modulators (SERMs) and then infected cultures with a seasonal influenza A virus (IAV) to determine whether estrogenic signaling could affect the outcome of IAV infection and whether these effects were sex dependent. Estradiol, raloxifene, and bisphenol A decreased IAV titers in hNECs from female, but not male, donors. The estrogenic decrease in viral titer was dependent on the genomic estrogen receptor-2 (ESR2) as neither genomic ESR1 nor nongenomic GPR30 was expressed in hNEC cultures and addition of the genomic ER antagonist ICI 182,780 reversed the antiviral effects of E2. Treatment of hNECs with E2 had no effect on interferon or chemokine secretion but significantly downregulated cell metabolic processes, including genes that encode for zinc finger proteins, many of which contain estrogen response elements in their promoters. These data provide novel insights into the cellular and molecular mechanisms of how natural and synthetic estrogens impact IAV infection in respiratory epithelial cells derived from humans. PMID:26684252

  2. Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes.

    Science.gov (United States)

    Ku, Ming-Chun; Fang, Chieh-Ming; Cheng, Juei-Tang; Liang, Huei-Chen; Wang, Tzu-Fan; Wu, Chih-Hsing; Chen, Chiao-Chen; Tai, Jung-Hsiang; Chen, Shu-Hui

    2016-01-01

    Proteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin. PMID:27353345

  3. Female Mice Avoid Male Odor from the Same Strain via the Vomeronasal System in an Estrogen-Dependent Manner.

    Science.gov (United States)

    Yano, Saori; Sakamoto, Kentaro Q; Habara, Yoshiaki

    2015-11-01

    Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the AOB induced by urine from the cognate males. These results suggest that female mice avoid odor from genetically similar males in an estrogen-dependent manner via the vomeronasal system and the excitability of the mitral cells in the AOB is presumed to be regulated by estrogen. PMID:26377346

  4. Reproducibility of fifteen urinary estrogens and estrogen metabolites over a 2- to 3-year period in premenopausal women

    OpenAIRE

    Eliassen, A. Heather; Ziegler, Regina G.; Rosner, Bernard; Veenstra, Timothy D.; Roman, John M.; Xu, Xia; Hankinson, Susan E

    2009-01-01

    Endogenous estrogens play an integral role in the etiology of breast, endometrial, and possibly ovarian cancer. Estrogen metabolism yields products that are potentially both estrogenic and genotoxic, yet individual metabolic patterns are just beginning to be explored in epidemiologic studies. Within the Nurses’ Health Study II, we examined reproducibility of 15 urinary estrogens and estrogen metabolites (EM) among 110 premenopausal women with three luteal phase urine samples collected over th...

  5. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A;

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1), and their...... ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.¿Results: Higher...

  6. Bioinformatics Analysis of Estrogen-Responsive Genes.

    Science.gov (United States)

    Handel, Adam E

    2016-01-01

    Estrogen is a steroid hormone that plays critical roles in a myriad of intracellular pathways. The expression of many genes is regulated through the steroid hormone receptors ESR1 and ESR2. These bind to DNA and modulate the expression of target genes. Identification of estrogen target genes is greatly facilitated by the use of transcriptomic methods, such as RNA-seq and expression microarrays, and chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq). Combining transcriptomic and ChIP-seq data enables a distinction to be drawn between direct and indirect estrogen target genes. This chapter discusses some methods of identifying estrogen target genes that do not require any expertise in programming languages or complex bioinformatics. PMID:26585125

  7. Voltammetric Determination of Estrogens Based on the Enhancement Effect of Surfactant at Carbon Paste Electrode

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Highly sensitive voltammetric method for the determination of estrogens, based on the enhancement effect of cetyltrimethylammonium bromide (CTAB) has been described. In the presence of CTAB, the oxidation peak currents of estrogens (estradiol, estrone, estriol, estradiol valerate and diethylstilbestrol) at the carbon paste electrode (CPE) increased significantly after open-circuit accumulation. The peak current was proportional to the concentration of estradiol over the range from 5×10-9 to 2.5×10-6 mol\\5L-1. The detection limit was 8×10-10 mol\\5L-1 at 6 min of accumulation. The total amounts of estrogens in the blood serums were determined and the average recovery was 104.92%. Under the conditions used, the electrode process of estradiol was examined and the mechanism for peak current enhancement was also discussed.

  8. Estrogen directly activates AID transcription and function

    OpenAIRE

    Pauklin, Siim; Sernández, Isora V.; Bachmann, Gudrun; Ramiro, Almudena R.; Petersen-Mahrt, Svend K.

    2009-01-01

    The immunological targets of estrogen at the molecular, humoral, and cellular level have been well documented, as has estrogen's role in establishing a gender bias in autoimmunity and cancer. During a healthy immune response, activation-induced deaminase (AID) deaminates cytosines at immunoglobulin (Ig) loci, initiating somatic hypermutation (SHM) and class switch recombination (CSR). Protein levels of nuclear AID are tightly controlled, as unregulated expression can lead to alterations in th...

  9. Metabolic Impact of Estrogen Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Villa P

    2010-01-01

    Full Text Available Menopause is associated with unfavourable changes in the blood lipid profile as well as with a deterioration of glucose tolerance, which may help in increasing the incidence of cardiovascular diseases. In the same way Hormone Replacement Therapy (HRT has different metabolic impact in relationship to the dose of estrogen component, the type of progestin and the route of administration. Most of the studies analyzed the effect of the combined estroprogestin therapy, therefore, the impact of the estrogen component alone isn’t always differentiable but principal results are generally consistent. This review aimes to expound the metabolic impact of the estrogen replacement administration in postmenopausal women. A literature review was conducted to identify all the prospective, the randomized trials and to compare the effects of both low and high-dose therapy and route of administration (oral and transdermal. The results of estrogen replacement therapy on glucose metabolism showed minimal changes and differences among treatments. Some studies showed that neither peroral nor transdermal estradiol replacement therapy induced any negative effects on glucose metabolism. The estrogen substitution increases the rate of apolipoprotein metabolism in various degrees, depending on the type of lipoprotein. At present a considerable data document an increase in HDL and a reduction of LDL cholesterol, following estrogen therapy. Studies have clearly established that the estrogen treatment decreases total plasma cholesterol and increases or maintains plasma triglyceride levels. In conclusion the studies of ERT’s effects on glucose and lipid metabolism are heterogeneous but all together the ERT impact may be considered neutral. However the low doses of estrogen therapy may give some beneficial effects. Above all the treatment may prevent the physiological worsening of the glucose and lipid metabolism in menopause.

  10. Estrogen receptors in mouse testis and sperm

    Czech Academy of Sciences Publication Activity Database

    Dostálová, Pavla; Děd, Lukáš; Pěknicová, Jana

    Montréal: Society for the Study of Reproduction, 2013 - (Suarez, S.). s. 340-340 [SSR 46th Annual Meeteing. Reproduction Health: Nano to Global. 22.07.2013-26.07.2013, Montréal] R&D Projects: GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : Estrogen receptor α * Estrogen receptor β * Reproduction * Spermatogenesis Subject RIV: EB - Genetics ; Molecular Biology

  11. Estrogen receptor β in male mice

    Czech Academy of Sciences Publication Activity Database

    Dostálová, Pavla; Děd, Lukáš; Dorosh, Andriy; Elzeinová, Fatima; Pěknicová, Jana

    Elsinore: International Society of Andrology, 2014. s. 48-48. [18th European Testis Workshop. 13.05.2014-17.05.2014, Elsinore] R&D Projects: GA MŠk(CZ) CZ1.05/1.1.00/02.0109; GA ČR GA14-05547S Institutional support: RVO:86652036 Keywords : estrogen receptor alpha * estrogen receptor beta * spermatozoa Subject RIV: EB - Genetics ; Molecular Biology

  12. Pyrolysis of wastewater biosolids significantly reduces estrogenicity.

    Science.gov (United States)

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

    2016-11-01

    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. PMID:27344259

  13. Estrogenic effects of several BPA analogs in the developing zebrafish brain

    Directory of Open Access Journals (Sweden)

    Joel eCano-Nicolau

    2016-03-01

    Full Text Available Important set of studies have demonstrated the endocrine disrupting activity of Bisphenol A (BPA. The present work aimed at defining estrogenic-like activity of several BPA structural analogs, including BPS, BPF, BPAF, and BPAP, on 4-day or 7-day post-fertilization (dpf zebrafish larva as an in vivo model. We measured the induction level of the estrogen-sensitive marker cyp19a1b gene (Aromatase B, expressed in the brain, using three different in situ/in vivo strategies: 1 Quantification of cyp19a1b transcripts using RT-qPCR in wild type 7-dpf larva brains exposed to bisphenols ; 2 Detection and distribution of cyp19a1b transcripts using in situ hybridization on 7-dpf brain sections (hypothalamus; and 3 Quantification of the cyp19a1b promoter activity in live cyp19a1b-GFP transgenic zebrafish (EASZY assay at 4-dpf larval stage. These three different experimental approaches demonstrated that BPS, BPF or BPAF exposure, similarly to BPA, significantly activates the expression of the estrogenic marker in the brain of developing zebrafish. In vitro experiments using both reporter gene assay in a glial cell context and competitive ligand binding assays strongly suggested that up-regulation of cyp19a1b is largely mediated by the zebrafish estrogen nuclear receptor alpha (zfERα. Importantly, and in contrast to other tested bisphenol A analogs, the bisphenol AP (BPAP did not show estrogenic activity in our model.

  14. A Transcriptional Fingerprint of Estrogen in Human Breast Cancer Predicts Patient Survival

    Directory of Open Access Journals (Sweden)

    Jianjun Yu

    2008-01-01

    Full Text Available Estrogen signaling plays an essential role in breast cancer progression, and estrogen receptor (ER status has long been a marker of hormone responsiveness. However, ER status alone has been an incomplete predictor of endocrine therapy, as some ER+ tumors, nevertheless, have poor prognosis. Here we sought to use expression profiling of ER+ breast cancer cells to screen for a robust estrogen-regulated gene signature that may serve as a better indicator of cancer outcome. We identified 532 estrogen-induced genes and further developed a 73-gene signature that best separated a training set of 286 primary breast carcinomas into prognostic subtypes by stepwise cross-validation. Notably, this signature predicts clinical outcome in over 10 patient cohorts as well as their respective ER+ subcohorts. Further, this signature separates patients who have received endocrine therapy into two prognostic subgroups, suggesting its specificity as a measure of estrogen signaling, and thus hormone sensitivity. The 73-gene signature also provides additional predictive value for patient survival, independent of other clinical parameters, and outperforms other previously reported molecular outcome signatures. Taken together, these data demonstrate the power of using cell culture systems to screen for robust gene signatures of clinical relevance.

  15. Alternate estrogen receptors promote invasion of inflammatory breast cancer cells via non-genomic signaling.

    Directory of Open Access Journals (Sweden)

    Kazufumi Ohshiro

    Full Text Available Although Inflammatory Breast Cancer (IBC is a rare and an aggressive type of locally advanced breast cancer with a generally worst prognosis, little work has been done in identifying the status of non-genomic signaling in the invasiveness of IBC. The present study was performed to explore the status of non-genomic signaling as affected by various estrogenic and anti-estrogenic agents in IBC cell lines SUM149 and SUM190. We have identified the presence of estrogen receptor α (ERα variant, ERα36 in SUM149 and SUM190 cells. This variant as well as ERβ was present in a substantial concentration in IBC cells. The treatment with estradiol (E2, anti-estrogenic agents 4-hydroxytamoxifen and ICI 182780, ERβ specific ligand DPN and GPR30 agonist G1 led to a rapid activation of p-ERK1/2, suggesting the involvement of ERα36, ERβ and GPR30 in the non-genomic signaling pathway in these cells. We also found a substantial increase in the cell migration and invasiveness of SUM149 cells upon the treatment with these ligands. Both basal and ligand-induced migration and invasiveness of SUM149 cells were drastically reduced in the presence of MEK inhibitor U0126, implicating that the phosphorylation of ERK1/2 by MEK is involved in the observed motility and invasiveness of IBC cells. We also provide evidence for the upregulation of p-ERK1/2 through immunostaining in IBC patient samples. These findings suggest a role of non-genomic signaling through the activation of p-ERK1/2 in the hormonal dependence of IBC by a combination of estrogen receptors. These findings only explain the failure of traditional anti-estrogen therapies in ER-positive IBC which induces the non-genomic signaling, but also opens newer avenues for design of modified therapies targeting these estrogen receptors.

  16. Efficiency of removal of compounds with estrogenic activity during wastewater treatment: effects of various removal techniques

    NARCIS (Netherlands)

    M.H. Lamoree; J.G.M. Derksen; S.C. van der Linden; C.A. Uijterlinde; P. de Voogt

    2010-01-01

    The effluents from wastewater treatment plants are known to contribute significantly to the total emission of estrogenic compounds, both from natural and anthropogenic sources, into the aquatic environment. As a logical consequence, occurrence of these compounds affects the quality of our surface wa

  17. Estrogen effects on cartilage and bone changes in models for osteoarthritis

    NARCIS (Netherlands)

    Y.H. Sniekers (Yvonne)

    2009-01-01

    textabstractOsteoarthritis (OA) is a frequently occurring musculoskeletal disorder, leading to joint pain and disability. Although all tissues in the joint can be affected, the focus of this thesis is on changes in bone and cartilage. Evidence from literature suggests that estrogen may have an OA-pr

  18. Estrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Ellervik, Christina; Tybjaerg-Hansen, Anne;

    2007-01-01

    Background- We hypothesized that the estrogen receptor (ESR1) IVS1-397T/C polymorphism affects high-density lipoprotein cholesterol response to hormone replacement therapy and risk of cardiovascular disease (CVD), cancer of reproductive organs, and hip fracture. Methods and Results- We studied cr...

  19. Effect of subacute exposure to lead and estrogen on immature pre-weaning rat leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Villagra, R.; Tchernitchin, N.N.; Tchernitchin, A.N. [Univ. of Chile Medical School, Santiago (Chile)

    1997-02-01

    Lead is an environmental pollutant known to cause damage to human health, affecting specially the central nervous system, reproductive organs, the immune system and kidney. From the perspective or reproduction, lead affects both men and women. Reported effects in women include infertility, miscarriage, pre-eclampsia, pregnancy hypertension and premature delivery. In experimental animals, lead affects female reproductive organs through different mechanisms. The heavy metal may interact at the enzyme level. It may interfere with the action of reproductive hormones at the target organ, modifying the activity of estrogen receptors in the pregnant uterus and inhibiting responses where estrogens play a role. Lead may induce imprinting mechanism, causing persistent changes in uterine estrogen receptors and ovary LH receptors following perinatal exposure. Finally, it may interfere at the level of hypothalamus-pituitary, decreasing pituitary response to growth hormone releasing factor, affecting levels of FSH and LH and increasing blood levels of glucocorticoids, which modify the action of estrogens in the uterus. This study examines the mechanisms of lead-induced interference with female reproductive and immune functions. 33 refs., 2 figs., 2 tabs.

  20. Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.

    Science.gov (United States)

    Eliassen, A Heather; Spiegelman, Donna; Xu, Xia; Keefer, Larry K; Veenstra, Timothy D; Barbieri, Robert L; Willett, Walter C; Hankinson, Susan E; Ziegler, Regina G

    2012-02-01

    Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio

  1. Evidence of a correlation of estrogen receptor level and avian osteoclast estrogen responsiveness.

    Science.gov (United States)

    Pederson, L; Kremer, M; Foged, N T; Winding, B; Ritchie, C; Fitzpatrick, L A; Oursler, M J

    1997-05-01

    Isolated osteoclasts from 5-week-old chickens respond to estradiol treatment in vitro with decreased resorption activity, increased nuclear proto-oncogene expression, and decreased lysosomal enzyme secretion. This study examines osteoclasts from embryonic chickens and egg-laying hens for evidence of estrogen responsiveness. Although osteoclasts from both of these sources express estrogen receptor mRNA and protein, estradiol treatment had no effect on resorption activity. In contrast to the lack of effect on resorption, estradiol treatment for 30 minutes resulted in steady-state mRNA levels of c-fos and c-jun increasing in osteoclasts from embryonic chickens and decreasing in osteoclasts from egg-laying hens. These data suggest that a nuclear proto-oncogene response may not be involved in estradiol-mediated decreased osteoclast resorption activity. To examine the influence of circulating estrogen on osteoclast estrogen responsiveness, 5-week-old chickens were injected with estrogen for 4 days prior to sacrifice. Estradiol treatment of osteoclasts from these chickens did not decrease resorption activity in vitro. Transfection of an estrogen receptor expression vector into osteoclasts from the estradiol-injected chickens and egg-laying hens restored estrogen responsiveness. Osteoclasts from 5-week-old chickens and estradiol treated 5-week-old chickens transfected with the estrogen receptor expression vector contained significantly higher levels of estrogen receptor protein and responded to estradiol treatment by decreasing secretion of cathepsins B and L and tartrate-resistant acid phosphatase. In contrast, osteoclasts from embryonic chickens, egg-laying hens, and estradiol-treated 5-week-old chickens either untransfected or transfected with an empty expression vector did not respond similarly. These data suggest that modulation of osteoclast estrogen responsiveness may be controlled by changes in the osteoclast estrogen receptor levels. PMID:9144340

  2. Sensitivity of the Autonomic Nervous System to Visual and Auditory Affect Across Social and Non-Social Domains in Williams Syndrome

    Science.gov (United States)

    Järvinen, Anna; Dering, Benjamin; Neumann, Dirk; Ng, Rowena; Crivelli, Davide; Grichanik, Mark; Korenberg, Julie R.; Bellugi, Ursula

    2012-01-01

    Although individuals with Williams syndrome (WS) typically demonstrate an increased appetitive social drive, their social profile is characterized by dissociations, including socially fearless behavior coupled with anxiousness, and distinct patterns of “peaks and valleys” of ability. The aim of this study was to compare the processing of social and non-social visually and aurally presented affective stimuli, at the levels of behavior and autonomic nervous system (ANS) responsivity, in individuals with WS contrasted with a typically developing (TD) group, with the view of elucidating the highly sociable and emotionally sensitive predisposition noted in WS. Behavioral findings supported previous studies of enhanced competence in processing social over non-social stimuli by individuals with WS; however, the patterns of ANS functioning underlying the behavioral performance revealed a surprising profile previously undocumented in WS. Specifically, increased heart rate (HR) reactivity, and a failure for electrodermal activity to habituate were found in individuals with WS contrasted with the TD group, predominantly in response to visual social affective stimuli. Within the auditory domain, greater arousal linked to variation in heart beat period was observed in relation to music stimuli in individuals with WS. Taken together, the findings suggest that the pattern of ANS response in WS is more complex than previously noted, with increased arousal to face and music stimuli potentially underpinning the heightened behavioral emotionality to such stimuli. The lack of habituation may underlie the increased affiliation and attraction to faces characterizing individuals with WS. Future research directions are suggested. PMID:23049519

  3. Sensitivity of the autonomic nervous system to visual and auditory affect across social and non-social domains in Williams syndrome

    Directory of Open Access Journals (Sweden)

    AnnaMaariaJärvinen

    2012-09-01

    Full Text Available Although individuals with Williams syndrome (WS typically demonstrate an increased appetitive social drive, their social profile is characterized by dissociations, including socially fearless behavior coupled with anxiousness, and distinct patterns of “peaks and valleys” of ability. The aim of this study was to compare the processing of social and non-social visually and aurally presented affective stimuli, at the levels of behavior and autonomic nervous system (ANS responsivity, in individuals with WS contrasted with a typically developing (TD group, with the view of elucidating the highly sociable and emotionally sensitive predisposition noted in WS. Behavioral findings supported previous studies of enhanced competence in processing social over non-social stimuli by individuals with WS; however, the patterns of ANS functioning underlying the behavioral performance revealed a surprising profile previously undocumented in WS. Specifically, increased heart rate (HR reactivity, and a failure for electrodermal activity (EDA to habituate were found in individuals with WS contrasted with the TD group, predominantly in response to visual social-affective stimuli. Within the auditory domain, greater arousal linked to variation in heart beat period was observed in relation to music stimuli in individuals with WS. Taken together, the findings suggest that the pattern of ANS response in WS is more complex than previously noted, with increased arousal to face and music stimuli potentially underpinning the heightened behavioral emotionality to such stimuli. The lack of habituation may underlie the increased affiliation and attraction to faces characterizing individuals with WS. Future research directions are suggested.

  4. Neuronal differentiation dictates estrogen-dependent survival and ERK1/2 kinetic by means of caveolin-1.

    Directory of Open Access Journals (Sweden)

    Floriana Volpicelli

    Full Text Available Estrogens promote a plethora of effects in the CNS that profoundly affect both its development and mature functions and are able to influence proliferation, differentiation, survival and neurotransmission. The biological effects of estrogens are cell-context specific and also depend on differentiation and/or proliferation status in a given cell type. Furthermore, estrogens activate ERK1/2 in a variety of cellular types. Here, we investigated whether ERK1/2 activation might be influenced by estrogens stimulation according to the differentiation status and the molecular mechanisms underling this phenomenon. ERK1/2 exert an opposing role on survival and death, as well as on proliferation and differentiation depending on different kinetics of phosphorylation. Hence we report that mesencephalic primary cultures and the immortalized cell line mes-c-myc A1 express estrogen receptor α and activate ERK1/2 upon E2 stimulation. Interestingly, following the arrest of proliferation and the onset of differentiation, we observe a change in the kinetic of ERKs phosphorylation induced by estrogens stimulation. Moreover, caveolin-1, a main constituent of caveolae, endogenously expressed and co-localized with ER-α on plasma membrane, is consistently up-regulated following differentiation and cell growth arrest. In addition, we demonstrate that siRNA-induced caveolin-1 down-regulation or disruption by means of ß-cyclodextrin treatment changes ERK1/2 phosphorylation in response to estrogens stimulation. Finally, caveolin-1 down-regulation abolishes estrogens-dependent survival of neurons. Thus, caveolin-1 appears to be an important player in mediating, at least, some of the non-genomic action of estrogens in neurons, in particular ERK1/2 kinetics of activation and survival.

  5. Effects on the reproductive system in domestic dowl (Gallus domesticus) after embryonic exposure to estrogenic substances

    OpenAIRE

    Hermansson, Alexandra

    2007-01-01

    Environmental pollutants with estrogenic activity have a potential to disrupt oestrogen-dependent developmental processes. Thus, the aim of this thesis was to investigated how embryonic exposure to the estrogenic pollutants EE2 (17 alpha- ethynyloestradiol) and o,p´-DDT (1-[2-chlorophenyl]-1-[4-chlorophenyl]-2,2,2-trichloro-ethane) affects the reproductive system in the domestic hen (Gallus domesticus). Hens exposed in ovo to 20 or 60 ng EE2/g egg or 37 or 75 micro g o,p´-DDT/g egg produced a...

  6. The role of estrogen in bipolar disorder, a review

    DEFF Research Database (Denmark)

    Meinhard, Ninja; Kessing, Lars Vedel; Vinberg, Maj

    2014-01-01

    estrogen levels and women with bipolar disorder including studies of the anti manic effects of the selective estrogen receptor modulator tamoxifen. METHOD: A systematically literature search on PubMed was conducted: two studies regarding the connection between serum estrogen levels and women with bipolar...... hormones, e.g. estrogen, are fluctuating and particularly postpartum there is a steep fall in the levels of serum estrogen. The role of estrogen in women with bipolar disorder is, however, not fully understood. AIM: The main objective of this review is to evaluate the possible relation between serum...... disorder were identified. Furthermore, four studies were found concerning the antimanic effects of tamoxifen. RESULTS: Both studies in the estrogen studies showed very low levels of estrogen in women with postpartum psychosis and significant improvement of symptoms after treatment with estrogen. The four...

  7. Pathway-based approaches for assessment of real-time exposure to an estrogenic wastewater treatment plant effluent on fathead minnow reproduction

    Science.gov (United States)

    Wastewater treatment plant (WWTP) effluents are known contributors of chemical mixtures into the environment. Of particular concern are endocrine-disrupting compounds, such as estrogens, that can affect hypothalamic-pituitary-gonadal axis function in exposed organisms. The presen...

  8. Estrogen and the selective estrogen receptor modulator (SERM) protection against cell death in estrogen receptor alpha and beta expressing U2OS cells

    OpenAIRE

    Kallio, Anu; Guo, Tao; Lamminen, Elisa; Seppänen, Jani; Kangas, Lauri; Väänänen, H Kalervo; Härkönen, Pirkko

    2008-01-01

    Estrogen and the selective estrogen receptor modulator (SERM) protection against cell death in estrogen receptor alpha and beta expressing U2OS cells SWEDEN (Kallio, Anu) SWEDEN Received: 2007-12-01 Revised: 2008-03-12 Accepted: 2008-03-12

  9. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

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

    International Nuclear Information System (INIS)

    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 (E2) 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. Estrogenic effects of fusarielins in human breast cancer cell lines

    DEFF Research Database (Denmark)

    Søndergaard, Teis; G. Klitgaard, Louise; Purup, Stig;

    2012-01-01

    from fungi that bind to the estrogen receptors and induce an estrogenic response in targeted cells. All four tested fusarielins stimulate MCF-7 cell proliferation with fusarielin H as the most potent, able to stimulate cell proliferation 4-fold in a resazurin metabolism assay at 25 μM. MDA-MB-231 cells...... without the estrogen receptor-α and MCF-10a cells without estrogen receptors were not stimulated by fusarielins. Furthermore, the stimulation was prevented in MCF-7 cells when fusarielins were incubated in the presence of the estrogen receptor antagonist fulvestrant. These observations suggest that...... fusarielins bind to the estrogen receptor and act as weak mycoestrogens....

  12. Estrogen and progesterone receptors in primary cutaneous melanoma.

    Science.gov (United States)

    Ellis, D L; Wheeland, R G; Solomon, H

    1985-01-01

    Using a variety of techniques, estrogen and progesterone receptors have previously been identified in variable percentages of malignant melanomas. We examined 10 primary superficial spreading melanomas (SSM) with a fluorescent hormone-binding technique for estrogen and progesterone cytoplasmic receptors. Of these 6 SSM were markedly positive for estrogen and progesterone binding. Patients with dysplastic nevus syndrome (DNS) or a family history of DNS were markedly positive for estrogen and progesterone binding. A single patient with lentigo maligna and another patient with lentigo maligna melanoma were negative for estrogen and progesterone binding. None of the 21 control intradermal nevi examined for estrogen and progesterone binding exhibited marked positivity. PMID:3965520

  13. Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

    Science.gov (United States)

    Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

    2008-01-01

    Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

  14. Estrogen receptor-mediated neuroprotection: The role of the Alzheimer’s disease-related gene seladin-1

    Directory of Open Access Journals (Sweden)

    Alessandro Peri

    2008-09-01

    Full Text Available Alessandro Peri, Mario SerioDepartment of Clinical Physiopathology, Endocrine Unit, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe, University of Florence, Florence, ItalyAbstract: Experimental evidence supports a protective role of estrogen in the brain. According to the fact that Alzheimer’s disease (AD is more common in postmenopausal women, estrogen treatment has been proposed. However, there is no general consensus on the beneficial effect of estrogen or selective estrogen receptor modulators in preventing or treating AD. It has to be said that several factors may markedly affect the efficacy of the treatment. A few years ago, the seladin-1 gene (for selective Alzheimer’s disease indicator-1 has been isolated and found to be down-regulated in brain regions affected by AD. Seladin-1 has been found to be identical to the gene encoding the enzyme 3-beta-hydroxysterol delta-24-reductase, involved in the cholesterol biosynthetic pathway, which confers protection against β-amyloid-mediated toxicity and from oxidative stress, and is an effective inhibitor of caspase-3 activity, a key mediator of apoptosis. Interestingly, we found earlier that the expression of this gene is up-regulated by estrogen. Furthermore, our very recent data support the hypothesis that seladin-1 is a mediator of the neuroprotective effects of estrogen. This review will summarize the current knowledge regarding the neuroprotective effects of seladin-1 and the relationship between this protein and estrogen.Keywords: seladin-1, DHCR24, estrogen, brain, Alzheimer’s disease

  15. Sex differences in estrogen receptor promoter expression in the area postrema

    Institute of Scientific and Technical Information of China (English)

    Chunxiao Zhang; Tomohiro Hamada

    2013-01-01

    Estrogen receptor α is widely distributed in the rat brain, but the tissue- or target-specificity of the estrogen receptor α gene promoters remains unknown. In the present study, we used transgenic rats expressing enhanced green fluorescent protein under the control of the estrogen receptor α 0/B promoter to examine expression driven by this promoter in two significant nuclei that regulate cardiovascular activity, the area postrema and the nucleus tractus solitarius. Immunohistochemistry showed that enhanced green fluorescent protein-labeled cells were distributed in the area postrema and the nucleus tractus solitarius of both female and male transgenic rats, and a neural network of enhanced green fluorescent protein-positive fibers was seen between the area postrema and the nucleus tractus solitarius. The number of enhanced green fluorescent protein-labeled cells in the area postrema of female rats was significantly higher than in the males, but no significant difference was found in the number of enhanced green fluorescent protein-labeled cells in the nucleus tractus solitarius. The sex differences in the number of enhanced green fluorescent protein-labeled cells in the area postrema was not affected after ovariectomy or 17β-estradiol benzoate treatment in adult rats. Our results suggest that the effects of estrogen in the area postrema are related to the expression of estrogen receptor α under the control of the 0/B promoter, and changes in the sex hormone environment in the adult period do not affect estrogen receptor α expression in the area postrema or the nucleus tractus solitarius.

  16. Effects of treadmill exercise training on cerebellar estrogen and estrogen receptors, serum estrogen, and motor coordination performance of ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Saidah Rauf

    2015-06-01

    Full Text Available Objective(s: The present study aims at examining the motor coordination performance, serum and cerebellar estrogen, as well as ERβ levels, of ovariectomized rats (as menopausal model following regular exercise. Materials and Methods:Ten female Sprague Dawley ratsaged 12 weeks old were randomly divided into two groups; all of which underwent ovariectomy. The first group was treated with regular exercise of moderate intensity, in which the rats were trained to run on a treadmill for 60 min per day for 12 weeks. The second group served as control. Rotarod test was carried out before and after exercise treatment. All rats were euthanized thereafter, and blood and cerebellums of the rats were collected. The serum and cerebellar estrogen as well as cerebellar ERβ levels were measured using ELISA assays. Results: The number of falls in the rotarod task of the exercise group was significantly lower than that of control group. The cerebellar estrogen level of the exercise group was significantly higher than that of control group. Accordingly, there was a significantly negative correlation between the number of falls and cerebellar estrogen level in the exercise group. Conclusion:The present study shows that a lengthy period of regular exercise improves the cerebellar estrogen level and motor coordination performance in ovariectomized rats.

  17. Estrogen Receptor β Activation Rapidly Modulates Male Sexual Motivation through the Transactivation of Metabotropic Glutamate Receptor 1a.

    Science.gov (United States)

    Seredynski, Aurore L; Balthazart, Jacques; Ball, Gregory F; Cornil, Charlotte A

    2015-09-23

    In addition to the transcriptional activity of their liganded nuclear receptors, estrogens, such as estradiol (E2), modulate cell functions, and consequently physiology and behavior, within minutes through membrane-initiated events. The membrane-associated receptors (mERs) underlying the acute effects of estrogens on behavior have mostly been documented in females where active estrogens are thought to be of ovarian origin. We determined here, by acute intracerebroventricular injections of specific agonists and antagonists, the type(s) of mERs that modulate rapid effects of brain-derived estrogens on sexual motivation in male Japanese quail. Brain aromatase blockade acutely inhibited sexual motivation. Diarylpropionitrile (DPN), an estrogen receptor β (ERβ)-specific agonist, and to a lesser extent 17α-estradiol, possibly acting through ER-X, prevented this effect. In contrast, drugs targeting ERα (PPT and MPP), GPR30 (G1 and G15), and the Gq-mER (STX) did not affect sexual motivation. The mGluR1a antagonist LY367385 significantly inhibited sexual motivation but mGluR2/3 and mGluR5 antagonists were ineffective. LY367385 also blocked the behavioral restoration induced by E2 or DPN, providing functional evidence that ERβ interacts with metabotropic glutamate receptor 1a (mGluR1a) signaling to acutely regulate male sexual motivation. Together these results show that ERβ plays a key role in sexual behavior regulation and the recently uncovered cooperation between mERs and mGluRs is functional in males where it mediates the acute effects of estrogens produced centrally in response to social stimuli. The presence of an ER-mGluR interaction in birds suggests that this mechanism emerged relatively early in vertebrate history and is well conserved. Significance statement: The membrane-associated receptors underlying the acute effects of estrogens on behavior have mostly been documented in females, where active estrogens are thought to be of ovarian origin. Using acute

  18. Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

    Energy Technology Data Exchange (ETDEWEB)

    Bugel, Sean M., E-mail: Sean.Bugel@oregonstate.edu [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Bonventre, Josephine A. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); White, Lori A. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States); Tanguay, Robert L. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Cooper, Keith R. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States)

    2014-07-01

    Highlights: • Reproductive biomarker genes in Newark Bay killifish are desensitized to estrogen. • Gene desensitization indicates pre-transcriptional effects on estrogen signaling. • Desensitization does not have a metabolic or epigenetic basis (gene methylation). • Modulation of vitellogenin and choriogenin genes correlates with reproductive impacts. • Choriogenin L appears less prone to false negatives and may be a sensitive biomarker. - Abstract: Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen-responsive genes in this model population. First, a dose–response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β-estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β-estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi-chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng

  19. Maternal and neonatal FTO rs9939609 polymorphism affect insulin sensitivity markers and lipoprotein profile at birth in appropriate-for-gestational-age term neonates.

    Science.gov (United States)

    Gesteiro, Eva; Sánchez-Muniz, Francisco J; Ortega-Azorín, Carolina; Guillén, Marisa; Corella, Dolores; Bastida, Sara

    2016-06-01

    The influence of maternal fat mass and obesity (FTO) gene polymorphism on neonatal insulin sensitivity/resistance biomarkers and lipoprotein profile has not been tested. The study aimed to assess the association between the FTO rs9939609 polymorphism in mother-neonate couples and neonatal anthropometrical measurements, insulin sensitivity/resistance, and lipid and lipoprotein concentrations at birth. Fifty-three term, appropriate-for-gestational-age, Caucasian newborns together with their respective mothers participated in a cross-sectional study. Sixty-six percent of mothers and neonates carried the A allele (being AA or AT). TT mothers gained less weight during pregnancy, but non-significant maternal gene influence was found for neonatal bodyweight, body mass index, or ponderal index. Neonates from AA + AT mothers showed lower glucose, insulin, and homeostatic model assessment insulin resistance (HOMA-IR) but higher homeostatic model assessment insulin sensitivity (HOMA-IS) and homocysteine than neonates whose mothers were TT. AA + AT neonates had higher insulin and HOMA-IR than TT. The genotype neonatal × maternal association was tested in the following four groups of neonates: TT neonates × TT mothers (nTT × mTT), TT neonates × AA + AT mothers (nTT × mAA + AT), AA + AT neonates × TT mothers (nAA + AT × mTT), and AA + AT neonates × AA + AT mothers (nAA + AT × mAA + AT). Non-significant interactions between neonatal and maternal alleles were found for any parameter tested. However, maternal alleles affected significantly glucose, insulin, HOMA-IR, and homocysteine while neonatal alleles the arylesterase activity. Most significant differences were found between nATT + AA × mTT and nATT + AA × mAA + AT. Glycemia, insulinemia, and HOMA-IR were lower, while the Mediterranean diet adherence (MDA) was higher in the mAA + AT vs. mTT whose children were AA + AT. This dietary fact seems to counterbalance the potential negative effect on glucose homeostasis of

  20. Is Estrogen a Therapeutic Target for Glaucoma?

    Science.gov (United States)

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

    2016-01-01

    This article's objective is to provide an overview of the association between estrogen and glaucoma. A literature synthesis was conducted of articles published in peer-reviewed journals screened through May 5, 2015, using the PubMed database. Keywords used were "estrogen and glaucoma," "reproductive factors and glaucoma," and "estrogen, nitric oxide and eye." Forty-three journal articles were included. Results indicated that 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 glaucoma (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 years 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 postmenopausal 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

  1. High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish.

    Science.gov (United States)

    Green, Jon M; Metz, Jeremy; Lee, Okhyun; Trznadel, Maciej; Takesono, Aya; Brown, A Ross; Owen, Stewart F; Kudoh, Tetsuhiro; Tyler, Charles R

    2016-06-21

    Rapid embryogenesis, together with genetic similarities with mammals, and the desire to reduce mammalian testing, are major incentives for using the zebrafish model in chemical screening and testing. Transgenic zebrafish, engineered for identifying target gene expression through expression of fluorophores, have considerable potential for both high-content and high-throughput testing of chemicals for endocrine activity. Here we generated an estrogen responsive transgenic zebrafish model in a pigment-free "Casper" phenotype, facilitating identification of target tissues and quantification of these responses in whole intact fish. Using the ERE-GFP-Casper model we show chemical type and concentration dependence for green fluorescent protein (GFP) induction and both spatial and temporal responses for different environmental estrogens tested. We also developed a semiautomated (ArrayScan) imaging and image analysis system that we applied to quantify whole body fluorescence responses for a range of different estrogenic chemicals in the new transgenic zebrafish model. The zebrafish model developed provides a sensitive and highly integrative system for identifying estrogenic chemicals, their target tissues and effect concentrations for exposures in real time and across different life stages. It thus has application for chemical screening to better direct health effects analysis of environmental estrogens and for investigating the functional roles of estrogens in vertebrates. PMID:27227508

  2. Estrogenicity of glabridin in Ishikawa cells.

    Directory of Open Access Journals (Sweden)

    Melissa Su Wei Poh

    Full Text Available 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.

  3. Estrogenicity of glabridin in Ishikawa cells.

    Science.gov (United States)

    Su Wei Poh, Melissa; Voon Chen Yong, Phelim; Viseswaran, Navaratnam; Chia, Yoke Yin

    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

  4. TRIM5α and TRIMCyp form apparent hexamers and their multimeric state is not affected by exposure to restriction-sensitive viruses or by treatment with pharmacological inhibitors

    Directory of Open Access Journals (Sweden)

    Berthoux Lionel

    2009-11-01

    Full Text Available Abstract Proteins of the TRIM5 family, such as TRIM5α and the related TRIMCyp, are cytoplasmic factors that can inhibit incoming retroviruses. This type of restriction requires a direct interaction between TRIM5 proteins and capsid proteins that are part of mature, intact retroviral cores. In such cores, capsids are arranged as hexameric units. Multiple lines of evidence imply that TRIM5 proteins themselves interact with retroviral cores as multimers. Accordingly, stabilization by crosslinking agents has revealed that TRIM5α and TRIMCyp are present as trimers in mammalian cells. We report here that TRIM5 proteins seem to form dimers, trimers, hexamers and multimers of higher complexity in mammalian cells. The hexameric form in particular seems to be the most abundant multimer. Multimerization did not involve disulfide bridges and was not affected by infection with restriction-sensitive viruses or by treatment with the known TRIM5 inhibitors arsenic trioxide, MG132 and cyclosporine A. We conclude that TRIM5 multimerization results from more than one protein-protein interface and that it is seemingly not triggered by contact with retroviral cores.

  5. Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary

    Directory of Open Access Journals (Sweden)

    Wood Charles E

    2008-06-01

    Full Text Available Abstract There has been considerable investigation of the potential for soyfoods to reduce risk of cancer, and in particular cancer of the breast. Most interest in this relationship is because soyfoods are essentially a unique dietary source of isoflavones, compounds which bind to estrogen receptors and exhibit weak estrogen-like effects under certain experimental conditions. In recent years the relationship between soyfoods and breast cancer has become controversial because of concerns – based mostly on in vitro and rodent data – that isoflavones may stimulate the growth of existing estrogen-sensitive breast tumors. This controversy carries considerable public health significance because of the increasing popularity of soyfoods and the commercial availability of isoflavone supplements. In this analysis and commentary we attempt to outline current concerns regarding the estrogen-like effects of isoflavones in the breast focusing primarily on the clinical trial data and place these concerns in the context of recent evidence regarding estrogen therapy use in postmenopausal women. Overall, there is little clinical evidence to suggest that isoflavones will increase breast cancer risk in healthy women or worsen the prognosis of breast cancer patients. Although relatively limited research has been conducted, and the clinical trials often involved small numbers of subjects, there is no evidence that isoflavone intake increases breast tissue density in pre- or postmenopausal women or increases breast cell proliferation in postmenopausal women with or without a history of breast cancer. The epidemiologic data are generally consistent with the clinical data, showing no indication of increased risk. Furthermore, these clinical and epidemiologic data are consistent with what appears to be a low overall breast cancer risk associated with pharmacologic unopposed estrogen exposure in postmenopausal women. While more research is required to definitively

  6. Estrogen regulation of TRPM8 expression in breast cancer cells

    International Nuclear Information System (INIS)

    The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer. RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques. TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E2, 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca2+ entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER+) status of the tumours. Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha

  7. Estrogen regulation of TRPM8 expression in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Sevestre Henri

    2010-05-01

    Full Text Available Abstract Background The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8 is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha in breast cancer. Methods RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques. Results TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E2, 10 nM increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca2+ entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER+ status of the tumours. Conclusion Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha.

  8. Determination of estrogens and estrogenic activities in water from three rivers in Tianjin, China

    Institute of Scientific and Technical Information of China (English)

    Kaifeng Rao; Bingli Lei; Na Li; Mei Ma; Zijian Wang

    2013-01-01

    Studies on estrogenic disrupting compounds (EDCs) occurrence and identification of main responsible compounds in river water discharged into the sea are of significance.In the present research,we screened estrogenic activities of 10 river water samples from 3 main rivers discharged into Bohai Sea in Tianjin using a recombinant two-hybrid yeast assay and chemical analysis by gas chromatography-mass spectrometry.All sample extracts induced significant estrogenic activity,with 17β-estradiol equivalents (EEQ)of raw water ranging from 5.72 to 59.06 ng/L.Six most concerned EDCs in the river water samples including estrone,17β-estradiol,17α-ethinylestradiol,estriol,diethylstilbestrol and estradiol valerate were determined,with their concentrations up to 50.70,31.40,24.40,37.20,2.56,and 8.47 ng/L,respectively.Through causality analysis by comparing the EEQ values of yeast assay and chemical analysis,17α-ethinylestradiol and 17ββ-estradiol were identified as the main contributors to the estrogenic effects of the river samples,accounting for the whole estrogenic activities (62.99% to 185.66%),and estrogen antagonistic compounds might presented in the heavy polluted water samples.The proposed approach using both chemical analysis and bioassay could be used for identification and evaluation of the estrogenic activity of EDCs in river water.

  9. Estrogen/estrogen receptor alpha signaling in mouse posterofrontal cranial suture fusion.

    Directory of Open Access Journals (Sweden)

    Aaron W James

    Full Text Available BACKGROUND: While premature suture fusion, or craniosynostosis, is a relatively common condition, the cause is often unknown. Estrogens are associated with growth plate fusion of endochondral bones. In the following study, we explore the previously unknown significance of estrogen/estrogen receptor signaling in cranial suture biology. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, estrogen receptor (ER expression was examined in physiologically fusing (posterofrontal and patent (sagittal mouse cranial sutures by quantitative RT-PCR. Next, the cranial suture phenotype of ER alpha and ER beta knockout (alphaERKO, betaERKO mice was studied. Subsequently, mouse suture-derived mesenchymal cells (SMCs were isolated; the effects of 17-beta estradiol or the estrogen antagonist Fulvestrant on gene expression, osteogenic and chondrogenic differentiation were examined in vitro. Finally, in vivo experiments were performed in which Fulvestrant was administered subcutaneously to the mouse calvaria. Results showed that increased ERalpha but not ERbeta transcript abundance temporally coincided with posterofrontal suture fusion. The alphaERKO but not betaERKO mouse exhibited delayed posterofrontal suture fusion. In vitro, addition of 17-beta estradiol enhanced both osteogenic and chondrogenic differentiation in suture-derived mesenchymal cells, effects reversible by Fulvestrant. Finally, in vivo application of Fulvestrant significantly diminished calvarial osteogenesis, inhibiting suture fusion. CONCLUSIONS/SIGNIFICANCE: Estrogen signaling through ERalpha but not ERbeta is associated with and necessary for normal mouse posterofrontal suture fusion. In vitro studies suggest that estrogens may play a role in osteoblast and/or chondrocyte differentiation within the cranial suture complex.

  10. Sex-dependent influence of endogenous estrogen in pulmonary hypertension

    OpenAIRE

    Mair, Kirsty M.; Wright, Audrey F.; Duggan, Nicholas; Rowlands, David J.; Hussey, Martin J.; Roberts, Sonia; Fullerton, Josephine; Nilsen, Margaret; Loughlin, Lynn; Thomas, Matthew; MacLean, Margaret R.

    2014-01-01

    Rationale: The incidence of pulmonary arterial hypertension (PAH) is greater in women suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males exogenously administered estrogen can protect against PH; however in models that display female susceptibility estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and gender in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Met...

  11. Multicolor Imaging of Bifacial Activities of Estrogens.

    Science.gov (United States)

    Kim, Sung-Bae; Umezawa, Yoshio

    2016-01-01

    The present protocol introduces multicolor imaging of bifacial activities of an estrogen. For the multicolor imaging, the authors fabricated two single-chain probes emitting green or red bioluminescence (named Simer-G and -R, respectively) from click beetle luciferase (CBLuc) green and red: Simer-R consists of the ligand binding domain of estrogen receptor (ER LBD) and the Src homology-2 (SH2) domain of Src, which are sandwiched between split-CBLuc red (CBLuc-R). On the other hand, Simer-G emitting red light consists of the ER LBD and a common consensus sequence of coactivators (LXXLL motif), which are inserted between split-CBLuc green (CBLuc-G). This probe set creates fingerprinting spectra from the characteristic green and red bioluminescence in response to agonistic and antagonistic activities of a ligand of interest. The present protocol further provides a unique methodology to calculate characteristic estrogenicity scores of various ligands from the spectra. PMID:27424902

  12. Phytoestrogens: Plant-derived Estrogenic Compounds

    Directory of Open Access Journals (Sweden)

    Nevzat Konar

    2011-12-01

    Full Text Available Estrogen is a hormone, which is produced in ovary and testis; however, it has many biological effects besides the reproductive system. Phytoestrogens are the compounds, which have estrogen-like structure and activities, taking place in structure of various edible plants at different levels and in different compositions. These compounds attracted notice after the first quarter of 20th century upon they had been associated with infertility seen in some of animals fed with alfalfa, and these compounds have been identified in human-derived biological samples and its effects on health have been taken under study in the recent 30 years. These materials have especially antioxidant role in plants while they have activities in animals and humans as estrogen agonist and antagonists. Based on their chemical structure, they may be gathered under especially isoflavon and lignan groups while some of members of coumestan and stilbene groups are also identified as phytoestrogenic compound.

  13. A new in vitro screening bioassay for the ecotoxicological evaluation of the estrogenic responses of environmental chemicals using roach (Rutilus rutilus) liver explant culture.

    Science.gov (United States)

    Gerbron, Marie; Geraudie, Perrine; Rotchell, Jeanette; Minier, Christophe

    2010-10-01

    There is growing evidence that many chemicals released in the environment are able to disturb the normal endocrinology of organisms affecting the structure and function of their reproductive system. This has prompted the scientific community to develop appropriate testing methods to identify active compounds and elucidate mechanisms of action. Of particular interest are in vitro screening methods that can document the effects of these endocrine disrupting compounds on fish. In this study, an in vitro bioassay was developed in the roach (Rutilus rutilus) for evaluating the estrogenicity or antiestrogenicity potency of environmental pollutants by measuring vitellogenin (VTG) induction in cultured liver explants. The cell viability was assessed by the measurement of nonspecific esterase activity using a fluorescein diacetate hydrolysis assay. Results showed that explants could be cultured for 72 h without any significant loss of activity. Dose-dependent responses have been measured with estrogenic model compounds such as 17-β-estradiol (E2) and 17-α-ethynylestradiol (EE2) or antiestrogenic compounds such as tamoxifen. Lowest observable effective concentrations were 1 nM for E2, 1 nM for EE2, and 100 nM for tamoxifen, showing a good sensitivity of the test system. Estrogenicity of butyl 4-hydroxybenzoate, 4-nonylphenol, and bisphenol A was tested. bisphenol A (100 μM) or butylparaben induced a twofold increase in VTG production when compared with 100 nM E2, whereas this production was only 20% with 100 μM 4-nonylphenol. Overall, this study shows that the bioassay could provide valuable information on endocrine disrupting chemicals including metabolites and mixtures of compounds. PMID:20549626

  14. Prevention of postmenopausal bone loss - effects of alternative administration forms of estrogens, alternative gestagens and calcium addition

    International Nuclear Information System (INIS)

    Calcium metabolism was examined in 133 healthy postmenopausal women every three months during two years of treatment with oral or percutaneous 17β-estradiol combined with different doses of calcium supplementation and/or different gestagens. Bone mineral content measured in the forearm (single photon absorptiometry), in the spine and in the total skeleton (dual photon absorptiometry) was unchanged in all estrogen-treated groups during the two years of treatment, and the responses in the groups with and without calcium supplementation and with different gestagens were not significantly different. Furthermore, the responses were independent of route of administration of the estrogen. Biochemical indices of bone turnover (serum alkaline phosphatase and fasting urinary hydroxyproline/creatinine) decreased highly significantly during estrogen treatment (p<0.001) independent of route of administration of the estrogen, of calcium supplementation, and of gestagen agent. We conclude that estrogen treatment independently of route of administration, prevents postmenopausal bone loss. The gestagen agents used here do not affect calcium metabolism, and calcium supplementation has no additive effect to estrogen therapy. (orig.)

  15. Prevention of postmenopausal bone loss - effects of alternative administration forms of estrogens, alternative gestagens and calcium addition

    Energy Technology Data Exchange (ETDEWEB)

    Riis, B.J.; Christiansen, C.

    1987-02-01

    Calcium metabolism was examined in 133 healthy postmenopausal women every three months during two years of treatment with oral or percutaneous 17..beta..-estradiol combined with different doses of calcium supplementation and/or different gestagens. Bone mineral content measured in the forearm (single photon absorptiometry), in the spine and in the total skeleton (dual photon absorptiometry) was unchanged in all estrogen-treated groups during the two years of treatment, and the responses in the groups with and without calcium supplementation and with different gestagens were not significantly different. Furthermore, the responses were independent of route of administration of the estrogen. Biochemical indices of bone turnover (serum alkaline phosphatase and fasting urinary hydroxyproline/creatinine) decreased highly significantly during estrogen treatment (p<0.001) independent of route of administration of the estrogen, of calcium supplementation, and of gestagen agent. We conclude that estrogen treatment independently of route of administration, prevents postmenopausal bone loss. The gestagen agents used here do not affect calcium metabolism, and calcium supplementation has no additive effect to estrogen therapy.

  16. Activation of estrogen response elements is mediated both via estrogen and muscle contractions in rat skeletal muscle myotubes

    DEFF Research Database (Denmark)

    Wiik, A.; Hellsten, Ylva; Berthelson, P.;

    2009-01-01

    The aim of the present study was to investigate the activation of estrogen response elements (EREs) by estrogen and muscle contractions in rat myotubes in culture and to assess whether the activation is dependent on the estrogen receptors (ERs). In addition, the effect of estrogen and contraction...... differentiated into myotubes and subjected to either estrogen or electrical stimulation. Activation of the ERE sequence was determined by measurement of luciferase activity. The results show that both ERalpha and ERbeta are expressed in myotubes from rats. Both estrogen stimulation and muscle contraction...... increased (P < 0.05) transactivation of the ERE sequence and enhanced ERbeta mRNA, whereas ERalpha was unaffected by estrogen and attenuated (P < 0.05) by muscle contraction. Use of ER antagonists showed that, whereas the estrogen-induced transactivation is mediated via ERs, the effect of muscle contraction...

  17. Pharmacogenomics of estrogens on changes in carotid artery intima-medial thickness and coronary arterial calcification: Kronos Early Estrogen Prevention Study

    OpenAIRE

    Miller, VM; Jenkins, GD; Biernacka, JM; Heit, JA; Huggins, GS; Hodis, HN.; Budoff, MJ; Lobo, RA; Taylor, HS; Manson, JE; Black, DM; Naftolin, F.; Mitchell Harman, S; de Andrade, M.

    2016-01-01

    © 2016 the American Physiological Society. Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate ge...

  18. Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability

    DEFF Research Database (Denmark)

    Breinholt, Vibeke; Hossaini, A.; Svendsen, Gitte W.; Brouwer, C.; Nielsen, S. E.

    2000-01-01

    The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, genistein and equol was investigated in immature female mice. Genistein and equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17-20, 100 mg/kg body weight], was found to significantly increase uterine...... lower potency. Bioavailability, metabolism, the ability to alter ER alpha distribution in the uterus and the estrogenic potential of parent compound and metabolites may thus contribute to the differences in in vivo estrogenicity of dietary flavonoids....

  19. Estrogen inhibits Dlk1/FA1 production: A potential mechanism for estrogen effects on bone turnover

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Bay-Jensen, Anne-Christine; Srinivasan, Bhuma;

    2011-01-01

    We have recently identified delta-like 1/fetal antigen 1 (Dlk1/FA1) as a novel regulator of bone mass that functions to mediate bone loss under estrogen deficiency in mice. In this report, we investigated the effects of estrogen (E) deficiency and E replacement on serum (s) levels of Dlk1/FA1 (s...... estrogen-replacement therapy (ERT, n = 166). s-Dlk1/FA1 and s-CTX were elevated in postmenopausal E-deficient women compared with premenopausal E-replete women (both p ...

  20. The selective estrogen enzyme modulators in breast cancer: a review.

    Science.gov (United States)

    Pasqualini, Jorge R

    2004-06-01

    It is well established that increased exposure to estradiol (E(2)) is an important risk factor for the genesis and evolution of breast tumors, most of which (approximately 95-97%) in their early stage are estrogen-sensitive. However, two thirds of breast cancers occur during the postmenopausal period when the ovaries have ceased to be functional. Despite the low levels of circulating estrogens, the tissular concentrations of these hormones are significantly higher than those found in the plasma or in the area of the breast considered as normal tissue, suggesting a specific tumoral biosynthesis and accumulation of these hormones. Several factors could be implicated in this process, including higher uptake of steroids from plasma and local formation of the potent E(2) by the breast cancer tissue itself. This information extends the concept of 'intracrinology' where a hormone can have its biological response in the same organ where it is produced. There is substantial information that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of E(2) from circulating precursors. Two principal pathways are implicated in the last steps of E(2) formation in breast cancer tissues: the 'aromatase pathway' which transforms androgens into estrogens, and the 'sulfatase pathway' which converts estrone sulfate (E(1)S) into E(1) by the estrone-sulfatase. The final step of steroidogenesis is the conversion of the weak E(1) to the potent biologically active E(2) by the action of a reductive 17beta-hydroxysteroid dehydrogenase type 1 activity (17beta-HSD-1). Quantitative evaluation indicates that in human breast tumor E(1)S 'via sulfatase' is a much more likely precursor for E(2) than is androgens 'via aromatase'. Human breast cancer tissue contains all the enzymes (estrone sulfatase, 17beta-hydroxysteroid dehydrogenase, aromatase) involved in the last steps of E(2) biosynthesis. This tissue also contains sulfotransferase for the formation of the

  1. Cumulative Estrogen Exposure and Prospective Memory in Older Women

    Science.gov (United States)

    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…

  2. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    Science.gov (United States)

    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…

  3. Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance

    International Nuclear Information System (INIS)

    Despite the beneficial effects of estrogens in women's health, there is a plethora of evidence that suggest an important role for these hormones, particularly 17β-estradiol (E2), in the development and progression of breast cancer. Most estrogenic responses are mediated by estrogen receptors (ERs), either ERα or ERβ, which are members of the nuclear receptor superfamily of ligand-dependent transcription factors. Selective estrogen receptor modulators (SERMs) are ER ligands that in some tissues (i.e. bone and cardiovascular system) act like estrogens but block estrogen action in others. Tamoxifen is the first SERM that has been successfully tested for the prevention of breast cancer in high-risk women and is currently approved for the endocrine treatment of all stages of ER-positive breast cancer. Raloxifene, a newer SERM originally developed for osteoporosis, also appears to have preventive effect on breast cancer incidence. Numerous studies have examined the molecular mechanisms for the tissue selective action of SERMs, and collectively they indicate that different ER ligands induce distinct conformational changes in the receptor that influence its ability to interact with coregulatory proteins (i.e. coactivators and corepressors) critical for the regulation of target gene transcription. The relative expression of coactivators and corepressors, and the nature of the ER and its target gene promoter also affect SERM biocharacter. This review summarizes the therapeutic application of SERMs in medicine; particularly breast cancer, and highlights the emerging understanding of the mechanism of action of SERMs in select target tissues, and the inevitable development of resistance

  4. Assessing the impacts of anthropogenic and hydro-climatic drivers on estrogen legacies and trajectories

    Science.gov (United States)

    Gall, Heather E.; Basu, Nandita B.; Mashtare, Michael L.; Rao, C.; Suresh, P.; Lee, Linda S.

    2016-01-01

    Intensification of concentrated animal feeding operations combined with the use of tile drains in agricultural fields has resulted in land-applied manure being a significant source of hormones to the environment. Currently, no model exists to simulate hormone fluxes from tile drains under field conditions. Therefore, we developed the Hormone Export and Recovery Dynamics (HERD) model, which incorporates hydro-climatic, biogeochemical, and anthropogenic drivers that affect hormone fate and transport. We validated HERD using known input (rainfall; lagoon effluent irrigation) and response data (tile drain flow; 17β-estradiol and estrone fluxes) from the 2009 growing season, 18 years after land-application activities began at a tile-drained field in Indiana. We used HERD to better understand the: (1) decision-making process underlying effluent irrigation activities; (2) contribution of macropore flow to estrogen transport; (3) potential for long-term applications to result in the development of legacy estrogen sources within the soil profile; and (4) potential recovery trajectory of estrogen transport following the cessation of animal waste applications. HERD adequately predicted irrigation events based on lagoon storage limits. Simple threshold exceedance logic for macropore flow activation accounted for ∼87% of the observed estrogen loads. Application history was found to be important, as not accounting for 18 years of application led to a severe underestimation of the observed estrogen loads; however, accounting for application history led to a much closer match between modeled and observed fluxes. Simulated trajectories after cessation of applications indicated that estrogens may continue to leach for several decades, which has important implications for mitigating hormone concentrations in receiving water bodies.

  5. Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Joan S. [Fox Chase Cancer Center, Alfred G. Knudson Chair of Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111 (United States); Jordan, V. Craig [Fox Chase Cancer Center, Alfred G. Knudson Chair of Cancer Research, 333 Cottman Avenue, Philadelphia, PA 19111 (United States)]. E-mail: v.craig.jordan@fccc.edu

    2005-12-11

    Despite the beneficial effects of estrogens in women's health, there is a plethora of evidence that suggest an important role for these hormones, particularly 17{beta}-estradiol (E{sub 2}), in the development and progression of breast cancer. Most estrogenic responses are mediated by estrogen receptors (ERs), either ER{alpha} or ER{beta}, which are members of the nuclear receptor superfamily of ligand-dependent transcription factors. Selective estrogen receptor modulators (SERMs) are ER ligands that in some tissues (i.e. bone and cardiovascular system) act like estrogens but block estrogen action in others. Tamoxifen is the first SERM that has been successfully tested for the prevention of breast cancer in high-risk women and is currently approved for the endocrine treatment of all stages of ER-positive breast cancer. Raloxifene, a newer SERM originally developed for osteoporosis, also appears to have preventive effect on breast cancer incidence. Numerous studies have examined the molecular mechanisms for the tissue selective action of SERMs, and collectively they indicate that different ER ligands induce distinct conformational changes in the receptor that influence its ability to interact with coregulatory proteins (i.e. coactivators and corepressors) critical for the regulation of target gene transcription. The relative expression of coactivators and corepressors, and the nature of the ER and its target gene promoter also affect SERM biocharacter. This review summarizes the therapeutic application of SERMs in medicine; particularly breast cancer, and highlights the emerging understanding of the mechanism of action of SERMs in select target tissues, and the inevitable development of resistance.

  6. CERAPP: Collaborative estrogen receptor activity prediction project

    DEFF Research Database (Denmark)

    Mansouri, Kamel; Abdelaziz, Ahmed; Rybacka, Aleksandra;

    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...

  7. Caffeic Acid Phenethyl Ester Increases Radiosensitivity of Estrogen Receptor-Positive and -Negative Breast Cancer Cells by Prolonging Radiation-Induced DNA Damage

    OpenAIRE

    Khoram, Nastaran Masoudi; Bigdeli, Bahareh; Nikoofar, Alireza; Goliaei, Bahram

    2016-01-01

    Purpose Breast cancer is an important cause of death among women. The development of radioresistance in breast cancer leads to recurrence after radiotherapy. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound of honeybee propolis, is known to have anticancer properties. In this study, we examined whether CAPE enhanced the radiation sensitivity of MDA-MB-231 (estrogen receptor-negative) and T47D (estrogen receptor-positive) cell lines. Methods The cytotoxic effect of CAPE on MDA-MB-2...

  8. Ligands specify estrogen receptor alpha nuclear localization and degradation

    Directory of Open Access Journals (Sweden)

    Caze-Subra Stéphanie

    2010-12-01

    Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

  9. [Determination of nine estrogenic steroids in milk using matrix solid phase dispersion-ultra performance liquid chromatography with mass spectrometric detector].

    Science.gov (United States)

    Liu, Hongcheng; Li, Ning; Lin, Tao; Shao, Jinliang; Li, Qiwan

    2015-11-01

    An analytical method for the multiresidue determination of nine estrogenic steroids in milk was developed by modified matrix solid phase dispersion (MSPD) purification and ultra performance liquid chromatography (UPLC) with mass spectrometric detector (MSD). The sensitivity and accuracy of MSD were better than that of ultraviolet detector. In comparison with traditional mass spectrometry, the merits of MSD were simpler in operation and shorter in starting time (5 min). The results showed that the limits of detection of the compounds with nucleophilic substitution were high in positive ion mode of MSD and were easily affected by environmental conditions. The matrix effects of milk samples reduced from 84%-160% to 80%-121% after MSPD purification. The intraday precision and interday precision of the nine estrogenic steroids were 0.87%-1.78% and 1.82%-3.79%, respectively. The average recoveries were 68.7%-94.7%, and the relative standard deviations (RSDs) were less than 10%. The limits of detection (LODs) were 0.5-10 μg/kg. The limits of quantification (LOQ) were 2-20 μg/kg. PMID:26939362

  10. Docosahexaenoic Acid Sensitizes Leukemia Lymphocytes to Barasertib and Everolimus by ROS-dependent Mechanism Without Affecting the Level of ROS and Viability of Normal Lymphocytes.

    Science.gov (United States)

    Zhelev, Zhivko; Ivanova, Donika; Lazarova, Desislava; Aoki, Ichio; Bakalova, Rumiana; Saga, Tsuneo

    2016-04-01

    The aim of the present study was: (i) to investigate the possibility of sensitizing leukemia lymphocytes to anticancer drugs using docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed after treatment of leukemia lymphocytes (Jurkat) with DHA in combination with: barasertib, lonafarnib, everolimus, and palbociclib. We selected two synergistic combinations, DHA with everolimus or barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (leukemia and normal). At the selected concentrations, DHA, everolimus and barasertib (applied separately) were cytotoxic towards leukemia lymphocytes, but not normal lymphocytes. In leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as everolimus and barasertib, that is cancer cell-specific (particularly for acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer chemotherapy, allowing therapeutic doses of everolimus and barasertib to be reduced, minimizing their side-effects. PMID:27069145

  11. Estrogen receptor-dependent effects of bisphenol a

    Directory of Open Access Journals (Sweden)

    P. Bulzomi

    2011-01-01

    Full Text Available Bisphenol A (BPA, commonly used as building block of polycarbonate plastics, significantly affects human and animal health interfering with the action of natural hormones. Within BPA disrupting effects, a mitogenic activity and, consequently, an increased incidence of neoplastic transformations has been reported in exposed organisms. Among the several mechanisms proposed for the mitogenic BPA effects, its ability to bind to estrogen receptors (ERα and ERβ deserves particular attention. Aim of this work is to investigate ERα- and ERβ-dependent mechanisms underlying BPA proliferative effect. Binding assay confirms that BPA binds to both ERs. Cell vitality assay and Western blot analysis of protein involved in cell proliferation demonstrate that BPA acts as a double side disruptor of estrogenic effects. In fact in the presence of ERα, BPA mimics E2, increasing cell proliferation. On the contrary, in the presence of ERβ, BPA acts as an E2 antagonist preventing the hormone-induced cancer cells apoptosis. These two divergent aspects could act synergistically in the exposed organisms leading to the disruption of the balance between proliferation and apoptosis typical of E2 effects.

  12. TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line

    DEFF Research Database (Denmark)

    Deng, Xiaohong; Fogh, Louise; Lademann, Ulrik Axel;

    2013-01-01

    affect sensitivity to the HER2-targeting drugs trastuzumab and lapatinib. SK-BR-3 human breast cancer cells were stably transfected with TIMP-1, characterized with regard to TIMP-1 protein expression, proliferation, and functionality of the secreted TIMP-1, and the sensitivity to trastuzumab and...... lapatinib was studied in five selected single-cell subclones expressing TIMP-1 protein at various levels plus the parental SK-BR-3 cell line. Both trastuzumab and lapatinib reduced cell viability, as determined by MTT assay, but the sensitivity to the drugs was not associated with the expression level of...

  13. Role of Estrogens on Human Male Reproductive System

    Institute of Scientific and Technical Information of China (English)

    Vincenzo Rochira; Lucia Zirilli; Bruno Madeo; Antonio Balestrieri; Cesare Carani; Antonio R. M. Granata

    2004-01-01

    This review focuses on estrogen role on human male physiology. Biological estrogen actions on male reproductive system are summarized with particular regard to the effects of congenital estrogen deprivation in men. The effects of estrogen on spermatogenesis, hormonal secretion and gonadotropin feedback and on sexual behavior are discussed. It is remarked that the role of estrogens in male reproduction is a very recent acquisition in reproductive endocrinology, but it promises new future fields of research to be investigated as well as the possible disclosure of new strategies in clinical practice.

  14. Radiation damage to specific complexes of DNA with proteins: estrogen response element DNA - estrogen receptor

    Czech Academy of Sciences Publication Activity Database

    Štísová, Viktorie; Běgusová, Marie; Goffinont, S.; Spotheim-Maurizot, M.

    Legnaro-Padova: INFN - Laboratori Nazionali di Legnaro, 2005. [International Symposium on Microdosimetry /14./. 13.11.2005-18.11.2005, Venezia] R&D Projects: GA MŠk(CZ) 1P05OC085; GA ČR(CZ) GA202/05/H031 Institutional research plan: CEZ:AV0Z10480505 Keywords : DNA-protein complex * radiation damage * estrogen receptor * estrogen response element DNA Subject RIV: BO - Biophysics

  15. Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump

    OpenAIRE

    Chen, Yuan; Vasilenko, Alex; Song, Xiulong; Valanejad, Leila; Verma, Ruchi; You, Sangmin; Yan, Bingfang; Shiffka, Stephanie; Hargreaves, Leeza; Nadolny, Christina; Deng, Ruitang

    2015-01-01

    Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such tr...

  16. Sex-specific effects of androgen and estrogen on proliferation of the embryonic chicken hypothalamic neurons.

    Science.gov (United States)

    Cao, Ailing; Zhang, Caiqiao

    2007-04-01

    Effects of androgen and estrogen on proliferation of hypothalamic neurons were evaluated by a chicken hypothalamic neuron-glia coculture model. Hypothalamic cells were dispersed from 17-day-old embryos and challenged with testosterone (T) and 17beta-estradiol (E2) alone or combined with androgen receptor antagonist flutamide, estrogen receptor antagonist tamoxifen, or aromatase inhibitor letrozole for 48 h. The neuron number was counted and the proliferating cells were identified by immunocytochemistry of proliferating cell nuclear antigen (PCNA) and 5-bromo-2-deoxyuridine (BrdU) incorporation. Results showed that both E2 and T stimulated proliferation of hypothalamic neurons. E2 showed more intensive effect on females and this promoting effect was abrogated by tamoxifen. T played more intensive effect on males and the effect was inhibited by flutamide, tamoxifen, or letrozole. The above results indicated that E2 stimulated neuron proliferation through estrogenic actions with more sensitive effect on females and T promoted neuron proliferation through both androgenic and estrogenic actions with more intense effect on males. These observations suggested that steroid hormones influence the proliferation of hypothalamic neurons in a sexually dimorphic manner during the development of chicken embryos. PMID:17873328

  17. Estrogen receptors in human vaginal tissue

    NARCIS (Netherlands)

    Wiegerinck, M.A.H.M.; Poortman, J.; Agema, A.R.; Thijssen, J.H.H.

    1980-01-01

    The presence of specific estrogen receptors could be demonstrated in vaginal tissue, obtained during operation from 38 women, age 27–75 yr. In 23 premenopausal women the receptor concentration in the vaginal tissue varied between 12 and 91 fmol/mg protein, no significant difference in the receptor

  18. Amping up estrogen receptors in breast cancer

    OpenAIRE

    Fowler, Amy M; Alarid, Elaine T

    2007-01-01

    This article highlights a recent study by Holst et al. in Nature Genetics that finds estrogen receptor-alpha (ER-α) amplification in early benign lesions and more advanced invasive carcinomas of the breast, and discusses the potential implications to our present understanding of the role of ER-α in breast tumorigenesis.

  19. [Pharmacodynamics of synthetic estrogens. Review article].

    Science.gov (United States)

    Sojo-Aranda, I; Cortés-Gallegos, V

    1990-10-01

    Some details about the function of natural and synthetical hormonas are reviewed, particularly estrogens as ethynyl estradiol and its 3, Methyl ether (mestranol); its peripheral concentration vs tissular hormonal contents, a relationship of biological importance as the first step in its hormonal action and the cummulative local effects that could explain some intra and extracellular phenomena. PMID:2292429

  20. [Pharmacodynamics of synthetic estrogens. A review].

    Science.gov (United States)

    Sojo-Aranda, I; Cortés-Gallegos, V

    1990-10-01

    Some details about the function of natural and synthetical hormonas are reviewed, particularly estrogens as ethynyl estradiol and its 3, Methyl ether (mestranol); its peripheral concentration vs tissular hormonal contents, a relationship of biological importance as the first step in its hormonal action and the cumulative local effects that could explain some intra and extracellular phenomena. PMID:2101377

  1. Combining docking and comparative molecular similarity indices analysis (COMSIA) to predict estrogen activity and probe molecular mechanisms of estrogen activity for estrogen compounds

    Institute of Scientific and Technical Information of China (English)

    YANG XuShu; WANG XiaoDong; JI Li; LI Rong; SUN Cheng; WANG LianSheng

    2008-01-01

    Estrogen compounds are suspected of disrupting endocrine functions by mimicking natural hormones,and such compounds may pose a serious threat to the health of humans and wildlife. Close attention has been paid to the prediction and molecular mechanisms of estrogen activity for estrogen compounds. In this article, estrogen receptor a subtype (Era) -based comparative molecular similarity indices analysis (COMSIA) was performed on 44 estrogen compounds with structural diversity to find out the structural relationship with the activity and to predict the activity. The model with the significant correlation and the best predictive power (R2 = 0.965, (Q2LOO = 0.599, R2pred = 0.825) was achieved. The COMSIA and docking results revealed the structural features for estrogen activity and key amino acid residues in binding pocket, and provided an insight into the interaction between the ligands and these amino acid residues.

  2. 3D-QSAR and docking studies of estrogen compounds based on estrogen receptor β

    Institute of Scientific and Technical Information of China (English)

    YANG XuShu; WANG XiaoDong; LUO Si; JI Li; QIN Liang; LI Rong; SUN Cheng; WANG LianSheng

    2009-01-01

    Close attention has been paid to estrogen compounds because these chemicals may pose a serious threat to the health of humans and wildlife.Estrogen receptor (ER) exists as two subtypes,ERo and ERβ.The difference in amino acids sequence of the binding sites of ERo and ERβ might lead to a result that some synthetic estrogens and naturally occurring steroidal ligands have different relative affinities and binding modes for ERa and ERβ.In this investigation,comparative molecular similarity indices analysis (CoMSIA) was performed on 50 estrogen compounds binding ERβ to find out the structural relationship with the activities.We also compared two alignment schemes employed in CoMSIA analysis,namely,atom-fit and receptor-based alignment,with respect to the predictive capability of their respective models for structurally diverse data sets.The model with the significant correlation and the best predictive power (R2=0.961,q2LOO=0.671,Rp2red=0.722) was achieved.The CoMSIA and docking results revealed the structural features related to an activity and provided an insight into molecular mechanisms of estrogenic activities for estrogen compounds.

  3. 3D-QSAR and docking studies of estrogen compounds based on estrogen receptor β

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Close attention has been paid to estrogen compounds because these chemicals may pose a serious threat to the health of humans and wildlife. Estrogen receptor (ER) exists as two subtypes, ERα and ERβ. The difference in amino acids sequence of the binding sites of ERα and ERβ might lead to a result that some synthetic estrogens and naturally occurring steroidal ligands have different relative affinities and binding modes for ERα and ERβ. In this investigation, comparative molecular similarity indices analysis (CoMSIA) was performed on 50 estrogen compounds binding ERβ to find out the structural relationship with the activities. We also compared two alignment schemes employed in CoMSIA analy-sis, namely, atom-fit and receptor-based alignment, with respect to the predictive capability of their respective models for structurally diverse data sets. The model with the significant correlation and the best predictive power (R2=0.961, qL 2OO=0.671, RP 2red=0.722) was achieved. The CoMSIA and docking results revealed the structural features related to an activity and provided an insight into molecular mechanisms of estrogenic activities for estrogen compounds.

  4. Estrogen and its role in gastrointestinal health and disease.

    LENUS (Irish Health Repository)

    Hogan, Aisling M

    2012-02-01

    INTRODUCTION: While the concept of a role of estrogen in gastrointestinal (in particular, colonic) malignancy has generated excitement in recent years, no review has examined the role of this potent and omnipresent steroid hormone in physiological states or its contribution to the development of benign pathological processes. Understanding these effects (and mechanisms therein) may provide a platform for a deeper understanding of more complex disease processes. METHODS: A literature search was conducted using the PubMed database and the search terms were "estrogen," "estrogen AND gastrointestinal tract," "estrogen AND colon," "estrogen AND esophagus," "estrogen AND small intestine," "estrogen AND stomach," "estrogen AND gallbladder," and "estrogen AND motility." Bibliographies of extracted studies were further cross-referenced. In all, 136 full-text articles were selected for review. A logical organ-based approach was taken to enable extraction of data of clinical relevance and meaningful interpretation thereof. Insight is provided into the hypotheses, theories, controversies, and contradictions generated over the last five decades by extensive investigation of estrogen in human, animal, and cell models using techniques as diverse as autoradiographic studies of baboons to human population analysis. CONCLUSIONS: Effects from esophagus through to the colon and rectum are summarized in this first concise collection of data pertaining to estrogenic actions in gastrointestinal health and disease. Mechanisms of these actions are discussed where possible. Undoubtedly, this hormone exerts many actions yet to be elucidated, and its potential therapeutic applications remain, as yet, largely unexplored.

  5. Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved

    OpenAIRE

    Yang, Chun Z.; Yaniger, Stuart I.; Jordan, V. Craig; Klein, Daniel J.; Bittner, George D

    2011-01-01

    Background: Chemicals having estrogenic activity (EA) reportedly cause many adverse health effects, especially at low (picomolar to nanomolar) doses in fetal and juvenile mammals. Objectives: We sought to determine whether commercially available plastic resins and products, including baby bottles and other products advertised as bisphenol A (BPA) free, release chemicals having EA. Methods: We used a roboticized MCF-7 cell proliferation assay, which is very sensitive, accurate, and repeatable,...

  6. Estrogen, male dominance and esophageal adenocarcinoma: Is there a link?

    Institute of Scientific and Technical Information of China (English)

    Huiqi Yang; Olga A Sukocheva; Damian J Hussey; David I Watson

    2012-01-01

    Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.

  7. Effect of selective estrogen receptor modulators on metabolic homeostasis.

    Science.gov (United States)

    Xu, Beibei; Lovre, Dragana; Mauvais-Jarvis, Franck

    2016-05-01

    Selective estrogen receptor modulators (SERMs) are estrogen receptor (ER) ligands that exhibit either estrogen agonistic or antagonistic activity in a tissue-specific manner. The first and second generation SERMs, tamoxifen and raloxifene, are used for treatment of ER positive breast cancer and postmenopausal osteoporosis respectively. The third-generation SERM, bazedoxifene (BZA), effectively prevents osteoporosis while blocking the estrogenic stimulation in breast and uterus. Notably, BZA combined with conjugated estrogens (CE) in a tissue-selective estrogen complex (TSEC) is a new menopausal treatment. Postmenopausal estrogen deficiency predisposes to metabolic syndrome and type 2 diabetes, and therefore the effects of SERMs and TSECs on metabolic homeostasis are gaining attention. In this article, we summarize current knowledge about the impact of SERMs on metabolic homeostasis and metabolic disorders in animal models and postmenopausal women. PMID:26133657

  8. ESTROGEN RECEPTORS OF HAIRS BLACKS AND WHITES

    Directory of Open Access Journals (Sweden)

    H. Laswati

    2014-12-01

    Full Text Available Background: Aging is termed as same as degenerative process, in which all part of tissue organs retarted the microstructure either macrostructure, forming and function even the colour, including black hair change to white hair. Several researchers have been recommended that estrogen hormone be able ease black to white hair, but hormone without any presenting of receptor won’t be work properly. The main aim of this study were to determine amount of estrogen receptor contents in famales and males black and white hairs included the microscopically structure. Method: Twelve females and males there were 50 -56 years old each pairs black and white head hairs were plucked along with follicles. This estrogen receptors analyzed using radioreceptor binding assay there were 5mm eah hair follices including the root cutted and each pair put its in 2 ml glass tube already filled in with 500 µl 125I-estradiol and incubated in 37oC for 3 hrs. Following times were over the tube flushed twice carefully the hair won’t be flushed. Then count by putting in the gamma counter chamber for 1 minute each. The values that shown in the monitor as CPM (count per minute, recorded as receptor of estradiol. Results: Mean (±SD sum estrogen receptor in females black and white hairs were 479.3 ± 37.5 and 387.7 ± 33.0, but significantly decreased in male black hair was 316.9±17.8 and 274.0 ± 19.8. All those pairs significantly different either female black and white hairs or male black and white hair and also significantly different among groups. Conclusion: The lowest estrogen receptors recorded in male white hairs and microstructure decreasing of melanin contents.

  9. Estrogens and male reproduction: a new concept

    Directory of Open Access Journals (Sweden)

    S. Carreau

    2007-06-01

    Full Text Available The mammalian testis serves two main functions: production of spermatozoa and synthesis of steroids; among them estrogens are the end products obtained from the irreversible transformation of androgens by a microsomal enzymatic complex named aromatase. The aromatase is encoded by a single gene (cyp19 in humans which contains 18 exons, 9 of them being translated. In rats, the aromatase activity is mainly located in Sertoli cells of immature rats and then in Leydig cells of adult rats. We have demonstrated that germ cells represent an important source of estrogens: the amount of P450arom transcript is 3-fold higher in pachytene spermatocytes compared to gonocytes or round spermatids; conversely, aromatase activity is more intense in haploid cells. Male germ cells of mice, bank voles, bears, and monkeys express aromatase. In humans, we have shown the presence of a biologically active aromatase and of estrogen receptors (alpha and ß in ejaculated spermatozoa and in immature germ cells in addition to Leydig cells. Moreover, we have demonstrated that the amount of P450arom transcripts is 30% lower in immotile than in motile spermatozoa. Alterations of spermatogenesis in terms of number and motility of spermatozoa have been described in men genetically deficient in aromatase. These last observations, together with our data showing a significant decrease of aromatase in immotile spermatozoa, suggest that aromatase could be involved in the acquisition of sperm motility. Thus, taking into account the widespread localization of aromatase and estrogen receptors in testicular cells, it is obvious that, besides gonadotrophins and androgens, estrogens produced locally should be considered to be physiologically relevant hormones involved in the regulation of spermatogenesis and spermiogenesis.

  10. Concentrations of estrogens in patients with preeclampsia.

    Science.gov (United States)

    Zeisler, Harald; Jirecek, Stefan; Hohlagschwandtner, Maria; Knöfler, Martin; Tempfer, Clemens; Livingston, Jeffrey C

    2002-06-28

    The role of estrogens in the pathophysiology of preeclampsia remains to be determined. The aim of our study was to compare serum concentrations of 17 beta-estradiol and estriol in women with preeclampsia to normotensive pregnant controls. Serum concentrations of estrogens were measured in women with mild (n = 24) and severe (n = 24) preeclampsia as well as is normotensive pregnant controls (n = 24). Patients were matched for gestational age. Pregnancies complicated by early onset severe preeclampsia are associated with increased rates of maternal and fetal morbidity. Subsequently, we created further subgroups before and after 34 weeks of gestation (34 + 0). Serum estrogen concentrations were determined by standard ELISA technique. Compared to normotensive controls, the differences between the overall median serum concentrations of 17 beta-estradiol in women with mild (3811 v. 3730 pg/ml, P = 0.9) and severe (3811 v. 3630 pg/ml, P = 0.1) preeclampsia were statistically not significant. The differences between the overall median serum concentrations of estroil in controls and in patients with mild (121 v. 76 ng/ml, P = 0.6) and severe (121 v. 79 ng/ml, P = 0.4) preeclampsia were similar. The differences between the median concentrations of 17 beta-estradiol in patient with early onset severe preeclampsia compared to patients with mild preeclampsia (3061 v. 3715 pg/ml, P = 0.004) and controls (3061 v. 3807 pg/ml, P = 0.006) were statistically significant. In addition, the differences between the median concentrations of estriol in women with early onset severe preeclampsia compared to controls were statistically significant (20 v. 92 ng/ml, P = 0.02). The differences between the median concentrations of estrogens in those with late onset severe preeclampsia compared to women with mild preeclampsia were not significant. We found significantly lower concentrations of estrogens in women with early onset severe preeclampsia. PMID:12422581

  11. Chronic inflammation and estradiol interact through MAPK activation to affect TMJ nociceptive processing by trigeminal caudalis neurons

    OpenAIRE

    Tashiro, A.; Okamoto, K.; Bereiter, D.A.

    2009-01-01

    The mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway plays a key role in mediating estrogen actions in the brain and neuronal sensitization during inflammation. Estrogen status is a risk factor in chronic temporomandibular muscle/joint disorders (TMJD); however, the basis for this relationship is not known. The present study tested the hypothesis that estrogen status acts through the MAPK/ERK signaling pathway to alter TMJ nociceptive processing. Single TMJ-r...

  12. Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells

    Directory of Open Access Journals (Sweden)

    Sun Xiao-Feng

    2010-11-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31 is obviously up-regulated in colorectal cancer (CRC, there is no study on the functional roles of miR-31 in CRC. Methods Anti-miR™ miRNA 31 inhibitor (anti-miR-31 is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116p53+/+ and HCT-116p53-/-colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU, cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines. Results Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116p53+/+ and 67.8% in HCT-116p53-/-cell line (p = 0.042 and 0.046. MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116p53+/+ or HCT-116p53-/-. However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044. Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116p53+/+ and HCT-116p53-/-(p = 0.040 and 0.001. The invasive ability of the cells were increased by 8-fold in HCT-116p53+/+ and 2-fold in HCT-116p53-/- (p = 0.045 and 0.009. Suppression of miR-31 had no effect on cell cycle and colony formation (p > 0.05. Conclusions Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells.

  13. [Pharmacological, metabolic and clinical aspects of new oral contraceptive associations containing natural estrogens].

    Science.gov (United States)

    Ferrari, S; Piacenti, I; Napolitano, A; Cagnacci, A

    2014-02-01

    Introduction of new compounds containing natural estrogens represented a major development in the field of hormonal contraception. Micronized estradiol (E2) and its estere valerate (EV), is more easily metabolized by the liver than ethynylestradiol (EE). This causes minimal metabolic impact, but the weak estrogenic activity needs not be antagonized by androgenic progestin and requires progestin capable to stabilize the endometrium. Dienogest (DNG), an antiandrogenic progestin with a short half-life, is associated with estradiol valerate (EV) in a quadriphasic fashion. In comparison to EE/levonorgestrel (LNG), EV/DNG is more neutral on metabolism and coagulation. Furthermore, it does not seem to negatively affect the cardiovascular system and breast. Cycle control is optimal with a higher prevalence of amenorrhea and reduction of menstrual flow. For this reason EV/DNG can be tehrapeutic for heavy menstrual bleedings. Nomegestrol acetate (NOMAc), an anti-andogen progestin with a long half-life is combined in monophasic regimen with micronized E2. E2/NOMAc is more neutral than EE/LNG on metabolism and more neutral than EE/DRSP on coagulation. NOMAc reduces peripheral tissue estrogen formation, and this may be beneficial for the breast. The two formulations exert a high contraceptive efficacy similar to the ones containing EE, but with less estrogen-related side-effects. The additional benefits due to DNG and NOMAc need to be further explored. PMID:24569408

  14. Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

    International Nuclear Information System (INIS)

    Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERαColII, expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERαColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERαColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERαColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  15. Effects of treadmill exercise training on cerebellar estrogen and estrogen receptors, serum estrogen, and motor coordination performance of ovariectomized rats

    OpenAIRE

    Saidah Rauf; Sri Kadarsih Soejono; Ginus Partadiredja

    2015-01-01

    Objective(s): The present study aims at examining the motor coordination performance, serum and cerebellar estrogen, as well as ERβ levels, of ovariectomized rats (as menopausal model) following regular exercise. Materials and Methods: Ten female Sprague Dawley rats aged 12 weeks old were randomly divided into two groups; all of which underwent ovariectomy. The first group was treated with regular exercise of moderate intensity, in which the rats were trained to run on a treadmill for 60 min ...

  16. Expression of estrogen receptor and sensitivity to endocrine therapy of MCF-7 human breast cancer cells cultured in stem cell culture in vitro%乳腺癌MCF-7细胞体外干细胞培养条件下雌激素受体表达与治疗敏感性初探

    Institute of Scientific and Technical Information of China (English)

    张斌; 张霞; 张改容; 刘越坚; 张阳

    2012-01-01

    目的 通过比较观察激素敏感的MCF-7细胞在体外干细胞培养和常规培养条件下雌激素受体(ER)变化及对内分泌治疗药物的敏感性变化,初步探讨肿瘤干细胞与内分泌耐药的关系.方法 分别于常规培养及干细胞培养条件下(悬浮球培养)培养激素敏感的MCF-7细胞株,流式细胞仪检测分子表型CD44+CD24–/low 与CD44+CD24+亚群细胞比例变化,免疫细胞化学法测定Erα和Erβ的表达变化,MTT法检测细胞对他莫西芬的敏感程度.分别以t检验、卡方检验、方差分析进行统计分析.结果 干细胞培养条件下CD44+CD24–/low亚群细胞的比例为(1.60±0.08)%,比常规培养条件下的(0.27±0.08)%显著增加(t=-12.10,P=0.00),而CD44+CD24+亚群细胞比例由(5.59±0.88)%增至(30.63±4.40)%(t=-5.58,P=0.00).干细胞培养条件培养下Erα和Erβ表达率较常规培养下调,分别由85.27%和90.53%降至69.43%和73.20%,差异有统计学意义(χ2=214.64,P=0.00;χ2=303.58,P=0.00),且对他莫西芬的敏感性降低,IC50值由(9.82±0.31)μmol/L升至(16.46±0.50)μmol/L,再次诱导分化后ER并未出现上调,对他莫西芬的敏感性仍旧降低(F=113.63,P=0.00).结论 与常规培养相比较,体外干细胞培养条件下可以培养出含高比例具有干细胞特性的CD44+CD24–/low与CD44+CD24+亚群细胞的微球囊,其ER仍为阳性表达,但对他莫昔芬治疗敏感性减低,推测其可能是乳腺癌内分泌耐药的原因.%Objective To explore estrogen receptor( ER) expression and endocrine resistance of horn one- sensitive MCF-7 cells in nomal culture or in sten cell culture in vitro. M ethods The MCF-7 cells were cultured in nomal culture or in sten cell culture in vitro ( suspension sphere). The proportion of CE44+ CEB4~/low phenotype and CE44+ CEB4+ phenotype cells were detemined using flow cytanetry ( FCM). The Era and Erp expression was detected using immunohistochanical method. The susceptibility to tamoxifen

  17. Glucocorticoid and Estrogen Receptors Are Reduced in Mitochondria of Lung Epithelial Cells in Asthma

    OpenAIRE

    Simoes, Davina C M; Psarra, Anna-Maria G.; Mauad, Thais; Pantou, Ioanna; Roussos, Charis; Sekeris, Constantine E.; Gratziou, Christina

    2012-01-01

    Mitochondrial glucocorticoid (mtGR) and estrogen (mtER) receptors participate in the coordination of the cell’s energy requirement and in the mitochondrial oxidative phosphorylation enzyme (OXPHOS) biosynthesis, affecting reactive oxygen species (ROS) generation and induction of apoptosis. Although activation of mtGR and mtER is known to trigger anti-inflammatory signals, little information exists on the presence of these receptors in lung tissue and their role in respiratory physiology and d...

  18. Effect of estrogen on plasma ceruloplasmin level in rats exposed to acute stress

    OpenAIRE

    Ganaraja B; Pavithran P; Ghosh S

    2004-01-01

    BACKGROUND: Plasma ceruloplasmin, a copper containing protein, belongs to a class called acute phase proteins. Reduced level of ceruloplasmin was associated with Wilson′s disease and Menke′s kinky hair disease in man, primarily affecting copper metabolism. Stress was known to increase Ceruloplasmin. Several stress associated changes were commonly observed in women at menopause and also those who underwent overiectomy. Present experiment investigated the effect of estrogen on cer...

  19. The influence of estrogen therapies on bone mineral density in premenopausal women with anorexia nervosa and amenorrhea.

    Science.gov (United States)

    Lebow, Jocelyn; Sim, Leslie

    2013-01-01

    Low bone mineral density is one of the primary risks of chronic amenorrhea, and the effects of potentially long-term menstrual disruption on bone mass are serious concerns for individuals with a past or current anorexia nervosa (AN) diagnosis. As such, estrogen therapies are frequently used to address amenorrhea associated with AN. A systematic review of the literature was conducted to examine the effectiveness of estrogen therapies on bone mineral density in women with amenorrhea. Data regarding the effectiveness of oral contraceptives were of low quality and mixed, with the majority of studies finding no benefit of these treatments on bone mineral density. Hormone replacement therapy findings were also mixed, though promising results were found in a study comparing transdermal administration of physiologic estrogen, delivered in developmentally sensitive incremental doses to placebo controls. Though this study suggests a possible role for estrogen therapies in addressing bone density loss in women with AN, in general, more studies are needed. Clinical drawbacks of using these therapies in the treatment of AN, including the loss of menses resumption as a clinical marker for weight and nutritional rehabilitation, must be considered in the decision to use estrogen therapies, particularly given the uncertain effectiveness of most of these treatments. PMID:23601427

  20. Sex Steroid Hormones Matter for Learning and Memory: Estrogenic Regulation of Hippocampal Function Inmale and Female Rodents

    Science.gov (United States)

    Frick, Karyn M.; Kim, Jaekyoon; Tuscher, Jennifer J.; Fortress, Ashley M.

    2015-01-01

    Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17ß-estradiol (E[subscript 2]), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes…

  1. Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only

    Directory of Open Access Journals (Sweden)

    D.G. Evans

    2016-05-01

    Interpretation: RNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.

  2. Estrogen-dependent visceral hypersensitivity following stress in rats: An fMRI study.

    Science.gov (United States)

    Hubbard, Catherine S; Karpowicz, Jane M; Furman, Andrew J; da Silva, Joyce Teixeira; Seminowicz, David A; Traub, Richard J

    2016-01-01

    We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control groups

  3. The androgen receptor and estrogen receptor

    OpenAIRE

    Oosterkamp, H.M.; Bernards, R.A.

    2002-01-01

    The androgen receptor (AR) and the estrogen receptors (ER) are members of the nuclear receptor (NR) family. These NRs are distinguished from the other transcription factors by their ability to control gene expression upon ligand binding (steroids, retinoids, thyroid hormone, vitamin D, fatty acids, and other small hydrophobic molecules). Their combined effects are vast, influencing virtually every fundamental biological process, from development and homeostasis, to proliferation and different...

  4. Immunoresponsiveness in endometriosis: implications of estrogenic toxicants.

    OpenAIRE

    Rier, S E; Martin, D. C.; Bowman, R E; J.L. Becker

    1995-01-01

    Endometriosis is a reproductive disease characterized by the growth of endometrial cells at sites outside the uterus. This disease is a serious disorder associated with chronic pain and infertility, which may be present in 6 million women in this country. Traditional medical therapy has consisted of hormonal regimens that limit the action of endogenous estrogen. The etiology of endometriosis is unknown, but studies suggest that soluble factors known as cytokines play a role in disease pathoge...

  5. Cancer of endometrium and prolonged estrogen therapy.

    Science.gov (United States)

    Fremont-smith, M; Meigs, J V; Graham, R M; Gilbert, H H

    1946-07-01

    A causal link between prolonged estrogen (E) therapy and endometrial cancer is argued for in this report of a case who was treated with large amounts of estrogenic substances almost continuously for an 8-year period. In 1919 a 25-year-old woman was admitted with asthma of 1-year duration. Asthma onset had been very severe, requiring administration of epinephrine hydrochloride every few hours and frequent hospital observation. In 1928, the patient was amenorrheic for 8 months; in 1936, she experienced amenorrhea for 4 months. In 1937 (patient now 45 years old), the relationship between amenorrhea and increased severity of asthma was suspected. At this time, the patient also complained of hot flashes and sweats. Treatment with estrogenic substances was begun in 1937 and continued through 1945. 3 unusual features were noted during therapy: 1) persistence of hot flashes; 2) persistence of high urine titers of follicle stimulating hormone (FSH) despite adequate E doses; and 3) absence of bleeding when E was temporarily withdrawn. By 1945, endometrial cancer had been identified by vaginal smear and verified by biopsy. Because of the previous absence of respose of FSH to prolonged E therapy, Es were omitted for 4 weeks, and after this period the vaginal smear showed complete absence of intrinsic estrogenic stimulation, and the urine titer of FSH was high. E given for 10 days caused moderate pituitary inhibition. Determination of 17-keto-steroids made before and after therapy was abnormally low. Except for the state of chronic illness and the continuous administration of asthma medication (chronic alarm reaction?), there is no explanation of carcinoma grade 2. PMID:12334535

  6. Estrogen and Hippocampal Plasticity in Rodent Models

    OpenAIRE

    Foy, Michael R.; Baudry, Michel; Brinton, Roberta Diaz; Thompson, Richard F.

    2008-01-01

    Accumulating evidence indicates that ovarian hormones regulate a wide variety of non-reproductive functions in the central nervous system by interacting with several molecular and cellular processes. A growing animal literature using both adult and aged rodent models indicates that 17β-estradiol, the most potent of the biologically relevant estrogens, facilitates some forms of learning and memory, in particular those that involve hippocampal-dependent tasks. A recently developed triple-transg...

  7. Exogenous pubertal induction by oral versus transdermal estrogen therapy.

    Science.gov (United States)

    Kenigsberg, Lisa; Balachandar, Sadana; Prasad, Kris; Shah, Bina

    2013-04-01

    Hypogonadal adolescent girls need estrogen therapy for the induction of puberty. For years, oral conjugated estrogens have been used for this purpose, starting at a very low dose, with gradual increments over time, to allow for the maturation of the reproductive organs, in order to mimic physiologic conditions. Several concerns, mainly due to first pass through the liver, are manifest with oral estrogen therapy. With the advent of transdermal estrogens and its improved efficacy profile as well as reduced side effects, it seems reasonable to consider it for pubertal induction. The primary objective of this study was to compare and contrast oral versus transdermal estrogen with regard to metabolism and physiology and to review current available data on transdermal estrogens with respect to exogenous pubertal induction. PMID:22112543

  8. Estrogen, Progesterone and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ho Shuk-Mei

    2003-10-01

    Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

  9. Estrogen sulfotransferases in breast and endometrial cancers.

    Science.gov (United States)

    Pasqualini, Jorge Raul

    2009-02-01

    Estrogen sulfotransferase is significantly more active in the normal breast cell (e.g., Human 7) than in the cancer cell (e.g., MCF-7). The data suggest that in breast cancer sulfoconjugated activity is carried out by another enzyme, the SULT1A, which acts at high concentration of the substrates. In breast cancer cells sulfotransferase (SULT) activity can be stimulated by various progestins: medrogestone, promegestone, and nomegestrol acetate, as well as by tibolone and its metabolites. SULT activities can also be controlled by other substances including phytoestrogens, celecoxib, flavonoids (e.g., quercetin, resveratrol), and isoflavones. SULT expression was localized in breast cancer cells, which can be stimulated by promegestone and correlated with the increase of the enzyme activity. The estrogen sulfotransferase (SULT1E1), which acts at nanomolar concentration of estradiol, can inactivate most of this hormone present in the normal breast; however, in the breast cancer cells, the sulfotransferase denoted as SULT1A1 is mainly present, and this acts at micromolar concentrations of E(2). A correlation was postulated among breast cancer cell proliferation, the effect of various progestins, and sulfotransferase stimulation. In conclusion, it is suggested that factors involved in the stimulation of the estrogen sulfotransferases could provide new possibilities for the treatment of patients with hormone-dependent breast and endometrial cancers. PMID:19250196

  10. Relevant Factors of Estrogen Changes of Myopia in Adolescent Females

    Directory of Open Access Journals (Sweden)

    Juan-Fen Gong

    2015-01-01

    Full Text Available Background: Gender is one of the risk factors accounting for the high prevalence of adolescent myopia. Considerable research results have shown that myopia incidence of female is higher than that of male. This study aimed to analyze the correlation between ocular parameters and serum estrogen level and to investigate the vision changes along with estrogen change in menstrual cycle of adolescent females. Methods: A total of 120 young females aged between 15 and 16 years, diagnosed with myopia were recruited. Spherical lens, cylindrical lens, axis, interpupillary distance (IPD, and vision in each tested eye of the same subject were measured by automatic optometry and comprehensive optometry, with repetition of all measurements in the menstrual cycle of the 2 nd or 3 rd days, 14 th days, and 28 th days, respectively. Serum estradiol (E 2 levels were assayed by chemiluminescence immunoassay at the same three times points of the menstrual cycle mentioned above. Results: In young females with myopia, the spherical lens showed a statistically significant difference among all different time in menstrual cycle (all P < 0.0001. The cylindrical lens, axis, and IPD were changed significantly during the menstrual cycle (P < 0.05. The vision of the three different time points in menstrual cycle had a significant difference (χ2 = 6.35, P = 0.042. The vision during the 14 th and 28 th day was higher compared to that on the 2 nd or 3 rd days (P = 0.021. Serum E 2 levels were significantly different at different time points in menstrual cycle (P < 0.05. E 2 levels reached its maximum value on the 14 th day and the minimum value on the 2 nd or 3 rd day. Conclusions: In adolescent females, the spherical lens and other related ocular parameters vary sensitively with different levels of E 2 in menstrual cycle. Vision in late menstrual stage is significantly higher than that in premenstrual stage.

  11. Tamoxifen stimulates arachidonic acid release from rat liver cells by an estrogen receptor-independent, non-genomic mechanism

    International Nuclear Information System (INIS)

    Tamoxifen is widely prescribed for the treatment of breast cancer. Its success has been attributed to the modulation of the estrogen receptor. I have previously proposed that the release of arachidonic acid from cells may also mediate cancer prevention. Rat liver cells were radiolabelled with arachidonic acid. The release of [3H] arachidonic acid after various times of incubation of the cells with tamoxifen was measured. Tamoxifen, at micromolar concentrations, stimulates arachidonic acid release. The stimulation is rapid and is not affected by pre-incubation of the cells with actinomycin or the estrogen antagonist ICI-182,780. The stimulation of AA release by tamoxifen is not mediated by estrogen receptor occupancy and is non-genomic

  12. Estrogen receptor prevents p53-dependent apoptosis in breast cancer

    OpenAIRE

    Bailey, Shannon T.; Shin, Hyunjin; Westerling, Thomas; Liu, Xiaole Shirley; Brown, Myles

    2012-01-01

    More than two-thirds of breast cancers express the estrogen receptor (ER) and depend on estrogen for growth and survival. Therapies targeting ER function, including aromatase inhibitors that block the production of estrogens and ER antagonists that alter ER transcriptional activity, play a central role in the treatment of ER+ breast cancers of all stages. In contrast to ER− breast cancers, which frequently harbor mutations in the p53 tumor suppressor, ER+ breast cancers are predominantly wild...

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

    Science.gov (United States)

    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

  14. Estrogen signaling in the proliferative endometrium: implications in endometriosis

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Pereira da Costa e Silva

    2016-02-01

    Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

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

    Science.gov (United States)

    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.

  16. Estrogens and the pathophysiology of the biliary tree

    Institute of Scientific and Technical Information of China (English)

    Domenico Alvaro; Maria Grazia Mancino; Paolo Onori; Antonio Franchitto; Gianfranco Alpini; Heather Francis; Shannon Glaser; Eugenio Gaudio

    2006-01-01

    The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor (ER) subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently,estrogens have been shown to target the biliary tree,where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors (ER-α) and (ER-β) subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades [ERK1/2 (extracellular regulated kinases 1/2, PI3- kinase/AKT (phosphatidylinositol-3'kinase/AKT)] typical of growth factors such as insulin like growth factor (IGF1), nerve growth factor (NGF)and vascular endothelial growth factor (VEGF), thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.

  17. Estrogen-related and other disease diagnoses preceding Parkinson's disease

    DEFF Research Database (Denmark)

    Latourelle, Jeanne C; Dybdal, Merete; Destefano, Anita L;

    2010-01-01

    Estrogen exposure has been associated with the occurrence of Parkinson's disease (PD), as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different...... mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms....

  18. Estrogen Actions in the Male Reproductive System Involve Estrogen Response Element-Independent Pathways

    OpenAIRE

    Weiss, Jeffrey; Bernhardt, Miranda L.; Laronda, Monica M.; Hurley, Lisa A.; Glidewell-Kenney, Christine; Pillai, Suresh; Tong, Minghan; Korach, Kenneth S.; Jameson, J. Larry

    2008-01-01

    The estrogen receptor-α (ERα) acts through multiple pathways, including estrogen response element (ERE)-dependent (classical) and ERE-independent (nonclassical) mechanisms. We previously created a mouse model harboring a two-amino-acid mutation of the DNA-binding domain (E207A, G208A) that precludes direct binding of ERα to an ERE. After crossing heterozygous mutant mice with an ERα knockout (ERKO) line, it was possible to assess the degree of physiological rescue by the isolated ERα nonclass...

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

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Caroline [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056 (United States); Grimaldi, Marina; Boulahtouf, Abdelhay [Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier (France); Pakdel, Farzad [Institut de Recherche sur la Santé, Environnement et Travail (IRSET), INSERM U1085, Université de Rennes 1, Rennes (France); Brion, François; Aït-Aïssa, Sélim [Unité Écotoxicologie In Vitro et In Vivo, INERIS, Parc ALATA, 60550 Verneuil-en-Halatte (France); Cavaillès, Vincent [Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier (France); Bourguet, William [U1054, Centre de Biochimie Structurale, CNRS UMR5048, Université Montpellier 1 et 2, 34290 Montpellier (France); Gustafsson, Jan-Ake [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056 (United States); Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge (Sweden); 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

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

    International Nuclear Information System (INIS)

    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

  1. Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

    OpenAIRE

    Vanacker, J M; K. Pettersson; Gustafsson, J.A.; Laudet, V

    1999-01-01

    The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classica...

  2. Immunohistochemical detection of estrogen receptors in canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Elena Atanaskova Petrov

    2016-03-01

    Full Text Available Mammary tumors are among the most common neoplasms in intact female dogs.They have a complex morphology, usually affecting middle age and older bitches. Almost 50% of the mammary tumors in dogs are malignant neoplasms. Prognosis is based on several factors: stage, age, tumor size, metastasis, histopathology, ovariectomy status and hormone-receptor activity. Immunohistochemical (IHC measurement has become increasingly an important diagnostic and prognostic parameter, with the development of monoclonal antibodies against nuclear estrogen and progestin receptors. The aim of this study was to detect the presence of ER receptors in malignant canine mammary tumors and to identify their association with the clinical course of the tumor. Mammary tumor samples have been obtained by mastectomy from dogs presented at our clinic. Detailed clinical examination, CBC and basic serum biochemical profile were performed in all patients. Surgery was the only treatment. Histopathological examination and immunohistochemical detection of estrogen α receptors (ERα was performed on 8 formalin-fixed, paraffin-embedded tissue samples, using the PT LINK immunoperoxidase technique. Histopathological examination of the mammary tumor samples (n=11 revealed tubular adenocarcinoma (n=6,54.5% and ductal adenocarcinoma (n=3, 27.3%, one patient with benign adenoma and one with mastitis. Patients with positive ER tumors are alive, without remission, while 3 of the patients that were ER negative died due to lung metastases. According to our results, it can be concluded that the appearance and development of canine mammary tumors is highly connected with ovarian steroid hormones and that immunostaining of the tumors may be used as a good prognostic parameter in these patients.

  3. Estrogen and insulin transport through the blood-brain barrier.

    Science.gov (United States)

    May, Aaron A; Bedel, Nicholas D; Shen, Ling; Woods, Stephen C; Liu, Min

    2016-09-01

    Obesity is associated with insulin resistance and reduced transport of insulin through the blood-brain barrier (BBB). Reversal of high-fat diet-induced obesity (HFD-DIO) by dietary intervention improves the transport of insulin through the BBB and the sensitivity of insulin in the brain. Although both insulin and estrogen (E2), when given alone, reduce food intake and body weight via the brain, E2 actually renders the brain relatively insensitive to insulin's catabolic action. The objective of these studies was to determine if E2 influences the ability of insulin to be transported into the brain, since the receptors for both E2 and insulin are found in BBB endothelial cells. E2 (acute or chronic) was systemically administered to ovariectomized (OVX) female rats and male rats fed a chow or a high-fat diet. Food intake, body weight and other metabolic parameters were assessed along with insulin entry into the cerebrospinal fluid (CSF). Acute E2 treatment in OVX female and male rats reduced body weight and food intake, and chronic E2 treatment prevented or partially reversed high-fat diet-induced obesity. However, none of these conditions increased insulin transport into the CNS; rather, chronic E2 treatment was associated less-effective insulin transport into the CNS relative to weight-matched controls. Thus, the reduction of brain insulin sensitivity by E2 is unlikely to be mediated by increasing the amount of insulin entering the CNS. PMID:27182046

  4. Transcriptomic analysis identifies gene networks regulated by estrogen receptor α (ERα) and ERβ that control distinct effects of different botanical estrogens

    OpenAIRE

    Gong, Ping; Madak-Erdogan, Zeynep; Li, Jilong; Cheng, Jianlin; Greenlief, C. Michael; Helferich, William G.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.

    2014-01-01

    The estrogen receptors (ERs) ERα and ERβ mediate the actions of endogenous estrogens as well as those of botanical estrogens (BEs) present in plants. BEs are ingested in the diet and also widely consumed by postmenopausal women as dietary supplements, often as a substitute for the loss of endogenous estrogens at menopause. However, their activities and efficacies, and similarities and differences in gene expression programs with respect to endogenous estrogens such as estradiol (E2) are not f...

  5. How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study

    OpenAIRE

    Zheng, Yanhua; Stener-Victorin, Elisabet; Ng, Ernest H. Y.; Li, Juan; Wu, Xiaoke; Ma, Hongxia

    2015-01-01

    Introduction Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov: NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study t...

  6. A single night of partial sleep loss impairs fasting insulin sensitivity but does not affect cephalic phase insulin release in young men

    OpenAIRE

    Cedernaes, Jonathan; Lampola, Lauri; Axelsson, Emil K; Liethof, Lisanne; Hassanzadeh, Sara; Yeganeh, Adine; Broman, Jan-Erik; Schiöth, Helgi B; Benedict, Christian

    2016-01-01

    The present study sought to investigate whether a single night of partial sleep deprivation (PSD) would alter fasting insulin sensitivity and cephalic phase insulin release (CPIR) in humans. A rise in circulating insulin in response to food-related sensory stimulation may prepare tissues to break down ingested glucose, e.g. by stimulating rate-limiting glycolytic enzymes. In addition, given insulin's anorexigenic properties once it reaches the brain, the CPIR may serve as an early peripheral ...

  7. Global sensitivity analysis of an end-to-end marine ecosystem model of the North Sea: Factors affecting the biomass of fish and benthos

    OpenAIRE

    Morris, David J.; Speir, Douglas C.; Cameron, Angus I; Heath, Michael R.

    2014-01-01

    Comprehensive analysis of parameter and driver sensitivity is key to establishing the credibility of models representing complex systems. This is especially so for models of natural systems where experimental manipulation of the real-world to provide controlled validation data is not possible. End-to-end ecosystem models (nutrients to birds and mammals) of marine ecosystems fall into this category with applications for evaluating the effects of climate change and fishing on nutrient fluxes an...

  8. Cocaine Dose and Self-Administration History, but Not Initial Cocaine Locomotor Responsiveness, Affects Sensitization to the Motivational Effects of Cocaine in Rats

    OpenAIRE

    Mandt, Bruce H.; Gomez, Emily; Johnston, Nickie L.; Zahniser, Nancy R.; Allen, Richard M.

    2012-01-01

    Cocaine addiction is a significant and complex disease. Part of this complexity is caused by the variability of the drug experience early in drug use (initial responsiveness, amount of use, etc.). In rats, individual differences in initial cocaine responsiveness and cocaine self-administration history both predict the development of cocaine sensitization, a putative mechanism contributing to the development of cocaine addiction. Here, we sought to determine the role of these factors and cocai...

  9. Developing an environmentally appropriate, socially acceptable and gender-sensitive technology for safe-water supply to households in arsenic affected areas in rural Bangladesh

    NARCIS (Netherlands)

    Amin, N.

    2010-01-01

    To confront the arsenic crisis in Bangladesh, several options for a safe water supply in the rural As-affected areas are available. Most of these options have shown a minimum scope to mitigate arsenic-related risks because of their poor performance and non-acceptability by the rural households. In t

  10. G-protein-coupled estrogen receptor agonist suppresses airway inflammation in a mouse model of asthma through IL-10.

    Science.gov (United States)

    Itoga, Masamichi; Konno, Yasunori; Moritoki, Yuki; Saito, Yukiko; Ito, Wataru; Tamaki, Mami; Kobayashi, Yoshiki; Kayaba, Hiroyuki; Kikuchi, Yuta; Chihara, Junichi; Takeda, Masahide; Ueki, Shigeharu; Hirokawa, Makoto

    2015-01-01

    Estrogen influences the disease severity and sexual dimorphism in asthma, which is caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERαβ), G-protein-coupled estrogen receptor (GPER) was recently established as an estrogen receptor on the cell membrane. Although GPER is associated with immunoregulatory functions of estrogen, the pathophysiological role of GPER in allergic inflammatory lung disease has not been examined. We investigated the effect of GPER-specific agonist G-1 in asthmatic mice. GPER expression in asthmatic lung was confirmed by immunofluorescent staining. OVA-sensitized BALB/c and C57BL/6 mice were treated with G-1 by daily subcutaneous injections during an airway challenge phase, followed by histological and biochemical examination. Strikingly, administration of G-1 attenuated airway hyperresponsiveness, accumulation of inflammatory cells, and levels of Th2 cytokines (IL-5 and IL-13) in BAL fluid. G-1 treatment also decreased serum levels of anti-OVA IgE antibodies. The frequency of splenic Foxp3+CD4+ regulatory T cells and IL-10-producing GPER+CD4+ T cells was significantly increased in G-1-treated mice. Additionally, splenocytes isolated from G-1-treated mice showed greater IL-10 production. G-1-induced amelioration of airway inflammation and IgE production were abolished in IL-10-deficient mice. Taken together, these results indicate that extended GPER activation negatively regulates the acute asthmatic condition by altering the IL-10-producing lymphocyte population. The current results have potential importance for understanding the mechanistic aspects of function of estrogen in allergic inflammatory response. PMID:25826377

  11. G-protein-coupled estrogen receptor agonist suppresses airway inflammation in a mouse model of asthma through IL-10.

    Directory of Open Access Journals (Sweden)

    Masamichi Itoga

    Full Text Available Estrogen influences the disease severity and sexual dimorphism in asthma, which is caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERαβ, G-protein-coupled estrogen receptor (GPER was recently established as an estrogen receptor on the cell membrane. Although GPER is associated with immunoregulatory functions of estrogen, the pathophysiological role of GPER in allergic inflammatory lung disease has not been examined. We investigated the effect of GPER-specific agonist G-1 in asthmatic mice. GPER expression in asthmatic lung was confirmed by immunofluorescent staining. OVA-sensitized BALB/c and C57BL/6 mice were treated with G-1 by daily subcutaneous injections during an airway challenge phase, followed by histological and biochemical examination. Strikingly, administration of G-1 attenuated airway hyperresponsiveness, accumulation of inflammatory cells, and levels of Th2 cytokines (IL-5 and IL-13 in BAL fluid. G-1 treatment also decreased serum levels of anti-OVA IgE antibodies. The frequency of splenic Foxp3+CD4+ regulatory T cells and IL-10-producing GPER+CD4+ T cells was significantly increased in G-1-treated mice. Additionally, splenocytes isolated from G-1-treated mice showed greater IL-10 production. G-1-induced amelioration of airway inflammation and IgE production were abolished in IL-10-deficient mice. Taken together, these results indicate that extended GPER activation negatively regulates the acute asthmatic condition by altering the IL-10-producing lymphocyte population. The current results have potential importance for understanding the mechanistic aspects of function of estrogen in allergic inflammatory response.

  12. Estrogen receptors alpha mediates postischemic inflammation in chronically estrogen-deprived mice.

    Science.gov (United States)

    Cordeau, Pierre; Lalancette-Hébert, Mélanie; Weng, Yuan Cheng; Kriz, Jasna

    2016-04-01

    Estrogens are known to exert neuroprotective and immuneomodulatory effects after stroke. However, at present, little is known about the role of estrogens and its receptors in postischemic inflammation after menopause. Here, we provide important in vivo evidence of a distinct shift in microglial phenotypes in the model of postmenopause brain. Using a model-system for live imaging of microglial activation in the context of chronic estrogen- and ERα-deficiency associated with aging, we observed a marked deregulation of the TLR2 signals and/or microglial activation in ovariectomized and/or ERα knockout mice. Further analysis revealed a 5.7-fold increase in IL-6, a 4.7-fold increase in phospho-Stat3 levels suggesting an overactivation of JAK/STAT3 pathway and significantly larger infarction in ERα knockouts chronically deprived of estrogen. Taken together, our results suggest that in the experimental model of menopause and/or aging, ERα mediates innate immune responses and/or microglial activation, and ischemia-induced production of IL-6. Based on our results, we propose that the loss of functional ERα may lead to deregulation of postischemic inflammatory responses and increased vulnerability to ischemic injury in aging female brains. PMID:26973103

  13. Serum estrogen levels and hippocampus β-estrogen receptor expressions in patients with epilepsy

    International Nuclear Information System (INIS)

    Objective: To investigate the relationship between serum estrogen (estrodial) levels estrogen β-receptor expressions in hippocampus and occurrence of seizure attack in patients of both sexes. Methods: The serum estrodial (E2) levels were detected in 8male and 9 female epileptic patients with radioimmunoassay. β-estrgen receptor (β-ER) in hippocampus were blotted with immuno-histochemical method in the 27 specimens from epilepsy surgery. Results: Few differences of E2 levels were found between those in epileptics and non-epileptics (n=30 as controls) (P>0.05). However the β-ER expression in hippocampus was significantly up-regulated in specimens from 8 female patients with catamenial epilepsy (P<0.05) as compared with that in the other 19 surgical specinens of this study and 27 other surgical specimen with different non-epileptic diseases as controls. Conclusion: Serum estrogen is not responsible for occurrence of seizure attack in patients with epilepsy. But the increased expression of β-estrogen receptors in hippocampus may be closely related with seizure in catamenial epilepsy. (authors)

  14. Nonsteroidal Bivalent Estrogen Ligands - An Application of the Bivalent Concept to the Estrogen Receptor

    Science.gov (United States)

    Shan, Min; Carlson, Kathryn E.; Bujotzek, Alexander; Wellner, Anja; Gust, Ronald; Weber, Marcus; Katzenellenbogen, John A.; Haag, Rainer

    2013-01-01

    The estrogen receptor (ER) is a hormone-regulated transcription factor that binds, as a dimer, to estrogens and to specific DNA sequences. To explore at a fundamental level the geometric and topological features of bivalent-ligand binding to the ER dimer, dimeric ER crystal structures were used to rationally design nonsteroidal bivalent estrogen ligands. Guided by this structure-based ligand design, we prepared two series of bivalent ligands (agonists and antagonists) tethered by flexible spacers of varying lengths (7–47Å) and evaluated their ER-binding affinities for the two ER subtypes and their biological activities in cell lines. Bivalent ligands based on the agonist diethylstilbestrol (DES) proved to be poor candidates, but bivalent ligands based on the antagonist hydroxytamoxifen (OHT) were well suited for intensive study. Binding affinities of the OHT-based bivalent ligands were related to spacer length in a distinctive fashion, reaching two maximum values at 14 and 29Å in both ER subtypes. These results demonstrate that the bivalent concept can operate in determining ER-ligand binding affinity and suggest that two distinct modes operate for the binding of bivalent estrogen ligands to the ER dimers, an intermolecular as well as an intramolecular mode. Our insights, particularly the possibility of intramolecular bivalent binding on a single ER monomer, may provide an alternative strategy to prepare more selective and active ER antagonists for endocrine therapy of breast cancer. PMID:23312071

  15. Generation of a fluorescent transgenic zebrafish for detection of environmental estrogens

    Energy Technology Data Exchange (ETDEWEB)

    Chen Hao; Hu Jingying; Yang Jian; Wang Yuexiang; Xu Hui; Jiang Qiu; Gong Yuebo; Gu Yinliang [Department of Molecular Genetics, Shanghai Medical School and Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, 200032 (China); Song Houyan, E-mail: hysong@shmu.edu.cn [Department of Molecular Genetics, Shanghai Medical School and Key Laboratory of Molecular Medicine, Ministry of Education, Fudan University, 200032 (China)

    2010-01-21

    To establish a novel in vivo test system for rapid detection of environmental estrogens, an ere-zvtg1: gfp transgenic zebrafish line has been generated. In this transgenic line, under control conditions, GFP was exclusively expressed in the liver of mature adult female fish. Male and larval transgenic fish did not express GFP but could be induced to express GFP in the liver after exposure to 17-{alpha}-ethynylestradiol (EE{sub 2}). Concurrent accumulation of zvtg1 and gfp mRNAs in embryos and larvae after EE{sub 2} exposure was observed, which indicated that the expression of gfp transgene was driven by the zvtg1 promoter. Green fluorescence was first observed in the liver at 53, 74, 100 or 131 h post-fertilization (hpf) after exposure to 100, 10, 1 or 0.1 ng/L EE{sub 2} from 1 to 2 cell stage, respectively. As for mature male transgenic zebrafish, green fluorescence was observed after exposure to 100, 10, 1 or 0.1 ng/L EE{sub 2} for 2, 3, 4 or 7 days, respectively; as for mature female, fluorescence was increased after exposure to relatively high concentrations of EE{sub 2} (10 and 100 ng/L). Green fluorescence in the liver was increased with prolonging of exposure time and was repeatedly induced after removal and re-addition of EE{sub 2}. We also demonstrated that GFP expression could be induced by other estrogenic compounds, including {beta}-estradiol (E{sub 2}, 0.1 {mu}g/L), cadmium chloride (CdCl{sub 2}, 10 {mu}g/L), zearalenone (50 {mu}g/L), estriol (E{sub 3}, 1 {mu}g/L), diethylstilbestrol (DES, 50 ng/L) bisphenol A (BPA, 1 mg/L) but not by weakly estrogenic compounds such as nonylphenol (NP, up to 10 mg/L), or non-estrogenic steroid hormones such as progesterone (up to 100 mg/L) and 17-hydroxysteroid (up to 50 mg/L). These data suggest the transgenic zebrafish is sensitive and specific for detection of estrogenic compounds. Because the observed-effect concentrations are as low as those of environment and the observed-effect exposure times are very short

  16. Generation of a fluorescent transgenic zebrafish for detection of environmental estrogens

    International Nuclear Information System (INIS)

    To establish a novel in vivo test system for rapid detection of environmental estrogens, an ere-zvtg1: gfp transgenic zebrafish line has been generated. In this transgenic line, under control conditions, GFP was exclusively expressed in the liver of mature adult female fish. Male and larval transgenic fish did not express GFP but could be induced to express GFP in the liver after exposure to 17-α-ethynylestradiol (EE2). Concurrent accumulation of zvtg1 and gfp mRNAs in embryos and larvae after EE2 exposure was observed, which indicated that the expression of gfp transgene was driven by the zvtg1 promoter. Green fluorescence was first observed in the liver at 53, 74, 100 or 131 h post-fertilization (hpf) after exposure to 100, 10, 1 or 0.1 ng/L EE2 from 1 to 2 cell stage, respectively. As for mature male transgenic zebrafish, green fluorescence was observed after exposure to 100, 10, 1 or 0.1 ng/L EE2 for 2, 3, 4 or 7 days, respectively; as for mature female, fluorescence was increased after exposure to relatively high concentrations of EE2 (10 and 100 ng/L). Green fluorescence in the liver was increased with prolonging of exposure time and was repeatedly induced after removal and re-addition of EE2. We also demonstrated that GFP expression could be induced by other estrogenic compounds, including β-estradiol (E2, 0.1 μg/L), cadmium chloride (CdCl2, 10 μg/L), zearalenone (50 μg/L), estriol (E3, 1 μg/L), diethylstilbestrol (DES, 50 ng/L) bisphenol A (BPA, 1 mg/L) but not by weakly estrogenic compounds such as nonylphenol (NP, up to 10 mg/L), or non-estrogenic steroid hormones such as progesterone (up to 100 mg/L) and 17-hydroxysteroid (up to 50 mg/L). These data suggest the transgenic zebrafish is sensitive and specific for detection of estrogenic compounds. Because the observed-effect concentrations are as low as those of environment and the observed-effect exposure times are very short, this transgenic fish is a promising candidate system for monitoring

  17. VASCULAR AGING IN WOMEN: IS ESTROGEN THE FOUNTAIN OF YOUTH?

    Directory of Open Access Journals (Sweden)

    CarlosHermenegildo

    2012-06-01

    In this review, we discuss clinical and experimental data on the effects of aging, estrogens and hormonal replacement therapy on vascular function of females to delve into how menopause and aging contribute jointly to vascular aging and how estrogen modulates the vascular responses at different ages.

  18. The Tissue Selective Estrogen Complex: A Promising New Menopausal Therapy

    Directory of Open Access Journals (Sweden)

    Sebastian Mirkin

    2012-09-01

    Full Text Available Menopause is associated with health concerns including vasomotor symptoms, vulvar/vaginal atrophy (VVA, and osteoporosis. Estrogen therapy or combined estrogen-progestin therapy (EPT are primary treatment options for menopausal symptom relief and osteoporosis prevention. Because EPT has been associated with some safety/tolerability concerns relating to undesirable effects of estrogen and progestin, alternative options are needed. The tissue selective estrogen complex (TSEC is a novel class of agents pairing a selective estrogen receptor modulator (SERM with 1 or more estrogens. The TSEC combines the established efficacy of estrogens on menopausal symptoms and bone with the protective effects of a SERM on the reproductive tract. The pairing of bazedoxifene (BZA with conjugated estrogens (CE has been evaluated in a series of phase 3 clinical trials. BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg have shown efficacy in reducing the frequency and severity of hot flushes, relieving VVA symptoms, and maintaining bone mass while protecting the endometrium and breast. These BZA/CE doses have been associated with a favorable safety/tolerability profile, with higher rates of cumulative amenorrhea and lower incidences of breast pain than those reported for EPT. Thus, BZA/CE may be a promising alternative to conventional EPT for treating non-hysterectomized, postmenopausal women.

  19. Scanning for Clues to Better Use Selective Estrogen Receptor Modulators

    OpenAIRE

    Machiela, Mitchell J.; Chanock, Stephen J.

    2013-01-01

    Ingle and colleagues present timely findings identifying genetic variants associated with response to selective estrogen receptor modulator therapy that when substantiated in follow-up may represent an important step towards understanding estrogen-dependent induction of BRCA1 expression and advancing individualized preventive medicine in women at high risk for developing breast cancer.

  20. Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus

    Directory of Open Access Journals (Sweden)

    Spenser Reed

    2014-03-01

    Full Text Available Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA ratio. Diets identical in composition were formulated and two groups of birds (n = 12 were randomly separated upon hatching into two diets, Zn(+ (zinc adequate control, 42.3 μg/g zinc, and Zn(− (zinc deficient, 2.5 μg/g zinc. Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn(+ control versus Zn(− group (p < 0.05. Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn(+ control group (p < 0.05, and hepatic Δ6 desaturase was significantly higher in the Zn(+ group (p < 0.001. The LA:DGLA ratio was significantly elevated in the Zn(− group compared to the Zn(+ group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001. This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation.

  1. A major QTL affects temperature sensitive adult lethality and inbreeding depression in life span in Drosophila melanogaster.

    DEFF Research Database (Denmark)

    Vermeulen, Corneel J.; Bijlsma, R.; Loeschcke, Volker

    2008-01-01

    Background The study of inbreeding depression has major relevance for many disciplines, including conservation genetics and evolutionary biology. Still, the molecular genetic basis of this phenomenon remains poorly characterised, as knowledge on the mechanistic causes of inbreeding depression and...... the molecular properties of genes that give rise to or modulate its deleterious effects is lacking. These questions warrant the detailed study of genetic loci giving rise to inbreeding depression. However, the complex and polygenic nature of general inbreeding depression makes this a daunting task......-chromosome. Conclusion This demonstrates that analysis of large conditional lethal effects is a viable strategy for delineating genes which are sensitive to inbreeding depression....

  2. Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

    DEFF Research Database (Denmark)

    Olsen, M.H.; Hansen, T.W.; Christensen, M.K.; Gustafsson, F.; Rasmussen, S.; Wachtell, K.; Ibsen, H.; Torp-Pedersen, C.; Hildebrandt, P.R.

    2008-01-01

    BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the...... factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years. RESULTS: In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0...

  3. Mouse monoclonal antibodies against estrogen receptor.

    Science.gov (United States)

    De Rosa, Caterina; Rossi, Valentina; Abbondanza, Ciro

    2014-01-01

    The production of monoclonal antibodies, by cloning hybridoma derived from the fusion of myeloma cells and spleen lymphocytes, has allowed to obtain great advances in many fields of biological knowledge. The use of specific antibodies to the estrogen receptor, in fact, has been an invaluable method to bring out its mechanisms of action and its effects, both genomic and extra-genomic. Here we describe, step by step, the production of monoclonal antibodies, starting from protocol for antigen preparation to the selection of antibody-secreting hybridoma. PMID:25182770

  4. Effects of estrogen and testosterone treatment on serotonin transporter binding in the brain of surgically postmenopausal women--a PET study.

    Science.gov (United States)

    Jovanovic, Hristina; Kocoska-Maras, Ljiljana; Rådestad, Angelique Flöter; Halldin, Christer; Borg, Jacqueline; Hirschberg, Angelica Lindén; Nordström, Anna-Lena

    2015-02-01

    Sex hormones and the serotonergic system interact in the regulation of mood, learning, memory and sexual behaviour. However, the mechanisms have not been fully explored. The serotonin transporter protein (5-HTT) regulates synaptic concentrations of serotonin and is a primary target for selective serotonin reuptake inhibitors. The aim of this study was to explore how estrogen treatment alone or in combination with testosterone affects 5-HTT binding potentials measured by positron emission tomography (PET) in specific brain regions of postmenopausal women. Ten healthy surgically postmenopausal women (years since oophorectomy 7.5 ± 4.0, mean ± SD) underwent PET examinations at baseline, after three months of estrogen treatment (transdermal estradiol 100 μg/24 hours) and after another three months of combined estrogen and testosterone (testosterone undecanoate 40 mg daily) treatment using the radioligand [(11)C] MADAM developed for examination of the serotonin transporter. The 5-HTT binding potentials decreased significantly in several cortical regions, as well as in limbic and striatal regions after both estrogen treatment alone and combined estrogen/testosterone treatment in comparison to baseline. The observed decrease in 5-HTT could either be due to direct effects on serotonin transporter expression or be the result of indirect adaptation to estrogen and /or testosterone effects on synaptic serotonin levels. Although the mechanism still needs further exploration, the study supports the view that gonadal hormones play a role in serotonin regulated mood disorders. PMID:25462800

  5. Isolation and identification of pathogenic bacteria from genital tract of the Arabian mares affected with genital tract infection and antimicrobial sensitivity

    Directory of Open Access Journals (Sweden)

    H. F. AL-Abidy

    2010-01-01

    Full Text Available This study was conducted for isolation and identification of the pathogenic bacteria presented in the genital tract infectionof the Arabian mares, and shows the anti microbial sensitivity. The study included 75 samples taken from infected maressuffering from genital tract infection diagnosed on the basis of case history and clinical signs which included bloody purulentdischarge ranched from yellow to green in colure, fetid oder with congested and oedematous vagina and from some abortioncases, and from mares suffered from tetanus disease symptoms during the period between October 2007 to April 2008 in studfarms breeding mares in Mosul. The samples were collected by swabs from the clitoris, clitorial fossa and the vagina. Isolationof bacteria was performed using aerobic and anaerobic culture techniques. Results of the present study showed a total ofisolation 75% from all samples taken with a high percentage isolation of Clostridium tetani (16.6%, followed by Archanobacterium pyogenes (10.6%, and Pseudomonas aeruginosa (8%, (6.7% for each Enterobacter aerogenes, Klebsiellapneumonia, Streptococcus dysagalactiae subsp equisimilis, and (5.3% for each bacteria Actinobacillus equilli, Streptococcuszooepidemicus, Staphylococcus aureus, then Proteus vulgaris (2.6%, and Escherichia coli (1.3%. The most bacterial isolateswere resistant to amoxicillin (100%, ampicillin (90.9 %, and erythromycin (65.9%, while the most isolates were sensitive tokanamycin (70.4%. It could be concluted that the most important bacteria causing genital tract infection of mares could beClostridium tetani and Archanobacterium pyogenes, Pseudomonas aeruginosa. The most bacterial isolates were resistant toamoxicillin, ampicillin and erythromycin.

  6. Dietary zinc deficiency affects blood linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio; a sensitive physiological marker of zinc status in vivo (Gallus gallus).

    Science.gov (United States)

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P; Tako, Elad

    2014-01-01

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn⁺ (zinc adequate control, 42.3 μg/g zinc), and Zn⁻ (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn⁺ control versus Zn⁻ group (p biomarker to assess dietary zinc manipulation. PMID:24658588

  7. Ontogeny of the mouse estrogen receptor: the pelvic region

    International Nuclear Information System (INIS)

    The appearance of estrogen receptors was examined during the course of fetal and neonatal development in the pelvic region of the mouse; 3H-diethylstilbestrol (DES) was administered via the maternal circulation to developing mice on days 4, 7, 10, 13, 14, 15, and 17 of gestation or to neonates on the day of birth. Localization of the ligand was monitored autoradiographically. The earliest appearance of estrogen receptors occurred in the mesenchyme around the genital ducts on day 13 of pregnancy. On subsequent days, estrogen-concentrating cells appeared in certain mammary-gland cells, connective-tissue strands, in perichondrium associated with specific developing bones, skin, interstitial tissue of the testis, in a sheath of cells surrounding the colon, and in the urethra. The significance of cells containing estrogen receptors in these locations is discussed in reference to a transplacental action of estrogens and the clinical ramifications of DES

  8. Radiosensitivity of mouse seminal vesicle cells which show proliferative response to androgen and estrogen

    International Nuclear Information System (INIS)

    Injections of either androgen or estrogen have been shown to induce proliferation of epithelial cells in the seminal vesicle of castrated mice. Uptake of 5-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) by the whole seminal vesicle was used as an index for cell proliferation. Although uptake of [125I]IdUrd induced by androgen was about four times as great as that induced by estrogen, both values decreased with a similar pattern after irradiation. Uptake of [125I]IdUrd showed a dose-dependent decrease up to 1000 rad; the values remained unchanged until 4000 rad. Uptake of [125I]IdUrd by the radiosensitive cell population was calculated by substracting [I-125]IdUrd uptake attributable to the radioresistant cell population from total [I-125]IdUrd uptake. Androgen- and estrogen-responsive cells were equally sensitive to irradiation. Recovery of androgen-responsive cells from radiation-induced decrease was examined with or without androgen stimulation. Although recovery occurred without androgen, it was significantly enhanced by androgen stimulation following irradiation. Irradiation seems useful for investigation of kinetic characteristics of epithelial stem cells in the seminal vesicle of mice

  9. Selective Estrogen Receptor β Agonist LY500307 as a Novel Therapeutic Agent for Glioblastoma.

    Science.gov (United States)

    Sareddy, Gangadhara R; Li, Xiaonan; Liu, Jinyou; Viswanadhapalli, Suryavathi; Garcia, Lauren; Gruslova, Aleksandra; Cavazos, David; Garcia, Mike; Strom, Anders M; Gustafsson, Jan-Ake; Tekmal, Rajeshwar Rao; Brenner, Andrew; Vadlamudi, Ratna K

    2016-01-01

    Glioblastomas (GBM), deadly brain tumors, have greater incidence in males than females. Epidemiological evidence supports a tumor suppressive role of estrogen; however, estrogen as a potential therapy for GBM is limited due to safety concerns. Since GBM express ERβ, a second receptor for estrogen, targeting ERβ with a selective agonist may be a potential novel GBM therapy. In the present study, we examined the therapeutic effect of the selective synthetic ERβ agonist LY500307 using in vitro and in vivo GBM models. Treatment with LY500307 significantly reduced the proliferation of GBM cells with no activity on normal astrocytes in vitro. ERβ agonists promoted apoptosis of GBM cells, and mechanistic studies using RNA sequencing revealed that LY500307 modulated several pathways related to apoptosis, cell cycle, and DNA damage response. Further, LY500307 sensitized GBM cells to several FDA-approved chemotherapeutic drugs including cisplatin, lomustine and temozolomide. LY500307 treatment significantly reduced the in vivo tumor growth and promoted apoptosis of GBM tumors in an orthotopic model and improved the overall survival of tumor-bearing mice in the GL26 syngeneic glioma model. Our results demonstrate that LY500307 has potential as a therapeutic agent for GBM. PMID:27126081

  10. Trefoil Factor 3 Is Oncogenic and Mediates Anti-Estrogen Resistance in Human Mammary Carcinoma

    Directory of Open Access Journals (Sweden)

    Nagarajan Kannan

    2010-12-01

    Full Text Available We report herein that trefoil factor 3 (TFF3 is oncogenic and mediates anti-estrogen resistance in human mammary carcinoma. Forced expression of TFF3 in mammary carcinoma cells increased cell proliferation and survival, enhanced anchorage-independent growth, and promoted migration and invasion. Moreover, forced expression of TFF3 increased tumor size in xenograft models. Conversely, depletion of endogenous TFF3 with small interfering RNA (siRNA decreased the oncogenicity and invasiveness of mammary carcinoma cells. Neutralization of secreted TFF3 by antibody promoted apoptosis, decreased cell growth in vitro, and arrested mammary carcinoma xenograft growth. TFF3 expression was significantly correlated to decreased survival of estrogen receptor (ER-positive breast cancer patients treated with tamoxifen. Forced expression of TFF3 in mammary carcinoma cells increased ER transcriptional activity, promoted estrogen-independent growth, and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. siRNA-mediated depletion or antibody inhibition of TFF3 significantly enhanced the efficacy of antiestrogens. Increased TFF3 expression was observed in tamoxifen-resistant (TAMR cells and antibody inhibition of TFF3 in TAMR cells improved tamoxifen sensitivity. Functional antagonism of TFF3 therefore warrants consideration as a novel therapeutic strategy for mammary carcinoma.

  11. Elucidation of the pharmacokinetics of prednisone and prednisolone: elimination and the effect of estrogen

    International Nuclear Information System (INIS)

    Several aspects of the pharmacokinetics of the interconvertible glucocorticoids prednisone and prednisolone have been studied. The pharmacokinetics of prednisolone were examined in postmenopausal women taking conjugated estrogens and age-matched control women. The subjects received iv bolus doses of 0.14 and 0.55 mg/kg prednisolone. Expected increases in clearance and volume of distribution with increasing dose were observed for total prednisolone in all subjects. At both doses, significant decreases in total and unbound prednisolone clearance were observed in the women taking estrogen compared to the controls. Volume of distribution was unchanged. The decreases in clearance are smaller than those observed in young women taking oral contraceptives indicating that factors other than estrogen administration may influence prednisolone clearance in oral contraceptive users. While the protein binding of prednisolone is well characterized, little is known about the protein binding of prednisone. Equilibrium dialysis employing [3H]prednisone was used to study the binding of prednisone in human plasma containing endogenous hydrocortisone. Plasma was obtained from volunteers with normal and elevated transcortin binding capacities (CAP/sub T/). Prednisolone binding exhibits marked concentration dependence and sensitivity to CAP/sub T/. In contrast, prednisone binding is independent of concentration and CAP/sub T/

  12. Feeding a higher plane of nutrition and providing exogenous estrogen increases mammary gland development in Holstein heifer calves.

    Science.gov (United States)

    Geiger, A J; Parsons, C L M; Akers, R M

    2016-09-01

    Feeding heifers a higher plane of nutrition postweaning but before puberty can negatively affect mammary gland development and future milk yield. However, enhanced nutrition preweaning may promote development and future production. Our objectives were to determine the effects of enhanced feeding preweaning and exogenous estrogen immediately postweaning on mammary gland development and the composition of the mammary parenchyma (PAR) and mammary fat pad (MFP). Thirty-six Holstein heifer calves (water. Starter feeding began at wk 5 and was balanced between treatments. Udders were evaluated by palpation and physical measurements weekly. Subsets of calves were killed at weaning (n=6 per diet) and at the conclusion of the trial (n=6 per treatment). Udders were removed, dissected, and weighed. At wk 8, EH calves had longer front and rear teats. Providing estrogen to EH calves increased the length of rear teats during wk 9 and 10. Enhanced-fed calves had 5.2-fold more trimmed mammary gland mass than R calves. Providing estrogen to EH calves further increased mammary gland weight. Masses of PAR and MFP were markedly greater for EH calves than for R calves (e.g., 7.3-fold greater PAR tissue). Estrogen increased the mass of both PAR and MFP in EH calves. Feeding a higher plane of nutrition increased total protein, DNA, and fat in the MFP and total protein and DNA in the PAR. Dual-energy x-ray absorptiometry estimates of mammary fat mass were highly correlated with biochemical analyses of fat content. From histological study, we observed that the degree of expansion of epithelium into the adjacent stromal tissue and the complexity of ductal development were minimal in R, increased in EH, and increased by estrogen in both dietary treatments. Results provide compelling evidence that preweaning nutrition and estrogen administration immediately postweaning markedly increase mammary gland development in dairy calves. Cellular and molecular mechanisms responsible for these

  13. Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1.

    Science.gov (United States)

    Tran, Quang-Kim; Firkins, Rachel; Giles, Jennifer; Francis, Sarah; Matnishian, Vahe; Tran, Phuong; VerMeer, Mark; Jasurda, Jake; Burgard, Michelle Ann; Gebert-Oberle, Briana

    2016-05-13

    Estrogen exerts many effects on the vascular endothelium. Calmodulin (CaM) is the transducer of Ca(2+) signals and is a limiting factor in cardiovascular tissues. It is unknown whether and how estrogen modifies endothelial functions via the network of CaM-dependent proteins. Here we show that 17β-estradiol (E2) up-regulates total CaM level in endothelial cells. Concurrent measurement of Ca(2+) and Ca(2+)-CaM indicated that E2 also increases free Ca(2+)-CaM. Pharmacological studies, gene silencing, and receptor expression-specific cell studies indicated that the G protein-coupled estrogen receptor 1 (GPER/GPR30) mediates these effects via transactivation of EGFR and subsequent MAPK activation. The outcomes were then examined on four distinct members of the intracellular CaM target network, including GPER/GPR30 itself and estrogen receptor α, the plasma membrane Ca(2+)-ATPase (PMCA), and endothelial nitric-oxide synthase (eNOS). E2 substantially increases CaM binding to estrogen receptor α and GPER/GPR30. Mutations that reduced CaM binding to GPER/GPR30 in separate binding domains do not affect GPER/GPR30-Gβγ preassociation but decrease GPER/GPR30-mediated ERK1/2 phosphorylation. E2 increases CaM-PMCA association, but the expected stimulation of Ca(2+) efflux is reversed by E2-stimulated tyrosine phosphorylation of PMCA. These effects sustain Ca(2+) signals and promote Ca(2+)-dependent CaM interactions with other CaM targets. Consequently, E2 doubles CaM-eNOS interaction and also promotes dual phosphorylation of eNOS at Ser-617 and Ser-1179. Calculations using in-cell and in vitro data revealed substantial individual and combined contribution of these effects to total eNOS activity. Taken together, E2 generates a feedforward loop via GPER/GPR30, which enhances Ca(2+)/CaM signals and functional linkage in the endothelial CaM target network. PMID:26987903

  14. Synthesis of a dendritic estrogen cluster: A potential tool for studies of nuclear versus extranuclear pathways of estrogen actions

    Institute of Scientific and Technical Information of China (English)

    Jian Chen; Hu Zheng; Yan Song; Yu Feng Liang; Qing Rong Qi

    2012-01-01

    A novel estrogen dendrimer has been synthesized through a combination of divergent and convergent approaches in 9 practical steps and in good yields.It was characterized and confirmed by elemental analysis,FT-IR,MS,1H NMR,13C NMR.The dendrimer contains 16 estrone units and is potentially a useful tool for the studies of estrogen actions.

  15. Developing an environmentally appropriate, socially acceptable and gender-sensitive technology for safe-water supply to households in arsenic affected areas in rural Bangladesh

    OpenAIRE

    Amin, N

    2010-01-01

    To confront the arsenic crisis in Bangladesh, several options for a safe water supply in the rural As-affected areas are available. Most of these options have shown a minimum scope to mitigate arsenic-related risks because of their poor performance and non-acceptability by the rural households. In this research, therefore, the development of an appropriate technology for an As-free, safe drinking water supply is considered from a local perspective and a societal context. To achieve the goal a...

  16. Estrogen biosynthesis in human uterine adenomyosis

    International Nuclear Information System (INIS)

    Estrogen biosynthesis (aromatiase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrical cancer tissues. Homogenates were incubated with [1,2,6,7-3H]androstenedione and NADPH at 37 deg. C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4-14C]estrone and [4-14C]estradiol-17β were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3H/14C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol.h-1.g-1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progresterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease. (author)

  17. Estrogen biosynthesis in human uterine adenomyosis

    Energy Technology Data Exchange (ETDEWEB)

    Urabe, Mamoru; Yamamoto, Takara; Kitawaki, Jo; Honjo, Hideo; Okada, Hiroji (Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto (Japan))

    1989-01-01

    Estrogen biosynthesis (aromatiase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrical cancer tissues. Homogenates were incubated with (1,2,6,7-{sup 3}H)androstenedione and NADPH at 37 deg. C for 1 h. After stopping the enzymatic reaction with ethyl acetate, (4-{sup 14}C)estrone and (4-{sup 14}C)estradiol-17{beta} were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the {sup 3}H/{sup 14}C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol{sup .}h{sup -1.}g{sup -1} wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progresterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease. (author).

  18. Licorice root components in dietary supplements are selective estrogen receptor modulators with a spectrum of estrogenic and anti-estrogenic activities.

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, Lisa J., E-mail: robinsonlj@msx.upmc.edu [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Yaroslavskiy, Beatrice B.; Griswold, Reed D.; Zadorozny, Eva V.; Guo, Lida; Tourkova, Irina L. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Blair, Harry C. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Veteran' s Affairs Medical Center, Pittsburgh, PA 15243 (United States)

    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}.

  20. Estrogen alters proenkephalin RNAs in the paraventricular nucleus of the hypothalamus following stress.

    Science.gov (United States)

    Yukhananov, R Y; Handa, R J

    1997-08-01

    Gonadal steroids modulate activity of the hypothalamo-pituitary-adrenal axis (HPA) following stress, but the regulatory pathways of this modulation are unknown. A possible site of action is the synthesis of CRH and/or enkephalin in cells of the paraventricular nucleus of the hypothalamus (PVN). To investigate this possibility, we utilized two stressors, i.p. hypertonic saline injection (HSI) or exposure to novel environment, and examined the response of CRH or c-fos mRNAs and proenkephalin (PPE) mRNA and heteronuclear RNA (hnRNA, primary transcript). Male rats were gonadectomized and treated with estrogen or dihydrotestosterone propionate (DHTP) for 2 weeks. In situ hybridization revealed that novelty or HSI elevated levels of PPE hnRNA and c-fos mRNA in the PVN. Estrogen attenuated the elevation of PPE hnRNA in the PVN following HSI, and enhanced the c-fos mRNA response to novelty. In contrast, DHTP did not affect PPE hnRNA, but inhibited the c-fos mRNA response to novelty. These data indicate that in male rats estrogen receptor but not androgen receptor may modulate the endocrine stress response by altering PPE transcription in the PVN and that this effect depends on the type of stressor. PMID:9295199

  1. Glutathione-S-transferase in Nereis succinea (Polychaeta) and its induction by xeno-estrogen.

    Science.gov (United States)

    Ayoola, James A O; García-Alonso, Javier; Hardege, Jörg D

    2011-10-01

    The need to replace or at least to reduce the use of vertebrates in toxicity tests is a timely major concern in research and industry but to date, efforts made to minimize their use are still far from complete. Increasing demands for toxicity tests put considerable pressures upon the development of future fast and efficient test methods using invertebrates. In fact, to date, few studies provide links between biochemical and cellular effects of xeno-estrogens in aquatic invertebrates. Glutathione-S-transferase (GST) activity, as a biomarker of stress exposure, was measured in the population of clamworms (Nereis succinea) from Cardiff Bay. In addition, we examined the effect of single exposure to nonylphenol (NP) on this enzymatic activity. Field study results showed a relationship between the worm's size, reproductive status, and GST activity from the field population. In addition, we show a significant increase in the GST activity at 100 μg/L NP with sex-specific responses. The xeno-estrogens, which could affect reproduction of nereid by interfering in normal endocrinological pathways, are eliminated through GST by conjugation with glutathione. This work shows for the first time that GST activity depends on sex and stage of the clamworms and also that the xeno-estrogen NP induces its activity. This study supports the use of this species as a bioindicator of aquatic pollution and lays the foundation to causally link toxic exposure with reproductive output. PMID:20549611

  2. Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera

    International Nuclear Information System (INIS)

    Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with 201Tl (84 patients) or 99mTc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for 201Tl (78 patients) or 99mTc-sestamibi (80 patients) exercise CZT SPECT. The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for 201Tl than for 99mTc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26 % error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for 99mTc-sestamibi and 30.5 and 13.1ppm for 201Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for 99mTc-sestamibi and 39 and 91 MBq for 201Tl, respectively. Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for 99mTc-sestamibi and in non-obese subjects. (orig.)

  3. Energy Effectiveness of Direct UV and UV/H2O2 Treatment of Estrogenic Chemicals in Biologically Treated Sewage

    Directory of Open Access Journals (Sweden)

    Kamilla M. S. Hansen

    2012-01-01

    Full Text Available Continuous exposure of aquatic life to estrogenic chemicals via wastewater treatment plant effluents has in recent years received considerable attention due to the high sensitivity of oviparous animals to disturbances of estrogen-controlled physiology. The removal efficiency by direct UV and the UV/H2O2 treatment was investigated in biologically treated sewage for most of the estrogenic compounds reported in wastewater. The investigated compounds included parabens, industrial phenols, sunscreen chemicals, and steroid estrogens. Treatment experiments were performed in a flow through setup. The effect of different concentrations of H2O2 and different UV doses was investigated for all compounds in an effluent from a biological wastewater treatment plant. Removal effectiveness increased with H2O2 concentration until 60 mg/L. The treatment effectiveness was reported as the electrical energy consumed per unit volume of water treated required for 90% removal of the investigated compound. It was found that the removal of all the compounds was dependent on the UV dose for both treatment methods. The required energy for 90% removal of the compounds was between 28 kWh/m3 (butylparaben and 1.2 kWh/m3 (estrone for the UV treatment. In comparison, the UV/H2O2 treatment required between 8.7 kWh/m3 for bisphenol A and benzophenone-7 and 1.8 kWh/m3 for ethinylestradiol.

  4. Chlropyrifos-methyl shows anti-androgenic activity without estrogenic activity in rats

    International Nuclear Information System (INIS)

    Chlorpyrifos-methyl (CPM), an organophosphate insecticide, widely used for grain storage and agriculture, has been suspected as endocrine disrupter by a few in vitro studies. This study was performed to investigate the (anti-) estrogenicity and (anti-) androgenicity of CPM in vivo using immature rat uterotrophic assay and rat Hershberger assay. CPM with or without 17β-estradiol were administered to 20 days old female rats to investigate its (anti-) estrogenic activity. Uterine and vaginal weight, uterine epithelial cell height were not affected by the treatment of CPM (2, 10, 50, 250 mg/kg). CPM 250 mg/kg potentiated relative vagina weight in 17β-estradiol treated immature female rats without any changing of uterine weight. Relative liver weight was increased with decrease of body weight by CPM 250 mg/kg treatment. Uterine cell proliferation tested with bromodeoxyuridine labeling index was not observed in CPM treated rats. CPM with or without testosterone propionate were administered to castrated rat of 51 days old for 10 days to investigate the (anti-)androgenic activity,. The weight of relative and absolute androgen-dependent accessory sex organs; seminal vesicle with coagulating glands (SV/CG), ventral prostate gland (VP), glans penis (GP), levator ani plus bulbocarvernosus muscle (LABC) and Cowper's gland (CG,) were unchanged by the treatment of CPM alone. While CPM induced the increase of relative adrenal gland weight, CPM 50 mg/kg decreased the weights of CV/CG, VP, CG and LABC without change of GP without changing of GP when it was treated with TP. In conclusion, CPM dose not show estrogenic and anti-estrogenic activity in immature female rats, but it represents anti-androgenic activity by inhibition of the TP-stimulated increase of the weight of accessory sex organs

  5. Estrogen Signaling Modulates Allergic Inflammation and Contributes to Sex Differences in Asthma

    Science.gov (United States)

    Keselman, Aleksander; Heller, Nicola

    2015-01-01

    Asthma is a chronic airway inflammatory disease that affects ~300 million people worldwide. It is characterized by airway constriction that leads to wheezing, coughing, and shortness of breath. The most common treatments are corticosteroids and β2-adrenergic receptor antagonists, which target inflammation and airway smooth muscle constriction, respectively. The incidence and severity of asthma is greater in women than in men, and women are more prone to develop corticosteroid-resistant or “hard-to-treat” asthma. Puberty, menstruation, pregnancy, menopause, and oral contraceptives are known to contribute to disease outcome in women, suggesting a role for estrogen and other hormones impacting allergic inflammation. Currently, the mechanisms underlying these sex differences are poorly understood, although the effect of sex hormones, such as estrogen, on allergic inflammation is gaining interest. Asthma presents as a heterogeneous disease. In typical Th2-type allergic asthma, interleukin (IL)-4 and IL-13 predominate, driving IgE production and recruitment of eosinophils into the lungs. Chronic Th2-inflammation in the lung results in structural changes and activation of multiple immune cell types, leading to a deterioration of lung function over time. Most immune cells express estrogen receptors (ERα, ERβ, or the membrane-bound G-protein-coupled ER) to varying degrees and can respond to the hormone. Together these receptors have demonstrated the capacity to regulate a spectrum of immune functions, including adhesion, migration, survival, wound healing, and antibody and cytokine production. This review will cover the current understanding of estrogen signaling in allergic inflammation and discuss how this signaling may contribute to sex differences in asthma and allergy. PMID:26635789

  6. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

    International Nuclear Information System (INIS)

    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

  7. The role of estrogens at men. Part 2. Private clinical endocrinology and pathophysiology of estrogens at men

    Directory of Open Access Journals (Sweden)

    I. A. Tyuzikov

    2015-04-01

    Full Text Available Until now, estrogens are traditionally considered primarily as key hormones that perform critical functions in females, however, their role in males is not less important, although it remains understudied. However, a deep understanding of male physiology and endocrinology, it is imperative to solve practical problems of gender pathogenetic therapy of men,s diseases, is impossible today without taking into account the key role of testosterone in males, and without rethinking the role of estrogens, 80 % of which in males formed as a result of testosterone aromatisation. Thus, the violation of the synthesis and metabolism of testosterone in men naturally lead to disorder of the synthesis and metabolism of estrogen, which allows to express the idea that without estrogens, testosterone alone can not provide the entire range of the male body physiological effects. The second part of the literature review highlights exactly the Private Endocrinology and Pathophysiology of estrogens in men, which prove this assertion. The most important systems in which the regulation of the primary role of estrogens is presented in both sexes are central nervous system and bones, and possible mechanisms of these pathophysiological effects of estrogen in males are reviewed in detail. In addition, issues of influence of estrogens at the state of the male breast (gynecomastia, and shows close interaction of estrogens and androgens in providing function of male reproductive and cardiovascular systems. Today we know that the pathogenesis of such common disease in men as benign prostatic hyperplasia (BPH, is closely associated with the pathophysiology of both androgens and estrogens, so mechanisms of estrogens participation in the processes of prostatic proliferation (BPH are examined in detail in this review. Urgent problem of men,s health is prostate cancer, which has a hormonal nature, so current data available on the hormonal mechanisms of this disease with estrogens are

  8. Factors affecting the myocardial activity acquired during exercise SPECT with a high-sensitivity cardiac CZT camera as compared with conventional Anger camera

    Energy Technology Data Exchange (ETDEWEB)

    Verger, Antoine; Karcher, Gilles [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); INSERM U947 and Universite de Lorraine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Imbert, Laetitia [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Centre Alexis Vautrin, Department of Radiotherapy, Vandoeuvre (France); Yagdigul, Yalcine; Roch, Veronique [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Fay, Renaud [INSERM, Centre d' Investigation Clinique CIC-P 9501, Nancy (France); Djaballah, Wassila [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); INSERM U947 and Universite de Lorraine, Nancy (France); Rouzet, Francois; Le Guludec, Dominique [AP-HP, Hopital Bichat, Department of Nuclear Medicine, Paris (France); INSERM U 773 and Denis Diderot University, Paris (France); Fourquet, Nicolas [Clinique Pasteur, Toulouse (France); Poussier, Sylvain [INSERM U947 and Universite de Lorraine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); Marie, Pierre-Yves [CHU-Nancy, Department of Nuclear Medicine, Nancy (France); Nancyclotep experimental imaging platform, Nancy (France); INSERM U1116 and Universite de Lorraine, Nancy (France); CHU-Nancy, Allee du Morvan, Medecine Nucleaire, Hopital de Brabois, Vandoeuvre-les-Nancy (France)

    2014-03-15

    Injected doses are difficult to optimize for exercise SPECT since they depend on the myocardial fraction of injected activity (MFI) that is detected by the camera. The aim of this study was to analyse the factors affecting MFI determined using a cardiac CZT camera as compared with those determined using conventional Anger cameras. Factors affecting MFI were determined and compared in patients who had consecutive exercise SPECT acquisitions with {sup 201}Tl (84 patients) or {sup 99m}Tc-sestamibi (87 patients) with an Anger or a CZT camera. A predictive model was validated in a group of patients routinely referred for {sup 201}Tl (78 patients) or {sup 99m}Tc-sestamibi (80 patients) exercise CZT SPECT. The predictive model involved: (1) camera type, adjusted mean MFI being ninefold higher for CZT than for Anger SPECT, (2) tracer type, adjusted mean MFI being twofold higher for {sup 201}Tl than for {sup 99m}Tc-sestamibi, and (3) logarithm of body weight. The CZT SPECT model led to a +1 ± 26 % error in the prediction of the actual MFI from the validation group. The mean MFI values estimated for CZT SPECT were more than twofold higher in patients with a body weight of 60 kg than in patients with a body weight of 120 kg (15.9 and 6.8 ppm for {sup 99m}Tc-sestamibi and 30.5 and 13.1ppm for {sup 201}Tl, respectively), and for a 14-min acquisition of up to one million myocardial counts, the corresponding injected activities were only 80 and 186 MBq for {sup 99m}Tc-sestamibi and 39 and 91 MBq for {sup 201}Tl, respectively. Myocardial activities acquired during exercise CZT SPECT are strongly influenced by body weight and tracer type, and are dramatically higher than those obtained using an Anger camera, allowing very low-dose protocols to be planned, especially for {sup 99m}Tc-sestamibi and in non-obese subjects. (orig.)

  9. Immunoekspresi Reseptor α pada Poket Periodontal Lebih Banyak daripada Reseptor Estrogen β

    Directory of Open Access Journals (Sweden)

    Yuliana Mahdiyah Da’at Arina

    2013-07-01

    Full Text Available Studies have been reported on the association between menopause and periodontal disease related to estrogen deficiency. Although the estrogen receptor has been demonstrated on some oral tissues, the presence of estrogen receptors on periodontal pockets has not been discussed. This study was conducted to determine the difference of estrogen receptor α and β on periodontal pockets between menopausal and reproductive women. The results showed that the estrogen receptors α and β were expressed on periodontal pockets. The immunoexpression of estrogen receptor α in periodontal pocket epithelium of menopausal women was higher than that of estrogen receptor β, similarly to the reproductive women, but there was no significant difference in the immunoexpression of estrogen receptors α and β between menopausal and reproductive women. We concluded that the influence of estrogen on the periodontal pockets is more via estrogen receptor α both on menopausal and reproductive women.DOI: 10.14693/jdi.v15i1.84

  10. Estrogen enhances vasoconstrictive remodeling after injury in male rabbits

    Directory of Open Access Journals (Sweden)

    Francisco Y.A.

    2005-01-01

    Full Text Available The complete spectrum of estrogen vascular effects remains unclear. In particular, estrogen effects in the vascular response to profound injury in males have not been explored in detail. Therefore, we submitted 44 male New Zealand rabbits weighing 3.4 ± 0.6 kg to overdistention balloon injury of the right iliac artery. Rabbits were given 17ß-estradiol (5.45 µmol/day, sc or vehicle for 7 days before and 14 days after injury, when the arteries were examined by post-mortem histomorphometry. Arteriographic caliber was assessed in vivo at baseline and before sacrifice. On day 14 after injury, in vivo arteriographic caliber (baseline = 2.44 ± 0.43 mm was decreased by 23.1 ± 0.1% in controls and by 44.5 ± 0.1% in estrogen-treated rabbits (P < 0.001. Neither the neointimal area nor the neointima/media area ratio changed after estrogen treatment. Collagen fraction was increased in the media and neointima of estrogen-treated rabbits vs control (1.38 ± 1.30 vs 0.35 ± 0.67, respectively, P = 0.01. Taken together, these findings suggest that estrogen increased negative vascular remodeling. Transcription of endothelial and inducible nitric oxide synthases (eNOS and iNOS was analyzed by RT-PCR. eNOS mRNA expression was marginally increased after estrogen (P = 0.07 and injury. iNOS mRNA was increased 2- to 3-fold on day 14 after injury. With estrogen treatment, iNOS mRNA increased in uninjured arteries and exhibited a further 5.5-fold increase after injury. We concluded that estrogen increased lumen loss after balloon injury in male rabbits, likely by increased negative remodeling, which may be related to increased iNOS transcriptional rates.

  11. Functional adaptation in female rats: the role of estrogen signaling.

    Directory of Open Access Journals (Sweden)

    Susannah J Sample

    Full Text Available BACKGROUND: Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERβ, a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER. GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females. METHODOLOGY/PRINCIPAL FINDINGS: We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17β-estradiol, or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG gene expression of ERα, ERβ, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced. CONCLUSIONS: Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on

  12. Packing of transmembrane domain 2 of carnitine palmitoyltransferase-1A affects oligomerization and malonyl-CoA sensitivity of the mitochondrial outer membrane protein.

    Science.gov (United States)

    Jenei, Zsuzsanna A; Warren, Gemma Z L; Hasan, Muhammad; Zammit, Victor A; Dixon, Ann M

    2011-12-01

    The purpose of this study was to investigate the sequence-dependence of oligomerization of transmembrane domain 2 (TM2) of rat carnitine palmitoyltransferase 1A (rCPT1A), to elucidate the role of this domain in the function of the full-length enzyme. Oligomerization of TM2 was studied qualitatively using complementary genetic assays that facilitate measurement of helix-helix interactions in the Escherichia coli inner membrane, and multiple quantitative biophysical methods. The effects of TM2-mutations on oligomerization and malonyl-CoA inhibition of the full-length enzyme (expressed in the yeast Pichia pastoris) were quantified. Changes designed to disrupt close-packing of the GXXXG(A) motifs reduced the oligomeric state of the corresponding TM2 peptides from hexamer to trimer (or lower), a reduction also observed on mutation of the TM2 sequence in the full-length enzyme. Disruption of these GXXXG(A) motifs had a parallel effect on the malonyl-CoA sensitivity of rCPT1A, reducing the IC(50) from 30.3 ± 5.0 to 3.0 ± 0.6 μM. For all measurements, wild-type rCPT1A was used as a control alongside various appropriate (e.g., molecular mass) standards. Our results suggest that sequence-determined, TM2-mediated oligomerization is likely to be involved in the modulation of malonyl-CoA inhibition of CPT1A in response to short- and long-term changes in protein-protein and protein-lipid interactions that occur in vivo. PMID:21917985

  13. Contribution of a Membrane Estrogen Receptor to the Estrogenic Regulation of Body Temperature and Energy Homeostasis

    OpenAIRE

    Roepke, Troy A.; Bosch, Martha A.; Rick, Elizabeth A.; Lee, Benjamin; Wagner, Edward J.; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Scanlan, Thomas S.; Rønnekleiv, Oline K.; Martin J Kelly

    2010-01-01

    The hypothalamus is a key region of the central nervous system involved in the control of homeostasis, including energy and core body temperature (Tc). 17β-Estradiol (E2) regulates Tc, in part, via actions in the basal hypothalamus and preoptic area. E2 primarily controls hypothalamic functions via the nuclear steroid receptors, estrogen receptor α/β. However, we have previously described an E2-responsive, Gq-coupled membrane receptor that reduces the postsynaptic inhibitory γ-aminobutyric ac...

  14. Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

    Directory of Open Access Journals (Sweden)

    Hyun Yang

    2012-02-01

    Full Text Available Endocrine disruptors (EDs are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D9k (CaBP-9k, that may be used to assess estrogenic activity of EDs.

  15. Estrogen Therapy and Cognition: A Review of the Cholinergic Hypothesis

    OpenAIRE

    Gibbs, Robert B.

    2009-01-01

    The pros and cons of estrogen therapy for use in postmenopausal women continue to be a major topic of debate in women’s health. Much of this debate focuses on the potential benefits vs. harm of estrogen therapy on the brain and the risks for cognitive impairment associated with aging and Alzheimer’s disease. Many animal and human studies suggest that estrogens can have significant beneficial effects on brain aging and cognition and reduce the risk of Alzheimer’s-related dementia; however, oth...

  16. The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions

    OpenAIRE

    Kow, Lee-Ming; Pfaff, Donald W.

    2004-01-01

    The membrane actions of estrogens can facilitate their genomic actions. To determine whether this facilitation bears on CNS mechanisms for estrogen-dependent behaviors, ovariectomized rats were subjected to a two-pulse treatment of estrogen directly in the hypothalamic ventromedial nucleus. Two days later, each rat was given progesterone and then tested for lordosis behavior, the induction of which requires the genomic actions of estrogen. When estrogen was given in both pulses (15 min to 2 h...

  17. Raloxifene and Desmethylarzoxifene Block Estrogen-Induced Malignant Transformation of Human Breast Epithelial Cells

    OpenAIRE

    Kastrati, Irida; Edirisinghe, Praneeth D.; Hemachandra, L-P-Madhubani P.; Chandrasena, Esala R.; Choi, Jaewoo; Wang, Yue-Ting; Bolton, Judy L.; Thatcher, Gregory R.J.

    2011-01-01

    There is association between exposure to estrogens and the development and progression of hormone-dependent gynecological cancers. Chemical carcinogenesis by catechol estrogens derived from oxidative metabolism is thought to contribute to breast cancer, yet exact mechanisms remain elusive. Malignant transformation was studied in MCF-10A human mammary epithelial cells, since estrogens are not proliferative in this cell line. The human and equine estrogen components of estrogen replacement ther...

  18. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kita, Ayako; Higa, Mari [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Doi, Akira [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Satoh, Ryosuke [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Sugiura, Reiko, E-mail: sugiurar@phar.kindai.ac.jp [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan)

    2015-02-13

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2{sup +} gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2{sup +} gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking.

  19. Imp2, the PSTPIP homolog in fission yeast, affects sensitivity to the immunosuppressant FK506 and membrane trafficking in fission yeast

    International Nuclear Information System (INIS)

    Cytokinesis is a highly ordered process that divides one cell into two cells, which is functionally linked to the dynamic remodeling of the plasma membrane coordinately with various events such as membrane trafficking. Calcineurin is a highly conserved serine/threonine protein phosphatase, which regulates multiple biological functions, such as membrane trafficking and cytokinesis. Here, we isolated imp2-c3, a mutant allele of the imp2+ gene, encoding a homolog of the mouse PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1), using a genetic screen for mutations that are synthetically lethal with calcineurin deletion in fission yeast. The imp2-c3 mutants showed a defect in cytokinesis with multi-septated phenotypes, which was further enhanced upon treatment with the calcineurin inhibitor FK506. Notably, electron micrographs revealed that the imp2-c3 mutant cells accumulated aberrant multi-lamella Golgi structures and putative post-Golgi secretory vesicles, and exhibited fragmented vacuoles in addition to thickened septa. Consistently, imp2-c3 mutants showed a reduced secretion of acid phosphatase and defects in vacuole fusion. The imp2-c3 mutant cells exhibited a weakened cell wall, similar to the membrane trafficking mutants identified in the same genetic screen such as ypt3-i5. These findings implicate the PSTPIP1 homolog Imp2 in Golgi/vacuole function, thereby affecting various cellular processes, including cytokinesis and cell integrity. - Highlights: • We isolated imp2-c3, in a synthetic lethal screen with calcineurin in fission yeast. • The imp2+ gene encodes a component of the actin contractile ring similar to Cdc15. • The imp2-c3 mutants showed defects in cytokinesis, which were exacerbated by FK506. • The imp2-c3 mutants were defective in membrane trafficking and cell wall integrity. • Our study revealed a novel role for Imp2 in the Golgi/vacuolar membrane trafficking

  20. [Estrogen receptor alpha in obesity and diabetes].

    Science.gov (United States)

    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). PMID:27197110

  1. Potentiation of excitatory transmission in substantia gelatinosa neurons of rat spinal cord by inhibition of estrogen receptor alpha

    Directory of Open Access Journals (Sweden)

    Li Kai-Cheng

    2010-12-01

    Full Text Available Abstract Background It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. One of the estrogen receptor (ER subtypes, estrogen receptor alpha (ERα, is expressed in the spinal laminae I-V, including substantia gelatinosa (SG, lamina II. However, it is unclear how ERs are involved in the modulation of nociceptive transmission. Results In the present study, a selective ERα antagonist, methyl-piperidino-pyrazole (MPP, was used to test the potential functional roles of spinal ERα in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of MPP on SG neurons in the dorsal root-attached spinal cord slice prepared from adult rats. We found that MPP increased glutamatergic excitatory postsynaptic currents (EPSCs evoked by the stimulation of either Aδ- or C-afferent fibers. Further studies showed that MPP treatment dose-dependently increased spontaneous EPSCs frequency in SG neurons, while not affecting the amplitude. In addition, the PKC was involved in the MPP-induced enhancement of synaptic transmission. Conclusions These results suggest that the selective ERα antagonist MPP pre-synaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive transmission evoked by Aδ- and C-fiber stimulation could be potentiated by blocking ERα in the spinal neurons. Thus, the spinal estrogen may negatively regulate the nociceptive transmission through the activation of ERα.

  2. Evaluation of the Biological Activity of Opuntia ficus indica as a Tissue- and Estrogen Receptor Subtype-Selective Modulator.

    Science.gov (United States)

    An, Byoung Ha; Jeong, Hyesoo; Zhou, Wenmei; Liu, Xiyuan; Kim, Soolin; Jang, Chang Young; Kim, Hyun-Sook; Sohn, Johann; Park, Hye-Jin; Sung, Na-Hye; Hong, Cheol Yi; Chang, Minsun

    2016-06-01

    Phytoestrogens are selective estrogen receptor modulators (SERMs) with potential for use in hormone replacement therapy (HRT) to relieve peri/postmenopausal symptoms. This study was aimed at elucidating the molecular mechanisms underlying the SERM properties of the extract of Korean-grown Opuntia ficus-indica (KOFI). The KOFI extract induced estrogen response element (ERE)-driven transcription in breast and endometrial cancer cell lines and the expression of endogenous estrogen-responsive genes in breast cancer cells. The flavonoid content of different KOFI preparations affected ERE-luciferase activities, implying that the flavonoid composition likely mediated the estrogenic activities in cells. Oral administration of KOFI decreased the weight gain and levels of both serum glucose and triglyceride in ovariectomized (OVX) rats. Finally, KOFI had an inhibitory effect on the 17β-estradiol-induced proliferation of the endometrial epithelium in OVX rats. Our data demonstrate that KOFI exhibited SERM activity with no uterotrophic side effects. Therefore, KOFI alone or in combination with other botanical supplements, vitamins, or minerals may be an effective and safe alternative active ingredient to HRTs, for the management of postmenopausal symptoms. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26989859

  3. Bulk derivatization and cation exchange restricted access media-based trap-and-elute liquid chromatography–mass spectrometry method for determination of trace estrogens in serum

    International Nuclear Information System (INIS)

    Highlights: • Analysis of estrogens in small volume samples at low parts-per-trillion concentration. • Charged bulk derivatization facilitates on-line ion exchange sample preparation. • On-line WCX restricted access media traps analytes, but not proteins and lipids. • Complete preparation and LC–MS/MS analysis completed in 30 min/sample. - Abstract: Estrone (E1), estradiols (α/β-E2), and estriol (E3) are four major metabolically active estrogens exerting strong biological activities at very low circulating concentrations. This paper reports a sensitive and efficient method with automated, on-line clean-up and detection to determine trace estrogens in a small volume of serum samples using liquid chromatography–electrospray ionization–tandem mass spectrometry directly, without off-line liquid–liquid or solid-phase extraction pretreatments. Serum aliquots (charcoal stripped fetal bovine serum, 100 μL) were spiked with four estrogen standards and their corresponding isotope-labeled internal standards, then bulk derivatized with 2-fluoro-1-methyl-pyridium p-toluenesulfonate (2-FMP) to establish the calibration curves and perform method validation. Calibration was established in the concentration ranges of 5–1000 pg mL−1, and demonstrated good linearity of R2 from 0.9944 to 0.9997 for the four derivatized estrogens. The lower detection limits obtained were 3–7 pg mL−1. Good accuracy and precision in the range of 86–112% and 2.3–11.9%, respectively, were observed for the quality control (QC) samples at low, medium, and high concentration levels. The stability tests showed that the derivatized serum samples were stable 8 h after derivatization at room temperature and at least to 48 h if stored at −20 °C. The method was applied to measure trace estrogens in real human and bovine serum samples, and three of four estrogen compounds studied were observed and quantified

  4. Estrogen receptor alpha localization in the testes of men with normal spermatogenesis Estrogen receptor alpha localization in the testes of men with normal spermatogenesis

    Directory of Open Access Journals (Sweden)

    Eliza Filipiak

    2012-10-01

    Full Text Available It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER a and
    b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
    the localization of ERa in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men
    revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume
    of the testes was normal, hence obstructive azoospermia was suspected. The tissues from testicular surgical
    biopsies were fixed in Bouin’s fluid and embedded in paraffin. Assessments of the seminiferous epithelium (scoring
    10 to –1, the number of Leydig cells (scoring 1 to 5, the areal fraction of intertubular space (IS, measurements
    of seminiferous tubule diameter, and the thickness of the tubular wall, were performed on microscopic
    sections. Immunohistochemical staining was applied with monoclonal antibodies against ERa. The mean spermatogenesis
    score was 10 points; IS — 30.6 ± 8.1%; seminiferous tubule diameter — 193.9 ± 19.4 μm; thickness of
    tubular wall — 7.44 ± 1.1 μm; number of Leydig cells — 1.6 ± 1.1 points. Immunohistochemical staining showed
    the localization of ERa to be in the Sertoli and Leydig cell cytoplasm, while ERa was absent in germ cells. The
    results of testicular tissue analysis confirmed its normal structure and normal, full spermatogenesis. The presence
    of ERa in Sertoli and Leydig cells in normal human testis demonstrated in this study suggests that estrogens may
    affect testicular function.It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER a and
    b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
    the localization of ERa in the testes of adult men with normal spermatogenesis. Semen

  5. Non-enzymatic modifications of prostaglandin H synthase 1 affect bifunctional enzyme activity - Implications for the sensitivity of blood platelets to acetylsalicylic acid.

    Science.gov (United States)

    Kassassir, Hassan; Siewiera, Karolina; Talar, Marcin; Stec-Martyna, Emilia; Pawlowska, Zofia; Watala, Cezary

    2016-06-25

    Due to its ability to inhibit the blood platelet PGHS-1, acetylsalicylic acid (ASA, Aspirin(®)) is widely used as a preventive agent in atherothrombotic diseases. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair effective ASA-mediated acetylation process. On the other hand, it is proposed that ASA can prevent some of the late complications of diabetes by lowering the extent of glycation at protein free amino groups. The aim of this work was to evaluate the extents of non-enzymatic N-glycosylation (glycation) and acetylation of blood platelet PGHS-1 (COX-1) and the competition between glycation and acetylation was investigated in order to demonstrate how these two reactions may compete against platelet PGHS-1. When PGHS-1 was incubated with glycating/acetylating agents (glucose, Glu; 1,6-bisphosphofructose, 1,6-BPF; methylglyoxal, MGO, acetylsalicylic acid, ASA), the enzyme was modified in 13.4 ± 1.6, 5.3 ± 0.5, 10.7 ± 1.2 and 6.4 ± 1.1 mol/mol protein, respectively, and its activity was significantly reduced. The prior glycation/carbonylation of PGHS-1 with Glu, 1,6-BPF or MGO decreased the extent of acetylation from 6.4 ± 1.1 down to 2.5 ± 0.2, 3.6 ± 0.3 and 5.2 ± 0.2 mol/mol protein, respectively, but the enzyme still remained susceptible to the subsequent inhibition of its activity with ASA. When PGHS-1 was first acetylated with ASA and then incubated with glycating/carbonylating agents, we observed the following reductions in the enzyme modifications: from 13.4 ± 1.6 to 8.7 ± 0.6 mol/mol protein for Glu, from 5.3 ± 0.5 to 3.9 ± 0.3 mol/mol protein for 1,6-BPF and from 10.7 ± 1.2 to 7.5 ± 0.5 mol/mol protein for MGO, however subsequent glycation/carbonylation did not significantly affect PGHS-1 function. Overall, our outcomes allow to better understand the structural aspects of the chemical competition between glycation and acetylation of PGHS-1

  6. Sensitivity of spectral reflectance values to different burn and vegetation ratios: A multi-scale approach applied in a fire affected area

    Science.gov (United States)

    Pleniou, Magdalini; Koutsias, Nikos

    2013-05-01

    The aim of our study was to explore the spectral properties of fire-scorched (burned) and non fire-scorched (vegetation) areas, as well as areas with different burn/vegetation ratios, using a multisource multiresolution satellite data set. A case study was undertaken following a very destructive wildfire that occurred in Parnitha, Greece, July 2007, for which we acquired satellite images from LANDSAT, ASTER, and IKONOS. Additionally, we created spatially degraded satellite data over a range of coarser resolutions using resampling techniques. The panchromatic (1 m) and multispectral component (4 m) of IKONOS were merged using the Gram-Schmidt spectral sharpening method. This very high-resolution imagery served as the basis to estimate the cover percentage of burned areas, bare land and vegetation at pixel level, by applying the maximum likelihood classification algorithm. Finally, multiple linear regression models were fit to estimate each land-cover fraction as a function of surface reflectance values of the original and the spatially degraded satellite images. The main findings of our research were: (a) the Near Infrared (NIR) and Short-wave Infrared (SWIR) are the most important channels to estimate the percentage of burned area, whereas the NIR and red channels are the most important to estimate the percentage of vegetation in fire-affected areas; (b) when the bi-spectral space consists only of NIR and SWIR, then the NIR ground reflectance value plays a more significant role in estimating the percent of burned areas, and the SWIR appears to be more important in estimating the percent of vegetation; and (c) semi-burned areas comprising 45-55% burned area and 45-55% vegetation are spectrally closer to burned areas in the NIR channel, whereas those areas are spectrally closer to vegetation in the SWIR channel. These findings, at least partially, are attributed to the fact that: (i) completely burned pixels present low variance in the NIR and high variance in the

  7. Estrogen receptor α AF-2 mutation results in antagonist reversal and reveals tissue selective function of estrogen receptor modulators

    OpenAIRE

    Arao, Yukitomo; Hamilton, Katherine J.; Ray, Manas K.; Scott, Gregory; Mishina, Yuji; Korach, Kenneth S.

    2011-01-01

    The estrogen receptor (ER) is a ligand-dependent transcription factor containing two transcriptional activation domains. AF-1 is in the N terminus of the receptor protein and AF-2 activity is dependent on helix 12 of the C-terminal ligand-binding domain. Two point mutations of leucines 543 and 544 to alanines (L543A, L544A) in helix 12 minimized estrogen-dependent transcriptional activation and reversed the activity of the estrogen antagonists ICI182780 (ICI) and tamoxifen (TAM) into agonists...

  8. DNA microarray data integration by ortholog gene analysis reveals potential molecular mechanisms of estrogen-dependent growth of human uterine fibroids

    Directory of Open Access Journals (Sweden)

    Shou Jianyong

    2007-04-01

    Full Text Available Abstract Background Uterine fibroids or leiomyoma are a common benign smooth muscle tumor. The tumor growth is well known to be estrogen-dependent. However, the molecular mechanisms of its estrogen-dependency is not well understood. Methods Differentially expressed genes in human uterine fibroids were either retrieved from published papers or from our own statistical analysis of downloaded array data. Probes for the same genes on different Affymetrix chips were mapped based on probe comparison information provided by Affymetrix. Genes identified by two or three array studies were submitted for ortholog analysis. Human and rat ortholog genes were identified by using ortholog gene databases, HomoloGene and TOGA and were confirmed by synteny analysis with MultiContigView tool in the Ensembl genome browser. Results By integrated analysis of three recently published DNA microarray studies with human tissue, thirty-eight genes were found to be differentially expressed in the same direction in fibroid compared to adjacent uterine myometrium by at least two research groups. Among these genes, twelve with rat orthologs were identified as estrogen-regulated from our array study investigating uterine expression in ovariectomized rats treated with estrogen. Functional and pathway analyses of the twelve genes suggested multiple molecular mechanisms for estrogen-dependent cell survival and tumor growth. Firstly, estrogen increased expression of the anti-apoptotic PCP4 gene and suppressed the expression of growth inhibitory receptors PTGER3 and TGFBR2. Secondly, estrogen may antagonize PPARγ signaling, thought to inhibit fibroid growth and survival, at two points in the PPAR pathway: 1 through increased ANXA1 gene expression which can inhibit phospholipase A2 activity and in turn decrease arachidonic acid synthesis, and 2 by decreasing L-PGDS expression which would reduce synthesis of PGJ2, an endogenous ligand for PPARγ. Lastly, estrogen affects retinoic

  9. EARLY MORNING URINE ESTROGEN-GLUCURONIDE DETERMINATION FOR OVULATION PREDICTION

    Institute of Scientific and Technical Information of China (English)

    ZHUMei-Guang; TULCHINSKYD

    1989-01-01

    Monitoring of ovulation is necessary for induction of ovulation in clinical trials. Bakerfound that the conoentration of estrogen glucuronides was high in female urine and devel-oped a RIA method for direct measurment. Adlevcrefutz and some other five groups

  10. Postmenopausal Estrogen Therapy and Risk of Gallstone Disease

    DEFF Research Database (Denmark)

    Simonsen, Maja Hellfritzsch; Erichsen, Rune; Frøslev, Trine;

    2013-01-01

    BACKGROUND: Female gender and increasing age are key risk factors for gallstone disease; therefore, postmenopausal women are at high risk. Estrogen increases cholesterol saturation of bile and may further increase gallstone risk, but population-based evidence is sparse. OBJECTIVE: Our objective was...... to examine the association between postmenopausal estrogen therapy and risk of gallstone disease and the impact of duration of treatment and use of opposing progestin. STUDY DESIGN: We conducted a population-based case-control study. Cases were postmenopausal women (defined as aged ≥45 years) with...... gallstone disease identified in the period 1996-2010. For each case, we selected ten population controls matched to cases by age and sex. We defined exposure as any use of estrogen (opposed and unopposed by progestin). Cases/controls were categorized as current estrogen users if their last prescription was...

  11. STUDY OF ESTROGEN BINDING SITE ON HUMAN EJACULATED SPERMATOZOA

    Institute of Scientific and Technical Information of China (English)

    CHUJin-Shong; WANGYi-Fei

    1989-01-01

    The specific estrogen binding site for 17β-estradiol has been investigated on human spermatozoa by electron microscopec autoradiography. The results show that the binding sites were distributed over the surface of human spermatozoa: acrosomal cap, equatorial

  12. A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings.

    Science.gov (United States)

    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

  13. Role of estrogen receptor-α on food demand elasticity.

    Science.gov (United States)

    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. PMID:25869426

  14. Estrogenicity of selected biphenyls evaluated using a recombinant yeast assay

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, T.W.; Kraut, D.H.; Sayler, G.S.; Layton, A.C. [Univ. of Tennessee, Knoxville, TN (United States)

    1998-09-01

    The estrogenic activity of biphenyl and 4-hydroxylated derivatives with varied levels of chloro- and/or hydroxyl substitution was measured in a Saccharomyces cerevisiae-based lac-Z ({beta}-galactosidase) reporter assay, {beta}-Galactosidase activity was compared with competitive binding to soluble mouse uterine estrogen receptor protein. The comparison of relative potency for biphenyls hydroxylated on one ring and chlorinated on the other ring (n = 5) revealed excellent correlation between the two systems (r{sup 2} = 0.995). However, estrogenicities of biphenyls hydroxylated and chlorinated on the same ring were not in agreement. Although weak ligand binding was demonstrated for these compounds, {beta}-galactosidase activity was not observed. Rather, these compounds were shown to be cytotoxic to yeast. The results of this study further support the hypothesis that both an unhindered phenolic ring and molecular symmetry are structural features associated with estrogenicity.

  15. Brain endogenous estrogen levels determine responses to estrogen replacement therapy via regulation of BACE1 and NEP in female Alzheimer’s transgenic mice

    OpenAIRE

    Li, Rena; He, Ping; Cui, Jie; Staufenbiel, Matthias; Harada, Nobuhiro; Shen, Yong

    2012-01-01

    Estrogens have been found to improve memory and reduce risk of dementia, although conflicting results such as failure of estrogen replacement therapy for treatment of Alzheimer’s disease (AD) also has been reported. Only recently, our published human brain studies showed a depletion of brain estrogen in women with Alzheimer’s disease, while other studies have demonstrated cognitive impairment believed to be caused by inhibition of endogenous estrogen synthesis in females. To investigate wheth...

  16. A systematic comparison of three commercial estrogen receptor assays in a single clinical outcome breast cancer cohort.

    Science.gov (United States)

    Kornaga, Elizabeth N; Klimowicz, Alexander C; Guggisberg, Natalia; Ogilvie, Travis; Morris, Don G; Webster, Marc; Magliocco, Anthony M

    2016-08-01

    Breast cancers are routinely assessed for estrogen receptor status using immunohistochemical assays to assist in patient prognosis and clinical management. Specific assays vary between laboratories, and several antibodies have been validated and recommended for clinical use. As numerous factors can influence assay performance, many laboratories have opted for ready-to-use assays using automated stainers to improve reproducibility and consistency. Three commonly used autostainer vendors-Dako, Leica, and Ventana-all offer such estrogen receptor assays; however, they have never been directly compared. Here, we present a systematic comparison of three platform-specific estrogen receptor ready-to-use assays using a retrospective, tamoxifen-treated, breast cancer cohort from patients who were treated in Calgary, Alberta, Canada from 1985 to 2000. We found all assays showed good intra-observer agreement. Inter-observer pathological scoring showed some variability: Ventana had the strongest agreement followed closely by Dako, whereas Leica only showed substantial agreement. We also analyzed each estrogen receptor assay with respect to 5-year disease-free survival, and found that all performed similarly in univariate and multivariate models. Determination of measures of test performance found that the Leica assay had a lower negative predictive value than Dako or Ventana, compared with the original ligand-binding assay, while other measures-sensitivity, specificity, positive predictive value, and accuracy-were comparable between the three ready-to-use assays. When comparing against disease-free survival, the difference in negative predictive value between the vendor assays were not as extreme, but Dako and Ventana still performed slightly better than Leica. Despite some discordance, we found that all ready-to-use assays were comparable with or superior to the ligand-binding assay, endorsing their continued use. Our analysis also allowed for exploration of estrogen receptor

  17. Estrogen formulations and beauty care practices in Japanese women

    OpenAIRE

    Takeda T; Wong TF; Kitamura M; Yaegashi N

    2012-01-01

    Takashi Takeda, Tze Fang Wong, Mari Kitamura, Nobuo YaegashiDepartment of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Miyagi, JapanPurpose: Traditionally, oral estrogens have been used for hormone replacement therapy. However, in Japan, additional estrogen formulations have been used, including transdermal patches and transdermal gels. The latter have a unique commonality with cosmetics because both of them are applied to the skin. Beauty care is one of the most ...

  18. Functional role of estrogen in pituitary tumor pathogenesis

    OpenAIRE

    Heaney, Anthony P.; Fernando, Manory; Melmed, Shlomo

    2002-01-01

    Pituitary hyperplasia and lactotroph replication are induced by estrogen. The product of the pituitary tumor transforming gene (PTTG) exhibits in vitro and in vivo transforming activity and induces basic bFGF secretion, thereby modulating pituitary angiogenesis and tumor formation. We demonstrated previously that pituitary pttg is induced by estrogen and bFGF, the latter being expressed in a concordant fashion with pttg in experimental and human pituitary adenomas. We now elucidate the role o...

  19. Weak estrogenic transcriptional activities of Bisphenol A and Bisphenol S

    OpenAIRE

    GRIGNARD ELISE; Bremer, Susanne; LAPENNA SILVIA

    2011-01-01

    In 2011, the European Commission has restricted the use of Bisphenol A in plastic infant feeding bottles. In a response to this restriction, Bisphenol S is now often used as a component of plastic substitutes for the production of babybottles. One of the major concerns leading to the restriction of Bisphenol A was its weak estrogenic activity. By using two highly standardised transactivation assays, we could demonstrate that the estrogenic activity of Bisphenol A and Bisphenol S i...

  20. 2', 3', 4'-trihydroxychalcone is an Estrogen Receptor Alpha Coagonist

    OpenAIRE

    Herber, Candice Blair

    2014-01-01

    Estrogens in hormone replacement therapy (HRT) decrease menopausal symptoms, but increase the risks of reproductive cancers. The beneficial effects of estrogen on peripheral tissues and the adverse proliferative effects on the uterus and mammary gland are mediated by ERalpha. Currently HRT is approved only for short-term use. Short-term HRT works for decreasing symptoms associated with menopause, however, long-term usage is needed to prevent subclinical diseases. Because estradiol-bound ERalp...

  1. Estrogen induces Vav1 expression in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Ming-juan Du

    Full Text Available Vav1, a guanine nucleotide exchange factor (GEF for Rho family GTPases, is a hematopoietic protein involved in a variety of cellular events. In recent years, aberrant expression of Vav1 has been reported in non-hematopoietic cancers including human breast cancer. It remains to be answered how Vav1 is expressed and what Vav1 does in its non-resident tissues. In this study, we aimed to explore the mechanism for Vav1 expression in breast cancer cells in correlation with estrogen-ER pathway. We not only verified the ectopic expression of Vav1 in human breast cancer cell lines, but also observed that Vav1 expression was induced by 17β-estradiol (E2, a typical estrogen receptor (ER ligand, in ER-positive cell lines. On the other hand, Tamoxifen, a selective estrogen receptor modulator (SERM, and ICI 182,780, an ER antagonist, suppressed the expression of Vav1. The estrogen receptor modulating Vav1 expression was identified to be α form, not β. Furthermore, treatment of E2 increased the transcription of vav1 gene by enhancing the promoter activity, though there was no recognizable estrogen response element (ERE. Nevertheless, two regions at the vav1 gene promoter were defined to be responsible for E2-induced activation of vav1 promoter. Chromatin immunoprecipitation (ChIP and co-immunoprecipitation (Co-IP analyses suggested that ERα might access to the vav1 promoter via interacting with transcription factors, c-Myb and ELF-1. Consequently, the enhanced expression of Vav1 led to the elevation of Cyclin D1 and the progression of cell cycle. The present study implies that estrogen-ER modulates the transcription and expression of Vav1, which may contribute to the proliferation of cancerous cells.

  2. Estrogenicity of paper and cardboard used as food containers

    OpenAIRE

    Lopez-Espinosa, Maria Jose; Granada, Alicia; Araque, Patricia; Molina-Molina, Jose Manuel; Puertollano, Maria Carmen; Rivas, Ana Maria; Fernandez, Mariana; Cerrillo, Isabel; Olea-Serrano, Maria Fatima; Lopez, Concepcion; Olea, Nicolas

    2007-01-01

    Abstract Bisphenol-A (BPA), dibutyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP), common chemical residues in food packaging materials, were investigated in paper and cardboard containers used for take-away food. Estrogenicity of aqueous extracts was tested in E-Screen bioassay and presence of chemicals by high performance liquid chromatography and gas chromatography/mass spectrometry. Estrogenicity was demonstrated in 90% of extracts (geometric mean [GM] = 11.97 pM estrad...

  3. Toxicogenomics-based in vitro alternatives for estrogenicity testing

    OpenAIRE

    Wang, S.

    2013-01-01

    Testing chemicals for their endocrine-disrupting potential, including interference with estrogen receptor signaling, is an important aspect to assess the safety of currently used and newly developed chemicals. The standard test for disruption of normal estrogen function is the in vivo uterotrophic assay in immature or ovariectomised rodents with uterus weight as a crucial read-out parameter. Due to the high costs, ethical objections and labour intensiveness of the in vivo uterotrophic assay, ...

  4. A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings

    OpenAIRE

    Andrea Gogos; Sbisa, Alyssa M.; Jeehae Sun; Andrew Gibbons; Madhara Udawela; Brian Dean

    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 ...

  5. Palmitoylation of Estrogen Receptors Is Essential for Neuronal Membrane Signaling

    OpenAIRE

    Meitzen, John; Luoma, Jessie I.; Boulware, Marissa I.; Hedges, Valerie L.; Peterson, Brittni M.; Tuomela, Krista; Britson, Kyla A.; Mermelstein, Paul G.

    2013-01-01

    In addition to activating nuclear estrogen receptor signaling, 17β-estradiol can also regulate neuronal function via surface membrane receptors. In various brain regions, these actions are mediated by the direct association of estrogen receptors (ERs) activating metabotropic glutamate receptors (mGluRs). These ER/mGluR signaling partners are organized into discrete functional microdomains via caveolin proteins. A central question that remains concerns the underlying mechanism by which these s...

  6. Relevant Factors of Estrogen Changes of Myopia in Adolescent Females

    OpenAIRE

    Juan-Fen Gong; Hong-Li Xie; Xin-Jie Mao; Xue-Bo Zhu; Zuo-Kai Xie; Hai-Hong Yang; Yang Gao; Xiao-Feng Jin; Yu Pan; Fen Zhou

    2015-01-01

    Background: Gender is one of the risk factors accounting for the high prevalence of adolescent myopia. Considerable research results have shown that myopia incidence of female is higher than that of male. This study aimed to analyze the correlation between ocular parameters and serum estrogen level and to investigate the vision changes along with estrogen change in menstrual cycle of adolescent females. Methods: A total of 120 young females aged between 15 and 16 years, diagnosed with myo...

  7. Sex-Dependent Influence of Endogenous Estrogen in Pulmonary Hypertension

    Science.gov (United States)

    Mair, Kirsty M.; Wright, Audrey F.; Duggan, Nicholas; Rowlands, David J.; Hussey, Martin J.; Roberts, Sonia; Fullerton, Josephine; Nilsen, Margaret; Loughlin, Lynn; Thomas, Matthew

    2014-01-01

    Rationale: The incidence of pulmonary arterial hypertension is greater in women, suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males, exogenously administered estrogen can protect against pulmonary hypertension (PH). However, in models that display female susceptibility, estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and sex in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH: the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of sex on pulmonary expression of aromatase in these models and in lungs from patients with pulmonary arterial hypertension. Measurements and Main Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was caused by reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor α also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased bone morphogenetic protein receptor 2 and Id1 expression compared with male. Anastrozole treatment reversed the impaired bone morphogenetic protein receptor 2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared with male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential. PMID:24956156

  8. Artery Wall Imaging and Effects of Postmenopausal Estrogen Therapy

    OpenAIRE

    Rodriguez-Macias Wallberg, Kenny A.

    2005-01-01

    Postmenopausal estrogen therapy, initiated early in the menopause, seems to protect against development of atherosclerosis and cardiovascular diseases. This thesis concerns studies of artery wall thickness and arterial stiffness estimated by noninvasive ultrasound techniques in long-term estrogen treated postmenopausal women who initiated therapy at the time of the menopause. A noninvasive 25 MHz high-frequency ultrasound technique was validated in the imaging of superficial arteries by using...

  9. Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds on both receptor types

    NARCIS (Netherlands)

    Bovee, T.F.H.; Helsdingen, J.R.; Rietjens, I.M.C.M.; Keijer, J.; Hoogenboom, L.A.P.

    2004-01-01

    Previously, we described the construction of a rapid yeast bioassay stably expressing human estrogen receptor (hER) and yeast enhanced green fluorescent protein (yEGFP) in response to estrogens. In the present study, the properties of this assay were further studied by testing a series of estrogenic

  10. Estrogenic Impact on Cardiac Ischemic/Reperfusion Injury.

    Science.gov (United States)

    Sivasinprasasn, Sivaporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-02-01

    The increase in cardiovascular disease and metabolic syndrome incidence following the onset of menopause has highlighted the role of estrogen as a cardiometabolic protective agent. Specifically regarding the heart, estrogen induced an improvement in cardiac function, preserved calcium homeostasis, and inhibited the mitochondrial apoptotic pathway. The beneficial effects of estrogen in relation to cardiac ischemia/reperfusion (I/R) injury, such as reduced infarction and ameliorated post-ischemic recovery, have also been shown. Nevertheless, controversial findings exist and estrogen therapy is reported to be related to a higher rate of thromboembolic events and atrial fibrillation in post-menopausal women. Therefore, greater clarification is needed to evaluate the exact potential of estrogen use in cases of cardiac I/R injury. This article reviews the effects of estrogen, in both acute and chronic treatment, and collates the studies with regard to their in vivo, in vitro, or clinical trial settings in cases of cardiac I/R injury and myocardial infarction. PMID:26786980

  11. Selective estrogen receptor modulators promising for cardiac syndrome X

    Directory of Open Access Journals (Sweden)

    Chen Y

    2010-01-01

    Full Text Available Cardiac syndrome X (CSX is defined as a typical anginal-like chest pain with a transient ischemic electrocardiogram, but without abnormal coronary angiography. It is usually accepted that endothelial dysfunction, inflammation, oxidative stress and estrogen deficiency are the main reasons of CSX. There are some methods to treat CSX including statins, b blocker, angiotensin converting enzyme inhibitors, nitrates, estrogen, and so on. The estrogen replacement therapy (ERT, in particular, has been reported by many researchers to significantly reduce the frequency of chest pain after administration of estrogen, which has been explained as estrogen acting on its receptor to improve the endothelial function. However, it has been suggested that ERT must not be used for coronary heart disease due to its adverse effects. However, some selective estrogen receptor modulators (SERMs can inhibit inflammatory response as well as oxidative stress, and improve the endothelial function, to reduce the occurrence of chest pain. Here, we hypothesize that SERMs may be the beneficial selection for patients with CSX.

  12. The in vitro estrogenic activities of triclosan and triclocarban.

    Science.gov (United States)

    Huang, Hongyu; Du, Guizhen; Zhang, Wei; Hu, Jialei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2014-09-01

    Triclosan (TCS) and triclocarban (TCC), as broad spectrum antibacterial agents, are distributed widely in the environment and humans. Most studies have focused on their distribution and biodegradation, but the endocrine-disrupting effects of these chemicals, especially their estrogenic effects, are still unclear. In the present study, we investigated the estrogenic effects of TCS and TCC using a series of in vitro assays, including the ER reporter gene assay in the CV-1 cells, E-screen assay and evaluation of estrogen-responsive genes in the MCF-7 cells. The tested concentrations of TCS and TCC were both from 1 × 10(-9) to 1 × 10(-6)  M. Results showed that TCS and TCC exerted estrogenic activities by inducing luciferase activities in an ER reporter gene assay, promoting the proliferation of the MCF-7 cells, up-regulating the expression of pS2 and down-regulating ERα expression at both the mRNA and protein levels in the MCF-7 cells. We further found that TCS and TCC could alter the expression of multiple microRNAs (mir-22, mir-206 and mir-193b) in the MCF-7 cells, which would help understand the mechanisms of their estrogenic effects on regulating the expression of ERα. In brief, our results demonstrated the potential estrogenic effects and profiled in vitro data for further risk assessment of TCS and TCC. PMID:24740835

  13. Combined effects of estrogenic chemicals with the same mode of action using an estrogen receptor binding bioassay.

    Science.gov (United States)

    Yang, Rong; Li, Na; Ma, Mei; Wang, Zijian

    2014-11-01

    The increasing amounts of various estrogenic chemicals coexisting in the aquatic environment may pose environmental risks. While the concept of estradiol equivalent (EEQ) has been frequently applied in studying estrogenic mixtures, few experiments have been done to prove its reliability. In this study, the reliability of EEQ and the related model concentration addition (CA) was verified based on the two-hybrid recombinant yeast bioassay when all mixture components had the same mode of action and target of action. Our results showed that the measured estrogenic effects could be well predicted by CA and EEQ for all laboratory-made mixtures using two designs, despite the varying estrogenic activity, concentration levels and ratios of the test chemicals. This suggests that when an appropriate endpoint and its relevant bioassay are chosen, CA should be valid and the application of EEQ in predicting the effect of non-equi-effect mixtures is feasible. PMID:25461542

  14. Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse

    Directory of Open Access Journals (Sweden)

    Marie Laure Kottler

    2011-10-01

    Full Text Available The precise role of estrogen in the pathogenesis of pelvic organ prolapse (POP is still unclear, while the results concerning the effect of selective estrogen receptor modulators on pelvic organ prolapse are contradictory. Our aim was to test whether alteration in the expression of estrogen receptors in the pelvic floor of preand post-menopausal women is related to genital prolapse status. The mRNA levels of ERα and ERβ in 60 biopsy specimens were measured. Significantly higher expression of ERα and higher ERα/ERβ ratio were demonstrated in post-menopausal women compared to pre-menopausal women. Higher expression of ERα and higher ERα/ERβ ratio were detected in all studied groups with POP, thus it did not reach significance in the post-menopausal group. Pre-menopausal and post-menopausal women presenting pelvic organ prolapse had no difference in the ERα expression. Our preliminary study may indicate that pelvic organ prolapse is associated with higher expression of ERα/ERβ in the pelvic floor of both pre- and post-menopausal women; thus not reaching statistical significance in the post-menopausal women was probably due to the group’s size. We believe that the inevitable changes in the estrogen receptor expression over women’s different lifetimes may affect the risk of genital prolapse progression, and might contribute to the further search for appropriate selective estrogen receptor modulators as a treatment for women with pelvic organ prolapse. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 3, pp. 521–527

  15. The antiestrogens tamoxifen and fulvestrant abolish estrogenic impacts of 17α-ethinylestradiol on male calling behavior of Xenopus laevis.

    Science.gov (United States)

    Hoffmann, Frauke; Kloas, Werner

    2012-01-01

    Various synthetic chemicals released to the environment can interfere with the endocrine system of vertebrates. Many of these endocrine disrupting compounds (EDCs) exhibit estrogenic activity and can interfere with sexual development and reproductive physiology. More recently, also chemicals with different modes of action (MOAs), such as antiestrogenic, androgenic and antiandrogenic EDCs, have been shown to be present in the environment. However, to date EDC-research primarily focuses on exposure to EDCs with just one MOA, while studies examining the effects of simultaneous exposure to EDCs with different MOAs are rare, although they would reflect more real, natural exposure situations. In the present study the combined effects of estrogenic and antiestrogenic EDCs were assessed by analyzing the calling behavior of short-term exposed male Xenopus laevis. The estrogenic 17α-ethinylestradiol (EE2), and the antiestrogenic EDCs tamoxifen (TAM) and fulvestrant (ICI) were used as model substances. As previously demonstrated, sole EE2 exposure (10-10 M) resulted in significant alterations of the male calling behavior, including altered temporal and spectral parameters of the advertisement calls. Sole TAM (10-7 M, 10-8 M, 10-10 M) or ICI (10-7 M) exposure, on the other hand, did not affect any of the measured parameters. If frogs were co-exposed to EE2 (10-10 M) and TAM (10-7 M) the effects of EE2 on some parameters were abolished, but co-exposure to EE2 and ICI (10-7 M) neutralized all estrogenic effects. Thus, although EDCs with antiestrogenic MOA might not exhibit any effects per se, they can alter the estrogenic effects of EE2. Our observations demonstrate that there is need to further investigate the combined effects of EDCs with various, not only opposing, MOAs as this would reflect realistic wildlife situations. PMID:23028589

  16. Role of estrogen receptor ligand and estrogen response element sequence on interaction with chicken ovalbumin upstream promoter transcription factor (COUP-TF).

    Science.gov (United States)

    Klinge, C M

    1999-11-01

    Estrogen-responsive genes are regulated by altering the balance of estrogen receptor (ER) interaction with transcription activators and inhibitors. Here we examined the role of ER ligand on ER interaction with the Chicken Ovalbumin Upstream Promoter Transcription Factor (COUP-TF) orphan nuclear receptor. COUP-TF binding to half-site estrogen response elements (EREs) was increased by the addition of estradiol (E2) -liganded ER (E2-ER), but not by ER liganded with the antiestrogens 4-hydroxytamoxifen (4-OHT-ER) or tamoxifen aziridine (TAz-ER). ER did not bind to single half-sites. Conversely, COUP-TF enhanced the ERE binding of purified E2-ER, but did not affect TAz-ER-ERE binding. In contrast, only antiestrogens enhanced direct interaction between ER and COUP-TF as assessed by GST pull-down assays. Identical results were obtained using either purified bovine or recombinant human ERalpha. Co-immunoprecipitation assays showed that ER and COUP-TF interact in extracts from MCF-7 and ERalpha-transfected MDA-MB-231 cells. Here we document that ER ligand impacts COUP-TF-ER interaction. COUP-TF interaction is mediated by the DNA binding and ligand-binding domains of ER. We suggest that changes in ER conformation induced by DNA binding reduce ER-COUP-TF interaction. Transient transfection of human MCF-7 breast cancer cells with a COUP-TFI expression vector repressed E2-induced luciferase reporter gene expression from single or multiple tandem copies of a consensus ERE. COUP-TFI stimulated 4-OHT-induced luciferase activity from a minimal ERE. Alone, COUP-TFI increased transcription from ERE half-sites or a single ERE in a sequence-dependent manner. These data provide evidence that the ERE sequence and its immediate flanking regions influence whether COUP-TF enhances, inhibits, or has no effect on ER ligand-induced ERE reporter gene expression and that COUP-TFI activates gene transcription from ERE half-sites. We suggest that COUP-TFI plays a role in mitigating estrogen

  17. Occurrence of selected estrogenic compounds and estrogenic activity in surface water and sediment of Langat River (Malaysia).

    Science.gov (United States)

    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. PMID:27353134

  18. Estrogen withdrawal from osteoblasts and osteocytes causes increased mineralization and apoptosis.

    Science.gov (United States)

    Brennan, M Á; Haugh, M G; O'Brien, F J; McNamara, L M

    2014-07-01

    Recent studies have demonstrated increased bone mineral heterogeneity following estrogen withdrawal in vivo. Such changes likely contribute to fracture risk during post-menopausal osteoporosis since tissue mineralization is correlated with bone strength and stiffness. However, the cellular mechanisms responsible for increased mineral variability have not yet been distinguished. The objective of this study is to elucidate how alterations in mineral distribution are initiated during estrogen depletion. Specifically, we tested two separate hypotheses; (1) estrogen deficiency directly alters osteoblast mineralization and (2) estrogen deficiency increases bone cell apoptosis. Osteoblast-like cells (MC3T3-E1) and osteocyte-like cells (MLO-Y4) were pretreated with or without estrogen (17β-estradiol) for 14 days. Estrogen deficiency was subsequently induced by either withdrawing estrogen from cells or blocking estrogen receptors using an estrogen antagonist, fulvestrant (ICI 182,780). Cell number (Hoechst DNA), alkaline phosphatase activity (p-NPP), mineralization (alizarin red) and apoptosis (Caspase 3/7) were evaluated. Whether estrogen withdrawal altered apoptosis rates in the presence of an apoptosis promoting agent (etoposide) was also determined. Interestingly, estrogen withdrawal from cells accustomed to estrogen exposure caused significantly increased osteoblast mineralization and osteocyte apoptosis compared with continued estrogen treatment. In contrast, blocking estrogen receptors with fulvestrant abrogated the mineralization induced by estrogen treatment. When apoptosis was induced using etoposide, cells undergoing estrogen withdrawal increased apoptosis compared to cells with continued estrogen treatment. Recognizing the underlying mechanisms regulating bone cell mineralization and apoptosis during estrogen deficiency and their consequences is necessary to further our knowledge of osteoporosis. PMID:24446157

  19. Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation.

    Science.gov (United States)

    Ho, Ming-Fen; Bongartz, Tim; Liu, Mohan; Kalari, Krishna R; Goss, Paul E; Shepherd, Lois E; Goetz, Matthew P; Kubo, Michiaki; Ingle, James N; Wang, Liewei; Weinshilboum, Richard M

    2016-03-01

    We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype. In the present study, we pursued mechanisms underlying the E2-SNP-dependent regulation of TCL1A expression and, in parallel, our subsequent observations that SNPs at a distance from EREs can regulate ERα binding and that ER antagonists can reverse phenotypes associated with those SNPs. Specifically, we performed a series of functional genomic studies using a large panel of lymphoblastoid cell lines with dense genomic data that demonstrated that TCL1A SNPs at a distance from EREs can modulate ERα binding and expression of TCL1A as well as the expression of downstream immune mediators. Furthermore, 4-hydroxytamoxifen or fulvestrant could reverse these SNP-genotype effects. Similar results were found for SNPs in the IL17A cytokine and CCR6 chemokine receptor genes. These observations greatly expand our previous results and support the existence of a novel molecular mechanism that contributes to the complex interplay between estrogens and immune systems. They also raise the possibility of the pharmacological manipulation of the expression of proinflammatory cytokines and chemokines in a SNP genotype-dependent fashion. PMID:26866883

  20. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin

    Institute of Scientific and Technical Information of China (English)

    Yuan Guang Meng; Wei Dong Han; Ya Li Zhao; Ke Huang; Yi Ling Si; Zhi Qiang Wu; Yi Ming Mu

    2007-01-01

    LRP16 was previously identified as an estrogen-induced gene in breast cancer cells.The responsiveness of LRPl6to estrogen and its functional effects in endometrial cancer(EC)cells are still unclear.Here,we show that the mRNAlevel and promoter activity of the LRP16 gene were significantly increased by 17β-estradiol(E2)in estrogen receptorα(ERα)-positive Ishikawa human EC cells.Although the growth rate of Ishikawa cells was not obviously affected byectopic expression of LIP16,the results of a Transwell assay showed an approximate one-third increase of the invasivecapacity of LRP16-overexpressing cells.As a result of molecular screening,we observed that the expression of E-cadherin,an essential adhesion molecule associated with tumor metastasis,was repressed by LRP16.Further promoter analysesdemonstrated that LRP16 inhibited E-cadherin transactivation in a dose-dependent manner.However,the inhibition wasabolished by estrogen deprivation.indicating that the downregulation of E-cadherin transcription by LRP16 requiresERa mediation.Chromatin immunoprecipitation analyses revealed that the binding of ERa to the E-cadherin promoterwas antagonized by LRP16,suggesting that LRP16 could interfere with ERα-mediated transcription.These results sug-gest that the upregulation of LRP16 by estrogen could be involved in invasive growth by downregulating E-cadherin inhuman ECs.

  1. A comparative study of vaginal estrogen cream and sustained-release estradiol vaginal tablet (Vagifem in the treatment of atrophic vaginitis in Isfahan, Iran in 2010-2012

    Directory of Open Access Journals (Sweden)

    Pardis Hosseinzadeh

    2015-01-01

    Full Text Available Background: Atrophic vaginitis is a disease, which affects up to 50% of postmenopausal women. This study compared the effectiveness and user-friendliness of Vagifem (an estradiol vaginal tablet and vaginal estrogen cream in the treatment of atrophic vaginitis. Materials and Methods: One hundred and sixty postmenopausal women with symptoms of atrophic vaginitis were randomly divided into two groups of treatment with Vagifem or with vaginal estrogen cream for 12 weeks. Patients used the medication daily for the first 2 weeks of the study, and twice weekly. Severity of vaginal atrophy and four main symptoms of atrophic vaginitis including dysuria, dyspareunia, vaginal itching, and dryness were evaluated and compared before and after treatment. In addition, patients were asked regarding user-friendliness and hygienic issues of medications. Results: Both vaginal estrogen cream and Vagifem significantly improved symptoms of atrophic vaginitis but in terms of effectiveness for the treatment symptoms of atrophic vaginitis, there was no significant difference between the two medications. Vagifem compared to estrogen cream resulted in significantly lower rate of hygienic problems (0% versus 23%, P < 0.001, and was reported by the patients as a significantly easier method of treatment (90% versus 55%, P < 0.0001. Conclusion: This investigation showed that Vagifem is an appropriate medication for the treatment of atrophic vaginitis, which is as effective as vaginal estrogen creams and is more user-friendly.

  2. Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors.

    Science.gov (United States)

    Madureira, Tânia Vieira; Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia; Urbatzka, Ralph; Castro, L Filipe C; Rocha, Eduardo

    2015-12-01

    Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol-EE2) at 1, 10 and 50μM; (2) an ER antagonist (ICI 182,780) at 10 and 50μM; and (3) mixtures of both (Mix I-10μM EE2 and 50μM ICI; Mix II-1μM EE2 and 10μM ICI and Mix III-1μM EE2 and 50μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A-VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase-Uox, 17β-hydroxysteroid dehydrogenase 4-17β-HSD4, peroxin 11α-Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα mRNA increased after all EE2 treatments, while ERβ-1 had an inverse pattern. The EE2 action was reversed by ICI 182,780 in a concentration-dependent manner, for VtgA, ERα and Uox. Overall, our data show the great value of primary brown trout hepatocytes to study the effects of estrogenic/anti-estrogenic inputs in peroxisome kinetics and in ER and PPARα signaling, backing the still open hypothesis of crosstalk interactions between these pathways and calling for more mechanistic

  3. Pharmacogenomics of estrogens on changes in carotid artery intima-medial thickness and coronary arterial calcification: Kronos Early Estrogen Prevention Study.

    Science.gov (United States)

    Miller, Virginia M; Jenkins, Gregory D; Biernacka, Joanna M; Heit, John A; Huggins, Gordon S; Hodis, Howard N; Budoff, Matthew J; Lobo, Rogerio A; Taylor, Hugh S; Manson, JoAnn E; Black, Dennis M; Naftolin, Frederick; Harman, S Mitchell; de Andrade, Mariza

    2016-01-01

    Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n = 606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in the same KEEPS participants 4 yr after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β-estradiol (50 μg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Twenty SNPs within the innate immunity pathway most related with CIMT after 4 yr were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, single nucleotide polymorphisms (SNPs) within the innate immunity pathway were found to alter the treatment effect on 4 yr change in CIMT (i.e., significant interaction between treatment and genetic variation in the innate immunity pathway; P 5 Agatston units after 4 yr. Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT. PMID:26508701

  4. In vitro binding of the purified hormone-binding subunit of the estrogen receptor to oligonucleotides containing natural or modified sequences of an estrogen-responsive element.

    Science.gov (United States)

    Medici, N; Nigro, V; Abbondanza, C; Moncharmont, B; Molinari, A M; Puca, G A

    1991-04-01

    Estrogen receptor (ER) was purified from calf uterus by immunoaffinity chromatography in the absence of the ligand. The purified ER consists of a mixture of monomer and homodimer forms of 67-kDa hormone-binding subunit (no 90-kDa heat shock protein is present). The purified ER was incubated with a 32P-labeled 61-basepair oligonucleotide containing the sequence of the estrogen response element (ERE) of the Xenopus laevis A2 vitellogenin gene. DNA mobility shift assays showed formation of specific complexes of the ERE containing oligonucleotide with ER, formation which did not require and was not affected by estradiol or antiestrogenic molecules. Both the monomer and the dimer were equally able to interact with the ERE-containing oligonucleotide. Sucrose gradient experiments showed that only the ER monomer is able to interact with an oligonucleotide in which a single mutation destroyed the dyad symmetry of ERE. Multiple symmetric mutations which did not alter the dyad symmetry of ERE nevertheless totally destroyed the ability of the oligonucleotide to form complexes with either the monomeric or dimeric form of ER. These results suggest that ER is able to bind to ERE independently of the presence of estradiol or other proteins and, therefore, that estradiol does not act by modulating the ability of ER to bind to ERE on DNA. PMID:1922088

  5. The response to estrogen deprivation on cartilage collagen degradation markers; CTX-II is unique compared to other markers of collagen turnover

    DEFF Research Database (Denmark)

    Bay-Jensen, Anne-Christine; Tabassi, Nadine; Sondergaard, Lene;

    2009-01-01

    ABSTRACT: INTRODUCTION: The urinary level of type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomized rats, suggesting that estrogen deprivation induces cartilage breakdown. Here we investigate whether this response to estrogen holds true for other type...... II collagen turnover markers known to be affected in osteoarthritis, and whether it relates to its presence in specific areas of cartilage tissue. METHODS: The type II collagen degradation markers CTX-II and Helix-II were measured in body fluids of pre- and postmenopausal women and of ovariectomized...... rats receiving estrogen or not. Levels of PIIANP, a marker of type II collagen synthesis, were also measured in rats. Rat knee cartilage was analyzed for immunoreactivity of CTX-II and PIIANP and for type II collagen expression. RESULTS: As expected, urinary levels of CTX-II are significantly increased...

  6. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C;

    2013-01-01

    with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH......-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This crosstalk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens...... of children with growth disorders and of adults with GH deficiency....

  7. Estrogenic Regulation of the GnRH Neuron

    Directory of Open Access Journals (Sweden)

    Sally eRadovick

    2012-04-01

    Full Text Available Reproductive function is regulated by the secretion of luteinizing hormone (LH and follicle-stimulating hormone (FSH from the pituitary and the steroid hormones from the gonads. The dynamic changes in the levels of the reproductive hormones regulate secondary sex characteristics, gametogenesis, cellular function and behavior. Hypothalamic GnRH neurons, with cell bodies located in the basal hypothalamus, represent the final common pathway for neuronally derived signals to the pituitary. As such, they serve as integrators of a dizzying array of signals including sensory inputs mediating information about circadian, seasonal, behavioral, pheromonal and emotional cues. Additionally, information about peripheral physiological function may also be included in the integrative signal to the GnRH neuron. These signals may communicate information about metabolic status, disease or infection. Gonadal steroid hormones arguably exert the most important effects on GnRH neuronal function. In both males and females, the gonadal steroid hormones exert negative feedback regulation on axis activity at both the level of the pituitary and the hypothalamus. These negative feedback loops regulate homeostasis of steroid hormone levels. In females, a cyclic reversal of estrogen feedback produces a positive feedback loop at both the hypothalamic and pituitary levels. Central positive feedback results in a dramatic increase in GnRH secretion (Sisk and others 2001; Clarke 1993; Moenter, Brand and Karsch 1992; Xia and others 1992. This is coupled with an increase in pituitary sensitivity to GnRH (Turzillo, DiGregorio and Nett 1995; Savoy-Moore and others 1980, which produces the massive surge in secretion of LH that triggers ovulation.

  8. Designer interface peptide grafts target estrogen receptor alpha dimerization.

    Science.gov (United States)

    Chakraborty, S; Asare, B K; Biswas, P K; Rajnarayanan, R V

    2016-09-01

    The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide "I-box" derived from ER residues 503-518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479-485), LQQQHQRLAQ (residues 497-506), and LSHIRHMSNK (residues 511-520) and reported the suitability of using LQQQHQRLAQ (ER 497-506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. PMID:27462021

  9. Postmenopausal vaginal atrophy: evaluation of treatment with local estrogen therapy

    Directory of Open Access Journals (Sweden)

    Minkin MJ

    2014-03-01

    Full Text Available Mary Jane Minkin,1 Ricardo Maamari,2 Suzanne Reiter3 1Department of Gynecology and Reproductive Medicine, Yale University School of Medicine, New Haven, CT, USA; 2Novo Nordisk Inc., Plainsboro, NJ, USA; 3Mid-County Health Center, Largo, FL, USA Abstract: Postmenopausal vaginal atrophy, resulting from decreased estrogen production, frequently requires treatment. Estrogen preparations provide the most effective treatment; local application is preferred to systemic drugs when treating only vaginal symptoms. As local estrogen therapies have comparable efficacy, this study aimed to understand treatment practices, assess experiences with different forms of local estrogen-delivering applicators, and evaluate satisfaction. Women who were US residents aged ≥18 years, menopausal (no spontaneous menstrual period for ≥1 year or with a double oophorectomy, and receiving local estrogen therapy for 1–6 months (vaginal cream [supplied with a reusable applicator] or vaginal tablets [supplied with a single-use/disposable applicator], completed an online questionnaire. Data from 200 women (100 cream users and 100 tablet users; mean therapy duration 3.48 months showed that most stored medication in the room in which it was applied (88% and applied it at bedtime (71%, a procedure for which cream users required, on average, more than twice the time of tablet users (5.08 minutes versus 2.48 minutes. Many cream users applied larger-than-prescribed amounts of cream, attempting to achieve greater efficacy (42%, or lower-than-recommended doses (45%, most frequently to avoid messiness (33% or leakage (30%. More tablet users (69% than cream users (14% were "extremely satisfied" with their applicator. Postmenopausal women using local estrogen therapy were generally more satisfied with the application of vaginal tablets than cream. Patient satisfaction may help to facilitate accurate dosing. Positive perceptions of medication will help to optimize treatment, which

  10. The estrogenic burden on vascular risk in male-to-female transsexuals.

    Science.gov (United States)

    Lioudaki, Eirini; Ganotakis, Emmanuel S; Mikhailidis, Dimitri P; Nair, Devi R

    2010-01-01

    Transsexualism refers to individuals that identify themselves as members of the opposite gender and who strive to acquire the physical appearance and psychosocial role compatible with that gender. Gender reassignment therapy is applied through hormonal treatment ± surgical intervention in addition to psychological support. Hormone treatment for male-to-female transsexuals includes estrogen supplementation ± suppression of androgen secretion or action. Sex hormones are important determinants of the metabolic profile. The impact on cardiovascular disease appears to be gender-related but overall evidence remains conflicting. Gender reassignment therapy has been associated with elevated triglyceride concentrations, often accompanied by an increase in high density lipoprotein levels, reduced circulating homocysteine (Hcy), uric acid and creatinine levels as well as an adverse effect on glycemic control. Markers of inflammation, oxidative stress and endothelial function are also affected in various ways, while alterations in hemostatic and fibrinolytic factors favor thrombosis (arterial and/or venous). Male-to-female transsexuals may be adversely affected by both estrogen administration and androgen deprivation, as reported in prostate cancer. Therefore, vascular risk factor screening and potential intervention may be required prior to and during gender reassignment therapy (both hormone and surgical). PMID:21128891

  11. Estrogen influences the differentiation, maturation and function of dendritic cells in rats with experimental autoimmune encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Qing-hong ZHANG; Yu-zhen HU; Jun CAO; Yan-qing ZHONG; Yu-feng ZHAO; Qi-bing MEI

    2004-01-01

    AIM: To examine if estrogen can affect the immune response at the dendritic cells (DCs) level in rats with experimental autoimmune encephalomyelitis (EAE). METHODS: Lewis rats were immunized with inoculum containing MBP68-86. DCs were derived from spleen monocytes of EAE rats with IL-4 and GM-CSF in presence of 17β-estradiol (E2). Nitric oxide (NO) was detected by Griess reagent. The surface markers and cytokines production of DCs were shown by flow cytometry. DCs were cocultured with MBP-specific T cells, [3H]-TdR incoportation was used to reveal the antigen presentability, the supematant of the coculture were collected to examine the cytokines secretion by ELISA. RESULTS: E2 activated DCs by accelerating the maturation process characterized by upregulation of MHC II and costimulating molecule B7-1, B7-2, drastic high expression of CD40. IFN-γ-producing DCs were also elevated without any alteration of IL-10. Estradiol-treated DCs (E2-DCs) secreted more NO in the culture supernatant. By contrast, E2-DCs showed decreased antigen presentation ability with reduced secretion of IFN-γ but no alteration of IL-10 in the coculture with T cells. CONCLUSION: Estrogen can affect the differentiation, maturation and function of DCs from EAE rats, which may be attributed to its protection against EAE and the remission of multiple sclerosis patients in pregnancy.

  12. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells.

    Science.gov (United States)

    Piccolella, Margherita; Crippa, Valeria; Messi, Elio; Tetel, Marc J; Poletti, Angelo

    2014-01-01

    In the initial stages, human prostate cancer (PC) is an androgen-sensitive disease, which can be pharmacologically controlled by androgen blockade. This therapy often induces selection of androgen-independent PC cells with increased invasiveness. We recently demonstrated, both in cells and mice, that a testosterone metabolite locally synthetized in prostate, the 5α-androstane-3β, 17β-diol (3β-Adiol), inhibits PC cell proliferation, migration and invasion, acting as an anti-proliferative/anti-metastatic agent. 3β-Adiol is unable to bind androgen receptor (AR), but exerts its protection against PC by specifically interacting with estrogen receptor beta (ERβ). Because of its potential retro-conversion to androgenic steroids, 3β-Adiol cannot be used "in vivo", thus, the aims of this study were to investigate the capability of four ligands of ERβ (raloxifen, tamoxifen, genistein and curcumin) to counteract PC progression by mimicking the 3β-Adiol activity. Our results demonstrated that raloxifen, tamoxifen, genistein and curcumin decreased DU145 and PC3 cell proliferation in a dose-dependent manner; in addition, all four compounds significantly decreased the detachment of cells seeded on laminin or fibronectin. Moreover, raloxifen, tamoxifen, genistein and curcumin-treated DU145 and PC3 cells showed a significant decrease in cell migration. Notably, all these effects were reversed by the anti-estrogen, ICI 182,780, suggesting that their actions are mediated by the estrogenic pathway, via the ERβ, the only isoform present in these PCs. In conclusion, these data demonstrate that by selectively activating the ERβ, raloxifen, tamoxifen, genistein and curcumin inhibit human PC cells proliferation and migration favoring cell adesion. These synthetic and natural modulators of ER action may exert a potent protective activity against the progression of PC even in its androgen-independent status. PMID:24184124

  13. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

    Energy Technology Data Exchange (ETDEWEB)

    Veiga, G.A.L. [Departamento de Reprodução Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Milazzotto, M.P. [Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP (Brazil); Nichi, M.; Lúcio, C.F.; Silva, L.C.G.; Angrimani, D.S.R.; Vannucchi, C.I. [Departamento de Reprodução Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-13

    In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs.

  14. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

    International Nuclear Information System (INIS)

    In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs

  15. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

    Directory of Open Access Journals (Sweden)

    G.A.L. Veiga

    2015-04-01

    Full Text Available In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA and oxytocin (OTR mRNA was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation, mid (20 to 40 days and late pregnancy (41 to 60 days, and parturition (first stage of labor. All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs.

  16. Effects of CYP7B1-mediated catalysis on estrogen receptor activation.

    Science.gov (United States)

    Pettersson, Hanna; Lundqvist, Johan; Norlin, Maria

    2010-09-01

    Most of the many biological effects of estrogens are mediated via the estrogen receptors ERalpha and beta. The current study examines the role of CYP7B1-mediated catalysis for activation of ER. Several reports suggest that CYP7B1 may be important for hormonal action but previously published studies are contradictory concerning the manner in which CYP7B1 affects ERbeta-mediated response. In the current study, we examined effects of several CYP7B1-related steroids on ER activation, using an estrogen response element (ERE) reporter system. Our studies showed significant stimulation of ER by 5-androstene-3beta,17beta-diol (Aene-diol) and 5alpha-androstane-3beta,17beta-diol (3beta-Adiol). In contrast, the CYP7B1-formed metabolites from these steroids did not activate the receptor, indicating that CYP7B1-mediated metabolism abolishes the ER-stimulating effect of these compounds. The mRNA level of HEM45, a gene known to be stimulated by estrogens, was strongly up-regulated by Aene-diol but not by its CYP7B1-formed metabolite, further supporting this concept. We did not observe stimulation by dehydroepiandrosterone (DHEA) or 7alpha-hydroxy-DHEA, previously suggested to affect ERbeta-mediated response. As part of these studies we examined metabolism of Aene-diol in pig liver which is high in CYP7B1 content. These experiments indicate that CYP7B1-mediated metabolism of Aene-diol is of a similar rate as the metabolism of the well-known CYP7B1 substrates DHEA and 3beta-Adiol. CYP7B1-mediated metabolism of 3beta-Adiol has been proposed to influence ERbeta-mediated growth suppression. Our results indicate that Aene-diol also might be important for ER-related pathways. Our data indicate that low concentrations of Aene-diol can trigger ER-mediated response equally well for both ERalpha and beta and that CYP7B1-mediated conversion of Aene-diol into a 7alpha-hydroxymetabolite will result in loss of action. PMID:20553962

  17. Testosterone and estrogen impact social evaluations and vicarious emotions: A double-blind placebo-controlled study.

    Science.gov (United States)

    Olsson, Andreas; Kopsida, Eleni; Sorjonen, Kimmo; Savic, Ivanka

    2016-06-01

    The abilities to "read" other peoples' intentions and emotions, and to learn from their experiences, are critical to survival. Previous studies have highlighted the role of sex hormones, notably testosterone and estrogen, in these processes. Yet it is unclear how these hormones affect social cognition and emotion using acute hormonal administration. In the present double-blind placebo-controlled study, we administered an acute exogenous dose of testosterone or estrogen to healthy female and male volunteers, respectively, with the aim of investigating the effects of these steroids on social-cognitive and emotional processes. Following hormonal and placebo treatment, participants made (a) facial dominance judgments, (b) mental state inferences (Reading the Mind in the Eyes Test), and (c) learned aversive associations through watching others' emotional responses (observational fear learning [OFL]). Our results showed that testosterone administration to females enhanced ratings of facial dominance but diminished their accuracy in inferring mental states. In men, estrogen administration resulted in an increase in emotional (vicarious) reactivity when watching a distressed other during the OFL task. Taken together, these results suggest that sex hormones affect social-cognitive and emotional functions at several levels, linking our results to neuropsychiatric disorders in which these functions are impaired. (PsycINFO Database Record PMID:26751627

  18. Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice.

    Science.gov (United States)

    Karadayian, A G; Mac Laughlin, M A; Cutrera, R A

    2012-09-10

    Melatonin has antioxidant and neuroprotective properties in human beings and experimental models, as well as 'anti-estrogenic' effects. Ethanol (EtOH) affects various behavioral parameters during a period known as ethanol-induced hangover. Our study evaluated the neuroprotective effect of melatonin on motor performance during ethanol hangover in male and female Swiss mice. The females were subjected to specific hormonal states: ovariectomized (OVX) and OVX estrogenized (OVX-E(2)). Mice received melatonin (25 μg/ml) or vehicle in their drinking water for seven days and were given intraperitoneal (i.p.) injections of EtOH (3.8 g/kg) or saline on the morning of the eighth day. Motor performance was evaluated by the tightrope test 6h after EtOH exposure (hangover onset). During ethanol hangover, males exhibited lower motor performance than controls (phangover (phangover led to a better motor performance in OVX compared with intact females (phangover. PMID:22819771

  19. Destruction of estrogenic activity in water using UV advanced oxidation

    International Nuclear Information System (INIS)

    The transformation of the steroidal Endocrine Disrupting Compounds (EDCs), 17-β-estradiol (E2) and 17-α-ethinyl estradiol (EE2) by direct UV photolysis and UV/H2O2 advanced oxidation was studied from the perspective of the removal of estrogenic activity associated with the compounds. First, experiments were performed to link the oxidation of E2 and EE2 with subsequent reduction in estrogenic activity. No statistically significant difference between removal rates was observed, implying that the oxidation products of E2 and EE2 are not as estrogenic (measured by the Yeast Estrogen Screen (YES)) as the parent compounds. Utilizing the YES, 90% removal of estrogenic activity of E2 and EE2 at environmentally relevant concentrations (∼ 3 μg L-1) was achieved using a combination of 5 mg L-1 H2O2 and a UV fluence of less than 350 mJ cm-2. Thus, these compounds, when considered at environmentally relevant levels, are significantly degraded at much lower UV fluences than previously thought. A steady state OH radical model was used to predict oxidation of EE2 in laboratory and natural waters

  20. The estrogenic and androgenic potential of pyrethroids in vitro. Review.

    Science.gov (United States)

    Saillenfait, Anne-Marie; Ndiaye, Dieynaba; Sabaté, Jean-Philippe

    2016-08-01

    Synthetic pyrethroids are used worldwide as insecticides. Their metabolites are regularly detected in the urine of adults and children from the general population. There is increasing concern that they may induce sex-hormone disrupting effects. The present work reviews available published information on the (anti)estrogenic and (anti)androgenic activity of pyrethroids in in vitro screening tests. In recent years, a large number of pyrethroids have been evaluated using various common testing methods. In tests using recombinant yeast or mammalian cells, the pyrethroids were found to be essentially negative or weakly estrogenic. More inconsistent results were found regarding their estrogenic action in proliferation tests. Conflicting findings were also reported across studies and/or assays which evaluated their anti-estrogenic or anti-androgenic potential. Some studies have suggested that certain pyrethroids may have potential antagonist activity. However, no strong interaction with the estrogenic or androgenic pathway was reported. The present review confirms the interest in performing a screening battery and in adopting an integrative approach for identifying the potential of different compounds from a chemical family to interfere with the endocrine system. PMID:26921664