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Sample records for emitting estrogen receptor-directed

  1. Bromine-80m-labeled estrogens: Auger-electron emitting, estrogen receptor-directed ligands with potential for therapy of estrogen receptor positive cancers

    SciTech Connect

    DeSombre, E.R.; Mease, R.C.; Hughes, A.; Harper, P.V.; DeJesus, O.T.; Friedman, A.M.

    1988-01-01

    A triphenylbromoethylene, 1,1-bis(p-hydroxyphenyl)-2-bromo-2-phenylethylene, Br-BHPE, and a bromosteroidal estrogen, 17..cap alpha..- bromovinylestradiol, BrVE/sub 2/, were labeled with the Auger electron emitting nuclide bromine-80m, prepared by the (p,n) reaction with /sup 80/Se. To assess their potential as estrogen receptor (ER) directed therapeutic substrates the bromine-80m labeled estrogens were injected into immature female rats and the tissue distribution studied at 0.5 and 2 hours. Both radiobromoestrogens showed substantial diethylstilbesterol (DES)-inhibitable localization in the ER rich tissues, uterus, pituitary, ovary and vagina at both time points. While the percent dose per gram tissue was higher for the Br-BHPE, the BrVE/sub 2/ showed higher tissue to blood ratios, especially at 2 hr, reflecting the lower blood concentrations of radiobromine following administration of the steroidal bromoestrogen. Comparing intraperitoneal, intravenous and subcutaneous routes of administration for the radiobromine labeled Br-BHPE, the intraperitoneal route was particularly advantageous to provide maximum, DES-inhibitable concentrations in the peritoneal, ER-rich target organs, the uterus, ovary and vagina. While uterine concentrations after BrBHPE were from 10--48% dose/g and after BrVE/sub 2/ were 15--25% dose/g, similar treatment with /sup 80m/Br as sodium bromide showed uniform low concentrations in all tissues at about the levels seen in blood. The effective specific activity of (/sup 80m/Br)BrBHPE, assayed by specific binding to ER in rat uterine cytosol, was 8700 Ci/mmole. 23 refs., 9 figs., 2 tabs.

  2. The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.

    PubMed

    Tennessen, Jason M; Baker, Keith D; Lam, Geanette; Evans, Janelle; Thummel, Carl S

    2011-02-02

    Metabolism must be coordinated with development to provide the appropriate energetic needs for each stage in the life cycle. Little is known, however, about how this temporal control is achieved. Here, we show that the Drosophila ortholog of the estrogen-related receptor (ERR) family of nuclear receptors directs a critical metabolic transition during development. dERR mutants die as larvae with low ATP levels and elevated levels of circulating sugars. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program normally associated with proliferating cells, supporting the dramatic growth that occurs during larval development. This study shows that dERR plays a central role in carbohydrate metabolism, demonstrates that a proliferative metabolic program is used in normal developmental growth, and provides a molecular context to understand the close association between mammalian ERR family members and cancer.

  3. Estrogen

    MedlinePlus

    ... life', the end of monthly menstrual periods). Some brands of estrogen are also used to treat vaginal ... prevent osteoporosis should consider a different treatment. Some brands of estrogen are also to relieve symptoms of ...

  4. Determination of sterols, estrogens and inorganic ions in waste water and size-segregated aerosol particles emitted from waste water treatment.

    PubMed

    Beck, Melanie; Radke, Michael

    2006-08-01

    Concentrations of steroids and inorganic ions were measured in waste water of an aerated sand trap as well as in aerosol particles emitted from this tank at the waste water treatment plant (WWTP) of Bayreuth, Germany, in January and February 2003. The investigations comprised seven sterols, two estrogens, and several inorganic ions. Since an appropriate method for the determination of sterols in waste water was not available, a new method based on solid phase extraction was developed. The concentrations of the sterols coprostanol and cholesterol amounted to 30-180 microg l(-1) in waste water and to 400-5000 pg m(-3) in aerosol particles. All other sterols were present in markedly lower concentrations. The mean concentrations of the two estrogens estrone and 17beta-estradiol were about 165 pg m(-3) in aerosol particles. The steroid concentrations in both waste water and aerosol particles varied greatly over time, however with the exception of coprostanol, no clear correlation was detected between concentrations in waste water and aerosol particles.

  5. Growth Factor Receptor-Directed Therapy in Human Breast Cancer

    DTIC Science & Technology

    1997-12-01

    ligands which bind to EGFR, including EGF, TGF- 4 a a a, amphiregulin, and cripto - 1, and by the capability of EGFR to transactivate other type-I tyrosine...amplification in breast cancer was recently reported by Watson et al. (69). In this analysis, encompassing over 5,000 breast tumors, the amplification rate was...activation of c-myc oncogene expression. Oncogene 7: 1587-1594. 58. Shiu, R., Watson , P. and Dubik, D. (1993) C-myc oncogene expression in estrogen

  6. Estrogen Injection

    MedlinePlus

    ... carefully for side effects.tell your doctor what herbal products you are taking, especially St. John's wort.tell your doctor if you have or have ever had yellowing of the skin or eyes during pregnancy or during your treatment with an estrogen product, endometriosis (a condition in ...

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

    DOEpatents

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

    2006-08-15

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

  8. Interleukin-2 receptor-directed therapies for cutaneous lymphomas.

    PubMed

    Foss, Francine M; Waldmann, Thomas A

    2003-12-01

    Our emerging understanding of the IL-2/IL-2R system opens the possibility for more specific immunotherapy of CTCL. This understanding, taken in conjunction with the ability to produce humanized antibodies to the IL-2R subunit by genetic engineering; to arm these antibodies, as well as IL-2 itself with toxins or with alpha- and beta-emitting radionuclides; and to modulate IL-2R subunits to optimize targeting of these agents provides a rational therapeutic strategy for the treatment of IL-2R-expressing CTCL. Although most of these studies were conducted in HTLV-1-associated T-cell lymphomas or CTCL, it is likely that these agents may be applicable to other T-cell lymphomas, including the anaplastic large cell lymphomas, peripheral T-cell lymphomas, and the natural killer lymphomas, because these cells express the IL-2 receptor.

  9. Estrogens and aging skin

    PubMed Central

    Thornton, M. Julie

    2013-01-01

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

  10. Estrogen and Osteoporosis.

    ERIC Educational Resources Information Center

    Lindsay, Robert

    1987-01-01

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

  11. Estrogen and Osteoporosis.

    ERIC Educational Resources Information Center

    Lindsay, Robert

    1987-01-01

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

  12. Estrogens and postcoital contraception.

    PubMed

    Notelovitz, M

    1981-07-01

    The contraceptive effect of large doses of estrogens administered postcoitally is not fully understood, although numerous reports have described the use of a 4 to 6 day course of high dose oral diethylstilbestrol (DES), ethinyl estradiol, conjugated estrogens, and combinations of estrogen and progestogen. Because estrogens are effective postovulatory rather than postcoital contraceptives, it is necessary to know the exact time of unprotected intercouse in relation to a woman's menstrual cycle. Depending on the frequency and timing of intercouse, a 5-day course of postcoital estrogen, introduced within 72 hours, yields a pregancy rate of .03-.3%. Failures are usually due to inadequate doses of estrogen, errors in timing, or multiple exposures. A lowering of basal body temperature after postovulatory administration of high doses of estrogen indicates successful intervention. Existence of various conditions such as hypertension and migraine contraindicate the use of postcoital estrogens. DES and possibly other estrogens are associated with teratogenic and potentially carcinogenic effects. 70 to 80% of women taking postcoital estrogens report side effects such as nausea, weight gain and headache. No randomized studies have compared the efficacy, side effects, or safety of the available estrogens. The use of informed coinsent procedures is advised because of the potency of high dose estrogens.

  13. Postmenopausal skin and estrogen.

    PubMed

    Archer, David F

    2012-10-01

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

  14. Environmental Estrogens and Obesity

    PubMed Central

    Newbold, Retha R.; Padilla-Banks, Elizabeth; Jefferson, Wendy N.

    2009-01-01

    Many chemicals in the environment, in particular those with estrogenic activity, can disrupt the programming of endocrine signaling pathways that are established during development and result in adverse consequences that may not be apparent until much later in life. Most recently, obesity and diabetes join the growing list of adverse consequences that have been associated with developmental exposure to environmental estrogens during critical stages of differentiation. These diseases are quickly becoming significant public health issues and are fast reaching epidemic proportions worldwide. In this review, we summarize the literature from experimental animal studies documenting an association of environmental estrogens and the development of obesity, and further describe an animal model of exposure to diethylstilbestrol (DES) that has proven useful in studying mechanisms involved in abnormal programming of various differentiating estrogen- target tissues. Other examples of environmental estrogens including the phytoestrogen genistein and the environmental contaminant Bisphenol A are also discussed. Together, these data suggest new targets (i.e., adipocyte differentiation and molecular mechanisms involved in weight homeostasis) for abnormal programming by estrogenic chemicals, and provide evidence that support the scientific hypothesis termed “the developmental origins of adult disease”. The proposal of an association of environmental estrogens with obesity and diabetes expands the focus on the diseases from intervention/treatment to include prevention/avoidance of chemical modifiers especially during critical windows of development. PMID:19433252

  15. Estrogen, schizophrenia and neurodevelopment.

    PubMed

    Seeman, Mary V

    2006-07-01

    Women are relatively protected against schizophrenia. The illness has a similar rate in women and men, but it starts later in women and is less severe. It is tempting to attribute this to the neuroprotective effect of estrogen, but the story is not straightforward and contains many unknowns. Women begin their schizophrenia trajectory later in development compared with men and this probably accounts for their relatively superior prognosis. Estrogen agonists are potential therapeutic agents but need to be proven safe, and the timing of administration may be crucial. This article examines what is known about estrogen and the development of schizophrenia.

  16. Estrogen and Bazedoxifene

    MedlinePlus

    ... neck, and chest) in women who are experiencing menopause (stage of life when menstrual periods become less ... and break easily) in women who have undergone menopause. Estrogen is in a class of medications called ...

  17. [Estrogens and vascular thrombosis].

    PubMed

    Colmou, A

    1982-09-01

    The incidence of thromboses among young women has increased with widespread use of oral contraceptives (OCs) due to the significant thromboembolic risk of estrogen. Estrogens intervene at the vascular, platelet, and plasma levels as a function of hormonal variations in the menstrual cycle, increasing the aggregability of the platelets and thrombocytes, accelerating the formation of clots, and decreasing the amount of antithrombin III. Estrogens are used in medicine to treat breast and prostate cancers and in gynecology to treat dysmenorrhea, during the menopause, and in contraception. Smoking, cardiovascular disease and hypertension, hypercholesterolemia, and diabetes are contraindicators to estrogen use. Thrombosis refers to blockage of a blood vessel by a clot or thrombus. Before estrogens are prescribed, a history of phlebitis, obesity, hyperlipidemia, or significant varicosities should be ruled out. A history of venous thrombosis, hyperlipoproteinemia, breast nodules, serious liver condition, allergies to progesterone, and some ocular diseases of vascular origin definitively rule out treatment with estrogens. A family history of infarct, embolism, diabetes, cancer, or vascular accidents at a young age signals a need for greater patient surveillance. All patients receiving estrogens should be carefully observed for signs of hypertension, hypercholesterolemia, hypercoagulability, or diabetes. Nurses have a role to play in carefully eliciting the patient's history of smoking, personal and family medical problems, and previous and current laboratory results, as well as in informing the patients of the risks and possible side effects of OCs, especially for those who smoke. Nurses should educate patients receiving estrogens, especially those with histories of circulatory problems, to avoid standing in 1 position for prolonged periods, avoid heat which is a vasodilator, avoid obesity, excercise regularly, wear appropriate footgear, and follow other good health

  18. The Measurement of Estrogens

    NASA Astrophysics Data System (ADS)

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

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

  19. Removal of estrogens and estrogenicity through drinking water treatment.

    PubMed

    Schenck, Kathleen; Rosenblum, Laura; Wiese, Thomas E; Wymer, Larry; Dugan, Nicholas; Williams, Daniel; Mash, Heath; Merriman, Betty; Speth, Thomas

    2012-03-01

    Estrogenic compounds have been shown to be present in surface waters, leading to concerns over their possible presence in finished drinking waters. In this work, two in vitro human cell line bioassays for estrogenicity were used to evaluate the removal of estrogens through conventional drinking water treatment using a natural water. Bench-scale studies utilizing chlorine, alum coagulation, ferric chloride coagulation, and powdered activated carbon (PAC) were conducted using Ohio River water spiked with three estrogens, 17β-estradiol, 17α-ethynylestradiol, and estriol. Treatment of the estrogens with chlorine, either alone or with coagulant, resulted in approximately 98% reductions in the concentrations of the parent estrogens, accompanied by formation of by-products. The MVLN reporter gene and MCF-7 cell proliferation assays were used to characterize the estrogenic activity of the water before and after treatment. The observed estrogenic activities of the chlorinated samples showed that estrogenicity of the water was reduced commensurate with removal of the parent estrogen. Therefore, the estrogen chlorination by-products did not contribute appreciably to the estrogenic activity of the water. Coagulation alone did not result in significant removals of the estrogens. However, addition of PAC, at a typical drinking water plant dose, resulted in removals ranging from approximately 20 to 80%.

  20. Radiobrominated triphenylethylenes as estrogen receptor binding radiopharmaceuticals

    SciTech Connect

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

    1985-05-01

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

  1. Estrogen and the cardiovascular system.

    PubMed

    Knowlton, A A; Lee, A R

    2012-07-01

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

  2. Removal of Estrogens and Estrogenicity through Drinking Water Treatment

    EPA Science Inventory

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

  3. Removal of Estrogens and Estrogenicity through Drinking Water Treatment

    EPA Science Inventory

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

  4. Estrogen supplements in menopause.

    PubMed

    Booher, D L

    1990-01-01

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

  5. Menopause, estrogens and frailty.

    PubMed

    Nedergaard, Anders; Henriksen, Kim; Karsdal, Morten Asser; Christiansen, Claus

    2013-05-01

    The controversy surrounding the results from the Women's Health Initiative (WHI) trials published a decade ago caused a significant decline in the use of menopausal hormone replacement therapy. However, these results have been vehemently contested and several lines of evidence suggest that in perimenopausal and non-obese women, estrogen therapy may indeed be of benefit. There is ample proof that menopause causes a loss of musculoskeletal tissue mass and quality, thereby causing a loss of health and quality of life. There is also solid evidence that hormone replacement therapy in itself prevents most of these effects in connective tissue in itself. Besides the independent, direct effects on the musculoskeletal tissues, estrogen deficiency also reduces the ability to adequately respond and adapt to external mechanical and metabolic stressors, e.g. exercise, which are otherwise the main stimuli that should maintain musculoskeletal integrity and metabolic function. Thus, normophysiological estrogen levels appear to exert a permissive effect on musculoskeletal adaptations to loading, thereby likely improving the outcome of rehabilitation following critical illness, musculoskeletal trauma or orthopedic surgical therapy. These effects add to the evidence supporting the use of estrogen therapy, particularly accelerated gain of functional capacity and independence following musculoskeletal disuse.

  6. Estrogens, Neuroinflammation, and Neurodegeneration

    PubMed Central

    Villa, Alessandro; Vegeto, Elisabetta; Poletti, Angelo

    2016-01-01

    Inflammatory activation of microglia is a hallmark of several disorders of the central nervous system. In addition to protecting the brain against inflammatory insults, microglia are neuroprotective and play a significant role in maintaining neuronal connectivity, but the prolongation of an inflammatory status may limit the beneficial functions of these immune cells. The finding that estrogen receptors are present in monocyte-derived cells and that estrogens prevent and control the inflammatory response raise the question of the role that this sex steroid plays in the manifestation and progression of pathologies that have a clear sex difference in prevalence, such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease. The present review aims to provide a critical review of the current literature on the actions of estrogen in microglia and on the involvement of estrogen receptors in the manifestation of selected neurological disorders. This current understanding highlights a research area that should be expanded to identify appropriate replacement therapies to slow the progression of such diseases. PMID:27196727

  7. Estrogen, inflammation, and platelet phenotype.

    PubMed

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G

    2008-01-01

    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  8. DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression.

    PubMed

    Perillo, Bruno; Ombra, Maria Neve; Bertoni, Alessandra; Cuozzo, Concetta; Sacchetti, Silvana; Sasso, Annarita; Chiariotti, Lorenzo; Malorni, Antonio; Abbondanza, Ciro; Avvedimento, Enrico V

    2008-01-11

    Modifications at the N-terminal tails of nucleosomal histones are required for efficient transcription in vivo. We analyzed how H3 histone methylation and demethylation control expression of estrogen-responsive genes and show that a DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. This process is driven by receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites and is achieved by activation of resident LSD1 demethylase. Localized demethylation produces hydrogen peroxide, which modifies the surrounding DNA and recruits 8-oxoguanine-DNA glycosylase 1 and topoisomeraseIIbeta, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription. Our data show a strategy that uses controlled DNA damage and repair to guide productive transcription.

  9. DNA and chromosome breaks induced by {sup 123}I-estrogen in CHO cells

    SciTech Connect

    Schwartz, J.L. |; Mustafi, R.; Hughes, A.; DeSombre, E.R.

    1997-07-01

    The effects of the Auger electron-emitting isotope I-123, covalently bound to estrogen, on DNA single- and double-strand breakage and on chromosome breakage was determined in estrogen positive Chinese hamster ovary (CHO-ER) cells. Exposure to the {sup 123}I-estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.2. The corresponding ratio with {sup 60}Co gamma rays was 15.6. The dose-response was biphasic suggesting that either receptor sites are saturated at high does, or that there is a nonrandom distribution of breaks induced by the {sup 123}I-estrogen. The {sup 123}I-estrogen treatment induced chromosome aberrations with an efficiency of about 1 aberration for each 1,000 disintegrations per cell. This corresponds to the mean lethal dose of {sup 123}I-estrogen for these cells suggesting that the lethal event induced by the Auger electron emitter bound to estrogen is a chromosome aberration. Most of the chromosome-type aberrations were dicentrics and rings, suggesting that {sup 123}I-estrogen-induced chromosome breaks are rejoined. The F-ratio, the ratio of dicentrics to centric rings, was 5.8 {plus_minus} 1.7, which is similar to that seen with high LET radiations. Their results suggest that I-123 bound to estrogen is an efficient clastogenic agent, that the cytotoxic damage produced by I-123 bound to estrogen is very like high LET-induced damage, and the I-123 in the estrogen-receptor-DNA complex is probably in close proximity to the sugar-phosphate backbone of the DNA.

  10. DNA and chromosome breaks induced by iodine-123-labeled estrogen in Chinese hamster ovary cells

    SciTech Connect

    Schwartz, J.L. |; Mustafi, R.; Hughes, A.; DeSombre, E.R.

    1996-08-01

    The effects of the Auger electron-emitting isotope {sup 123}I, covalently bound to estrogen, on DNA single- and double-strand breakage and on chromosome breakage was determined in estrogen receptor-positive Chinese hamster ovary (CHO-ER) cells. Exposure to the {sup 123}I-labeled estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.8. The corresponding ratio with {sup 60}Co {gamma} rays was 15.6. The dose response was biphasic, suggesting either that receptor sites are saturated at high doses, or that there is a nonrandom distribution of breaks induced by the {sup 123}I-labeled estrogen. The {sup 123}I-labeled estrogen treatment induced chromosome aberrations with an efficiency of about 1 aberration for each 1000 disintegrations per cell. This corresponds to the mean lethal dose of {sup 123}I-labeled estrogen for these cells, suggesting that the lethal event induced by the Auger electron emitter bound to estrogen is a chromosome aberration. Most of the chromosome-type aberrations were dicentrics and rings, suggesting that {sup 123}I-labeled estrogen-induced chromosome breaks are rejoined. The F ratio, the ratio of dicentrics to centric rings, was 5.8 {+-} 1.7, which is similar to that seen with high-LET radiations. Our results suggest that {sup 123}I bound to estrogen is an efficient clastogenic agent, the cytotoxic damage produced by {sup 123}I bound to estrogen is very like damage induced by high-LET radiation, and the {sup 123}I in the estrogen receptor-DNA complex is probably in proximity to the sugar-phosphate backbone of the DNA. 40 refs., 7 figs.

  11. Estrogenicity of Medicinal Botanicals.

    DTIC Science & Technology

    1998-06-01

    Medicinal botanicals PLANT EXTRACTS have been used for centuries to relieve various gynecological symptoms, and are of increasing interest to those...seeking alternative health care and self-treatment. However, women who have or are at risk for breast cancer pose a particular problem when using such...hops, vitex and cohosh. These studies verify that certain medicinal botanicals demonstrate measurable and significant estrogenic activities in

  12. Exercise, Eating, Estrogen, and Osteoporosis.

    ERIC Educational Resources Information Center

    Brown, Jim

    1986-01-01

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

  13. Estrogenic effects from household stoves.

    PubMed

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

    2002-09-01

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

  14. Exercise, Eating, Estrogen, and Osteoporosis.

    ERIC Educational Resources Information Center

    Brown, Jim

    1986-01-01

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

  15. Light-emitting Diodes

    PubMed Central

    Opel, Daniel R.; Hagstrom, Erika; Pace, Aaron K.; Sisto, Krisanne; Hirano-Ali, Stefanie A.; Desai, Shraddha

    2015-01-01

    Background: In the early 1990s, the biological significance of light-emitting diodes was realized. Since this discovery, various light sources have been investigated for their cutaneous effects. Study design: A Medline search was performed on light-emitting diode lights and their therapeutic effects between 1996 and 2010. Additionally, an open-label, investigator-blinded study was performed using a yellow light-emitting diode device to treat acne, rosacea, photoaging, alopecia areata, and androgenetic alopecia. Results: The authors identified several case-based reports, small case series, and a few randomized controlled trials evaluating the use of four different wavelengths of light-emitting diodes. These devices were classified as red, blue, yellow, or infrared, and covered a wide range of clinical applications. The 21 patients the authors treated had mixed results regarding patient satisfaction and pre- and post-treatment evaluation of improvement in clinical appearance. Conclusion: Review of the literature revealed that differing wavelengths of light-emitting diode devices have many beneficial effects, including wound healing, acne treatment, sunburn prevention, phototherapy for facial rhytides, and skin rejuvenation. The authors’ clinical experience with a specific yellow light-emitting diode device was mixed, depending on the condition being treated, and was likely influenced by the device parameters. PMID:26155326

  16. Estrogen receptors in breast carcinoma.

    PubMed

    Huaman, A

    1979-11-01

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

  17. Presence of estrogenic activity from emission of fossil fuel combustion as detected by a recombinant yeast bioassay

    NASA Astrophysics Data System (ADS)

    Wang, Jingxian; Wu, Wenzhong; Henkelmann, Bernhard; You, Li; Kettrup, Antonius; Schramm, Karl-Werner

    Estrogenic activities of emission samples generated by fossil fuel combustion were investigated with human estrogen receptor (ER) recombinant yeast bioassay. The results showed that there were weak but clear estrogenic activities in combustion emissions of fossil fuels including coal, petroleum, and diesel. The estrogenic relative potency (RP) of fossil fuel combustion was the highest in petroleum-fired car, followed by coal-fired stove, diesel-fired agrimotor, coal-fired electric power station. On the other hand, the estrogenic relative inductive efficiency (RIE) was the highest in coal-fired stove and coal-fired electric power station, followed by petroleum-fired car and diesel-fired agrimotor. The estrogenic activities in the sub-fractions from chromatographic separation of emitted materials were also determined. The results indicated that different chemical fractions in these complex systems have different estrogenic potencies. The GC/MS analysis of the emission showed that there were many aromatic carbonyls, big molecular alcohol, PAHs and derivatives, and substituted phenolic compounds and derivatives which have been reported as environmental estrogens. The existence of estrogenic substances in fossil fuel combustion demands further investigation of their potential adverse effects on human and on the ecosystem. The magnitude of pollution due to global usage of fossil fuels makes it imperative to understand the issue of fossil fuel-derived endocrine activities and the associated health risks, particularly the aggregated risks stemmed from exposure to toxicants of multiple sources.

  18. Estrogen therapy for postmenopausal osteoporosis.

    PubMed

    Fitzpatrick, Lorraine A

    2006-08-01

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

  19. Risks of estrogens and progestogens.

    PubMed

    L'Hermite, M

    1990-09-01

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

  20. Selective Estrogen Receptor Modulators

    PubMed Central

    2016-01-01

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

  1. Light emitting ceramic device

    DOEpatents

    Valentine, Paul; Edwards, Doreen D.; Walker, Jr., William John; Slack, Lyle H.; Brown, Wayne Douglas; Osborne, Cathy; Norton, Michael; Begley, Richard

    2010-05-18

    A light-emitting ceramic based panel, hereafter termed "electroceramescent" panel, is herein claimed. The electroceramescent panel is formed on a substrate providing mechanical support as well as serving as the base electrode for the device. One or more semiconductive ceramic layers directly overlay the substrate, and electrical conductivity and ionic diffusion are controlled. Light emitting regions overlay the semiconductive ceramic layers, and said regions consist sequentially of a layer of a ceramic insulation layer and an electroluminescent layer, comprised of doped phosphors or the equivalent. One or more conductive top electrode layers having optically transmissive areas overlay the light emitting regions, and a multi-layered top barrier cover comprising one or more optically transmissive non-combustible insulation layers overlay said top electrode regions.

  2. Estrogen, testosterone, and gender differences.

    PubMed

    Dluzen, Dean E

    2005-08-01

    The purpose of this report is to gain some current perspective on the definition, bases, and trends for research associated with gender differences. To accomplish this goal an analysis on the number of citations from a 1994-2004 Medline search with the terms estrogen, testosterone, gender differences, sex differences as well as the combinations of these terms was performed. Other combinations of terms included separate searches of estrogen, testosterone, and their combination within males or females, and an analysis of gender and sex differences with the terms human and animal. The salient results from this survey include: (1) An overall greater ratio of estrogen:testosterone citations when these terms were searched alone or in combination with gender differences; (2) an overall greater ratio of testosterone:estrogen citations when these terms were combined with sex differences or conducted separately within males or females, although this trend was shifting toward decreased testosterone and increased estrogen citation numbers toward the latter years of the survey; (3) a trend for increasing numbers of estrogen and gender differences citations over the period of the survey; (4) a clear indication for the term gender differences to be associated with the search term human; and (5) a very small number of citations when the terms estrogen and testosterone were combined. Interpretations and implications of these results are discussed.

  3. Estrogen receptor signaling during vertebrate development

    PubMed Central

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

    2014-01-01

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

  4. Light-Emitting Pickles

    ERIC Educational Resources Information Center

    Vollmer, M.; Mollmann, K-P.

    2015-01-01

    We present experiments giving new insights into the classical light-emitting pickle experiment. In particular, measurements of the spectra and temperatures, as well as high-speed recordings, reveal that light emission is connected to the polarity of the electrodes and the presence of hydrogen.

  5. Light-Emitting Pickles

    ERIC Educational Resources Information Center

    Vollmer, M.; Mollmann, K-P.

    2015-01-01

    We present experiments giving new insights into the classical light-emitting pickle experiment. In particular, measurements of the spectra and temperatures, as well as high-speed recordings, reveal that light emission is connected to the polarity of the electrodes and the presence of hydrogen.

  6. Red Emitting VCSEL

    NASA Astrophysics Data System (ADS)

    Jetter, Michael; Roßbach, Robert; Michler, Peter

    This chapter describes the progress in development of vertical-cavity surface-emitting lasers (VCSEL) emitting in the red spectral region around 650 nm for data transmission over polymer optical fibers (POF). First, growth issues of red VCSEL using two different material systems, namely AlGaAs and AlGaInP, are introduced. In particular, the optical and electrical state-of-the-art characteristics as low threshold currents ({≤} 1 mA) and high output powers (several mW) are presented with a special focus on emission wavelength. Also the thermal budget and heat removal in the devices are pointed out with regard to the geometry of the VCSEL. Small-signal modulation response in terms of maximum resonance frequency in dependance on temperature behavior are discussed. Applications of these devices in optical interconnects are described and digital data transmission at data rates up to 2.1 Gbit/s over step-index POF is reported. These properties make red emitting VCSEL perfectly suited for high-speed low power consuming light sources for optical data communication via POF. By introducing InP quantum dots as gain material in red emitting VCSEL nearly temperature independent record low threshold current densities of around 10 A/cm2 could be observed.

  7. The epigenetics of estrogen

    PubMed Central

    Zhao, Zaorui; Fan, Lu

    2011-01-01

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

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

    PubMed

    Loza Arredondo, M C; González Juarez, N A

    1994-11-01

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

  9. Fish populations surviving estrogen pollution.

    PubMed

    Wedekind, Claus

    2014-02-10

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

  10. White light emitting diodes

    NASA Astrophysics Data System (ADS)

    Baur, J.; Schlotter, P.; Schneider, J.

    Using blue-emitting GaN LEDs on SiC substrate chips as primary light sources, we have fabricated green, yellow, red and white light emitting diodes (LUCOLEDs). The generation of mixed colors, as turquoise and magenta, is also demonstrated. The underlying physical principle is that of luminescence downconversion (Stokes shift), as typical for organic dye molecules and many inorganic phosphors. For white light generation via the LUCOLED principle, the phosphor Y3Al5O12:Ce3+(4f1) is ideally suited. The optical characteristics of Ce3+(4f1) in Y3Al5O12(YAG) are discussed in detail. Possibilities to "tune" the white color by various substitutions in the garnet lattice are shortly outlined.

  11. Estrogenic flavonoids: structural requirements for biological activity.

    PubMed

    Miksicek, R J

    1995-01-01

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

  12. Estrogens and selective estrogen receptor modulators in acromegaly.

    PubMed

    Duarte, Felipe H; Jallad, Raquel S; Bronstein, Marcello D

    2016-11-01

    Despite recent advances in acromegaly treatment by surgery, drugs, and radiotherapy, hormonal control is still not achieved by some patients. The impairment of IGF-1 generation by estrogens in growth hormone deficient patients is well known. Patients on oral estrogens need higher growth hormone doses in order to achieve normal IGF-1 values. In the past, estrogens were one of the first drugs used to treat acromegaly. Nevertheless, due to the high doses used and the obvious side effects in male patients, this strategy was sidelined with the development of more specific drugs, as somatostatin receptor ligands and dopamine agonists. In the last 15 years, the antagonist of growth hormone receptor became available, making possible IGF-1 control of the majority of patients on this particular drug. However, due to its high cost, pegvisomant is still not available in many centers around the world. In this setting, the effect of estrogens and also of selective estrogen receptor modulators on IGF-1 control was reviewed, and proved to be an ancillary tool in the management of acromegaly. This review describes data concerning their efficacy and place in the treatment algorithm of acromegaly.

  13. VASCULAR ACTIONS OF ESTROGENS: FUNCTIONAL IMPLICATIONS

    PubMed Central

    Miller, Virginia M.; Duckles, Sue P.

    2009-01-01

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

  14. Estrogen and Progestin (Hormone Replacement Therapy)

    MedlinePlus

    ... depression. Estrogen also prevents thinning of the bones (osteoporosis) in menopausal women. Progestin is added to estrogen ... you are taking this medication for prevention of osteoporosis. Follow all dietary and exercise recommendations, as both ...

  15. Mixture interactions of xenoestrogens with endogenous estrogens.

    EPA Science Inventory

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

  16. Mixture interactions of xenoestrogens with endogenous estrogens.

    EPA Science Inventory

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

  17. Estrogen actions in the cardiovascular system.

    PubMed

    Mendelsohn, M E

    2009-01-01

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

  18. Estrogen in the limbic system.

    PubMed

    ter Horst, Gert J

    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), the main representative of the group, is highly lipophylic and can easily pass the blood-brain barrier to modulate neuronal activity. Particularly the limbic system, a group of tightly interconnected forebrain areas controlling mood and emotion, is rich in estrogen receptors. To date two cytoplasmatic and/or nuclear estrogen receptors named ER-alpha (ERalpha) and ER-beta (ERbeta) have been identified. In the brain, ERalpha plays a critical role in regulating reproductive neuroendocrine behavior and function. ERbeta appears to play an important role in nonreproductive behaviors, such as learning and memory, anxiety, and mood. Five splice variants of ERbeta, named Erb1, Erb2, Erb1d3, Erb2d3, and Erb1d4, have been identified with possibly different biological activities. There is evidence of a thus far not definitely characterized membrane-linked ER receptor named mER-X. In this review, the anatomy of the limbic system and the distribution of estrogen receptors (ERs) are described in relation to coping with stress and the higher prevalence of stress-related psychiatric disorders in women. Effects of cyclic estrogen administration and chronic stress on recovery and neuronal plasticity are illustrated with own results. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Fish populations surviving estrogen pollution

    PubMed Central

    2014-01-01

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

  20. P450 enzymes of estrogen metabolism.

    PubMed

    Martucci, C P; Fishman, J

    1993-01-01

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

  1. Melasma Associated with Topical Estrogen Cream

    PubMed Central

    Schiechert, Rachel A.; Zaiac, Martin N.

    2017-01-01

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

  2. Interactions of dietary estrogens with human estrogen receptors and the effect on estrogen receptor-estrogen response element complex formation.

    PubMed Central

    Nikov, G N; Hopkins, N E; Boue, S; Alworth, W L

    2000-01-01

    Epidemiologic and experimental studies support the hypothesis that dietary estrogens from plant sources (phytoestrogens) may play a role in the prevention of breast and prostate cancer. The molecular mechanisms for such chemopreventive effect are still unclear. We investigated the possibility that phytoestrogens may bind differentially to estrogen receptor proteins (ER[alpha] and ERss) and affect the interactions of the ligand-ER complexes with different estrogen response element (ERE) sequences. We used fluorescence polarization to measure the binding affinities of genistein, coumestrol, daidzein, glyceollin, and zearalenone for human ER[alpha] and ERss. Competition binding experiments revealed higher affinity of the phytoestrogens for ERss than for ER[alpha]. Genistein [median inhibitory concentration 12nM] is the most potent and has the same relative binding affinity for ERss as 17ss-estradiol. We also studied the effect of these phytoestrogens on the ability of ER[alpha] and ERss to associate with specific DNA sequences (EREs). The direct binding of human recombinant estrogen receptors to fluorescein-labeled EREs indicates that phytoestrogens can cause conformational changes in both human ERs, which results in altered affinities of the complexes for the ERE from the Xenopus vitellogenin A2 gene and an ERE from the human pS2 gene. PMID:11017892

  3. Estrogens and Male Lower Urinary Tract Dysfunction

    PubMed Central

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

    2016-01-01

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

  4. Unbalanced estrogen metabolism in thyroid cancer.

    PubMed

    Zahid, Muhammad; Goldner, Whitney; Beseler, Cheryl L; Rogan, Eleanor G; Cavalieri, Ercole L

    2013-12-01

    Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p < 0.0001), demonstrating high specificity and sensitivity. These findings indicate that estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of estrogen-DNA adducts might play a role in the initiation of thyroid cancer. Copyright © 2013 UICC.

  5. Unbalanced Estrogen Metabolism in Thyroid Cancer

    PubMed Central

    Zahid, Muhammad; Goldner, Whitney; Beseler, Cheryl L.; Rogan, Eleanor G.; Cavalieri, Ercole L.

    2013-01-01

    Well-differentiated thyroid cancer most frequently occurs in premenopausal women. Greater exposure to estrogens may be a risk factor for thyroid cancer. To investigate the role of estrogens in thyroid cancer, a spot urine sample was obtained from 40 women with thyroid cancer and 40 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates significantly differed between cases and controls (p<0.0001), demonstrating high specificity and sensitivity. These findings indicate that estrogen metabolism is unbalanced in thyroid cancer and suggest that formation of estrogen-DNA adducts might play a role in the initiation of thyroid cancer. PMID:23686454

  6. Estrogen mediation of hormone responses to exercise.

    PubMed

    Kraemer, Robert R; Francois, Michelle; Castracane, V Daniel

    2012-10-01

    The roles of estrogens extend from the regulation of reproduction to other functions involved in control of metabolism, fluid balance, as well as gastrointestinal, lung, and brain function, with a strong effect on other hormones that subsequently alter the physiology of multiple tissues. As such, alteration of endogenous estrogens across the menstrual cycle, or from oral contraception and estrogen replacement therapy, can affect these tissues. Due to the important effects that estrogens have on different tissues, there are many investigations concerning the effects of a human estrogenic environment on endocrine responses to exercise. The following review will describe the consequences of varying estrogen levels on pituitary, adrenal, gonadal, and endocrine function, followed by discussion of the outcomes of different estrogen levels on endocrine tissues in response to exercise, problems encountered for interpretation of findings, and recommended direction for future research. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Estrogen and estrogen receptors in cardiovascular oxidative stress.

    PubMed

    Arias-Loza, Paula-Anahi; Muehlfelder, Melanie; Pelzer, Theo

    2013-05-01

    The cardiovascular system of a premenopausal woman is prepared to adapt to the challenges of increased cardiac output and work load that accompany pregnancy. Thus, it is tempting to speculate whether enhanced adaptability of the female cardiovascular system might be advantageous under conditions that promote cardiovascular disease. In support of this concept, 17β-estradiol as the major female sex hormone has been shown to confer protective cardiovascular effects in experimental studies. Mechanistically, these have been partially linked to the prevention and protection against oxidative stress. Current evidence indicates that estrogens attenuate oxidative stress at two levels: first, by preventing generation of reactive oxygen species (ROS) and, second, by scavenging ROS in the myocardium and in the vasculature. The purpose of this review is to give an overview on current concepts on conditions and mechanisms by which estrogens protect the cardiovascular system against ROS-mediated cellular injury.

  8. Light Emitting Diode (LED)

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A special lighting technology was developed for space-based commercial plant growth research on NASA's Space Shuttle. Surgeons have used this technology to treat brain cancer on Earth, in two successful operations. The treatment technique called photodynamic therapy, requires the surgeon to use tiny pinhead-size Light Emitting Diodes (LEDs) (a source releasing long wavelengths of light) to activate light-sensitive, tumor-treating drugs. Laser light has been used for this type of surgery in the past, but the LED light illuminates through all nearby tissues, reaching parts of a tumor that shorter wavelengths of laser light carnot. The new probe is safer because the longer wavelengths of light are cooler than the shorter wavelengths of laser light, making the LED less likely to injure normal brain tissue near the tumor. It can also be used for hours at a time while still remaining cool to the touch. The LED probe consists of 144 tiny pinhead-size diodes, is 9-inches long, and about one-half-inch in diameter. The small balloon aids in even distribution of the light source. The LED light source is compact, about the size of a briefcase, and can be purchased for a fraction of the cost of a laser. The probe was developed for photodynamic cancer therapy by the Marshall Space Flight Center under a NASA Small Business Innovative Research program grant.

  9. Light Emitting Diodes (LEDs)

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A special lighting technology was developed for space-based commercial plant growth research on NASA's Space Shuttle. Surgeons have used this technology to treat brain cancer on Earth, in two successful operations. The treatment technique, called Photodynamic Therapy, requires the surgeon to use tiny, pinhead-size Light Emitting Diodes (LEDs) (a source that releases long wavelengths of light ) to activate light-sensitive, tumor-treating drugs. 'A young woman operated on in May 1999 has fully recovered with no complications and no evidence of the tumor coming back,' said Dr. Harry Whelan, a pediatric neurologist at the Medical Hospital of Wisconsin in Milwaukee. Laser light has been used for this type of surgery in the past, but the LED light illuminates through all nearby tissues, reaching parts of a tumor that shorter wavelengths of laser light carnot. The new probe is safer because the longer wavelengths of light are cooler than the shorter wavelengths of laser light, making the LED less likely to injure normal brain tissue near the tumor. It can be used for hours at a time while still remaining cool to the touch. The LED light source is compact, about the size of a briefcase, and can be purchased for a fraction of the cost of a laser. The LEDs, developed and managed by NASA's Marshall Space Flight Center, have been used on seven Space Shuttle flights inside the Microgravity Astroculture Facility. This technology has also been successfully used to further commercial research in crop growth.

  10. Light Emitting Diode (LED)

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A special lighting technology was developed for space-based commercial plant growth research on NASA's Space Shuttle. Surgeons have used this technology to treat brain cancer on Earth, in two successful operations. The treatment technique called photodynamic therapy, requires the surgeon to use tiny pinhead-size Light Emitting Diodes (LEDs) (a source releasing long wavelengths of light) to activate light-sensitive, tumor-treating drugs. Laser light has been used for this type of surgery in the past, but the LED light illuminates through all nearby tissues, reaching parts of a tumor that shorter wavelengths of laser light carnot. The new probe is safer because the longer wavelengths of light are cooler than the shorter wavelengths of laser light, making the LED less likely to injure normal brain tissue near the tumor. It can also be used for hours at a time while still remaining cool to the touch. The LED probe consists of 144 tiny pinhead-size diodes, is 9-inches long, and about one-half-inch in diameter. The small balloon aids in even distribution of the light source. The LED light source is compact, about the size of a briefcase, and can be purchased for a fraction of the cost of a laser. The probe was developed for photodynamic cancer therapy by the Marshall Space Flight Center under a NASA Small Business Innovative Research program grant.

  11. Light Emitting Diodes (LEDs)

    NASA Technical Reports Server (NTRS)

    1997-01-01

    A special lighting technology was developed for space-based commercial plant growth research on NASA's Space Shuttle. Surgeons have used this technology to treat brain cancer on Earth, in two successful operations. The treatment technique, called Photodynamic Therapy, requires the surgeon to use tiny, pinhead-size Light Emitting Diodes (LEDs) (a source that releases long wavelengths of light ) to activate light-sensitive, tumor-treating drugs. 'A young woman operated on in May 1999 has fully recovered with no complications and no evidence of the tumor coming back,' said Dr. Harry Whelan, a pediatric neurologist at the Medical Hospital of Wisconsin in Milwaukee. Laser light has been used for this type of surgery in the past, but the LED light illuminates through all nearby tissues, reaching parts of a tumor that shorter wavelengths of laser light carnot. The new probe is safer because the longer wavelengths of light are cooler than the shorter wavelengths of laser light, making the LED less likely to injure normal brain tissue near the tumor. It can be used for hours at a time while still remaining cool to the touch. The LED light source is compact, about the size of a briefcase, and can be purchased for a fraction of the cost of a laser. The LEDs, developed and managed by NASA's Marshall Space Flight Center, have been used on seven Space Shuttle flights inside the Microgravity Astroculture Facility. This technology has also been successfully used to further commercial research in crop growth.

  12. Commonly occurring plant flavonoids have estrogenic activity.

    PubMed

    Miksicek, R J

    1993-07-01

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

  13. The role of environmental estrogens and autoimmunity.

    PubMed

    Chighizola, Cecilia; Meroni, Pier Luigi

    2012-05-01

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

  14. Targeted Radiotherapy of Estrogen Receptor Positive Tumors

    SciTech Connect

    Raghavan Rajagopalan

    2006-08-31

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

  15. Estrogen turns down "the AIRE".

    PubMed

    Bakhru, Pearl; Su, Maureen A

    2016-04-01

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

  16. [Transdermal estrogenic therapy in menopause].

    PubMed

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

    1989-01-01

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

  17. The Estrogen Hypothesis of Obesity

    PubMed Central

    Grantham, James P.; Henneberg, Maciej

    2014-01-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  20. Estrogens and the intervertebral disc.

    PubMed

    Calleja-Agius, J; Muscat-Baron, Y; Brincat, M P

    2009-09-01

    Intervertebral discs are an integral part of the vertebral column. It has been shown that menopause has a negative effect on bone and on intervertebral discs. Estrogen has a beneficial effect of preserving the health of collagen-containing tissues, including the intervertebral disc. The intervertebral disc allows for mobility of the spine, and maintains a uniform stress distribution of the area of the vertebral endplates. Also, the disc influences spinal height. The disc tissue is adapted for this biomechanical function. The function of the spine is impaired if there is a loss of disc tissue. Narrowing of the disc space due to degeneration of intervertebral discs is associated with a significantly increased risk of vertebral fractures. Estrogen should be seen as the first-choice therapy for bones and other collagen-rich tissues, such as intervertebral discs, because it maintains homeostasis of the bone-remodelling unit. Unlike bisphosphonates, estrogen is unique in its ability to regenerate bone collagen after its disintegration, apart from suppressing osteoclastic activity. Besides, there is insufficient data on deterioration in bone qualities and micro-cracks in patients on long-term bisphosphonates.

  1. Estrogen and ERα: Culprits in Cervical Cancer?

    PubMed Central

    Chung, Sang-Hyuk; Franceschi, Silvia; Lambert, Paul F.

    2010-01-01

    Estrogen and its receptors are implicated in the promotion and prevention of various cancers. While the uterine cervix is highly responsive to estrogen, the role of estrogen in cervical cancer, which is strongly associated with human papillomavirus (HPV) infections, is poorly understood. Recent studies in HPV transgenic mouse models provide evidence that estrogen and its nuclear receptor promote cervical cancer in combination with HPV oncogenes. While epidemiological studies further support this hypothesis, there is little experimental data assessing the hormonal responsiveness of human cervical cancers. If these cancers are dependent upon estrogen, then drugs targeting estrogen and its receptors may be effective in treating and/or preventing cervical cancer, the second leading cause of death by cancer amongst women worldwide. PMID:20456973

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

    PubMed

    Murakami, Gen

    2016-01-01

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

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

    PubMed Central

    Murakami, Gen

    2016-01-01

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

  4. Estrogenic activity, estrogens, and calcium in runoff post-layer litter application from rainfall simulated events

    USDA-ARS?s Scientific Manuscript database

    Estrogens in runoff from fields fertilized with animal wastes have been implicated as endocrine disruptors of fish in recipient surface waters. The goal of this study was to measure estrogenic activity in runoff post-application of animal waste with the greatest potential for estrogenic activity - ...

  5. Unbalanced Estrogen Metabolism in Ovarian Cancer

    PubMed Central

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

    2013-01-01

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

  6. Estrogens and Cognition: Friends or Foes?

    PubMed Central

    Korol, Donna L.; Pisani, Samantha L.

    2015-01-01

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

  7. The role of estrogen and estrogen receptors in chemoresistance.

    PubMed

    Sui, M; Zhang, H; Fan, W

    2011-01-01

    Drug resistance is one of the major obstacles limiting the success of cancer chemotherapy. Biological mechanisms contributing to drug resistance may be present de novo and related to inherent features or may be raised after exposure to anticancer drugs. In recent years, both clinical observations and experimental studies suggested that steroid hormones and their receptors might also affect the therapeutic efficacy of antineoplastic drugs. Estrogens and estrogen receptors (ER) are well-known for their critical roles in the development and progression of breast tumors. It has long been known that breast tumors expressing ERα protein (ERα+) behave in a fundamentally different fashion than ERα-negative (ERα-) tumors with regard to their responses to hormonal therapy. Data obtained from both laboratory and clinical investigations suggested that some chemotherapeutic agents are clearly less effective in ERα+ tumors than ERα- tumors, although the mechanisms of ERα-mediated chemoresistance are not entirely clear. Moreover, recent studies from our laboratory and others demonstrated that the combination of antiestrogenic agents with chemotherapeutic drugs is of significant therapeutic benefit in ERα+ breast cancer over chemotherapy alone. In addition, the ERα-derived peptides, microRNAs specifically targeting ERα, as well as agents targeting estrogen-related receptors (ERRs) may hold promise to sensitize ERα+ breast tumors to chemotherapy. Considering that ERs are expressed in ˜ 65% of human breast cancer, the ERα-mediated chemoresistance has become a big challenge for clinical treatment. The hope to overcome this drug resistance relies on further clarification of specific pathways or molecules contributing to the resistance. More exhaustive and systematic studies are essential to reach deeper understandings on the underlying mechanisms and to develop novel approaches to sensitize ERα+ breast tumors to chemotherapy.

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

    PubMed

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

    2007-04-11

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

  9. Androgen, Estrogen and the Bone Marrow Microenvironment

    DTIC Science & Technology

    2009-12-01

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

  10. Estrogenic Potentials of Traditional Chinese Medicine.

    PubMed

    Kiyama, Ryoiti

    2017-09-25

    Estrogen, a steroid hormone, is associated with several human activities, including environmental, industrial, agricultural, pharmaceutical and medical fields. In this review paper, estrogenic activity associated with traditional Chinese medicines (TCMs) is discussed first by focusing on the assays needed to detect estrogenic activity (animal test, cell assay, ligand-binding assay, protein assay, reporter-gene assay, transcription assay and yeast two-hybrid assay), and then, their sources, the nature of activities (estrogenic or anti-estrogenic, or other types), and pathways/functions, along with the assay used to detect the activity, which is followed by a summary of effective chemicals found in or associated with TCM. Applications of estrogens in TCM are then discussed by a comprehensive search of the literature, which include basic study/pathway analysis, cell functions, diseases/symptoms and medicine/supplements. Discrepancies and conflicting cases about estrogenicity of TCM among assays or between TCM and their effective chemicals, are focused on to enlarge estrogenic potentials of TCM by referring to omic knowledge such as transcriptome, proteome, glycome, chemome, cellome, ligandome, interactome and effectome.

  11. Quantum chemical studies of estrogenic compounds

    USDA-ARS?s Scientific Manuscript database

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

  12. Estrogen potency of oral contraceptive pills.

    PubMed

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

    1975-01-01

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

  13. Estrogen, aging and the cardiovascular system

    PubMed Central

    Stice, James P.; Lee, Jennifer S.; Pechenino, Angela S.; Knowlton, Anne A.

    2014-01-01

    Estrogen is a powerful hormone with pleiotropic effects. Estrogens have potent antioxidant effects and are able to reduce inflammation, induce vasorelaxation and alter gene expression in both the vasculature and the heart. Estrogen treatment of cultured cardiac myocytes and endothelial cells rapidly activates NFκB, induces heat-shock protein (HSP)-72, a potent intracellular protective protein, and protects cells from simulated ischemia. In in vivo models, estrogens protect against ischemia and trauma/hemorrhage. Estrogens may decrease the expression of soluble epoxide hydrolase, which has deleterious effects on the cardiovascular system through metabolism of epoxyeicosatrienoic acids. Natural (endogenous) estrogens in premenopausal women appear to protect against cardiovascular disease and yet controlled clinical trials have not indicated a benefit from estrogen replacement postmenopause. Much remains to be understood in regards to the many properties of this powerful hormone and how changes in this hormone interact with aging-associated changes. The unexpected negative results of trials of estrogen replacement postmenopause probably arise from our lack of understanding of the many effects of this hormone. PMID:19371207

  14. Estrogenic activity of naturally occurring anthocyanidins.

    PubMed

    Schmitt, E; Stopper, H

    2001-01-01

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

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

    EPA Pesticide Factsheets

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

  16. Estrogens and Stem Cells in Thyroid Cancer

    PubMed Central

    Zane, Mariangela; Catalano, Veronica; Scavo, Emanuela; Bonanno, Marco; Pelizzo, Maria Rosa; Todaro, Matilde; Stassi, Giorgio

    2014-01-01

    Recent discoveries highlight the emerging role of estrogens in the initiation and progression of different malignancies through their interaction with stem cell (SC) compartment. Estrogens play a relevant role especially for those tumors bearing a gender disparity in incidence and aggressiveness, as occurs for most thyroid diseases. Although several experimental lines suggest that estrogens promote thyroid cell proliferation and invasion, their precise contribution in SC compartment still remains unclear. This review underlines the interplay between hormones and thyroid function, which could help to complete the puzzle of gender discrepancy in thyroid malignancies. Defining the association between estrogen receptors’ status and signaling pathways by which estrogens exert their effects on thyroid cells is a potential tool that provides important insights in pathogenetic mechanisms of thyroid tumors. PMID:25120531

  17. [Estrogen receptors and the mammary gland].

    PubMed

    Barrón, A; Bermejo, L; Castro, I

    1997-01-01

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

  18. Infrared emitting device and method

    DOEpatents

    Kurtz, Steven R.; Biefeld, Robert M.; Dawson, L. Ralph; Howard, Arnold J.; Baucom, Kevin C.

    1997-01-01

    An infrared emitting device and method. The infrared emitting device comprises a III-V compound semiconductor substrate upon which are grown a quantum-well active region having a plurality of quantum-well layers formed of a ternary alloy comprising InAsSb sandwiched between barrier layers formed of a ternary alloy having a smaller lattice constant and a larger energy bandgap than the quantum-well layers. The quantum-well layers are preferably compressively strained to increase the threshold energy for Auger recombination; and a method is provided for determining the preferred thickness for the quantum-well layers. Embodiments of the present invention are described having at least one cladding layer to increase the optical and carrier confinement in the active region, and to provide for waveguiding of the light generated within the active region. Examples have been set forth showing embodiments of the present invention as surface- and edge-emitting light emitting diodes (LEDs), an optically-pumped semiconductor laser, and an electrically-injected semiconductor diode laser. The light emission from each of the infrared emitting devices of the present invention is in the midwave infrared region of the spectrum from about 2 to 6 microns.

  19. High performance light emitting transistors

    NASA Astrophysics Data System (ADS)

    Namdas, Ebinazar B.; Ledochowitsch, Peter; Yuen, Jonathan D.; Moses, Daniel; Heeger, Alan J.

    2008-05-01

    Solution processed light emitting field-effect transistors (LEFETs) with peak brightness exceeding 2500cd/m2 and external quantum efficiency of 0.15% are demonstrated. The devices utilized a bilayer film comprising a hole transporting polymer, poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b] thiophene) and a light emitting polymer, Super Yellow, a polyphenylenevinylene derivative. The LEFETs were fabricated in the bottom gate architecture with top-contact Ca /Ag as source/drain electrodes. Light emission was controlled by the gate voltage which controls the hole current. These results indicate that high brightness LEFETs can be made by using the bilayer film (hole transporting layer and a light emitting polymer).

  20. Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

    PubMed Central

    Engler-Chiurazzi, E.B.; Brown, C.M.; Povroznik, J.M.; Simpkins, J.W.

    2016-01-01

    There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury. PMID:26891883

  1. Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury.

    PubMed

    Engler-Chiurazzi, E B; Brown, C M; Povroznik, J M; Simpkins, J W

    2017-10-01

    There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Vascular Effects of Estrogenic Menopausal Hormone Therapy

    PubMed Central

    Reslan, Ossama M.; Khalil, Raouf A.

    2011-01-01

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

  3. Blue light emitting thiogallate phosphor

    DOEpatents

    Dye, Robert C.; Smith, David C.; King, Christopher N.; Tuenge, Richard T.

    1998-01-01

    A crystalline blue emitting thiogallate phosphor of the formula RGa.sub.2 S.sub.4 :Ce.sub.x where R is selected from the group consisting of calcium, strontium, barium and zinc, and x is from about 1 to 10 atomic percent, the phosphor characterized as having a crystalline microstructure on the size order of from about 100 .ANG. to about 10,000 .ANG. is provided together with a process of preparing a crystalline blue emitting thiogallate phosphor by depositing on a substrate by CVD and resultant thin film electroluminescent devices including a layer of such deposited phosphor on an ordinary glass substrate.

  4. Criteria for successful estrogen therapy in osteoporosis.

    PubMed

    Lindsay, R

    1993-01-01

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

  5. Estrogens from sewage in coastal marine environments.

    PubMed

    Atkinson, Shannon; Atkinson, Marlin J; Tarrant, Ann M

    2003-04-01

    Estrogens are ancient molecules that act as hormones in vertebrates and are biologically active in diverse animal phyla. Sewage contains natural and synthetic estrogens that are detectable in streams, rivers, and lakes. There are no studies reporting the distribution of steroidal estrogens in marine environments. We measured estrogens in sewage, injection-well water, and coastal tropical and offshore tropical water in the Pacific Ocean, western Atlantic Ocean, and Caribbean Sea. Concentrations of unconjugated estrone ranged from undetectable (< 40 pg/L) in the open ocean to nearly 2,000 pg/L in Key West, Florida, and Rehoboth Bay, Delaware (USA); estrone concentrations were highest near sources of sewage. Enzymatic hydrolysis of steroid conjugates in seawater samples indicated that polar conjugates comprise one-half to two-thirds of "total estrone" (unconjugated plus conjugated) in Hawaiian coastal samples. Adsorption to basalt gravel and carbonate sand was less than 20% per week and indicates that estrogens can easily leach into the marine environment from septic fields and high-estrogen groundwater. Of 20 sites (n = 129 samples), the mean values from 12 sites were above the threshold concentration for uptake into coral, indicating that there is a net uptake of anthropogenic steroidal estrogen into these environments, with unknown impacts.

  6. Role of estrogen in diastolic dysfunction.

    PubMed

    Zhao, Zhuo; Wang, Hao; Jessup, Jewell A; Lindsey, Sarah H; Chappell, Mark C; Groban, Leanne

    2014-03-01

    The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after menopause and may lead to heart failure. While evidence suggests that estrogens protect the premenopausal heart from hypertension and ventricular remodeling, the specific mechanisms involved remain elusive. Moreover, whether there is a protective role of estrogens against cardiovascular disease, and specifically LVDD, continues to be controversial. Clinical and basic science have implicated activation of the renin-angiotensin-aldosterone system (RAAS), linked to the loss of ovarian estrogens, in the pathogenesis of postmenopausal diastolic dysfunction. As a consequence of increased tissue ANG II and low estrogen, a maladaptive nitric oxide synthase (NOS) system produces ROS that contribute to female sex-specific hypertensive heart disease. Recent insights from rodent models that mimic the cardiac phenotype of an estrogen-insufficient or -deficient woman (e.g., premature ovarian failure or postmenopausal), including the ovariectomized congenic mRen2.Lewis female rat, provide evidence showing that estrogen modulates the tissue RAAS and NOS system and related intracellular signaling pathways, in part via the membrane G protein-coupled receptor 30 (GPR30; also called G protein-coupled estrogen receptor 1). Complementing the cardiovascular research in this field, the echocardiographic correlates of LVDD as well as inherent limitations to its use in preclinical rodent studies will be briefly presented. Understanding the roles of estrogen and GPR30, their interactions with the local RAAS and NOS system, and the relationship of each of these to LVDD is necessary to identify new therapeutic targets and alternative treatments for diastolic heart failure that achieve the cardiovascular benefits of estrogen replacement without its side effects and contraindications.

  7. Role of estrogen in diastolic dysfunction

    PubMed Central

    Zhao, Zhuo; Wang, Hao; Jessup, Jewell A.; Lindsey, Sarah H.; Chappell, Mark C.

    2014-01-01

    The prevalence of left ventricular diastolic dysfunction (LVDD) sharply increases in women after menopause and may lead to heart failure. While evidence suggests that estrogens protect the premenopausal heart from hypertension and ventricular remodeling, the specific mechanisms involved remain elusive. Moreover, whether there is a protective role of estrogens against cardiovascular disease, and specifically LVDD, continues to be controversial. Clinical and basic science have implicated activation of the renin-angiotensin-aldosterone system (RAAS), linked to the loss of ovarian estrogens, in the pathogenesis of postmenopausal diastolic dysfunction. As a consequence of increased tissue ANG II and low estrogen, a maladaptive nitric oxide synthase (NOS) system produces ROS that contribute to female sex-specific hypertensive heart disease. Recent insights from rodent models that mimic the cardiac phenotype of an estrogen-insufficient or -deficient woman (e.g., premature ovarian failure or postmenopausal), including the ovariectomized congenic mRen2.Lewis female rat, provide evidence showing that estrogen modulates the tissue RAAS and NOS system and related intracellular signaling pathways, in part via the membrane G protein-coupled receptor 30 (GPR30; also called G protein-coupled estrogen receptor 1). Complementing the cardiovascular research in this field, the echocardiographic correlates of LVDD as well as inherent limitations to its use in preclinical rodent studies will be briefly presented. Understanding the roles of estrogen and GPR30, their interactions with the local RAAS and NOS system, and the relationship of each of these to LVDD is necessary to identify new therapeutic targets and alternative treatments for diastolic heart failure that achieve the cardiovascular benefits of estrogen replacement without its side effects and contraindications. PMID:24414072

  8. Double Light-Emitting Diode

    NASA Technical Reports Server (NTRS)

    Johnson, R. L.; Hall, T. C.

    1985-01-01

    Two GaAs light-emitting diodes packaged as single unit offer greater reliability than conventional single-diode package. One diode is primary light source. If it fails, backup diode switched in. Each diode has separate power lead, so either or both switched on or off at same time.

  9. Infrared emitting device and method

    DOEpatents

    Kurtz, S.R.; Biefeld, R.M.; Dawson, L.R.; Howard, A.J.; Baucom, K.C.

    1997-04-29

    The infrared emitting device comprises a III-V compound semiconductor substrate upon which are grown a quantum-well active region having a plurality of quantum-well layers formed of a ternary alloy comprising InAsSb sandwiched between barrier layers formed of a ternary alloy having a smaller lattice constant and a larger energy bandgap than the quantum-well layers. The quantum-well layers are preferably compressively strained to increase the threshold energy for Auger recombination; and a method is provided for determining the preferred thickness for the quantum-well layers. Embodiments of the present invention are described having at least one cladding layer to increase the optical and carrier confinement in the active region, and to provide for waveguiding of the light generated within the active region. Examples have been set forth showing embodiments of the present invention as surface- and edge-emitting light emitting diodes (LEDs), an optically-pumped semiconductor laser, and an electrically-injected semiconductor diode laser. The light emission from each of the infrared emitting devices of the present invention is in the midwave infrared region of the spectrum from about 2 to 6 microns. 8 figs.

  10. Surface-emitting laser logic

    SciTech Connect

    Olbright, G.R.; Bryan, R.P.; Brennan, T.M.; Lear, K.; Poirier, G.E.; Fu, W.S. ); Jewell, J.L.; Lee, Y.H. )

    1990-10-31

    We describe a new class of optical logic devices which consist of integrated phototransistors and surface-emitting lasers. The devices function as optical neurons having high gain and, as arrays, are ideal for neural networks, parallel optical signal processing and optical computing applications. 3 refs., 3 figs.

  11. Broadband light-emitting diode

    DOEpatents

    Fritz, Ian J.; Klem, John F.; Hafich, Michael J.

    1998-01-01

    A broadband light-emitting diode. The broadband light-emitting diode (LED) comprises a plurality of III-V compound semiconductor layers grown on a semiconductor substrate, with the semiconductor layers including a pair of cladding layers sandwiched about a strained-quantum-well active region having a plurality of different energy bandgaps for generating light in a wavelength range of about 1.3-2 .mu.m. In one embodiment of the present invention, the active region may comprise a first-grown quantum-well layer and a last-grown quantum-well layer that are oppositely strained; whereas in another embodiment of the invention, the active region is formed from a short-period superlattice structure (i.e. a pseudo alloy) comprising alternating thin layers of InGaAs and InGaAlAs. The use a short-period superlattice structure for the active region allows different layers within the active region to be simply and accurately grown by repetitively opening and closing one or more shutters in an MBE growth apparatus to repetitively switch between different growth states therein. The broadband LED may be formed as either a surface-emitting LED or as an edge-emitting LED for use in applications such as chemical sensing, fiber optic gyroscopes, wavelength-division-multiplexed (WDM) fiber-optic data links, and WDM fiber-optic sensor networks for automobiles and aircraft.

  12. Broadband light-emitting diode

    DOEpatents

    Fritz, I.J.; Klem, J.F.; Hafich, M.J.

    1998-07-14

    A broadband light-emitting diode is disclosed. The broadband light-emitting diode (LED) comprises a plurality of III-V compound semiconductor layers grown on a semiconductor substrate, with the semiconductor layers including a pair of cladding layers sandwiched about a strained-quantum-well active region having a plurality of different energy bandgaps for generating light in a wavelength range of about 1.3--2 {micro}m. In one embodiment of the present invention, the active region may comprise a first-grown quantum-well layer and a last-grown quantum-well layer that are oppositely strained; whereas in another embodiment of the invention, the active region is formed from a short-period superlattice structure (i.e. a pseudo alloy) comprising alternating thin layers of InGaAs and InGaAlAs. The use a short-period superlattice structure for the active region allows different layers within the active region to be simply and accurately grown by repetitively opening and closing one or more shutters in an MBE growth apparatus to repetitively switch between different growth states therein. The broadband LED may be formed as either a surface-emitting LED or as an edge-emitting LED for use in applications such as chemical sensing, fiber optic gyroscopes, wavelength-divisionmultiplexed (WDM) fiber-optic data links, and WDM fiber-optic sensor networks for automobiles and aircraft. 10 figs.

  13. Estrogen and thyroid diseases: an update.

    PubMed

    Lu, Yihan; Li, Jian; Li, Jing

    2016-08-01

    Most of thyroid diseases show female predilection, especially autoimmune thyroid diseases (AITD) and thyroid cancer (TC). We give an updated brief review here, focusing on estrogen, estrogen receptor (ER) and AITD as well as TC. Estrogen can regulate the functions of nearly all immunocyte subsets, which may contribute to the development of AITD. However, there was still lack of direct studies on ER subtype-specific effects on AITD. Recently, the local expression of ER subtypes and their individual mediated actions in the pathogenesis of TC have already received much attention. ERα activation seems to exacerbate the development of TC, while wild-type ERβ (ERβ1) plays a protective role against TC.

  14. Vaginal Estrogen for Genitourinary Syndrome of Menopause

    PubMed Central

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

    2016-01-01

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

  15. Raloxifene. Not better than estrogen.

    PubMed Central

    2000-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2010-01-01

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

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

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

    2004-01-01

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

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

    PubMed

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

    2004-11-01

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

  1. Breast Cancer and Estrogen-Alone Update

    MedlinePlus

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

  2. Estrogen May Influence Women's Depression Risk

    MedlinePlus

    ... news/fullstory_167353.html Estrogen May Influence Women's Depression Risk Early menstruation, more frequent periods seem to ... reproductive years may have a lower risk of depression, a new study finds. Previous research has suggested ...

  3. Noncontraceptive estrogens and nonfatal myocardial infarction.

    PubMed

    Jick, H; Dinan, B; Rothman, K J

    1978-04-03

    We obtained information on 107 women younger than 46 years discharged from a hospital with a diagnosis of acute myocardial infarction. In the series there were 17 women aged 39 to 45 years who were otherwise apparently healthy and had had a natural menopause, hysterectomy, or tubal ligation or whose spouse had had a vasectomy. Among them, nine (53%) were taking noncontraceptive estrogens just prior to admission. Among 34 control women, four (12%) were taking estrogens. The relative risk estimate, comparing estrogen users with nonusers, is 7.5, with 90% confidence limits of 2.4 and 24. All but one of the 17 ml subjects were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 38 years who both smoke and take estrogens appears to be substantial.

  4. Pyrolysis of wastewater biosolids significantly reduces estrogenicity.

    PubMed

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

    2016-11-05

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

  5. Vascular cell signaling by membrane estrogen receptors.

    PubMed

    Kim, Kyung Hee; Moriarty, Katie; Bender, Jeffrey R

    2008-10-01

    The definition of estrogen's actions has expanded from transcriptional regulation to the rapid, membrane-initiated activation of numerous signal transduction cascades. Multiple biological effects of estrogen have been shown in numerous animals, cellular and molecular studies, which support the favorable effects of estrogen on vascular structure, function, and cell signaling. Work from several laboratories has shown that these effects are mediated by distinct forms of estrogen receptor (ER) alpha. This includes estrogen-stimulated rapid activation of endothelial nitric oxide synthase (eNOS), resulting in the elaboration of the athero-protective, angiogenesis-promoting product nitric oxide (NO). We have described the expression of ER46, an N-terminus truncated isoform of the ERalpha, in human endothelial cells (EC), and its critical role in membrane-initiated, rapid responses to 17beta-estradiol (E2). We have proposed an ER46-centered, eNOS activating molecular complex in human EC caveolar membranes, containing c-Src, phosphatidylinositol 3-kinase (PI3K), Akt and eNOS. Our previous studies support estrogen-induced rapid eNOS activation via a sequential c-Src/PI3K/Akt cascade in EC. In this review, we describe estrogen-induced, rapid, non-genomic actions in endothelium, driven by c-Src-ER46-caveolin-1 interactions, with consequent activation of eNOS. Amidst ongoing controversies in hormone replacement therapy, these molecular and cellular data, defining favorable estrogenic effects on the endothelium, provide a strong impetus to resolve these clinical questions.

  6. Function of Estrogen Receptor Tryosine Phosphorylation

    DTIC Science & Technology

    1998-07-01

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

  7. Estrogenic activity in Finnish municipal wastewater effluents.

    PubMed

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

    2016-01-01

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

  8. Assessment of estrogen receptor--histone interactions.

    PubMed Central

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

    1981-01-01

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

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

    PubMed Central

    S Katzenellenbogen, Benita; A Katzenellenbogen, John

    2000-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture.

    PubMed Central

    Zava, D T; Blen, M; Duwe, G

    1997-01-01

    We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods, herbs, and spices and in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans. Results show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked differences in their ability to induce end products of estrogen action and to regulate cell proliferation. All of the different classes of estrogens stimulated cell proliferation at concentrations that half-saturated ER, but only some classes were able to induce estrogen-regulated end products. Genistein, a common phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its effects on cell proliferation and ability to induce estrogen-regulated end products. Moreover, we found that many of the foods, herbs, and spices commonly consumed by humans contain significant amounts of phytoestrogens, and consumption of soy milk, a phytoestrogen-rich food, markedly increases the levels of phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet high in phytoestrogens would significantly reduce the binding of weak xenoestrogens to ER in target tissues in vivo. PMID:9168008

  12. White light-emitting organic electroluminescent devices

    DOEpatents

    Shiang, Joseph John; Duggal, Anil Raj; Parthasarathy, Gautam

    2006-06-20

    A light-emitting device comprises a light-emitting member, which comprises two electrodes, at least two organic electroluminescent ("EL") materials disposed between the electrodes, a charge blocking material disposed between the electrodes, and at least one photoluminescent ("PL") material. The light-emitting member emits electromagnetic ("EM") radiation having a first spectrum in response to a voltage applied across the two electrodes. The PL material absorbs a portion of the EM radiation emitted by the light-emitting member and emits EM radiation having second spectrum different than the first spectrum. Each of the organic EL materials emits EM radiation having a wavelength range selected from the group consisting of blue and red wavelength ranges.

  13. Porous light-emitting compositions

    SciTech Connect

    Burrell, Anthony K; McCleskey, Thomas Mark; Jia, Quanxi; Bauer, Eve; Mueller, Alexander H

    2012-04-17

    Light-emitting devices are prepared by coating a porous substrate using a polymer-assisted deposition process. Solutions of metal precursor and soluble polymers having binding properties for metal precursor were coated onto porous substrates. The coated substrates were heated at high temperatures under a suitable atmosphere. The result was a substrate with a conformal coating that did not substantially block the pores of the substrate.

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

    SciTech Connect

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

    2008-08-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2014-08-15

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

  19. Detection of estrogenic activity from kraft mill effluents by the yeast estrogen screen.

    PubMed

    Chamorro, S; Hernández, V; Monsalvez, E; Becerra, J; Mondaca, M A; Piña, B; Vidal, G

    2010-02-01

    Estrogenic activity of kraft pulp mill effluents (P. radiata, E. globulus and mixed -50% E. globulus and 50% P. radiata) was evaluated by the yeast estrogen screen assay. The estrogenic activity values were relatively low, ranking between 1.475 and 0.383 ng/L of EE2 eq. (Estrogenic equivalent of 17 alpha-ethynylestradiol), where the highest value corresponds to the E. globulus effluent and the lowest value to the P. radiata effluent. Analysis by solid phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) of chemical compounds present in all three effluents detected at least five major groups of organic compounds, corresponding to fatty acids, hydrocarbons, phenols, sterols and triterpenes. Comparison of analytical and biological data suggests that sterols could be the cause of the estrogenic activity in the evaluated effluent.

  20. SCREENING CHEMICALS FOR ESTROGEN RECEPTOR ...

    EPA Pesticide Factsheets

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

  1. Effect of vaginal estrogen on pessary use

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Smiley, Dia A.; Khalil, Raouf A.

    2010-01-01

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

  3. Estrogenic compounds, estrogen receptors and vascular cell signaling in the aging blood vessels.

    PubMed

    Smiley, Dia A; Khalil, Raouf A

    2009-01-01

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

  4. Visible light emitting vertical cavity surface emitting lasers

    DOEpatents

    Bryan, R.P.; Olbright, G.R.; Lott, J.A.; Schneider, R.P. Jr.

    1995-06-27

    A vertical cavity surface emitting laser that emits visible radiation is built upon a substrate, then having mirrors, the first mirror on top of the substrate; both sets of mirrors being a distributed Bragg reflector of either dielectrics or other materials which affect the resistivity or of semiconductors, such that the structure within the mirror comprises a plurality of sets, each having a thickness of {lambda}/2n where n is the index of refraction of each of the sets; each of the mirrors adjacent to spacers which are on either side of an optically active bulk or quantum well layer; and the spacers and the optically active layer are from one of the following material systems: In{sub z}(Al{sub y}Ga{sub 1{minus}y}){sub 1{minus}z}P, InAlGaAs, AlGaAs, InGaAs, or AlGaP/GaP, wherein the optically active region having a length equal to m {lambda}/2n{sub eff} where m is an integer and n{sub eff} is the effective index of refraction of the laser cavity, and the spacer layer and one of the mirrors being transmissive to radiation having a wavelength of {lambda}/n, typically within the green to red portion of the visible spectrum. 10 figs.

  5. Visible light emitting vertical cavity surface emitting lasers

    DOEpatents

    Bryan, Robert P.; Olbright, Gregory R.; Lott, James A.; Schneider, Jr., Richard P.

    1995-01-01

    A vertical cavity surface emitting laser that emits visible radiation is built upon a substrate, then having mirrors, the first mirror on top of the substrate; both sets of mirrors being a distributed Bragg reflector of either dielectrics or other materials which affect the resistivity or of semiconductors, such that the structure within the mirror comprises a plurality of sets, each having a thickness of .lambda./2n where n is the index of refraction of each of the sets; each of the mirrors adjacent to spacers which are on either side of an optically active bulk or quantum well layer; and the spacers and the optically active layer are from one of the following material systems: In.sub.z (Al.sub.y Ga.sub.1-y).sub.1-z P, InAlGaAs, AlGaAs, InGaAs, or AlGaP/GaP, wherein the optically active region having a length equal to m .lambda./2n.sub.eff where m is an integer and n.sub.eff is the effective index of refraction of the laser cavity, and the spacer layer and one of the mirrors being transmissive to radiation having a wavelength of .lambda./n, typically within the green to red portion of the visible spectrum.

  6. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis.

    PubMed

    Pacifici, R

    1996-08-01

    In summary, available data demonstrate that IL-1 and TNF are the causative agents underlying the bone loss induced by estrogen deficiency. Indeed, these factors are produced in bone and the bone marrow, released in larger amounts from cells of estrogen-deficient subjects, and indispensable for reproducing the effects of estrogen deficiency in bone. These observations support the hypothesis that the bone sparing effect of estrogen is due to the ability of the hormone to block osteoclastogenesis, the activation of mature osteoclasts and, as recently demonstrated, the rate of apoptotic osteoclast death. Although IL-1 and TNF play a prominent causal role in these events, the bone-sparing effect of estrogen is mediated by numerous cytokines which, by simultaneously stimulating multiple target cells, induce effects that are not accounted for by any one single factor (Fig. 2). The ability of estrogen to regulate some, but not all, the cytokines involved in this process is not inconsistent with this hypothesis because cytokines have potent synergistic effects. Thus, a considerable increase in bone resorption may result from a relatively small increase in the concentration of only a few of the bone-resorbing factors present in the bone microenvironment. This concept is best illustrated by the study of Miyaura et al. demonstrating that the concentrations of either IL-1, IL-6, IL-6 receptor, or prostaglandins detected in the bone marrow of OVX mice are insufficient to account for the increased bone resorption caused by estrogen withdrawal. In contrast, the increase in bone resorption induced by OVX can be explained by the cumulative effects of these cytokines. Thus, a better understanding of the cooperative effects of cytokines and a recognition that the contribution of individual cytokines to postmenopausal bone loss varies with the passage of time after menopause are necessary to fully understand the mechanism of action of estrogen in bone. Although the relevance of

  7. Is Estrogen a Therapeutic Target for Glaucoma?

    PubMed Central

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

    2016-01-01

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

  8. Estrogen and colorectal cancer incidence and mortality.

    PubMed

    Lavasani, Sayeh; Chlebowski, Rowan T; Prentice, Ross L; Kato, Ikuko; Wactawski-Wende, Jean; Johnson, Karen C; Young, Alicia; Rodabough, Rebecca; Hubbell, F Allan; Mahinbakht, Ali; Simon, Michael S

    2015-09-15

    The preponderance of observational studies describe an association between the use of estrogen alone and a lower incidence of colorectal cancer. In contrast, no difference in the incidence of colorectal cancer was seen in the Women's Health Initiative (WHI) randomized, placebo-controlled trial with estrogen alone after a mean intervention of 7.1 years and cumulative follow-up of 13.2 years. This study extends these findings by providing detailed analyses of the effects of estrogen alone on the histology, grade, and stage of colorectal cancer, relevant subgroups, and deaths from and after colorectal cancer. The WHI study was a randomized, double-blind, placebo-controlled trial involving 10,739 postmenopausal women with prior hysterectomy. Participants were assigned to conjugated equine estrogen at 0.625 mg/d (n = 5279) or a matching placebo (n = 5409). Rates of colorectal cancer diagnoses and deaths from and after colorectal cancer were assessed throughout the study. Colorectal cancer rates in the estrogen-alone and placebo groups were comparable: 0.14% and 0.12% per year, respectively (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.83-1.58; P = .43). Bowel screening examinations were comparable between the 2 groups throughout the study. The grade, stage, and location of colorectal cancer did not differ between the randomization groups. There were more colorectal cancer deaths in the estrogen-alone group (34 [0.05%] vs 24 [0.03%]; HR, 1.46, 95% CI, 0.86-2.46; P = .16), but the difference was not statistically significant. The colorectal cancer incidence was higher for participants with a history of colon polyp removal in the estrogen-alone group (0.23% vs 0.02%; HR, 13.47; nominal 95% CI, 1.76-103.0; P < .001). The use of estrogen alone in postmenopausal women with prior hysterectomy does not influence the incidence of colorectal cancer or deaths from or after colorectal cancer. A possibly higher risk of colorectal cancer in women with

  9. Is Estrogen a Therapeutic Target for Glaucoma?

    PubMed

    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

  10. Estrogen therapy in systemic lupus erythematosus.

    PubMed

    Askanase, Anca D

    2004-01-01

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

  11. Estrogenicity of Glabridin in Ishikawa Cells

    PubMed Central

    Su Wei Poh, Melissa; Viseswaran, Navaratnam

    2015-01-01

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

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

    EPA Science Inventory

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

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

    SciTech Connect

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

    1996-06-07

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  17. Effect of estrogen on iron metabolism in mammals.

    PubMed

    Yang, Xiao; Xu, Man-Man; Wang, Jun; Xie, Jun-Xia

    2016-10-25

    Estrogen is a steroid hormone produced mainly by the ovaries. It combines with the nuclear receptors to exert the biological effects influencing the metabolism of body. Elevated levels of estrogen are often associated with altered iron levels in mammals. Furthermore, the findings of estrogen response element (ERE) have demonstrated that estrogen affects iron metabolism directly in peripheral tissues. In this review, we will briefly summarize the effect of estrogen on iron metabolism in mammals, and discuss recent progress in the mechanisms of estrogen on some iron related proteins in order to provide guidance for clinical use of estrogen. Estrogen and iron metabolism are closely related, but the exact regulatory mechanisms still need further exploration.

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

    PubMed

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

    2004-10-01

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

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

    PubMed

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

    2007-05-01

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

  20. Estrophilin immunoreactivity versus estrogen receptor binding activity in meningiomas: evidence for multiple estrogen binding sites

    SciTech Connect

    Lesch, K.P.; Schott, W.; Gross, S.

    1987-09-01

    The existence of estrogen receptors in human meningiomas has long been a controversial issue. This may be explained, in part, by apparent heterogeneity of estrogen binding sites in meningioma tissue. In this study, estrogen receptors were determined in 58 meningiomas with an enzyme immunoassay using monoclonal antibodies against human estrogen receptor protein (estrophilin) and with a sensitive radioligand binding assay using /sup 125/I-labeled estradiol (/sup 125/I-estradiol) as radioligand. Low levels of estrophilin immunoreactivity were found in tumors from 62% of patients, whereas radioligand binding activity was demonstrated in about 46% of the meningiomas examined. In eight (14%) tissue samples multiple binding sites for estradiol were observed. The immunoreactive binding sites correspond to the classical, high affinity estrogen receptors: the Kd for /sup 125/I-estradiol binding to the receptor was approximately 0.2 nM and the binding was specific for estrogens. The second, low affinity class of binding sites considerably influenced measurement of the classical receptor even at low ligand concentrations. The epidemiological and clinical data from patients with meningiomas, and the existence of specific estrogen receptors confirmed by immunochemical detection, may be important factors in a theory of oncogenesis.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Estrogenic and anti-estrogenic activity of 23 commercial textile dyes.

    PubMed

    Bazin, Ingrid; Ibn Hadj Hassine, Aziza; Haj Hamouda, Yosra; Mnif, Wissem; Bartegi, Ahgleb; Lopez-Ferber, Miguel; De Waard, Michel; Gonzalez, Catherine

    2012-11-01

    The presence of dyes in wastewater effluent of textile industry is well documented. In contrast, the endocrine disrupting effects of these dyes and wastewater effluent have been poorly investigated. Herein, we studied twenty-three commercial dyes, usually used in the textile industry, and extracts of blue jean textile wastewater samples were evaluated for their agonistic and antagonistic estrogen activity. Total estrogenic and anti-estrogenic activities were measured using the Yeast Estrogen Screen bioassay (YES) that evaluates estrogen receptor binding-dependent transcriptional and translational activities. The estrogenic potencies of the dyes and wastewater samples were evaluated by dose-response curves and compared to the dose-response curve of 17β-estradiol (E2), the reference compound. The dose-dependent anti-estrogenic activities of the dyes and wastewater samples were normalized to the known antagonistic effect of 4-hydroxytamoxifen (4-OHT) on the induction of the lac Z reporter gene by E2. About half azo textile dyes have anti-estrogenic activity with the most active being Blue HFRL. Most azo dyes however have no or weak estrogenic activity. E2/dye or E2/waste water ER competitive binding assays show activity of Blue HFRL, benzopurpurine 4B, Everzol Navy Blue FBN, direct red 89 BNL 200% and waste water samples indicating a mechanism of action common to E2. Our results indicate that several textile dyes are potential endocrine disrupting agents. The presence of some of these dyes in textile industry wastewater may thus impact the aquatic ecosystem. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Oral Contraceptive Estrogen Content and Adverse Effects

    PubMed Central

    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 oral contraceptives and disease is critically reviewed. The review indicates that there is no incontrovertible evidence to support such a relationship. Implications of the recommendations in the Report for physicians and patients are discussed. PMID:21263837

  5. MEMBRANE ESTROGEN RECEPTOR REGULATION OF HYPOTHALAMIC FUNCTION

    PubMed Central

    Micevych, Paul E.; Kelly, Martin J.

    2012-01-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  8. Effect of estrogenic compounds (estrogen or phytoestrogens) combined with exercise on bone and muscle mass in older individuals.

    PubMed

    Chilibeck, Philip D; Cornish, Stephen M

    2008-02-01

    Exercise has a beneficial effect on bone, possibly by stimulating estrogen receptor alpha. Because estrogen up-regulates this receptor, estrogen therapy combined with exercise training may be optimal for increasing bone mineral density. Studies combining estrogen therapy and exercise training in postmenopausal women show mixed results, but indicate that the combination of interventions may be more effective for increasing bone mass than either intervention alone. Plant-like estrogens (i.e phytoestrogens such as soy isoflavones) may act as weak estrogen agonists or antagonists, have small beneficial effects on bone, and may interact with exercise for increasing bone mineral density. Phytoestrogen derived from flaxseed (flax lignans) has not been evaluated as extensively as soy isoflavones and thus its effect on bone is difficult to determine. Estrogen or soy isoflavones given to postmenopausal women results in a small increase in lean tissue mass that may be mediated through estrogen receptor alpha on muscle or through decreased inflammation.

  9. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  10. Cumulative Estrogen Exposure and Prospective Memory in Older Women

    ERIC Educational Resources Information Center

    Hesson, Jacqueline

    2012-01-01

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

  11. Cumulative Estrogen Exposure and Prospective Memory in Older Women

    ERIC Educational Resources Information Center

    Hesson, Jacqueline

    2012-01-01

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

  12. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Patient package inserts for estrogens. 310.515... package inserts for estrogens. (a) Requirement for a patient package insert. FDA concludes that the safe and effective use of drug products containing estrogens requires that patients be fully informed of...

  13. Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  14. Estrogen modifies an electrocommunication signal by altering the electrocyte sodium current in an electric fish, Sternopygus.

    PubMed

    Dunlap, K D; McAnelly, M L; Zakon, H H

    1997-04-15

    Many species of electric fish emit sexually dimorphic electrical signals that are used in gender recognition. In Sternopygus, mature females produce an electric organ discharge (EOD) that is higher in frequency and shorter in pulse duration than that of mature males. EOD pulse duration is determined by ion currents in the electrocytes, and androgens influence EOD pulse duration by altering the inactivation kinetics of the electrocyte sodium current. We examined whether estrogen modulates the female-specific EOD and, if so, whether it regulates EOD pulse duration by acting on the same androgen-sensitive ion current in the electrocytes. We implanted gonadectomized Sternopygus with either empty SILASTIC capsules (control), one capsule filled with estradiol-17beta (E2; low dose), or three capsules of E2 (high dose). Twelve days after implantation, E2-treated fish had plasma E2 levels approximately 3.3-fold (low dose) or approximately 7.1-fold (high dose) higher than controls. After implantation, both E2-treated groups had higher EOD frequency and shorter EOD pulse duration than controls and their own preimplantation values. Through immunocytochemistry, we identified immunoreactive estrogen receptors in the nuclei of electrocytes, indicating that these cells are directly responsive to estrogen. In addition, voltage-clamp studies showed that E2 affected the electrocyte ion currents kinetics: the sodium inactivation time constant was significantly lower in E2-treated fish than in controls. Thus, sexual dimorphism in the electrocommunication signal results, at least in part, from estrogens and androgens acting in opposite directions on the same ion current in the electrocytes.

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

    PubMed

    Behr, Maximilian; Oehlmann, Jörg; Wagner, Martin

    2011-10-01

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

  16. Luminescence conversion of blue light emitting diodes

    NASA Astrophysics Data System (ADS)

    Schlotter, P.; Schmidt, R.; Schneider, J.

    Using blue-emitting GaN/6HSiC chips as primary light sources, we have fabricated green, yellow, red and white emitting LEDs. The generation of mixed colors, as turquoise and magenta is also demonstrated. The underlying physical principle is that of luminescence down-conversion (Stokes shift), as typical for organic luminescent dye molecules. A white emitting LED, using an inorganic converter, Y3Al5O12:Ce3+( ), has also been realized.

  17. Nitride light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Mukai, T.; Nagahama, S.; Iwasa, N.; Senoh, M.; Yamada, T.

    2001-08-01

    We review the progress in the field of InGaN-based light-emitting diodes (LEDs) and discuss the issue of threading dislocations and the luminous efficiency. The first candela-class blue LEDs have been developed. An InGaN layer was used to produce these LEDs instead of a GaN active layer. The quantum-well structure InGaN active layer dramatically improved the external quantum efficiency. There are a number of threading dislocations in nitride-based LEDs. InGaN LEDs, however, have quite high external quantum efficiency. With regard to this, it is thought that the fluctuation of the indium mole fraction is strongly related to the high external quantum efficiency. Considering the density of threading dislocations in the nitride-based LEDs, we discuss what can improve the external quantum efficiency of nitride-based LEDs.

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

    PubMed

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

    2013-07-11

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

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

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Ultrafiltration Tandem Mass Spectrometry of Estrogens for Characterization of Structure and Affinity for Human Estrogen Receptors

    PubMed Central

    Sun, Yongkai; Gu, Chungang; Liu, Xuemei; Liang, Wenzhong; Yao, Ping; Bolton, Judy L.; van Breemen, Richard B.

    2006-01-01

    Although hormone replacement therapy (HRT) is used by post-menopausal women for the relief of menopausal symptoms and the potential reduction of osteoporosis, HRT also increases their risk of Alzheimer’s disease, stroke, breast cancer, and endometrial cancer. Since the majority of these effects are associated primarily with estrogen binding to only one of the estrogen receptors (ER), new assays are needed that can more efficiently evaluate ER-binding and identify ligands selective for ER-α and ER-β. High performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) was combined with ultrafiltration as a new method to investigate the relative binding of compounds to the ERs and to evaluate the structures of these estrogens. Mixtures of estradiol and six equine estrogens including equilin, equilenin, 8,9-dehydroestrone, and their 17β-hydroxyl derivatives were assayed simultaneously to determine their relative binding to human ER-α and ER-β. Estrogens containing a 17β-OH group were found to have higher relative affinities for the estrogen receptors than their ketone analogs. In addition, 17β-EN showed selectivity for binding to ER-β over ER-α. The results were compared to the IC50 values obtained by using a conventional radiolabled estradiol competitive binding assay. Finally, the utility of negative ion electrospray tandem mass spectrometry for the unambiguous identification these estrogen isomers was investigated. Several characteristic recyclization pathways during tandem mass spectrometry were identified, which might be useful for distinguishing related estrogens. PMID:15694777

  1. Association between Physical Activity and Urinary Estrogens and Estrogen Metabolites in Premenopausal Women

    PubMed Central

    Fortner, Renee T.; Xu, Xia; Hankinson, Susan E.; Eliassen, A. Heather; Ziegler, Regina G.

    2012-01-01

    Objective: The objective of the study was to evaluate in premenopausal women the relationships of physically active and sedentary behaviors reported for adulthood and adolescence with a comprehensive profile of estrogen metabolism. Methodology: Fifteen estrogens and estrogen metabolites (jointly termed EM) were measured using liquid chromatography-tandem mass spectrometry in luteal phase urines from 603 premenopausal women in the Nurses' Health Study II. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by level of exposure after adjustment for age, body mass index, alcohol intake, menstrual cycle length, and sample collection timing. Results: High overall physical activity in adulthood (42+ metabolic equivalent h/wk vs. <3 metabolic equivalent h/wk) was associated with a 15% lower level of urinary estradiol (Ptrend = 0.03) and 15% lower level of 16-hydroxylation pathway EM (Ptrend = 0.03). Levels of 2- and 4-hydroxylation pathway EM did not differ significantly by physical activity. High overall activity was also positively associated with four ratios: 2-pathway EM to parent estrogens (Ptrend = 0.05), 2-pathway catechols to parent estrogens (Ptrend = 0.03), 2-pathway catechols to methylated 2-pathway catechols (Ptrend < 0.01), and 2-hydroxyestrone to 16α-hydroxyestrone (Ptrend = 0.01). Similar patterns of association were noted for walking and vigorous physical activity, but there was little evidence of associations with sedentary behaviors or activity during adolescence. Conclusions: High levels of physical activity were associated with lower levels of parent estrogens and 16-hydroxylation pathway EM and preferential metabolism to 2-pathway catechols. The results of our analysis, the largest, most comprehensive examination of physical activity and estrogen metabolism to date, may be useful in future studies investigating the etiology of diseases linked to both physical activity and endogenous estrogen. PMID:22855335

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

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

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

  3. Selectively targeting estrogen receptors for cancer treatment

    PubMed Central

    Shanle, Erin K.; Xu, Wei

    2010-01-01

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

  4. Estrogen receptor expert system overview and examples

    EPA Science Inventory

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

  5. Estrogen and its role in thyroid cancer.

    PubMed

    Derwahl, Michael; Nicula, Diana

    2014-10-01

    Proliferative thyroid diseases are more prevalent in females than in males. Upon the onset of puberty, the incidence of thyroid cancer increases in females only and declines again after menopause. Estrogen is a potent growth factor both for benign and malignant thyroid cells that may explain the sex difference in the prevalence of thyroid nodules and thyroid cancer. It exerts its growth-promoting effect through a classical genomic and a non-genomic pathway, mediated via a membrane-bound estrogen receptor. This receptor is linked to the tyrosine kinase signaling pathways MAPK and PI3K. In papillary thyroid carcinomas, these pathways may be activated either by a chromosomal rearrangement of the tyrosine receptor kinase TRKA, by RET/PTC genes, or by a BRAF mutation and, in addition, in females they may be stimulated by high levels of estrogen. Furthermore, estrogen is involved in the regulation of angiogenesis and metastasis that are critical for the outcome of thyroid cancer. In contrast to other carcinomas, however, detailed knowledge on this regulation is still missing for thyroid cancer. © 2014 Society for Endocrinology.

  6. Estrogen increases renal oxytocin receptor gene expression.

    PubMed

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

    1995-04-01

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

  7. Aerobic Exercise, Estrogens, and Breast Cancer Risk

    DTIC Science & Technology

    2011-11-01

    cycle length of 24 to 35 days and a sedentary lifestyle (two or less weekly sessions of moderate intensity exercise) were randomized into the WISER...on endogenous sex hormone levels, menstrual cycle characteristics, and estrogen metabolism in sedentary , eumenorrheic, healthy premenopausal women... sedentary , healthy women. A comprehensive evaluation on women’s hormonal profile included changes in circulating serum levels of estradiol

  8. Estrogens and Antiestrogens in Prostate Cancer

    DTIC Science & Technology

    2003-01-01

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

  9. HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS

    EPA Science Inventory

    HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS.

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

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

  10. Histopathologic Effects of Estrogens on Marine Fishes

    EPA Science Inventory

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

  11. Women's Skills Linked to Estrogen Levels.

    ERIC Educational Resources Information Center

    Weiss, R.

    1988-01-01

    Summarizes the result of research which considers the effect of women's hormone level on specific skills. Reports that low estrogen levels allow women to excel at spatial skills, but perform poorly at complex motor tasks and speech articulation. Discusses some implications and further research ideas. (YP)

  12. HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS

    EPA Science Inventory

    HUMAN HEALTH IMPACT OF ENVIRONMENTAL ESTROGENIC CHEMICALS.

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

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

  13. Function of Estrogen Receptor Tryosine Phosphorylation

    DTIC Science & Technology

    1999-07-01

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

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

    EPA Pesticide Factsheets

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

  15. In vitro estrogenicity of polybrominated flame retardants.

    PubMed

    Nakari, Tarja; Pessala, Piia

    2005-09-10

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

  16. Estrogen receptor expert system overview and examples

    EPA Science Inventory

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

  17. Function of Estrogen Receptor Tryosine Phosphorylation

    DTIC Science & Technology

    1997-07-01

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

  18. Histopathologic Effects of Estrogens on Marine Fishes

    EPA Science Inventory

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

  19. Targeted estrogen delivery reverses the metabolic syndrome

    PubMed Central

    Finan, Brian; Yang, Bin; Ottaway, Nickki; Stemmer, Kerstin; Müller, Timo D; Yi, Chun-Xia; Habegger, Kirk; Schriever, Sonja C; García-Cáceres, Cristina; Kabra, Dhiraj G; Hembree, Jazzminn; Holland, Jenna; Raver, Christine; Seeley, Randy J; Hans, Wolfgang; Irmler, Martin; Beckers, Johannes; de Angelis, Martin Hrabě; Tiano, Joseph P; Mauvais-Jarvis, Franck; Perez-Tilve, Diego; Pfluger, Paul; Zhang, Lianshan; Gelfanov, Vasily; DiMarchi, Richard D; Tschöp, Matthias H

    2013-01-01

    We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex-independent efficacy over either of the individual hormones alone to correct obesity, hyperglycemia and dyslipidemia in mice. The therapeutic benefits are driven by pleiotropic dual hormone action to improve energy, glucose and lipid metabolism, as shown by loss-of-function models and genetic action profiling. Notably, the peptide-based targeting strategy also prevents hallmark side effects of estrogen in male and female mice, such as reproductive endocrine toxicity and oncogenicity. Collectively, selective activation of estrogen receptors in GLP-1–targeted tissues produces unprecedented efficacy to enhance the metabolic benefits of GLP-1 agonism. This example of targeting the metabolic syndrome represents the discovery of a new class of therapeutics that enables synergistic co-agonism through peptide-based selective delivery of small molecules. Although our observations with the GLP-1–estrogen conjugate justify translational studies for diabetes and obesity, the multitude of other possible combinations of peptides and small molecules may offer equal promise for other diseases. PMID:23142820

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

    PubMed

    Velasco-Murillo, V

    2001-01-01

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

  1. Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation

    PubMed Central

    McEwen, Bruce; Akama, Keith; Alves, Stephen; Brake, Wayne G.; Bulloch, Karen; Lee, Susan; Li, Chenjian; Yuen, Genevieve; Milner, Teresa A.

    2001-01-01

    Estrogens (E) and progestins regulate synaptogenesis in the CA1 region of the dorsal hippocampus during the estrous cycle of the female rat, and the functional consequences include changes in neurotransmission and memory. Synapse formation has been demonstrated by using the Golgi technique, dye filling of cells, electron microscopy, and radioimmunocytochemistry. N-methyl-d-aspartate (NMDA) receptor activation is required, and inhibitory interneurons play a pivotal role as they express nuclear estrogen receptor alpha (ERα) and show E-induced decreases of GABAergic activity. Although global decreases in inhibitory tone may be important, a more local role for E in CA1 neurons seems likely. The rat hippocampus expresses both ERα and ERβ mRNA. At the light microscopic level, autoradiography shows cell nuclear [3H]estrogen and [125I]estrogen uptake according to a distribution that primarily reflects the localization of ERα-immunoreactive interneurons in the hippocampus. However, recent ultrastructural studies have revealed extranuclear ERα immunoreactivity (IR) within select dendritic spines on hippocampal principal cells, axon terminals, and glial processes, localizations that would not be detectable by using standard light microscopic methods. Based on recent studies showing that both types of ER are expressed in a form that activates second messenger systems, these findings support a testable model in which local, non-genomic regulation by estrogen participates along with genomic actions of estrogens in the regulation of synapse formation. PMID:11416193

  2. Selective estrogen receptor modulators and the combination therapy conjugated estrogens/bazedoxifene: A review of effects on the breast.

    PubMed

    Pickar, James H; Komm, Barry S

    2015-09-01

    Traditional menopausal hormone therapy containing estrogens/progestin has been associated with an increased risk of breast cancer, and estrogen exposure is known to promote growth and proliferation of a majority of breast cancers. Therefore, it is important for clinicians to consider the breast safety profile of any hormone-based therapy used in postmenopausal women. This review provides an overview of the breast safety and tolerability profiles of currently marketed selective estrogen receptor modulators, antiestrogens, and the first tissue selective estrogen complex combining conjugated estrogens with the selective estrogen receptor modulator bazedoxifene in postmenopausal women. Selective estrogen receptor modulators and antiestrogens act as estrogen receptor antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and raloxifene protect against breast cancer in high-risk women. Postmenopausal women using selective estrogen receptor modulators for prevention or treatment of osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal treatments do not adversely affect their risk of breast cancer and may, in the case of raloxifene, even be protective. There are limited data on breast cancer in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene use for up to two years did not increase mammographic breast density or breast pain/tenderness, and there was no evidence of an increased risk of breast cancer, suggesting that conjugated estrogens/bazedoxifene has an improved breast safety profile compared with traditional menopausal hormone therapies. Future research will continue to focus on development of selective estrogen receptor modulators and selective estrogen receptor modulator combinations capable of achieving the ideal balance of estrogen receptor agonist and antagonist effects. © The Author(s) 2015.

  3. Estrogenic activity in sediments from European mountain lakes.

    PubMed

    Garcia-Reyero, Natalia; Piña, Benjamin; Grimalt, Joan O; Fernández, Pilar; Fonts, Roger; Polvillo, Oliva; Martrat, Belen

    2005-03-15

    Superficial and bottom sediment samples from 83 European mountain lakes, ranging from Norway to the Pyrenees and East Europe, were tested for estrogenic compounds by the recombinant yeast assay. The results showed widespread potential estrogenic activity arriving at remote lakes. Tatra Mountains (Slovakia) and Scotland Highlands were the regions with the highest prevalence of lakes with high estrogenic values. Comparison of the estrogenic activity in the superficial layer of sediments with pre-industrial age sections showed that estrogenic compounds were predominantly deposited in recent times. Chemical analysis showed that highly estrogenic sediments were significantly enriched in both polycyclic aromatic hydrocarbons (PAH) and organochlorine compounds. For PAH, enrichment ratios in highly estrogenic samples versus nonestrogenic ones were inversely correlated with the vapor pressure value for each compound, indicating a significant relationship between estrogenicity and accumulation of less volatile PAH. Two PAH of predominantly diagenetic origin, retene and perylene, did not show specific enrichment in estrogenic samples. Principal component analysis revealed a strong correlation between estrogenic activity and the presence of contaminants of anthropogenic origin. These data reveal significant amounts of estrogenic compounds in remote lakes, relate them to the overall human activity, and suggest that they may affect organisms inhabiting these ecosystems.

  4. Requirement of metabolic activation for estrogenic activity of Pueraria mirifica.

    PubMed

    Lee, Y S; Park, J S; Cho, S D; Son, J K; Cherdshewasart, W; Kang, K S

    2002-12-01

    A wide range of chemicals derived from plant and human-made xenobiotics are reported to have hormonal activities. The present study was performed to examine the estrogenic effect of Kwao Keur, Pueraria mirifica (PM), that has been used as a rejuvenating folk medicine in Thailand, using recombinant yeast, MCF-7 cell proliferation and HepG2 cell transient transfection assay. In recombinant yeast assay, 0.025, 0.25, 2.5, 25, 2.5 x 10(2), 2.5 x 10(3), 2.5 x 10(4) ng/ml concentrations of PM did not show any estrogenic activities, while 10(-9) of 17 beta-estradiol (positive control) showed high estrogenic activity. Estrogenic activities were induced at 2.5 ng/ml to 25 microg/ml concentrations of PM in a dose-dependent manner on MCF-7 cells and the estrogenic effect of PM was blocked by tamoxifen treatment, a well-known anti-estrogen. PM also showed estrogenic effect on human hepatoma cell line, HepG2 cells, containing estrogen receptor and luciferase reporter gene. Taken together, PM in itself may have no estrogenicity in yeast system, but it has estrogenicity in MCF-7 & HepG2 cells that have human metabolic enzymes. The results indicated that PM may require metabolic activation for estrogenic activity.

  5. Identification of an estrogenic hormone receptor in Caenorhabditis elegans

    SciTech Connect

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

    2007-12-28

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

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

    PubMed Central

    Ribeiro, Jennifer R.; Freiman, Richard N.

    2014-01-01

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

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

    PubMed

    Li, Rena; Cui, Jie; Shen, Yong

    2014-05-25

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

  8. KEEPS: The Kronos Early Estrogen Prevention Study.

    PubMed

    Harman, S M; Brinton, E A; Cedars, M; Lobo, R; Manson, J E; Merriam, G R; Miller, V M; Naftolin, F; Santoro, N

    2005-03-01

    Observational studies have indicated that hormone therapy given at or after menopause is linked to substantial reduction in cardiovascular disease and its risk factors. Recent findings from the Women's Health Initiative (WHI) clinical trial, however, indicate that combined estrogen plus progestin hormone therapy, as well as estrogen-alone hormone therapy (given to women without a uterus), is ineffective in preventing the new onset of cardiac events in previously healthy late menopausal women. Further, the secondary prevention trial, the Heart and Estrogen/progestin Replacement Study (HERS), also failed to demonstrate any benefit of initiation of hormone therapy in women with established coronary heart disease. In light of these results, a hypothesis has arisen that early initiation of hormone therapy, in women who are at the inception of their menopause, will delay the onset of subclinical cardiovascular disease in women. The rationale that earlier intervention than that performed in the WHI and HERS trials will provide cardiovascular benefit to women is the driving force behind the Kronos Early Estrogen Prevention Study, or KEEPS. KEEPS is a multicenter, 5-year clinical trial that will evaluate the effectiveness of 0.45 mg of conjugated equine estrogens, 50 microg weekly transdermal estradiol (both in combination with cyclic oral, micronized progesterone, 200 mg for 12 days each month), and placebo in preventing progression of carotid intimal medial thickness and the accrual of coronary calcium in women aged 42-58 years who are within 36 months of their final menstrual period. A total of 720 women are planned to be enrolled in 2005, with an anticipated close-out of the trial in 2010. This overview summarizes the recruitment and methodology of the KEEPS trial.

  9. New Selective Estrogen and Androgen Receptor Modulators

    PubMed Central

    Clarke, Bart L.; Khosla, Sundeep

    2010-01-01

    Purpose of Review The present review focuses on the most significant recent findings regarding selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs). SERMs, which interact with estrogen receptor (ER)-α and ER-β in multiple tissues, continue to generate clinical interest in potential applications in as many disorders as the tissues in which the two known receptors are found. SARMs have been demonstrated to have fewer clinical applications to date, but continue to be investigated for use in multiple disorders in which androgen receptor (AR) modulation is likely to be important. Both types of compounds hold great promise for therapeutic use in multiple hormonal disorders involving tissue-specific effects mediated by estrogen or androgen receptors. Recent Findings While SERMs have been available for clinical use for 50 years, recent investigation has focused on large randomized clinical trials for newer indications of older agents, or smaller clinical trials of newer agents with improved clinical activity and reduced side effects in specific tissues. In particular, the large, prospective, randomized, controlled, multi-year STAR and RUTH clinical trials have recently shown interesting similarities and differences between tamoxifen and raloxifene in estrogen-responsive tissues. Lasofoxifene and arzoxifene are two newer SERMs that have recently been demonstrated to improve bone mineral density and lower serum cholesterol values compared to older SERMs in smaller clinical trials. SARMs are a newer category of drug still being investigated mostly at the basic and preclinical level, with fewer clinical trials available for review. SARMs are currently being investigated mostly for use in prostate cancer at different stages, but hold promise for multiple other applications. Summary Recent clinical trials indicate that selective estrogen receptor modulators are useful in treatment of disorders of bone and mineral metabolism and

  10. Bridging the Gap From Screening Assays to Estrogenic Effects in Fish: Potential Roles of Multiple Estrogen Receptor Subtypes

    PubMed Central

    2015-01-01

    This study seeks to delineate the ligand interactions that drive biomarker induction in fish exposed to estrogenic pollutants and provide a case study on the capacity of human (h) estrogen receptor (ER)-based in vitro screening assays to predict estrogenic effects in aquatic species. Adult male Japanese medaka (Oryzias latipes) were exposed to solutions of singular steroidal estrogens or to the estrogenic extract of an anaerobic swine waste lagoon. All exposure concentrations were calibrated to be equipotent based on the yeast estrogen screen (YES), which reports activation of hERα. These exposures elicited significantly different magnitudes of hepatic vitellogenin and choriogenin gene induction in the male medaka. Effects of the same YES-calibrated solutions in the T47D-KBluc assay, which reports activation of hERα and hERβ, generally recapitulated observations in medaka. Using competitive ligand binding assays, it was found that the magnitude of vitellogenin/choriogenin induction by different estrogenic ligands correlated positively with preferential binding affinity for medaka ERβ subtypes, which are highly expressed in male medaka liver prior to estrogen exposure. Results support emerging evidence that ERβ subtypes are critically involved in the teleost estrogenic response, with the ERα:ERβ ratio being of particular importance. Accordingly, incorporation of multiple ER subtypes into estrogen screening protocols may increase predictive value for the risk assessment of aquatic systems, including complex estrogenic mixtures. PMID:24422420

  11. Long Persistent Light Emitting Diode Indicators

    ERIC Educational Resources Information Center

    Jia, Dongdong; Ma, Yiwei; Hunter, D. N.

    2007-01-01

    An undergraduate laboratory was designed for undergraduate students to make long persistent light emitting diode (LED) indicators using phosphors. Blue LEDs, which emit at 465 nm, were characterized and used as an excitation source. Long persistent phosphors, SrAl[subscript 2]O[subscript 4]:Eu[superscript 2+],Dy[superscript 3+] (green) and…

  12. Green emitting phosphors and blends thereof

    SciTech Connect

    Setlur, Anant Achyut; Siclovan, Oltea Puica; Nammalwar, Prasanth Kumar; Sathyanarayan, Ramesh Rao; Porob, Digamber G.; Chandran, Ramachandran Gopi; Heward, William Jordan; Radkov, Emil Vergilov; Briel, Linda Jane Valyou

    2010-12-28

    Phosphor compositions, blends thereof and light emitting devices including white light emitting LED based devices, and backlights, based on such phosphor compositions. The devices include a light source and a phosphor material as described. Also disclosed are phosphor blends including such a phosphor and devices made therefrom.

  13. Long Persistent Light Emitting Diode Indicators

    ERIC Educational Resources Information Center

    Jia, Dongdong; Ma, Yiwei; Hunter, D. N.

    2007-01-01

    An undergraduate laboratory was designed for undergraduate students to make long persistent light emitting diode (LED) indicators using phosphors. Blue LEDs, which emit at 465 nm, were characterized and used as an excitation source. Long persistent phosphors, SrAl[subscript 2]O[subscript 4]:Eu[superscript 2+],Dy[superscript 3+] (green) and…

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

    PubMed

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

    2005-03-01

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

  15. Effects of Endogenous Ovarian Estrogen Versus Exogenous Estrogen Replacement on Blood Flow and ERα and ERβ Levels in the Bladder

    PubMed Central

    Ablove, Tova S.; Austin, Jason L.; Phernetton, Terry M.; Magness, Ronald R.

    2011-01-01

    Objective Determine the effect of endogenous estrogen versus estrogen replacement therapy (ERT) on bladder blood flow (BBF) and estrogen receptors (ERs). Methods BBF was determined with radio-labeled microspheres in luteal, follicular, pregnant, oophorectomized (Ovx) sheep, and Ovx sheep with ERT. Estrogen receptors (ERα, ERβ) were quantified using Western blot analysis. Results Compared to luteal and follicular ewes, BBF was reduced in pregnancy and following oophorectomy. Estrogen replacement therapy in Ovx sheep restored BBF to luteal levels. Estrogen receptor α predominated, whereas ERβ was not detectable. Estrogen receptor-α levels were unaffected by the ovarian cycle and increased in pregnancy, as well as in Ovx sheep with and without chronic ERT. Conclusion The combination of diminished BBF and elevated ERα levels in both pregnant and Ovx sheep suggests an inverse relationship between BBF and ERα in the bladder. Although chronic ERT in Ovx sheep restored BBF, it did not restore ERα back to luteal levels. PMID:19535742

  16. Light emitting device having peripheral emissive region

    DOEpatents

    Forrest, Stephen R

    2013-05-28

    Light emitting devices are provided that include one or more OLEDs disposed only on a peripheral region of the substrate. An OLED may be disposed only on a peripheral region of a substantially transparent substrate and configured to emit light into the substrate. Another surface of the substrate may be roughened or include other features to outcouple light from the substrate. The edges of the substrate may be beveled and/or reflective. The area of the OLED(s) may be relatively small compared to the substrate surface area through which light is emitted from the device. One or more OLEDs also or alternatively may be disposed on an edge of the substrate about perpendicular to the surface of the substrate through which light is emitted, such that they emit light into the substrate. A mode expanding region may be included between each such OLED and the substrate.

  17. Short-wavelength bottom-emitting VCSELs

    NASA Astrophysics Data System (ADS)

    Choquette, Kent D.; Barton, Jonathon S.; Geib, Kent M.; Allerman, Andrew A.; Hindi, Jana J.

    1999-04-01

    The fabrication and performance of selectively oxidized 850 nm vertical cavity surface emitting laser (VCSEL) diodes which emit through transparent GaP substrates is reported. Emission through the substrate is advantageous for many VCSEL configurations, such as for the incorporation of optical elements in the substrate or flip-chip integration to microelectronic circuitry. The short wavelength bottom- emitting VCSELs are fabricated by wafer fusion using an inert gas low temperature annealing process. The electrical characteristics of n- and p-type GaAs/GaAs and GaAs/GaP wafer bonded interfaces have been examined to optimize the annealing temperature. A significant reduction of the current-voltage characteristics of the VCSELs bonded to GaP substrates has been achieved whereby the bottom-emitting VCSELs show similar threshold voltage as compared to top- emitting lasers.

  18. Shielding of emitting dust particles

    NASA Astrophysics Data System (ADS)

    Luca Delzanno, Gian; Lapenta, Giovanni; Rosenberg, Marlene

    2003-10-01

    In the present work we focus on the role of electron emission (either thermionic or photoelectric) in charging an object immersed in a plasma. In fact, it is well known that the higher mobility of the plasma electrons (that would lead to negatively charged objects) can be overcome by electron emission, thus reversing the object polarity. Moreover, recent work [1] has shown how electron emission can fundamentally affect the shielding potential around the dust. In particular, depending on the physical parameters of the system (that were chosen such to correspond to common experimental conditions), the shielding potential can develop an attractive potential well. The aim of the present work is two-fold. First, we will present a parametric study in order to enlight the conditions for the formation, as well as the stability of the well. Furthermore, simulations will be presented with physical parameters corresponding to the ionosphere, thus extending our study to the case of meteroids. [1] G.L. Delzanno, G. Lapenta, M. Rosenberg, "Attractive Potential among Thermionically Emitting Microparticles", submitted.

  19. Effects of transdermal estrogen replacement therapy on cardiovascular risk factors.

    PubMed

    Menon, Dileep V; Vongpatanasin, Wanpen

    2006-01-01

    The prevalence of hypertension and cardiovascular disease increases dramatically after menopause in women, implicating estrogen as having a protective role in the cardiovascular system. However, recent large clinical trials have failed to show cardiovascular benefit, and have even demonstrated possible harmful effects, of opposed and unopposed estrogen in postmenopausal women. While these findings have led to a revision of guidelines such that they discourage the use of estrogen for primary or secondary prevention of heart disease in postmenopausal women, many investigators have attributed the negative results in clinical trials to several flaws in study design, including the older age of study participants and the initiation of estrogen late after menopause.Because almost all clinical trials use oral estrogen as the primary form of hormone supplementation, another question that has arisen is the importance of the route of estrogen administration with regards to the cardiovascular outcomes. During oral estrogen administration, the concentration of estradiol in the liver sinusoids is four to five times higher than that in the systemic circulation. This supraphysiologic concentration of estrogen in the liver can modulate the expression of many hepatic-derived proteins, which are not observed in premenopausal women. In contrast, transdermal estrogen delivers the hormone directly into the systemic circulation and, thus, avoids the first-pass hepatic effect.Although oral estrogen exerts a more favorable influence than transdermal estrogen on traditional cardiovascular risk factors such as high- and low-density lipoprotein-cholesterol levels, recent studies have indicated that oral estrogen adversely influences many emerging risk factors in ways that are not seen with transdermal estrogen. Oral estrogen significantly increases levels of acute-phase proteins such as C-reactive protein and serum amyloid A; procoagulant factors such as prothrombin fragments 1+2; and several

  20. Estrogen therapy in gynecological cancer survivors.

    PubMed

    Guidozzi, F

    2013-12-01

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

  1. Extra-gonadal sites of estrogen biosynthesis and function

    PubMed Central

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

    2016-01-01

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

  2. Circulating microparticles and endogenous estrogen in newly menopausal women.

    PubMed

    Jayachandran, M; Litwiller, R D; Owen, W G; Miller, V M

    2009-04-01

    Estrogen modulates antithrombotic characteristics of the vascular endothelium and the interaction of blood elements with the vascular surface. A marker of these modulatory activities is formation of cell-specific microparticles. This study examined the relationship between blood-borne microparticles and endogenous estrogen at menopause. Platelet activation and plasma microparticles were characterized from women being screened (n = 146) for the Kronos Early Estrogen Prevention Study. Women were grouped according to serum estrogen (< 20 pg/ml; low estrogen, n = 21 or > 40 pg/ml; high estrogen, n = 11). Age, body mass index, blood pressure and blood chemistries were the same in both groups. No woman was hypertensive, diabetic or a current smoker. Platelet counts, basal and activated expression of P-selectin on platelet membranes were the same, but activated expression of glycoprotein IIb/IIIa was greater in the high-estrogen group. Numbers of endothelium-, platelet-, monocyte- and granulocyte-derived microparticles were greater in the low-estrogen group. Of the total numbers of microparticles, those positive for phosphatidylserine and tissue factor were also greater in the low-estrogen group. These results suggest that, with declines in endogenous estrogen at menopause, numbers of procoagulant microparticles increase and thus may provide a means to explore mechanisms for cardiovascular risk development in newly menopausal women.

  3. The Interplay between Estrogen and Fetal Adrenal Cortex

    PubMed Central

    Kaludjerovic, Jovana; Ward, Wendy E.

    2012-01-01

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

  4. Signaling by estrogens and tamoxifen in the human endometrium.

    PubMed

    Gielen, Susanne C J P; Santegoets, Lindy A M; Hanifi-Moghaddam, Payman; Burger, Curt W; Blok, Leen J

    2008-04-01

    Tamoxifen is used as adjuvant treatment for postmenopausal breast cancer patients. The mechanism of action of tamoxifen in breast cancer patients is that tamoxifen inhibits growth of cancer cells by competitive antagonism for estrogens at the estrogen receptor (ER). In the endometrium, tamoxifen has an effect that varies with the ambient concentration of estrogen: in premenopausal women (high estrogen levels), tamoxifen displays an estrogen-antagonistic effect, while in postmenopausal women (low estrogen levels), tamoxifen displays an estrogen-agonistic mode of action. Here, using microarray technology we have compared estrogen signaling with tamoxifen signaling in the human endometrium. It was observed that on the one hand tamoxifen-treatment results in modulation of expression of specific genes (370 genes) and on the other hand tamoxifen-treatment results in modulation of a set of genes which are also regulated by estrogen treatment (142 genes). Upon focusing on regulation of proliferation, we found that tamoxifen-induced endometrial proliferation is largely accomplished by using the same set of genes as are regulated by estradiol. So, as far as regulation of proliferation goes, tamoxifen seems to act as estrogen agonist. Furthermore, tamoxifen-specific gene regulation may explain why tamoxifen-induced endometrial tumors behave more aggressively than sporadic endometrial tumors.

  5. Estrogen Deficiency and the Origin of Obesity during Menopause

    PubMed Central

    Lizcano, Fernando; Guzmán, Guillermo

    2014-01-01

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

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

    PubMed

    Tinkler, Gregory Paul; Voytko, Mary Lou

    2005-03-01

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

  7. An estrogen replacement therapy containing nine synthetic plant-based conjugated estrogens promotes neuronal survival.

    PubMed

    Zhao, Lixia; Chen, Shuhua; Brinton, Roberta D

    2003-07-01

    Epidemiological data from retrospective and case-control studies have indicated that estrogen replacement therapy can decrease the risk of developing Alzheimer's disease. In addition, estrogen replacement therapy has been found to promote neuronal survival both in vivo and in vitro. We have shown that conjugated equine estrogens (CEE), containing 238 different molecules composed of estrogens, progestins, and androgens, exerted neurotrophic and neuroprotective effects in cultured neurons. In the current study, we sought to determine whether a steroidal formulation of nine synthetic conjugated estrogens (SCE) chemically derived from soybean and yam extracts is as effective as the complex multisteroidal formulation of CEE. Analyses of the neuroprotective efficacy indicate that SCE exhibited significant neuroprotection against beta amyloid, hydrogen peroxide, and glutamate-induced toxicity in cultured hippocampal neurons. Indices of neuroprotection included an increase in neuronal survival, a decrease in neurotoxin-induced lactate dehydrogenase release, and a reduction in neurotoxin-induced apoptotic cell death. Furthermore, SCE was found to attenuate excitotoxic glutamate-induced [Ca2+]i rise. Quantitative analyses indicate that the neuroprotective efficacy of SCE was comparable to that of the multisteroidal CEE formulation. Data derived from these investigations predict that SCE could exert neuroprotective effects comparable to CEE in vivo and therefore could reduce the risk of Alzheimer's disease in postmenopausal women.

  8. Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer.

    PubMed

    Mishra, Sweta; Tai, Qin; Gu, Xiang; Schmitz, James; Poullard, Ashley; Fajardo, Roberto J; Mahalingam, Devalingam; Chen, Xiaodong; Zhu, Xueqiong; Sun, Lu-Zhe

    2015-12-29

    The role of estrogen signaling in regulating prostate tumorigenesis is relatively underexplored. Although, an increasing body of evidence has linked estrogen receptor beta (ERß) to prostate cancer, the function of estrogen receptor alpha (ERα) in prostate cancer is not very well studied. We have discovered a novel role of ERα in the pathogenesis of prostate tumors. Here, we show that prostate cancer cells express ERα and estrogen induces oncogenic properties in prostate cancer cells through ERα. Importantly, ERα knockdown in the human prostate cancer PacMetUT1 cells as well as pharmacological inhibition of ERα with ICI 182,780 inhibited osteoblastic lesion formation and lung metastasis in vivo. Co-culture of pre-osteoblasts with cancer cells showed a significant induction of osteogenic markers in the pre-osteoblasts, which was attenuated by knockdown of ERα in cancer cells suggesting that estrogen/ERα signaling promotes crosstalk between cancer and osteoblastic progenitors to stimulate osteoblastic tumorigenesis. These results suggest that ERα expression in prostate cancer cells is essential for osteoblastic lesion formation and lung metastasis. Thus, inhibition of ERα signaling in prostate cancer cells may be a novel therapeutic strategy to inhibit the osteoblastic lesion development as well as lung metastasis in patients with advanced prostate cancer.

  9. Estrogenic chemicals and estrogenicity in river waters of South Korea and seven Asian countries.

    PubMed

    Duong, Cuong N; Ra, Jin Sung; Cho, Jaeweon; Kim, Sang D; Choi, Hoon K; Park, Ji-Hyung; Kim, Kyoung W; Inam, Edu; Kim, Sang Don

    2010-01-01

    The effects of treatment processes on estrogenicity were evaluated by examining estradiol equivalent (EEQ) concentrations in influents and effluents of sewage treatment plants (STPs) located along Yeongsan and Seomjin rivers in Korea. The occurrence and distribution of estrogenic chemicals were also estimated for surface water in Korea and compared with seven other Asian countries including Laos, Cambodia, Vietnam, China, Indonesia, Thailand and Malaysia. Target compounds were nonylphenol (NP), octylphenol (OP), bisphenol A (BPA), estrone (E1), 17beta-estradiol (E2), 17alpha-ethynylestradiol (EE2) and genistein (Gen). Water samples were pretreated and analyzed by liquid-liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS). The results showed that the treatment processes of Korean STPs were sufficient to reduce the estrogenic activity of municipal wastewater. The concentrations of phenolic xenoestrogens (i.e., NP, OP and BPA) in samples of Yeongsan and Seomjin rivers were smaller than those reported by previous studies in Korea. In most samples taken from the seven Asian countries, the presence of E2 and EE2 was a major contributor toward estrogenic activity. The EEQ concentrations in surface water samples of the seven Asian countries were at a higher level in comparison to that reported in European countries, America and Japan. However, further studies with more sampling frequencies and sampling areas should be carried out for better evaluation of the occurrence and distribution of estrogenic compounds in these Asian countries. Copyright 2009 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2017-01-01

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

  11. Sensing Estrogen with Electrochemical Impedance Spectroscopy

    PubMed Central

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

    2016-01-01

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

  12. Estrogen binding by leukocytes during phagocytosis,

    PubMed Central

    1977-01-01

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

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

    PubMed Central

    Liang, Rubing; Zhou, Jing; Liu, Jianhua

    2011-01-01

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

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

    PubMed

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

    2015-11-01

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

  15. Comparison of immunocytochemical estrogen receptor assay, estrogen receptor enzyme immunoassay, and radioligand-labeled estrogen receptor assay in human breast cancer and uterine tissue

    SciTech Connect

    Heubner, A.; Beck, T.; Grill, H.J.; Pollow, K.

    1986-08-01

    Determination of estrogen receptor content in 82 breast cancer specimens with immunocytochemical estrogen receptor assay (ER-EIA) (Abbott) was compared with our routinely used binding assay using /sup 125/I-estradiol as radioligand with Scatchard plot analysis of the binding data. Although the estrogen receptor content measured with the ER-EIA was approximately 2-fold higher compared with the binding assay, the immunochemical method proved to be a useful alternative for estrogen receptor determination. Furthermore, it is possible to detect estrogen receptors in FPLC Superose 12 (size exclusion column) eluates or in the fractions obtained after sucrose density centrifugation using the ER-EIA. Forty breast cancer samples were analyzed utilizing the immunocytochemical technique (ER-ICA) for visualization of the estrogen receptor content in frozen tumor tissues in relationship to the quantitative results obtained with the ER-EIA assay. Specific staining for estrogen receptor was confined only to the cell nucleus, was distributed irregularly among the tumor cells, and was variable in intensity. The staining intensity and the percentage of positively stained cells increased with increasing level of cytosolic estrogen receptor. In 27 of 40 cases the immunocytochemical results correlated well with the ER-EIA assay. Nine cases were ER-ICA negative with positive ER-EIA, and four were ER-ICA positive with negative ER-EIA.

  16. Immunosuppression Following Exposure to Exogenous Estrogens

    DTIC Science & Technology

    1983-08-01

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

  17. Oophorectomy, estrogen, and dementia: a 2014 update.

    PubMed

    Rocca, Walter A; Grossardt, Brandon R; Shuster, Lynne T

    2014-05-25

    Current evidence suggests that estrogen may have beneficial, neutral, or detrimental effects on the brain depending on age, type of menopause (natural versus induced), or stage of menopause (early versus late), consistent with the timing hypothesis. Three studies have now compared women who underwent bilateral oophorectomy before menopause with referent women and consistently showed an increased risk of cognitive decline and dementia. These studies suggest a sizeable neuroprotective effect of estrogen naturally produced by the ovaries before age 50 years. In this article, we focus on neuroprotection as related to cognitive decline and dementia. Several case-control studies and cohort studies also showed neuroprotective effects in women who received estrogen treatment (ET) in the early postmenopausal stage (most commonly at ages 50-60 years). The majority of women in those observational studies had undergone natural menopause and were treated for the relief of menopausal symptoms. However, the clinical trials by the Women's Health Initiative showed that women who initiated ET alone or in combination with a progestin in the late postmenopausal stage (ages 65-79 years) experienced an increased risk of dementia and cognitive decline regardless of the type of menopause. Three observational studies have now formally tested the timing hypothesis, and showed that the neuroprotective or harmful effects of estrogen depend on age at the time of initiation of treatment and on stage of menopause. Therefore, women who undergo bilateral oophorectomy before the onset of menopause or women who experience premature or early natural menopause should be considered for hormonal treatment until the average age of natural menopause (around age 50 years). Recommendations for the use of ET by women who experience natural menopause at typical ages remain less certain, and more research is needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Estrogens as Antioxidant Modulators in Human Fertility

    PubMed Central

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

    2013-01-01

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

  19. Wheat Under LED's (Light Emitting Diodes)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Astroculture is a suite of technologies used to produce and maintain a closed controlled environment for plant growth. The two most recent missions supported growth of potato, dwarf wheat, and mustard plants, and provided scientists with the first opportunity to conduct true plant research in space. Light emitting diodes have particular usefulness for plant growth lighting because they emit a much smaller amount of radiant heat than do conventional lighting sources and because they have potential of directing a higher percentage of the emitted light onto plants surfaces. Furthermore, the high output LED's have emissions in the 600-700 nm waveband, which is of highest efficiency for photosynthesis by plants.

  20. Organic light emitting devices for illumination

    DOEpatents

    Hack, Michael [Lambertville, NJ; Lu, Min-Hao Michael [Lawrenceville, NJ; Weaver, Michael S [Princeton, NJ

    2012-01-24

    An organic light emitting device an a method of obtaining illumination from such a device is provided. The device has a plurality of regions, each region having an organic emissive layer adapted to emit a different spectrum of light. The regions in combination emit light suitable for illumination purposes. The area of each region may be selected such that the device is more efficient than an otherwise equivalent device having regions of equal size. The regions may have an aspect ratio of at least about four. All parts of any given region may be driven at the same current.

  1. Organic light emitting devices for illumination

    SciTech Connect

    Hack, Michael; Lu, Min-Hao Michael; Weaver, Michael S.

    2010-02-16

    An organic light emitting device is provided. The device has a plurality of regions, each region having an organic emissive layer adapted to emit a different spectrum of light. The regions in combination emit light suitable for illumination purposes. The area of each region may be selected such that the device is more efficient that an otherwise equivalent device having regions of equal size. The regions may have an aspect ratio of at least about four. All parts of any given region may be driven at the same current.

  2. Wheat Under LED's (Light Emitting Diodes)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Astroculture is a suite of technologies used to produce and maintain a closed controlled environment for plant growth. The two most recent missions supported growth of potato, dwarf wheat, and mustard plants, and provided scientists with the first opportunity to conduct true plant research in space. Light emitting diodes have particular usefulness for plant growth lighting because they emit a much smaller amount of radiant heat than do conventional lighting sources and because they have potential of directing a higher percentage of the emitted light onto plants surfaces. Furthermore, the high output LED's have emissions in the 600-700 nm waveband, which is of highest efficiency for photosynthesis by plants.

  3. Steroid binding domain of porcine estrogen receptor

    SciTech Connect

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

    1987-05-05

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

  4. Estrogens sensitize anterior pituitary gland to apoptosis.

    PubMed

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

    2004-10-01

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

  5. Estrogenic activity of isoflavonoids from Onobrychis ebenoides.

    PubMed

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

    2006-05-01

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

  6. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    EPA Pesticide Factsheets

    Data from a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating using predictive computational models on high-throughput screening data to screen thousands of chemicals against the estrogen receptor.This dataset is associated with the following publication:Mansouri , K., A. Abdelaziz, A. Rybacka, A. Roncaglioni, A. Tropsha, A. Varnek, A. Zakharov, A. Worth, A. Richard , C. Grulke , D. Trisciuzzi, D. Fourches, D. Horvath, E. Benfenati , E. Muratov, E.B. Wedebye, F. Grisoni, G.F. Mangiatordi, G.M. Incisivo, H. Hong, H.W. Ng, I.V. Tetko, I. Balabin, J. Kancherla , J. Shen, J. Burton, M. Nicklaus, M. Cassotti, N.G. Nikolov, O. Nicolotti, P.L. Andersson, Q. Zang, R. Politi, R.D. Beger , R. Todeschini, R. Huang, S. Farag, S.A. Rosenberg, S. Slavov, X. Hu, and R. Judson. (Environmental Health Perspectives) CERAPP: Collaborative Estrogen Receptor Activity Prediction Project. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA, 1-49, (2016).

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

    EPA Pesticide Factsheets

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

  8. Selective Estrogen Receptor Modulators and Phytoestrogens

    PubMed Central

    Oseni, Tawakalitu; Patel, Roshani; Pyle, Jennifer; Jordan, V. Craig

    2008-01-01

    Scientific achievements in the last two decades have revolutionized the treatment and prevention of breast cancer. This is mainly because of targeted therapies and a better understanding of the relationship between estrogen, its receptor, and breast cancer. One of these discoveries is the use of synthetic selective estrogen modulators (SERMs) such as tamoxifen in the treatment strategy for estrogen receptor (ER) positive breast cancer. Hundreds of thousands of lives have been saved because of this advance. Not only is tamoxifen used in the treatment strategy for patients who have breast cancer, but also for prevention in high risk premenopausal women. Another synthetic SERM, raloxifene, which was initially used to prevent osteoporosis, is also as effective as tamoxifen for prevention in high risk postmenopausal women. In certain regions of the world, particularly in Asia, a low incidence of breast cancer has been observed. These women have diets that are high in soy and low in fat, much unlike the western diet. Interest in the protective effects of soy derivatives has led to the research of phytoestrogens, metabolites of soy that are described by some as natural SERMs. As a result, many clinical questions have been raised as to whether phytoestrogens, which are also found in other natural foods, can protect against breast cancer. This article reviews the development and role of the more common SERMs, tamoxifen and raloxifene. In addition, this paper will also highlight the emerging studies on phytoestrogens and their similarity to SERMs. PMID:18843590

  9. Estrogen Regulation of Apoptosis in Osteoblasts

    PubMed Central

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

    2010-01-01

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

  10. The role of estrogen in intrusive memories.

    PubMed

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

    2013-11-01

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

  11. Estrogens, episodic memory, and Alzheimer's disease: a critical update.

    PubMed

    Henderson, Victor W

    2009-05-01

    Estrogen-containing hormone therapy initiated during late postmenopause does not improve episodic memory (an important early symptom of Alzheimer's disease), and it increases dementia risk. Cognitive consequences of exogenous estrogen exposures during midlife are less certain. Observational evidence implies that use of hormone therapy at a younger age close to the time of menopause may reduce risk of Alzheimer's disease later in life. However, there are concerns that observational findings may be systematically biased. Partial insight on this critical issue may be gleaned from results of ongoing clinical trials involving midlife postmenopausal women (Early versus Late Intervention Trial with Estrogen; Kronos Early Estrogen Prevention Study). The effects of exogenous midlife estrogen exposures and Alzheimer risk can also be approached through better animal models, through carefully designed cohort studies, and through use of surrogate outcomes in randomized controlled trials in midlife women. Selective estrogen receptor modulators have the potential to affect cognitive outcomes and also merit additional study.

  12. Brain estrogen production and the encoding of recent experience

    PubMed Central

    Vahaba, Daniel M.; Remage-Healey, Luke

    2015-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  14. Uncovering the Mechanisms of Estrogen Effects on Hippocampal Function

    PubMed Central

    Spencer, Joanna L.; Waters, Elizabeth M.; Romeo, Russell D.; Wood, Gwendolyn E.; Milner, Teresa A.; McEwen, Bruce S.

    2008-01-01

    Estrogens have direct effects on the brain areas controlling cognition. One of the most studied of these regions is the dorsal hippocampal formation, which governs the formation of spatial and episodic memory formation. In laboratory animals, most investigators report that estrogen enhances synaptic plasticity and improves performance on hippocampal-dependent cognitive behaviors. This review summarizes work conducted in our laboratory and others toward identifying estrogen’s actions in the hippocampal formation, and the mechanisms for these actions. Physiologic and pharmacologic estrogen affects cognitive behavior in mammals, which may be applicable to human health and disease. The effects of estrogen in the hippocampal formation that lead to modulation of hippocampal function include effects on cell morphology, synapse formation, signaling, and excitability that have been studied in laboratory mice, rats, and primates. Finally, estrogen may signal through both nuclear and extranuclear hippocampal estrogen receptors to achieve its downstream effects. PMID:18078984

  15. Lignans as food constituents with estrogen and antiestrogen activity.

    PubMed

    Aehle, Elke; Müller, Ulrike; Eklund, Patrik C; Willför, Stefan M; Sippl, Wolfgang; Dräger, Birgit

    2011-12-01

    Phytoestrogens are plant-derived food ingredients assumed to contribute to the prevention of hormone-dependent cancers, osteoporosis, cardiovascular disease, and menopausal symptoms. Lignans occur in numerous food plants and various structures; they are common constituents of human diet, and estrogen activity has been assessed for lignan metabolites formed in the mammalian intestine. We examined natural lignans and semisynthetic norlignans for estrogen and antiestrogen activity. A transformed yeast strain (Saccharomyces cerevisiae) expressing the estrogen receptor alpha and a reporter system was applied as test system. Some plant lignans showed estrogen activity while others and the semisynthetic norlignans were moderately active antiestrogens. Docking of lignans to protein models of estrogen receptor alpha in the active and inactive form sustained the results of the yeast estrogen assay and supported the concept of plant lignans as phytoestrogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Estrogen as Jekyll and Hyde: regulation of cell death.

    PubMed

    Zhou, Wen; Zhu, Xiaoxia

    2014-01-01

    Sustained estrogenic exposure increases the risk and/or the progression of various cancers, including those of the breast, endometrium and ovary. Unexpectedly, physiological level of estrogen together with a novel IKKα inhibitor BAY11-7082 could effectively induce cell apoptosis in ER-positive breast cancer cells, suggesting combining estrogen with IKKα inhibition may be beneficial for breast cancer patients. This opinion article touches upon the dual role estrogen played in inducing cancer cell death and asks whether use of estrogen in combination with IKKα-targeted therapy would be possible reconsider the newly identified crosstalk between ER and NFκB pathway which can be utilized to switch the effects of estrogen on cell death.

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

    PubMed Central

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

    2011-01-01

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

  18. Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

    PubMed Central

    Woolfrey, Kevin M.; Penzes, Peter

    2013-01-01

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

  19. Estrogen Receptor Alpha G525L Knock-In-Mice

    DTIC Science & Technology

    2006-03-01

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

  20. Genetic Susceptibility to Estrogen-Induced Mammary Cancers

    DTIC Science & Technology

    2001-11-01

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

  1. Zinc finger protein 131 inhibits estrogen signaling by suppressing estrogen receptor {alpha} homo-dimerization

    SciTech Connect

    Oh, Yohan; Chung, Kwang Chul

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer ZNF131 directly interacts with ER{alpha}. Black-Right-Pointing-Pointer The binding affinity of ZNF131 to ER{alpha} increases upon E2 stimulation. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Black-Right-Pointing-Pointer ZNF131 inhibits ER{alpha}-dimerization and E2-induced breast cancer cell proliferation. Black-Right-Pointing-Pointer ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor. -- Abstract: Steroid hormone estrogen elicits various physiological functions, many of which are mediated through two structurally and functionally distinct estrogen receptors, ER{alpha} and ER{beta}. The functional role of zinc finger protein 131 (ZNF131) is poorly understood, but it is assumed to possess transcriptional regulation activity due to the presence of a DNA binding motif. A few recent reports, including ours, revealed that ZNF131 acts as a negative regulator of ER{alpha} and that SUMO modification potentiates the negative effect of ZNF131 on estrogen signaling. However, its molecular mechanism for ER{alpha} inhibition has not been elucidated in detail. Here, we demonstrate that ZNF131 directly interacts with ER{alpha}, which consequently inhibits ER{alpha}-mediated trans-activation by suppressing its homo-dimerization. Moreover, we show that the C-terminal region of ZNF131 containing the SUMOylation site is necessary for its inhibition of estrogen signaling. Taken together, these data suggest that ZNF131 inhibits estrogen signaling by acting as an ER{alpha}-co-repressor.

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

    PubMed

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

    2015-05-01

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

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

    SciTech Connect

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

    2011-02-01

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

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

    PubMed

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

    2009-12-14

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

  5. Radioimmunotherapy with alpha-emitting nuclides.

    PubMed

    McDevitt, M R; Sgouros, G; Finn, R D; Humm, J L; Jurcic, J G; Larson, S M; Scheinberg, D A

    1998-09-01

    This review discusses the application of alpha particle-emitting radionuclides in targeted radioimmunotherapy. It will outline the production and chemistry of astatine-211, bismuth-212, lead-212, actinium-225, bismuth-213, fermium-255, radium-223 and terbium-149, which at present are the most promising alpha-emitting isotopes available for human clinical use. The selective cytotoxicity offered by alpha particle-emitting radioimmunoconstructs is due to the high linear energy transfer and short particle path length of these radionuclides. Based upon the pharmacokinetics of alpha particle-emitting radioimmunoconstructs, both stochastic and conventional dosimetric methodology is discussed, as is the preclinical and initial clinical use of these radionuclides conjugated to monoclonal antibodies for the treatment of human neoplasia.

  6. Organic emitters: Light-emitting fabrics

    NASA Astrophysics Data System (ADS)

    Ortí, Enrique; Bolink, Henk J.

    2015-04-01

    Light-emitting fibres that suit integration with textiles are prepared by dip-coating a steel wire with an electroluminescent material and then cleverly wrapping the structure with a carbon nanotube sheet that functions as a transparent electrode.

  7. Temperature compensation of light-emitting diodes

    NASA Technical Reports Server (NTRS)

    Deboo, G. J.; Burrous, C. N.

    1972-01-01

    Circuit which includes a thermistor-resistor combination to compensate for temperature fluctuations by supplying input voltage to light-emitting diode, maintains constant light output. Similar circuits can be used for temperature-induced variations in photodiode applications.

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

    NASA Astrophysics Data System (ADS)

    Korach, Kenneth S.

    1994-12-01

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

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

    PubMed

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

    2008-03-15

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

  10. Estrogen enhances wound healing in the penis of rats.

    PubMed

    Mowa, C N; Hoch, R; Montavon, C L; Jesmin, S; Hindman, G; Hou, G

    2008-10-01

    Estrogen receptor (ER) alpha and beta and aromatase are expressed in various cell-types and compartments of the penis, including the epidermis of glans penis. Here, we hypothesize that estrogen helps maintain the viability and integrity of glans penis and test the hypothesis by treating lesioned glans penis with either 17beta-estradiol or vehicle only. Estrogen was found to facilitate wound healing and increase vascular endothelial growth factor (VEGF) immunoreactivity compared to control, as revealed by scanning electron microscopy, histology, and immunohistochemistry. We conclude that estrogen plays a role in maintaining glans penis integrity, in part, by facilitating penile healing, possibly via up-regulating VEGF levels.

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

    PubMed

    Massaro, Donald; Massaro, Gloria Decarlo

    2004-12-01

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

  12. Estrogen signaling and unfolded protein response in breast cancer.

    PubMed

    Rajapaksa, Gayani; Thomas, Christoforos; Gustafsson, Jan-Åke

    2016-10-01

    Activation of the unfolded protein response (UPR) confers resistance to anti-estrogens and chemotherapeutics in estrogen receptor α (ERα)-positive and triple-negative breast cancers. Among the regulators of the UPR in breast cancer is estrogen signaling. Estrogen regulates major components of the UPR and ER expression is associated with the sensitivity of tumor cells to UPR-regulated apoptosis. Recent studies have confirmed the crosstalk between the ERs and UPR and suggest novel therapeutic strategies that combine targeting of both signaling pathways. These remedies may be more effective in repressing oncogenic adaptive mechanisms and benefit patients with resistant disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

    Nielsen, S; Notides, A C

    1975-02-13

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

  14. Visualization of Estrogen Receptor Transcriptional Activation in Zebrafish

    PubMed Central

    Halpern, Marnie E.

    2011-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    SciTech Connect

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

    2014-10-01

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

  17. Plasma estrogen concentrations after oral and vaginal estrogen administration in women with atrophic vaginitis.

    PubMed

    Dorr, Mary Beth; Nelson, Anita L; Mayer, Philip R; Ranganath, Radhika P; Norris, Paul M; Helzner, Eileen C; Preston, Richard A

    2010-11-01

    In this open-label, randomized, multiple-dose, two-treatment crossover study, 24 postmenopausal women with moderate to severe atrophic vaginitis received 0.3 mg conjugated estrogens daily for 14 days: 7 days orally (0.3 mg tablet) and 7 days vaginally (0.5 g cream). Steady-state plasma concentrations of E2 and estrone were one-third lower after vaginal versus oral administration of conjugated estrogens. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Regulation of estrogen receptors and MMP-2 expression by estrogens in human retinal pigment epithelium.

    PubMed

    Marin-Castaño, Maria E; Elliot, Sharon J; Potier, Mylen; Karl, Michael; Striker, Liliane J; Striker, Gary E; Csaky, Karl G; Cousins, Scott W

    2003-01-01

    Age-related macular degeneration (ARMD) is characterized by progressive thickening and accumulation of various lipid-rich extracellular matrix (ECM) deposits under the retinal pigment epithelium (RPE). ECM dysregulation probably contributes to the pathologic course of ARMD. By activating estrogen receptors (ERs), estrogens regulate the expression of genes relevant in the turnover of ECM, among them matrix metalloproteinase (MMP)-2. Estrogen deficiency may predispose to dysregulated synthesis and degradation of ECM, leading to accumulation of collagens and other proteins between the RPE and its basement membrane. The purposes in the current study were to confirm the expression of ERs in human RPE, to elucidate whether these ERs are functional, and to test whether 17beta-estradiol (E(2)) regulates expression of ERs and MMP-2. Expression of ERs was examined in freshly isolated human RPE monolayer and in cultured human RPE cells, by using total RNA for RT-PCR and protein extracts for Western blot analysis. Supernatants were collected from freshly isolated human RPE and from cultured human RPE to assess MMP-2 activity by zymography and protein expression by Western blot. The transcriptional activity of ERs was studied in transfection experiments with an estrogen-responsive reporter construct. All these studies were preformed in the presence or absence of E(2) (10(-11) and 10(-7) M). Human RPE isolated from female and male individuals expressed both ER subtypes alpha and beta at the mRNA and protein levels. Treatment of cultured RPE cells with 10(-10) M E(2) increased expression of mRNA and protein of both receptor subtypes. E(2) (10(-10) M) also increased MMP-2 activity (approximately 2.2-fold) and protein expression (approximately 2.5-fold). In contrast, there was no change in ER levels and MMP-2 activity at higher E(2) concentrations (10(-8) M), compared with baseline. Preincubation of cells with 10(-7) M pyrrolidinedithiocarbamate (PDTC), an inhibitor of nuclear

  19. Estrogen receptor mRNA in mineralized tissues of rainbow trout: calcium mobilization by estrogen.

    PubMed

    Armour, K J; Lehane, D B; Pakdel, F; Valotaire, Y; Graham, R; Russell, R G; Henderson, I W

    1997-07-07

    RT-PCR was undertaken on total RNA extracts from bone and scales of the rainbow trout, Oncorhynchus mykiss. The rainbow trout estrogen receptor (ER)-specific primers used amplified a single product of expected size from each tissue which, using Southern blotting, strongly hybridized with a 32P-labelled rtER probe under stringent conditions. These data provide the first in vivo evidence of ER mRNA in bone and scale tissues of rainbow trout and suggest that the effects of estrogen observed in this study (increased bone mineral and decreased scale mineral contents, respectively) may be mediated directly through ER.

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

    PubMed

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

    2015-12-01

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

  1. Stable blue phosphorescent organic light emitting devices

    SciTech Connect

    Forrest, Stephen R.; Thompson, Mark; Giebink, Noel

    2014-08-26

    Novel combination of materials and device architectures for organic light emitting devices is provided. An organic light emitting device, is provided, having an anode, a cathode, and an emissive layer disposed between the anode and the cathode. The emissive layer includes a host and a phosphorescent emissive dopant having a peak emissive wavelength less than 500 nm, and a radiative phosphorescent lifetime less than 1 microsecond. Preferably, the phosphorescent emissive dopant includes a ligand having a carbazole group.

  2. Rapid Signaling Actions of Environmental Estrogens in Developing Granule Cell Neurons Are Mediated by Estrogen Receptor β

    PubMed Central

    Le, Hoa H.; Belcher, Scott M.

    2010-01-01

    Estrogenic endocrine disrupting chemicals (EDCs) constitute a diverse group of man-made chemicals and natural compounds derived from plants and microbial metabolism. Estrogen-like actions are mediated via the nuclear hormone receptor activity of estrogen receptor (ER)α and ERβ and rapid regulation of intracellular signaling cascades. Previous study defined cerebellar granule cell neurons as estrogen responsive and that granule cell precursor viability was developmentally sensitive to estrogens. In this study experiments using Western blot analysis and pharmacological approaches have characterized the receptor and signaling modes of action of selective and nonselective estrogen ligands in developing cerebellar granule cells. Estrogen treatments were found to briefly increase ERK1/2-phosphorylation and then cause prolonged depression of ERK1/2 activity. The sensitivity of granule cell precursors to estrogen-induced cell death was found to require the integrated activation of membrane and intracellular ER signaling pathways. The sensitivity of granule cells to selective and nonselective ER agonists and a variety of estrogenic and nonestrogenic EDCs was also examined. The ERβ selective agonist DPN, but not the ERα selective agonist 4,4′,4′-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol or other ERα-specific ligands, stimulated cell death. Only EDCs with selective or nonselective ERβ activities like daidzein, equol, diethylstilbestrol, and bisphenol A were observed to induce E2-like neurotoxicity supporting the conclusion that estrogen sensitivity in granule cells is mediated via ERβ. The presented results also demonstrate the utility of estrogen sensitive developing granule cells as an in vitro assay for elucidating rapid estrogen-signaling mechanisms and to detect EDCs that act at ERβ to rapidly regulate intracellular signaling. PMID:20926581

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

    PubMed Central

    Katchy, Anne; Williams, Cecilia

    2016-01-01

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

  4. Chemiluminescence of CdTe nanocrystals catalyzed by sodium hexametaphosphate and its sensitive application for determination of estrogens.

    PubMed

    Wang, Lun; Yuan, Fei; Chen, Hong-Qi; Ling, Bo; Xu, Juan

    2012-06-01

    A novel flow injection nanocrystals (NCs) chemiluminescence (CL) analysis method has been established for the determination of estradiol, estriol and estrone based on the enhancement of CdTe NCs-KMnO(4) CL reaction catalyzed by sodium hexametaphosphate. Glutathione (GSH)-capped CdTe nanocrystals were synthesized in aqueous medium, and the CdTe NCs emitted at around 555 nm was selected as the light emitter in CdTe NCs-KMnO(4) chemiluminescence (CL) system. It has been found that sodium hexametaphosphate (SHMP) enhanced the CL of the CdTe NCs-KMnO(4) system and estrogens increased these CL signals again in near neutral solution. UV-visible spectra, photoluminescence (PL) spectra, transmission electron microscopy (TEM) and CL spectra were used to characterize CdTe nanoparticles and investigate the mechanism of the CL reaction. On the basis of the enhancement, a novel flow-injection CL method has been established for the determination of estrogens. Under the optimum experimental conditions, three linear relationships were obtained. The method described is simple, sensitive, and has been successfully utilized for the determination of estrogens in tap water samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Chemiluminescence of CdTe nanocrystals catalyzed by sodium hexametaphosphate and its sensitive application for determination of estrogens

    NASA Astrophysics Data System (ADS)

    Wang, Lun; Yuan, Fei; Chen, Hong-Qi; Ling, Bo; Xu, Juan

    2012-06-01

    A novel flow injection nanocrystals (NCs) chemiluminescence (CL) analysis method has been established for the determination of estradiol, estriol and estrone based on the enhancement of CdTe NCs-KMnO4 CL reaction catalyzed by sodium hexametaphosphate. Glutathione (GSH)-capped CdTe nanocrystals were synthesized in aqueous medium, and the CdTe NCs emitted at around 555 nm was selected as the light emitter in CdTe NCs-KMnO4 chemiluminescence (CL) system. It has been found that sodium hexametaphosphate (SHMP) enhanced the CL of the CdTe NCs-KMnO4 system and estrogens increased these CL signals again in near neutral solution. UV-visible spectra, photoluminescence (PL) spectra, transmission electron microscopy (TEM) and CL spectra were used to characterize CdTe nanoparticles and investigate the mechanism of the CL reaction. On the basis of the enhancement, a novel flow-injection CL method has been established for the determination of estrogens. Under the optimum experimental conditions, three linear relationships were obtained. The method described is simple, sensitive, and has been successfully utilized for the determination of estrogens in tap water samples.

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

    PubMed

    Korol, Donna L; Pisani, Samantha L

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Estrogens are becoming well known for their robust enhancement on cognition particularly for learning and memory that relies upon functioning of the hippocampus and related neural systems. What is also emerging is that estrogen modulation of cognition is not uniform, at times enhancing yet at other times impairing learning. This review explores the bidirectional effects of estrogens on learning from a multiple memory systems view, focusing on the hippocampus and striatum, whereby modulation by estrogens sorts according to task attributes and neural systems engaged during cognition. We highlight our findings showing that the ability to solve hippocampus-sensitive tasks typically improves under relatively high estrogen status while the ability to solve striatum-sensitive tasks degrades with estrogen exposures. Though constrained by dose and timing of exposure, these opposing enhancements and impairments of cognition can be observed following treatments with different estrogenic compounds including the hormone estradiol, the isoflavone genistein found in soybeans, and agonists that are selective for specific estrogen receptors, suggesting that activation of a single receptor type is sufficient to produce the observed shifts in learning strategies. Using this multi-dimensional framework will allow us to extend our thinking of the relationship between estrogens and cognition to other brain regions and cognitive functions. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2011-11-01

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

  8. Environmental estrogens in an urban aquatic ecosystem: I. Spatial and temporal occurrence of estrogenic activity in effluent-dominated systems.

    PubMed

    Martinovic-Weigelt, Dalma; Minarik, Thomas A; Curran, Erin M; Marchuk, Jascha S; Pazderka, Matt J; Smith, Eric A; Goldenstein, Rachel L; Miresse, Christine L; Matlon, Thomas J; Schultz, Melissa M; Schoenfuss, Heiko L

    2013-11-01

    The present study investigated occurrence of environmental estrogens (EEs) in waterways managed by the Metropolitan Water Reclamation District of Greater Chicago ('District') - one of the largest and most complex water districts in the United States. The objectives of the study were: (i) to document spatial and temporal occurrence of EEs in the Chicago Area Waterways (CAWs); (ii) to determine whether water reclamation plant (WRP) effluents contribute to estrogenic pollution of the receiving streams; (iii) to determine whether the mandated water quality monitoring data could be used to predict estrogenic pollution in the receiving streams; and (iv) to determine whether snow melt, storm runoff and combined sewer overflows may also be contributors of estrogenic activity to these systems. The estrogenic potency of the waterways was assessed using a cell-based reporter gene assay. The water quality data was readily available as part of the District's regular monitoring program. Our findings indicate that EEs are commonly found in the CAWs, and that WRP effluents are one of, but not the only important contributor to estrogenic activity. Mean estrogenic activities in CAWs (11ng estradiol equivalents (EEQs/L)) are well within the values reported for other urban areas and WRP effluents. The estrogenic activity exhibited significant seasonal variation with highest values noted during the spring and summer months. When comparing the mean estrogenic activity of general use waters, secondary contact waters and WRP effluents, we found that general use waters had significantly lower estrogenic activity (ca 5ng EEQ/L) than the other two matrices (ca 15 and 17ng EEQ/L respectively). Our analyses indicate that estrogenic activity of the waterways was not reliably associated with mandated water quality parameters, and that such measurements may not be useful for predicting estrogenic activity, especially so in the complex urban systems. One of the prominent findings of this study is

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

    SciTech Connect

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

    1986-05-20

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

  10. Effect of estrogens on boar sperm capacitation in vitro

    PubMed Central

    2010-01-01

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

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

    PubMed Central

    Farzaneh, Shabnam; Zarghi, Afshin

    2016-01-01

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

  12. Emerging Estrogenic Pollutants in the Aquatic Environment and Breast Cancer.

    PubMed

    Lecomte, Sylvain; Habauzit, Denis; Charlier, Thierry D; Pakdel, Farzad

    2017-09-15

    The number and amount of man-made chemicals present in the aquatic environment has increased considerably over the past 50 years. Among these contaminants, endocrine-disrupting chemicals (EDCs) represent a significant proportion. This family of compounds interferes with normal hormonal processes through multiple molecular pathways. They represent a potential risk for human and wildlife as they are suspected to be involved in the development of diseases including, but not limited to, reprotoxicity, metabolic disorders, and cancers. More precisely, several studies have suggested that the increase of breast cancers in industrialized countries is linked to exposure to EDCs, particularly estrogen-like compounds. Estrogen receptors alpha (ERα) and beta (ERβ) are the two main transducers of estrogen action and therefore important targets for these estrogen-like endocrine disrupters. More than 70% of human breast cancers are ERα-positive and estrogen-dependent, and their development and growth are not only influenced by endogenous estrogens but also likely by environmental estrogen-like endocrine disrupters. It is, therefore, of major importance to characterize the potential estrogenic activity from contaminated surface water and identify the molecules responsible for the hormonal effects. This information will help us understand how environmental contaminants can potentially impact the development of breast cancer and allow us to fix a maximal limit to the concentration of estrogen-like compounds that should be found in the environment. The aim of this review is to provide an overview of emerging estrogen-like compounds in the environment, sum up studies demonstrating their direct or indirect interactions with ERs, and link their presence to the development of breast cancer. Finally, we emphasize the use of in vitro and in vivo methods based on the zebrafish model to identify and characterize environmental estrogens.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-01-01

    Vitellogenin (Vtg) is a phospho-lipo-glycoprotein produced by oviparous animals in response to estrogen receptor (ER) binding. The presence of Vtg in juvenile and male fish liver and plasma has been used as biomarker to evaluate levels of environmental contaminants as dioxin and PCBs. Interaction of dioxins and PCBs with aryl hydrocarbon receptor (AhR) may affect reproduction by recruitment of estrogen receptor alpha (ERalpha). The aim of this study was to investigate the effects of PCB-126, a co-planar PCB prototypical AhR agonist, and of PCB-153, a non-coplanar PCB lacking dioxine-like activity, on Vtg expression in young fish (Spaurus aurata) after a 12 or 24h exposure to PCBs as well as 48h following PCBs removal. Vtg expression was evaluated by immunohistochemistry and by Western-blot analysis. Our results showed an increased Vtg expression following PCBs administration, with a maximum level after 12h of exposure to either PCB-126, PCB-153 or a mixture of both PCBs. Following this estrogenic activity, an anti-estrogenic activity was detected after 24h of incubation with PCB-126 (alone or mixed with PCB-153), suggested by a decrease in Vtg expression likely through AhR, as a consequence of a hypothetic defence mechanism to endogenous or exogenous ligands. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-11-01

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

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

    PubMed Central

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

    2012-01-01

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

  17. Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways.

    PubMed

    Alonso-Magdalena, Paloma; Ropero, Ana Belén; Soriano, Sergi; García-Arévalo, Marta; Ripoll, Cristina; Fuentes, Esther; Quesada, Iván; Nadal, Ángel

    2012-05-22

    Bisphenol-A (BPA) is an estrogenic monomer commonly used in the manufacture of numerous consumer products such as food and beverage containers. Widespread human exposure to significant doses of this compound has been reported. Traditionally, BPA has been considered a weak estrogen, based on its lower binding affinity to the nuclear estrogen receptors (ERs) compared to 17-β estradiol (E2) as well as its low transcriptional activity after ERs activation. However, in vivo animal studies have demonstrated that it can interfere with endocrine signaling pathways at low doses during fetal, neonatal or perinatal periods as well as in adulthood. In addition, mounting evidence suggests a variety of pathways through which BPA can elicit cellular responses at very low concentrations with the same or even higher efficiency than E2. Thus, the purpose of the present review is to analyze with substantiated scientific evidence the strong estrogenic activity of BPA when it acts through alternative mechanisms of action at least in certain cell types. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2012-12-01

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

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

    USDA-ARS?s Scientific Manuscript database

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

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

    PubMed

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

    2017-02-17

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

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

    PubMed

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

    2003-10-29

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

  2. Estrogens are neuroprotective factors for hypertensive encephalopathy.

    PubMed

    Pietranera, Luciana; Brocca, Maria Elvira; Roig, Paulina; Lima, Analia; Garcia-Segura, Luis Miguel; De Nicola, Alejandro F

    2015-02-01

    Estrogens are neuroprotective factors for brain diseases, including hypertensive encephalopathy. In particular, the hippocampus is highly damaged by high blood pressure, with several hippocampus functions being altered in humans and animal models of hypertension. Working with a genetic model of primary hypertension, the spontaneously hypertensive rat (SHR), we have shown that SHR present decreased dentate gyrus neurogenesis, astrogliosis, low expression of brain derived neurotrophic factor (BDNF), decreased number of neurons in the hilus of the dentate gyrus, increased basal levels of the estrogen-synthesizing enzyme aromatase, and atrophic dendritic arbor with low spine density in the CA1 region compared to normotensive Wistar Kyoto (WKY) ratsl. Changes also occur in the hypothalamus of SHR, with increased expression of the hypertensinogenic peptide arginine vasopressin (AVP) and its V1b receptor. Following chronic estradiol treatment, SHR show decreased blood pressure, enhanced hippocampus neurogenesis, decreased the reactive astrogliosis, increased BDNF mRNA and protein expression in the dentate gyrus, increased neuronal number in the hilus of the dentate gyrus, further increased the hyperexpression of aromatase and replaced spine number with remodeling of the dendritic arbor of the CA1 region. We have detected by qPCR the estradiol receptors ERα and ERβ in hippocampus from both SHR and WKY rats, suggesting direct effects of estradiol on brain cells. We hypothesize that a combination of exogenously given estrogens plus those locally synthesized by estradiol-stimulated aromatase may better alleviate the hippocampal and hypothalamic encephalopathy of SHR. This article is part of a Special Issue entitled "Sex steroids and brain disorders". Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2013-03-01

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

  4. Estrogenic activity of UV filter mixtures

    SciTech Connect

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

    2006-11-15

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

  5. Estrogenic activity of UV filter mixtures.

    PubMed

    Kunz, Petra Y; Fent, Karl

    2006-11-15

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

  6. Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats.

    PubMed

    Markowska, Alicja L; Savonenko, Alena V

    2002-12-15

    Recent studies suggest that some aspects of learning and memory may be altered by a midlife loss of estrogen, indicating a potential causal relationship between the deficiency of ovarian hormones and cognitive aging. In this study, the effects of estrogen withdrawal and replacement were tested in middle-aged Fischer-344 rats using different memory tasks. Estrogen withdrawal accelerated the rate of cognitive aging. A deficit first occurred 4 months after ovariectomy in working memory, which was tested in a delayed-nonmatching-to-position task, and progressed from long-delay to short-delay trials. Reference memory, which was tested in a place discrimination task and a split-stem T-maze, was not affected by aging or ovariectomy. The efficacy of estrogen in ameliorating the cognitive deficit in old rats depended on the type of treatment (acute vs chronic) and whether the aging-related decline in a particular cognitive process was aggravated by estrogen withdrawal. Chronic estrogen treatment (implants) was effective in improving working memory only when primed with repeated injections of estrogen, indicating that simulating the estrogen fluctuations of the estrous cycle may be more effective than the widely used mode of chronic pharmacological treatment. A challenge with scopolamine revealed that ovariectomy-induced cognitive deterioration coincided with a compromised cholinergic system. Importantly, the estrogen treatment that had restored effectively the cognitive abilities of old ovariectomized rats did not reduce their sensitivity to scopolamine. Taking into consideration that estrogen was highly effective against the amnestic action of scopolamine when tested in young-adult rats, these data emphasize that mechanisms of the protective effect of estrogen differ in young and old rats.

  7. Estrogen-dependent changes in estrogen receptor-β mRNA expression in middle-aged female rat brain.

    PubMed

    Yamaguchi, Naoko; Yuri, Kazunari

    2014-01-16

    During aging, estrogen production and circulating levels of estrogen are markedly decreased in females. Although several differences exist in the process of reproductive aging between women and female rats, the results of many studies suggest that the female rat, especially the middle-aged or aged ovariectomized female, is an important animal model of hormone loss in women. In target tissues including the brain, the actions of estrogen are mediated mainly via the alpha and beta subtypes of the estrogen receptor (ER-α and ER-β). Estrogen treatment is known to change the expression of ER-α mRNA and protein in specific regions of the brain in middle-aged female rodents. In contrast, we do not know if estrogen regulates the expression of ER-β in the brain at this stage of life. In the present study, we performed in situ hybridization on brain sections of ovariectomized and estrogen-treated middle-aged female rats to reveal the effects of estrogen on the expression of ER-β throughout the brain. Our results showed that estrogen treatment decreased the number of ER-β mRNA-positive cells in the mitral cell and external plexiform layers of the olfactory bulb, central amygdaloid nucleus, medial geniculate nucleus, posterior hypothalamic nucleus, suprachiasmatic nucleus, and reticular part of the substantia nigra. As compared to the results of previous studies of young females, our data revealed that the regions in which expression of ER-β mRNA expression is affected by estrogen differ in middle age. These results suggest that the effects of estrogen on ER-β expression change with age. © 2013 Published by Elsevier B.V.

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

    PubMed Central

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

    1994-01-01

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

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

    PubMed

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

    2014-10-01

    Endocrine disrupting compounds (EDCs) of natural or synthetic origin can interfere with the balance of the hormonal system, either by altering hormone production, secretion, transport, or their binding and consequently lead to an adverse outcome in intact animals. An important aspect is the prediction of effects of combined exposure to two or more EDCs at the same time. The yeast estrogen assay (YES) is a broadly used method to assess estrogenic potential of chemicals. Besides exhibiting good predictivity to identify compounds which interfere with the estrogen receptor, it is easy to handle, rapid and therefore allows screening of a large number of single compounds and varying mixtures. Herein, we applied the YES assay to determine the potential combination effects of binary mixtures of two estrogenic compounds, bisphenol A and genistein, as well as one classical androgen that in vitro also exhibits estrogenic activity, trenbolone. In addition to generating data from combined exposure, we fitted these to a four-parametric logistic dose-response model. As all compounds tested share the same mode of action dose additivity was expected. To assess this, the Loewe model was utilized. Deviations between the Loewe additivity model and the observed responses were always small and global tests based on the whole dose-response data set indicated in general a good fit of the Loewe additivity model. At low concentrations concentration additivity was observed, while at high concentrations, the observed effect was lower than additivity, most likely reflecting receptor saturation. In conclusion, our results suggest that binary combinations of genistein, bisphenol A and trenbolone in the YES assay do not deviate from expected additivity. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2000-05-01

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

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

    PubMed

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

    2014-10-01

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

  15. Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women.

    PubMed

    Sisti, Julia S; Hankinson, Susan E; Caporaso, Neil E; Gu, Fangyi; Tamimi, Rulla M; Rosner, Bernard; Xu, Xia; Ziegler, Regina; Eliassen, A Heather

    2015-08-01

    Prior studies have found weak inverse associations between breast cancer and caffeine and coffee intake, possibly mediated through their effects on sex hormones. High-performance liquid chromatography/tandem mass spectrometry was used to quantify levels of 15 individual estrogens and estrogen metabolites (EM) among 587 premenopausal women in the Nurses' Health Study II with mid-luteal phase urine samples and caffeine, coffee, and/or tea intakes from self-reported food frequency questionnaires. Multivariate linear mixed models were used to estimate geometric means of individual EM, pathways, and ratios by intake categories, and P values for tests of linear trend. Compared with women in the lowest quartile of caffeine consumption, those in the top quartile had higher urinary concentrations of 16α-hydroxyestrone (28% difference; Ptrend = 0.01) and 16-epiestriol (13% difference; Ptrend = 0.04), and a decreased parent estrogens/2-, 4-, 16-pathway ratio (Ptrend = 0.03). Coffee intake was associated with higher 2-catechols, including 2-hydroxyestradiol (57% difference, ≥4 cups/day vs. ≤6 cups/week; Ptrend = 0.001) and 2-hydroxyestrone (52% difference; Ptrend = 0.001), and several ratio measures. Decaffeinated coffee was not associated with 2-pathway metabolism, but women in the highest (vs. lowest) category of intake (≥2 cups/day vs. ≤1-3 cups/month) had significantly lower levels of two 16-pathway metabolites, estriol (25% difference; Ptrend = 0.01) and 17-epiestriol (48% difference; Ptrend = 0.0004). Tea intake was positively associated with 17-epiestriol (52% difference; Ptrend = 0.01). Caffeine and coffee intake were both associated with profiles of estrogen metabolism in premenopausal women. Consumption of caffeine and coffee may alter patterns of premenopausal estrogen metabolism. ©2015 American Association for Cancer Research.

  16. Caffeine, coffee and tea intake and urinary estrogens and estrogen metabolites in premenopausal women

    PubMed Central

    Sisti, Julia S.; Hankinson, Susan E.; Caporaso, Neil E.; Gu, Fangyi; Tamimi, Rulla M.; Rosner, Bernard; Xu, Xia; Ziegler, Regina; Eliassen, A. Heather

    2015-01-01

    Background Prior studies have found weak inverse associations between breast cancer and caffeine and coffee intake, possibly mediated through their effects on sex hormones. Methods High-performance liquid chromatography/tandem mass spectrometry was used to quantify levels of 15 individual estrogens and estrogen metabolites (EM) among 587 premenopausal women in the Nurses’ Health Study II with mid-luteal phase urine samples and caffeine, coffee and/or tea intakes from self-reported food frequency questionnaires. Multivariate linear mixed models were used to estimate geometric means of individual EM, pathways and ratios by intake categories, and P-values for tests of linear trend. Results Compared to women in the lowest quartile of caffeine consumption, those in the top quartile had higher urinary concentrations of 16α-hydroxyestrone (28% difference; P-trend=0.01) and 16-epiestriol (13% difference; P-trend=0.04), and a decreased parent estrogens/2-, 4-, 16-pathway ratio (P-trend=0.03). Coffee intake was associated with higher 2-catechols, including 2-hydroxyestradiol (57% difference, ≥4 cups/day vs. ≤6 cups/week; P-trend=0.001) and 2-hydroxyestrone (52% difference; P-trend=0.001), and several ratio measures. Decaffeinated coffee was not associated with 2-pathway metabolism, but women in the highest (vs. lowest) category of intake (≥2 cups/day vs. ≤1–3 cups/month) had significantly lower levels of two 16-pathway metabolites, estriol (25% difference; P-trend=0.01) and 17-epiestriol (48% difference; Ptrend=0.0004). Tea intake was positively associated with 17-epiestriol (52% difference; Ptrend=0.01). Conclusion Caffeine and coffee intake were both associated with profiles of estrogen metabolism in premenopausal women. Impact Consumption of caffeine and coffee may alter patterns of premenopausal estrogen metabolism. PMID:26063478

  17. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    PubMed

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-09-02

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

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

    PubMed

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

    2013-10-01

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

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

    PubMed

    Ladikou, Eleni-Eirini; Kassi, Eva

    2017-03-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2005-02-01

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

  2. Evaluation of the estrogenic activity of Leguminosae plants.

    PubMed

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

    2005-03-01

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

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

    EPA Science Inventory

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

  4. Estrogen Receptor Alpha G525L Knock-In Mice

    DTIC Science & Technology

    2007-03-01

    development. Although the G525L mutation significantly reduces ERα response to endogenous estrogens, the ERα selective agonist propyl pyrazole triol (PPT...endogenous estrogens but not to the synthetic nonsteroidal ERα selective agonist propyl pyrazole triol (PPT). Therefore, ERα signaling pathways can be

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

    EPA Science Inventory

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

  6. Estrogen Metabolism and Prostate Cancer Risk: A Prospective Study

    DTIC Science & Technology

    2008-05-01

    We have also prepared an article for publication of the results (see attached article ). 15. SUBJECT TERMS Prostate Cancer, Estrogens...completed determinations of the estrogen metabolites using gas-chromatography and carried out statistical analysis. We have also prepared an article ...

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

    PubMed

    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

    2014-08-15

    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. To clarify the influence of endogenous estrogen and sex in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. 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. 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. 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.

  8. Nonylphenol and estrogenic activity in aquatic environmental samples

    SciTech Connect

    Tanghe, T.; Devriese, G.; Verstraete, W.

    1999-03-01

    The authors surveyed a series of surface waters and sewage treatment plants in Flanders (north of Belgium) for the presence of estrogenic activity and a xeno-estrogenic compound para-nonylphenol (NP), respectively. The surface waters of rural origin, used for drinking water production were free of significant levels of estrogenic activity and NP. Domestic sewage, after proper treatment, appeared to be no major source of this chemical. Yet, in some industrial effluents and surface waters of highly industrialized regions, NP and/or estrogenic activity was prominent, that is, <1 to 122 {micro}g NP/L and 11 to 42 {micro}g NP/L, respectively. This is because of the ongoing use of NP polyethoxylates in industry. The response of the recombinant yeast estrogen assay to the environmental samples tested was not consistent with the detected concentrations of NP. Standard addition of a natural estrogen, 17{beta}-estradiol, generated no or a reduced response compared to the standard curve concentration. Application of humic acids to standard series of NP and 17{beta}-estradiol resulted in a dose-dependent decrease of the estrogenic response. It appears that this bioassay is subject to considerable interferences due to the complexity of environmental samples. Parallel implementation of extensive chemical screening for xenobiotics and use of the bioassay are needed for adequate assessment of the potential estrogenic hazard to avoid false negative evaluations.

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

    USDA-ARS?s Scientific Manuscript database

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

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

    PubMed

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

    2009-01-01

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

  11. Estrogens and Coronary Artery Disease: New Clinical Perspectives.

    PubMed

    Meyer, M R; Barton, M

    2016-01-01

    In premenopausal women, endogenous estrogens are associated with reduced prevalence of arterial hypertension, coronary artery disease, myocardial infarction, and stroke. Clinical trials conducted in the 1990s such as HERS, WHI, and WISDOM have shown that postmenopausal treatment with horse hormone mixtures (so-called conjugated equine estrogens) and synthetic progestins adversely affects female cardiovascular health. Our understanding of rapid (nongenomic) and chronic (genomic) estrogen signaling has since advanced considerably, including identification of a new G protein-coupled estrogen receptor (GPER), which like the "classical" receptors ERα and ERβ is highly abundant in the cardiovascular system. Here, we discuss the role of estrogen receptors in the pathogenesis of coronary artery disease and review natural and synthetic ligands of estrogen receptors as well as their effects in physiology, on cardiovascular risk factors, and atherosclerotic vascular disease. Data from preclinical and clinical studies using nonselective compounds activating GPER, which include selective estrogen receptor modulators such as tamoxifen or raloxifene, selective estrogen receptor downregulators such as Faslodex™ (fulvestrant/ICI 182,780), vitamin B3 (niacin), green tea catechins, and soy flavonoids such as genistein or resveratrol, strongly suggest that activation of GPER may afford therapeutic benefit for primary and secondary prevention in patients with or at risk for coronary artery disease. Evidence from preclinical studies suggest similar efficacy profiles for selective small molecule GPER agonists such as G-1 which are devoid of uterotrophic activity. Further clinical research in this area is warranted to provide opportunities for future cardiovascular drug development.

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

    PubMed

    Coe, J E; Ross, M J

    1988-01-01

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

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

    PubMed Central

    Cui, Jie; Shen, Yong; Li, Rena

    2012-01-01

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

  14. Side-emitting fiber optic position sensor

    SciTech Connect

    Weiss, Jonathan D.

    2008-02-12

    A side-emitting fiber optic position sensor and method of determining an unknown position of an object by using the sensor. In one embodiment, a concentrated beam of light source illuminates the side of a side-emitting fiber optic at an unknown axial position along the fiber's length. Some of this side-illuminated light is in-scattered into the fiber and captured. As the captured light is guided down the fiber, its intensity decreases due to loss from side-emission away from the fiber and from bulk absorption within the fiber. By measuring the intensity of light emitted from one (or both) ends of the fiber with a photodetector(s), the axial position of the light source is determined by comparing the photodetector's signal to a calibrated response curve, look-up table, or by using a mathematical model. Alternatively, the side-emitting fiber is illuminated at one end, while a photodetector measures the intensity of light emitted from the side of the fiber, at an unknown position. As the photodetector moves further away from the illuminated end, the detector's signal strength decreases due to loss from side-emission and/or bulk absorption. As before, the detector's signal is correlated to a unique position along the fiber.

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

    PubMed

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

    2016-05-24

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

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

    PubMed

    Simpson, E R; Jones, M E

    2006-01-01

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

  17. Regioselective deuterium labeling of estrone and catechol estrogen metabolites.

    PubMed

    Stack, Douglas E; Ritonya, Justin; Jakopovic, Scott; Maloley-Lewis, Brittney

    2014-12-01

    Increased exposure to estrogens and estrogen metabolites is linked with increased rates of breast, ovarian and other human cancers. Metabolism of estrogen can led to formation of electrophilic o-quinones capable of binding to DNA. In order to gain insight into the mechanism of estrogen-induced DNA damage, estrone and catechol estrogens derived from estrone, have been regioselectively labeled with deuterium at the 1-position. Estrone-1-d, estrone-1,2,4-d3, 4-hydroxyestrone-1-d and 2-hydroxyestrone-1-d have been synthesized with or without deuteriums at the 16-position. The key labeling step involves deuterated trifluoroacetic acid exchange catalyzed by t-butyl alcohol. This economical, straightforward labeling technique makes available a range of estrone compounds containing deuterium at the 1-position. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Estrogens and the control of energy homeostasis: a brain perspective.

    PubMed

    López, Miguel; Tena-Sempere, Manuel

    2015-08-01

    Despite their prominent roles in the control of reproduction, estrogens pervade many other bodily functions. Key metabolic pathways display marked sexual differences, and estrogens are potent modulators of energy balance, as evidenced in extreme conditions of estrogen deficiency characterized by hyperphagia and decreased energy expenditure, and leading to obesity. Compelling evidence has recently demonstrated that, in addition to their peripheral effects, the actions of estrogens on energy homeostasis are exerted at central levels, to regulate almost every key aspect of metabolic homeostasis, from feeding to energy expenditure, to glucose and lipid metabolism. We review herein the state-of-the-art of the role of estrogens in the regulation of energy balance, with a focus on their central effects and modes of action. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  20. Highly efficient white top-emitting organic light-emitting diodes comprising laminated microlens films.

    PubMed

    Thomschke, Michael; Reineke, Sebastian; Lüssem, Björn; Leo, Karl

    2012-01-11

    White top-emitting organic light-emitting diodes (OLEDs) attract much attention, as they are optically independent from the substrate used. While monochrome top-emitting OLEDs can be designed easily to have high-emission efficiency, white light emission faces obstacles. The commonly used thin metal layers as top electrodes turn the device into a microresonator having detrimental narrow and angular dependent emission characteristics. Here we report on a novel concept to improve the color quality and efficiency of white top-emitting OLEDs. We laminate a refractive index-matched microlens film on the top-emitting device. The microlens film acts both as outcoupling-enhancing film and an integrating element, mixing the optical modes to a broadband spectrum.

  1. Dietary soy isoflavones inhibit estrogen effects in the postmenopausal breast.

    PubMed

    Wood, Charles E; Register, Thomas C; Franke, Adrian A; Anthony, Mary S; Cline, J Mark

    2006-01-15

    Soy isoflavones are promising dietary agents for prevention of breast cancer. Isoflavones bind estrogen receptors (ER) and may variably act as either estrogen agonists or antagonists depending on the estrogen environment. In this study, we used a postmenopausal primate model to evaluate interactive effects of dietary soy isoflavones and estrogen on risk markers for breast cancer. The experiment followed a randomized factorial design in which 31 ovariectomized adult female cynomolgus monkeys were divided into social groups of three to four animals each and rotated through eight different diets containing the human equivalent of 0, 60, 120, or 240 mg/d soy isoflavones with a dose of oral micronized 17beta-estradiol (E(2)) corresponding to either a low (0.09 mg/d) or a high (0.5 mg/d) postmenopausal estrogen environment. Treatment periods lasted 4 months with a 1-month washout period between diets. The highest isoflavone dose resulted in significantly lower breast proliferation and uterine size in the high-estrogen environment. These effects were accompanied by divergent changes in breast markers of ER activation in which pS2 expression was significantly lower and progesterone receptor expression was significantly higher following the 240 mg isoflavone dose. All isoflavone doses resulted in lower serum estrone and E(2) concentrations in the high-estrogen environment. In contrast, isoflavone treatment had no significant estrogen agonist effects and minimal antagonistic effects in the lower-estrogen environment. These findings show that in the presence of estrogen higher doses of dietary soy isoflavones may alter ER signaling and induce selective antagonistic effects in the breast.

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

    PubMed Central

    Liu, Ran; Yang, Shao-Hua

    2013-01-01

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

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

    PubMed

    Zetterberg, Madeleine; Celojevic, Dragana

    2015-02-01

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

  4. Prediction of Estrogenic Bioactivity of Environmental Chemical Metabolites.

    PubMed

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

    2016-09-19

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

  5. Visible light surface emitting semiconductor laser

    DOEpatents

    Olbright, Gregory R.; Jewell, Jack L.

    1993-01-01

    A vertical-cavity surface-emitting laser is disclosed comprising a laser cavity sandwiched between two distributed Bragg reflectors. The laser cavity comprises a pair of spacer layers surrounding one or more active, optically emitting quantum-well layers having a bandgap in the visible which serve as the active optically emitting material of the device. The thickness of the laser cavity is m .lambda./2n.sub.eff where m is an integer, .lambda. is the free-space wavelength of the laser radiation and n.sub.eff is the effective index of refraction of the cavity. Electrical pumping of the laser is achieved by heavily doping the bottom mirror and substrate to one conductivity-type and heavily doping regions of the upper mirror with the opposite conductivity type to form a diode structure and applying a suitable voltage to the diode structure. Specific embodiments of the invention for generating red, green, and blue radiation are described.

  6. Epigenetic regulation of estrogen-dependent memory

    PubMed Central

    Fortress, Ashley M.; Frick, Karyn M.

    2014-01-01

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

  7. Epigenetic regulation of estrogen-dependent memory.

    PubMed

    Fortress, Ashley M; Frick, Karyn M

    2014-10-01

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

  8. Contemporary Alternatives to Plant Estrogens for Menopause

    PubMed Central

    Geller, Stacie E.; Studee, Laura

    2006-01-01

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

  9. CERAPP: Collaborative Estrogen Receptor Activity Prediction ...

    EPA Pesticide Factsheets

    Humans potentially 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. Many of these chemicals never have been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for assessment in costly in vivo tests, for instance, within the EPA Endocrine Disruptor Screening Program. Here, we describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) demonstrating the efficacy of using predictive computational models on high-throughput screening data to screen thousands of chemicals against the ER. CERAPP combined multiple models developed in collaboration among 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1677 compounds provided by EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were tested using an evaluation set of 7522 chemicals collected from the literature. To overcome the limitations of single models, a consensus was built weighting models using a scoring function (0 to 1) based on their accuracies. Individual model scores ranged from 0.69 to 0.85, showing

  10. Estrogen Signaling in Hypothalamic Circuits Controling Reproduction

    PubMed Central

    Kelly, Martin J.; Qiu, Jian

    2010-01-01

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

  11. Androgens and estrogens in skeletal sexual dimorphism

    PubMed Central

    Laurent, Michaël; Antonio, Leen; Sinnesael, Mieke; Dubois, Vanessa; Gielen, Evelien; Classens, Frank; Vanderschueren, Dirk

    2014-01-01

    Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. PMID:24385015

  12. Plasma Interaction with Electron-Emitting Surfaces

    SciTech Connect

    Campanell, Michael

    2014-09-01

    Electron emission from surfaces occurs in many plasma systems. Several types including secondary, thermionic and photon-induced emissions are intense under certain conditions. Understanding the effects of emission on the sheaths that govern plasma-surface interaction is important. This dissertation predicts some emitting sheath phenomena that were not reported in past studies. For example, most previous theoretical models assumed that an emitting sheath potential is always negative and that ions always accelerate into the wall. We show when the emission is intense that the sheath potential can become positive, fundamentally changing how the plasma and wall interact. In this inverse sheath state, ions are repelled, suggesting for instance that (a) no presheath exists in the plasma interior, (b) emitting walls could be used in applications to stop sputtering. Another topic considered is the transit of emitted electrons across the plasma to other surfaces, which is possible in low collisionality plasma systems. When transit occurs, the flux balance is a complex global problem where the sheaths at opposite surfaces are coupled through their exchange of emitted electrons. We also show that secondary emission can trigger a variety of sheath instability phenomena that change the state of the plasma-wall system or cause oscillations preventing steady state. Lastly, we analyze a mechanism where emitted electrons return to the same surface and knock out secondaries, which return and knock out more secondaries, etc., feedback amplifying the emission intensity. The four phenomena will be analyzed theoretically and verified with particle-in-cell simulations: (a) inverse sheath, (b) sheath coupling via transiting electrons, (c) sheath instabilities, (d) returning electron amplification. Consequences of these processes on the sheath potentials, wall heating, loss rate of charge, and cross field transport (near-wall conductivity) are discussed throughout. Possible implications are

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

    PubMed

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

    2009-02-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-06-01

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

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

    SciTech Connect

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

    2009-04-15

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

  17. The influence of estrogen on skeletal muscle: sex matters.

    PubMed

    Enns, Deborah L; Tiidus, Peter M

    2010-01-01

    As women enter menopause, the concentration of estrogen and other female hormones declines. This hormonal decrease has been associated with a number of negative outcomes, including a greater incidence of injury as well as a delay in recovery from these injuries. Over the past two decades, our understanding of the protective effects of estrogen against various types of injury and disease states has grown immensely. In skeletal muscle, studies with animals have demonstrated that sex and estrogen may potentially influence muscle contractile properties and attenuate indices of post-exercise muscle damage, including the release of creatine kinase into the bloodstream and activity of the intramuscular lysosomal acid hydrolase, beta-glucuronidase. Furthermore, numerous studies have revealed an estrogen-mediated attenuation of infiltration of inflammatory cells such as neutrophils and macrophages into the skeletal muscles of rats following exercise or injury. Estrogen has also been shown to play a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. Although the mechanisms by which estrogen exerts its influence upon indices of skeletal muscle damage, inflammation and repair have not been fully elucidated, it is thought that estrogen may potentially exert its protective effects by: (i) acting as an antioxidant, thus limiting oxidative damage; (ii) acting as a membrane stabilizer by intercalating within membrane phospholipids; and (iii) binding to estrogen receptors, thus governing the regulation of a number of downstream genes and molecular targets. In contrast to animal studies, studies with humans have not as clearly delineated an effect of estrogen on muscle contractile function or on indices of post-exercise muscle damage and inflammation. These inconsistencies have been attributed to a number of factors, including age and fitness level of subjects, the type and intensity of exercise

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2016-12-01

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

  20. 21 CFR 862.1270 - Estrogens (total, in pregnancy) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estrogens (total, in pregnancy) test system. 862... Test Systems § 862.1270 Estrogens (total, in pregnancy) test system. (a) Identification. As estrogens (total, in pregnancy) test system is a device intended to measure total estrogens in plasma, serum, and...

  1. 21 CFR 862.1270 - Estrogens (total, in pregnancy) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    PubMed

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

    2013-09-15

    This study describes the modification of the ER-Calux assay for testing water samples without sample extraction (NE-(ER-Calux) assay). The results are compared to those obtained with ER-Calux assay and a theoretical estrogenic potential obtained by GC-MSD. For spiked tap and waste water samples there was no statistical difference between estrogenic potentials obtained by the three methods. Application of NE-(ER-Calux) to "real" influent and effluents from municipal waste water treatment plants and receiving surface waters found that the NE-(ER-Calux) assay gave higher values compared to ER-Calux assay and GC-MSD. This is explained by the presence of water soluble endocrine agonists that are usually removed during extraction. Intraday dynamics of the estrogenic potential of a WWTP influent and effluent revealed an increase in the estrogenic potential of the influent from 12.9 ng(EEQ)/L in the morning to a peak value of 40.0 ng(EEQ)/L in the afternoon. The estrogenic potential of the effluent was estrogenic potential was 92-98%. Daytime estrogenic potential values varied significantly. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Phytoestrogens are partial estrogen agonists in the adult male mouse.

    PubMed Central

    Mäkelä, S; Santti, R; Salo, L; McLachlan, J A

    1995-01-01

    The intake, as well as serum and urinary concentrations, of phytoestrogens is high in countries where incidence of prostate cancer is low, suggesting a chemopreventive role for phytoestrogens. Their significance could be explained by the ability to antagonize the action of more potent endogenous estrogens in initiation or promotion of tumor formation. We have studied estrogenicity and antiestrogenicity of dietary soy and two phytoestrogens, coumestrol and daidzein, in our neoDES mouse model for the study or prostatic neoplasia. Soy was chosen because it is rich in phytoestrogens, is widely used in Oriental diets, and has antiestrogenic and anticarcinogenic properties in the neoDES mouse when given from fertilization onward. In short-term tests with adult animals, no evidence for estrogenicity or antiestrogenicity (capability to antagonize the action of 17 beta-estradiol) of soy was found when development of epithelial metaplasia and expression of c-fos protooncogene in prostate were used as end points of estrogen action. Estrogenic activity of coumestrol and daidzein on c-fos expression was subtle. Coumestrol, either given alone or in combination with 17 beta-estradiol, had no effect on development of epithelial metaplasia. These marginal or missing effects in adult males could be interpreted by assuming that the neonatal period is more critical for estrogenic or antiestrogenic action of soy and phytoestrogens. Once initiated, estrogen-related lesions would develop spontaneously. Alternatively, the chemopreventive action of soy is not due to antiestrogenicity of soy-derived phytoestrogens. Images Figure 1. Figure 2. PMID:8593857

  4. Estrogen/isoflavone interactions in cynomolgus macaques (Macaca fascicularis).

    PubMed

    Cline, J Mark; Wood, Charles E

    2009-09-01

    Soy isoflavones are phytoestrogenic components of dietary soy, which are widely consumed for their potential health benefits. Soy isoflavones appear to decrease breast and endometrial cancer risk in human observational studies, but paradoxically stimulate growth of breast cancer cells in culture and uterine enlargement in rodents. We have shown that these compounds are not estrogenic in cynomolgus monkeys even at relatively high doses, but that they reduce estrogen-induced proliferative responses of the breast and endometrium. This effect may be mediated through estrogen receptor interactions and/or modulation of endogenous estrogen metabolism. Interindividual variation in isoflavone absorption and metabolism contributes to the degree of estrogen antagonistic effect. Our recent studies have also shown that individual isoflavone metabolites such as glyceollins may have unique selective estrogen receptor modulator-like activity, acting as tissue-specific antagonists without agonist activity. Rodent studies and human epidemiologic data suggest that timing of exposure and dose relative to endogenous estrogen concentrations are important determinants of effect, and studies of dietary soy on breast development and pubertal maturation are under way. Because soy isoflavones are both abundant in standard monkey chow diets and widely available as dietary supplements for human beings, these findings have broad relevance to the health of human and nonhuman primates.

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

    PubMed

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

    2013-09-01

    Glyphosate is an active ingredient of the most widely used herbicide and it is believed to be less toxic than other pesticides. However, several recent studies showed its potential adverse health effects to humans as it may be an endocrine disruptor. This study focuses on the effects of pure glyphosate on estrogen receptors (ERs) mediated transcriptional activity and their expressions. Glyphosate exerted proliferative effects only in human hormone-dependent breast cancer, T47D cells, but not in hormone-independent breast cancer, MDA-MB231 cells, at 10⁻¹² to 10⁻⁶M in estrogen withdrawal condition. The proliferative concentrations of glyphosate that induced the activation of estrogen response element (ERE) transcription activity were 5-13 fold of control in T47D-KBluc cells and this activation was inhibited by an estrogen antagonist, ICI 182780, indicating that the estrogenic activity of glyphosate was mediated via ERs. Furthermore, glyphosate also altered both ERα and β expression. These results indicated that low and environmentally relevant concentrations of glyphosate possessed estrogenic activity. Glyphosate-based herbicides are widely used for soybean cultivation, and our results also found that there was an additive estrogenic effect between glyphosate and genistein, a phytoestrogen in soybeans. However, these additive effects of glyphosate contamination in soybeans need further animal study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Advances in menopausal therapy: the tissue-selective estrogen complex.

    PubMed

    Moore, Anne

    2013-03-01

    Most menopausal women experience vasomotor symptoms, vulvar-vaginal atrophy, and/or bone loss. Although available estrogen and progestin therapies are effective in treating menopausal symptoms and preventing bone loss, some women may seek a therapy that provides symptom relief and has an improved tolerability profile. One option is a tissue-selective estrogen complex (TSEC), or the pairing of estrogen(s) with a selective estrogen receptor modulator (SERM) to achieve the benefits of each component with fewer side effects. The first TSEC in clinical development combines the SERM bazedoxifene (BZA) with conjugated estrogens (CEs). The purpose of this article is to review published data for BZA/CE. Data were obtained from phase 3 BZA/CE clinical trial study articles. Daily BZA 20 mg/CE 0.625 mg or 0.45 mg effectively relieved hot flushes, maintained or increased bone mineral density, treated vulvar-vaginal atrophy, and improved quality of life. Further, BZA prevented stimulation of the endometrium by CE, and resulted in rates of amenorrhea and breast pain similar to placebo. These results support the use of a TSEC consisting of BZA/CE as a promising therapy for managing the signs and symptoms from reduced estrogen levels associated with menopause. ©2012 The Author(s) Journal compilation ©2012 American Association of Nurse Practitioners.

  7. Tissue-selective estrogen complexes for postmenopausal women.

    PubMed

    Mirkin, Sebastian; Komm, Barry S

    2013-11-01

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

  8. Synthesis and Functional Analysis of Novel Bivalent Estrogens

    PubMed Central

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

    2010-01-01

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

  9. Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

    PubMed Central

    Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

    2015-01-01

    Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

  10. In vitro estrogenic activity of Achillea millefolium L.

    PubMed

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

    2007-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Characterization of evolutionary trend in squamate estrogen receptor sensitivity.

    PubMed

    Yatsu, Ryohei; Katsu, Yoshinao; Kohno, Satomi; Mizutani, Takeshi; Ogino, Yukiko; Ohta, Yasuhiko; Myburgh, Jan; van Wyk, Johannes H; Guillette, Louis J; Miyagawa, Shinichi; Iguchi, Taisen

    2016-11-01

    Steroid hormones are a key regulator of reproductive biology in vertebrates, and are largely regulated via nuclear receptor families. Estrogen signaling is regulated by two estrogen receptor (ER) subtypes alpha and beta in the nucleus. In order to understand the role of estrogen in vertebrates, these ER from various species have been isolated and were functionally analyzed using luciferase reporter gene assays. Interestingly, species difference in estrogen sensitivity has been noted in the past, and it was reported that snake ER displayed highest estrogen sensitivity. Here, we isolated additional ER from three lizards: chameleon (Bradypodion pumilum), skink (Plestiodon finitimus), and gecko (Gekko japonicus). We have performed functional characterization of these ERs using reporter gene assay system, and found high estrogen sensitivity in all three species. Furthermore, comparison with results from other tetrapod ER revealed a seemingly uniform gradual pattern of ligand sensitivity evolution. In silico 3D homology modeling of the ligand-binding domain revealed structural variation at three sites, helix 2, and juncture between helices 8 and 9, and caudal region of helix 10/11. Docking simulations indicated that predicted ligand-receptor interaction also correlated with the reporter assay results, and overall squamates displayed highest stabilized interactions. The assay system and homology modeling system provides tool for in-depth comparative analysis of estrogen function, and provides insight toward the evolution of ER among vertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. INTERACTION OF ESTROGEN AND PROGESTERONE IN CHICK OVIDUCT DEVELOPMENT

    PubMed Central

    Oka, Takami; Schimke, Robert T.

    1969-01-01

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

  14. Developmental synergism of steroidal estrogens in sex determination.

    PubMed

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

    1999-02-01

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

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

    SciTech Connect

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

    1981-08-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. p150/Glued Modifies Nuclear Estrogen Receptor Function

    PubMed Central

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

    2009-01-01

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

  18. Estrogens Mediate Cardiac Hypertrophy in a Stimulus-Dependent Manner

    PubMed Central

    Haines, Christopher D.; Harvey, Pamela A.

    2012-01-01

    The incidence of cardiac hypertrophy, an established risk factor for heart failure, is generally lower in women compared with men, but this advantage is lost after menopause. Although it is widely believed that estrogens are cardioprotective, there are contradictory reports, including increased cardiac events in postmenopausal women receiving estrogens and enhanced cardiac protection from ischemic injury in female mice without estrogens. We exposed aromatase knockout (ArKO) mice, which produce no estrogens, to both pathologic and physiologic stimuli. This model allows an investigation into the effects of a complete, chronic lack of estrogens in male and female hearts. At baseline, female ArKO mice had normal-sized hearts but decreased cardiac function and paradoxically increased phosphorylation of many progrowth kinases. When challenged with the pathological stimulus, isoproterenol, ArKO females developed 2-fold more hypertrophy than wild-type females. In contrast, exercise-induced physiological hypertrophy was unaffected by the absence of estrogens in either sex, although running performance was blunted in ArKO females. Thus, loss of estrogen signaling in females, but not males, impairs cardiac function and sensitizes the heart to pathological insults through up-regulation of multiple hypertrophic pathways. These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention. PMID:22759381

  19. Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

    SciTech Connect

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

    2006-08-01

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

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

    PubMed

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

    2006-08-01

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

  1. Analytical techniques for steroid estrogens in water samples - A review.

    PubMed

    Fang, Ting Yien; Praveena, Sarva Mangala; deBurbure, Claire; Aris, Ahmad Zaharin; Ismail, Sharifah Norkhadijah Syed; Rasdi, Irniza

    2016-12-01

    In recent years, environmental concerns over ultra-trace levels of steroid estrogens concentrations in water samples have increased because of their adverse effects on human and animal life. Special attention to the analytical techniques used to quantify steroid estrogens in water samples is therefore increasingly important. The objective of this review was to present an overview of both instrumental and non-instrumental analytical techniques available for the determination of steroid estrogens in water samples, evidencing their respective potential advantages and limitations using the Need, Approach, Benefit, and Competition (NABC) approach. The analytical techniques highlighted in this review were instrumental and non-instrumental analytical techniques namely gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS), enzyme-linked immuno sorbent assay (ELISA), radio immuno assay (RIA), yeast estrogen screen (YES) assay, and human breast cancer cell line proliferation (E-screen) assay. The complexity of water samples and their low estrogenic concentrations necessitates the use of highly sensitive instrumental analytical techniques (GC-MS and LC-MS) and non-instrumental analytical techniques (ELISA, RIA, YES assay and E-screen assay) to quantify steroid estrogens. Both instrumental and non-instrumental analytical techniques have their own advantages and limitations. However, the non-instrumental ELISA analytical techniques, thanks to its lower detection limit and simplicity, its rapidity and cost-effectiveness, currently appears to be the most reliable for determining steroid estrogens in water samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-11-17

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

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

    PubMed

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

    1981-03-01

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

  4. Fragranced consumer products: Chemicals emitted, ingredients unlisted

    SciTech Connect

    Steinemann, Anne C.; MacGregor, Ian C.; Gordon, Sydney M.; Gallagher, Lisa G.; Davis, Amy L.; Ribeiro, Daniel S.; Wallace, Lance A.

    2011-04-15

    Fragranced consumer products are pervasive in society. Relatively little is known about the composition of these products, due to lack of prior study, complexity of formulations, and limitations and protections on ingredient disclosure in the U.S. We investigated volatile organic compounds (VOCs) emitted from 25 common fragranced consumer products-laundry products, personal care products, cleaning supplies, and air fresheners-using headspace analysis with gas chromatography/mass spectrometry (GC/MS). Our analysis found 133 different VOCs emitted from the 25 products, with an average of 17 VOCs per product. Of these 133 VOCs, 24 are classified as toxic or hazardous under U.S. federal laws, and each product emitted at least one of these compounds. For 'green' products, emissions of these compounds were not significantly different from the other products. Of all VOCs identified across the products, only 1 was listed on any product label, and only 2 were listed on any material safety data sheet (MSDS). While virtually none of the chemicals identified were listed, this nonetheless accords with U.S. regulations, which do not require disclosure of all ingredients in a consumer product, or of any ingredients in a mixture called 'fragrance.' Because the analysis focused on compounds emitted and listed, rather than exposures and effects, it makes no claims regarding possible risks from product use. Results of this study contribute to understanding emissions from common products, and their links with labeling and legislation.

  5. Light-Emitting Diodes: Solving Complex Problems

    ERIC Educational Resources Information Center

    Planinšic, Gorazd; Etkina, Eugenia

    2015-01-01

    This is the fourth paper in our Light-Emitting Diodes series. The series aims to create a systematic library of LED-based materials and to provide readers with the description of experiments and the pedagogical treatment that would help their students construct, test, and apply physics concepts and mathematical relations. The first paper provided…

  6. Do Atoms Really "Emit" Absorption Lines?

    ERIC Educational Resources Information Center

    Brecher, Kenneth

    1991-01-01

    Presents three absorption line sources that enhance student understanding of the phenomena associated with the interaction of light with matter and help dispel the misconception that atoms "emit" absorption lines. Sources include neodymium, food coloring and other common household liquids, and fluorescent materials. (MDH)

  7. Optical Physics of Microcavity Surface Emitting Lasers

    DTIC Science & Technology

    2007-11-02

    in confinement factor balances the change in mirror reflectance. For TM and HEM modes, no minima exists since the mirror reflectance is approximately...Noble. "Model of Intra and Extracavity Photodetection for Planar Resonant Cavity Light Emitting Diodes." 24th International Symposium on Compound

  8. Demonstrating the Light-Emitting Diode.

    ERIC Educational Resources Information Center

    Johnson, David A.

    1995-01-01

    Describes a simple inexpensive circuit which can be used to quickly demonstrate the basic function and versatility of the solid state diode. Can be used to demonstrate the light-emitting diode (LED) as a light emitter, temperature sensor, light detector with both a linear and logarithmic response, and charge storage device. (JRH)

  9. Light-Emitting Diodes: Learning New Physics

    ERIC Educational Resources Information Center

    Planinšic, Gorazd; Etkina, Eugenia

    2015-01-01

    This is the third paper in our Light-Emitting Diodes series. The series aims to create a systematic library of LED-based materials and to provide the readers with the description of experiments and pedagogical treatment that would help their students construct, test, and apply physics concepts and mathematical relations. The first paper, published…

  10. Demonstrating the Light-Emitting Diode.

    ERIC Educational Resources Information Center

    Johnson, David A.

    1995-01-01

    Describes a simple inexpensive circuit which can be used to quickly demonstrate the basic function and versatility of the solid state diode. Can be used to demonstrate the light-emitting diode (LED) as a light emitter, temperature sensor, light detector with both a linear and logarithmic response, and charge storage device. (JRH)

  11. Light-Emitting Diodes: Learning New Physics

    ERIC Educational Resources Information Center

    Planinšic, Gorazd; Etkina, Eugenia

    2015-01-01

    This is the third paper in our Light-Emitting Diodes series. The series aims to create a systematic library of LED-based materials and to provide the readers with the description of experiments and pedagogical treatment that would help their students construct, test, and apply physics concepts and mathematical relations. The first paper, published…

  12. Light-Emitting Diodes: A Hidden Treasure

    ERIC Educational Resources Information Center

    Planinšic, Gorazd; Etkina, Eugenia

    2014-01-01

    LEDs, or light-emitting diodes, are cheap, easy to purchase, and thus commonly used in physics instruction as indicators of electric current or as sources of light (Fig. 1). In our opinion LEDs represent a unique piece of equipment that can be used to collect experimental evidence, and construct and test new ideas in almost every unit of a general…

  13. Light-Emitting Diodes: Solving Complex Problems

    ERIC Educational Resources Information Center

    Planinšic, Gorazd; Etkina, Eugenia

    2015-01-01

    This is the fourth paper in our Light-Emitting Diodes series. The series aims to create a systematic library of LED-based materials and to provide readers with the description of experiments and the pedagogical treatment that would help their students construct, test, and apply physics concepts and mathematical relations. The first paper provided…

  14. Collection and Analysis of Aircraft Emitted Particles

    NASA Technical Reports Server (NTRS)

    Wilson, James Charles

    1999-01-01

    The University of Denver Aerosol Group proposed to adapt an impactor system for the collection of particles emitted by aircraft. The collection substrates were electron microscope grids which were analyzed by Dr. Pat Sheridan using a transmission electron microscope. The impactor was flown in the SNIFF behind aircraft and engine emissions were sampled. This report details the results of that work.

  15. Light-Emitting Diodes: A Hidden Treasure

    ERIC Educational Resources Information Center

    Planinšic, Gorazd; Etkina, Eugenia

    2014-01-01

    LEDs, or light-emitting diodes, are cheap, easy to purchase, and thus commonly used in physics instruction as indicators of electric current or as sources of light (Fig. 1). In our opinion LEDs represent a unique piece of equipment that can be used to collect experimental evidence, and construct and test new ideas in almost every unit of a general…

  16. Do Atoms Really "Emit" Absorption Lines?

    ERIC Educational Resources Information Center

    Brecher, Kenneth

    1991-01-01

    Presents three absorption line sources that enhance student understanding of the phenomena associated with the interaction of light with matter and help dispel the misconception that atoms "emit" absorption lines. Sources include neodymium, food coloring and other common household liquids, and fluorescent materials. (MDH)

  17. High performance inverted top-emitting organic light-emitting diodes with enhanced intrinsic quantum yield

    NASA Astrophysics Data System (ADS)

    Wu, Yukun; Guo, Runda; Wang, Hongbo; Zhang, Zhensong; Zhao, Yi

    2015-09-01

    Inverted top-emitting organic light-emitting diodes (ITOLEDs) with aluminum as cathode and semitransparent silver as anode are investigated. Comparing the blue, green and red ITOLEDs with conventional BEOLEDs based on iridium complex, it is surprising that the red ITOLED exhibits a higher efficiency nearly twice as that of the bottom-emitting counterpart, while blue and green ITOLEDs are comparable to BEOLEDs. We explain that the role of the strong microcavity effect improved the spontaneous emission of emitters in all ITOLEDs, however, only the intrinsic quantum yield of the red emitters is improved due to its comparable radiative and nonradiative decay rates.

  18. CERAPP: Collaborative Estrogen Receptor Activity Prediction Project

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Is there a role for estrogen activity assays? Recombinant cell bioassay for estrogen: Development and applications.

    PubMed

    Klein, Karen Oerter

    2015-07-01

    There are many questions which cannot be answered without a very sensitive estradiol assay. A recombinant cell bioassay (RCBA) for estradiol was developed in 1994. The sensitivity of the bioassay is 0.02-0.2 pg/ml (0.07-0.7 pmol/L), more than 20 times more sensitive than commercial RIAs and 10 times more sensitive than newer mass spectrometry assays. The RCBA for estradiol opened the door to study low levels of estradiol equivalents (EE) across the physiological spectrum of life from prepubertal children through menopause and across the spectrum from normal physiology, in boys as well as girls, to pathology, including: premature thelarche; estradiol suppression in children treated with GnRH analogues for precocious puberty; aromatase inhibition in boys with growth hormone deficiency; the differences between oral and transdermal routes of estrogen administration in girls with Turner's syndrome; women with breast cancer treated with aromatase inhibitors; and women with urogenital atrophy treated with low dose vaginal estrogen. A bioassay also allows study of endocrine disruptors, like phytoestrogens and other environmental compounds, which are relevant to public health and alternative medicine options. This paper reviews the assay and the last 20 years of applications. A bioassay for estrogen has a role because measuring biological effect is theoretically useful, increasing the understanding of physiology in addition to biochemical levels, giving different information than other assays, and opening the door to measure very low levels of estrogen activity in both humans and the environment. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    DTIC Science & Technology

    2010-07-01

    14. ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs preferentially in women. In murine models of SLE, it is...Systemic Lupus , Estrogen, BCR Signaling, B Cell Maturation, B Cell Selection 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF...effects of estradiol require the presence of antigen. Reportable outcomes: Invitation to AARDA 2011 symposium “Sex, Pregnancy , and

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

    DTIC Science & Technology

    2011-07-01

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

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

    DTIC Science & Technology

    2012-07-01

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

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

    PubMed

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

    2016-01-01

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

  5. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products

    PubMed Central

    Myers, Sharon L.; Yang, Chun Z.; Bittner, George D.; Witt, Kristine L.; Tice, Raymond R.; Baird, Donna D.

    2014-01-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products. PMID:24849798

  6. Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio).

    PubMed

    Goundadkar, Basavaraj B; Katti, Pancharatna

    2017-09-01

    The present study is an attempt to investigate the effects of long-term (75days) exposure to environmental estrogens (EE) on the swimming behaviour of zebrafish (Danio rerio). Adult zebrafish were exposed semi-statically to media containing commonly detected estrogenic water contaminants (EE2, DES and BPA) at a concentration (5ng/L) much lower than environmentally recorded levels. Time spent in swimming, surface preference, patterns and path of swimming were recorded (6mins) for each fish using two video cameras on day 15, 30 60 and 75. Video clips were analysed using a software program. Results indicate that chronic exposure to EE leads to increased body weight and size of females, reduced (P<0.05) swimming time, delay in latency, increased (P<0.05) immobility, erratic movements and freezing episodes. We conclude that estrogenic contamination of natural aquatic systems induces alterations in locomotor behaviour and associated physiological disturbances in inhabitant fish fauna. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Blocking Estrogen Signaling After the Hormone: Pyrimidine-Core Inhibitors of Estrogen Receptor-Coactivator Binding

    PubMed Central

    Parent, Alexander A.; Gunther, Jillian R.; Katzenellenbogen, John A.

    2009-01-01

    As an alternative approach to blocking estrogen action, we have developed small molecules that directly disrupt the key estrogen receptor (ER)/coactivator interaction necessary for gene activation. The more direct, protein-protein nature of this disruption might be effective even in hormone-refractory breast cancer. We have synthesized a pyrimidine-core library of moderate size, members of which act as α-helix mimics to block ERα/coactivator interaction. Structure- activity relationships have been explored with various C, N, O and S-substituents on the pyrimidine core. Time-resolved fluorescence resonance energy transfer and cell-based reporter gene assays show that the most active members inhibit the ERα/steroid receptor coactivator interaction with Ki’s in the low micromolar range. Through these studies, we have obtained a refined pharmacophore model for activity in this pyrimidine series. Furthermore, the favorable activities of several of these compounds support the feasibility that this coactivator binding inhibition mechanism for blocking estrogen action might provide a potential alternative approach to endocrine therapy. PMID:18785725

  8. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products.

    PubMed

    Myers, Sharon L; Yang, Chun Z; Bittner, George D; Witt, Kristine L; Tice, Raymond R; Baird, Donna D

    2015-05-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products.

  9. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  10. Si-based blue light emitting diode

    NASA Astrophysics Data System (ADS)

    Namavar, Fereydoon

    1994-05-01

    Phase 1 results demonstrated for the first time a strong, stable blue-green emission from C-implanted red-emitting porous silicon. The objective of Phase 1 was to obtain blue-green emission from porous Si structure either by increasing the bandgap of the substrate by growth of Si-C random alloys prior to forming nanostructures with quantum confined properties, or by increasing the confinement energy of red-emitting Si nanostructures. Porous structures fabricated from group 4 alloys epitaxially grown by chemical vapor deposition (CVD) resulted in an enhancement in light emission of about one order of magnitude after incorporation of a very small amount of carbon in the epitaxial grown films. Strong blue-green light emission was observed by the naked eye from C-implanted and annealed porous Si. Using AlGaAs as a reference, we observed that the intensity of blue-green emission was one order of magnitude higher than that of the original red-emitting porous Si. Catholuminescence measurements of our samples performed at the University of Colorado show blue emission at 1.80 eV and 2.80 eV. Fourier transform infrared (FTIR) spectra of a blue-green emitting porous structure shows an IR absorption line identical to that of SiC and electron diffraction studies clearly show reflections corresponding to beta-SiC. Phase 1 results indicate that blue-green light is from SiC nanostructures with quantum confined properties. This material may be used to fabricate blue light-emitting Si-based devices which can be easily integrated into Si technology.

  11. Neurobiology of estrogen status in deep craniofacial pain.

    PubMed

    Bereiter, David A; Okamoto, Keiichiro

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  13. Estrogens and the cognitive symptoms of schizophrenia: Possible neuroprotective mechanisms.

    PubMed

    McGregor, Claire; Riordan, Alexander; Thornton, Janice

    2017-06-30

    Schizophrenia is a complex neuropsychiatric illness with marked sex differences. Women have later onset and lesser symptoms, which has led to the hypothesis that estrogens are protective in schizophrenia. Cognitive dysfunction is a hallmark of the disease and the symptom most correlated with functional outcome. Here we describe a number of mechanisms by which estrogens may be therapeutic in schizophrenia, with a focus on cognitive symptoms. We review the relationship between estrogens and brain derived neurotrophic factor, neuroinflammation, NMDA receptors, GABA receptors, and luteinizing hormone. Exploring these pathways may enable novel treatments for schizophrenia and a greater understanding of this devastating disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. [Estrogen receptor alpha in obesity and diabetes].

    PubMed

    Cahua-Pablo, José Ángel; Flores-Alfaro, Eugenia; Cruz, Miguel

    2016-01-01

    Estradiol (E2) is an important hormone in reproductive physiology, cardiovascular, skeletal and in the central nervous system (CNS). In human and rodents, E2 and its receptors are involved in the control of energy and glucose metabolism in health and metabolic diseases. The estrogen receptor (ER) belongs to the superfamily of nuclear receptors (NR), which are transcription factors that regulate gene expression. Three ER, ER-alpha, ER-beta and the G protein-coupled ER (GPER; also called GPR30) in tissues are involved in glucose and lipid homeostasis. Also, it may have important implications for risk factors associated with metabolic syndrome (MS), insulin resistance (IR), obesity and type 2 diabetes (T2D).

  15. Maternal Regulation of Estrogen Receptor α Methylation

    PubMed Central

    Champagne, Frances A.; Curley, James P.

    2008-01-01

    Summary Advances in molecular biology have provided tools for studying the epigenetic factors which modulate gene expression. DNA methylation is an epigenetic modification which can have sustained effects on transcription and is associated with long-term gene silencing. In this review, we focus on the regulation of estrogen receptor alpha (ERα) expression by hormonal and environmental cues, the consequences of these cues for female maternal and sexual behavior and recent studies which explore the role of DNA methylation in mediating these developmental effects, with particular focus on the mediating role of maternal care. The methylation status of ERα has implications for reproductive behavior, cancer susceptibility and recovery from ischemic injury suggesting an epigenetic basis for risk and resilience across the life span. PMID:18644464

  16. The removal of estrogenic activity with UV/chlorine technology and identification of novel estrogenic disinfection by-products.

    PubMed

    Li, Man; Xu, Bi; Liungai, Zhiqi; Hu, Hong-Ying; Chen, Chao; Qiao, Juan; Lu, Yun

    2016-04-15

    As a recently developed disinfection technology, ultraviolet (UV)/chlorine treatment has received much attention. Many studies have evaluated its effects on pathogen inactivation, contaminant removal, and formation of disinfection by-products (DBPs), but its potential for environmental estrogen removal and estrogenic DBP generation, which can also be a risk to both ecosystem and human health, have not been evaluated. In this study, UV/chlorine treatment resulted in a greater removal of estrogenic activity in synthetic effluent samples containing 17β-estradiol (E2) than did UV or chlorine treatment alone regardless of the water quality. For both the UV/chlorine and chlorine treatments, there was significant interference from NH3-N, although the UV/chlorine treatment was less affected. Estrogen receptor based affinity chromatography was used to isolate the specific estrogenic DBPs, and a novel product, with high estrogenic activity compared to E2, Δ9(11)-dehydro-estradiol, was identified. It was generated by all three treatments, and might be previously mistakenly recognized as estrone (E1). This study demonstrated that UV/chlorine is a better treatment for the removal of 17β-estradiol than chlorine and UV alone. The new identified estrogenic DBP, Δ9(11)-dehydro-estradiol, which can be isolated by affinity chromatography, could be an emerging concern in the future.

  17. Validation and application of a robust yeast estrogen bioassay for the screening of estrogenic activity in animal feed.

    PubMed

    Bovee, Toine F H; Bor, Gerrit; Heskamp, Henri H; Hoogenboom, Ron L A P; Nielen, Michel W F

    2006-06-01

    Previously we described the construction and properties of a rapid yeast bioassay stably expressing human estrogen receptor alpha (hERalpha) and yeast enhanced green fluorescent protein (yEGFP), the latter in response to estrogens. In the present study this yeast estrogen assay was validated as a qualitative screening method for the determination of estrogenic activity in animal feed. This validation was performed according to EC Decision 2002/657. Twenty blank animal feed samples, including milk replacers and wet and dry feed samples, were spiked with 17beta-estradiol (E2beta) at 5 ng g(-1), 17alpha-ethynylestradiol (EE2) at 5 ng g(-1), diethylstilbestrol (DES) at 10 ng g(-1), zearalenone at 1.25 microg g(-1) or equal at 200 microg g(-1). All of these blank and low estrogen spiked feed samples fulfilled the CCalpha and CCbeta criterions, meaning that all 20 blank feed samples gave a signal below the determined decision limit CCalpha and were thus classified as compliant, and at least 19 out of the 20 spiked samples gave a signal above this CCalpha (beta = 5%) and were thus classified as suspect. The method was specific and estrogens in feed were stable for up to 98 days. In this study we also present long-term performance data and several examples of estrogens found in the routine screening of animal feed. This is the first successful example of a developed, validated and applied bioassay for the screening of hormonal substances in feed.

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

    PubMed

    Khan, Deena; Ansar Ahmed, S

    2015-01-01

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

  19. Effect of combining in vitro estrogenicity data with kinetic characteristics of estrogenic compounds on the in vivo predictive value.

    PubMed

    Punt, Ans; Brand, Walter; Murk, Albertinka J; van Wezel, Annemarie P; Schriks, Merijn; Heringa, Minne B

    2013-02-01

    With the ultimate aim of increasing the utility of in vitro assays for toxicological risk assessment, a method was developed to calculate in vivo estrogenic potencies from in vitro estrogenic potencies of compounds by taking into account systemic availability. In vitro estrogenic potencies of three model compounds (bisphenol A, genistein, and 4-nonylphenol) relative to ethinylestradiol (EE2), determined with the estrogen receptor alpha (ERα) transcriptional activation assay using hER-HeLa-9903 cells, were taken from literature and used to calculate the EE2 equivalent (EE2EQ) effect doses in the predominantly ERα-dependent rat uterotrophic assay. Compound-specific differences in hepatic clearance relative to the reference compound EE2 were determined in vitro to examine whether in vivo estrogenic potencies reported in literature could be more accurately estimated. The EE2EQ doses allowed to predict in vivo uterotrophic responses within a factor of 6-25 and the inclusion of the hepatic clearance further improved the prediction with a factor 1.6-2.1 for especially genistein and bisphenol A. Yet, the model compounds still were less potent in vivo than predicted based on their EE2 equivalent estrogenic potency and hepatic clearance. For further improvement of the in vitro to in vivo predictive value of in vitro assays, the relevance of other kinetic characteristics should be studied, including binding to carrier proteins, oral bioavailability and the formation of estrogenic metabolites. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Channel catfish (Ictalurus punctatus) leukocytes express estrogen receptor isoforms ERα and ERβ2 and are functionally modulated by estrogens

    USGS Publications Warehouse

    Iwanowicz, Luke R.; Stafford, James L.; Patiño, Reynaldo; Bengten, Eva; Miller, Norman W.; Blazer, Vicki

    2014-01-01

    Estrogens are recognized as modulators of immune responses in mammals and teleosts. While it is known that the effects of estrogens are mediated via leukocyte-specific estrogen receptors (ERs) in humans and mice, leucocyte-specific estrogen receptor expression and the effects of estrogens on this cell population is less explored and poorly understood in teleosts. Here in, we verify that channel catfish (Ictalurus punctaus) leukocytes express ERα and ERβ2. Transcripts of these isoforms were detected in tissue-associated leukocyte populations by PCR, but ERβ2 was rarely detected in PBLs. Expression of these receptors was temporally regulated in PBLs following polyclonal activation by concanavalin A, lipopolysaccharide or alloantigen based on evaluation by quantitative and end-point PCR. Examination of long-term leukocyte cell lines demonstrated that these receptors are differentially expressed depending on leukocyte lineage and phenotype. Expression of ERs was also temporally dynamic in some leukocyte lineages and may reflect stage of cell maturity. Estrogens affect the responsiveness of channel catfish peripheral blood leukocytes (PBLs) to mitogens in vitro. Similarly, bactericidal activity and phorbol 12-myristate 13-acetate induced respiratory burst was modulated by 17β-estradiol. These actions were blocked by the pure ER antagonist ICI 182780 indicating that response is, in part, mediated via ERα. In summary, estrogen receptors are expressed in channel catfish leukocytes and participate in the regulation of the immune response. This is the first time leukocyte lineage expression has been reported in teleost cell lines.

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

    PubMed Central

    Khan, Deena; Ansar Ahmed, S.

    2016-01-01

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

  2. Estrogens Can Disrupt Amphibian Mating Behavior

    PubMed Central

    Hoffmann, Frauke; Kloas, Werner

    2012-01-01

    The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline. PMID:22355410

  3. Bioassay of estrogenicity and chemical analyses of estrogens in streams across the United States associated with livestock operations

    USGS Publications Warehouse

    Alvarez, David A.; Shappell, Nancy W.; Billey, L.O.; Bermudez, Dietrich S.; Wilson, Vickie S.; Kolpin, Dana W.; Perkins, Stephanie D.; Evans, Nicola; Foreman, William T.; Gray, James L.; Shipitalo, J.M.; Meyer, Michael T.

    2013-01-01

    Animal manures, used as a nitrogen source for crop production, are often associated with negative impacts on nutrient levels in surface water. The concentrations of estrogens in streams from these manures also are of concern due to potential endocrine disruption in aquatic species. Streams associated with livestock operations were sampled by discrete samples (n = 38) or by time-integrated polar organic chemical integrative samplers (POCIS,n = 19). Samples were analyzed for estrogens by gas chromatography-tandem mass spectrometry (GC-MSM2) and estrogenic activity was assessed by three bioassays: Yeast Estrogen Screen (YES), T47D-KBluc Assay, MCF-7 Estrogenicity Screen (E-Screen). Samples were collected from 19 streams within small (∼1-30 km2) watersheds in 12 U.S. states representing a range of hydrogeologic conditions, dominated by: dairy (3), grazing beef (3), feedlot cattle (1); swine (5); poultry (3); and 4 areas where no livestock were raised or manure was applied. Water samples were consistently below the United Kingdom proposed Lowest Observable Effect Concentration for 17b-estradiol in fish (10 ng/L) in all watersheds, regardless of land use. Estrogenic activity was often higher in samples during runoff conditions following a period of manure application. Estrone was the most commonly detected estrogen (13 of 38 water samples, mean 1.9, maximum 8.3 ng/L). Because of the T47D-KBluc assay’s sensitivity towards estrone (1.4 times 17β-estradiol) it was the most sensitive method for detecting estrogens, followed by the E-Screen, GC-MS2, and YES. POCIS resulted in more frequent detections of estrogens than discrete water samples across all sites, even when applying the less-sensitive YES bioassay to the POCIS extracts.

  4. Conserved estrogen binding and signaling functions of the G protein-coupled estrogen receptor 1 (GPER) in mammals and fish.

    PubMed

    Thomas, P; Alyea, R; Pang, Y; Peyton, C; Dong, J; Berg, A H

    2010-01-01

    Recent studies by several research groups have shown that G protein estrogen receptor-1 (GPER) formerly known as GPR30, mediates 17beta-estradiol (E2) activation of signal transduction pathways in a variety of human cancer cells and displays E2 binding typical of a membrane estrogen receptor. However, the importance of GPER as an estrogen receptor has been questioned by Otto and co-workers. Some of the pitfalls in investigating the functions of recombinant steroid membrane receptors that may explain the negative results of these investigators are discussed. The characteristics of GPER have also been investigated in a teleost fish, Atlantic croaker, where it has been shown to mediate E2 inhibition of oocyte maturation. Investigations on newly discovered homologous proteins from distantly related vertebrate groups are valuable for determining their fundamental, evolutionarily conserved functions. Therefore, the functions of croaker and human GPERs were compared. The comparisons show that croaker and human GPER have very similar estrogen binding characteristics, typical of estrogen membrane receptors, and activate the same estrogen signaling pathways via stimulatory G proteins (Gs) resulting in increased cAMP production. These results suggest that the estrogen binding and estrogen signaling functions of GPER arose early in vertebrate evolution, prior to the divergence of the teleosts from the tetrapods, more than 200 million years ago. The finding that estrogen membrane signaling through GPER has been conserved for such a long period in two distantly related vertebrate groups, mammals and fish, suggests that this is a fundamental function of GPER in vertebrates, and likely its major physiological role. Copyright 2009 Elsevier Inc. All rights reserved.

  5. Bioassay of estrogenicity and chemical analyses of estrogens in streams across the United States associated with livestock operations.

    PubMed

    Alvarez, D A; Shappell, N W; Billey, L O; Bermudez, D S; Wilson, V S; Kolpin, D W; Perkins, S D; Evans, N; Foreman, W T; Gray, J L; Shipitalo, M J; Meyer, M T

    2013-06-15

    Animal manures, used as a nitrogen source for crop production, are often associated with negative impacts on nutrient levels in surface water. The concentrations of estrogens in streams from these manures also are of concern due to potential endocrine disruption in aquatic species. Streams associated with livestock operations were sampled by discrete samples (n = 38) or by time-integrated polar organic chemical integrative samplers (POCIS, n = 19). Samples were analyzed for estrogens by gas chromatography-tandem mass spectrometry (GC-MS(2)) and estrogenic activity was assessed by three bioassays: Yeast Estrogen Screen (YES), T47D-KBluc Assay, MCF-7 Estrogenicity Screen (E-Screen). Samples were collected from 19 streams within small (≈ 1-30 km(2)) watersheds in 12 U.S. states representing a range of hydrogeologic conditions, dominated by: dairy (3), grazing beef (3), feedlot cattle (1); swine (5); poultry (3); and 4 areas where no livestock were raised or manure was applied. Water samples were consistently below the United Kingdom proposed Lowest Observable Effect Concentration for 17β-estradiol in fish (10 ng/L) in all watersheds, regardless of land use. Estrogenic activity was often higher in samples during runoff conditions following a period of manure application. Estrone was the most commonly detected estrogen (13 of 38 water samples, mean 1.9, maximum 8.3 ng/L). Because of the T47D-KBluc assay's sensitivity towards estrone (1.4 times 17β-estradiol) it was the most sensitive method for detecting estrogens, followed by the E-Screen, GC-MS(2), and YES. POCIS resulted in more frequent detections of estrogens than discrete water samples across all sites, even when applying the less-sensitive YES bioassay to the POCIS extracts. Published by Elsevier Ltd.

  6. Estrogen regulation of chicken riboflavin carrier protein gene is mediated by ERE half sites without direct binding of estrogen receptor.

    PubMed

    Bahadur, Urvashi; Ganjam, Goutham K; Vasudevan, Nandini; Kondaiah, Paturu

    2005-02-28

    Estrogen is an important steroid hormone that mediates most of its effects on regulation of gene expression by binding to intracellular receptors. The consensus estrogen response element (ERE) is a 13bp palindromic inverted repeat with a three nucleotide spacer. However, several reports suggest that many estrogen target genes are regulated by diverse elements, such as imperfect EREs and ERE half sites (ERE 1/2), which are either the proximal or the distal half of the palindrome. To gain more insight into ERE half site-mediated gene regulation, we used a region from the estrogen-regulated chicken riboflavin carrier protein (RCP) gene promoter that contains ERE half sites. Using moxestrol, an analogue of estrogen and transient transfection of deletion and mutation containing RCP promoter/reporter constructs in chicken hepatoma (LMH2A) cells, we identified an estrogen response unit (ERU) composed of two consensus ERE 1/2 sites and one non-consensus ERE 1/2 site. Mutation of any of these sites within this ERU abolishes moxestrol response. Further, the ERU is able to confer moxestrol responsiveness to a heterologous promoter. Interestingly, RCP promoter is regulated by moxestrol in estrogen responsive human MCF-7 cells, but not in other cell lines such as NIH3T3 and HepG2 despite estrogen receptor-alpha (ER-alpha) co transfection. Electrophoretic mobility shift assays (EMSAs) with promoter regions encompassing the half sites and nuclear extracts from LMH2A cells show the presence of a moxestrol-induced complex that is abolished by a polyclonal anti-ERalpha antibody. Surprisingly, estrogen receptor cannot bind to these promoter elements in isolation. Thus, there appears to be a definite requirement for some other factor(s) in addition to estrogen receptor, for the generation of a suitable response of this promoter to estrogen. Our studies therefore suggest a novel mechanism of gene regulation by estrogen, involving ERE half sites without direct binding of ER to the

  7. Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc).

    EPA Science Inventory

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

  8. Modeling mixtures of environmental estrogens found in U.S. surface waters with an in vitro estrogen mediated transcriptionai activation assay (T47D-KBluc).

    EPA Science Inventory

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

  9. BIOCHEMICAL AND ANALYTICAL CHARACTERIZATION OF ESTROGENICALLY ACTIVE WASTEWATER: COMPARISON OF FIELD EXTRAPOLATIONS TO THE MEASURED CONCENTRATION OF ESTROGENS IN SEWAGE EFFLUENT

    EPA Science Inventory

    Estrogenically active wastewater was observed at two municipal wastewater treatment plants (WWTPs) utilizing caged male channel catfish in a previous study. The focus of this investigation was to identify and characterize the compound(s) responsible for this estrogenic response. ...

  10. Microbial transformation of synthetic estrogen 17alpha-ethinylestradiol.

    PubMed

    Cajthaml, Tomás; Kresinová, Zdena; Svobodová, Katerina; Sigler, Karel; Rezanka, Tomás

    2009-12-01

    Natural estrogens such as estrone, 17beta-estradiol, estriol, and the particularly recalcitrant synthetic estrogen 17alpha-ethinylestradiol used as oral contraceptive, accumulate in the environment and may give rise to health problems. The processes participating in their removal from soil, wastewater, water-sediments, groundwater-aquifer material, and wastewater or sewage treatment plant effluents may involve the action of bacterial and microbial consortia, and in some cases fungi and algae. This review discusses the different efficiencies of bacterial degradation of 17alpha-ethinylestradiol under aerobic and anaerobic conditions, the role of sulfate-, nitrate-, and iron-reducing conditions in anaerobic degradation, and the role of sorption. The participation of autotrophic ammonia oxidizing bacteria and heterotrophic bacteria in cometabolic degradation of estrogens, the estrogen-degrading action of ligninolytic fungi and their extracellular enzymes (lignin peroxidase, manganese-dependent peroxidase, versatile peroxidase, laccase), and of algae are discussed in detail.

  11. Estrogenic involvement in social learning, social recognition and pathogen avoidance.

    PubMed

    Choleris, Elena; Clipperton-Allen, Amy E; Phan, Anna; Valsecchi, Paola; Kavaliers, Martin

    2012-04-01

    Sociality comes with specific cognitive skills that allow the proper processing of information about others (social recognition), as well as of information originating from others (social learning). Because sociality and social interactions can also facilitate the spread of infection among individuals the ability to recognize and avoid pathogen threat is also essential. We review here various studies primarily from the rodent literature supporting estrogenic involvement in the regulation of social recognition, social learning (socially acquired food preferences and mate choice copying) and the recognition and avoidance of infected and potentially infected individuals. We consider both genomic and rapid estrogenic effects involving estrogen receptors α and β, and G-protein coupled estrogen receptor 1, along with their interactions with neuropeptide systems in the processing of social stimuli and the regulation and expression of these various socially relevant behaviors.

  12. SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE

    EPA Science Inventory

    Rationale: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans. Objectives: To examine the role of estrogen receptors in modulat...

  13. Comparison of estrogen mixtures in vitro vs. in vivo

    EPA Science Inventory

    Numerous sources contribute to widespread contamination of drinking water sources with both natural and synthetic estrogens, which isa concern for potential ecological and human health effects. In vitro screening assays are valuable tools for identifying mechanisms of toxicity bu...

  14. ROLE OF ESTROGEN RECEPTOR-α ON FOOD DEMAND ELASTICITY

    PubMed Central

    Minervini, Vanessa; Rowland, Neil E.; Robertson, Kimberly L.; Foster, Thomas C.

    2016-01-01

    Estrogens have been shown to have an inhibitory effect on food intake under free-feeding conditions, yet the effects of estrogens on food-maintained operant responding have been studied to a much lesser extent and, thus, are not well understood. Therefore, the purpose of the present experiment was to use a behavioral economics paradigm to assess differences in demand elasticity between mice with knockout of the estrogen receptor subtype α, knockout of subtype β, and their wild type controls. The mice responded in a closed economy, and the price of food was increased by increasing the fixed-ratio response requirement every four sessions. Overall, we found that mice with the knockout of receptor subtype α had the most elastic demand functions. Therefore, under these conditions, estrogens increased food seeking via activation of the receptor subtype α. The results were inconsistent with those reported by previous studies that employed free-feeding conditions. PMID:25869426

  15. Role of estrogen receptor-α on food demand elasticity.

    PubMed

    Minervini, Vanessa; Rowland, Neil E; Robertson, Kimberly L; Foster, Thomas C

    2015-05-01

    Estrogens have been shown to have an inhibitory effect on food intake under free-feeding conditions, yet the effects of estrogens on food-maintained operant responding have been studied to a much lesser extent and, thus, are not well understood. Therefore, the purpose of the present experiment was to use a behavioral economics paradigm to assess differences in demand elasticity between mice with knockout of the estrogen receptor subtype α, knockout of subtype β, and their wild type controls. The mice responded in a closed economy, and the price of food was increased by increasing the fixed-ratio response requirement every four sessions. Overall, we found that mice with the knockout of receptor subtype α had the most elastic demand functions. Therefore, under these conditions, estrogens increased food seeking via activation of the receptor subtype α. The results were inconsistent with those reported by previous studies that employed free-feeding conditions.

  16. Estrogen Intake and Copper Depositions: Implications for Alzheimer's Disease?

    PubMed Central

    Amtage, Florian; Birnbaum, Dzelila; Reinhard, Thomas; Niesen, Wolf-Dirk; Weiller, Cornelius; Mader, Irina; Meyer, Philipp T.; Rijntjes, Michel

    2014-01-01

    We present a patient with chronic postmenopausal estrogen intake with presence of Kayser-Fleischer ring in the cornea and Alzheimer's disease and discuss the pathophysiological mechanisms of estrogen intake and copper accumulation in various tissues, including the central nervous system. Sonography was compatible with copper accumulation in the basal ganglia, but the patient showed no clinical signs of Wilson's disease. Magnetic resonance imaging and positron emission tomography revealed a typical pattern for Alzheimer's disease. We propose increased copper levels as a direct effect of estrogen intake due to an augmented ATP7A-mRNA in the intestine. Moreover, we discuss the impact of elevated free serum copper on accompanying Alzheimer's disease, knowing that copper plays a crucial role in the formation of amyloid plaques and tau aggregation. This might offer a partial explanation for the observation that postmenopausal estrogen therapy is associated with a higher risk of mild cognitive impairment and Alzheimer's disease. PMID:25076894

  17. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS Requirements for Specific New Drugs or Devices § 310.515 Patient...) Exemptions. This section does not apply to estrogen-progestogen oral contraceptives. Labeling requirements...

  18. Modeling environmental loading rates of municipal wastewater contaminants: steroidal estrogens

    EPA Science Inventory

    Estrogenic compounds in municipal wastewater are of substantial interest because of suspicion that they may cause reproductive disruption in aquatic invertebrates, and because of their potential to contaminate human drinking water sources. Previous work suggests the primary contr...

  19. Modeling environmental loading rates of municipal wastewater contaminants: steroidal estrogens

    EPA Science Inventory

    Estrogenic compounds in municipal wastewater are of substantial interest because of suspicion that they may cause reproductive disruption in aquatic invertebrates, and because of their potential to contaminate human drinking water sources. Previous work suggests the primary contr...

  20. A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings

    PubMed Central

    Gogos, Andrea; Sbisa, Alyssa M.; Sun, Jeehae; Gibbons, Andrew; Udawela, Madhara; Dean, Brian

    2015-01-01

    Gender differences in schizophrenia have been extensively researched and it is being increasingly accepted that gonadal steroids are strongly attributed to this phenomenon. Of the various hormones implicated, the estrogen hypothesis has been the most widely researched one and it postulates that estrogen exerts a protective effect by buffering females against the development and severity of the illness. In this review, we comprehensively analyse studies that have investigated the effects of estrogen, in particular 17β-estradiol, in clinical, animal, and molecular research with relevance to schizophrenia. Specifically, we discuss the current evidence on estrogen dysfunction in schizophrenia patients and review the clinical findings on the use of estradiol as an adjunctive treatment in schizophrenia patients. Preclinical research that has used animal models and molecular probes to investigate estradiol's underlying protective mechanisms is also substantially discussed, with particular focus on estradiol's impact on the major neurotransmitter systems implicated in schizophrenia, namely, the dopamine, serotonin, and glutamate systems. PMID:26491441

  1. Estrogen-induced myelotoxicity in dogs: A review

    PubMed Central

    Sontas, Hasan B.; Dokuzeylu, Banu; Turna, Ozge; Ekici, Hayri

    2009-01-01

    Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow toxicity in dogs. The condition is characterized by hematologic abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia. Despite intensive therapy with blood or platelet-rich transfusions, broad-spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is unfavorable. Due to the the risk of stimulating the development of uterine diseases and the potential for inducing aplastic anemia, estrogen use in dogs is best avoided where possible. This paper describes the causes of estrogen-induced myelotoxicity, the clinical presentation of the patients, the diagnosis, and the treatment options in the dog. PMID:20046604

  2. SPONTANEOUS AIRWAY HYPERRESPONSIVENESS IN ESTROGEN RECEPTOR-A DEFICIENT MICE

    EPA Science Inventory

    Rationale: Airway hyperresponsiveness is a critical feature of asthma. Substantial epidemiologic evidence supports a role for female sex hormones in modulating lung function and airway hyperresponsiveness in humans. Objectives: To examine the role of estrogen receptors in modulat...

  3. Comparison of estrogen mixtures in vitro vs. in vivo

    EPA Science Inventory

    Numerous sources contribute to widespread contamination of drinking water sources with both natural and synthetic estrogens, which isa concern for potential ecological and human health effects. In vitro screening assays are valuable tools for identifying mechanisms of toxicity bu...

  4. Estrogen Induces c-myc Gene Expression via an Upstream Enhancer Activated by the Estrogen Receptor and the AP-1 Transcription Factor

    PubMed Central

    Wang, Chunyu; Mayer, Julie Ann; Mazumdar, Abhijit; Fertuck, Kirsten; Kim, Heetae; Brown, Myles

    2011-01-01

    c-myc oncogene is implicated in tumorigenesis of many cancers, including breast cancer. Although c-myc is a well-known estrogen-induced gene, its promoter has no estrogen-response element, and the underlying mechanism by which estrogen induces its expression remains obscure. Recent genome-wide studies by us and others suggested that distant elements may mediate estrogen induction of gene expression. In this study, we investigated the molecular mechanism by which estrogen induces c-myc expression with a focus on these distal elements. Estrogen rapidly induced c-myc expression in estrogen receptor (ER)-positive breast cancer cells. Although estrogen had little effect on c-myc proximal promoter activity, it did stimulate the activity of a luciferase reporter containing a distal 67-kb enhancer. Estrogen induction of this luciferase reporter was dependent upon both a half-estrogen response element and an activator protein 1 (AP-1) site within this enhancer, which are conserved across 11 different mammalian species. Small interfering RNA experiments and chromatin immunoprecipitation assays demonstrated the necessity of ER and AP-1 cross talk for estrogen to induce c-myc expression. TAM67, the AP-1 dominant negative, partially inhibited estrogen induction of c-myc expression and suppressed estrogen-induced cell cycle progression. Together, these results demonstrate a novel pathway of estrogen regulation of gene expression by cooperation between ER and AP-1 at the distal enhancer element and that AP-1 is involved in estrogen induction of the c-myc oncogene. These results solve the long-standing question in the field of endocrinology of how estrogen induces c-myc expression. PMID:21835891

  5. The estrogenic activity of phthalate esters in vitro.

    PubMed

    Harris, C A; Henttu, P; Parker, M G; Sumpter, J P

    1997-08-01

    A large number of phthalate esters were screened for estrogenic activity using a recombinant yeast screen. a selection of these was also tested for mitogenic effect on estrogen-responsive human breast cancer cells. A small number of the commercially available phthalates tested showed extremely weak estrogenic activity. The relative potencies of these descended in the order butyl benzyl phthalate (BBP) > dibutyl phthalate (DBP) > diisobutyl phthalate (DIBP) > diethyl phthalate (DEP) > diisiononyl phthalate (DINP). Potencies ranged from approximately 1 x 10(6) to 5 x 10(7) times less than 17beta-estradiol. The phthalates that were estrogenic in the yeast screen were also mitogenic on the human breast cancer cells. Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity in these in vitro assays. A number of metabolites were tested, including mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mon-n-octyl phthalate; all were wound to be inactive. One of the phthalates, ditridecyl phthalate (DTDP), produced inconsistent results; one sample was weakly estrogenic, whereas another, obtained from a different source, was inactive. analysis by gel chromatography-mass spectometry showed that the preparation exhibiting estrogenic activity contained 0.5% of the ortho-isomer of bisphenol A. It is likely that the presence of this antioxidant in the phthalate standard was responsible for the generation of a dose-response curve--which was not observed with an alternative sample that had not been supplemented with o,p'-bisphenol A--in the yeast screen; hence, DTDP is probably not weakly estrogenic. The activities of simple mixtures of BBP, DBP, and 17beta-estradiol were assessed in the yeast screen. No synergism was observed, although the activities of the mixtures were approximately additive. In summary, a small number of phthalates are weakly estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vitro. No data has

  6. The estrogenic activity of phthalate esters in vitro.

    PubMed Central

    Harris, C A; Henttu, P; Parker, M G; Sumpter, J P

    1997-01-01

    A large number of phthalate esters were screened for estrogenic activity using a recombinant yeast screen. a selection of these was also tested for mitogenic effect on estrogen-responsive human breast cancer cells. A small number of the commercially available phthalates tested showed extremely weak estrogenic activity. The relative potencies of these descended in the order butyl benzyl phthalate (BBP) > dibutyl phthalate (DBP) > diisobutyl phthalate (DIBP) > diethyl phthalate (DEP) > diisiononyl phthalate (DINP). Potencies ranged from approximately 1 x 10(6) to 5 x 10(7) times less than 17beta-estradiol. The phthalates that were estrogenic in the yeast screen were also mitogenic on the human breast cancer cells. Di(2-ethylhexyl) phthalate (DEHP) showed no estrogenic activity in these in vitro assays. A number of metabolites were tested, including mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mon-n-octyl phthalate; all were wound to be inactive. One of the phthalates, ditridecyl phthalate (DTDP), produced inconsistent results; one sample was weakly estrogenic, whereas another, obtained from a different source, was inactive. analysis by gel chromatography-mass spectometry showed that the preparation exhibiting estrogenic activity contained 0.5% of the ortho-isomer of bisphenol A. It is likely that the presence of this antioxidant in the phthalate standard was responsible for the generation of a dose-response curve--which was not observed with an alternative sample that had not been supplemented with o,p'-bisphenol A--in the yeast screen; hence, DTDP is probably not weakly estrogenic. The activities of simple mixtures of BBP, DBP, and 17beta-estradiol were assessed in the yeast screen. No synergism was observed, although the activities of the mixtures were approximately additive. In summary, a small number of phthalates are weakly estrogenic in vitro. No data has yet been published on whether these are also estrogenic in vitro. No data has

  7. Exercise (and Estrogen) Make Fat Cells “Fit”

    PubMed Central

    Vieira-Potter, Victoria J.; Zidon, Terese M.; Padilla, Jaume

    2016-01-01

    Adipose tissue inflammation links obesity and metabolic disease. Both exercise and estrogen improve metabolic health, enhance mitochondrial function, and have anti-inflammatory effects. We hypothesize that there is an inverse relationship between mitochondrial function and inflammation in adipose tissue and that exercise acts as an estrogen “mimetic”. Explicitly, exercise may improve adipose tissue “immunometabolism” by improving mitochondrial function and reducing inflammation. Summary Exercise improves adipose tissue metabolic health by reducing inflammation and improving mitochondrial function. PMID:25906425

  8. Agonistic and antagonistic estrogens in licorice root (Glycyrrhiza glabra).

    PubMed

    Simons, Rudy; Vincken, Jean-Paul; Mol, Loes A M; The, Susan A M; Bovee, Toine F H; Luijendijk, Teus J C; Verbruggen, Marian A; Gruppen, Harry

    2011-07-01

    The roots of licorice (Glycyrrhiza glabra) are a rich source of flavonoids, in particular, prenylated flavonoids, such as the isoflavan glabridin and the isoflavene glabrene. Fractionation of an ethyl acetate extract from licorice root by centrifugal partitioning chromatography yielded 51 fractions, which were characterized by liquid chromatography-mass spectrometry and screened for activity in yeast estrogen bioassays. One third of the fractions displayed estrogenic activity towards either one or both estrogen receptors (ERs; ERα and ERβ). Glabrene-rich fractions displayed an estrogenic response, predominantly to the ERα. Surprisingly, glabridin did not exert agonistic activity to both ER subtypes. Several fractions displayed higher responses than the maximum response obtained with the reference compound, the natural hormone 17β-estradiol (E(2)). The estrogenic activities of all fractions, including this so-called superinduction, were clearly ER-mediated, as the estrogenic response was inhibited by 20-60% by known ER antagonists, and no activity was found in yeast cells that did not express the ERα or ERβ subtype. Prolonged exposure of the yeast to the estrogenic fractions that showed superinduction did, contrary to E(2), not result in a decrease of the fluorescent response. Therefore, the superinduction was most likely the result of stabilization of the ER, yeast-enhanced green fluorescent protein, or a combination of both. Most fractions displaying superinduction were rich in flavonoids with single prenylation. Glabridin displayed ERα-selective antagonism, similar to the ERα-selective antagonist RU 58668. Whereas glabridin was able to reduce the estrogenic response of E(2) by approximately 80% at 6 × 10(-6) M, glabrene-rich fractions only exhibited agonistic responses, preferentially on ERα.

  9. Membrane Estrogen and HER-2 Receptors in Human Breast Cancer

    DTIC Science & Technology

    2002-07-01

    glucocorticoid receptor : Is DNA binding dispensable? Cell, 93 : 487-490. 39.) Pietras, R. and Szego, C. (1975). Endometrial cell calcium and oestrogen action...the outer surfaces of isolated endometrial cells. Nature, 265:69-72. 47.) Pietras R. Szego C. (1979). Metabolic and proliferative responses to...uterine cAMP by estrogen within seconds 11 1975 Rapid endometrial cell calcium mobilization by estrogen 9 Corticosterone Binding to plasma membranes

  10. Human Colon Microbiota Transform Polycyclic Aromatic Hydrocarbons to Estrogenic Metabolites

    PubMed Central

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

    2005-01-01

    Ingestion is an important exposure route for polycyclic aromatic hydrocarbons (PAHs) to enter the human body. Although the formation of hazardous PAH metabolites by human biotransformation enzymes is well documented, nothing is known about the PAH transformation potency of human intestinal microbiota. Using a gastrointestinal simulator, we show that human intestinal microbiota can also bioactivate PAHs, more in particular to estrogenic metabolites. PAH compounds are not estrogenic, and indeed, stomach and small intestine digestions of 62.5 nmol naphthalene, phenanthrene, pyrene, and benzo(a)pyrene showed no estrogenic effects in the human estrogen receptor bioassay. In contrast, colon digests of these PAH compounds displayed estrogenicity, equivalent to 0.31, 2.14, 2.70, and 1.48 nmol 17α-ethynylestradiol (EE2), respectively. Inactivating the colon microbiota eliminated these estrogenic effects. Liquid chromatography–mass spectrometry analysis confirmed the microbial PAH transformation by the detection of PAH metabolites 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene in colon digests of pyrene and benzo(a)pyrene. Furthermore, we show that colon digests of a PAH-contaminated soil (simulated ingestion dose of 5 g/day) displayed estrogenic activity equivalent to 0.58 nmol EE2, whereas stomach or small intestine digests did not. Although the matrix in which PAHs are ingested may result in lower exposure concentrations in the gut, our results imply that the PAH bioactivation potency of colon microbiota is not eliminated by the presence of soil. Moreover, because PAH toxicity is also linked to estrogenicity of the compounds, the PAH bioactivation potency of colon microbiota suggests that current risk assessment may underestimate the risk from ingested PAHs. PMID:15626640

  11. Circulatory estrogen level protects against breast cancer in obese women.

    PubMed

    Suba, Zsuzsanna

    2013-05-01

    Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass. Obesity is associated with dysmetabolism and endangers the healthy equilibrium of sexual hormone-production and regular menstrual cycles in women, which are the prerequisites not only for reproductive capacity but also for somatic health. At the same time, literary data support that anovulatory infertility is a very strong risk for breast cancer in young women either with or without obesity. In the majority of premenopausal women, obesity associated insulin resistance is moderate and may be counteracted by their preserved circulatory estrogen level. Consequently, it is not obesity but rather the still sufficient estrogen-level, which may be protective against breast cancer in young adult females. In obese older women, never using hormone replacement therapy (HRT) the breast cancer risk is high, which is associated with their continuous estrogen loss and increasing insulin-resistance. By contrast, obese postmenopausal women using HRT, have a decreased risk for breast cancer as the protective effect of estrogen-substitution may counteract to their obesity associated systemic alterations. The revealed inverse correlation between circulatory estrogen-level and breast cancer risk in obese women should advance our understanding of breast cancer etiology and promotes primary prevention measures. New patents recommend various methods for the prevention and treatment of obesity

  12. Estrogen Effects on Cognitive and Synaptic Health Over the Lifecourse

    PubMed Central

    Hara, Yuko; Waters, Elizabeth M.; McEwen, Bruce S.; Morrison, John H.

    2015-01-01

    Estrogen facilitates higher cognitive functions by exerting effects on brain regions such as the prefrontal cortex and hippocampus. Estrogen induces spinogenesis and synaptogenesis in these two brain regions and also initiates a complex set of signal transduction pathways via estrogen receptors (ERs). Along with the classical genomic effects mediated by activation of ER α and ER β, there are membrane-bound ER α, ER β, and G protein-coupled estrogen receptor 1 (GPER1) that can mediate rapid nongenomic effects. All key ERs present throughout the body are also present in synapses of the hippocampus and prefrontal cortex. This review summarizes estrogen actions in the brain from the standpoint of their effects on synapse structure and function, noting also the synergistic role of progesterone. We first begin with a review of ER subtypes in the brain and how their abundance and distributions are altered with aging and estrogen loss (e.g., ovariectomy or menopause) in the rodent, monkey, and human brain. As there is much evidence that estrogen loss induced by menopause can exacerbate the effects of aging on cognitive functions, we then review the clinical trials of hormone replacement therapies and their effectiveness on cognitive symptoms experienced by women. Finally, we summarize studies carried out in nonhuman primate models of age- and menopause-related cognitive decline that are highly relevant for developing effective interventions for menopausal women. Together, we highlight a new understanding of how estrogen affects higher cognitive functions and synaptic health that go well beyond its effects on reproduction. PMID:26109339

  13. Circulatory Estrogen Level Protects Against Breast Cancer in Obese Women

    PubMed Central

    Suba, Zsuzsanna

    2013-01-01

    Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass. Obesity is associated with dysmetabolism and endangers the healthy equilibrium of sexual hormone-production and regular menstrual cycles in women, which are the prerequisites not only for reproductive capacity but also for somatic health. At the same time, literary data support that anovulatory infertility is a very strong risk for breast cancer in young women either with or without obesity. In the majority of premenopausal women, obesity associated insulin resistance is moderate and may be counteracted by their preserved circulatory estrogen level. Consequently, it is not obesity but rather the still sufficient estrogen-level, which may be protective against breast cancer in young adult females. In obese older women, never using hormone replacement therapy (HRT) the breast cancer risk is high, which is associated with their continuous estrogen loss and increasing insulin-resistance. By contrast, obese postmenopausal women using HRT, have a decreased risk for breast cancer as the protective effect of estrogen-substitution may counteract to their obesity associated systemic alterations. The revealed inverse correlation between circulatory estrogen-level and breast cancer risk in obese women should advance our understanding of breast cancer etiology and promotes primary prevention measures. New patents recommend various methods for the prevention and treatment of obesity

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

    PubMed

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

    2005-01-01

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

  15. Characterization and Consequences of Estrogen Receptor Exon Five Deletion.

    DTIC Science & Technology

    1997-08-01

    the assembly of an adhesion belt (whose contraction has been implicated in lumen formation during gland development) [17], and tight junctions...down regulation by gonadotropins. Molecular Endocrinology, 1997. 11: p. 172-182. 87. Kuiper , G., et al., Cloning of a novel estrogen receptor...and K. Korach, Editorial: A new actor in the estrogen receptor drama - enter ER-B3. Endocrinology, 1997. 138(3): p. 861-862. 90. Kuiper , G.G.J.M., et

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

    DTIC Science & Technology

    2005-06-01

    ER+ cell lines are sensitive to estrogen, we tested whether 17P3-estradiol can stimulate transcriptional activation of an estrogen- responsive...MSI in sporadic colon cancer is transcriptional silencing of the cDNA. Results show that MMR-proficient cells have hMLHI1 gene by methylation of the...three independent experiments.,0 14) 0 a) The asterisk indicates significantd frence (P • 0-05) from other mecan "- " - - values with student t tests

  17. Sex-Dependent Influence of Endogenous Estrogen in Pulmonary Hypertension

    PubMed Central

    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

  18. Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone

    DTIC Science & Technology

    2007-03-01

    and white. 14. ABSTRACT Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or...metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors are tracked in living mice by whole-body imaging, and...macrometastases or micrometastases are detected by intravital imaging or fluorescence microscopy. Tumor growth is estrogen dependent and required for

  19. Caffeine as an indicator of estrogenic activity in source water.

    PubMed

    Montagner, C C; Umbuzeiro, G A; Pasquini, C; Jardim, W F

    2014-08-01

    Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. In this work, the presence of caffeine has been correlated with the estrogenic activity of water samples measured using the BLYES assay. After testing 96 surface water samples, it was concluded that caffeine can be used to prioritize samples to be tested for estrogenic activity in water quality programs evaluating emerging contaminants with endocrine disruptor activity.

  20. SUMER: Solar Ultraviolet Measurements of Emitted Radiation

    NASA Technical Reports Server (NTRS)

    Wilhelm, K.; Axford, W. I.; Curdt, W.; Gabriel, A. H.; Grewing, M.; Huber, M. C. E.; Jordan, S. D.; Kuehne, M.; Lemaire, P.; Marsch, E.

    1992-01-01

    The experiment Solar Ultraviolet Measurements of Emitted Radiation (SUMER) is designed for the investigations of plasma flow characteristics, turbulence and wave motions, plasma densities and temperatures, structures and events associated with solar magnetic activity in the chromosphere, the transition zone and the corona. Specifically, SUMER will measure profiles and intensities of Extreme Ultraviolet (EUV) lines emitted in the solar atmosphere ranging from the upper chromosphere to the lower corona; determine line broadenings, spectral positions and Doppler shifts with high accuracy, provide stigmatic images of selected areas of the Sun in the EUV with high spatial, temporal and spectral resolution and obtain full images of the Sun and the inner corona in selectable EUV lines, corresponding to a temperature from 10,000 to more than 1,800,000 K.

  1. Vertical-Cavity Surface-Emitting Lasers

    NASA Astrophysics Data System (ADS)

    Wilmsen, Carl W.; Temkin, Henryk; Coldren, Larry A.

    2002-01-01

    1. Introduction to VCSELs L. A. Coldren, C. W. Wilmsen and H. Temkin; 2. Fundamental issues in VCSEL design L. A. Coldren and Eric R. Hegblom; 3. Enhancement of spontaneous emission in microcavities E. F. Schubert and N. E. J. Hunt; 4. Epitaxy of vertical-cavity lasers R. P. Schneider Jr and Y. H. Young; 5. Fabrication and performance of vertical-cavity surface-emitting lasers Kent D. Choquette and Kent Geib; 6. Polarization related properties of vertical cavity lasers Dmitri Kuksenkov and Henryk Temkin; 7. Visible light emitting vertical cavity lasers Robert L. Thornton; 8. Long-wavelength vertical-cavity lasers Dubrakovo I. Babic, Joachim Piprek and John E. Bowers; 9. Overview of VCSEL applications Richard C. Williamson; 10. Optical interconnection applications and required characteristics Kenichi Kasahara; 11. VCSEL-based fiber-optic data communications Kenneth Hahn and Kirk Giboney; 12. VCSEL-based smart pixels for free space optoelectronic processing C. W. Wilmsen.

  2. Ultrasonic Vocalizations Emitted by Flying Squirrels

    PubMed Central

    Murrant, Meghan N.; Bowman, Jeff; Garroway, Colin J.; Prinzen, Brian; Mayberry, Heather; Faure, Paul A.

    2013-01-01

    Anecdotal reports of ultrasound use by flying squirrels have existed for decades, yet there has been little detailed analysis of their vocalizations. Here we demonstrate that two species of flying squirrel emit ultrasonic vocalizations. We recorded vocalizations from northern (Glaucomys sabrinus) and southern (G. volans) flying squirrels calling in both the laboratory and at a field site in central Ontario, Canada. We demonstrate that flying squirrels produce ultrasonic emissions through recorded bursts of broadband noise and time-frequency structured frequency modulated (FM) vocalizations, some of which were purely ultrasonic. Squirrels emitted three types of ultrasonic calls in laboratory recordings and one type in the field. The variety of signals that were recorded suggest that flying squirrels may use ultrasonic vocalizations to transfer information. Thus, vocalizations may be an important, although still poorly understood, aspect of flying squirrel social biology. PMID:24009728

  3. Principles of phosphorescent organic light emitting devices.

    PubMed

    Minaev, Boris; Baryshnikov, Gleb; Agren, Hans

    2014-02-07

    Organic light-emitting device (OLED) technology has found numerous applications in the development of solid state lighting, flat panel displays and flexible screens. These applications are already commercialized in mobile phones and TV sets. White OLEDs are of especial importance for lighting; they now use multilayer combinations of organic and elementoorganic dyes which emit various colors in the red, green and blue parts of the visible spectrum. At the same time the stability of phosphorescent blue emitters is still a major challenge for OLED applications. In this review we highlight the basic principles and the main mechanisms behind phosphorescent light emission of various classes of photofunctional OLED materials, like organic polymers and oligomers, electron and hole transport molecules, elementoorganic complexes with heavy metal central ions, and clarify connections between the main features of electronic structure and the photo-physical properties of the phosphorescent OLED materials.

  4. Radioimmunotherapy with alpha-particle emitting radionuclides.

    PubMed

    Zalutsky, M R; Pozzi, O R

    2004-12-01

    An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides decaying by the emission of alpha-particles offer the possibility of matching the cell specific reactivity of monoclonal antibodies with radiation with a range of only a few cell diameters. Furthermore, alpha-particles have important biological advantages compared with external beam radiation and beta-particles including a higher biological effectiveness, which is nearly independent of oxygen concentration, dose rate and cell cycle position. In this review, the clinical settings most likely to benefit from alpha-particle radioimmunotherapy will be discussed. The current status of preclinical and clinical research with antibodies labeled with 3 promising alpha-particle emitting radionuclides - (213)Bi, (225)Ac, and (211)At - also will be summarized.

  5. Method of making organic light emitting devices

    SciTech Connect

    Shiang, Joseph John; Janora, Kevin Henry; Parthasarathy, Gautam; Cella, James Anthony; Chichak, Kelly Scott

    2011-03-22

    The present invention provides a method for the preparation of organic light-emitting devices comprising a bilayer structure made by forming a first film layer comprising an electroactive material and an INP precursor material, and exposing the first film layer to a radiation source under an inert atmosphere to generate an interpenetrating network polymer composition comprising the electroactive material. At least one additional layer is disposed on the reacted first film layer to complete the bilayer structure. The bilayer structure is comprised within an organic light-emitting device comprising standard features such as electrodes and optionally one or more additional layers serving as a bipolar emission layer, a hole injection layer, an electron injection layer, an electron transport layer, a hole transport layer, exciton-hole transporting layer, exciton-electron transporting layer, a hole transporting emission layer, or an electron transporting emission layer.

  6. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc).

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  7. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc).

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  8. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc)

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  9. Determining estrogenic activity in serum from ovariectomized rats treated with environmental compounds using an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc)

    EPA Science Inventory

    The use of cell-based assays to quantify low levels of estrogen in human serum is an accepted method. These assays are more sensitive but less specific than radioimmunoassays (RIA). Thus, we hypothesized that estrogen responsive T47D-KBluc cells would detect estrogenic activity i...

  10. Bioinspired Hybrid White Light-Emitting Diodes.

    PubMed

    Weber, Michael D; Niklaus, Lukas; Pröschel, Marlene; Coto, Pedro B; Sonnewald, Uwe; Costa, Rubén D

    2015-10-07

    The first bioinspired hybrid white-light-emitting diodes (bio-HLEDs) featuring protein cascade coatings are presented. For easy fabrication a new strategy to stabilize proteins in rubber-like material was developed. The synergy between the excellent features of fluorescent proteins and the easily processed rubber produces bio-HLEDs with less than 10% loss in luminous efficiency over 100 hours. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Safety of light emitting diodes in toys.

    PubMed

    Higlett, M P; O'Hagan, J B; Khazova, M

    2012-03-01

    Light emitting diodes (LEDs) are increasingly being used in toys. An assessment methodology is described for determining the accessible emission limits for the optical radiation from the toys, which takes account of expected use and reasonably foreseeable misuse of toys. Where data are available, it may be possible to assess the toy from the data sheet alone. If this information is not available, a simple measurement protocol is proposed.

  12. Surface emitting lasers with combined output

    NASA Technical Reports Server (NTRS)

    Carlin, Donald B. (Inventor)

    1990-01-01

    Surface emitting lasers are laterally aligned and coupled together and also have their light output signals combined. This results in greater phase and frequency coherency and narrower and reduced amplitude sidelobes. Preferably, not more than two lasers are longitudinally aligned along the same axis for still greater coherency compared with adding the light output signals of more than two longitudinally aligned lasers. The lasers can be of the DH-LOC type or of the QW type.

  13. Spontaneous radiation emitted by moving tethered systems

    NASA Technical Reports Server (NTRS)

    Dobrowolny, M.

    1986-01-01

    Some concepts related to radiation emitted by a large conductor moving through a magnetoplasma are outlined and referred to the case of long tethers. Some recent results of a theoretical calculation of Alfven wings, their structure and the power associated with are shown. How the problem of radiation from TSS or for any large conductor moving through a magnetoplasma should be approached is presented. The approach is that of the theory of antennas in plasmas.

  14. PULSE PROFILES FROM THERMALLY EMITTING NEUTRON STARS

    SciTech Connect

    Turolla, R.; Nobili, L.

    2013-05-10

    The problem of computing the pulse profiles from thermally emitting spots on the surface of a neutron star in general relativity is reconsidered. We show that it is possible to extend Beloborodov's approach to include (multiple) spots of finite size in different positions on the star surface. The results for the pulse profiles are expressed by comparatively simple analytical formulae which involve only elementary functions.

  15. Free and conjugated estrogens and androgens in stallion semen.

    PubMed

    Lemazurier, Emmanuel; Moslemi, Safa; Sourdaine, Pascal; Desjardins, Isabelle; Plainfosse, Bruno; Seralini, Gilles-Eric

    2002-02-01

    The steroid content of semen from a total of 11 mature fertile stallions was studied during two breeding seasons and one winter. The levels of free and conjugated substrates (testosterone and androstenedione), and products (estradiol and estrone), of aromatase were measured by radioimmunoassay with a validated method. The results were seasonally and monthly highly variable with characteristic peaks. The concentrations of free and conjugated estrogens were always higher in the gel-free ejaculate than in the gel except in one subfertile stallion used as comparison. Furthermore, the steroid production and the maximal resulting aromatase activity, estimated by the estrogens/androgens ratio, peaked in April-May and June. The breeding season (spring and summer) presents a clear estrogenic profile with estrogens/androgens ratios higher in contrast to the nonbreeding period (autumn and winter). The involvement of estrogens in the regulation of reproduction and equine spermatogenesis is discussed, and estrogens production and thus equine aromatase is proposed as a strong marker of testicular endocrine function.

  16. Interlinking of hypoxia and estrogen in thyroid cancer progression.

    PubMed

    Rajoria, S; Hanly, E; Nicolini, A; George, A L; Geliebter, J; Shin, E J; Suriano, R; Carpi, A; Tiwari, R K

    2014-01-01

    Estrogen aids in neo-vascularization of various tumors during hypoxic conditions, however the role of estrogen within the hypoxic environment of thyroid cancer is not known. In a series of experimentations, using human thyroid cancer cells, we observed that estrogen and hypoxia modulate the hypoxia inducible factor-1 (HIF-1) signaling which is abrogated by the anti-estrogen fulvestrant and the HIF-1 inhibitor YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole). Furthermore, we found that the conditioned medium from estrogen treated thyroid cancer cells lead to enhanced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs) which is abrogated by HIF-1 inhibitor. These findings, in addition to our previous and other scientific literature data, lead us to conclude that estrogen and hypoxia are interlinked in thyroid cancer and can equally modulate epithelial-endothelial cell interactions by mediating key cellular, metabolic and molecular processes of thyroid cancer progression. We believe that the hormonal component and cellular adaptation to oxygen tension of cancer cells are functionally equivalent with a cellular transition that can be exploited clinically for a combinational approach for thyroid cancer treatment involving antiestrogens as well as anti-hypoxic agents.

  17. Estrogen Biology: New Insights into GPER Function and Clinical Opportunities

    PubMed Central

    Prossnitz, Eric R.; Barton, Matthias

    2014-01-01

    Estrogens play an important role in the regulation of normal physiology, aging and many disease states. Although the nuclear estrogen receptors have classically been described to function as ligand-activated transcription factors mediating genomic effects in hormonally regulated tissues, more recent studies reveal that estrogens also mediate rapid signaling events traditionally associated with G protein-coupled receptors. The G protein-coupled estrogen receptor GPER (formerly GPR30) has now become recognized as a major mediator of estrogen’s rapid cellular effects throughout the body. With the discovery of selective synthetic ligands for GPER, both agonists and antagonists, as well as the use of GPER knockout mice, significant advances have been made in our understanding of GPER function at the cellular, tissue and organismal levels. In many instances, the protective/beneficial effects of estrogen are mimicked by selective GPER agonism and are absent or reduced in GPER knockout mice, suggesting an essential or at least parallel role for GPER in the actions of estrogen. In this review, we will discuss recent advances and our current understanding of the role of GPER and certain drugs such as SERMs and SERDs in physiology and disease. We will also highlight novel opportunities for clinical development towards GPER-targeted therapeutics, for molecular imaging, as well as for theranostic approaches and personalized medicine. PMID:24530924

  18. Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

    PubMed

    Xin, D; Wang, H; Yang, J; Su, Y-F; Fan, G-W; Wang, Y-F; Zhu, Y; Gao, X-M

    2010-02-01

    The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

  19. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens.

    PubMed

    Boué, Stephen M; Wiese, Thomas E; Nehls, Suzanne; Burow, Matthew E; Elliott, Steven; Carter-Wientjes, Carol H; Shih, Betty Y; McLachlan, John A; Cleveland, Thomas E

    2003-04-09

    Seven legume extracts containing phytoestrogens were analyzed for estrogenic activity. Methanol extracts were prepared from soybean (Glycine max L.), green bean (Phaseolus vulgaris L.), alfalfa sprout (Medicago sativa L.), mung bean sprout (Vigna radiata L.), kudzu root (Pueraria lobata L.), and red clover blossom and red clover sprout (Trifolium pratense L.). Extracts of kudzu root and red clover blossom showed significant competitive binding to estrogen receptor beta (ERbeta). Estrogenic activity was determined using an estrogen-dependent MCF-7 breast cancer cell proliferation assay. Kudzu root, red clover blossom and sprout, mung bean sprout, and alfalfa sprout extracts displayed increased cell proliferation above levels observed with estradiol. The pure estrogen antagonist, ICI 182,780, suppressed cell proliferation induced by the extracts, suggesting an ER-related signaling pathway was involved. The ER subtype-selective activities of legume extracts were examined using transiently transfected human embryonic kidney (HEK 293) cells. All seven of the extracts exhibited preferential agonist activity toward ERbeta. Using HPLC to collect fractions and MCF-7 cell proliferation, the active components in kudzu root extract were determined to be the isoflavones puerarin, daidzin, genistin, daidzein, and genistein. These results show that several legumes are a source of phytoestrogens with high levels of estrogenic activity.

  20. Xenoestrogens are potent activators of nongenomic estrogenic responses

    PubMed Central

    Watson, Cheryl S.; Bulayeva, Nataliya N.; Wozniak, Ann L.; Alyea, Rebecca A.

    2007-01-01

    Studies of the nuclear transcriptional regulatory activities of nonphysiological estrogens have not explained their actions in mediating endocrine disruption in animals and humans at the low concentrations widespread in the environment. However, xenoestrogens have rarely been tested for their ability to participate in the plethora of nongenomic steroid signaling pathways elucidated over the last several years. Here we review what is known about such responses in comparison to our recent evidence that xenoestrogens can rapidly and potently elicit signaling through nongenomic pathways culminating in functional endpoints. Both estradiol (E2) and compounds representing various classes of xenoestrogens (diethylstilbestrol, coumestrol, bisphenol A, DDE, nonylphenol, endosulfan, and dieldrin) act via a membrane version of the estrogen receptor-α on pituitary cells, and can provoke Ca++ influx via L-type channels, leading to prolactin (PRL) secretion. These hormones and mimetics can also cause the oscillating activation of extracellular regulated kinases (ERKs). However, individual estrogen mimetics differ in their potency and temporal phasing of these activations compared to each other and to E2. It is perhaps in these ways that they disrupt some endocrine functions when acting in combination with physiological estrogens. Our quantitative assays allow comparison of these outcomes for each mimetic, and let us build a detailed picture of alternative signaling pathway usage. Such an understanding should allow us to determine the estrogenic or antiestrogenic potential of different types of xenoestrogens, and help us to develop strategies for preventing xenoestrogenic disruption of estrogen action in many tissues. PMID:17174995

  1. A novel mechanism of non-feminizing estrogens in neuroprotection.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Covey, Douglas F; Simpkins, James W

    2016-11-03

    Estrogens are potent and efficacious neuroprotectants both in vitro and in vivo in a variety of models of neurotoxicity. We determined the structural requirements for neuroprotection in an in vitro assay using a panel of >70 novel estratrienes, synthesized to reduce or eliminate estrogen receptor (ER) binding. We observed that neuroprotection could be enhanced by as much as 200-fold through modifications that positioned a large bulky group at the C2 or C4 position of the phenolic A ring of the estratriene. Further, substitutions on the B, C or D rings either reduced or did not markedly change neuroprotection. Collectively, there was a negative correlation between binding to ERs and neuroprotection with the more potent compounds showing no ER binding. In an in vivo model for neuroprotection, transient cerebral ischemia, efficacious compounds were active in protection of brain tissue from this pro-oxidant insult. We demonstrated that these non-feminizing estrogens engage in a redox cycle with glutathione, using the hexose monophosphate shunt to apply cytosolic reducing potential to cellular membranes. Together, these results demonstrate that non-feminizing estrogens are neuroprotective and protect brain from the induction of ischemic- and Alzheimer's disease (AD)-like neuropathology in an animal model. These features of non-feminizing estrogens make them attractive compounds for assessment of efficacy in AD and stroke, as they are not expected to show the side effects of chronic estrogen therapy that are mediated by ER actions in the liver, uterus and breast.

  2. Fate and removal of estrogens in municipal wastewater.

    PubMed

    Racz, LeeAnn; Goel, Ramesh K

    2010-01-01

    Natural and synthetic estrogens are some of the most potent endocrine disrupting compounds found in municipal wastewater. Much research has been conducted on the source and fate of estrogens in wastewater treatment plants. Sorption and biodegradation are the primary removal mechanisms for estrogens in activated sludge systems, which are widely used biological treatment techniques for municipal wastewater treatment. However, when removal of estrogens in a wastewater treatment plant is incomplete, these compounds enter the environment through wastewater discharges or waste activated sludge at concentrations that can cause endocrine-reproductive system alterations in birds, reptiles and mammals. Therefore, studies have also focused on potential advanced treatment technologies with the aim of removing the compounds before discharging wastewater effluent or disposing waste sludge. This review discusses the physiological effects of these estrogens and the degree of problems estrogens pose as they enter the wastewater stream. Thereafter, this review also analyzes their fate in wastewater treatment systems and how they may reach drinking water sources. Furthermore, this review includes a discussion on various treatment technologies being investigated and future research trends for this pressing environmental issue.

  3. Regional differences in the prostate of the neonatally estrogenized mouse

    SciTech Connect

    Pylkkaenen, L.S.; Santti, R.; Newbold, R.; McLachlan, J.A. )

    1991-01-01

    Neonatal estrogenization of the mouse with diethylstilbestrol resulted in time-of-exposure and dose-dependent inhibition of the growth of the prostatic lobes observed at the age of 2 mon. The critical time was the days 1-6 of postnatal life. In neonatally estrogenized (neoDES) mice, responses to 5 alpha-dihydrotestosterone in terms of nuclear 3H-thymidine labelling were altered concomitantly with the inhibition of growth and were in accordance with changes in the relative volumes of epithelium, glandular lumina, and interacinar stroma. Secondary estrogen treatment of neoDES mice with 17 beta-estradiol did not increase 3H-thymidine labelling in the prostate of control or neoDES mice. However, it induced squamous epithelial metaplasia in periurethral collecting ducts and proximal parts of coagulating glands of neoDES animals. In control mice only slight epithelial hyperplasia could be observed after similar treatment. Estrogen receptors, located immunocytochemically in nuclei of stromal cell, corresponded with the sites of increased estrogen sensitivity, observed as metaplastic transformation. When the neoDES animals aged, epithelial hyperplasia and dysplasia could be observed at distinct prostatic sites, ie, the periurethral collecting ducts and the coagulating glands and periurethral glands, and stromal inflammation become more extensive. Almost identical location of the epithelial changes and the altered estrogen response is suggestive of causal relationship.

  4. Estrogen modulates mesenchyme-epidermis interactions in the adult nipple.

    PubMed

    Wu, Hsing-Jung; Oh, Ji Won; Spandau, Dan F; Tholpady, Sunil; Diaz, Jesus; Schroeder, Laura J; Offutt, Carlos D; Glick, Adam B; Plikus, Maksim V; Koyama, Sachiko; Foley, John

    2017-04-15

    Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, the specific pathways involved remain to be identified. By recombining cells from the ventral skin of the K14-PTHrP transgenic mice [which overexpress parathyroid hormone-related protein (PTHrP) in their developing epidermis and mammary glands] with those from wild type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially expressed transcripts that are involved in WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling. Considering that some of the growth factor pathways are targets for estrogen regulation, we examined the upstream role of this hormone in maintaining the nipple. Ablation of estrogen signaling through ovariectomy produced nipples with abnormally thin epidermis, and we identified TGFβ as a negatively regulated target of estrogen signaling. Estrogen treatment represses Tgfβ1 at the transcript and protein levels in K14-PTHrP fibroblasts in vitro, while ovariectomy increases Tgfb1 levels in K14-PTHrP ventral skin. Moreover, ectopic delivery of Tgfβ1 protein into nipple connective tissue reduced epidermal proliferation. Taken together, these results show that specialized nipple epidermis is maintained by estrogen-induced repression of TGFβ signaling in the local fibroblasts. © 2017. Published by The Company of Biologists Ltd.

  5. Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata.

    PubMed

    Wallace, M L; Smoller, B R

    1998-04-01

    In some situations, hair growth is under hormonal control. Androgenic alopecia is characterized as hormonally driven hair loss in the genetically susceptible individual. During pregnancy, hair growth is increased, as estrogen appears to prolong the anagen phase. However, postpartum hair loss is common, and thus may be related to a decrease in estrogen and or progesterone levels. In contrast, alopecia areata is not considered to be under hormonal control. We compared the immunohistochemical staining characteristics of nine cases of androgenic alopecia with those of 13 cases of alopecia areata using estrogen receptor (ER) and progesterone receptor (PR) markers. Estrogen receptor positivity in the dermal papilla was found in only two of 13 cases of alopecia areata, and in one case of androgenic alopecia. Six of 13 cases of alopecia areata demonstrated focal reactivity with the progesterone marker in a similar location, while only three cases of androgenic alopecia showed positivity with this antibody. Examination of the perifollicular fibroblasts for the ER marker showed positivity in one of 13 cases of alopecia areata and in one case of androgenic alopecia. Two cases of alopecia areata revealed focal staining in this location for the PR marker, while the androgenic alopecia cases failed to stain. These results indicate that estrogen and progesterone receptor expression is not significantly increased or decreased in the pilosebaceous units or surrounding mesenchymal cells in androgenic alopecia vs. alopecia areata. Therefore, an indirectly mediated process of estrogen/progesterone control on hair growth and development must be presumed for cases of androgenic alopecia.

  6. Effects of estrogen on growth plate senescence and epiphyseal fusion.

    PubMed

    Weise, M; De-Levi, S; Barnes, K M; Gafni, R I; Abad, V; Baron, J

    2001-06-05

    Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes this phenomenon. Juvenile ovariectomized female rabbits received either 70 microg/kg estradiol cypionate or vehicle i.m. once a week. Growth plates from the proximal tibia, distal tibia, and distal femur were analyzed after 2, 4, 6, or 8 weeks of treatment. In vehicle-treated animals, there was a gradual senescent decline in tibial growth rate, rate of chondrocyte proliferation, growth plate height, number of proliferative chondrocytes, number of hypertrophic chondrocytes, size of terminal hypertrophic chondrocytes, and column density. Estrogen treatment accelerated the senescent decline in all of these parameters. In senescent growth plates, epiphyseal fusion was observed to be an abrupt event in which all remaining chondrocytes were rapidly replaced by bone elements. Fusion occurred when the rate of chondrocyte proliferation approached zero. Estrogen caused this proliferative exhaustion and fusion to occur earlier. Our data suggest that (i) epiphyseal fusion is triggered when the proliferative potential of growth plate chondrocytes is exhausted; and (ii) estrogen does not induce growth plate ossification directly; instead, estrogen accelerates the programmed senescence of the growth plate, thus causing earlier proliferative exhaustion and consequently earlier fusion.

  7. Behavioral effects of brain-derived estrogens in birds

    PubMed Central

    Balthazart, Jacques; Taziaux, Melanie; Holloway, Kevin; Ball, Gregory F.; Cornil, Charlotte A.

    2012-01-01

    In birds as in other vertebrates, estrogens produced in the brain by aromatization of testosterone have widespread effects on behavior. Research conducted with male Japanese quail demonstrates that effects of brain estrogens on all aspects of sexual behavior, including appetitive and consummatory components as well as learned aspects, can be divided in two main classes based on their time-course. First, estrogens via binding to estrogen receptors regulate the transcription of a variety of genes involved primarily in neurotransmission. These neurochemical effects ultimately result in the activation of male copulatory behavior after a latency of a few days. Correlatively, testosterone and its aromatized metabolites increase the transcription of the aromatase mRNA resulting in an increased concentration and activity of the enzyme that actually precedes behavioral activation. Second, recent studies with quail demonstrate that brain aromatase activity (AA) can also be modulated within minutes by phosphorylation processes regulated by changes in intracellular calcium concentration such as those associated with glutamatergic neurotransmission. The rapid up or down-regulations of brain estrogen concentration presumably resulting from these changes in AA affect, by non-genomic mechanisms with relatively short latencies (frequency increases or decreases respectively within 10–15 min), the expression of male sexual behavior in quail and also in rodents. Brain estrogens thus affect behavior on different time-scales by genomic and non-genomic mechanisms similar to those of a hormone or a neurotransmitter. PMID:19456326

  8. Molecular cloning, characterization, and chromosome mapping of reptilian estrogen receptors.

    PubMed

    Katsu, Yoshinao; Matsubara, Kazumi; Kohno, Satomi; Matsuda, Yoichi; Toriba, Michihisa; Oka, Kaori; Guillette, Louis J; Ohta, Yasuhiko; Iguchi, Taisen

    2010-12-01

    In many vertebrates, steroid hormones are essential for ovarian differentiation during a critical developmental stage as well as promoting the growth and differentiation of the adult female reproductive system. Although studies have been extensively conducted in mammals and a few fish, amphibians, and bird species, the molecular mechanisms of sex steroid hormone (estrogens) action have been poorly examined in reptiles. Here, we evaluate hormone receptor and ligand interactions in two species of snake, the Okinawa habu (Protobothrops flavoviridis, Viperidae) and the Japanese four-striped rat snake (Elaphe quadrivirgata, Colubridae) after the isolation of cDNAs encoding estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Using a transient transfection assay with mammalian cells, the transcriptional activity of reptilian (Okinawa habu, Japanese four-striped rat snake, American alligator, and Florida red-belly freshwater turtle) ESR1 and ESR2 was examined. All ESR proteins displayed estrogen-dependent activation of transcription via an estrogen-response element-containing promoter; however, the responsiveness to various estrogens was different. Further, we determined the chromosomal locations of the snake steroid hormone receptor genes. ESR1 and ESR2 genes were localized to the short and long arms of chromosome 1, respectively, whereas androgen receptor was localized to a pair of microchromosomes in the two snake species examined. These data provide basic tools that allow future studies examining receptor-ligand interactions and steroid endocrinology in snakes and also expands our knowledge of sex steroid hormone receptor evolution.

  9. Molecular Cloning, Characterization, and Chromosome Mapping of Reptilian Estrogen Receptors

    PubMed Central

    Katsu, Yoshinao; Matsubara, Kazumi; Kohno, Satomi; Matsuda, Yoichi; Toriba, Michihisa; Oka, Kaori; Guillette, Louis J.; Ohta, Yasuhiko; Iguchi, Taisen

    2010-01-01

    In many vertebrates, steroid hormones are essential for ovarian differentiation during a critical developmental stage as well as promoting the growth and differentiation of the adult female reproductive system. Although studies have been extensively conducted in mammals and a few fish, amphibians, and bird species, the molecular mechanisms of sex steroid hormone (estrogens) action have been poorly examined in reptiles. Here, we evaluate hormone receptor and ligand interactions in two species of snake, the Okinawa habu (Protobothrops flavoviridis, Viperidae) and the Japanese four-striped rat snake (Elaphe quadrivirgata, Colubridae) after the isolation of cDNAs encoding estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Using a transient transfection assay with mammalian cells, the transcriptional activity of reptilian (Okinawa habu, Japanese four-striped rat snake, American alligator, and Florida red-belly freshwater turtle) ESR1 and ESR2 was examined. All ESR proteins displayed estrogen-dependent activation of transcription via an estrogen-response element-containing promoter; however, the responsiveness to various estrogens was different. Further, we determined the chromosomal locations of the snake steroid hormone receptor genes. ESR1 and ESR2 genes were localized to the short and long arms of chromosome 1, respectively, whereas androgen receptor was localized to a pair of microchromosomes in the two snake species examined. These data provide basic tools that allow future studies examining receptor-ligand interactions and steroid endocrinology in snakes and also expands our knowledge of sex steroid hormone receptor evolution. PMID:20926589

  10. Phytochemicals Targeting Estrogen Receptors: Beneficial Rather Than Adverse Effects?

    PubMed

    Lecomte, Sylvain; Demay, Florence; Ferrière, François; Pakdel, Farzad

    2017-06-28

    In mammals, the effects of estrogen are mainly mediated by two different estrogen receptors, ERα and ERβ. These proteins are members of the nuclear receptor family, characterized by distinct structural and functional domains, and participate in the regulation of different biological processes, including cell growth, survival and differentiation. The two estrogen receptor (ER) subtypes are generated from two distinct genes and have partially distinct expression patterns. Their activities are modulated differently by a range of natural and synthetic ligands. Some of these ligands show agonistic or antagonistic effects depending on ER subtype and are described as selective ER modulators (SERMs). Accordingly, a few phytochemicals, called phytoestrogens, which are synthesized from plants and vegetables, show low estrogenic activity or anti-estrogenic activity with potentially anti-proliferative effects that offer nutraceutical or pharmacological advantages. These compounds may be used as hormonal substitutes or as complements in breast cancer treatments. In this review, we discuss and summarize the in vitro and in vivo effects of certain phytoestrogens and their potential roles in the interaction with estrogen receptors.

  11. Does antimatter emit a new light?

    NASA Astrophysics Data System (ADS)

    Santilli, Ruggero Maria

    1997-08-01

    Contemporary theories of antimatter have a number of insufficiencies which stimulated the recent construction of the new isodual theory based on a certain anti-isomorphic map of all (classical and quantum) formulations of matter called isoduality. In this note we show that the isodual theory predicts that antimatter emits a new light, called isodual light, which can be distinguished from the ordinary light emitted by matter via gravitational interactions (only). In particular, the isodual theory predicts that all stable antiparticles such as the isodual photon, the positron and the antiproton experience antigravity in the field of matter (defined as the reversal of the sign of the curvature tensor). The antihydrogen atom is therefore predicted to: experience antigravity in the field of Earth; emit the isodual photon; and have the same spectroscopy of the hydrogen atom, although subjected to an anti-isomorphic isodual map. In this note we also show that the isodual theory predicts that bound states of elementary particles and antiparticles (such as the positronium) experience ordinary gravitation in both fields of matter and antimatter, thus bypassing known objections against antigravity. A number of intriguing and fundamental, open theoretical and experimental problems of “the new physics of antimatter” are pointed out.

  12. Organic Polymer Light Emitting Display for Digital Mammography

    DTIC Science & Technology

    2003-03-01

    J . Gruener, R.N. Marks, R.H. Friend, S.C. Moratti and A.B. Holmes, " Light - Emitting Diodes Fabricated with Conjugated ...surprised when a group at Cambridge University (U.K.) demonstrated the first light - emitting plastic device - the organic polymer light - emitting diode (OLED... Polymers - Recent Progress," Synthetic Metals, 67, 3 (1994). 2. J . Kido, M. Kimura, and K. Nagai, "Multilayer White Light - Emitting

  13. Histone methylase MLL1 and MLL3 coordinate with estrogen receptors in estrogen-mediated HOXB9 expression

    PubMed Central

    Ansari, Khairul I.; Shrestha, Bishakha; Hussain, Imran; Kasiri, Sahba; Mandal, Subhrangsu S.

    2011-01-01

    Homeobox gene HOXB9 is a critical player in development of mammary gland and sternum and in regulation of Renin which is closely linked with blood pressure control. Our studies demonstrated that HOXB9 gene is transcriptionally regulated by estrogen (E2). HOXB9 promoter contains several estrogen-response elements (ERE). Reporter assay based experiments demonstrated that HOXB9 promoter EREs are estrogen-responsive. Estrogen receptors ERα and ERβ are essential for E2-mediated transcriptional activation of HOXB9. Chromatin immuno-precipitation assay demonstrated that ERs bind to HOXB9 EREs as a function of E2. Similarly, histone methylases MLL1 and MLL3 also bind to HOXB9 EREs and play critical role in E2-mediated transcriptional activation of HOXB9. Overall, our studies demonstrated that HOXB9 is an E2-responsive gene and ERs coordinate with MLL1 and MLL3 in E2-mediated transcriptional regulation of HOXB9. PMID:21428455

  14. Analysis of 3D models of octopus estrogen receptor with estradiol: evidence for steric clashes that prevent estrogen binding.

    PubMed

    Baker, Michael E; Chandsawangbhuwana, Charlie

    2007-09-28

    Relatives of the vertebrate estrogen receptor (ER) are found in Aplysia californica, Octopus vulgaris, Thais clavigera, and Marisa cornuarietis. Unlike vertebrate ERs, invertebrate ERs are constitutively active and do not bind estradiol. To investigate the molecular basis of the absence of estrogen binding, we constructed a 3D model of the putative steroid-binding domain on octopus ER. Our 3D model indicates that binding of estradiol to octopus ER is prevented by steric clashes between estradiol and amino acids in the steroid-binding pocket. In this respect, octopus ER resembles vertebrate estrogen-related receptors (ERR), which have a ligand-binding pocket that cannot accommodate estradiol. Like ERR, octopus ER also may have the activation function 2 domain (AF2) in a configuration that can bind to coactivators in the absence of estrogens, which would explain constitutive activity of octopus ER.

  15. Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats.

    PubMed

    Mazzucco, C A; Lieblich, S E; Bingham, B I; Williamson, M A; Viau, V; Galea, L A M

    2006-09-15

    This study investigated the involvement of estrogen receptors alpha and beta in estradiol-induced enhancement of hippocampal neurogenesis in the adult female rat. Subtype selective estrogen receptor agonists, propyl-pyrazole triol (estrogen receptor alpha agonist) and diarylpropionitrile (estrogen receptor beta agonist) were examined for each receptor's contribution, individual and cooperative, for estradiol-enhanced hippocampal cell proliferation. Estradiol increases hippocampal cell proliferation within 4 h [Ormerod BK, Lee TT, Galea LA (2003) Estradiol initially enhances but subsequently suppresses (via adrenal steroids) granule cell proliferation in the dentate gyrus of adult female rats. J Neurobiol 55:247-260]. Therefore, animals received s.c. injections of estradiol (10 microg), propyl-pyrazole triol and diarylpropionitrile alone (1.25, 2.5, 5.0 mg/0.1 ml dimethylsulfoxide) or in combination (2.5 mg propyl-pyrazole triol+2.5 mg diarylpropionitrile/0.1 ml dimethylsulfoxide) and 4 h later received an i.p. injection of the cell synthesis marker, bromodeoxyuridine (200 mg/kg). Diarylpropionitrile enhanced cell proliferation at all three administered doses (1.25 mg, P<0.008; 2.5 mg, P<0.003; 5 mg, P<0.005), whereas propyl-pyrazole triol significantly increased cell proliferation (P<0.0002) only at the dose of 2.5 mg. Our results demonstrate both estrogen receptor alpha and estrogen receptor beta are individually involved in estradiol-enhanced cell proliferation. Furthermore both estrogen receptor alpha and estrogen receptor beta mRNA was found co-localized with Ki-67 expression in the hippocampus albeit at low levels, indicating a potential direct influence of each receptor subtype on progenitor cells and their progeny. Dual receptor activation resulted in reduced levels of cell proliferation, supporting previous studies suggesting that estrogen receptor alpha and estrogen receptor beta may modulate each other's activity. Our results also suggest that a component

  16. Evaluation of estrogenic activity in diets for experimental animals using in vitro assay.

    PubMed

    Kato, Hideo; Iwata, Toshio; Katsu, Yoshinao; Watanabe, Hajime; Ohta, Yasuhiko; Iguchi, Taisen

    2004-03-10

    We used a modified yeast-based human estrogen receptor alpha (ER alpha) bioassay to determine the estrogenic activity in 22 kinds of diets for experimental animals. The estrogenic activity of each diet was reevaluated by comparison with a calibration curve of 17 beta-estradiol. Almost all of the diets had estrogenic activity. The diets for rabbits and guinea pigs had the highest estrogenic activity compared to any other diets, including those for rats and mice. Estrogenic activity was found in dried skim milk, fishmeal, soybean meal, and alfalfa meal. In the NIH-07 diet opened for the ingredients, estrogenic activity was nearly all derived from the alfalfa meal. Multiple assays were performed to evaluate potential seasonal variations in the estrogenic potency in the raw materials of the rat and mouse diets. We found that the estrogenic activity in these raw materials changed throughout the year.

  17. Passive secondary biological treatment systems reduce estrogens in dairy shed effluent.

    PubMed

    Gadd, Jennifer B; Northcott, Grant L; Tremblay, Louis A

    2010-10-01

    Steroid estrogens are found at high concentrations in untreated dairy shed effluents. Reduction of estrogenic activity and steroid estrogen concentrations was assessed in two systems used to treat dairy shed effluents: the two-pond system and the advanced pond system. Both include anaerobic and aerobic treatment stages. Samples of effluent were collected from the systems and analyzed for free estrogens, conjugated estrogens and total estrogenic activity using E-Screen assay. Both systems showed increases of up to 8000% in aqueous free estrogens and estrogenic activity after anaerobic treatment, followed by decreases after aerobic treatment (36-83%). The complete systems decreased total steroid estrogen concentrations by 50-100% and estrogen activity by 62-100%, with little difference between systems. Removal rates were lower in winter for both systems. Final effluents from the advanced pond system contained total estrogens at <15-1400 ng/L and estrogenic activity at 3.2-43 ng/L. Final effluent from the two-pond system contained total estrogens at <15-300 ng/L and estrogenic activity at 3.3-25 ng/L. At times the final effluent EEQs exceeded guideline values for protection of freshwater fish and suggest further treatment may be required.

  18. Occurrence of selected estrogenic compounds and estrogenic activity in surface water and sediment of Langat River (Malaysia).

    PubMed

    Praveena, Sarva Mangala; Lui, Tang Seok; Hamin, Nur'Aqilah; Razak, Siti Quistina Noorain Abdul; Aris, Ahmad Zaharin

    2016-07-01

    The occurrence and estrogenic activities of steroid estrogens, such as the natural estrone (E1), 17β estradiol (E2), and estriol (E3), as well as the synthetic 17α-ethynylestradiol (EE2), were investigated in eight sampling points along the Langat River (Malaysia). Surface water samples were collected at 0.5 m and surface sediment 0-5 cm from the river surface. Instrument analysis of steroid estrogens was determined by UPLC-ESI-MS with an ultra-performance liquid chromatograph (Perkin Elmer FX15) coupled to a Q Trap function mass spectrophotometer (model 3200: AB Sciex). Steroid estrogen concentrations were higher in the Langat River sediments than those in its surface water. In surface water, E1 was not detected in any sampling point, E2 was only detected in two midstream sampling points (range 0-0.004 ng/L), E3 in three sampling points (range 0-0.002 ng/L), and EE2 in four sampling points (range 0-0.02 ng/L). E1 and E2 were detected in sediments from all sampling points, E3 in five sampling points, while EE2 only in one midstream sample (3.29E-4 ng/g). Sewage treatment plants, farming waste, and agricultural activities particularly present midstream and downstream were identified as potential sources of estrogens. Estrogenic activity expressed as estradiol equivalents (EEQs) was below 1 ng/L in all samples for both surface water and sediment, indicating therefore a low potential estrogenic risk to the aquatic environment. Although the health risks are still uncertain for drinking water consumers exposed to low levels of steroid estrogen concentrations, Langat River water is unacceptable for direct drinking purposes without treatment. Further studies of endocrine disruptors in Malaysian waters are highly recommended.

  19. Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor: predictions across species.

    PubMed Central

    Tong, W; Perkins, R; Strelitz, R; Collantes, E R; Keenan, S; Welsh, W J; Branham, W S; Sheehan, D M

    1997-01-01

    The recognition of adverse effects due to environmental endocrine disruptors in humans and wildlife has focused attention on the need for predictive tools to select the most likely estrogenic chemicals from a very large number of chemicals for subsequent screening and/or testing for potential environmental toxicity. A three-dimensional quantitative structure-activity relationship (QSAR) model using comparative molecular field analysis (CoMFA) was constructed based on relative binding affinity (RBA) data from an estrogen receptor (ER) binding assay using calf uterine cytosol. The model demonstrated significant correlation of the calculated steric and electrostatic fields with RBA and yielded predictions that agreed well with experimental values over the entire range of RBA values. Analysis of the CoMFA three-dimensional contour plots revealed a consistent picture of the structural features that are largely responsible for the observed variations in RBA. Importantly, we established a correlation between the predicted RBA values for calf ER and their actual RBA values for human ER. These findings suggest a means to begin to construct a more comprehensive estrogen knowledge base by combining RBA assay data from multiple species in 3D-QSAR based predictive models, which could then be used to screen untested chemicals for their potential to bind to the ER. Another QSAR model was developed based on classical physicochemical descriptors generated using the CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) program. The predictive ability of the CoMFA model was superior to the corresponding CODESSA model. Images Figure 2. Figure 3. Figure 4. Figure 5. PMID:9353176

  20. Molecular Characterization of a B-ring Unsaturated Estrogen: Implications for Conjugated Equine Estrogen Components of Premarin

    PubMed Central

    Hsieh, Robert W.; Rajan, Shyamala S.; Sharma, Sanjay K.; Greene, Geoffrey L.

    2008-01-01

    Conjugated equine estrogens (CEEs) are routinely used for hormone replacement therapy (HRT), making it important to understand the activities of individual estrogenic components. Although 17β-estradiol (17β-E2), the most potent estrogen in CEE, has been extensively characterized, the actions of nine additional less potent estrogens are not well understood. Structural differences between CEEs and 17β-E2 result in altered interactions with the two estrogen receptors (ERα and ERβ) and different biological activities. To better understand these interactions, we have determined the crystal structure of the CEE analog, 17β-methyl-17α-dihydroequilenin (NCI 122), in complex with the ERα ligand-binding domain and a peptide from the glucocorticoid receptor-interacting protein 1 (GRIP1) coactivator. NCI 122 has chemical properties, including an unsaturated B-ring and 17α-hydroxyl group, which are shared with some of the estrogens found in CEEs. Structural analysis of the NCI 122-ERα LBD-GRIP1 complex, combined with biochemical and cell-based comparisons of CEE components, suggests that factors such as decreased ligand flexibility, decreased ligand hydrophobicity and loss of a hydrogen bond between the 17-hydroxyl group and His524, contribute significantly to the reduced potency of CEEs on ERα. PMID:17949766