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Sample records for 17-beta estradiol e2

  1. Diagnosis-specific serum 17 beta-estradiol (E2) upper limits for treatment with menotropins using a 125I direct E2 assay.

    PubMed

    Haning, R V; Boehnlein, L M; Carlson, I H; Kuzma, D L; Zweibel, W J

    1984-12-01

    Statistical evaluation of 133 cycles of induction of ovulation using generalized linear models demonstrated that the occurrence and severity of ovarian hyperstimulation was influenced by the serum 17 beta-estradiol (E2) concentration (P less than 0.001), conception (P less than 0.001), and the endocrinologic diagnosis, polycystic ovary syndrome (PCO) or hypothalamic amenorrhea (HA) (P less than 0.01). When menotropins were administered between 5:00 P.M. and 8:00 P.M. and blood was drawn at 8:00 A.M., an upper limit for serum E2 in patients with HA of 2417 pg/ml or an upper limit for patients with PCO of 3778 pg/ml gave an approximate 5% risk of severe ovarian hyperstimulation in conception cycles and a 1.3% risk of severe hyperstimulation in nonconception cycles. Comparison of our E2 radioimmunoassay involving extraction and chromatography to the Pantex immunodirect Estradiol 125I kit (Pantex, Santa Monica, CA) demonstrated no detectable systematic error, allowing the use of these limits with either assay. The ovulating injection of human chorionic gonadotropin was given at 5:00 P.M. to 8:00 P.M. on the evening of blood drawing as soon as the first follicle reached an average diameter of 14 mm or greater. The ultrasound parameters allow the chance of pregnancy to be optimized and the chance of multiple gestation to be minimized. Serum E2 monitoring indicates when the risk of ovarian hyperstimulation is too great for human chorionic gonadotropin to be given. PMID:6437878

  2. [Biometric parameters of the uterus, ovaries and levels of 17 beta-estradiol (E2) after delivery in sheep].

    PubMed

    Krajnicáková, M; Elecko, J; Bekeová, E; Maracek, I; Hendrichovský, V

    1990-12-01

    Biometric changes of uterus, ovaries, follicles and 17 beta-oestradiol (E2) concentrations were investigated in 15 lambing ewes of the Slovak Merino breed in the puerperal period. The sex organs were excised immediately after bleeding from ewes slaughtered on days 1, 7, 17, 25 and 34 post partum (p. p.). Biometric parameters of the body and horns of uterus were measured by a calliper. The ovaries were weighed on an analytical balance, their length, width and height were measured at the same time. The size and number of follicles were determined on the ovary surface. The blood for E2 detection was collected from vena jugularis three and one day before delivery (days -1, -3). Blood samples were also collected after delivery on days 1, 7, 17, 25 and 34. E2 concentrations in the blood serum of ewes were determined by RIA-test-ESTRA kits, designed in one institute at Kosice. The highest weight of uterus body in the test ewes was recorded on day 1 p. p. In the following days the weight of uterus body had a decreasing trend. There were significant differences in the weight of uterus body from day 17 to day 34 p. p., in comparison with the first day after lambing (P less than 0.01). A significant decrease in the length of uterus body was observed from day 17 to day 34 of observation (P less than 0.01; P less than 0.001). An increase in the length of a nongravid horn, observed on day 7 p. p., was followed by a gradual decrease until day 34, similarly like in its weight. No statistically significant differences were found out in the ovary length, width and height. Neither were any greater changes recorded in the weight of ovaries from day 1 to day 34 after delivery. The highest number of small structures (28) observed on day 7 p. p. in the ipsilateral ovary was decreasing in the course of puerperium and the number of follicles larger than 2, 4 and 5 mm was increasing. The highest concentrations of E2 were not recorded on day -1 before delivery. The significantly lowest

  3. Photodegradation of the steroid hormones 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) in dilute aqueous solution.

    PubMed

    Mazellier, Patrick; Méité, Ladji; De Laat, Joseph

    2008-11-01

    The photochemical transformation of natural estrogenic steroid 17beta-estradiol (E2) and the synthetic oral contraceptive 17alpha-ethinylestradiol (EE2) has been studied in dilute non buffered aqueous solution (pH 5.5-6.0) upon monochromatic (254 nm) and polychromatic (lambda>290 nm) irradiation. Upon irradiation at 254 nm, the quantum yields of E2 and EE2 photolysis were similar and evaluated to be 0.067+/-0.007 and 0.062+/-0.007, respectively. Upon polychromatic excitation, and by using phenol as chemical actinometer, the photolysis efficiencies have been determined to be 0.07+/-0.01 and 0.08+/-0.01 for E2 and EE2, respectively. For both estrogens, photodegradation by-products were identified with GC/MS and LC/MS. In a first step, a model compound--5,6,7,8-tetrahydro-2-naphthol (THN)--, which represents the photoactive phenolic group, was used to obtain basic photoproduct structural informations. Numerous primary and secondary products were observed, corresponding to hydroxylated phenolic- or quinone-type compounds. PMID:18762316

  4. Occurrence and Pathways of Manure-borne 17beta-Estradiol in Vadose Zone Water

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reproductive hormones, such as 17beta-estradiol (E2), can cause physiological and reproductive disorders in numerous species at low part per trillion concentrations. The persistence and transport pathways of manure-borne E2 in agricultural soils were determined by comparing the occurrence of E2 in t...

  5. Effects of endocrine disruptors on genes associated with 17beta-estradiol metabolism and excretion.

    PubMed

    Hanet, Nathalie; Lancon, Allan; Delmas, Dominique; Jannin, Brigitte; Chagnon, Marie-Christine; Cherkaoui-Malki, Moustapha; Latruffe, Norbert; Artur, Yves; Heydel, Jean-Marie

    2008-11-01

    In order to provide a global analysis of the effects of endocrine disruptors on the hormone cellular bioavailability, we combined 17beta-estradiol (E2) cellular flow studies with real-time PCR and Western blot expression measurements of genes involved in the hormone metabolism and excretion. Three endocrine disruptors commonly found in food were chosen for this study, which was conducted in the estrogen receptor (ER) negative hepatoblastoma HepG2 cell line: bisphenol A (BPA), genistein (GEN) and resveratrol (RES). We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention. Thus, we demonstrate that bisphenol A, genistein and resveratrol modulate 17beta-estradiol cellular bioavailability in HepG2 and that these modulations most probably involve regulations of 17beta-estradiol phase II and III metabolism proteins. Up to now, the estrogenicity of environmental estrogenic pollutants has been based on the property of these compounds to bind to ERs. Our results obtained with ER negative cells provide strong evidence for the existence of ER-independent pathways leading to endocrine disruption. PMID:18634814

  6. Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey

    SciTech Connect

    Slikker, W. Jr.; Bailey, J.R.; Newport, D.; Lipe, G.W.; Hill, D.E.

    1982-11-01

    The synthetic estrogen component of many oral contraceptives, 17 alpha-ethynylestradiol-17 beta (EE2) and the naturally occurring estrogen, estradiol-17 beta (E2) were studied in four pregnant rhesus monkeys (71% term: 108-121 days gestational age). Under ketamine anesthesia, catheters were implanted in the maternal femoral artery and fetal interplacental artery. After simultaneous i.v. administration of (/sup 3/H)EE2-(/sup 14/C)E2 to the maternal animal, serial blood samples were drawn from both mother and fetus. The estrogens and metabolites were identified and quantified by the comigration of radioactivity with reference standards in several high-performance liquid chromatography systems and subsequent selective enzyme hydrolysis of the conjugates. Only estrone (E1), E1 sulfate, EE2 and EE2-3 sulfate were observed in the fetal circulation, whereas the major radiolabeled compounds in the maternal circulation consisted of the above plus E2, E1 glucuronide and EE2-3 glucuronide. In order to determine whether the placenta could convert E2 to its metabolite E1, the placentas of three term rhesus monkeys were perfused in situ via the umbilical artery with 120 ml (15 ml/min) of Hanks' balanced salt solution (pH 7.4) containing (/sup 3/H)E2. High-performance liquid chromatographic analysis of umbilical vein samples revealed that 96% of the E2 was metabolized to E1. These studies indicate that the placenta can metabolize the potent naturally occurring estrogen E2 to the less potent E1. In contrast, the synthetic estrogen EE2 does not undergo this placental metabolic conversion and thus enters the fetal circulation as the parent compound.

  7. Stimulation of Growth and Changes in the Hepatic Transcriptome by Estradiol-17-Beta in the Yellow Perch (Perca flavescens)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary estradiol-17-beta (E2) on growth and liver transcriptomics were investigated in the yellow perch (Perca flavescens). Following a 3-month treatment, E2 significantly stimulated an increase in length and weight of juvenile male and female perch relative to controls. The increas...

  8. Modeling of Coupled Degradation, Sorption, and Transport of 17beta-Estradiol in Undisturbed Soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of 17 beta-estradiol in the environment, even at part-per trillion concentrations, may raise significant concern regarding the health of aquatic organisms. Once 17 beta-estradiol is released into the environment from human and animal sources, its fate and transport is controlled by fact...

  9. Antigenotoxic effect of allicin against estradiol-17beta-induced genotoxic damage in cultured mammalian cells.

    PubMed

    Siddique, Yasir Hasan; Beg, Tanveer; Ara, Gulshan; Gupta, Jyoti; Afzal, Mohammad

    2010-07-01

    Antigenotoxic activity of allicin, one of the sulphur compounds of garlic (Allium sativum) which possesses antioxidant and thiol disulphide exchange activity, was studied against estradiol-17beta-induced genotoxic damage using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameters. Approximately 10, 20 and 40 microM of estradiol-17beta was tested for its genotoxic effect in the presence of metabolic activation and was found to be genotoxic at 20 and 40 microM. Approximately 20 microM of estradiol-17beta was treated along with 5, 10 and 15 microM of allicin, separately, in the presence of metabolic activation. Similar treatments were given with 40 microM of estradiol-17beta. Treatments along with allicin result in the reduction of CAs and SCEs, suggesting its anti-genotoxic activity in human lymphocytes in vitro against estradiol-17beta-induced genotoxic damage. PMID:20582805

  10. Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

    NASA Technical Reports Server (NTRS)

    Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

    1992-01-01

    With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

  11. Combinatory effects of phytoestrogens and 17beta-estradiol on proliferation and apoptosis in MCF-7 breast cancer cells.

    PubMed

    Schmidt, Simone; Michna, Horst; Diel, Patrick

    2005-04-01

    Phytoestrogens have been described to be weak estrogens, SERMs or exhibit antiestrogenic properties. However, information about their activity in presence of estrogens is limited. Therefore, we have analysed the dose dependent combinatory activity of the phytoestrogens genistein (Gen), daidzein (Dai) and coumestrol (Cou), and 17beta-estradiol (E2) on cell proliferation and apoptosis induction in human MCF-7 breast cancer cells. Neither additive nor antagonistic effects on proliferation could be observed, but in contrast all phytoestrogens possessed the ability to inhibit apoptosis in the presence of 17beta-estradiol. In summary, our in vitro results demonstrate that Gen does not exhibit any antiestrogenic properties. The additive growth stimulatory effects of Gen, Dai and Cou in the presence of E2 are not the result of a stimulation of proliferation; these phytoestrogens, at least in MCF-7 cells, could be characterised as inhibitors of apoptosis. PMID:15876409

  12. Comparison of three enzyme immunoassays for measuring 17beta-estradiol in flushed dairy manure wastewater.

    PubMed

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

    2004-01-01

    Natural steroidal estrogens are an environmental concern because low nanogram per liter concentrations in water can adversely affect aquatic vertebrate species by disrupting the normal function of their endocrine systems. There is a critical need to accurately measure estrogens in dairy wastes, a potential source of estrogens such as 17beta-estradiol, to assess the risk of estrogen contamination of agricultural drainage waters resulting from land application. Commercially available enzyme immunoassay (EIA) kits have been used for measuring 17beta-estradiol in livestock manure, but it is not known if different EIAs provide similar results. We compared three EIAs by measuring 17beta-estradiol in two samples of flushed dairy manure wastewater (FDMW). The measured concentrations of 17beta-estradiol in FDMW differed according to the immunoassay used. The differences were attributed to a matrix interference associated with coextracted humic substances. Future research should develop methods that enable routine measurement of 17beta-estradiol in livestock wastes by more conclusive analytical techniques such as gas chromatography-mass spectrometry. PMID:15356254

  13. Promotion of human adipocyte precursor replication by 17beta-estradiol in culture.

    PubMed Central

    Roncari, D A; Van, R L

    1978-01-01

    The influence of 17beta-estradiol and 17alpha-estradiol on adult human omental adipocyte precursors grown in a propagating culture system was studied. Cells were grown in subculture in the presence or absence of hormone. 17beta-estradiol resulted in significant promotion of adipocyte precursor replication, as determined by cell counting and incorporation of radioactive thymidine into DNA. The hormone stimulated cell multiplication in the concentration range 0.5--500 ng/ml growth medium. The highest level tested was 500 ng/ml. The maximal effects were obtained at 50 ng/ml (P less than 0.001 by paired t test, 48 h after hormone addition). All 10 cell strains (five were derived from men and five from women) that were tested responded similarly to the hormone. 17beta-estradiol did not affect cell size. 17alpha-estradiol did not promote the replication of adipocyte precursors, nor did it influence cell size. Thus, 17beta-estradiol, which is the active isomer in known target tissues, stimulates the multiplication of human adipocyte precursors in culture. Images PMID:690182

  14. Fate of nonylphenol and 17beta-estradiol contained in composted sewage sludge after land application.

    PubMed

    Minamiyama, M; Ochi, S; Suzuki, Y

    2008-01-01

    Many environmental problems caused by endocrine disrupters (EDs) have been reported. Because little is known about the fate of EDs accumulated in sewage sludge, we carried out a study to clarify the fate of EDs in composted sludge after its application to soil. Nonylphenol (NP) and 17beta-estradiol (E2) were measured for leachate and soil. High concentrations of NP and E2 were detected in the leachate at the early stage, but they decreased rapidly. Also, the high contents of NP and E2 in soil decreased significantly within 300 days. Because the decrease of NP and E2 in the soil was much larger than that of NP and E2 in the leachate, there must have been a physicochemical or biological decomposition mechanism in the soil layer. We also tried to clarify the transfer of NPs to plants from compost. In the experimental conditions of this study, the transfer of NPs to plants from compost was not observed. PMID:18235167

  15. 17beta-estradiol-induced activation of ERK1/2 through endogenous androgen receptor-estradiol receptor alpha-Src complex in human prostate cells.

    PubMed

    Chieffi, Paolo; Kisslinger, Annamaria; Sinisi, Antonio A; Abbondanza, Ciro; Tramontano, Donatella

    2003-09-01

    We examined the effect of estrogens on mitogen-activated protein kinase (MAPK) in EPN cells, a line of epithelial cells derived from human normal prostate. 17beta-estradiol (E2) caused a rapid and transient activation of MAPK (ERK1/2) within 5 min. This effect was counteracted by the anti-estrogen ICI 182-780 and by MEK inhibitor PD098059. The activation of ERK1/2 through 17beta-estradiol triggered simultaneous association of endogenous androgen receptor, estrogen receptor alpha and Src. In addition, E2 stimulated the proliferation of EPN cells, suggesting that the formation of the ternary complex and the consequent activation of ERKs are implicated in the mechanism regulating proliferation of epithelial prostate cells. PMID:12888920

  16. Naturally-occurring estradiol-17{beta}-fatty acid esters, but not estradiol-17{beta}, preferentially induce mammary tumorigenesis in female rats: Implications for an important role in human breast cancer

    SciTech Connect

    Mills, Laura H.; Yu Jina; Xu Xiaomeng; Lee, Anthony J.; Zhu Baoting

    2008-06-15

    Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17{beta}-fatty acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an estradiol-17{beta} pellet developed large pituitary tumors (average weight = 251 {+-}103 mg) and had to be terminated early, but only 48% of them developed mammary tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing estradiol-17{beta}-stearate and estradiol-17{beta}-palmitate (two representative estradiol-17{beta}-fatty acid esters) or in the 29 animals implanted with estradiol-17{beta}-stearate alone (in the same molar dose as estradiol-17{beta}), 73% and 79%, respectively, of them developed mammary tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of estrogen esterase than other tissues, which catalyzes the releases of bioactive estrogens from their fatty acid esters. In conclusion, while estradiol-17{beta} is much stronger in inducing pituitary tumor (100% incidence) than mammary tumor, estradiol-17{beta}-fatty acid esters have a higher efficacy than estradiol-17{beta} in inducing mammary tumor and yet it only has little ability to induce uterine out-growth and pituitary tumorigenesis. This study establishes the endogenous estrogen-17{beta}-fatty acid esters as preferential inducers of mammary tumorigenesis.

  17. Pregnancy rates after ewes were treated with estradiol-17beta and oxytocin.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cervical dilation may improve transcervical sheep embryo-transfer procedures, if the cervical dilation method does not reduce pregnancy rates. This experiment was conducted to determine whether estradiol-17beta-oxytocin treatment, which dilates the cervix in luteal-phase ewes, affects pregnancy rat...

  18. Persistence and Fate of 17beta-estradiol and testosterone in agricultural soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Steroidal hormones are constantly released into the environment by man-made and natural sources. The goal of this study was to examine the persistence and fate of 17beta-estradiol and testosterone, the two primary natural hormones. Incubation experiments were conducted under aerobic and anaerobic co...

  19. Cytochrome P450-mediated 17beta-estradiol metabolism in zebrafish (Danio rerio).

    PubMed

    Scornaienchi, Marcus L; Thornton, Cammi; Willett, Kristine L; Wilson, Joanna Y

    2010-09-01

    Cytochrome P4501 (CYP1) and CYP3A proteins are primarily responsible for the metabolism of 17beta-estradiol (E(2)) in mammals. We have cloned and heterologously expressed CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP1D1, and CYP3A65 from zebrafish (Danio rerio) to determine the CYP-mediated metabolism of E(2) in a non-mammalian species. Constructs of each CYP cDNA were created using a leader sequence from the bacterial ompA gene to allow appropriate expression in Escherichia coli without 5' modification of the gene. Membrane vesicles were purified, and functional CYP protein was verified using carbon monoxide difference spectra and fluorescent catalytic assays with the substrates 7-ethoxyresorufin and 7-benzyloxy-4-(trifluoromethyl)-coumarin. Rates of in vitro E(2) metabolism into 4-hydroxyE(2) (4-OHE(2)), 2-hydroxyE(2) (2-OHE(2)), and 16alpha-hydroxyE(1) (16alpha-OHE(1)) metabolites were determined by gas chromatography/mass spectrometry. The 2-OHE(2) metabolite was produced by all CYPs tested, while 4-OHE(2) was only detected following incubation with CYP1A, CYP1B1, CYP1C1, and CYP1C2. The 16alpha-OHE(1) metabolite was only produced by CYP1A. The highest rates of E(2) metabolism were from CYP1A and CYP1C1, followed by CYP1C2. CYP1B1, CYP1D1, and CYP3A65 had low rates of E(2) metabolism. E(2) metabolism by zebrafish CYP1A, CYP1C1, and CYP1C2 produced similar ratios of 4-OHE(2) to 2-OHE(2) as previous studies with mammalian CYP1As. CYP1B1 formed the highest ratio of 4-OHE(2) to 2-OHE(2) metabolites. Contrary to mammals, these results suggest that fish CYP1A and CYP1C proteins are primarily responsible for E(2) metabolism, with only minor contributions from CYP3A65 and CYP1B1. Similar to mammals, 2-OHE(2) is the predominant metabolite from CYP-mediated E(2) metabolism in fish, suggesting that all vertebrate species produce the same major E(2) metabolite. PMID:20522564

  20. Calmodulin-stimulated phosphorylation of 17 beta-estradiol receptor on tyrosine.

    PubMed Central

    Migliaccio, A; Rotondi, A; Auricchio, F

    1984-01-01

    The calf uterine 17 beta-estradiol receptor is a phosphoprotein. Phosphorylation-dephosphorylation of the receptor is controlled by a cytosol receptor kinase that activates the hormone binding and by a nuclear phosphatase that inactivates this binding. This report concerns the nature of the 17 beta-estradiol receptor kinase. Highly purified calf uterus 17 beta-estradiol receptor preinactivated by the nuclear phosphatase was used as substrate of the purified receptor kinase. Ca2+ and calmodulin stimulate both the kinase-dependent activation of the hormone binding and 32P incorporation from [gamma-32P]-ATP into the receptor. Maximal stimulation of hormone binding activation requires 1 microM Ca2+ and 0.6 microM calmodulin. Fifteen micromolar trifluoperazine is the lowest concentration that will prevent completely Ca2+-calmodulin stimulation of the kinase. The receptor is phosphorylated by the receptor kinase exclusively on tyrosine. Phosphorylation of proteins on tyrosine is a rare event implicated in hormone-induced cell growth and cell transformation. Images PMID:6207535

  1. An enriched environment and 17-beta estradiol produce similar pro-cognitive effects on ovariectomized rats.

    PubMed

    Ortiz-Pérez, A; Espinosa-Raya, J; Picazo, O

    2016-02-01

    Estrogen depletion due to aging, surgery or pathological events can cause a multitude of problems, including neurodegenerative alterations. In rodents without ovaries, 17-beta estradiol (E2) has been shown to produce beneficial effects on cognition, stimulating brain regions (e.g., the neocortex, hippocampus and amygdala) related to cognition and learning. Another treatment that stimulates these brain regions is an enriched environment (EE), which is a complex set of external factors in the immediate surroundings that facilitates greater stimulation of sensorial, cognitive and motor circuits of the brain. The aim of the present study was to test, using an animal model of ovariectomy-induced impairment of memory, the relative effect of E2 (with a time-released pellet; 1 μg/rat/day), EE exposure and a combination of both treatments. Experimental and control groups were submitted to two memory tests 18 weeks post-surgery: the autoshaping learning task (ALT) for measuring associative learning and the novel object recognition test (NORT) for evaluating short- and long-term memory. To assess potential motor impairments caused by treatments, all rats were tested after the ALT in an automatic activity counter. Results from ALT show that the ovariectomy blocked the conditioned responses displayed, an effect rescued by chronic treatment with estrogen or EE exposure. The combination of both treatments did not improve the results obtained separately. In the NORT, the exploration time for recognizing a novel object was similar in the short run with all groups, but greater in the long run with hormone administration or EE exposure. As with the ALT, in the NORT there was no improvement shown by the combination treatment. These data were not masked by changes in spontaneous activity because this parameter was not modified in the rats by either treatment. Possible action mechanisms are proposed, taking into account the role of corticosterone and BDNF on cognition. PMID:26872959

  2. Effect of agricultural antibiotics on the persistence and transformation of 17beta-estradiol in a Sequatchie loam.

    PubMed

    Chun, Soul; Lee, Jaehoon; Geyer, Roland; White, David C; Raman, D Raj

    2005-01-01

    A laboratory incubation study was conducted to investigate the effect of agricultural antibiotics (sulfamethazine, tylosin, and chlortetracycline) on the persistence and transformation of 17beta-estradiol in Sequatchie loam. We measured concentrations of 17beta-estradiol and its primary metabolite (estrone) in soils spiked with antibiotics and 17beta-estradiol. Dehydrogenase activity (DHA) was also measured as an indicator of the total microbial activity of the soils. The presence of antibiotics significantly decreased transformation of 17beta-estradiol to estrone. There was a positive correlation between the DHA and the concentrations of estrone in soil spiked with 17beta-estradiol only, implying that the reaction is mainly catalyzed by dehydrogenases. However, the positive correlation was weakened in soil spiked with 17beta-estradiol and antibiotics together. We recommend that any study evaluating the fate and transport of estrogenic hormones in soil should include the effect of agricultural antibiotics because antibiotics and estrogenic hormones are commonly excreted together in environmental samples. PMID:16190018

  3. Factors affecting retention of estradiol-17 beta silicone rubber implants in ears of steers.

    PubMed

    Parrott, J C; Basson, R P; Carroll, L H; Elliston, N G; Ferguson, T H; Gorham, P E; Grueter, H P; McAskill, J W; Wagner, J F

    1985-10-01

    A series of trials were conducted to identify the factors causing loss of estradiol-17 beta (E2-beta) silicone rubber implants from the ears of cattle and to evaluate methods of reducing this loss. Surface application of cattle feces to the ears before implanting resulted in an increase in loss of implants compared with the loss from dry, clean ears (30.6 vs 8.6%; P less than .05). Washing ears with a povidone-iodine antiseptic solution before implanting or treating implant sites with an antibiotic after implanting reduced (P less than .05) implant loss when ears were coated with the fecal slurry. Coating silicone rubber implants with .5 to 2 mg of oxytetracycline hydrochloride (OTC) reduced (P less than .0001) implant loss from 39.8 to 13.8% when ears were coated with fecal slurry. When silicone rubber implants with a 1.5-mg coating of OTC were implanted in cattle before submerging in a dipping vat, implant loss was reduced from 6.2 to 2.7%. In studies designed to evaluate mechanical factors affecting implant loss, implants that were placed in the middle of the ear in tight skin moved .79 cm toward the insertion site during a 14-d period after administration compared with 2.82 cm when placed in the base of the ear. When placed in the middle of the ear in tight skin, only 2 of 399 (.5%) implants were lost from steers submerged in a dipping vat immediately following implantation compared with 42 of 394 (10.7%) when placed in the base of the ear (P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3934122

  4. Regioselective 2-hydroxylation of 17{beta}-estradiol by rat cytochrome P4501B1

    SciTech Connect

    Rahman, Mostafizur; Hayes Sutter, Carrie; Emmert, Gary L.; Sutter, Thomas R. . E-mail: tsutter@memphis.edu

    2006-11-01

    Previous work demonstrated that human cytochrome P4501B1 (CYP1B1) forms predominantly 4-hydroxyestradiol (4-OHE2), a metabolite which is carcinogenic in animal models. Here, we present results from kinetic studies characterizing the formation of 4-OHE2 and 2-hydroxyestradiol (2-OHE2) by rat CYP1B1 using 17{beta}-estradiol (E2) as a substrate. K {sub m} and K {sub cat} values were estimated using the Michaelis-Menten equation. For rat CYP1B1, the apparent K {sub m} values for the formation of 4-OHE2 and 2-OHE2 were 0.61 {+-} 0.23 and 1.84 {+-} 0.73 {mu}M; the turnover numbers (K {sub cat}) were 0.23 {+-} 0.02 and 0.46 {+-} 0.05 pmol/min/pmol P450; and the catalytic efficiencies (K {sub cat}/K {sub m}) were 0.37 and 0.25, respectively. For human CYP1B1, the apparent K {sub m} values for the formation of 4-OHE2 and 2-OHE2 were 1.22 {+-} 0.25 and 1.10 {+-} 0.26; the turnover numbers were 1.23 {+-} 0.06 and 0.33 {+-} 0.02; and the catalytic efficiencies were 1.0 and 0.30, respectively. The turnover number ratio of 4- to 2-hydroxylation was 3.7 for human CYP1B1 and 0.5 for rat CYP1B1. These results indicate that, although rat CYP1B1 is a low K {sub m} E2 hydroxylase, its product ratio, unlike the human enzyme, favors 2-hydroxylation. The K {sub i} values of the inhibitor 2,4,3',5'-tetramethoxystilbene (TMS) for E2 4- and 2-hydroxylation by rat CYP1B1 were 0.69 and 0.78 {mu}M, respectively. The K {sub i} values of 7,8-benzoflavone ({alpha}-NF) for E2 4- and 2-hydroxylation by rat CYP1B1 were 0.01 and 0.02 {mu}M, respectively. The knowledge gained from this study will support the rational design of CYP1B1 inhibitors and clarify results of CYP1B1 related carcinogenesis studies performed in rats.

  5. Sorption and transport of 17beta-estradiol and testosterone in undisturbed soil columns.

    PubMed

    Sangsupan, H A; Radcliffe, D E; Hartel, P G; Jenkins, M B; Vencill, W K; Cabrera, M L

    2006-01-01

    Land-applied domestic animal wastes contain appreciable amounts of 17beta-estradiol (henceforth, estradiol) and testosterone. These sex hormones may be transported through soil to groundwater and streams, where they may adversely affect the environment. Previous column transport studies with these hormones used repacked soil and did not consider preferential flow. We, therefore, determined the sorption and transport characteristics of estradiol and testosterone in undisturbed soil columns (15-cm i.d. by 32-cm height). In the sorption experiment, isotherms for estradiol and testosterone were nonlinear with Freundlich exponents (n) less than one. Sorption of both hormones decreased with soil depth, and estradiol sorbed more strongly than testosterone. Average estradiol Freundlich sorption coefficients (K(f)) values were 36.9 microg(1 - n) mL(n) g(-1) for the 0- to 10-cm soil depth and 25.7 microg(1 - n) mL(n) g(-1) for the 20- to 30-cm soil depth. Average testosterone K(f) values were 26.7 microg(1 - n) mL(n) g(-1) for the 0- to 10-cm soil depth and 14.0 microg(1 - n) mL(n) g(-1) for the 20- to 30-cm soil depth. In the transport experiment, 27% of the estradiol and 42% of the testosterone leached through the soil columns. Approximately 50% of the remaining soil-bound hormones were sorbed in the top 10 cm of soil. In almost all instances, breakthrough concentrations of estradiol, testosterone, and a chloride tracer peaked simultaneously. Simultaneous breakthrough and HYDRUS-1D transport parameters indicated both chemical and physical nonequilibrium processes affected hormone transport. This suggests hormones placed on soil surfaces may contaminate groundwater under conditions of preferential flow. PMID:17071897

  6. Mechanism of the anti-inflammatory effect Of 17beta-estradiol on brain following trauma-hemorrhage.

    PubMed

    Akabori, Hiroya; Moeinpour, Fariba; Bland, Kirby I; Chaudry, Irshad H

    2010-01-01

    Although 17beta-estradiol (E2) is reported to improve the inflammatory response after trauma-hemorrhage (T-H), it remains unknown whether E2 plays any role in the central nervous system after T-H. Microglial cells, resident central macrophages, are thought to play a central role in exacerbating cell-mediated inflammation. We hypothesized that T-H up-regulates microglial cell-mediated inflammatory response in the brain, and E2 produces central anti-inflammatory effects via negative regulation of microglial cells. Male Sprague-Dawley rats were subjected to sham operation (cannulation plus laparotomy) or T-H (midline laparotomy; mean blood pressure, 35 +/- 5 mmHg for 90 min followed by resuscitation) and immediately killed after resuscitation. Rats received vehicle or E2 (1 mg/kg body weight i.v.) at the onset of resuscitation. In other experiments, minocycline (40 mg/kg body weight i.p.), microglia inhibitor, was administered 1 h before T-H to prevent inflammatory response in the microglia after T-H. The plasma and hypothalamic tumor necrosis factor (TNF-alpha) levels were increased, along with the activation of microglial cells in T-H rats compared with shams. Furthermore, T-H increased microglial TNF-alpha productive capacity in vitro. 17beta administration after T-H prevented these inflammatory responses. In rats pretreated with minocycline, decreased microglial TNF-alpha production and hypothalamic TNF-alpha levels were observed, but plasma TNF-alpha levels were not altered after T-H. Thus, T-H induces inflammatory responses even in the hypothalamus, and E2 seems to be a useful adjunct for down-regulating microglial cell-mediated inflammatory response after T-H. PMID:19536048

  7. Differential expression of CYP102 in Bacillus megaterium by 17-beta-estradiol and 4-sec-butylphenol.

    PubMed

    Rowley, Christopher W; Rajnarayanan, Rajendram V; Hopkins, Nancy E; Alworth, William L

    2003-01-01

    Previously we have reported the induction of CYP102 in Bacillus megaterium by 17beta-estradiol (E2) and 4-sec-butylphenol (4-sBP). Electrophoretic mobility shift assay analyses demonstrated that E2 and 4-sBP both cause a dose-dependent disassociation of the Bm3R1 repressor protein from its binding site on the operator sequence of the CYP102 gene. Equimolar combinations of E2 and 4-sBP demonstrated additive induction of CYP102 compared to equivalent samples of E2 and 4-sBP added alone. Two gene constructs were used in this investigation. One construct designated BMC143 contained the entire regulatory region of CYP102. The other gene construct, designated BMA45, had the "Barbie box" sequence deleted. While the induction of CYP102 by 4-sBP was much higher in the BMC 143 construct, E2 induced CYP102 in both constructs to the same extent. This difference in induction of CYP102 by these two inducers indicates that they act at different sites, either on the Bm3R1 repressor protein or on positive regulatory sites, or that they act, in part, through different mechanisms. PMID:12480527

  8. Transport of 17beta-estradiol and testosterone in a field lysimeter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2) and testosterone (T) are present in sources such as waste treatment effluent and manures, and can potentially disrupt aquatic organisms at low concentrations. Laboratory studies consistently indicate limited mobility and rapid attenuation of E2 and T in soils; however, these hormo...

  9. Selective turnover of the essential fatty acid ester components of estradiol-17 beta lipoidal derivatives formed by human mammary cancer cells in culture.

    PubMed

    Martyn, P; Smith, D L; Adams, J B

    1987-10-01

    The properties of fatty acyl coenzyme A: estradiol-17 beta acyl transferase in microsomes derived from pooled human mammary cancer tissue have been examined. A pH optimum of 5.5 was found and addition of long-chained fatty acyl CoAs increased estradiol-17 beta (E2) 17-monoacyl ester synthesis; the apparent Km for E2 being 8 microM when oleoyl CoA, linolenoyl CoA or palmitoyl CoA were employed. Testosterone, dehydroepiandrosterone, and 5-androsterone-3 beta, 17 beta-diol acted as competitive inhibitors with Ki values of 36, 36 and 46 microM, respectively. The composition of E2 fatty acyl esters (E2-L) formed by incubation of [3H]E2 with human mammary cancer tissue and human mammary cancer cell lines has been determined by HPLC. Although the composition of E2-L in estrogen receptor negative cell lines (MDA-MB-231 and MDA-MB-330) was generally similar to that found for MCF-7 cells (estrogen receptor positive) and pooled human mammary cancer tissue, the former cell lines contained a 3-fold higher relative concentration of E2-17 beta stearate. MCF-7 cells were exposed to 30 nM [3H]E2 and the composition of the isolated [3H]E2-L fraction studied at various time intervals. At 0.5 h, the intracellular concentration of E2-L was 1.8 +/- 0.4 (SEM) pmol/mg DNA which increased to values of 3.6 +/- 0.6 and 4.3 +/- 0.5 at 4 h and 16 h, respectively. In the subsequent 3 h following transfer to medium lacking [3H]E2, the concentration of E2-L declined to 3.7 +/- 0.3 pmol/mg DNA. The subfraction of E2-L composed of E2-17 beta arachidonate, linolenate and docosahexaenoate, was seen to decline in relative abundance after 0.5 h and to reach significantly lower relative levels at 16 h, and again in the 3 h period following estrogen withdrawal. The data suggests that these components, derived from essential fatty acids, are more metabolically active. This may then provide a new lead to link these novel estrogen derivatives with the established relationship between unsaturated fatty acids

  10. Effect of cadmium on the interaction of 17beta-estradiol with the rainbow trout estrogen receptor.

    PubMed

    Nesatyy, Victor J; Ammann, Adrian A; Rutishauser, Barbara V; Suter, Marc J F

    2006-02-15

    The widely reported negative effects of xenoestrogens on the endocrine system of aquatic organisms gave raise to public concern and led to a number of screening and testing initiatives on the international level. Recent studies indicated that not only organic chemicals but also certain heavy metals, including cadmium, can mimic the effects of the endogenous estrogen receptor agonist 17beta-estradiol (E2) and lead to estrogen receptor activation. While the effects of cadmium on the endocrine system and its potential to harm living organisms are no longer in doubt, the exact mode of action is still essentially unknown. In the present study we utilized the rainbow trout ER alpha ligand binding domain (rtER-LBD) fused to glutathione-S-transferase, to study noncovalent interactions between cadmium and the rtER-LBD. ICP-MS data showed that the Cd uptake by the rtER-LBD was strongly pH-dependent. Previous results showing that Cd shields Cys residues of the rtER-LBD against chemical modification, and competitive binding experiments reported here provide insights into the specificity of the interaction of cadmium with the ER hormone binding cavity. It could, for instance, be shown that most of the cadmium adsorbed to the protein could be released into solution either under denaturing conditions, or by stripping from the protein surface using EDTA at physiological conditions. Competitive binding experiments using radio-labeled estradiol showed that, in contrast to previously published data, E2 has an affinity an order of magnitude higher for the ER than for Cd. ICP-MS experiments showed that, despite its higher affinity, increasing E2 concentrations were unable to replace Cd from the rtER-LBD that had been preequilibrated with Cd. These findings were independently confirmed by the [3H]-E2 binding assay. At the same time both ICP-MS and the [3H]-E2 binding assay showed that increasing Cd concentrations not only lead to a decrease in the specific estradiol binding, but also to

  11. Two direct radioimmunoassays for 17 beta-estradiol evaluated for use in monitoring in vitro fertilization.

    PubMed

    Haning, R V; Meier, S M; Boehnlein, L M; Gerrity, M; Shapiro, S S

    1984-05-01

    Two direct 125I radioimmunoassays for 17 beta-estradiol were evaluated by comparing results with those obtained by a comparison RIA involving extraction and chromatography (x) and with ultrasound parameters of ovarian activity. The correlation coefficients (R2) for the Immuchem Covalent-Coat Solid Phase 125I results (y1) and the Pantex Immuno-direct results (y2) with the comparison method results were 0.56 and 0.96, respectively, after log transformation of data (N = 42). Similar differences were observed in the correlations with the ultrasound parameters. We also evaluated the untransformed data by linear regression and obtained: y1 = 254 + 0. 410x (R2 = 0.65) and y2 = 48.2 + 0. 749x (R2 = 0.96). Between- and within-assay variations for a serum pool containing 17 beta-estradiol at 1278 pg/mL were respectively 9.0% and 9.4% for Immuchem , 3.3% and 6.7% for Pantex , and 7.3% and 9.4% for the comparison method; for the 267 pg/mL pool, these were 21.8% and 16.6% for Immuchem , 4.7% and 4.6% for Pantex , and 21.2% and 13.1% for the comparison method. Differences in the results obtained with the Pantex method and the comparison method were not clinically significant for monitoring superovulation for in vitro fertilization; the performance of the Immuchem method was less satisfactory. PMID:6713642

  12. The influence of body condition on 17-beta estradiol levels in relation to vitellogenesis in female Vipera aspis (Reptilia, Viperidae).

    PubMed

    Bonnet, X; Naulleau, G; Mauget, R

    1994-03-01

    Seventy-six wild Vipera aspis females were caught over 3 years and placed in outdoor enclosures; 39 reproduced and 37 did not. Almost all the reproductive females had a body condition index (BCI) greater than 0.70 when vitellogenesis began. Monthly blood samples were taken by cardiac puncture. The main plasma parameters of vitellogenesis were measured by spectrophotometry: total plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, proteins, and albumin. Plasma 17-beta estradiol levels were determined by RIA. Vitellogenesis started soon after hibernation in reproductive females with very high 17-beta estradiol concentrations (average of 4.00 ng/ml) and there was a marked mobilization of maternal reserves (fat bodies, liver, and vertebral bone) associated with very high values of plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, and proteins. The kinetics of the main plasma components were described throughout the vitellogenesis period (from March to early June), when all plasma parameters differed markedly between reproductive and nonreproductive females. After ovulation, the differences between the two groups of females disappeared except in the case of albumin, which remained at a very low level in reproductive females for 6 months. All nonreproductive females had low 17-beta estradiol plasma levels during vitellogenesis (average of 0.08 ng/ml) and there was no suggestion of mobilization of maternal reserves. After vitellogenesis plasma concentrations of estradiol were low in reproductive (an average of 0.08 ng/ml) and in nonreproductive animals (0.06 ng/ml). Five nonreproductive females kept in the laboratory were estrogenized by 17-beta estradiol silastic implants. The 17-beta estradiol concentrations were close to those measured in reproductive females during vitellogenesis. Maternal reserves were mobilized, with almost all metabolic parameters exhibiting the vitellogenic pattern. When the silastic implants were removed

  13. ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish liver, but not in testis

    PubMed Central

    Pinto, Patrícia IS; Singh, Pratap B; Condeça, João B; Teodósio, Helena R; Power, Deborah M; Canário, Adelino VM

    2006-01-01

    Background ICI 182,780 (ICI) belongs to a new class of antiestrogens developed to be pure estrogen antagonists and, in addition to its therapeutic use, it has been used to knock-out estrogen and estrogen receptor (ER) actions in several mammalian species. In the present study, the effects and mechanism of action of ICI were investigated in the teleost fish, sea bream (Sparus auratus). Methods Three independent in vivo experiments were performed in which mature male tilapia (Oreochromis mossambicus) or sea bream received intra-peritoneal implants containing estradiol-17 beta (E2), ICI or a combination of both compounds. The effects of E2 and ICI on plasma calcium levels were measured and hepatic and testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L, were analyzed by semi-quantitative RT-PCR in sea bream. Results E2 treatment caused an increase in calcium levels in tilapia, while ICI alone had no noticeable effect, as expected. However, pretreatment with ICI synergistically potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some E2 actions in gene expression in sea bream liver upregulating ER alpha, vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected in the expression of ERs in testis, while vitellogenin II and choriogenin L were upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic effect on the hepatic E2 down-regulation of ER beta b, but apparently blocked the ER alpha up-regulation by E2. Conclusion These results demonstrate that ICI has agonistic effects on several typical estrogenic responses in fish, but its actions are tissue-specific. The mechanisms for the ICI agonistic activity are still unknown; although the ICI induced up-regulation of ER alpha mRNA could be one of the factors contributing

  14. Assessment of Neuroprotective Effects of Local Administration of 17- Beta- Estradiol on Peripheral Nerve Regeneration in Ovariectomized Female Rats

    PubMed Central

    Nobakhti-Afshar, Ahmadreza; Najafpour, Alireza; Mohammadi, Rahim; Zarei, Leila

    2016-01-01

    Objective: To assess the neuroprotective effects of local administration of 17- beta- estradiol on nerve regeneration. Methods: Sixty female Wistar rats were overiectomized and divided into four experimental groups (n = 15), randomly: In autograft group a segment of sciatic nerve was transected and re-implanted reversely. In sham-surgery group sciatic nerve was exposed and manipulated. In transected group left sciatic nerve was transected and stumps were fixed in adjacent muscle. In treatment group defect was bridged using a silicon conduit filled with 10 µL (0.1 mg/mL) 17- beta- estradiol. Each group was subdivided into four subgroups of five animals each and nerve fibers were studied in a 12-week period. Results: Behavioral, functional, biomechanical, electrophysiological and gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in treatment group than in other groups (p<0.05). Immunohistochemical reactions to S-100 in treatment group were more positive than that in other groups. Conclusion: Local administration of 17-beta-estradiol improved functional recovery and morphometric indices of sciatic nerve. It could have clinical implications for the surgical management of patients after facial nerve transection. PMID:27540548

  15. Rapid vascular escape of arterially injected 16alpha-radioiodo, 17beta-estradiol

    SciTech Connect

    Scharl, A.; Holt, J.A. )

    1993-03-20

    The authors undertook this study because confirmation of a rapid vascular escape and slow release back into the circulatory system suggests that arterial injection of radiohalogenated steroid receptor ligands might provide an efficacious route of administration for imaging or treatment of receptor-rich malignant tumors in peripheral tissues. The authors injected radiolabeled 16alpha-iodo, 17beta-estradiol ([I]-E) into the femoral artery of swine in a solution that contained [[sup 125]I]-E in a known ratio to [[sup 99]Tc]-labeled red blood cells. Fractions of femoral venous blood were collected at short intervals during 10 min. They looked for changes in the ratio of the radiolabeles. [[sup 99m]Tc]-labeled red blood cells are known to remain in the vascular system for an hour or more. After passage of the injectate through the capillary bed of the swine leg, a dramatic decrease of the initial [sup 125]I:[sup 99m]Tc ratio to only 10% was observed in the femoral venous blood. This ratio increased gradually during the next 10 min to approximately 30% of that in the injectate, indicating that a significant portion (approximately 90%) of the [[sup 125]I]-E was initially trapped in the limb and then slowly re-entered the vascular system. To obtain visual confirmation of the rapid vascular escape of iodo-estrogen, they injected either an imageable form of [I]-E ([[sup 123]I]-E) or [[sup 99m]Tc]-labeled red blood cells into the dorsal aorta of superovulated rabbits, whose smaller size allowed whole-body imaging. The biodistributions of these radiopharmaceuticals were surveyed continuously by real-time planar gamma imaging. A large fraction of [I]-E escapes from the vascular system during the first pass through an organ or limb, without regard to the estrogen receptor content of the tissue. 28 refs., 3 figs., 1 tab.

  16. Role of Follicular Estradiol-17beta in Timing of Luteolysis in Heifers1

    PubMed Central

    Araujo, Reno R.; Ginther, O.J.; Ferreira, Jair C.; Palhão, Miller M.; Beg, Mohd A.; Wiltbank, Milo C.

    2009-01-01

    The hypothesis was tested that estradiol (E2) from the ovarian follicles controls time of luteolysis. Time of luteolysis was evaluated by multiple measures of corpus luteum (CL) structure (area, volume) and function (progesterone [P4], luteal blood flow). The hypothesis for experiment 1 was that repeated ablation of follicles would reduce circulating E2 and delay luteolysis. Heifers were randomly assigned on Day 9 (Day 0 = ovulation) to three groups. All follicles ≥4 mm were ablated on Day 9 (group FA9; n = 6); Days 9–15 (group FA15; n = 6); or Days 9–21 (group FA21; n = 7). As expected, follicular ablation delayed (P < 0.001) the rise in circulating E2 and peak E2 concentrations (FA9, Day 17.6 ± 0.7; FA15, Day 20.3 ± 0.3; FA21, Day 24.9 ± 0.3). Luteolysis (based on each measure) was delayed (P < 0.005) by repeated ablation of follicles, with earlier luteolysis (based on P4 decrease) in FA9 (Day 15.2 ± 0.8) than FA15 (Day 16.5 ± 0.4), and a further delay in FA21 (Day 18.3 ± 0.5). The hypothesis of experiment 2 was that exogenous treatment with E2 would stimulate prostaglandin F2alpha (PGF) secretion and prevent the delay in luteolysis associated with follicular ablations. Follicles ≥4 mm were ablated from Day 9 to Day 17 (n = 15). Heifers were treated on Days 13 and 15 with 1.0 mg of estradiol benzoate (FAE2; n = 7) or vehicle (FAV; n = 8). Treatment with E2 induced PGF secretion (detected by PGF metabolite) and induced earlier (P < 0.02) luteolysis in FAE2 than in FAV, whether determined by circulating P4 or by area, volume, or blood flow of CL. In summary, ablation of follicles (≥4 mm) delayed and treatment with E2 hastened luteolysis in heifers with ablated follicles. Thus, these results are consistent with an essential role for follicle E2 in timing of luteolysis. PMID:19264702

  17. Application of stable carbon isotope analysis to the detection of 17beta-estradiol administration to cattle.

    PubMed

    Buisson, C; Hebestreit, M; Weigert, A Preiss; Heinrich, K; Fry, H; Flenker, U; Banneke, S; Prevost, S; Andre, F; Schaenzer, W; Houghton, E; Le Bizec, B

    2005-11-01

    The use of anabolic agents in food producing animals is prohibited within the EU since 1988 (96/22/EC directive). The control of the illegal use of natural steroid hormones in cattle is still an exciting analytical challenge as far as no definitive method and non-ambiguous analytical criteria are available. The ability of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to demonstrate the administration of 17beta-estradiol to bovine has been investigated in this paper. By comparison of 13C/12C isotopic ratio of main urinary estradiol metabolite, i.e. 17alpha-estradiol, with two endogenous reference compounds (ERCs), i.e. dehydroepiandrosterone (DHEA) and 5-androstene-3beta,17alpha-diol, the differentiation of estradiol metabolite origin, either endogenous or exogenous, has been proved to be achievable. After treatment, the delta(13)C(VPDB)-values of 17alpha-estradiol reached -27 per thousand to -29 per thousand, whereas delta13CVPDB-values of DHEA remained between -13 per thousand and -20 per thousand depending on the diet, maize and grass, respectively. A significant difference of delta13CVPDB between ERCs and 17alpha-estradiol was measurable over a period of 2 weeks after estradiol ester administration to the animal. PMID:16233872

  18. 17beta-estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures

    NASA Technical Reports Server (NTRS)

    McCarthy, T. L.; Ji, C.; Shu, H.; Casinghino, S.; Crothers, K.; Rotwein, P.; Centrella, M.

    1997-01-01

    Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid hormone and prostaglandin E2 (PGE2) through cAMP-activated protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively in these cells. As reported, 1 microM PGE2 increased IGF-I P1 activity by 5-fold. 17beta-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory effect of PGE2 by up to 90% (ED50 approximately 0.1 nM). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17alpha-estradiol was 100-300-fold less effective. By contrast, 17beta-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up to 10-fold. 17beta-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent gene activation, but did not affect the 60-fold increase in cAMP induced by PGE2. There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding, while PGE2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity, consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind

  19. Effects of cadmium, estradiol-17beta and their interaction on gonadal condition and metamorphosis of male and female African clawed frog, Xenopus laevis

    USGS Publications Warehouse

    Sharma, Bibek; Patino, Reynaldo

    2010-01-01

    To assess interaction effects between cadmium (Cd, a putative xenoestrogen) and estradiol-17beta (E(2)) on sex differentiation and metamorphosis, Xenopus laevis were exposed to solvent-control (0.005% ethanol), Cd (10microgL(-1)), E(2) (1microgL(-1)), or Cd and E(2) (Cd+E(2)) in FETAX medium from fertilization to 75d postfertilization. Each treatment was applied to four aquaria, each with 30 fertilized eggs. Mortality was recorded and animals were sampled as they completed metamorphosis (Nieuwkoop and Faber stage 66). Gonadal sex of individuals (including >or= tadpoles NF stage 55 at day 75) was determined gross-morphologically and used to compute sex ratios. Time course and percent completion of metamorphosis, snout-vent length (SVL), hindlimb length (HLL) and weight were analyzed for each gender separately. Survival rates did not differ among treatments. The E(2) and Cd+E(2) treatments significantly skewed sex ratios towards females; however, no sex-ratio differences were observed between the control and Cd treatments or between the E(2) and Cd+E(2) treatments. Time course of metamorphosis was generally delayed and percent completion of metamorphosis was generally reduced in males and females exposed to Cd, E(2) or their combination compared to control animals. In males, but not females, the effect of Cd+E(2) was greater than that of individual chemicals. Weight at completion of metamorphosis was reduced only in females and only by the Cd+E(2) treatment. In conclusion, although Cd at an environmentally relevant concentration did not exhibit direct or indirect feminizing effects in Xenopus tadpoles, the metal and E(2) both had similar inhibitory effects on metamorphosis that were of greater magnitude in males than females.

  20. [Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause].

    PubMed

    Grio, R; Piacentino, R; Abbondanza, M; Cirnigliaro, C; Fusi, D; Corsello, F P; Arrichiello, G; Canestrelli, M; Marchino, G L

    1992-01-01

    Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy. PMID:1508379

  1. Effect of plasma lipoproteins in gonadotropin stimulation of 17 beta-estradiol production in the ovarian follicle of rainbow trout (Salmo gairdneri).

    PubMed

    Babin, P J

    1986-12-01

    The effect of trout plasma lipoproteins on the production of 17 beta-estradiol by trout ovarian follicles is investigated in vitro. 17 beta-Estradiol secretion into the medium was assayed as a function of follicular diameter in the presence of lipoproteins with and without salmonid gonadotropin (SGA-GTH). The presence of very low-density lipoproteins (VLDL) + chylomicrons (Chy), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) amplified the SGA-GTH effect at the lowest concentrations tested (less than 50 micrograms protein/ml). HDL is the most effective for increasing hormone accumulation on a microgram lipoprotein sterol basis. Autoradiography of 125I-labeled LDL showed that they were preferentially bound by thecal cells. Kinetics of 17 beta-estradiol release indicated that lipoprotein amplification occurred especially after 15 hr and subsequent metabolism of 17 beta-estradiol by follicular layers also led to an equilibrium. At the end of vitellogenesis apoprotein B lipoproteins (VLDL + Chy, LDL) apparently inhibited SGA-GTH stimulation. N',O'-Dibutyryl cAMP (10 mM) considerably stimulated 17 beta-estradiol production but lipoprotein amplification did not occur. Chloroquine (30 microM) inhibition of LDL and HDL amplification indicates that this process requires lysosomal degradation. Plasma lipoproteins in trout modulate SGA-GTH stimulation of 17 beta-estradiol production during exogenous vitellogenesis. Due to the ease and frequency with which the experiments can be carried out, the ovarian follicle of salmonids is an excellent model for the study of the role of lipoproteins in the regulation of ovarian steroids biosynthesis. PMID:3026884

  2. Aqueous exposure to 4-nonylphenol and 17beta-estradiol increases stress sensitivity and disrupts ion regulatory ability of juvenile Atlantic salmon.

    PubMed

    Lerner, Darren T; Björnsson, Björn Thrandur; McCormick, Stephen D

    2007-07-01

    Population declines of wild Atlantic salmon have been attributed to an array of anthropogenic disturbances, including dams, commercial and recreational fishing, habitat loss, and pollution. Environmental contaminants in particular, can act as environmental stressors on fish, typically causing disruption of ion homeostasis due to their close association with the aquatic environment. To examine the effects of the xenoestrogen 4-nonylphenol (NP) or 17beta-estradiol (E2) on stress sensitivity and ion regulation, we exposed juvenile Atlantic salmon continuously for 21 d to either 10 or 100 microg/L NP (NP-L or NP-H), 2 microg/L E2 (positive control), or vehicle control during the parr-smolt transformation in April. After treatment, fish were sampled in freshwater (FW), transferred to 30 per thousand seawater (SW) for 24 h, or subjected to a handling stress. Estradiol and NP-H increased plasma vitellogenin in males and females, and E2 increased gonadosomatic index only in males. In FW, E2 reduced sodium potassium-activated adenosine triphosphatase activity as well as plasma levels of growth hormone, insulin-like growth factor I, and triiodothyronine. Both E2 and NP-H reduced plasma sodium in FW and increased plasma chloride in SW. Plasma cortisol levels pre- and poststressor were significantly elevated by all treatments relative to controls, but only E2 increased plasma glucose before and after the stressor. These results indicate that exposure of anadromous salmonids to environmental estrogens heightens sensitivity to external stressors, impairs ion regulation in both FW and SW, and disrupts endocrine pathways critical for smolt development. PMID:17665683

  3. Effects of the lignan, arctiin, on 17-beta ethinyl estradiol promotion of preneoplastic liver cell foci development in rats.

    PubMed

    Kato, T; Hirose, M; Takahashi, S; Hasegawa, R; Kohno, T; Nishibe, S; Kato, K; Shirai, T

    1998-01-01

    Anti-promotional effects of arctiin, a lignan with antiestrogenic action, against 17-beta ethinyl estradiol (EE) and 2-acetylaminofluorene (2-AAF) were examined using a medium-term liver bioassay based upon the induction of glutathione S-transferase placental form (GST-P) positive foci in rat liver. Male F344 rats were initially injected with diethylnitrosamine (DEN, 200 mg/kg body weight) intraperitoneally and two weeks later were treated with arctiin (1%), EE (1.5 ppm or 5 ppm), 2-AAF (20 ppm), arctiin + EE (1.5 ppm or 5 ppm), or arctiin + 2-AAF (20 ppm) in the diet for 6 weeks and then killed, all rats being subjected to partial hepatectomy at week 3. EE and 2-AAF clearly increased the development of GST-P foci. Antipromotional effects of arctiin were observed only for 2-AAF. These findings provide experimental evidence that arctiin exerts weak-protective potential against hepatocarcinogenesis in rats. PMID:9615764

  4. Polymorphism of 17-beta estradiol in a transdermal drug delivery system.

    PubMed

    Variankaval, N E; Jacob, K I; Dinh, S M

    2002-03-01

    The inclusions in a typical transdermal drug delivery system (TDS) containing estradiol drug were characterized using microscopic, spectroscopic and thermal analytical techniques. Optical and scanning electron microscopy were used to determine the locations and morphologies of the crystals in the matrix. Two different types of crystals randomly distributed laterally inside the patch were observed. Solid aggregates were found surrounding needle-like inclusions. Optical imaging through the thickness of the patch and SEM sections of the patch revealed that these inclusions were found to occupy a single layer inside the adhesive matrix. No inclusions were observed either in the backing-matrix interface or the matrix-liner interface. The inclusions exhibited a wide range of sizes. The thickness of the crystals as determined by SEM ranged from 10-14 microm. Out of the four crystal forms of estradiol, two of which are solvates (EA and EM) and the other two are anhydrous (EC and ED). Forms EC and ED did not exhibit significant differences in the spectra. Thermal analysis revealed that this was due to the highly unstable nature of ED and its tendency to either convert spontaneously to EC or occur in mixtures with it. The Raman spectrum of the aggregates in the patch showed peaks that seemed characteristic of at least two different forms of estradiol. Only one of these forms is a completely hydrogen bonded system and therefore, was concluded to be estradiol hemihydrate. A splitting of the C17-O peak at 1284 cm(-1) and 1294 cm(-1) was attributed to the existence of at least two types of crystal forms - one that exhibits hydrogen bonding and one that does not. DSC on different concentrations of estradiol in acrylic adhesive showed a clear endotherm for 14 wt % estradiol and apparent endotherms for lower concentrations. The absence of crystallization exotherms is due to the extremely slow kinetics of crystals growth in the polymeric patch. PMID:15348624

  5. The Effect of Estradiol-17(beta), Goitrogen (T3), and Flutamide on Gene Expression in Medaka, Oryzias latipes

    SciTech Connect

    E.Haut, J

    2005-09-06

    Concern has been generated over the discovery of endocrine disrupting chemicals in rivers near sewage outflows. The presence of endocrine disrupting chemicals such as estradiol-17{beta} has been associated with a reduction of reproductive success in fish and an increase in the female phenotype and gonadal intersex in fish downstream of sewage treatment facilities. Such effects are believed to result from a disruption in the normal estrogenic pathways since estrogen plays a vital role in reproduction, sexual differentiation, the developments of secondary sex characteristics, and ovulation. Most studies have focused on the effect of a single endocrine disruptor on a single gene which does not provide for the interaction between genes. Microarray technology has made it possible to put an entire genome on a single chip so that researchers can get a clearer picture of the interaction of genes expressed in a cell and changes of said interactions when those cells are exposed to various conditions. Medaka males were exposed to known endocrine disruptors, estradial-17{beta} and goitrogen, and medaka females were exposed to flutamide. All treatments were then compared to controls. Total RNA was extracted from the livers of both treated and untreated males and hybridized to a microarray chip designed to have EST sequences specific to medaka. ESTs were identified through two-channel microarray analysis and compared to GenBank using blastn searches to identify up regulated genes. Choriogenins H and L, zona radiata, and vitellogenin, previously shown to be estrogen-induced in male fish were identified. Heat shock proteins (hsp70, hsp90, and hsp8) were also induced by estradiol-17{beta}, as was choriogenin Hminor. Exposure to goitrogen (T3) resulted in the induced expression of glutathione S-transferase and a GABA receptor protein in male medaka. Treatment with flutamide, an antiandrogen, caused the up regulation of choriogenin L, choriogenin Hminor, and zona radiata-2 in female

  6. Estradiol-17beta protects against hypoxia-induced hepatocyte injury through ER-mediated upregulation of Bcl-2 as well as ER-independent antioxidant effects.

    PubMed

    Lee, Min Young; Jung, Sun Chul; Lee, Jang Hern; Han, Ho Jae

    2008-04-01

    Although many previous studies have suggested that estrogen functions as a cytoprotective agent under oxidative stress conditions, the underlying mechanism by which this effect is exerted remains to be elucidated. This study assessed the effects of estradiol-17beta (E(2)) (10(-8) M) on hypoxia-induced cell injury and its related signaling in primary cultured chicken hepatocytes. Hypoxic conditions were found to augment the level of DNA damage and to reduce cell viability and the level of [(3)H]-thymidine incorporation, and these phenomena were prevented through treatment with E(2). Hypoxia also increased caspase-3 expression, but showed no evidence of an influence on the expression of Bcl-2. However, E(2) induced an increase in the level of Bcl-2 expression under hypoxic conditions and reduced the level of caspase-3 expression. The effects of E(2) on Bcl-2 and caspase expression were blocked by ICI 182780 (E(2) receptor (ER) antagonist, 10(-7) M). In addition, hypoxia resulted in an increase in the intracellular reactive oxygen species (ROS) generated. These effects were blocked by E(2), but not by E(2)-BSA and ICI 182780. Hypoxia also activated p38 mitogen-activated protein kinase (MAPK), c-JUN N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and nuclear factor-kappaB (NF-kappaB). These effects were blocked by E(2), but not by ICI 182780. The inhibition of p38 MAPK and JNK/SAPK blocked NF-kappaB activation. In conclusion, E(2) was found to protect against hypoxia-induced cell injury in chicken hepatocytes through ER-mediated upregulation of Bcl-2 expression and through reducing the activity of ROS-dependent p38 MAPK, JNK/SAPK and NF-kappaB. PMID:18379592

  7. 17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat Whole Bladder

    PubMed Central

    2016-01-01

    Purpose: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. Methods: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17β-estradiol (50 μg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. Results: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17β-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17β-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17β-estradiol treatment. Conclusions: These results suggest that 17β-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression. PMID:27032553

  8. Biodistribution and metabolism of 16. cap alpha. -((/sup 18/F)-fluoro)-17. beta. -estradiol

    SciTech Connect

    Mathias, C.J.; Brodack, J.W.; Kilbourn, M.R.; Carlson, K.A.; Katzenellenbogen, J.A.; Welch, M.J.

    1985-05-01

    The uptake of receptor-mediated radiopharmaceuticals as measured by target to non-target uptake ratios depends upon many parameters. These include blood flow to the tissue, blood volume, receptor concentration as well as metabolism of the tracer. In a rat tumor model (DMBA) induced mammary tumors with high concentration of estrogen receptors) uptake of /sup 18/F-estradiol was studied while blood flow was measured with the use of /sup 125/I-iodoantipyrine, blood volume was measured with the use of /sup 99m/Tc-labeled red blood cells, and the receptor concentration by in vitro assay. The results demonstrate no correlation between blood flow and uptake of ligand, or between receptor concentration and uptake of ligand. No correlation existed between blood volume and uptake or /sup 18/F-estradiol, even though the blood volume varied by a factor of --20 in the tumors studied. The distribution of the fluorine-18 may depend upon metabolites of the ligand rather than the ligand itself. The authors have developed a technique to separate metabolites from the administered compound in blood and tissues. The distribution of the compound in the blood at times >30 mins after injection was primarily within the red blood cells in a chemical form that was not extractable even in lysed blood samples. By injecting blood from one rate into another the authors have shown that the activity in blood 2 hours after injection of /sup 18/F-estradiol is not available for uptake in receptor rich tissue but remains in the blood and non-target tissues.

  9. PLASMA CLEARANCE OF VITELLOGENIN IN SHEEPSHEAD MINNOWS AFTER CESSATION OF EXPOSURE TO 17BETA-ESTRADIOL AND PARA-NONYLPHENOL

    EPA Science Inventory

    Two experiments were performed to determine the rate of vitellogenin plasma accumulation and clearance in male sheepshead minnows (Cyprinodon variegatus) during and after exposure to either 17b-estradiol (E2) or para-nonylphenol (p-NP). Adult fish were continuously exposed to aqu...

  10. 17beta-estradiol affords protection against 4-vinylcyclohexene diepoxide-induced ovarian follicle loss in Fischer-344 rats.

    PubMed

    Thompson, Kary E; Sipes, I Glenn; Greenstein, Ben D; Hoyer, Patricia B

    2002-03-01

    Repeated dosing with 4-vinylcyclohexene diepoxide (VCD) accelerates atresia via apoptosis in primordial and primary follicles in ovaries of rats. The mechanisms that control atresia and VCD-induced toxicity are unknown; however, they could involve 17beta-E2. Atresia slows as animals enter puberty, whereas circulating E2 levels increase with the the onset of cyclicity. This inverse relationship suggests that E2 may be involved in the control of atresia. Therefore, this study was designed to determine whether treatment of immature rats with E2 could protect follicles normally destroyed by VCD-induced apoptosis. Female F344 rats were treated daily with E2, ER analogs, and/or VCD for 15 d. VCD alone caused a 50% reduction in primordial and primary follicles. Coinjection of E2 (0.1 mg/kg) and VCD (80 mg/kg) selectively protected primary follicles from VCD-induced follicle loss. This protection was mimicked by an ER agonist, genistein (0.1 mg/kg), and prevented by an ER antagonist, 4-hydroxytamoxifen (2 mg/kg). VCD treatment increased caspase-3-like activity, whereas concurrent treatment with genistein and VCD restored caspase-3-like activity to control levels. VCD treatment had no effect on circulating E2 levels, uterine weight, or E2 binding to the ER, nor could it directly displace E2 from ERbeta. These observations support the idea that ER-mediated protection against VCD-induced follicle toxicity is obtained by reducing apoptosis in small preantral follicles, although VCD does not appear to directly interact with ER. PMID:11861533

  11. High-affinity binding of [3H]estradiol-17 beta by an estrogen receptor in the liver of the turtle.

    PubMed

    Ho, S M; Fehrer, S; Yu, M; Liang, L C; Press, D

    1988-06-01

    Specific [3H]estradiol-17 beta ([3H]E2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds [3H]E2 with high affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of [3H]E2 binding activity in both cytosolic and nuclear fractions. The exchange between [3H]E2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species. PMID:3417113

  12. Effects of follicle-stimulating hormone and 17beta-estradiol on proliferation of chicken embryonic ovarian germ cells in culture.

    PubMed

    Xie, Meina; Zhang, Caiqiao; Zeng, Weidong; Mi, Yuling

    2004-12-01

    The effects of follicle-stimulating hormone (FSH) and 17beta-estradiol (E2) on chicken ovarian germ cell proliferation were evaluated through a germ-somatic cell coculture model. Ovarian cells from the left ovaries of 18-day-old chicken embryos were cultured in serum-free McCoy's 5A medium at 39 degrees C and challenged with FSH (0.25-1.0 IU/mL) or E2 (10(-8)-10(-5) M) alone and in combination for 48 h. The number of germ cells was counted, and the proliferating cells were immunolocalized by a specific antibody against proliferating cell nuclear antigen (PCNA). The labeling index (LI) was determined for germ cells. Results revealed that germ cells could survive and kept proliferating under support of somatic cells. Germ cells were localized by expression of a specific antibody for stem cell factor receptor c-kit. Both FSH (0.25-1.0 IU/mL) and E2 (10(-7)-10(-5) M) alone induced a marked increase in germ cell number (P<0.05), and PCNA-LI of germ cells was greater in FSH-treated groups (0.25-1.0 IU/mL) and E2-treated groups (10(-8)-10(-5) M), compared with vehicle-treated group (P<0.05). Furthermore, FSH manifested a synergistic effect with E2 (10(-6)-10(-5) M) in stimulating germ cell proliferation. These results indicate that FSH might interact with estrogen to promote ovarian germ cell proliferation in embryonic chickens near hatching. PMID:15596398

  13. High-affinity binding of (/sup 3/H)estradiol-17 beta by an estrogen receptor in the liver of the turtle

    SciTech Connect

    Ho, S.M.; Fehrer, S.; Yu, M.; Liang, L.C.; Press, D.

    1988-06-01

    Specific (3H)estradiol-17 beta ((3H)E2) binding activity (EBA) with characteristics of an estrogen receptor (ER) was demonstrated in cytosols and nuclear extracts of the female turtle, Chrysemys picta. Three different receptor assays (dextran-coated charcoal assay, hydroxylapatite batch procedure, and DNA-cellulose chromatography) were evaluated in terms of their applicability in analyzing large numbers of samples. For the measurement of cytosolic EBA, the hydroxylapatite batch procedure was found to be the most reliable assay. On the other hand, the dextran-coated charcoal assay was found to be the most appropriate method for the measurement of nuclear EBA. Turtle hepatic EBA binds (3H)E2 with high affinity (cytosolic, 17.4 +/- 2.8 X 10(9) M-1; nuclear, 17.7 +/- 1.9 X 10(9) M-1), limited capacity (cytosolic, 133.7 +/- 4.6 fmol/g tissue; nuclear, 81.1 +/- 9.0 fmol/g tissue), and strict steroid specificity. The EBA bound natural estrogens (E2, estrone, estriol) as well as the nonsteroidal estrogen, diethylstilbestrol, but exhibited little affinity for androgens, progesterone, or corticosterone. The turtle hepatic EBA resembled mammalian and avian ERs in terms of binding characteristics; however, unlike mammalian and avian ERs it was shown to be heat-labile. Incubation at 30 degrees caused rapid loss of (3H)E2 binding activity in both cytosolic and nuclear fractions. The exchange between (3H)E2 and the endogenously bound estrogen was slow at 4 and 15 degrees, but the exchange process was facilitated in the presence of the chaotropic salt, NaSCN. Establishment of quantitation methods for both cytosolic and nuclear forms of EBA will enable future investigation of the mechanism and regulation of estrogen action in the liver of this turtle species.

  14. Larval exposure to 4-nonylphenol and 17beta-estradiol affects physiological and behavioral development of seawater adaptation in Atlantic salmon smolts.

    PubMed

    Lerner, Darren T; Björnsson, Björn Thrandur; McCormick, Stephen D

    2007-06-15

    Population declines of anadromous salmonids are attributed to anthropogenic disturbances including dams, commercial and recreational fisheries, and pollutants, such as estrogenic compounds. Nonylphenol (NP), a xenoestrogen, is widespread in the aquatic environment due to its use in agricultural, industrial, and household products. We exposed Atlantic salmon yolk-sac larvae to waterborne 10 or 100 microg L(-1) NP (NP-L or NP-H, respectively), 2 microg L(-1) 17beta-estradiol (E2), or vehicle, for 21 days to investigate their effects on smolt physiology and behavior 1 year later. NP-H caused approximately 50% mortality during exposure, 30 days after exposure, and 60 days after exposure. Mortality rates of NP-L and E2 fish were not affected until 60 days after treatment, when they were 4-fold greater than those of controls. Treatment with NP-L or E2 as yolk-sac larvae decreased gill sodium-potassium-activated adenosine triphosphatase (Na+,K(+)-ATPase) activity and seawater (SW) tolerance during smolt development, 1 year after exposure. Exposure to NP-L and E2 resulted in a latency to enter SW and reduced preference for SW approximately 2- and 5-fold, respectively. NP-L-exposed fish had 20% lower plasma insulin-like growth factor I (IGF-I) levels and 35% lower plasma triiodothyronine (T3). Plasma growth hormone and thyroxine (T4) were unaffected. Exposure to E2 did not affect plasma levels of IGF-I, GH, T3, or T4. Both treatment groups exhibited increased plasma cortisol and decreased osmoregulatory capacity in response to a handling stressor. These results suggest that early exposure to environmentally relevant concentrations of NP, and other estrogenic compounds, can cause direct and delayed mortalities and that this exposure can have long-term, "organizational" effects on life-history events in salmonids. PMID:17626455

  15. Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17{beta}-estradiol

    SciTech Connect

    Yanagihara, Nobuyuki . E-mail: yanagin@med.uoeh-u.ac.jp; Liu, Minhui; Toyohira, Yumiko; Tsutsui, Masato; Ueno, Susumu; Shinohara, Yuko; Takahashi, Kojiro; Tanaka, Kazumi

    2006-01-13

    Incubation of cultured bovine adrenal medullary cells with 17{beta}-estradiol (E{sub 2}) (0.3-100 nM) or membrane-impermeable E{sub 2}-bovine serum albumin (100 nM) acutely increased {sup 14}C-catecholamine synthesis from [{sup 14}C]tyrosine. The stimulatory effect of E{sub 2} was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor. E{sub 2} also increased tyrosine hydroxylase activity and p44/42MAPK phosphorylation, the former of which was attenuated by U0126, an inhibitor of p44/42MAPK kinase. The plasma membrane isolated from the gland showed two classes of specific binding sites of [{sup 3}H]E{sub 2} with apparent K {sub d}s of 3.2 and 106 nM, and B {sub max}s of 0.44 and 8.5 pmol/mg protein, respectively. The high-affinity binding of [{sup 3}H]E{sub 2} was most strongly inhibited by E{sub 2} and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants. These findings suggest that E{sub 2} acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla.

  16. Tissue expression of glandular kallikrein and its response to 17 beta-estradiol in the acclimatized carp.

    PubMed

    Haussmann, Denise; Vidal, Rene; Figueroa, Jaime

    2006-06-01

    Cyprinus carpio skeletal muscle kallikrein was isolated to apparent homogeneity, and a polyclonal antiserum against the purified protein was generated. Glandular kallikrein expression and tissue distribution were assessed using both Western blots and immunohistochemistry. A 39-kDa protein was detected in skeletal muscle, the gill, kidney, and pituitary gland, where an additional 72-kDa immunoreactive band was observed. Immunohistochemistry revealed immunoreactive kallikrein in the intermuscle tissue, epithelial gill cells, apical portion of distal and proximal tubular cells in the kidney, mucus and epithelial cells of the skin, intestinal tube, and prolactin-producing cells of the pituitary gland. In addition, the effect of 17beta-estradiol on kallikrein expression was analyzed in three different tissues of winter- and summer-acclimatized male carps. A 2.5-fold (p<0.05) increase in kallikrein immunoreactivity due to estrogen treatment was observed in winter-acclimatized carp muscle, but not in summer-acclimatized fish. In contrast, the gill responded differently, since a 2-fold (p<0.05) increase was found only in summer-acclimatized carps. Kallikrein immunoreactivity in the kidney increased both in summer- (2.5 fold) and in winter-acclimatized carps (1.5 fold). The signals obtained demonstrate the existence of tissue-specific variable responses to estrogen treatment in vivo, between winter and summer-acclimatized carp. PMID:16849838

  17. Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-{beta} estradiol and nonylphenol

    SciTech Connect

    Soverchia, L.; Ruggeri, B.; Palermo, F.; Mosconi, G.; Cardinaletti, G.; Scortichini, G.; Gatti, G.; Polzonetti-Magni, A.M. . E-mail: alberta.polzonetti@unicam.it

    2005-12-15

    Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17{beta} and different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP) on the expression of liver ER{beta}-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17{beta}) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10{sup -6} and 10{sup -7} M) of 4-nonylphenol (4-NP), or 10{sup -7} M of estradiol-17{beta}. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17{beta} and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17{beta} plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ER{beta}-1 mRNA in the liver, demonstrating that both estradiol-17{beta} and 4-NP modulate the vitellogenin

  18. Contrasting effects of increased and decreased dopamine transmission on latent inhibition in ovariectomized rats and their modulation by 17beta-estradiol: an animal model of menopausal psychosis?

    PubMed

    Arad, Michal; Weiner, Ina

    2010-06-01

    Women with schizophrenia have later onset and better response to antipsychotic drugs (APDs) than men during reproductive years, but the menopausal period is associated with increased symptom severity and reduced treatment response. Estrogen replacement therapy has been suggested as beneficial but clinical data are inconsistent. Latent inhibition (LI), the capacity to ignore irrelevant stimuli, is a measure of selective attention that is disrupted in acute schizophrenia patients and in rats and humans treated with the psychosis-inducing drug amphetamine and can be reversed by typical and atypical APDs. Here we used amphetamine (1 mg/kg)-induced disrupted LI in ovariectomized rats to model low levels of estrogen along with hyperfunction of the dopaminergic system that may be occurring in menopausal psychosis, and tested the efficacy of APDs and estrogen in reversing disrupted LI. 17beta-Estradiol (50, 150 microg/kg), clozapine (atypical APD; 5, 10 mg/kg), and haloperidol (typical APD; 0.1, 0.3 mg/kg) effectively reversed amphetamine-induced LI disruption in sham rats, but were much less effective in ovariectomized rats; 17beta-estradiol and clozapine were effective only at high doses (150 microg/kg and 10 mg/kg, respectively), whereas haloperidol failed at both doses. Haloperidol and clozapine regained efficacy if coadministered with 17beta-estradiol (50 microg/kg, an ineffective dose). Reduced sensitivity to dopamine (DA) blockade coupled with spared/potentiated sensitivity to DA stimulation after ovariectomy may provide a novel model recapitulating the combination of increased vulnerability to psychosis with reduced response to APD treatment in female patients during menopause. In addition, our data show that 17beta-estradiol exerts antipsychotic activity. PMID:20237462

  19. Effects of Lepidium meyenii Walp and Jatropha macrantha on blood levels of estradiol-17 beta, progesterone, testosterone and the rate of embryo implantation in mice.

    PubMed

    Oshima, Masami; Gu, Yeunhwa; Tsukada, Sekihito

    2003-10-01

    The effects of two Peruvian folk medicines, Lepidium meyenii Walp and Jatropha macrantha, on mouse sex steroid hormones and embryo implantation were investigated. Progesterone levels increased significantly in mice that received L. meyenii Walp, while testosterone levels increased significantly in mice that received L. meyenii Walp as well as in those that received both L. meyenii Walp and J. macrantha. However, there were no marked changes in blood levels of estradiol-17beta or the rate of embryo implantation. PMID:14600359

  20. Maternally derived testosterone and 17beta-estradiol in the eggs of Arctic-breeding glaucous gulls in relation to persistent organic pollutants.

    PubMed

    Verboven, Nanette; Verreault, Jonathan; Letcher, Robert J; Gabrielsen, Geir W; Evans, Neil P

    2008-08-01

    It is largely unknown if and how persistent organic pollutants (POPs) affect the transfer of maternal hormones to eggs. This occurs despite an increasing number of studies relating environmental conditions experienced by female birds at the time of egg formation to maternal hormonal effects. Here we report the concentrations of maternal testosterone, 17beta-estradiol and major classes of POPs (organochlorines, brominated flame retardants and metabolically-derived products) in the yolk of unincubated, third-laid eggs of the glaucous gull (Larus hyperboreus), a top-predator in the Arctic marine environment. Controlled for seasonal and local variation, positive correlations were found between the concentrations of certain POPs and testosterone. Contaminant-related changes in the relative concentrations of testosterone and 17beta-estradiol were also observed. In addition, yolk steroid concentrations were associated with contaminant profiles describing the proportions of different POPs present in the yolk. Eggs from nests in which two sibling eggs hatched or failed to hatch differed in POP profiles and in the relative concentrations of testosterone and 17beta-estradiol. Although the results of this correlative study need to be interpreted with caution, they suggest that contaminant-related changes in yolk steroids may occur, possibly affecting offspring performance over and above toxic effects brought about by POPs in eggs. PMID:18550446

  1. Vitellogenin mRNA regulation and plasma clearance in male sheepshead minnows, (Cyprinodon variegatus) after cessation of exposure to 17 beta-estradiol and p-nonylphenol.

    PubMed

    Hemmer, Michael J; Bowman, Christopher J; Hemmer, Becky L; Friedman, Stephanie D; Marcovich, Dragoslav; Kroll, Kevin J; Denslow, Nancy D

    2002-07-01

    Research was conducted to determine the kinetics of hepatic vitellogenin (VTG) mRNA regulation and plasma VTG accumulation and clearance in male sheepshead minnows (Cyprinodon variegatus) during and after cessation of exposure to either 17 beta-estradiol (E2) or para-nonylphenol (NP). Adult fish were continuously exposed to aqueous measured concentrations of 0.089 and 0.71 microg E2 per l, and 5.6 and 59.6 microg NP per l for 16 days using an intermittent flow-through dosing apparatus. Fish were sampled on days 8 and 16 of exposure followed by sampling at discrete intervals for up to 96 days post-exposure. At each interval five fish were randomly sampled from each concentration and hepatic VTG mRNA and serum VTG levels for individual fish determined by slot blot and direct enzyme-linked immunosorbent assay (ELISA), respectively. Exposure to E2 and NP resulted in a dose dependent increase in hepatic VTG mRNA and plasma VTG over the course of the 16-day exposure period. Mean plasma VTG levels at day 16 were >100 mg/ml for both high doses of E2 and NP, and >20 mg/ml for the low exposure treatments. Within 8 days post-exposure, hepatic VTG mRNA levels returned to baseline in both high and low E2 treatments but remained elevated 2-4 fold in the NP treatments. Due to a shortened sampling period, a clearance rate for plasma VTG in the 5.6 microg NP per l treatment could not determined. In the 0.089, 0.71 microg E2 per l, and 59.6 microg NP per l treatments, VTG levels began decreasing within 4 days after exposure cessation and exhibited an exponential rate of elimination from plasma. Clearance rates for 0.71 microg E2 per l and 59.6 microg NP per l were not significantly different (P=0.47), however, both demonstrated significantly higher rates of clearance (P<0.02) than observed in the 0.089 microg E2 per l treatment. Our results indicate that hepatic VTG mRNA rapidly diminishes after cessation of estrogenic exposure in sheepshead minnows, but plasma VTG clearance is

  2. Cosupplementation of isoflavones, prenylflavonoids, and lignans alters human exposure to phytoestrogen-derived 17beta-estradiol equivalents.

    PubMed

    Bolca, Selin; Wyns, Ciska; Possemiers, Sam; Depypere, Herman; De Keukeleire, Denis; Bracke, Marc; Verstraete, Willy; Heyerick, Arne

    2009-12-01

    The microbial metabolism of dietary phytoestrogens varies considerably among individuals and influences the final exposure to bioactive compounds. In view of the increasing number of food supplements combining several classes of phytoestrogens, the microbial potential to activate various proestrogens within an individual was evaluated in 3 randomized dietary crossovers. Treatment allocation was based on participants' eligibility (>45% in vitro bioactivation of >or=2 separate proestrogens by fecal cultures; n = 40/100). After a run-in of >or=4 d, participants were given soy-, hop-, and/or flax-based food supplements dosed either separately (SOY: 2.83 mg daidzein aglycone equivalents/supplement, HOP: 1.20 mg isoxanthohumol (IX)/supplement, or FLAX: 2.08 mg secoisolariciresinol (SECO) aglycone equivalents/supplement; reference intervention) or simultaneously (MIX; test intervention) 3 times/d for 5 d, followed by a wash-out period (>or=7 d) and the second intervention. Before and after each (co)supplementation, spot urine and serum were collected. In total, 22 equol, 19 8-prenylnaringenin (8-PN), and 21 enterolactone (ENL) producers completed the SOY+MIX, HOP+MIX, and FLAX+MIX trials, respectively. The microbial bioactivation of daidzein, IX, and SECO, generally decreased upon coincubation in vitro (equol: 4.4%, P = 0.164; 8-PN: 20.5%, P < 0.001; ENL: 44.3%, P < 0.001) and cosupplementation in vivo (equol: 28.3%, P = 0.009; 8-PN: 35.4%, P = 0.107; ENL: 35.9%, P = 0.003). Although the bioavailabilities of total isoflavones, prenylflavonoids, and lignans were not significantly affected upon coadministration, participants were exposed to lower phytoestrogen-derived 17beta-estradiol equivalents. In conclusion, the bioavailability of phytoestrogens, especially when given in mixtures, is subject to high interindividual variation. These findings support the importance of personalized screening when assessing the efficacy of such products and mixtures. PMID:19864398

  3. Environmental Technology Verification Report for Abraxis 17β-Estradiol (E2) Magnetic Particle Enzyme-Linked Immunosorbent Assay (ELISA) Test Kits

    EPA Science Inventory

    The EPA's National Risk Management Research Laboratory (NRMRL) and its verification organization partner, Battelle, operate the Advanced Monitoring Systems (AMS) Center under ETV. The AMS Center recently evaluated the performance of the Abraxis 17(beta)-estradiol (E2) magnetic p...

  4. Effect of four environmental toxicants on plasma Ca and estradiol 17[beta] and hepatic P450 in laying hens

    SciTech Connect

    Chen, S.W.; Dziuk, P.J.; Francis, B.M. . Dept. of Animal Sciences)

    1994-05-01

    In a previous study, the authors found that administration of phenobarbital to laying hens was associated with an increase in content of liver cytochrome P450 and a reduction of estradiol (E2) in serum. Thus, the authors hypothesized that other xenobiotics such as environmental toxicants that affect P450 might also affect E2 in laying hens. In experiment 1, the authors examined the effect of four environmental pollutants, three of which induced different isoenzymes of P450 and one inhibitor, on circulating E2 and related reproductive functions. Aroclor 1254 (PCB), 20 mg/d; dichlorodiphenyltrichloroethane (DDT), 40 mg/d; or benzo[a]pyrene (BZ), 5 mg/d, was administered for 5 d. An inhibitor, lead acetate, was injected for 2 d. Controls received corn oil or sodium acetate. No significant difference was observed due to administration of lead. Treatment with PCB or DDT decreased the concentration of E2 and increased P450. Only PCB significantly decreased plasma total calcium and egg lay. Therefore in experiment 2, the authors determined the dose-response effect of PCB. The PCB was given orally at doses of 0, 5, 10, and 25 mg in corn oil for 5 d. The depression of concentrations of E2 was associated with the induction of P450 in a dose-dependent manner. Egg production and plasma total calcium were reduced by the two highest doses, but eggshell thickness was not different from control in all regimens. Plasma E2 and plasma total calcium were negatively correlated with induction of P450. BZ is not a strong inducer of P450 and had no effect on E2 or reproduction, whereas DDT and PCB had a profound effect on P450 with consequent depression of circulating E2. These data indicate that the effects of environmental pollutants on reproduction in birds can be mediated through increased P450, thereby increasing the metabolism of steroid hormones and depressing concentration in circulation.

  5. [Biological and clinical safety of nomegestrol acetate administered alone then associated in inverse sequence with transdermal 17 beta estradiol, in women at risk of dyslipoproteinemia type IIa].

    PubMed

    Zartarian, M; Chevallier, T; Micheletti, M C; Leber, C; Jamin, C

    1998-12-01

    In this study including 26 patients with dyslipoproteinemia classified IIa, we evaluated biochemical and clinical safety of Nomegestrol acetate (Lutenyl) used for its antigonadotrophin property. It was administered alone, during 3 cycles at the dose of 5 mg/d for 21 days by cycle and then it was associated (at the same sequence and dose), without any wash out, for the next 6 cycles, with a 17 beta estradiol patch (Estraderm TTS 50), 50 micrograms/d from the 11th to the 21st day of each cycle. Nomegestrol acetate, alone, had no significant effect on glycemia, antithrombin III, triglycerides, total cholesterol, apoprotein A1, and LpA1 values compared to those at baseline but apoprotein B and Lp (a) values tended to decrease slightly. Serum progesterone levels were collapsed, and FSH values were low. Weight and blood pressure remained constant. Adding 17 beta estradiol enabled to significantly decrease and normalize the apoprotein B values after the first 3 cycles compared to the baseline values, then these values remained constant during the next 3 cycles. There was no effect on the other parameters (except for a significant increase in plasmatic estradiol values) on the antigonadotrophin property of Nomegestrol acetate, nor on weight and blood pressure which remained constant. Moreover, we observed an important decrease in the rate of amenorrheic cycles compared to those with Nomegestrol acetate alone. PMID:9949893

  6. 17beta-estradiol inhibits apoptosis in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements present in the coding sequence.

    PubMed

    Perillo, B; Sasso, A; Abbondanza, C; Palumbo, G

    2000-04-01

    We have found that 17beta-estradiol induces bcl-2 transcription in human breast cancer MCF-7 cells. To identify cis-acting elements involved in this regulation, we have analyzed hormone responsiveness of transiently transfected reporter constructs containing the bcl-2 major promoter (P(1)). Hormone inducibility was observed only when either of two sequences, located within the bcl-2 coding region and showing one and two mutations with respect to the consensus estrogen-responsive element, were inserted downstream from the P(1) promoter. Both sequences behaved as enhancers exclusively in cells expressing the estrogen receptor and were able to bind this receptor in in vitro assays. Transfections into MCF-7 cells of plasmids carrying a bcl-2 cDNA fragment which included these two elements revealed that their simultaneous presence resulted in an additive effect on reporter gene activity, whose size resembled the increase of endogenous bcl-2 mRNA level observed in untransfected cells after hormone treatment. Moreover, the identified elements were able to mediate up-regulation of bcl-2 expression by 17beta-estradiol, since exogenous bcl-2 mRNA was induced by hormone challenge of MCF-7 cells transiently transfected with a vector containing the bcl-2 coding sequence cloned under the control of a non-estrogen-responsive promoter. Finally, we show that hormone prevention of apoptosis, induced by incubating MCF-7 cells with hydrogen peroxide, was strictly related to bcl-2 up-regulation. Our results indicate that the bcl-2 major promoter does not contain cis-acting elements directly involved in transcriptional control by 17beta-estradiol and that hormone treatment inhibits programmed cell death in MCF-7 cells, inducing bcl-2 expression via two estrogen-responsive elements located within its coding region. PMID:10733592

  7. A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

    PubMed

    Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

    2015-02-01

    Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism. PMID:25474166

  8. Novel estrogens and their radical scavenging effects, iron-chelating, and total antioxidative activities: 17 alpha-substituted analogs of delta 9(11)-dehydro-17 beta-estradiol.

    PubMed

    Römer, W; Oettel, M; Menzenbach, B; Droescher, P; Schwarz, S

    1997-11-01

    Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17 alpha-substituted analogs of 17 beta-estradiol and their delta 9(11)-dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fenton's reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activity. Whereas the classical estrogen 17 beta-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides delta 9(11)-dehydro-17 beta-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17 beta-estradiol (J 843, J 872, and J 897) and delta 9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17 beta-estradiol, e.g., the introduction of a delta 9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation. PMID:9366006

  9. Characterization of high specific activity (16 alpha-123I)Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors

    SciTech Connect

    Pavlik, E.J.; Nelson, K.; Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Shih, W.J.; Spicer, J.A.; Preston, D.F.; Baranczuk, R.J.; Kenady, D.E. )

    1990-12-15

    16 alpha-(123I)Iodo-17 beta-estradiol (16 alpha-(123I)E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-(123I)E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-(123I)E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-(123I)E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-(123I)E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers.

  10. 17beta-estradiol, progesterone and testosterone concentrations in cystic fluids and response to GnRH treatment after emptying of ovarian cysts in dairy cows.

    PubMed

    Cairoli, F; Vigo, D; Battocchio, M; Faustini, M; Veronesi, M C; Maffeo, G

    2002-10-01

    The aim of this study was to determine possible links between steroidogenic activity of single ovarian cysts and response to intramuscular treatment with 20 microg of buserelin (GnRH-analogue) after cyst emptying, in pluriparous Friesian cows bearing a singleton cyst treated not earlier than 55 days post-partum. Progesterone, 17beta-estradiol and testosterone were determined in cystic fluids collected by needle aspiration of the cyst. Of the cows, 75.6% began ovarian cyclicity within 30 days after treatment with a conception rate of 64.7%. In this study it was found that as progesterone concentration in cystic fluids rose, the number of positive responses to the treatment fell. PMID:12354183

  11. Annual changes in fecal estradiol-17beta concentrations of the sun bear (Helarctos malayanus) in Sarawak, Malaysia.

    PubMed

    Onuma, Manabu; Suzuki, Masatsugu; Uchida, Eiji; Niiyama, Masami; Ohtaishi, Noriyuki

    2002-04-01

    Fecal estradiol concentrations were measured in three captive unmated female sun bears (Helarctos malayanus) from August 1998 to July 1999 in Sarawak, Malaysia and vaginal smears from one of the females was observed in August 1998 and March 1999. A single peak in fecal estradiol concentration was obvious for each bear in August or September 1998, and there was a much higher percentage of superficial vaginal anuclear cells in August 1998 than in March 1999. These results suggest that sun bears in Sarawak are likely to be a seasonal breeder associated with a peak of estrogen production in August or September. PMID:12014574

  12. 17Beta-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cells.

    PubMed

    Urata, Yoshishige; Ihara, Yoshito; Murata, Hiroaki; Goto, Shinji; Koji, Takehiko; Yodoi, Junji; Inoue, Satoshi; Kondo, Takahito

    2006-05-12

    The GSH/glutaredoxin (GRX) system is involved in the redox regulation of certain enzyme activities, and this system protects cells from H2O2-induced apoptosis by regulating the redox state of Akt (Murata, H., Ihara, Y., Nakamura, H., Yodoi, J., Sumikawa, K., and Kondo, T. (2003) J. Biol. Chem. 278, 50226-50233). Estrogens, such as 17beta-estradiol (E2), play an important role in development, growth, and differentiation and appear to have protective effects on oxidative stress mediated by estrogen receptor alpha (ERalpha). However, the role of the ERbeta-mediated pathway in this cytoprotection and the involvement of E2 in the redox regulation are not well understood. In the present study, we demonstrated that E2 protected cardiac H9c2 cells, expressing ERbeta from H2O2-induced apoptosis concomitant with an increase in the activity of Akt. E2 induced the expression of glutaredoxin (GRX) as well as gamma-glutamylcysteine synthetase, a rate-limiting enzyme for the synthesis of GSH. Inhibitors for both gamma-glutamylcysteine synthetase and GRX and ICI182,780, a specific inhibitor of ERs, abolished the protective effect of E2 on cell survival as well as the activity of Akt, suggesting that ERbeta is involved in the cytoprotection and redox regulation by E2. Transcription of the GRX gene was enhanced by E2. The promoter activity of GRX was up-regulated by an ERbeta-dependent element. These results suggest that the GRX/GSH system is involved in the cytoprotective and genomic effects of E2 on the redox state of Akt, a pathway that is mediated, at least in part, by ERbeta. This mechanism may also play an antiapoptotic role in cancer cells during carcinogenesis or chemotherapy. PMID:16549430

  13. 17beta-estradiol counteracts neuropathic pain: a behavioural, immunohistochemical, and proteomic investigation on sex-related differences in mice

    PubMed Central

    Vacca, Valentina; Marinelli, Sara; Pieroni, Luisa; Urbani, Andrea; Luvisetto, Siro; Pavone, Flaminia

    2016-01-01

    Sex differences play a role in pain sensitivity, efficacy of analgesic drugs and prevalence of neuropathic pain, even if the underlying mechanisms are far from being understood. We demonstrate that male and female mice react differently to structural and functional changes induced by sciatic nerve ligature, used as model of neuropathic pain. Male mice show a gradual decrease of allodynia and a complete recovery while, in females, allodynia and gliosis are still present four months after neuropathy induction. Administration of 17β-estradiol is able to significantly attenuate this difference, reducing allodynia and inducing a complete recovery also in female mice. Parallel to pain attenuation, 17β-estradiol treated-mice show a functional improvement of the injured limb, a faster regenerative process of the peripheral nerve and a decreased neuropathy-induced gliosis. These results indicate beneficial effects of 17β-estradiol on neuropathic pain and neuronal regeneration and focuses on the importance of considering gonadal hormones also in clinical studies. PMID:26742647

  14. An inter-laboratory study on the variability in measured concentrations of 17Beta-estradiol, testosterone and 11-ketotestosterone in white sucker: implications and recommendations

    EPA Science Inventory

    Endocrine-disrupting chemicals (EDCs) are exogenous substances that can lead to impacts on the reproduction of fish sometimes by altering circulating concentrations of 17â-estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT). Common methods to measure steroids in pla...

  15. Up-regulation of PI3K/Akt signaling by 17{beta}-estradiol through activation of estrogen receptor-{alpha}, but not estrogen receptor-{beta}, and stimulates cell growth in breast cancer cells

    SciTech Connect

    Lee, Young-Rae; Park, Jinny; Kim, Jong-Suk; Youn, Hyun Jo; Jung, Sung Hoo . E-mail: shjung@chonbuk.ac.kr

    2005-11-04

    Estrogen stimulates cell proliferation in breast cancer. The biological effects of estrogen are mediated through two intracellular receptors, estrogen receptor-{alpha} (ER{alpha}) and estrogen receptor-{beta} (ER{beta}). However, the role of ERs in the proliferative action of estrogen is not well established. Recently, it has been known that ER activates phosphatidylinositol-3-OH kinase (PI3K) through binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism with subsequent formation of phosphatidylinositol-3,4,5-trisphosphate (PIP{sub 3}), which is generated from phosphatidylinositol 4,5-bisphosphate via PI3K activation. The present study demonstrates that 17{beta}-estradiol (E2) up-regulates PI3K in an ER{alpha}-dependent manner, but not ER{beta}, and stimulates cell growth in breast cancer cells. In order to study this phenomenon, we have treated ER{alpha}-positive MCF-7 cells and ER{alpha}-negative MDA-MB-231 cells with 10 nM E2. Treatment of MCF-7 cells with E2 resulted in a marked increase in PI3K (p85) expression, which paralleled an increase in phospho-Akt (Ser-473) and PIP{sub 3} level. These observations also correlated with an increased activity to E2-induced cell proliferation. However, these effects of E2 on breast cancer cells were not observed in the MDA-MB-231 cell line, indicating that the E2-mediated up-regulation of PI3K/Akt pathway is ER{alpha}-dependent. These results suggest that estrogen activates PI3K/Akt signaling through ER{alpha}-dependent mechanism in MCF-7 cells.

  16. Rainfall and tillage effects on transport of fecal bacteria and sex hormones 17beta-estradiol and testosterone from broiler litter applications to a Georgia Piedmont Ultisol.

    PubMed

    Jenkins, Michael B; Truman, Clint C; Siragusa, Gregory; Line, Eric; Bailey, J Stan; Frye, Jonathan; Endale, Dinku M; Franklin, Dorcas H; Schomberg, Harry H; Fisher, Dwight S; Sharpe, Ronald R

    2008-09-15

    Poultry litter provides nutrients for crop and pasture production; however, it also contains fecal bacteria, sex hormones (17beta-estradiol and testosterone) and antibiotic residues that may contaminate surface waters. Our objective was to quantify transport of fecal bacteria, estradiol, testosterone and antibiotic residues from a Cecil sandy loam managed since 1991 under no-till (NT) and conventional tillage (CT) to which either poultry litter (PL) or conventional fertilizer (CF) was applied based on the nitrogen needs of corn (Zea mays L) in the Southern Piedmont of NE Georgia. Simulated rainfall was applied for 60 min to 2 by 3-m field plots at a constant rate in 2004 and variable rate in 2005. Runoff was continuously measured and subsamples taken for determining flow-weighted concentrations of fecal bacteria, hormones, and antibiotic residues. Neither Salmonella, nor Campylobacter, nor antimicrobial residues were detected in litter, soil, or runoff. Differences in soil concentrations of fecal bacteria before and after rainfall simulations were observed only for Escherichia coli in the constant rainfall intensity experiment. Differences in flow-weighted concentrations were observed only for testosterone in both constant and variable intensity rainfall experiments, and were greatest for treatments that received poultry litter. Total loads of E. coli and fecal enterococci, were largest for both tillage treatments receiving poultry litter for the variable rainfall intensity. Load of testosterone was greatest for no-till plots receiving poultry litter under variable rainfall intensity. Poultry litter application rates commensurate for corn appeared to enhance only soil concentrations of E. coli, and runoff concentrations of testosterone above background levels. PMID:18571694

  17. Glandular kallikreins in the teleost Cyprinus carpio: tissue distribution, possible involvement in prolactin processing, and effect of 17 beta-estradiol in vivo.

    PubMed

    Figueroa, J; Fernández, K; Haussmann, D; Richards, G; Barra, V; Kausel, G

    2002-09-01

    We examined glandular kallikrein (GK), a putative prolactin processing protease, in the teleost Cyprinus carpio. When employing an anti-Centropristis striata GK antibody proteins of 39 kDa in muscle, 52 kDa in gill, 52 kDa in kidney, and two proteins of 46 and 72 kDa in pituitary gland were detected. Immunoreactive kallikreins were recognized in intermuscle cell tissue, epithelial gill cells, apical region of tubular cells, and prolactin producing lactotrophs in pituitary gland, suggesting a osmoregulatory role for this enzyme. We found three prolactin (PRL) variants using anti-tilapia PRL antibodies, in pituitary gland 23 and 16 kDa, and in plasma 23 and 22 kDa forms. Clearly co-localization of GK and PRL in lactotrophs could be demonstrated. In winter-acclimatized male carp, where the pituitary PRL level is low, 17beta-estradiol treatment increased PRL but not GK immunoreactivity. In contrast to GK and PRL co-regulation by estrogen in mammalian pituitary gland, no similar effect on immunoreactive PRL and GK was observed in the ichtyc pituitary. No changes in GK immunostaining occurred in gill or muscle tissue in response to estrogen treatment. These results, taken with the observation of significantly increased GK immunoreactivity in the apical region of kidney tubular cells in estrogen treated male carp, indicate that the regulation of GK expression in pituitary and kidney could be different in fish with respect to mammals. PMID:12392686

  18. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    SciTech Connect

    Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  19. Hepatic estrogen receptor and plasma 17{beta}-estradiol concentrations as biomarkers of 2,3,7,8-TCDD exposure in avian hatchlings

    SciTech Connect

    Janz, D.M.; Bellward, G.D.

    1995-12-31

    The authors have been investigating the sensitivity of various toxicologically relevant endpoints as environmental biomarkers in avian hatchlings exposed in ovo to 2,3,7,8-TCDD. Potential biomarkers included various endocrine endpoints such as plasma 17{beta}-estradiol (E{sub 2}), hepatic estrogen receptor (ER) affinities and concentrations, and plasma thyroid hormones, which were compared to hepatic ethoxyresorufin O-deethylase (EROD) induction. The animal models used were domestic chickens and pigeons, and great blue herons. An experiment conducted in pigeon hatchlings compared ``early`` (embryonic day 4; E4) vs. ``late`` (E14) in ovo exposure to 1 {micro}g/kg and 3 {micro}g/kg of TCDD, respectively. Birds were sacrificed on day of hatch (H) and day 7 after hatch (D7). In the late exposure experiment, plasma E{sub 2} concentrations were reduced at H and elevated at D7 in the TCDD-exposed birds (p < 0.05). Hepatic ER concentrations were elevated at H (p < 0.01). Although EROD was half-maximally induced at H and D7 in the early exposure experiment in pigeons, there was no effect of TCDD treatment on E, or ER levels. The nominal TCDD concentration in these pigeons (1 {micro}g/kg egg) was within the range observed in wild piscivorous bird eggs collected from aquatic systems contaminated with TCDD and related chemicals (approx. 0.5--2 ng TEQ/g egg). In herons exposed to 2 {micro}g/kg of TCDD at the midpoint of incubation, hepatic ER affinities (Kd) and concentrations (Bmax) were elevated in treated birds at H (p < 0.05); however there was no effect on plasma E, levels. Liver [{sup 3}H]-TCDD concentrations were 11.3 {+-} 0.8 ng/g at H, and 0.8 {+-} 0.1 ng/g at D7, representing 9.9% and 4.9% of the nominal TCDD dose, respectively.

  20. Development of Simultaneous Derivative Spectrophotometric and HPLC Methods for Determination of 17-Beta-Estradiol and Drospirenone in Combined Dosage Form

    PubMed Central

    Aydoğmuş, Zeynep; Yılmaz, Ece Merve; Yörüsün, Sevgi; Akpınar, Samet

    2015-01-01

    Simple, rapid spectrophotometric, and reverse-phase high performance liquid chromatographic methods were developed for the concurrent analysis of 17-beta-estradiol (ESR) and drospirenone (DRS). The spectrophotometric method was based on the determination of first derivative spectra and determined ESR and DRS using the zero-crossing technique at 208 and 282 nm, respectively, in methanol. The linear range was 0.5–32.0 µg·mL−1 for DRS and 0.5–8.0 µg·mL−1 for EST. The limit of detection (LOD) values were 0.14 µg·mL−1 and 0.10 µg·mL−1 and limit of quantification (LOQ) values were 0.42 µg·mL−1 and 0.29 µg·mL−1 for ESR and DRS, respectively. The chromatographic method was based on the separation of both analytes on a C18 column with a mobile phase containing acetonitrile and water (70 : 30, v/v). Detection was performed with a UV-photodiode array detector at 279 nm. The linear range was 0.08–2.5 µg·mL−1 for DRS and 0.23–7.5 µg·mL−1 for EST. LOD values were 0.05 µg·mL−1 and 0.02 µg·mL−1 and LOQ values were 0.15 µg·mL−1 and 0.05 µg·mL−1 for ESR and DRS, respectively. These recommended methods have been applied for the simultaneous determination of ESR and DRS in their tablets. PMID:27347530

  1. Beneficial effect of 17{beta}-estradiol on hyperglycemia and islet {beta}-cell functions in a streptozotocin-induced diabetic rat model

    SciTech Connect

    Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting

    2010-11-15

    The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17{beta}-estradiol (E{sub 2}) on hyperglycemia and islet {beta}-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E{sub 2} orally at 500 {mu}g/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet {beta}-cell proliferation. E{sub 2} administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, and improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E{sub 2} were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E{sub 2} on islet cells was linked to the functions of the estrogen receptor {alpha}. Notably, these protective effects of E{sub 2} on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E{sub 2} can promote the regeneration of damaged pancreatic islets by stimulating {beta}-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E{sub 2} may be beneficial in diabetic patients with an accelerated loss of islet {beta}-cells.

  2. Effect of light irradiation and sex hormones on jurkat T cells: 17beta-estradiol but not testosterone enhances UVA-induced cytotoxicity in Jurkat lymphocytes.

    PubMed

    Cohly, Hari H P; Graham-Evans, Barbara; Ndebele, Kenneth; Jenkins, John K; McMurray, Robert; Yan, Jian; Yu, Hongtao; Angel, Michael F

    2005-04-01

    In Eastern cultures, such as India, it is traditionally recommended that women but not men cover their heads while working in the scorching sun. The purpose of this pilot study was to determine whether there was any scientific basis for this cultural tradition. We examined the differential cytotoxic effects of ultraviolet A light (UVA) on an established T cell line treated with female and male sex hormones. CD4+ Jurkat T cells were plated in 96 well plates at 2 x 106 cells/ml and treated with 17beta-estradiol (EST) or testosterone (TE). These cells were irradiated by UVA light with an irradiance of 170 J/cm2 for 15min at a distance of 6 cm from the surface of the 96-well plate. Controls included cells not treated with hormones or UVA. The effects of EST and TE were investigated between 1 and 20 ng/mL. Cytotoxicity by fluorescein-diacetate staining and COMET assay generating single strand DNA cleavage, tail length and tail moment measurements were examined. The effect of estrogen (5ng/mL) on apoptosis and its mediators was further studied using DNA laddering and western blotting for bcl-2 and p53. We found that EST alone, without UVA, enhanced Jurkat T cell survival. However, EST exhibited a dose-related cytotoxicity in the presence of UVA; up to 28% at 20 ng/ml. TE did not alter UVA-induced cytotoxicity. Since TE did not alter cell viability in the presence of UVA further damaging studies were not performed. COMET assay demonstrated the harmful effects of EST in the presence of UVA while EST without UVA. had no significant effect on the nuclear damage. Apoptosis was not present as indicated by the absence of DNA laddering on agarose gel electrophoresis at 5ng/ml EST or TE +/- UVA. Western blot showed that estrogen down regulated bcl-2 independently of UVA radiation while p53 was down regulated in the presence of UVA treatment. EST and TE have differential effects on UVA-induced cytotoxicity in Jurkat T-lymphocyte which suggested that women may be more susceptible

  3. Reconnaissance of 17 beta-estradiol, 11-ketotestosterone, vitellogenin, and gonad histopathology in common carp of United States streams; potential for contaminant-induced endocrine disruption

    USGS Publications Warehouse

    Goodbred, Steven L.; Gilliom, Robert J.; Gross, Timothy S.; Denslow, Nancy P.; Bryant, Wade B.; Schoeb, Trenton R.

    1997-01-01

    A reconnaissance of sex steroid hormones and other biomarkers in common carp was used to assess whether endocrine disruption may be occurring in fish in United States streams, to evaluate relations between endocrine disruption and contaminant levels, and to determine requirements for further studies. 17?-estradiol, 11-ketotestosterone, vitellogenin, and gonadal histopathology were measured in adult carp (usually 10--15 for each sex) at 25 sites (647 fish), representing a wide range of environmental settings typical of major regions of the nation. Fish were collected during August--December 1994, a period of gonadal maturation after spawning. Contaminants evaluated were organochlorine pesticides and polychlorinated biphenyls in tissue; phthalates, phenols, and polycyclic aromatic hydrocarbons in bed sediment; and dissolved pesticides in water. Mean site concentrations of steroid hormones spanned two orders of magnitude for both sexes. No significant regional differences in steroid hormones were detected for males, but females from the Northern and Southern Midcontinent were significantly different from other regions of the country in one or both hormones. Within all regions there were significant differences between sites in one or both hormones for both sexes. Most correlation coefficients between biomarkers and contaminants were negative. Contaminants that had significant (a=0.05) correlations with biomarkers were organochlorine pesticides, phenols, and dissolved pesticides. The strongest pattern common to both males and females was a negative correlation between the hormone ratio (E2/11-KT) and dissolved pesticides. The significant site-to-site differences in biomarkers, and the presence of significant correlations between biomarkers and contaminants, are evidence that fish in some streams may be experiencing endocrine disruption. Improved information is needed to evaluate whether endocrine disruption is actually occurring and if there are reproductive effects on

  4. Identification of two Isoforms of Vitelline Envelope Protein as Complementary Biomarkers to Vitellogenin in the Plasma of Rainbow Trout Exposed to 17beta-estradiol

    EPA Science Inventory

    In the present study, protein markers of estrogenic exposure in rainbow trout (Oncorhynchus mykiss) were isolated and identified using innovative sample preparation techniques followed by advanced MS and bioinformatics approaches. Juvenile trout were administered 17ß-estradiol t...

  5. A Computational Model of the Hypothalamic-pituitary-gonadal Axis in Male Fathead Minnows Exposed to 17 | *alpha* | -ethinylestradiol and 17 | *beta* | -estradiol

    EPA Science Inventory

    Estrogenic chemicals in the aquatic environment have been shown to cause a variety of reproductive anomalies in fish including full sex reversal, intersex, and altered population sex ratios. Two estrogens found in the aquatic environment, 17-ethinylestradiol and 17â-estradiol, h...

  6. DNA ARRAYS TO MONITOR GENE EXPRESSION IN RAT BLOOD AND UTERUS FOLLOWING 17-BETA-ESTRADIOL EXPOSURE: BIOMONITORING ENVIRONMENTAL EFFECTS USING SURROGATE TISSUES

    EPA Science Inventory

    DNA arrays to monitor gene expression in rat blood and uterus following 17-b-estradiol exposure - biomonitoring environmental effects using surrogate tissues
    John C. Rockett, Robert J. Kavlock, Christy R. Lambright, Louise G. Parks, Judith E. Schmid, Vickie S. Wilson, Carmen W...

  7. Evidence of a progesterone receptor in the liver of the green frog Rana esculenta and its down-regulation by 17 beta estradiol and progesterone.

    PubMed

    Paolucci, M; Guerriero, G; Ciarcia, G

    1999-12-01

    Progesterone is a versatile hormone showing an ample variety of effects. One of the numerous functions attributed to progesterone is the modulation of vitellogenesis in oviparous vertebrates. As a prerequisite for the possible involvement of progesterone in vitellogenesis modulation, we investigated the presence of a progesterone receptor (PR) in the liver of the female green frog Rana esculenta. 3H-Progesterone (3H-P) binding activity was found in both cytosol and nuclear extract of the liver of Rana esculenta. The progesterone-binding moiety showed the typical characteristics of a true receptor, such as high affinity, low capacity, and specificity for progesterone. It also bound to DNA-cellulose and was eluted with a linear salt gradient at a concentration of 0.05 M of NaCl. The progesterone-binding moiety was down regulated by steroid hormones, in that ovariectomy resulted in a significant increase, in both cytosol and nuclear extract, of 3H-P binding activity with respect to intact females. On the contrary, 3H-P binding activity was almost undetectable after estradiol and/or progesterone treatment. The progesterone binding moiety of Rana esculenta was analyzed by Western blotting with the aid of a monoclonal antibody raised against the subunits A and B of the chicken PR. An immunoreactive band of about 67 kDa was observed in the liver of both intact and treated females. The 67 kDa band showed an increased intensity in ovariectomized animals, while it was faint following treatment with estradiol and/or progesterone. This is the first report on the presence of a progesterone receptor (PR) in the liver of an amphibian. PR of Rana esculenta is down regulated by estradiol and/or progesterone and shows peculiar immunological and biochemical characteristics, which make it rather different from the PR of other vertebrates. PMID:10589507

  8. Interplay of phase II enzymes and transporters in futile cycling: influence of multidrug resistance-associated protein 2-mediated excretion of estradiol 17beta-D-glucuronide and its 3-sulfate metabolite on net sulfation in perfused TR(-) and Wistar rat liver preparations.

    PubMed

    Sun, Huadong; Zeng, Ying-Ying; Pang, K Sandy

    2010-05-01

    The hepatic disposition of estradiol 17beta-D-glucuronide (E(2)17G), a substrate of the organic anion-transporting polypeptides Oatp1a1, Oatp1a4, and Oatp1b2, was investigated in Wistar and TR(-) [multidrug resistance-associated protein (Mrp) 2-mutant] rats to elucidate how absence of Mrp2, the major excretory transporter for both E(2)17G and its 3-sulfate metabolite (E(2)3S17G), affected the net sulfation. With absence of Mrp2, lower microsomal desulfation activity and higher Mrp3 but unchanged immunoreactive protein expression of other transporters (Oatps and Mrp4) and estrogen sulfotransferase were found in TR(-) rats. In recirculating, perfused liver preparations, the rapid decay of E(2)17G and sluggish appearance of low levels of E(2)3S17G in perfusate for Wistar livers were replaced by a protracted, biexponential decay of E(2)17G and greater accumulation of E(2)3S17G, whose levels reached plateaus upon the almost complete obliteration of biliary excretion of E(2)17G and E(2)3S17G in the TR(-) liver. Much higher amounts of E(2)17G (28x) and E(2)3S17G (11x) in liver and reduced net sulfation (40 +/- 6 from 77 +/- 6% dose, P < 0.05) were observed at 2 h for the TR(-) versus the Wistar rats. With use of a physiologically based pharmacokinetic model, analytical solutions for the areas under the curve for the precursor and metabolite were obtained to reveal how enzyme- and transporter-mediated processes affected the hepatic disposition of the precursor and metabolite in futile cycling. The analytical solutions were useful to explain transporter-enzyme interplay in futile cycling and predicted that a shutdown of Mrp2 function led to decreased net sulfation of E(2)17G by raising the intracellular concentration of the metabolite, E(2)3S17G, which readily refurnished E(2)17G via desulfation. PMID:20124397

  9. FoxM1 influences embryo implantation and is regulated by 17 beta-estradiol and progesterone in mouse uteri and endometrium cells.

    PubMed

    Xie, Yunpeng; Cui, Dan; Kong, Ying

    2014-01-01

    To be a successful implantation, endometrial receptivity should be established. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion, and progression. FoxM1 regulates the expression of lots of targeted genes important to cell differentiation, proliferation and apoptosis; cell-cycle progression; and tumor angiogenesis, migration, invasion, and metastasis. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. To test our hypothesis, we observed the expression and distribution of FoxM1 during the early pregnancy of mouse. Then, we used Immunohistochemistry to examine the expression of FoxM1 induced by E2 and/or P4 in the ovariectomized mouse uterus and human endometrium cells. This study further investigated whether FoxM1 was an important factor in the implantation. Our results showed that FoxM1 expressed in the mouse uterus during early pregnancy (Day 1 to 5). The expression of FoxM1 gradually increased along pregnancy process; FoxM1 expression could be increased by E2. On the contrary, FoxM1 expression could be decreased by P4 and E2 plus P4. We also detected the proliferation of human endometrium cells. We found that E2 might promote cells proliferation, while P4 and E2 plus P4 inhibited cells proliferation; Inhibiting FoxM1 could interfere the embryo implantation of mouse. Amplification or inhibiting of FoxM1 in JAR cells can increase or decrease the adhesion rate to Rl95-2 and HEC-1A cells separately. Our data indicate that FoxM1 might play an important role during the process of mouse embryo implantation. PMID:25400737

  10. FoxM1 influences embryo implantation and is regulated by 17 beta-estradiol and progesterone in mouse uteri and endometrium cells

    PubMed Central

    Xie, Yunpeng; Cui, Dan; Kong, Ying

    2014-01-01

    To be a successful implantation, endometrial receptivity should be established. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion, and progression. FoxM1 regulates the expression of lots of targeted genes important to cell differentiation, proliferation and apoptosis; cell-cycle progression; and tumor angiogenesis, migration, invasion, and metastasis. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. To test our hypothesis, we observed the expression and distribution of FoxM1 during the early pregnancy of mouse. Then, we used Immunohistochemistry to examine the expression of FoxM1 induced by E2 and/or P4 in the ovariectomized mouse uterus and human endometrium cells. This study further investigated whether FoxM1 was an important factor in the implantation. Our results showed that FoxM1 expressed in the mouse uterus during early pregnancy (Day 1 to 5). The expression of FoxM1 gradually increased along pregnancy process; FoxM1 expression could be increased by E2. On the contrary, FoxM1 expression could be decreased by P4 and E2 plus P4. We also detected the proliferation of human endometrium cells. We found that E2 might promote cells proliferation, while P4 and E2 plus P4 inhibited cells proliferation; Inhibiting FoxM1 could interfere the embryo implantation of mouse. Amplification or inhibiting of FoxM1 in JAR cells can increase or decrease the adhesion rate to Rl95-2 and HEC-1A cells separately. Our data indicate that FoxM1 might play an important role during the process of mouse embryo implantation. PMID:25400737

  11. Association between progesterone and estradiol-17beta treatment and protein expression of pgr and PGRMC1 in porcine luminal epithelial cells: a real-time cell proliferation approach.

    PubMed

    Kempisty, B; Wojtanowicz-Markiewicz, K; Ziółkowska, A; Budna, J; Ciesiółka, S; Piotrowska, H; Bryja, A; Antosik, P; Bukowska, D; Wollenhaupt, K; Bruska, M; Brüssow, K P; Nowicki, M; Zabel, M

    2015-01-01

    The correct functionality (sensitivity and receptivity) of endometrial tissue is regulated by paracrine and endocrine pathways that activate several mediators or metabolic pathways and gene cascades. This study aimed to investigate the influence of E2 and P4 on progesterone receptor (PGR) and progesterone receptor membrane component 1 (PGRMC1) protein expression in porcine luminal epithelial cells and their influence on the proliferation of these cells in real-time. Surface uterine luminal epithelial cells were removed using sterile surgical blades from uterine horns of ten crossbred anestrus gilts. Following treatment with collagenase I, cells were separated and transferred into 48-well E-Plates for use in a realtime cell analyzer (RTCA). The luminal epithelial cells were cultured in vitro (IVC) in standard DMEM cell culture medium and incubated with E2 (10 pg/ml, 40 pg/ml, 500 pg/ml) and P4 (10 ng/ml, 40 ng/ ml, 500 ng/ml). The cell proliferation index was analyzed after 0-240 h, 0-120 h, 120-240 h. After using the RTCA analysis we found increased proliferation of luminal epithelial cells after treatment of low doses of P4 (10 and 40 ng/ml), (P < 0.001). Higher doses of P4 led to decrease of proliferation (P < 0.001). Conversely, higher doses of E2 (500 pg/ml) increased the proliferation index as compared to low doses (10 pg/ml) and control (P < 0.001). Confocal microscopic observations revealed that higher concentrations of E2 upregulate the expression of both PGR and PGRMC1. Additionally, P4 used in lower concentrations stimulated the expression of these receptors, too. Our study presents a new influence of E2 and P4 on the expression of PGR and PGRMC1 and on the real-time proliferation of porcine luminal epithelial cells. The relationship between PGR or PGRMC1 expression and the proliferation of luminal epithelial cells may be influenced (up- or down regulated) by E2 or P4 in a steroid type- and dose-dependent manner. PMID:25864740

  12. Water-compatible magnetic imprinted nanoparticles served as solid-phase extraction sorbents for selective determination of trace 17beta-estradiol in environmental water samples by liquid chromatography.

    PubMed

    Hao, Yi; Gao, Ruixia; Shi, Lu; Liu, Dechun; Tang, Yuhai; Guo, Zengjun

    2015-05-29

    Endocrine disrupting compounds (EDCs) are a potential risk for wildlife and humans for their existence in water. The efficient extraction and clean-up steps are required before detection of low concentration levels of EDCs. In this work, a novel water-compatible magnetic molecularly imprinted nanoparticles is synthesized for the selective extraction of 17β-estradiol (E2) in environmental water samples. The preparation is carried out by introducing aldehyde groups to the surface of amino-functionalized magnetic nanoparticles through a simple one-step modification, followed by copolymerization of functional monomer gelatin and template E2 via surface imprinting technique. The gelatin with abundant active groups could not only act as functional monomer reacting with template, but also assemble covalently at the surface of magnetic nanoparticles. At the same time, gelatin would improve the water-compatibility of imprinted materials for attaining high extraction efficiency. To obtain high imprinting effect, the preparation conditions are optimized in detail using Central composite design-response surface methodology. The resultant polymers have uniform spherical shape with a shell thickness of about 8nm, stable crystalline form, and super-paramagnetic property. Meanwhile, the obtained polymers have high capacity of 12.87mgg(-1) and satisfactory selectivity to template molecule. To testify the feasibility of the magnetic imprinted polymers in sample pretreatment, a method for determination of trace E2 in environmental water samples was set up by combination of solid-phase extraction (SPE) using the prepared polymers as sorbents and HPLC for rapid isolation and determination of E2. The limit of detection of proposed method is 0.04ngmL(-1), the intra- and inter-day relative standard deviations (RSDs) are less than 4.6% and 5.7%, respectively. The recoveries of E2 from environmental water samples are in the range from 88.3% to 99.1% with the RSDs less than 7.2%. PMID

  13. Land-cover effects on the fate and transport of surface-applied antibiotics and 17-beta-estradiol on a sandy outwash plain, Anoka County, Minnesota, 2008–09

    USGS Publications Warehouse

    Trost, Jared J.; Kiesling, Richard L.; Erickson, Melinda L.; Rose, Peter J.; Elliott, Sarah M.

    2013-01-01

    A plot-scale field experiment on a sandy outwash plain in Anoka County in east-central Minnesota was used to investigate the fate and transport of two antibiotics, sulfamethazine (SMZ) and sulfamethoxazole (SMX), and a hormone, 17-beta-estradiol (17BE), in four land-cover types: bare soil, corn, hay, and prairie. The SMZ, SMX, and 17BE were applied to the surface of five plots of each land-cover type in May 2008 and again in April 2009. The cumulative application rate was 16.8 milligrams per square meter (mg/m2) for each antibiotic and 0.6 mg/m2 for 17BE. Concentrations of each chemical in plant-tissue, soil, soil-water, and groundwater samples were determined by using enzyme-linked immunosorbent assay (ELISA) kits. Soil-water and groundwater sampling events were scheduled to capture the transport of SMZ, SMX, and 17BE during two growing seasons. Soil and plant-tissue sampling events were scheduled to identify the fate of the parent chemicals of SMZ, SMX, and 17BE in these matrices after two chemical applications. Areal concentrations (mg/m2) of SMZ and SMX in soil tended to decrease in prairie plots in the 8 weeks after the second chemical application, from April 2009 to June 2009, but not in other land-cover types. During these same 8 weeks, prairie plots produced more aboveground biomass and had extracted more water from the upper 125 centimeters of the soil profile compared to all other land-cover types. Areal concentrations of SMZ and SMX in prairie plant tissue did not explain the temporal changes in areal concentrations of these chemicals in soil. The areal concentrations of SMZ and SMX in the aboveground plant tissues in June 2009 and August 2009 were much lower, generally two to three orders of magnitude, than the areal concentrations of these chemicals in soil. Pooling all treatment plot data, the median areal concentration of SMZ and SMX in plant tissues was 0.01 and 0.10 percent of the applied chemical mass compared to 22 and 12 percent in soil

  14. Inhibitors of 17beta-hydroxysteroid dehydrogenase type 1.

    PubMed

    Brozic, P; Lanisnik Risner, T; Gobec, S

    2008-01-01

    Carcinogenesis of hormone-related cancers involves hormone-stimulated cell proliferation, which increases the number of cell divisions and the opportunity for random genetic errors. In target tissues, steroid hormones are interconverted between their potent, high affinity forms for their respective receptors and their inactive, low affinity forms. One group of enzymes responsible for these interconversions are the hydroxysteroid dehydrogenases, which regulate ligand access to steroid receptors and thus act at a pre-receptor level. As part of this group, the 17beta-hydroxysteroid dehydrogenases catalyze either oxidation of hydroxyl groups or reduction of keto groups at steroid position C17. The thoroughly characterized 17beta-hydroxysteroid dehydrogenase type 1 activates the less active estrone to estradiol, a potent ligand for estrogen receptors. This isoform is expressed in gonads, where it affects circulating levels of estradiol, and in peripheral tissue, where it regulates ligand occupancy of estrogen receptors. Inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 are thus highly interesting potential therapeutic agents for the control of estrogen-dependent diseases such as endometriosis, as well as breast and ovarian cancers. Here, we present the review on the recent development of inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 published and patented since the previous review of 17beta-hydroxysteroid dehydrogenase inhibitors of Poirier (Curr. Med. Chem., 2003, 10, 453). These inhibitors are divided into two separate groups according to their chemical structures: steroidal and non-steroidal 17beta-hydroxysteroid dehydrogenase type 1 inhibitors. Their estrogenic/ proliferative activities and selectivities over other 17beta-hydroxysteroid dehydrogenases that are involved in local regulation of estrogen action (types 2, 7 and 12) are also presented. PMID:18220769

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

    PubMed

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

    1999-10-01

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

  16. Synthesis of 3-hydroxyestra-1,3,5(10)-trien-17-one and 3,17 beta-dihydroxyestra-1,3,5(10)-triene 6 alpha-N-(epsilon-biotinyl) caproamide, tracer substances for developing immunoassays for estrone and estradiol.

    PubMed

    Luppa, P; Birkmayer, C; Hauptmann, H

    1994-01-01

    We describe the synthesis of 3-hydroxyestra-1,3,5(10)-trien-17-one 6 alpha-N-(epsilon-biotinyl)caproamide and 3,17 beta-dihydroxyestra-1,3,5(10)-triene 6 alpha-N-(epsilon-biotinyl) caproamide from 3-hydroxyestra-1,3,5(10)-trien-17-one and 3,17 beta-dihydroxyestra-1,3,5(10)-triene, via the 6-keto estrogenic derivatives. The reductive amination of these compounds is an effective step toward an epimeric mixture of the respective amines, which are easily biotinylated by use of N-(epsilon-biotinylcaproyl)-N- hydroxysuccinimide ester. The 6 alpha-epimers could be isolated from the alpha/beta-composition by application of isocratic HPLC, and overall yields were about 20% for the epimeric end products. The structures of the stereoisomers could clearly be assigned through 1H NMR studies. The ratios of the respective isomers obtained from the reductive amination were found to be 3(alpha):2(beta). The biotinylated estrogens can be used as tracers in a novel immunoassay concept for the determination of these analytes in human serum. Ring position 6 was selected for derivatization because of its distance from the functionalized positions 3 and 17 and, therefore, of a negligible alteration of the tracer's structure in comparison to underivatized estrone or estradiol. PMID:8031881

  17. Endocrine disrupter--estradiol--in Chesapeake Bay tributaries.

    PubMed

    Dorabawila, Nelum; Gupta, Gian

    2005-04-11

    Exogenous chemicals that interfere with natural hormonal functions are considered endocrine disrupting chemicals (EDCs). Estradiol (17beta-estradiol or E2) is the most potent of all xenoestrogens. Induction of vitellogenin (VTG) production in male fish occurs at E2 concentrations as low as 1 ng l-1. E2 reaches aquatic systems mainly through sewage and animal waste disposal. Surface water samples from ponds, rivers (Wicomico, Manokin and Pocomoke), sewage treatment plants (STPs), and coastal bays (Assawoman, Monie, Chincoteague, and Tangier Sound-Chesapeake Bay) on the Eastern Shore of Maryland were analyzed for E2 using enzyme linked immuno-sorbent assay (ELISA). E2 concentrations in river waters varied between 1.9 and 6.0 ng l-1. Highest E2 concentrations in river waters were observed immediately downstream of STPs. E2 concentrations in all the coastal bays tested were 2.3-3.2 ng l-1. PMID:15811666

  18. Mechanisms by Which 17β-Estradiol (E2) Suppress Neuronal cox-2 Gene Expression.

    PubMed

    Stacey, Winfred; Bhave, Shreyas; Uht, Rosalie M

    2016-01-01

    E2 attenuates inflammatory responses by suppressing expression of pro-inflammatory genes. Given that inflammation is increasingly being associated with neurodegenerative and psychiatric processes, we sought to elucidate mechanisms by which E2 down-regulates a component of an inflammatory response, cyclooxygenase- 2 (COX-2) expression. Although inflammatory processes in the brain are usually associated with microglia and astrocytes, we found that the COX-2 gene (cox-2) was expressed in a neuronal context, specifically in an amygdalar cell line (AR-5). Given that COX-2 has been reported to be in neurons in the brain, and that the amygdala is a site involved in neurodegenerative and neuropsychiatric processes, we investigated mechanisms by which E2 could down-regulate cox-2 expression in the AR-5 line. These cells express estrogen receptors alpha (ERα) and beta (ERβ), and as shown here cox-2. At the level of RNA, E2 and the ERβ selective ligand diarylpropionitrile (DPN) both attenuated gene expression, whereas the ERα selective ligand propyl pyrazole triol (PPT) had no effect. Neither ligand increased ERβ at the cox-2 promoter. Rather, DPN decreased promoter occupancy of NF-κB p65 and histone 4 (H4) acetylation. Treatment with the non-specific HDAC inhibitor Trichostatin A (TSA) counteracted DPN's repressive effects on cox-2 expression. In keeping with the TSA effect, E2 and DPN increased histone deacetylase one (HDAC1) and switch-independent 3A (Sin3A) promoter occupancy. Lastly, even though E2 increased CpG methylation, DPN did not. Taken together, the pharmacological data indicate that ERβ contributes to neuronal cox-2 expression, as measured by RNA levels. Furthermore, ER ligands lead to increased recruitment of HDAC1, Sin3A and a concomitant reduction of p65 occupancy and Ac-H4 levels. None of the events, however, are associated with a significant recruitment of ERβ at the promoter. Thus, ERβ directs recruitment to the cox-2 promoter, but does so in the

  19. Comparing biological effects of estrone (E1) and 17ß-estradiol (E2) in mature fathead minnows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of endocrine active compounds such as estrogens in treated wastewater effluent and their effects on aquatic life are causing concern among aquatic resource managers. Among the natural estrogens are 17ß-estradiol, 17a-estradiol, and estrone. Although 17ß-estradiol has received significa...

  20. Highly Sensitive Detection of Hormone Estradiol E2 Using Surface-Enhanced Raman Scattering Based Immunoassays for the Clinical Diagnosis of Precocious Puberty.

    PubMed

    Wang, Rui; Chon, Hyangah; Lee, Sangyeop; Cheng, Ziyi; Hong, Sung Hyun; Yoon, Young Ho; Choo, Jaebum

    2016-05-01

    The hormone estradiol (17β-estradiol, E2) plays an important role in sexual development and serves as an important diagnostic biomarker of various clinical conditions. Particularly, the serum E2 concentration is very low (<10 pg/mL) in prepubertal girls. Accordingly, many efforts to develop a sensitive method of detection and quantification of E2 in human serum have been made. Nonetheless, current clinical detection methods are insufficient for accurate assessment of E2 at low concentrations (<10 pg/mL). Thus, there is an urgent need for new technologies with efficient and sensitive detection of E2 for use in routine clinical diagnostics. In this study, we introduce a new E2 assay technique using a surface-enhanced Raman scattering (SERS)-based detection method. The SERS-based assay was performed with 30 blood samples to assess its clinical feasibility, and the results were compared with data obtained using the ARCHITECT chemiluminescence immunoassay. Whereas the commercial assay system was unable to quantify serum levels of E2 lower than 10 pg/mL, the limit of detection of E2 using the novel SERS-based assay described in this study was 0.65 pg/mL. Thus, the proposed SERS-based assay has a strong potential to be a valuable tool in the early diagnosis of precocious puberty due to its excellent analytical sensitivity. PMID:27070977

  1. A physiological mode of puberty induction in hypogonadal girls by low dose transdermal 17 beta-oestradiol.

    PubMed

    Illig, R; DeCampo, C; Lang-Muritano, M R; Prader, A; Torresani, T; Werder, E A; Willi, U; Schenkel, L

    1990-12-01

    Transdermal 17 beta-oestradiol administration (17 beta-E2), used mainly in menopausal women, allows a continuous 17 beta-E2 delivery through the skin into the systemic circulation, avoiding intestinal and hepatic passage. In order to explore whether transdermal 17 beta-E2 could be used for the induction of puberty, 17 beta-E2 patches with low dose delivery were administered in nine prepubertal girls with Turner syndrome (bone age greater than 10.5 years) for a mean period of 2.2 years. Treatment schedule: 5 micrograms/day for 6-9 months, 10 micrograms/day for 6-9 months, 25 micrograms/day for long-term substitution; addition of cyclic gestagen p.o. after 18-24 months. Breast development started within 3 months of therapy and menstruation occurred after 2 years. Growth rate increased from 3.2 to 5.0 cm/year during the 1st year of therapy, height prediction did not change. Serum oestradiol (E2) and urinary E2 conjugates increased proportionally with 17 beta-E2 doses, serum oestrone (E1) rose much less. The possibility to imitate time course, clinical events and hormonal changes of normal puberty, the absence of adverse drug reactions and the excellent acceptance and easy mode of application suggest that transdermal 17 beta-E2 is optimally suited for hormonal substitution in girls with hypogonadism. PMID:2126236

  2. A highly sensitive differential pulse anodic stripping voltammetry for determination of 17β-estradiol (E2) using CdSe quantum dots based on indirect competitive immunoassay.

    PubMed

    Chaisuwan, Nuanapa; Xu, He; Wu, Genying; Liu, Jianshe

    2013-08-15

    In this study a new and fast procedure was developed to determine trace 17β-estradiol (E2) concentrations using CdSe quantum dots (QDs) conjugation with bovine serum albumin (BSA)-E2. To increase the high efficiency of the method, the immunoassay design was restricted to an indirect competitive format. The E2 antigen and bioconjugate were incubated in a microtiter plate with an anti-E2 antibody and competition for antibody binding sites was established. The in situ bismuth-coated carbon electrodes were used for detecting the cadmium ions (Cd(2+)) released during the acid dissolution step. After optimization, the well-defined sharp anodic stripping voltammograms curves of the E2 concentration ranging from 50 to 1000 pg/mL was recorded, and the lowest detection limit was 50 pg/mL with 6% reproducibility and 7% repeatability. Finally, the assay was applied to tap water and wastewater samples. The detection limits were 52.56 ± 0.125 pg/mL for tap water and 51.42 ± 0.453 pg/mL for wastewater. These results show that the assay exhibited sensitive analytical performance in E2 detection with high sensitivity and accuracy with satisfactory results. PMID:23542084

  3. A guide to 17beta-hydroxysteroid dehydrogenases.

    PubMed

    Adamski, J; Jakob, F J

    2001-01-22

    17beta-Hydroxysteroid dehydrogenases (17beta-HSD) are pivotal in controlling the biological potency of steroid hormones by catalyzing oxidation or reduction at position 17. Several 17beta-HSDs may as well metabolize further substrates including alcohols, bile acids, fatty acids and retinols. This review summarizes recent progress in the field of 17beta-HSD research provides an update of nomenclature. PMID:11165003

  4. Synthesis of steroidal 17 beta-carboxamide derivatives.

    PubMed

    Formstecher, P; Lustenberger, P; Dautrevaux, M

    1980-03-01

    Several 17 beta-carboxamide derivatives of natural and fluorinated glucocorticoids have been synthesized. The 17 beta-carboxylic derivatives were obtained by periodic acid oxidation of their side chains. They were then activated by N-hydroxybenzotriazole (HOBT) and coupled to several primary amines. Using this method eleven 17 beta-carboxamide derivatives have been prepared in good yields. PMID:7376221

  5. Degradation of estradiol and ethinyl estradiol by activated sludge and by a defined mixed culture.

    PubMed

    Weber, Stefanie; Leuschner, Prisca; Kämpfer, Peter; Dott, Wolfgang; Hollender, Juliane

    2005-04-01

    The aerobic degradation of the natural hormone 17-beta-estradiol (E2) and the synthetic hormone 17-alpha-ethinyl estradiol (EE2) was investigated in batch experiments with activated sludge from a conventional and a membrane sewage treatment plant. E2 was converted to estrone (E1), the well known metabolite, and further completely transformed within 3 days. The turnover rates of E2 did not differ greatly between conventional and membrane activated sludge. EE2 was persistent in both sludges. By several transfers into fresh E2-medium an enrichment culture could be selected that used E2 as growth substrate. Further enrichment and isolation led to a defined mixed culture consisting of two strains, which were identified by a polyphasic approach as Achromobacter xylosoxidans and Ralstonia sp., respectively. The culture used E2 and E1 as growth substrates and transformed estriol (E3) and 16-alpha-hydroxyestrone but not the xenoestrogens bisphenol A, alpha-zearalenol, mestranol or EE2. The turnover rates of E2 were 0.025-0.1 microg h(-1) cfu(-1) and did not depend on the steroid concentration. PMID:15290133

  6. Production, purification, and functional analysis of recombinant human and mouse 17beta-hydroxysteroid dehydrogenase type 7.

    PubMed

    Törn, Svea; Nokelainen, Pasi; Kurkela, Riitta; Pulkka, Anitta; Menjivar, Marta; Ghosh, Sikha; Coca-Prados, Miguel; Peltoketo, Hellevi; Isomaa, Veli; Vihko, Pirkko

    2003-05-23

    17beta-Hydroxysteroid dehydrogenases (17HSDs) have a central role in the regulation of the biological activity of sex steroid hormones. There is increasing evidence that in addition to their importance in gonads, these hormones also have substantial metabolic roles in a variety of peripheral tissues. In the present study, the cDNA of human 17HSD type 7 was cloned. In silico, the gene corresponding to the cDNA was localized on chromosome 1q23, close to the locus of hereditary prostate cancer 1 (HPC1) (1q24-25) and primary open-angle glaucoma (GLC1A) (1q23-25). Further, a pseudogene was found on chromosome 1q44, close to the locus of predisposing for early-onset prostate cancer (PCaP) (1q42.2-43). Both human (h17HSD7) and mouse 17HSD type 7 (m17HSD7) were for the first time produced as recombinant proteins and purified for functional analyses. Further, kinetic parameters and specific activities were described. h17HSD7 converted estrone (E1) to a more potent estrogen, estradiol (E2), and dihydrotestosterone (DHT), a potent androgen, to an estrogenic metabolite 5alpha-androstane-3beta, 17beta-diol (3betaA-diol) equally, thereby catalyzing the reduction of the keto group in either 17- or 3-position of the substrate. Minor 3betaHSD-like activity towards progesterone (P) and 20-hydroxyprogesterone (20-OH-P), leading to the inactivation of P by h17HSD7, was also detected. m17HSD7 efficiently catalyzed the reaction from E1 to E2 and moderately converted DHT to an inactive metabolite 5alpha-androstane-3alpha,17beta-diol (3alphaA-diol) and to an even lesser degree 3betaA-diol. The mouse enzyme did not metabolize P or 20-OH-P. The expression of 17HSD type 7 was observed widely in human tissues, most distinctly in adrenal gland, liver, lung, and thymus. Based on the enzymatic characteristics and tissue distribution, we conclude that h17HSD7 might be an intracrine regulator of steroid metabolism, fortifying the estrogenic milieu in peripheral tissues. PMID:12732193

  7. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion. PMID:16595727

  8. Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): steady-state pharmacokinetics of MPA and E2 in surgically sterile women.

    PubMed

    Rahimy, M H; Ryan, K K; Hopkins, N K

    1999-10-01

    The steady-state pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate (MPA) and estradiol (E2, released from E2C by esterase enzymes) were characterized after administration to surgically sterile women. This report describes the pharmacokinetics of this multiple-dose and open-labeled study (pharmacodynamics are reported in a subsequent article in this issue). Women with regular menstrual cycles were studied for one control cycle, 3 consecutive treatment months, and 3-5 months of follow-up. Blood samples were drawn before each monthly dose and at specified time points after the third monthly injection. A total of 16 women were enrolled, 14 of whom completed the study. These 14 women (13 white, one black) ranged in age from 28 to 43.4 years, in body weight from 47.6 to 68.9 kg, and in height from 150 to 175 cm. Mean serum MPA concentrations peaked in the first week after administration of MPA/E2C (Lunelle Monthly Contraceptive Injection). The mean MPA Cmax and AUC0-t(last) were 1.25 ng/mL and 32.13 ng.day/mL, respectively. Serum MPA concentrations declined with a mean terminal half-life of 14.7 days, indicating that absorption from the injection site is prolonged after administration of MPA/E2C. The time for MPA concentrations to fall below the lower limit of quantitation (i.e., < 10 pg/mL) after the third injection ranged from 63 to 84 days. The average MPA trough (Cmin' day 28) concentrations for the three consecutive monthly injections ranged from 0.44 to 0.47 pg/mL, indicating that steady-state conditions were achieved after the first injection. The MPA Cmin values were well above threshold levels required to suppress ovulation throughout the injection interval. Absorption of E2 from the injection site was also prolonged after injection of MPA/E2C. Mean concentrations of E2 peaked at approximately 2 days after the third injection, and the average Cmax was 247 pg/mL. Serum E2 levels declined with a terminal half-life of approximately 8 days; E2

  9. In vitro impact of bisphenols BPA, BPF, BPAF and 17β-estradiol (E2) on human monocyte-derived dendritic cell generation, maturation and function.

    PubMed

    Švajger, Urban; Dolenc, Marija Sollner; Jeras, Matjaž

    2016-05-01

    Bisphenols (BPs) are widely spread pollutants that act as estrogen-like endocrine disruptors and are potentially affecting human health on a long run. We explored the effects of BPA, BPF and BPAF, on in vitro differentiation and maturation of MDDCs. Monocytes were treated with 17β-estradiol (E2) and each BP at the beginning of their differentiation into iMDDCs. We found that 10 and 50 μM of BPA and BPF, 10 and 30μM of BPAF and 10 and 50 nM of E2 did not affect cell viability. However, 50 μM of BPA and BPF, as well as 10 and 30 μM of BPAF, significantly decreased the endocytotic capacity of iMDDCs. Both, BPA (50 μM) and BPAF (30 μM) decreased the expression of CD1a and increased the amount of DC-SIGN molecules on iMDDCs. The E2 pre-treatment moderately decreased expression of CD80, CD86 and CD83 co-stimulatory molecules while increasing the numbers of HLA-DR on mMDDCs. Only BPAF significantly influenced the expression of CD80 and CD86 (both decreased), as well as CD83 and HLA-DR molecules (both increased) on mMDDCs. In addition, BPAF modulated DC maturation signaling pathways by lowering the phosphorylation of p65 NF-κB (nuclear factor-kappaB) and ERK (extracellular signal regulated kinase) 1/2 proteins. Consequently, the in vitro proliferation of allogeneic T cells, stimulated with differently pre-treated iMDDCs and mMDDCs, was significantly reduced only in case of BPAF. PMID:26945833

  10. Effects of estradiol and progesterone on the reproduction of the freshwater crayfish Cherax albidus.

    PubMed

    Coccia, E; De Lisa, E; Di Cristo, C; Di Cosmo, A; Paolucci, M

    2010-02-01

    In this study we have investigated the role of 17beta-estradiol and progesterone in the reproduction of the crayfish Cherax albidus by using vitellogenin (VTG) as a biomarker. Early-vitellogenic (EV), full-vitellogenic (FV), and non-vitellogenic (NV) females of Cherax albidus were treated with 17beta-estradiol, progesterone, or both for 4 weeks. Levels of VTG mRNA in the hepatopancreas were detected by RT-PCR. The PCR product was sequenced and showed 97% homology with Cherax quadricarinatus VTG. 17beta-estradiol was more effective than progesterone and 17beta-estradiol plus progesterone in increasing the vitellogenin transcript in the hepatopancreas of EV and FV females. On the contrary, progesterone was more effective than 17beta-estradiol and 17beta-estradiol plus progesterone in increasing the vitellogenin concentration in the hemolymph of EV and FV females. Hepatopancreas histology and fatty acid composition of females injected with hormones showed major modifications. No effects were registered in NV females. In conclusion, 17beta-estradiol and progesterone influence VTG synthesis, although our data indicate that they act through different pathways and are not effective until the proper hormonal environment is established, as demonstrated by their inefficacy in NV females. PMID:20203252

  11. Estradiol uptake, toxicity, metabolism, and adverse effects on cadmium-treated amphibian embryos.

    PubMed Central

    Fridman, Osvaldo; Corró, Lucrecia; Herkovits, Jorge

    2004-01-01

    The exposure of Bufo arenarum embryos to 25 micromol/L 17beta-estradiol (E2) resulted in 100% lethality within 48 hr, whereas 10 micromol//L E2 was the no observed effect concentration value for short-term chronic (7 days) exposure. The toxicity profile curves show that lethal effects were proportional to the E2 concentration and the time of exposure. The E2 uptake resulted in 20.1 ng E2/mg embryo at 8 hr posttreatment, but 67.3% of this value was achieved during the first 30 min of incubation with this estrogen. Regarding metabolism, the embryos synthesize estrone (E1) from E2 by means of 17beta-hydroxysteroid dehydrogenase. Simultaneous treatments of Bufo arenarum embryos with 1 mg/L Cd2+ and 0.1, 1, or 10 micromol/L E2 enhanced the lethality exerted by cadmium in 76.7, 80, and 83.3% of embryos, respectively. The results indicate that estrogenic endocrine disruptors could have an adverse effect on amphibian embryos and enhance the toxic effect of Cd on amphibian embryos. This study points to the possibility of using the AMPHITOX test as a screening method for potential endocrine disruption as well as the combined effects of chemical mixtures. PMID:15175173

  12. Arsenic and 17-β-estradiol bind to each other and neutralize each other's signaling effects.

    PubMed

    Kumar, Sukhdeep; Mukherjee, Tapan K; Guptasarma, Purnananda

    2016-09-01

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other's independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D (1)H and (13)C NMR spectroscopy. Binding leads to attenuation of E2's hydroxyl (1)H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other's levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. PMID:27346132

  13. Expression of 17beta- and 3beta-hydroxysteroid dehydrogenases and steroidogenic acute regulatory protein in non-luteinizing bovine granulosa cells in vitro.

    PubMed

    Sahmi, M; Nicola, E S; Silva, J M; Price, C A

    2004-08-31

    Granulosa cells of small follicles differentiate in vitro in serum-free medium, resulting in increased estradiol secretion and abundance of mRNA encoding cytochrome P450aromatase (P450arom). We tested the hypothesis that differentiation in vitro also involves increased expression of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSD) in the absence of steroidogenic acute regulatory protein (StAR) expression, as has been observed in vivo. Granulosa cells from small (<6 mm diameter) follicles were cultured for up to 6 days, and mRNA levels quantified by Northern hybridization or RT-PCR. Estradiol and progesterone concentrations in medium increased with time in culture, as did mRNA encoding P450arom, 3beta- and 17beta-HSD but not P450scc. Both P450arom and 17beta-HSD were significantly correlated with estradiol accumulation in culture medium. Progesterone secretion was correlated with 3beta-HSD but not P450scc mRNA levels. StAR mRNA was detectable by RT-PCR, did not change with duration of culture and was not correlated with progesterone secretion. FSH significantly stimulated P450arom and 17beta-HSD mRNA levels. Cell origin (from the antral or the basal layer of the membrana granulosa) did not affect steroidogenesis. We conclude that under the present cell culture system granulosa cells do not luteinize, and show expression of key steroidogenic enzymes in patterns similar to those occurring in differentiating follicles in vivo. Further, the data suggest that 17beta-HSD may be as important as P450arom in regulating estradiol secretion, and that 3beta-HSD is more important than P450scc as a regulator of progesterone secretion in non-luteinizing granulosa cells. PMID:15279910

  14. A comparative pharmacokinetic study of micronized estradiol valerate administered alone and in combination with medroxyprogesterone acetate in postmenopausal women.

    PubMed

    Saavedra, Iván; León, Jorge; Prado, Jaime; Sánchez, M Pilar; López, Fernando; Gaete, Leonardo

    2004-10-01

    The objective of this study was to evaluate a possible pharmacokinetic interaction between 17beta-estradiol (E2) and medroxyprogesterone (MP) when administered together in a combined tablet because both hormones have common metabolic routes of biotransformation. The study assessed the mean pharmacokinetics parameters of E2 found after 1-dose administration of 2 different tablets containing E2, 1 containing 2 mg of micronized 17beta-estradiol valerate (E2V) and the other, administered after 2 weeks, 2 mg of E2V in combination with 5 mg of medroxyprogesterone acetate (MPA). The subjects were 15 healthy postmenopausal women with normal laboratory and clinic tests. The study was randomized, double blind, crossover, with 2 periods and 2 sequences. The blood samples were obtained at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after each administration. The E2 serum concentrations were determined by electrochemoluminiscence assay. From these data, the following pharmacokinetic parameters were calculated for E2 alone and E2 in combination with MPA (E2V/MPA): Cmax = 104.89 +/- 26.96, 103.27 +/- 44.40; AUC0-24 =1900.30 +/- 392.23, 1783.70 +/- 756.39; AUC0-infinity = 5576.06 +/- 4065.87, 5317.89 +/- 3702.54; ka = 1.06 +/- 0.31, 1.09 +/- 0.13; t1/2 = 35.65 +/- 20.62, 36.12 +/- 18.04; MRT = 16.29 +/- 8.77, 16.27 +/- 4.88; V/F = 16.29 +/- 8.76, 16.27 +/- 4.88. No significant differences between the pharmacokinetic parameters of E2 and E2/MPA were found, which led us to conclude that there is no pharmacokinetic interaction. PMID:15385829

  15. Plasma luteinizing hormone concentration in mares treated with gondotropin-releasing hormone and estradiol.

    PubMed

    Garcia, M C; Ginther, O J

    1975-11-01

    Three experiments were performed to study the luteinizing hormone (LH) and ovulatory responses to various doses and methods of administration of gonadotropin-releasing hormone (GnRH) in estrous pony mares and the influence of estradiol-17beta (E2-17beta) on LH response to GnRH treatment. In experiment 1, single injections of synthetic GnRH were subcutaneously given to 5 groups of estrous (day 2) mares (3 mares/group) on a body weight basis as follows: group A--isotonic saline solution; group B--GnRH, 0.14 mug/kg; group C--GnRH, 0.28 mug/kg; group D--KGnRH, 0.59 mug/kg; and group E--GnRH, 2.37 mug/kg. Significant increase of plasma LH concentration lasting for approximately 2 hours occurred only in mares of group E given the largest dose of GnRH (2.37 mug/kg). Plasma LH concentration increase at 1 hour after treatment approached significane (P less than 0.10) in mares of group D given the next smaller dose. In experiment 2, GnRH (2.37 mug/kg) was intravenously infused for 24 hours to a group of 6 mares (group F); 6 other mares (group G) were given saline solution infusion. Mean plasma LH concentration was increased at 3 hours, continued to increase until 6 hours, and remained at approximately the 6-hour concentration throughout the period of GnRH infusion. In the 3rd experiment, 3 groups of mares (4 mares/group) were subcutaneously given the following treatments on days 2 and 3 of estrus, respectively: group H--corn oil and saline solution; group I--corn oil and GnRH, 0.59 mug/kg; and group J--estradiol-17beta, 0.5 mg, and GnRH, 0.59 mug/kg. Plasma LH response was not seen in group H mares given corn oil and saline solution. Mean plasma LH concentration at 1 hour after administration of GnRH approached significance (P less than 0.10) in group I mares given corn oil and GnRH. For the mares in group J given E2-17beta and GnRH, E2-17beta pretreatment increased plasma LH after 24 horus; significnat increases of plasma LH concentration were seen from 1 to 6 hours after

  16. Combination of automatic HPLC-RIA method for determination of estrone and estradiol in serum.

    PubMed

    Yasui, T; Yamada, M; Kinoshita, H; Uemura, H; Yoneda, N; Irahara, M; Aono, T; Sunahara, S; Mito, Y; Kurimoto, F; Hata, K

    1999-01-01

    We developed a highly sensitive assay for estrone and 17 beta-estradiol in serum. Estrone and 17 beta-estradiol, obtained by solid-phase extraction using a Sep pak tC18 cartridge, were purified by high-performance liquid chromatography (HPLC). Quantitation of estrone and 17 beta-estradiol were carried out by radioimmunoassay. Not insignificantly, this automatic system of extraction and HPLC succeeded in analyzing 80 samples a week. Intra-assay coefficients of variation (CV) for estrone and 17 beta-estradiol ranged from 19.5 to 28.7%, and from 8.5 to 13.7%, respectively. The minimum detectable dose for estrone and 17 beta-estradiol were 1.04 pg/ml and 0.64 pg/ml, respectively. The serum levels of 17 beta-estradiol using our method strongly correlated with those by Gas chromatography mass spectrometry (GC-MS). The serum levels of estrone and 17 beta-estradiol in 154 peri- and postmenopausal women were estimated to be between 15 and 27 pg/ml and between 3.5 and 24.0 pg/ml, respectively, while the serum level of 17 beta-estradiol in postmenopausal women, in particular, was estimated to be from 3.5 to 6.3 pg/ml. For postmenopausal women who suffered from vasomotor symptoms, the mean levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with daily 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) were 135.0 and 21.3 pg/ml at 12 months, respectively. On the other hand, levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with CEE and MPA every other day, were 73.4 and 15.3 pg/ml, respectively. These highly sensitive assays for estrone and 17 beta-estradiol are useful in measuring low levels of estrogen in postmenopausal women, and monitoring estrogen levels in women receiving CEE as hormone replacement therapy. PMID:10633293

  17. Enhanced osteoblast proliferation and collagen gene expression by estradiol

    SciTech Connect

    Ernest, M.; Schmid, Ch.; Froesch, E.R. )

    1988-04-01

    Estrogens play a crucial role in the development of postmenopausal osteoporosis. However, the mechanism by which estrogens exert their effects on bone is unknown. To examine possible direct effects of 17{beta}-estradiol on bone-forming cells, the authors used pure rat osteoblast-like cells in vitro as a model. Osteoblast-like cells prepared from calvaria of newborn rats were cultured serum-free in methylcellulose-containing medium for 21 days. Osteoblast-like cells proliferate selectively into clonally derived cell clusters of spherical morphorlogy. 17{beta}-Estradiol at concentrations of 0.1 nM and 1 nM enhanced osteoblast-like cell proliferation by 41% and 68% above vehicle-treated controls. The biologically inactive stereoisomer 17{alpha}-estradiol (same concentrations) had no effect. Moreover, the antiestrogen tamoxifen abolished the stimulation of osteoblast-like cell proliferation by 17{beta}-estradiol. After 21 days of culture, RNA was prepared and analyzed in a dot-hybridization assay for the abundance of pro{alpha}1(I) collagen mRNA. Steady-state mRNA levels were increased in cultures treated with 17{beta}-estradiol in a dose-dependent manner with maximal stimulation at 1 nM and 10 nM. At the same concentrations, the percentage of synthesized protein (labeled by ({sup 3}H)proline pulse) that was digestible by collagenase was increased, indicating that 17{beta}-estradiol acts as pretranslational levels to enhance synthesis of bone collagen. These data show that the osteoblast is a direct target for 17{beta}-estradiol.

  18. Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens; Knudson, Inge M; Kelly, Maureen; Mendelson, Jack H

    2008-03-01

    The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E(2)beta in cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys. PMID:17507915

  19. The androgen 5alpha-dihydrotestosterone and its metabolite 5alpha-androstan-3beta, 17beta-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor beta-expressing neurons in the hypothalamus.

    PubMed

    Lund, Trent D; Hinds, Laura R; Handa, Robert J

    2006-02-01

    Estrogen receptor beta (ERbeta) and androgen receptor (AR) are found in high levels within populations of neurons in the hypothalamus. To determine whether AR or ERbeta plays a role in regulating hypothalamo-pituitary-adrenal (HPA) axis function by direct action on these neurons, we examined the effects of central implants of 17beta-estradiol (E2), 5alpha-dihydrotestosterone (DHT), the DHT metabolite 5alpha-androstan-3beta, 17beta-diol (3beta-diol), and several ER subtype-selective agonists on the corticosterone and adrenocorticotropin (ACTH) response to immobilization stress. In addition, activation of neurons in the paraventricular nucleus (PVN) was monitored by examining c-fos mRNA expression. Pellets containing these compounds were stereotaxically implanted near the PVN of gonadectomized male rats. Seven days later, animals were killed directly from their home cage (nonstressed) or were restrained for 30 min (stressed) before they were killed. Compared with controls, E2 and the ERalpha-selective agonists moxestrol and propyl-pyrazole-triol significantly increased the stress induced release of corticosterone and ACTH. In contrast, central administration of DHT, 3beta-diol, and the ERbeta-selective compound diarylpropionitrile significantly decreased the corticosterone and ACTH response to immobilization. Cotreatment with the ER antagonist tamoxifen completely blocked the effects of 3beta-diol and partially blocked the effect of DHT, whereas the AR antagonist flutamide had no effect. Moreover, DHT, 3beta-diol, and diarylpropionitrile treatment significantly decreased restraint-induced c-fos mRNA expression in the PVN. Together, these studies indicate that the inhibitory effects of DHT on HPA axis activity may be in part mediated via its conversion to 3beta-diol and subsequent binding to ERbeta. PMID:16452668

  20. Human liver estrone (E1), Estradiol (E2) and dehydroepiandrosterone (DHEA) sulfotransferases (STs): Comparison with thermostable (TS) and thermolabile (TL) phenol sulfotransferase (PST) activities

    SciTech Connect

    Hernandez, J.S.; Watson, R.W.G.; Weinshilboum, R.M. )

    1991-03-11

    Sulfation plays an important role in the metabolism of E1, E2 and DHEA in humans. The relationship between the enzymes that catalyze the sulfation of E1, E2 and DHEA and TS and TL PST is unclear. The authors compared thermal stability, sensitivity to inhibition by 2,6-dichloro-4-nitrophenol (DCNP) and individual variation in the regulation of these steroid ST activities with those of TS PST and TL PST in the human liver. E2 ST and TS PST had very similar thermal stabilities. The thermal inactivation profile of E1 ST suggested that this activity might be related to both DHEA ST and TS PST. DCNP inhibition studies also showed similar profiles for E2 ST and TS PST, with a small resistant component for E2 ST. A multiphasic profile for DCNP inhibition of E1 ST activity was found. Finally, studies performed with human liver sample showed significant correlations between E2 ST and TS PST, E1 ST and DHEA ST, E2 St and E1 ST, and, to a lesser degree, between E1 ST and TS PST and E2 ST and DHEA ST. TL PST was not correlated significantly with any of the other activities. These results suggest that the sulfation of E2 in human liver is catalyzed predominantly by TS PST, although DHEA ST may also play a role. Their results also suggest that the sulfation of E1 is catalyzed by DHEA ST and by TS PST, although other ST(s) could also be involved.

  1. 17beta-oestradiol acutely regulates Cl- secretion in rat distal colonic epithelium.

    PubMed

    Condliffe, S B; Doolan, C M; Harvey, B J

    2001-01-01

    In this study we used the short circuit current (ISC) technique to measure the non-genomic effects of the female sex steroid 17beta-oestradiol (E2) on electrogenic transepithelial ion transport in rat distal colonic epithelium. Basal ISC was largely composed of a transepithelial Cl- secretory component with minimal electrogenic Na+ movement. E2 (1-100 nM) caused a significant decrease in basal ISC after 15 min. In addition, pre-treating colonic epithelial tissues with E2 (0.1-100 nM) for 10 min significantly reduced forskolin (20 microM)-induced Cl- secretion. E2 also down-regulated Cl- secretion which was pre-stimulated by forskolin. Cl- secretory responses to the Ca2+-dependent secretagogue carbachol (10 microM) were also significantly reduced in the presence of E2 (10- 100 nM). However, E2 had no effect on amiloride-sensitive Na+ absorption. The rapid anti-secretory effect of E2 was abolished in the presence of the intracellular Ca2+ chelator BAPTA (50 microM) or the protein kinase C (PKC) inhibitor chelerythrine chloride (1 microM). However, in the presence of the nuclear oestrogen receptor antagonist tamoxifen (10 microM), E2 still produced an inhibition of Cl- secretion. Testosterone, progesterone and 17alpha-oestradiol had no significant effect on colonic Cl- secretion. Also, E2 (100 nM) did not alter Cl- secretion in colonic epithelia isolated from male rats. We conclude that E2 inhibits colonic Cl- secretion via a non-genomic pathway that involves intracellular Ca2+ and PKC. It is possible that this gender-specific mechanism contributes to the salt and water retention associated with high E2 states. PMID:11136857

  2. Long-chain fatty acid esters of 5-androstene-3 beta, 17 beta-diol: composition and turnover in human mammary cancer cells in culture.

    PubMed

    Martyn, P; Adams, J B

    1989-08-01

    Long-chain fatty acid esters of the adrenal-derived estrogen 5-androstene-3 beta, 17 beta-diol (ADIOL) were found to accumulate in four human mammary cancer cell lines (MCF-7, ZR-75-1, MDA-MB-231 and MDA-MB-330) when explosed to 10-30 nM ADIOL for variable time periods. At each time point examined, the monoester fraction, which represented the major component of the total lipoidal fraction, contained fatty acids linked to either the 3 beta- or 17 beta-positions. However, there was considerable variation in the ratio of 3 beta- to 17 beta-monoesters in the four cell lines. By means of reverse phase HPLC and referral to authentic synthesized compounds, each monoester fraction was found to contain a number of long-chain fatty acid components whose composition resembled that previously determined for the fatty acid esters formed from 17 beta-estradiol. A specific and measurable turnover of a subfraction of ADIOL-17 beta-monoesters composed of essential fatty acids (22:6, 20:4, 18:3) occurred in MCF-7 cells, and to a lesser extent in ZR-75-1 cells. No changes were observed with time in any of the components of the 3 beta- or 17 beta-monoester fractions in MDA-MB-231 and MDA-MB-330 cells. These results, coupled with other studies, now suggest that a very rapid turnover of some components of these lipoidal derivatives may be occurring. If so, it is possible that the system of acylation-deacylation may be involved in a transport mechanism for estrogens and perhaps other steroid hormones. PMID:2588301

  3. UHMWPE carrying estradiol to treat the particle-induced osteolysis-Processing and characterizing.

    PubMed

    Liu, Aiqin; Qu, Shuxin; Chao, Mengmeng; Zhu, Minhao; Weng, Jie; Zhou, Zhongrong

    2009-08-01

    The objective of this study was to explore the possibility of UHMWPE implant used as the drug carrier to treat particle-induced osteolysis. 17beta-estradiol (E2), which had the potential application on osteolysis treatment and the high melting point, was added into UHMWPE powder to produce UHMWPE-E2 composites through hot press processing. The hydrophobicity, crystallinity, mechanical properties, and wear performance of the UHMWPE-E2 were characterized compared with the control UHMWPE. The thermal analysis and Fourier Transform Infrared Spectroscopy results demonstrated that the hot press processing would not alter the functional groups of E2 in this study. There were no significant differences in the hydrophobicity and crystallinity between the UHMWPE-E2 and UHMWPE. The UHMWPE-E2 showed satisfying mechanical properties, including ultimate tensile strength (47.2 +/- 3.6 MPa), yield strength (25.0 +/- 0.6 MPa) and elongation at break (320 +/- 25.5 %), which were similar with the control UHMWPE. The friction coefficients and worn scars were similar between the UHMWPE-E2 and the control UHMWPE. The wear mechanism of the UHMWPE-E2 and UHMWPE both were abrasive wear under dry friction. The UHMWPE-E2 possesses the approving mechanical properties and wear performance compared with the control UHMWPE, which might be used as the potential implanted drug carrier to prevent the particle-induced osteolysis in joint replacements. PMID:18563828

  4. The potential for estradiol and ethinylestradiol degradation in English rivers.

    PubMed

    Jürgens, Monika D; Holthaus, Karlijn I E; Johnson, Andrew C; Smith, JenniferJ L; Hetheridge, Malcom; Williams, Richard J

    2002-03-01

    Water samples were collected in spring, summer, and winter from English rivers in urban/industrial (River Aire and River Calder, Yorkshire, UK) and rural environments (River Thames, Oxfordshire, UK) to study the biodegradation potential of the key steroid estrogen 17beta-estradiol (E2) and its synthetic derivate ethinylestradiol (EE2). Microorganisms in the river water samples were capable of transforming E2 to estrone (E1) with half-lives of 0.2 to 9 d when incubated at 20 degrees C. The E1 was then further degraded at similar rates. The most rapid biodegradation rates were associated with the downstream summer samples of the River Aire and River Calder. E2 degradation rates were similar for spiking concentrations throughout the range of 20 ng/L to 500 microg/L. Microbial cleavage of the steroid ring system was demonstrated by release of radiolabeled CO2 from the aromatic ring of E2 (position 4). When E2 was degraded, the loss of estrogenicity, measured by the yeast estrogen screen (YES) assay, closely followed the loss of the parent molecule. Thus, apart from the transient formation of E1, the degradation of E2 does not form other significantly estrogenic intermediates. The E2 could also be degraded when incubated with anaerobic bed sediments. Compared to E2, EE2 was much more resistant to biodegradation, but both E2 and EE2 were susceptible to photodegradation, with half-lives in the order of 10 d under ideal conditions. PMID:11883412

  5. Lipocalin 2: a "sexy" adipokine that regulates 17Beta-estradiol and obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this article we review the findings of Guo et. al. (Endocrinology, 153: 1183-1193) that the protein, Lipocalin 2 is more highly expressed in subcutaneous adipose tissue than in gondal tissue of female mice. Of particular interest is that the paper by Guo et. al. observed that ablation of the Lip...

  6. FATHEAD MINNOW VITELLOGENIN: CDNA SEQUENCE AND MRNA AND PROTEIN EXPRESSION AFTER 17 BETA-ESTRADIOL TREATMENT

    EPA Science Inventory

    In the present study, a sensitive ribonuclease protection assay (RPA) for VTG mRNA was developed for the fathead minnow (Pimephales promelas), a species proposed for routine endocrine-disrupting chemical (EDC) screening.

  7. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    SciTech Connect

    Cooke, J.B.; Hinton, D.E.

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  8. Rat 17 beta-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene.

    PubMed

    Corton, J C; Bocos, C; Moreno, E S; Merritt, A; Marsman, D S; Sausen, P J; Cattley, R C; Gustafsson, J A

    1996-11-01

    To better understand the molecular mechanisms of the pleiotropic responses induced by exposure to peroxisome proliferator chemicals (PPCs), we conducted a systematic search for genes whose mRNA levels are modulated by the PPC WY-14,643 (WY) in rat liver. The sequence of one up-regulated cDNA (2480 bp) was predicted to encode a protein of 735 aa with 82% identity to the porcine 17 beta-hydroxysteroid dehydrogenase type IV (HSD IV). Like the porcine enzyme, the rat HSD IV contains' a region homologous to yeast hydratase-dehydrogenase-epimerases and to sterol carrier proteins, indicating that the rat HSD IV has broad substrate specificity and contributes to cholesterol metabolism. The rat HSD IV was regulated by diverse PPCs via two distinct mechanisms. Induction of HSD IV and acyl-CoA oxidase (ACO) proteins in rat liver at different treatment times and concentrations of gemfibrozil and di-n-butyl phthalate were almost identical, indicating that HSD IV mRNA induction involves the peroxisome proliferator-activated receptor alpha, a regulator of ACO. In contrast, HSD IV protein levels were only weakly induced by WY, a strong inducer of ACO protein, even though the levels of HSD IV and ACO mRNA were strongly stimulated by WY and gemfibrozil. Thus, HSD IV protein levels were uniquely regulated pretranslationally by WY via a novel mechanism. Increased conversion of estradiol to the less-active estrone by HSD IV induction may explain how phthalate exposure leads to decreases in serum estradiol levels and suppression of ovulation. PMID:8913347

  9. 17 beta-hydroxysteroid dehydrogenase activity in canine pancreas

    SciTech Connect

    Mendoza-Hernandez, G.; Lopez-Solache, I.; Rendon, J.L.; Diaz-Sanchez, V.; Diaz-Zagoya, J.C.

    1988-04-15

    The mitochondrial fraction of the dog pancreas showed NAD(H)-dependent enzyme activity of 17 beta-hydroxysteroid dehydrogenase. The enzyme catalyzes oxidoreduction between androstenedione and testosterone. The apparent Km value of the enzyme for androstenedione was 9.5 +/- 0.9 microM, the apparent Vmax was determined as 0.4 nmol mg-1 min-1, and the optimal pH was 6.5. In phosphate buffer, pH 7.0, maximal rate of androstenedione reduction was observed at 37 degrees C. The oxidation of testosterone by the enzyme proceeded at the same rate as the reduction of the androstenedione at a pH of 6.8-7.0. The apparent Km value and the optimal pH of the enzyme for testosterone were 3.5 +/- 0.5 microM and 7.5, respectively.

  10. Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17β-estradiol (NOMAC/E2): a double-blind, randomized study.

    PubMed

    Christin-Maitre, S; Serfaty, D; Chabbert-Buffet, N; Ochsenbein, E; Chassard, D; Thomas, J-L

    2011-06-01

    BACKGROUND Nomegestrol acetate/17β-estradiol (NOMAC/E(2)) is a new monophasic oral contraceptive combining NOMAC (2.5 mg), a highly selective progesterone-derived progestogen, with E(2) (1.5 mg), which is structurally identical to endogenous estrogen. The objective of this study was to compare the effects on ovarian activity of two different NOMAC/E(2) regimens. METHODS This was a double-blind, randomized study. Healthy, premenopausal women (aged 18-38 years, previous menstrual cycle length 28 ± 7 days) were randomized by computer-generated code to once-daily NOMAC/E(2) for three consecutive 28-day cycles: either 24 days with a 4-day placebo interval (n = 40) or 21 days with a 7-day placebo interval (n = 37) per cycle. Follicular growth (primary outcome measure), plasma hormone profiles and bleeding patterns were assessed. RESULTS There was no evidence of ovulation during treatment with either NOMAC/E(2) regimen. The largest follicle diameter was significantly smaller in the 24-day group than in the 21-day group [mean (SD) mm in cycle 2: 9.0 (3.0) versus 11.3 (5.3) (P = 0.02); in cycle 3: 9.2 (3.0) versus 11.5 (6.0) (P = 0.04)]. Mean FSH plasma levels were significantly lower in the 24-day versus the 21-day group on Day 24 of cycles 1 and 2. Withdrawal bleeding duration was significantly shorter in the 24-day than in the 21-day group [mean (SD) days after cycle 1: 3.5 (1.3) versus 5.0 (2.6) (P = 0.002); after cycle 2: 3.9 (1.6) versus 4.8 (1.7) (P = 0.03)]. CONCLUSIONS The 24-day NOMAC/E(2) regimen was associated with greater inhibition of follicular growth and shorter duration of withdrawal bleeding than the 21-day regimen, suggesting the shorter pill-free interval results in a greater margin of contraceptive efficacy and tolerability, and fewer withdrawal symptoms. PMID:21421664

  11. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    SciTech Connect

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S. . E-mail: mssantos@ci.uc.pt

    2007-05-15

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17{beta}-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca{sup 2+} delaying the opening of the permeability transition pore. The presence of 25 {mu}M E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H{sub 2}O{sub 2} in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

  12. 17{beta}-Hydroxysteroid dehydrogenase type 13 is a liver-specific lipid droplet-associated protein

    SciTech Connect

    Horiguchi, Yuka; Araki, Makoto; Motojima, Kiyoto

    2008-05-30

    17{beta}-Hydroxysteroid dehydrogenase (17{beta}HSD) type 13 is identified as a new lipid droplet-associated protein. 17{beta}HSD type 13 has an N-terminal sequence similar to that of 17{beta}HSD type 11, and both sequences function as an endoplasmic reticulum and lipid droplet-targeting signal. Localization of native 17{beta}HSD type 13 on the lipid droplets was confirmed by subcellular fractionation and Western blotting. In contrast to 17{beta}HSD type 11, however, expression of 17{beta}HSD type 13 is largely restricted to the liver and is not enhanced by peroxisome proliferator-activated receptor {alpha} and its ligand. Instead the expression level of 17{beta}HSD type 13 in the receptor-null mice was increased several-fold. 17{beta}HSD type 13 may have a distinct physiological role as a lipid droplet-associated protein in the liver.

  13. 17-beta-oestradiol-induced vasorelaxation in vitro is mediated by eNOS through hsp90 and akt/pkb dependent mechanism.

    PubMed

    Bucci, Mariarosaria; Roviezzo, Fiorentina; Cicala, Carla; Pinto, Aldo; Cirino, Giuseppe

    2002-04-01

    1. The L-arginine-NO pathway has been implicated in the vasorelaxant effect of 17-beta-oestradiol. Here we have addressed the involvement of two distinct activation steps of endothelial nitric oxide synthase (eNOS) in the 17-beta-oestradiol-induced vasorelaxant effect on rat aortic rings. 2. Rat aortic rings contracted with phenylephrine (PE) 1 microM relaxed in a concentration related fashion to 17-beta-oestradiol water soluble cyclodextrin-encapsulated (E2) only when endothelium was present. The pure anti-oestrogen of E2 receptor ICI 182,780 (20 microM) significantly inhibited E2-induced vasorelaxation. 3. Geldanamycin (10 microM), a specific inhibitor of heat shock protein 90 (hsp90) and N(omega)-nitro-L-arginine-methyl ester (L-NAME, 100 microM), a nitric oxide synthase inhibitor, significantly inhibited E2-induced vasorelaxation. 4. Incubation of rat aortic rings up to 6 h with LY 294002 (25 microM), a specific inhibitor of PI(3)K akt/pkb pathway reduced E2-induced vasorelaxation. 5. Incubation of rat isolated aorta with E2, induced prostacyclin (PGI(2)) release. PGI(2) levels, measured as 6-keto PGF(1alpha), were abolished by ibuprofen (10 microM), both L-NAME and GA did not influence basal or E2-stimulated PGI(2) confirming the specificity of these two compounds on eNOS pathway. 6. In conclusion, we demonstrate that E2 interaction with its receptor is followed by a vasorelaxant effect in rat aortic rings mediated by eNOS activation through both hsp90 and akt/pkb dependent mechanisms. PMID:11934809

  14. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

    NASA Technical Reports Server (NTRS)

    Krumenacker, J. S.; Hyder, S. M.; Murad, F.

    2001-01-01

    Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17beta-estradiol (E2) regulates the alpha(1) and beta(1) subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha(1) 10% and sGC beta(1) 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression.

  15. Genetic mapping of Eutr1, a locus controlling E2-induced pyometritis in the Brown Norway rat, to RNO5.

    PubMed

    Gould, Karen A; Pandey, Jyotsna; Lachel, Cynthia M; Murrin, Clare R; Flood, Lisa A; Pennington, Karen L; Schaffer, Beverly S; Tochacek, Martin; McComb, Rodney D; Meza, Jane L; Wendell, Douglas L; Shull, James D

    2005-11-01

    In certain rat strains, chronic estrogen administration can lead to pyometritis, an inflammation of the uterus accompanied by infection and the accumulation of intraluminal pus. In this article, we report that the Brown Norway (BN) rat is highly susceptible to pyometritis induced by 17beta-estradiol (E2). The susceptibility of the BN rat to E2-induced pyometritis appears to segregate as a recessive trait in crosses to the resistant August x Copenhagen Irish (ACI) strain. In a (BN x ACI)F(2) population, we find strong evidence for a major genetic determinant of susceptibility to E2-induced pyometritis on rat chromosome 5 (RNO5). Our data are most consistent with a model in which the BN allele of this locus, designated Eutr1 (Estrogen-induced uterine response 1), acts in an incompletely dominant manner to control E2-induced pyometritis. Furthermore, we have confirmed the contribution of Eutr1 to E2-induced uterine pyometritis using an RNO5 congenic rat strain. In addition to Eutr1, we obtained evidence suggestive of linkage for five additional loci on RNO2, 4, 11, 17, and X that control susceptibility to E2-induced pyometritis in the (BN x ACI)F(2) population. PMID:16284801

  16. Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat

    SciTech Connect

    Johnson, A.E.; Ball, G.F.; Coirini, H.; Harbaugh, C.R.; McEwen, B.S.; Insel, T.R. )

    1989-09-01

    Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist ({sup 125}I)d(CH2)5(Tyr(Me)2,Thr4,Tyr-NH2(9))OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.

  17. Comparison of effects of estradiol with those of octylmethoxycinnamate and 4-methylbenzylidene camphor on fat tissue, lipids and pituitary hormones.

    PubMed

    Seidlová-Wuttke, Dana; Christoffel, Julie; Rimoldi, Guillermo; Jarry, Hubertus; Wuttke, Wolfgang

    2006-07-01

    Octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC) are commercially used absorbers of ultraviolet (UV) light. In rats, they were shown to exert endocrine disrupting including uterotrophic, i.e. estrogenic effects. Estrogens have also metabolic effects, therefore the impact of oral application of the two UV absorbers at 2 doses for 3 months on lipids and hormones were compared with those of estradiol-17beta (E2). E2, OMC and 4MBC reduced weight gain, the size of fat depots and serum leptin, a lipocyte-derived hormone, when compared to the ovariectomized control animals. Serum triglycerides were also reduced by the UV screens but not by E2. On the other hand, E2 and OMC reduced serum cholesterol, low density lipoproteins and high density lipoproteins; this effect was not shared by 4MBC. While E2 inhibited, OMC and 4MBC stimulated serum LH levels. In the uterus, both UV filters had mild stimulatory effects. 4MBC inhibited serum T4 resulting in increased serum TSH levels. It is concluded that OMC and 4MBC have effects on several metabolic parameters such as fat and lipid homeostasis as well as on thyroid hormone production. Many of these effects are not shared by E2. Hence, other than estrogen-receptive mechanisms may be responsible for these effects. PMID:16368123

  18. Comparison of effects of estradiol with those of octylmethoxycinnamate and 4-methylbenzylidene camphor on fat tissue, lipids and pituitary hormones

    SciTech Connect

    Seidlova-Wuttke, Dana; Christoffel, Julie; Rimoldi, Guillermo; Jarry, Hubertus; Wuttke, Wolfgang . E-mail: ufkendo@med.uni-goettingen.de

    2006-07-01

    Octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC) are commercially used absorbers of ultraviolet (UV) light. In rats, they were shown to exert endocrine disrupting including uterotrophic, i.e. estrogenic effects. Estrogens have also metabolic effects, therefore the impact of oral application of the two UV absorbers at 2 doses for 3 months on lipids and hormones were compared with those of estradiol-17{beta} (E2). E2, OMC and 4MBC reduced weight gain, the size of fat depots and serum leptin, a lipocyte-derived hormone, when compared to the ovariectomized control animals. Serum triglycerides were also reduced by the UV screens but not by E2. On the other hand, E2 and OMC reduced serum cholesterol, low density lipoproteins and high density lipoproteins; this effect was not shared by 4MBC. While E2 inhibited, OMC and 4MBC stimulated serum LH levels. In the uterus, both UV filters had mild stimulatory effects. 4MBC inhibited serum T4 resulting in increased serum TSH levels. It is concluded that OMC and 4MBC have effects on several metabolic parameters such as fat and lipid homeostasis as well as on thyroid hormone production. Many of these effects are not shared by E2. Hence, other than estrogen-receptive mechanisms may be responsible for these effects.

  19. Estradiol Topical

    MedlinePlus

    ... a medication that is applied topically to the vagina. Estradiol is in a class of medications called ... swelling, redness, burning, irritation, or itching of the vagina vaginal discharge Some side effects can be serious. ...

  20. Modeling the photocatalytic mineralization in water of commercial formulation of estrogens 17-β estradiol (E2) and nomegestrol acetate in contraceptive pills in a solar powered compound parabolic collector.

    PubMed

    Colina-Márquez, José; Machuca-Martínez, Fiderman; Li Puma, Gianluca

    2015-01-01

    Endocrine disruptors in water are contaminants of emerging concern due to the potential risks they pose to the environment and to the aquatic ecosystems. In this study, a solar photocatalytic treatment process in a pilot-scale compound parabolic collector (CPC) was used to remove commercial estradiol formulations (17-β estradiol and nomegestrol acetate) from water. Photolysis alone degraded up to 50% of estradiol and removed 11% of the total organic carbon (TOC). In contrast, solar photocatalysis degraded up to 57% of estrogens and the TOC removal was 31%, with 0.6 g/L of catalyst load (TiO2 Aeroxide P-25) and 213.6 ppm of TOC as initial concentration of the commercial estradiols formulation. The adsorption of estrogens over the catalyst was insignificant and was modeled by the Langmuir isotherm. The TOC removal via photocatalysis in the photoreactor was modeled considering the reactor fluid-dynamics, the radiation field, the estrogens mass balance, and a modified Langmuir-Hinshelwood rate law, that was expressed in terms of the rate of photon adsorption. The optimum removal of the estrogens and TOC was achieved at a catalyst concentration of 0.4 g/L in 29 mm diameter tubular CPC reactors which approached the optimum catalyst concentration and optical thickness determined from the modeling of the absorption of solar radiation in the CPC, by the six-flux absorption-scattering model (SFM). PMID:26205059

  1. Bioindicators and reproductive effects of prolonged 17beta-oestradiol exposure in a marine fish, the sand goby (Pomatoschistus minutus).

    PubMed

    Robinson, Craig D; Brown, Elaine; Craft, John A; Davies, Ian M; Megginson, Colin; Miller, Colin; Moffat, Colin F

    2007-03-30

    The effects of 17beta-oestradiol (E2) on mortality, growth rates, sexual maturation, hepatic vitellogenin (VTG) mRNA expression and reproductive success were investigated during an 8-month, water-borne exposure of a marine fish, the sand goby (Pomatoschistus minutus). Indicators of oestrogenic exposure were investigated as predictors of population-level reproductive success. E2 exposure concentrations were <5 (below limit of detection), 16+/-3, 97+/-20 and 669+/-151 ng l(-1) (bootstrap means and standard errors). The carrier solvent (<20 microl l(-1) propan-2-ol) significantly reduced the rate of egg production compared to untreated fish, but did not significantly affect male VTG mRNA expression, brood size, or the other studied parameters. Fish exposed to 16 ng l(-1) E2 showed few adverse effects compared with solvent only-exposed fish. Exposure to 97 ng l(-1) E2 significantly inhibited male sexual maturation, induced male VTG mRNA expression and delayed spawning. The 97 ng l(-1) E2 exposed population also produced fertile eggs at a significantly slower rate than solvent controls; however, brood size, fertility and overall reproductive success were not significantly affected. Exposure to 669 ng l(-1) E2 significantly increased mortality, adversely affected haematological parameters and caused an almost total lack of reproductive activity, with both sexes failing to mature. Reproductive failure following exposure to 669 ng l(-1) E2 was evident in both sexes when crossed with untreated animals. This work indicates that marine fish are similarly as sensitive to oestrogenic exposure as freshwater fish, that exposure biomarkers such as VTG are more sensitive to exposure than are reproductive effects, and that the use of carrier solvents in long-term reproductive studies should be avoided. PMID:17289167

  2. At5g50600 encodes a member of the short-chain dehydrogenase reductase superfamily with 11beta- and 17beta-hydroxysteroid dehydrogenase activities associated with Arabidopsis thaliana seed oil bodies.

    PubMed

    d'Andréa, S; Canonge, M; Beopoulos, A; Jolivet, P; Hartmann, M A; Miquel, M; Lepiniec, L; Chardot, T

    2007-02-01

    In a previous work, we presented evidence for the presence of a protein encoded by At5g50600 in oil bodies (OBs) from Arabidopsis thaliana [P. Jolivet, E. Roux, S. D'Andrea, M. Davanture, L. Negroni, M. Zivy, T. Chardot, Protein composition of oil bodies in Arabidopsis thaliana ecotype WS, Plant Physiol. Biochem. 42 (2004) 501-509]. Using specific antibodies and proteomic techniques, we presently confirm the existence of this protein, which is a member of the short-chain steroid dehydrogenase reductase superfamily. We have measured its activity toward various steroids (cholesterol, dehydroepiandrosterone, cortisol, corticosterone, estradiol, estrone) and NAD(P)(H), either within purified OBs or as a purified bacterially expressed chimera. Both enzymatic systems (OBs purified from A. thaliana seeds as well as the chimeric enzyme) exhibited hydroxysteroid dehydrogenase (HSD) activity toward estradiol (17beta-hydroxysteroid) with NAD+ or NADP+, NADP+ being the preferred cofactor. Low levels of activity were observed with cortisol or corticosterone (11beta-hydroxysteroids), but neither cholesterol nor DHEA (3beta-hydroxysteroids) were substrates, whatever the cofactor used. Similar activity profiles were found for both enzyme sources. Purified OBs were found to be also able to catalyze estrone reduction (17beta-ketosteroid reductase activity) with NADPH. The enzyme occurring in A. thaliana OBs can be classified as a NADP+-dependent 11beta-,17beta-hydroxysteroid dehydrogenase/17beta-ketosteroid reductase. This enzyme probably corresponds to AtHSD1, which is encoded by At5g50600. However, its physiological role and substrates still remain to be determined. PMID:17074428

  3. Fate of glucuronide conjugated estradiol in soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The reproductive hormone, 17ß-estradiol (E2), is made more water soluble (polar) in the body by attachment of glucuronide acid to E2, facilitating urinary elimination. The fate of this potentially more mobile polar form of E2 is not well understood. Soil sorption studies were conducted using [14C] 1...

  4. Relationship between ovarian reserve and preovulatory estradiol during a fixed-time AI protocol in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estradiol production is essential for reproductive efficiency. This study compared numbers of follicles in beef cows that did or did not have elevated preovulatory estradiol during a fixed-time AI (FTAI) protocol. In experiment 1, 5 low estradiol (LowE2) and 5 high estradiol (HighE2) cows were slaug...

  5. PROMOTION BY 17BETA-ESTRADIOL AND BETA-HEXACHLOROCYCLOHEXANE OF HEPATOCELLULAR TUMORS IN MEDAKA, ORYZIAS LATIPES. (R825298)

    EPA Science Inventory

    Abstract

    A feature common to many laboratory and field studies with various fish species is a higher prevalence of hepatocellular neoplasia in females than in males. During female sexual maturation, endogenous estrogens stimulate substantial increases in synthetic acti...

  6. The effect of 17 beta-estradiol on cholesterol in human macrophages is influenced by the lipoprotein milieu

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen and testosterone are thought to modulate coronary heart disease (CHD) risk. To examine how these hormones affect human macrophage cholesterol transport, a key factor in atherogenesis, we obtained monocytes from healthy male and postmenopausal female donors (age 50-70 y). Cells were allowe...

  7. Effects of 17Beta-estradiol on cognitive performance of ovariectomized female rats exposed to 56Fe particles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On exploratory class missions to other planets astronauts will be exposed to types and doses of radiation (HZE particles) that are not experienced in low earth orbit. While it is likely that the crew will consist of both male and female astronauts, there has been little research on the effects of ...

  8. 17beta-hydroxysteroid dehydrogenase type 1 modulates breast cancer protein profile and impacts cell migration

    PubMed Central

    2012-01-01

    Introduction Human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a steroid-converting enzyme that has long been known to play critical roles in estradiol synthesis and more recently in dihydrotestosterone (DHT) inactivation, showing a dual function that promotes breast cancer cell proliferation. Previously, we reported the first observation of the influence of the enzyme on endogenous estrogen-responsive gene expression. Here, we demonstrate the impact of 17β-HSD1 expression on the breast cancer cell proteome and investigate its role in cell migration. Methods 17β-HSD1 was stably transfected in MCF7 cells and the proteome of the generated cells overexpressing 17β-HSD1 (MCF7-17βHSD1 cells) was compared to that of the wild type MCF7 cells. Proteomics study was performed using two-dimensional gel electrophoresis followed by mass spectrometry analysis of differentially expressed protein spots. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to investigate the transcription of individual gene. The effect of 17β-HSD1 on MCF7 cell migration was verified by a wound-healing assay. Results Proteomic data demonstrate that the expression of more than 59 proteins is modulated following 17β-HSD1 overexpression. 17β-HSD1 regulates the expression of important genes and proteins that are relevant to cell growth control, such as BRCA2 and CDKN1A interacting protein (BCCIP) and proliferating cell nuclear antigen (PCNA) which are down- and upregulated in MCF7-17βHSD1 cells, respectively. RT-qPCR data reveal that 17β-HSD1 increases the mRNA levels of estrogen receptors (ER) alpha and beta by 171 and 120%, respectively, while decreasing that of the androgen receptor by 64%. Interestingly, 17β-HSD1 increases the mRNA transcript (by 3.6 times) and the protein expression of the metastasis suppressor gene nm23-H1 and the expression of the two enzymes are closely correlated. We have further shown that 17β-HSD1 expression is associated with an

  9. Estradiol: micrograms or milligrams

    PubMed Central

    Wickramasuriya, Nalin; Shaw, Nicholas J

    2016-01-01

    Summary Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error. Learning points Girls with primary and secondary gonadal failure require assistance with pubertal induction. Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol. Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose. Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height. PMID

  10. Estradiol-Induced Object Recognition Memory Consolidation Is Dependent on Activation of mTOR Signaling in the Dorsal Hippocampus

    ERIC Educational Resources Information Center

    Fortress, Ashley M.; Fan, Lu; Orr, Patrick T.; Zhao, Zaorui; Frick, Karyn M.

    2013-01-01

    The mammalian target of rapamycin (mTOR) signaling pathway is an important regulator of protein synthesis and is essential for various forms of hippocampal memory. Here, we asked whether the enhancement of object recognition memory consolidation produced by dorsal hippocampal infusion of 17[Beta]-estradiol (E[subscript 2]) is dependent on mTOR…

  11. 16. cap alpha. -(/sup 77/Br)bromoestradiol-17. beta. : a high specific-activity, gamma-emitting tracer with uptake in rat uterus and induced mammary tumors

    SciTech Connect

    Katzenellenbogen, J.A.; Senderoff, S.G.; McElvany, K.D.; O'Brien, H.A. Jr.; Welch, M.J.

    1981-01-01

    16..cap alpha..-(/sup 77/Br)bromoestradiol-17..beta.. (compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 hr after administration of compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget tissue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabeled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors.

  12. Urinary testosterone-17 beta-glucuronide as an indicator of androgen output in mice.

    PubMed

    Tyler, J P; Simpson, J; Collins, W P

    1980-11-01

    The androgenic status of female mice was assessed by measuring the concentration of testosterone-17 beta-glucuronide in serial samples of unextracted urine. The subcutaneous administration of testosterone (50 micrograms in lauric acid ethyl ester) resulted in a significant increase (P < 0.01) of the mean +/- s.d. concentration of urinary testosterone-17 beta-glucuronide (25.9 +/- 6.5 to 71.7 +/- 12.9 ng/ml) within 2 h. The 2-h values after the administration of 50 micrograms androstenedione or 50 micrograms dehydroepiandrosterone were 22.8 +/- 4.4 to 81.8 +/- 7.8 ng/ml (P < 0.001) and 23.4 +/- 2.7 to 121.8 +/- 20.3 ng/ml (P < 0.001) respectively. The values decreased progressively over the next 24 h. After the induction of superovulation with PMSG and hCG, the values for testosterone-17 beta-glucuronide increased significantly (P < 0.01) during the periovulatory period (5--24 h after hCG injection). The mean +/- s.d. value in pregnancy was higher (61.8 +/- 11.6 ng/ml; P < 0.001) than that in non-pregnant animals (30.7 +/- 12.3 ng/ml) and remained relatively constant between Days 1 and 16. PMID:6448923

  13. Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model.

    PubMed

    He, Xue Ying; Wen, Guang Yeong; Merz, George; Lin, Dawei; Yang, Ying Zi; Mehta, Penkaj; Schulz, Horst; Yang, Song Yu

    2002-02-28

    A full-length cDNA of mouse type 10 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD10) was cloned from brain, representing the accurate nucleotide sequence information that rendered possible an accurate deduction of the amino acid sequence of the wild-type enzyme. A comparison of sequences and three-dimensional models of this enzyme revealed that structures previously reported by other groups carry either a truncated or mutated amino-terminal sequence. Fusion of the first 11 residues of the wild-type enzyme to the green fluorescent protein directed the reporter protein into mitochondria. Thus, the N-terminus was identified as a mitochondrial targeting signal that accounts for the intracellular localization of the mouse enzyme. This enzyme is normally associated with mitochondria, not with the endoplasmic reticulum as suggested by its trivial name 'endoplasmic reticulum-associated amyloid-beta biding protein (ERAB)'. After its C-terminal region was used to raise rabbit anti-17 betaHSD10 antibodies, immunogold electron microscopy showed that an abundance of this enzyme could be found in hippocampal synaptic mitochondria of betaAPP transgenic mice, but not in normal controls. High levels of this enzyme may disrupt steroid hormone homeostasis in synapses and contribute to synapse loss in the hippocampus of the mouse Alzheimer's disease model. PMID:11869808

  14. Comparison of effects of estradiol (E2) with those of octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC) - 2 filters of UV light - on several uterine, vaginal and bone parameters

    SciTech Connect

    Seidlova-Wuttke, D.; Jarry, H.; Christoffel, J.; Rimoldi, G.; Wuttke, W. . E-mail: ufkendo@med.uni-goettingen.de

    2006-02-01

    OMC and 4MBC are 2 absorbers of ultraviolet light which are used in unknown quantities in sunscreens, cosmetics and plastic products to protect against UV light-induced damage of the skin or of fragrances or plastic material. From there, they were shown to reach surface water and/or by direct contamination or ingestion the human. Under various conditions in mice and rats, both substances were shown to be estrogenic. Therefore, we compared in vitro and in vivo the effects of chronic application of these compounds at 2 doses with those of E2, all administered via food. No signs of toxicity were observed under application of 0.6 mg E2, 57.5 or 275 mg of OMC, 57.5 or 250 mg of 4MBC; these amounts were ingested with 21 g of control food, 17.8 g E2 food, 20.6 g or 22.3 g OMC food and 23.7 or 22.8 g 4MBC food. In the uterus, vagina and bone, E2 exerted the expected stimulatory effects which were minimally shared by OMC and 4MBC in the uterus and vagina as assessed by histology and determination of a variety of estrogen-regulated genes such as insulin-like growth factor-1, progesterone receptor and estrogen receptor {beta}. In the bone, OMC had no effect, while 4MBC shared the antiosteoporotic effects of E2 as measured by quantitative computer tomography in the metaphysis of the tibia. The mechanism of action of 4MBC, however, appears to be different as E2 reduced serum osteocalcin and the C-terminal breakdown products of collagen-1{alpha}1 which were both increased by 4MBC. Taken together, these data indicate a very weak estrogenic effect of OMC and 4MBC in the uterus and in the vagina but not in the bone where 4MBC exerted antiosteoporotic effects by a different mechanism than E2.

  15. Polymorphism of the pig 17beta-hydroxysteroid dehydrogenase type1 (HSD17B1) gene and its association with reproductive traits.

    PubMed

    Liu, L Q; Li, F E; Deng, C Y; Zuo, B; Zheng, R; Xiong, Y Z

    2009-08-01

    17beta-Hydroxysteroid dehydrogenase type 1 (HSD17B1) is a key enzyme of 17beta-estradiol biosynthesis, which might play an important role in follicular development of the ovary. In this study, we isolated the complete coding sequence of porcine HSD17B1 gene and its unique intron sequences of porcine HSD17B1 gene, identified a single nucleotide polymorphism (SNP: A/C) in intron 4, and developed a PCR-MvaI-RFLP genotyping assay. Association of the SNP and litter size was assessed in two populations (purebred Large White and a experimental synthetic Line (DIV) sows). Statistical analysis demonstrated that, in the first parity, AC animals in experimental synthetic Line (DIV) sows had 0.52 more piglets born compared to the CC animals (P<0.05). In the all parities, pigs with the AA genotype had an additional 1.11 and 0.96 piglets born alive compared to the CC animals (P<0.05) in both experimental synthetic Line (DIV) and purebred Large White, respectively. Experimental synthetic Line (DIV) sows inheriting the AC genotype had additional 0.84 piglets born alive compared to the CC animals (P<0.01) in all parities. In addition, significant additive effect of -0.55+/-0.24 piglets/litter and -0.48+/-0.22 piglets/litter on piglet born alive was detected in both experimental synthetic Line (DIV) sows and purebred Large White lines (P<0.05), respectively. Therefore, HSD17B1 gene was significantly associated with litter size in two populations and could be a useful molecular marker in selection for increasing litter size in pigs. PMID:18945563

  16. Comparison of effects of estradiol (E2) with those of octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC)--2 filters of UV light - on several uterine, vaginal and bone parameters.

    PubMed

    Seidlová-Wuttke, D; Jarry, H; Christoffel, J; Rimoldi, G; Wuttke, W

    2006-02-01

    OMC and 4MBC are 2 absorbers of ultraviolet light which are used in unknown quantities in sunscreens, cosmetics and plastic products to protect against UV light-induced damage of the skin or of fragrances or plastic material. From there, they were shown to reach surface water and/or by direct contamination or ingestion the human. Under various conditions in mice and rats, both substances were shown to be estrogenic. Therefore, we compared in vitro and in vivo the effects of chronic application of these compounds at 2 doses with those of E2, all administered via food. No signs of toxicity were observed under application of 0.6 mg E2, 57.5 or 275 mg of OMC, 57.5 or 250 mg of 4MBC; these amounts were ingested with 21 g of control food, 17.8 g E2 food, 20.6 g or 22.3 g OMC food and 23.7 or 22.8 g 4MBC food. In the uterus, vagina and bone, E2 exerted the expected stimulatory effects which were minimally shared by OMC and 4MBC in the uterus and vagina as assessed by histology and determination of a variety of estrogen-regulated genes such as insulin-like growth factor-1, progesterone receptor and estrogen receptor beta. In the bone, OMC had no effect, while 4MBC shared the antiosteoporotic effects of E2 as measured by quantitative computer tomography in the metaphysis of the tibia. The mechanism of action of 4MBC, however, appears to be different as E2 reduced serum osteocalcin and the C-terminal breakdown products of collagen-1alpha1 which were both increased by 4MBC. Taken together, these data indicate a very weak estrogenic effect of OMC and 4MBC in the uterus and in the vagina but not in the bone where 4MBC exerted antiosteoporotic effects by a different mechanism than E2. PMID:15979666

  17. ESTRADIOL AND THE ESTRADIOL METABOLITE, 2-HYDROXYESTRADIOL, ACTIVATE AMP-ACTIVATED PROTEIN KINASE IN C2C12 MYOTUBES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic loss of estradiol (E2) during menopause is associated with increased adiposity which can be prevented with E2 replacement. Rodent studies suggest that E2, or lack of, is a key mediator in menopause-related metabolic changes. We have previously demonstrated that E2 treatment produces a rap...

  18. 17Beta-oestradiol modulates glucocorticoid, neural and behavioural adaptations to repeated restraint stress in female rats.

    PubMed

    Lunga, P; Herbert, J

    2004-09-01

    Sex steroids have a role in modulating responses that extends beyond reproduction. The current study investigated the influence of the sex steroid 17beta-oestradiol on hypothalamic-pituitary-adrenal (HPA) and behavioural responses to acute or repeated restraint stress. Ovariectomized rats treated with 17beta-oestradiol or peanut oil via a subcutaneous silastic capsule were subjected to daily handling (non stressed), acute (single, 1 h) or daily (10 days, 1 h/day) restraint stress. Blood collected at the end of stress revealed that 17beta-oestradiol treatment augmented the corticosterone response to acute restraint. After daily exposure to restraint, the corticosterone response was noticeably diminished in untreated females but 17beta-oestradiol-treated rats still showed an exaggerated response compared to castrated, untreated females. Brain tissue collected 3 h after the end of restraint was probed using isotopic in situ hybridization for corticotropin-releasing factor (CRF) and vasopressin gene expression in the paraventricular nucleus (PVN) of the hypothalamus. 17beta-oestradiol treatment at the higher dose (120 microg/ml) decreased basal CRF mRNA. Stress caused an increase in CRF mRNA expression in 17beta-oestradiol-treated rats but not in the vehicle group. Repeated restraint stress caused an increase in PVN parvocellular vasopressin gene expression, which was more pronounced in 17beta-oestradiol-replaced rats. Animals were exposed to the elevated plus maze for 5 min as a test for anxiety. Non-stressed control rats with or without 17beta-oestradiol replacement spent the same percentage amount of time exploring the open arms of the maze. Previous exposure to acute restraint stress caused a marked reduction in the time spent exploring the open arms, indicating an increase in anxiety levels in these rats; this effect was observed in both vehicle and 17beta-oestradiol-treated rats. After repeated restraint stress, 17beta-oestradiol-replaced rats spent as much time

  19. Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17beta-oestradiol in the ovariectomised mouse uterus.

    PubMed

    Walter, Lisa M; Rogers, Peter A W; Girling, Jane E

    2010-08-01

    The angiogenic effects of 17beta-oestradiol (E(2)) in the mouse endometrium are mediated by vascular endothelial growth factor-A (VEGFA). We analysed the temporal and spatial changes in VEGFA isoform and (co)receptor expression in ovariectomised mouse uteri following E(2) treatment. VEGFA isoform and receptor mRNA were quantified in whole uterine tissue collected 2, 6, 12 and 24 h after E(2) or vehicle treatment. Laser capture microdissection was used to investigate mRNA expression in epithelial, stromal and myometrial tissues separately. Endothelial cell proliferation, VEGFA and VEGF receptor-2 (VEGFR2) protein were visualised using immunohistochemistry. Endometrial endothelial cell proliferation was only observed 24 h after E(2) treatment. In whole uterine tissue, total Vegfa, Vegfa(164) and Vegfa(120) mRNA expression increased 2 h post E(2) treatment, and then decreased by 24 h. Vegfa(188) expression was lower in E(2)-treated animals at all time points relative to control animals. Vegfr2 and neuropilin-1 (Nrp1) mRNA expression did not change following E(2) treatment; Nrp2 expression decreased by 24 h. When uterine compartments were considered separately at 24 h post E(2) or vehicle, stromal Vegfa(120), Vegfa(188) and Vegfr2 mRNA expression and myometrial Vegfa(120) and Vegfa(188) mRNA expression were reduced in E(2)-treated mice relative to controls, whereas epithelial Vegfa(188) mRNA expression increased. The highest VEGFA immunoexpression was observed in luminal epithelium; expression increased at 24 h relative to other time points. No changes were noted in VEGFR2 immunoexpression among treatment groups. We have provided the first evidence that VEGFA isoform and receptor mRNA expression are differentially regulated by E(2) in different uterine cell compartments. PMID:20530092

  20. Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride.

    PubMed

    Münster, U; Hammer, S; Blume-Peytavi, U; Schäfer-Korting, M

    2003-01-01

    Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites. Human skin regulates testosterone action by cell-type-specific activation or deactivation. Effects of 17alpha-estradiol in androgenetic alopecia are not due to 5alpha-reductase inhibition. Dutasteride may be useful in acne and androgenetic alopecia. PMID:14528059

  1. Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites.

    PubMed

    Martucci, C; Fishman, J

    1977-12-01

    The uterotrophic activities of the catechol metabolites of estradiol 2-hydroxyestrone, 2-methoxyestrone and 2-hydroxyestradiol were measured under conditions of continuous administration of sc implanted paraffin pellets. The activity of these estrogens was compared to that of estradiol-17beta and its other principal metabolites estrone, estriol and 15alpha-hydroxyestriol (estetrol). The major catechol estrogens, 2-hydroxyestrone and 2-methoxyestrone, and the pregnancy metabolite, 15alpha-hydroxyestriol, exhibited no uterotrophic activity. The minor catecholestrogen, 2-hydroxyestradiol, showed some activity whose character was different from that exhibited by implants of estradiol, estrone and estriol all of which were equipotent uterotrophic agents. Implants of 2-hydroxyestrone in the presence of estradiol or estriol pellets did not diminish the response to the latter indicating that the 2-hydroxyestrone is not antiestrogenic under these conditions. It is concluded that the direction of estradiol metabolism can have a profound influence on the expression of peripheral hormonal activity with hydroxylation at C-2 terminating and hydroxylation at C-16 extending it. PMID:590186

  2. Effects of long-term treatment with 8-prenylnaringenin and oral estradiol on the GH-IGF-1 axis and lipid metabolism in rats.

    PubMed

    Böttner, Martina; Christoffel, Julie; Wuttke, Wolfgang

    2008-08-01

    After the heart and estrogen/progestin replacement study and the women's health initiative study, the prospect of hormone replacement therapy (HRT) on cardiovascular diseases (CVD) has changed dramatically. These findings led to various attempts to search for alternatives for classical HRT, e.g. phytoestrogens. The flavanone 8-prenylnaringenin (8-PN) was identified as a phytoestrogen with strong estrogen receptor-alpha activity. As the pituitary and the liver are targets for estrogen action, we assessed the effect of ovariectomy (OVX) and long-term treatment (3 months) with 17-beta estradiol benzoate (E(2)B) and 8-PN on pituitary and liver functions in adult OVX rats. Tested doses were 6.8 and 68.4 mg/kg body weight (BW) of 8-PN and 0.17 and 0.7 mg/kg BW of E(2)B. Our results demonstrate that 8-PN and E(2)B decreased BW and increased uterus weight. The high doses of E(2)B and 8-PN increased serum GH and decreased serum IGF-1 levels. E(2)B dose dependently decreased cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) concentrations in OVX rats. The high dose of 8-PN showed an estrogenic activity regarding cholesterol and LDL regulation but had no effect on HDL concentrations. By contrast, the low dose of 8-PN augmented HDL levels compared with intact rats. Triglyceride levels were raised in response to the high E(2)B dose but unaffected by 8-PN treatment. Taken together, 8-PN displays an anti-atherosclerotic profile that appears to be even more beneficial than the one displayed by E(2)B, and thus might demonstrate a remarkable potential for the prevention of CVD associated with estrogen deficiency. PMID:18499805

  3. Molecular genetics and pathophysiology of 17{beta}-hydroxysteroid dehydrogenase 3 deficiency

    SciTech Connect

    Andersson, S.; Geissler, W.M.; Wu, L.

    1996-01-01

    Autosomal recessive mutations in the 17{beta}-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17{beta}-hydroxysteroid dehydrogenase isoenzymes. 29 refs., 2 figs., 3 tabs.

  4. The potential for estradiol and ethinylestradiol to sorb to suspended and bed sediments in some English rivers.

    PubMed

    Holthaus, Karlijn I E; Johnson, Andrew C; Jürgens, Monika D; Williams, Richard J; Smith, Jennifer J L; Carter, Joy E

    2002-12-01

    The endocrine-disrupting impact of steroid estrogens on fish will be strongly influenced by their distribution between sediment and water. Laboratory studies were performed to investigate the potential for sorption of 17beta-estradiol (E2) and 17alpha-ethinylestradiol (EE2) to bed and suspended sediments taken from five British rivers. Sediment material was collected from the Rivers Aire and Calder (located in urban and industrialized areas in Yorkshire, UK), the River Thames (at a relatively rural site in Oxfordshire, UK), and from the estuaries of the Rivers Tees and Tyne. Using anaerobic conditions to inhibit biodegradation, it was found that 80 to 90% of binding to bed sediments was complete within 1 d, but that an equilibrium had not been reached after 2 d. Bed sediments gave distribution coefficients (Kd) ranging from 4 to 74 L/kg for E2 and from 8 to 121 L/kg for EE2 for samples taken over a range of seasons and locations. Sorption to suspended sediment gave Kd values ranging from 21 to 122 L/kg for E2 and 19 to 260 L/kg for EE2. However, these Kd values suggest less than 1% removal of the steroid estrogens from the aqueous phase given the ambient suspended sediment concentration. In the bed sediments, higher Kd values were associated with smaller particle size and higher organic carbon content. In most cases, the Kd values obtained for EE2 were higher than those for E2 by a factor of up to three. PMID:12463545

  5. Transdermal estradiol treatment during breastfeeding: maternal and infant serum concentrations.

    PubMed

    Pinheiro, Emily; Bogen, Debra L; Hoxha, Denada; Wisner, Katherine L

    2016-04-01

    We examined estradiol (E2) and estrone (E1) concentrations in breastfeeding mother-infant dyads. The mothers had postpartum depression and were participants in a randomized clinical trial with three treatments (transdermal E2, sertraline, and placebo). Neither infant E1 and E2 concentrations nor infant growth differed across the treatments. Transdermal E2 administration of 50 to 200 mcg/day for breastfeeding women did not affect infant E1 or E2 concentrations or infant growth. PMID:25956588

  6. Synthesis and biological evaluation of two new radiolabelled estrogens: [125I](E)-3-methoxy-17alpha-iodovinylestra-1,3,5(10),6-tetraen-17beta-ol and.

    PubMed

    Melo e Silva, M C; Patrćio, L; Gano, L; Sá e Melo, M L; Inohae, E; Mataka, S; Thiemann, T

    2001-02-01

    The synthesis of two novel radiolabelled estrogen derivatives, [125I](E)-3-methoxy-17alpha-iodovinylestra-1,3,5(10),6-tetraen-17beta-ol (E[125I]IVDE) and [125I](Z)-3-methoxy-17alpha-iodovinylestra-1,3,5(10),6-tetraen-17beta-ol (Z[125I]IVDE), was carried out aiming to study the influence of the introduction of a C6-C7 double bond on the biological properties of the estradiol molecule. 3-Methoxyestra-1,3,5(10),6-tetraen-17-one was synthesised starting from a suitably protected estrone and subsequently converted into the 17alpha-ethynyl derivative. The radioiodinated derivatives were stereoselectively formed by radioiododestannylation of the corresponding tributylstannyl precursors. The biodistribution of the novel [125I]iodovinylestradiol derivatives was evaluated in immature female mice. Biological data indicated that the Z-isomer, owing to its higher in vivo uptake by the target tissue, has the preferable configuration for further development of similar compounds for estrogen receptor detection. PMID:11200884

  7. Rapid test by liquid chromatography/tandem mass spectrometry to evaluate equine urine reactivity towards 17beta-OH steroids.

    PubMed

    Fidani, Marco; Casagni, Eleonora; Montana, Marco; Pasello, Emanuela; Pecoraro, Chiara; Gambaro, Veniero

    2006-01-01

    Bacteria frequently found in equine urine samples may cause degradation of 17beta-OH steroids. A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to evaluate the microbiological contamination of equine urine as a marker of poor storage conditions. Norethandrolone was used as the internal standard, and the linearity, sensitivity, precision and accuracy of the method were evaluated. 17beta-OH oxidation was demonstrated for testosterone, nandrolone, trenbolone and boldenone, but did not occur in alpha-epimers such as alpha-boldenone and epitestosterone, demonstrating the stereoselectivity of the reaction. A rapid test was performed by spiking one of the four 17beta-OH steroids in samples of diluted equine urine. The steroids were transformed into their respective ketones in the presence of bacterial activity. The test allows direct injection of diluted samples into the LC/MS system, without the need for prior extraction. Results show that the best method of storage is freezing at -18 degrees C. Urine specimens should be analyzed as soon as possible after thawing. This allows bacterial degradation of equine urine to be arrested temporarily, so that the urine can be used for qualitative or quantitative analysis of 17beta-OH steroids. PMID:16862626

  8. Dissipation and transformation of 17B-estradiol-17-sulfate in soil-water systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen conjugates are known to be precursors of endocrine-disrupting free estrogens, e.g. 17B-estradiol (E2) and estrone (E1), in the environment. This study investigated the fate of a sulfate conjugated estrogen, 17B-estradiol-17-sulfate (E2-17S), in agricultural soils using laboratory batch stu...

  9. Monitoring reproduction in the critically endangered marsupial, Gilbert's potoroo (Potorous gilbertii): preliminary analysis of faecal oestradiol-17beta, cortisol and progestagens.

    PubMed

    Stead-Richardson, Ernie; Bradshaw, Don; Friend, Tony; Fletcher, Terry

    2010-01-01

    Gilbert's potoroo (Potorous gilbertii) was rediscovered in 1994 after having been presumed extinct for 120 years. Estimates indicate fewer than 40 individuals remain at Two Peoples Bay Nature Reserve on the south coast of Western Australia although a translocated population of approximately 20 animals has recently been established on nearby Bald Island. A captive breeding facility has been established adjacent to the mainland population but few young have been produced (8 since 1995). Faecal levels of oestradiol-17beta (E(2)) were monitored over a 2-year period in an effort to determine cyclic reproductive activity, and faecal cortisol levels were also monitored to gauge whether chronic stress may be a factor limiting breeding in captivity. Faecal steroids were monitored in six captive females, and four captive male potoroos, and four wild females. The only captive births recorded after 1998 were one in August 1999 and one in February 2001, both to the same female. Peaks in E(2) concentration, up to 10 ng g(-1) of dried faecal mass were measured and results to date suggest the main breeding period to be November-December based on elevated E(2) levels at this time. Clear patterns of reproductive activity in the captive females, however, were not evident. Analysis of epithelial cell counts from urinogenital swabs and faecal E(2) and progestagen (PM) levels from a single female kept at the Perth Zoo, suggest that Gilbert's potoroo has an oestrous cycle of approximately 39 days. Faecal cortisol levels in captive females were significantly lower than those in wild-caught individuals and thus there is no indication that elevated cortisol levels per se inhibited reproduction in captive females. PMID:19539621

  10. Sulfation of estradiol in human epidermal keratinocyte.

    PubMed

    Kushida, Akira; Hattori, Kenji; Yamaguchi, Nozomi; Kobayashi, Tetsuyuki; Date, Akira; Tamura, Hiroomi

    2011-01-01

    Epidermis is one of the well-known estrogen target tissues. Information regarding estrogen metabolism in epidermis is still very limited compared to that of estrogen action. In the breast cancer tissue, 17β-estradiol (E(2)) is inactivated by sulfation and the expression level of estrogen sulfotransferase (SULT1E1) is inversely correlated with its malignancy. However, there is little datum about inactivation of estradiol in skin. In order to detect and measure E(2) and its metabolites simultaneously, we established an assay method with radio HPLC. A majority of [(3)H] labeled E(2) was converted to E(2) sulfate in normal human epidermal keratinocyte (NHEK) cells. The estimated activity of sulfotransferase toward E(2) at 20 nM was 0.11±0.01 (pmol/min/mg protein). Significant induction of estrogen sulfotransferase activity was observed in calcium-differentiated NHEK cells (0.58±0.07 (pmol/min/mg protein)). The gene expression of SULT1E1 was fifteen-fold higher in differentiated keratinocyte than in proliferating keratinocyte, whereas that of steroid sulfatase was reduced. These results suggest that E(2) inactivation is primarily mediated by SULT1E1 in keratinocyte and E(2) action is likely suppressed in epidermal differentiation. PMID:21720030

  11. 16 alpha-(/sup 77/Br)bromoestradiol-17 beta: a high specific-activity, gamma-emitting tracer with uptake in rat uterus and uterus and induced mammary tumors

    SciTech Connect

    Katzenellenbogen, J.A.; Senderoff, S.G.; McElvany, K.D.; O'Brien, H.A. Jr.; Welch, M.J.

    1981-01-01

    16 alpha-(77Br)bromoestradiol-17 beta (Compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 h after administration of Compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget issue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabelled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that Compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors.

  12. The Orientation and Dynamics of Estradiol and Estradiol Oleate in Lipid Membranes and HDL Disc Models

    PubMed Central

    Vogel, Alexander; Scheidt, Holger A.; Feller, Scott E.; Metso, Jari; Badeau, Robert M.; Tikkanen, Matti J.; Wähälä, Kristiina; Jauhiainen, Matti; Huster, Daniel

    2014-01-01

    Estradiol (E2) and E2 oleate associate with high-density lipoproteins (HDLs). Their orientation in HDLs is unknown. We studied the orientation of E2 and E2 oleate in membranes and reconstituted HDLs, finding that E2 and E2 oleate are membrane-associated and highly mobile. Our combination of NMR measurements, molecular dynamics simulation, and analytic theory identifies three major conformations where the long axis of E2 assumes a parallel, perpendicular, or antiparallel orientation relative to the membrane’s z-direction. The perpendicular orientation is preferred, and furthermore, in this orientation, E2 strongly favors a particular roll angle, facing the membrane with carbons 6, 7, 15, and 16, whereas carbons 1, 2, 11, and 12 point toward the aqueous phase. In contrast, the long axis of E2 oleate is almost exclusively oriented at an angle of ∼60° to the z-direction. In such an orientation, the oleoyl chain is firmly inserted into the membrane. Thus, both E2 and E2 oleate have a preference for interface localization in the membrane. These orientations were also found in HDL discs, suggesting that only lipid-E2 interactions determine the localization of the molecule. The structural mapping of E2 and E2 oleate may provide a design platform for specific E2-HDL-targeted pharmacological therapies. PMID:24988346

  13. Characterization of 17beta-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate.

    PubMed

    Elo, J P; Akinola, L A; Poutanen, M; Vihko, P; Kyllönen, A P; Lukkarinen, O; Vihko, R

    1996-03-28

    In the present study, expressions of 17beta-hydroxysteroid dehydrogenase (17HSD) types 1, 2, and 3, 5alpha-reductase type 2 and human androgen receptor mRNAs were determined in 12 benign prostatic hyperplasia and 17 prostatic carcinoma specimens. 17HSD type 2 was found to be the principle isoenzyme expressed in the prostate. Significantly higher expressions of 17HSD type 2 and 5alpha-reductase type 2 were detected in benign prostatic hyperplasia compared with the carcinoma specimens. Expression of the androgen receptor in the 2 groups was not significantly different. 17HSD type 3 mRNA was not detected in any of the specimens investigated. Only low constructive expression of the 2.3 kb mRNA of 17HSD type 1 was seen. Immunohistochemical analysis indicated that this did not lead to significant enzyme expression, only faint staining for the enzyme protein being detected, mainly in uroepithelial cells. No significant correlation was found between any of the mRNAs analysed, but the data on 5alpha-reductase type 2 mRNA support the presence of an increased proportion of 5alpha-dihydrotesterone in the hyperplastic prostate. In cultured PC-3 prostatic cancer cells and in the transiently transfected human embryonic kidney 293 cells, 17HSD type 2 was found exclusively to convert 5alpha-dihydrotestosterone and testosterone into the less potent 17-keto compounds 5alpha-androstanedione and 4-androstenedione, respectively. We suggest that the 17HSD type 2 isoenzyme plays a part in the metabolic pathway, resulting in the inactivation of testosterone and 5alpha-dihydrotestosterone locally in the prostate. The enzyme expressed in the prostate could, therefore, protect cells from excessive androgen action. PMID:8608963

  14. Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels.

    PubMed

    Hudmon, A; Davenport, G; Coleman, E S; Sartin, J L

    2009-10-01

    Estradiol increases basal growth hormone (GH) concentrations in sheep and cattle. This study sought to determine the effects of estradiol on GH-releasing hormone (GRH)-stimulated GH release in sheep. Growth hormone secretory characteristics, the GH response to GRH, and steady-state GH mRNA concentrations were determined in castrated male lambs treated with 2 different doses of estradiol 17-beta for a 28-d experimental period. Although no differences between treatments in mean GH, basal GH, or GH pulse number were observed after 28 d of estradiol treatment, GH pulse amplitude was greater (P < 0.05) in the 2.00-cm implant-treated animals than in the control and 0.75-cm implant group. The effect of estradiol treatment on GRH-stimulated GH release revealed differences between the control and estradiol-treated animals (P < 0.05). The 15-min GH responses to 0.075 microg/kg hGRH in the control, 0.75-cm, and 2.00-cm implant groups, respectively, were 76 +/- 10, 22.6 +/- 2.1, and 43.6 +/- 15.0 ng/mL. Growth hormone mRNA content was determined for pituitary glands from the different treatment groups, and no differences in steady-state GH mRNA levels were observed. There were no differences in the mean plasma concentrations of IGF-I, cortisol, T(3), or T(4) from weekly samples. Growth hormone release from cultured ovine pituitary cells from control sheep was not affected by estradiol after 72 h or in a subsequent 3-h incubation with estradiol combined with GRH. These data suggest that estradiol has differing actions on basal and GRH-stimulated GH concentrations in plasma, but the increase in pulse amplitude does not represent an increased pituitary sensitivity to GRH. PMID:19616401

  15. Modeling the interaction of binary and ternary mixtures of estradiol with bisphenol A and bisphenol AF in an in vitro estrogen-mediated transcriptional activation assay (T47D-KBluc).

    PubMed

    Bermudez, Dieldrich S; Gray, Leon E; Wilson, Vickie S

    2010-08-01

    Exposure to xenoestrogens occurs against a backdrop to physiological levels of endogenous estrogens. Endogenous estrogen levels vary from low levels in early childhood to high levels during pregnancy and in young women. However, few studies have addressed how xenoestrogens interact with endogenous estrogens. The current study was designed to characterize the individual dose-response curves of estradiol-17beta (E(2)), bisphenol A (BPA), tetrabromo-bisphenol A (TBBPA), and bisphenol AF (BPAF, 4,4'-hexafluoroisopropylidene diphenol) on estrogen-dependent luciferase expression in T47D-KBluc cells and to determine how binary (8 x 8 factorial) and ternary (4 x 4 x 4 factorial) mixtures of an endogenous estrogen (E(2)) interact with BPA and/or BPAF. Log EC(50) and hillslope values with SEs, respectively, for individual compounds were as follows: E(2), -12.10M +/- 0.06071, 0.7702 +/- 0.1739; BPA, -6.679M +/- 0.08505, 1.194 +/- 0.2137; and BPAF, -7.648M +/- 0.05527, 1.273 +/- 0.1739. TBBPA was not evaluated in mixture studies because of its minimally estrogenic response at 3 x10(-5)M and elicited cytotoxicity at higher concentrations. Both the binary mixtures of E(2) with BPA and BPAF and the ternary mixture of E(2), BPA, and BPAF behaved in an additive manner. For binary mixtures, as E(2) concentration increased, higher concentrations of BPA and BPAF were necessary to induce a significant increase in the estrogenic response. Understanding the behavior of mixture interactions of xenoestrogens, like BPA and BPAF, with endogenous estrogens will allow a better assessment of the potential risk associated with exposure to these chemicals, individually or as mixtures. PMID:20498000

  16. Effect of exogenous estradiol on plasma concentrations of somatotropin, insulin-like growth factor-I, insulin-like growth factor binding protein activity, and metabolites in ovariectomized Angus and Brahman cows.

    PubMed

    Simpson, R B; Chase, C C; Spicer, L J; Carroll, J A; Hammond, A C; Welsh, T H

    1997-11-01

    To determine the effect of breed and estradiol-17 beta on selected hormones and metabolites, ovariectomized (> or = 3 mo) Angus (n = 14) and Brahman (n = 12) cows were paired by age and body weight and randomly assigned as either nonimplanted controls (CON) or implanted with estradiol (E2) for 45 d. After Day 7 and through Day 42, plasma concentration of somatotropin was greater for E2 than CON cows (treatment x day, P < 0.05). During an intensive blood sampling on Day 36, E2 cows tended (P < 0.10) to have greater somatotropin pulse amplitudes than CON cows, but other parameters of somatotropin release were not affected (P > 0.10) by E2 treatment. The effect of breed was apparent on Day 36 as Brahman cows had greater (P < 0.05) somatotropin pulse amplitude, basal secretion, and mean concentration than Angus cows. Overall, plasma concentration of IGF-I was greater (P < 0.01) for E2 than CON cows (158.3 vs. 104.2 ng/ml) and was greater for Brahman than Angus cows (164.1 vs. 98.4 ng/ml). However, there was a trend (P < 0.10) for a treatment x breed x day interaction for IGF-I (i.e., the magnitude of increase in IGF-I concentration was greater in E2-Angus than E2-Brahman cows). After Day 7 and through Day 42, total plasma IGF binding protein (IGFBP) activity was greater (P < 0.01) for E2 than CON cows. Ligand blotting revealed at least five forms of IGFBP activity, and E2 cows had greater (P < 0.05) binding activity of IGFBP-3 and the 30- and 32-kDa IGFBP than CON cows. Brahman cows had greater (P < 0.05) IGFBP-3 and the 32-kDa IGFBP than Angus cows. After Day 14 and through Day 42, concentration of urea nitrogen (PUN) was greater (P < 0.001) for CON than E2 cows (treatment x day, P < 0.001). Brahman had greater (P < 0.01) PUN than Angus cows (16.6 vs. 14.2 mg/dl). Plasma concentration of glucose was greater (P < 0.01) for E2 than CON cows (78.9 vs. 76.4 mg/dl) but was not affected (P > 0.10) by breed. In summary, these data suggest that some, but not all, of the

  17. Hepatic gene expression following consumption of soy protein isolate in female sprague-dawley rats differs from that produced by 17beta-estradiol treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although soy foods have been recognized as an excellent source of protein, there have been recent concerns regarding potential adverse effects of isoflavone phytochemicals found in soy products, which are known to bind and activate estrogen receptors. Here we used global hepatic gene expression prof...

  18. Uterine physiological responses and global gene expression in ovariectomized (ovx) rats treated with soy protein isolate (spi) or 17Beta-estradiol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concerns regarding increased endometrial cancer risk have been raised in women who consume soy products as the result of the estrogenicity of phytochemical components such as the isoflavones genistein and daidzein. Female Sprague-Dawley rats (N = 20/group) were fed AIN-93G diets with casein or SPI a...

  19. SPE-LC/ESI/MS: a simple and reproducible method for detection and quantification of 17beta-estradiol in aqueous samples

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Steroid estrogens contained in wastewater discharge from sewage treatment plants and agricultural run-off can alter endocrine function in exposed wildlife at part per trillion (ng/L) levels. Detection and quantification of estrogens in the environment at these levels pose numerous analytical challen...

  20. Mammary gland morphology and gene expression differ in female rats treated with 17 beta-estradiol or fed soy protein isolate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soy foods have been suggested to have both positive health benefits and potentially adverse effects as a result of their content of phytoestrogens. However, studies on the estrogenicity of soy foods are lacking. Here we directly compared the effects of soy protein isolate (SPI), the protein in soy i...

  1. PROMOTION BY 17&BETA;-ESTRADIOL AND &BETA;-HEXACHLOROCYCLOHEXANE OF HEPATOCELLULAR TUMORS IN MEDAKA, ORYZIAS LATIPES. AQUAT. (R828676C002)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. DETERMINING THE SENSITIVE DEVELOPMENTAL STAGES OF INTERSEX INDUCTION IN MEDAKA (ORYZIAS LATIPES) EXPOSED TO 17 BETA-ESTRADIOL OR TESTOSTERONE. (R825298)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  3. Differing transcriptional responses to pulsed or continuous estradiol exposure in human umbilical vein endothelial cells.

    PubMed

    Li, Jin; Wang, Hongliang; Johnson, Suzanne M; Horner-Glister, Emma; Thompson, John; White, Ian N H; Al-Azzawi, Farook

    2008-07-01

    This study used human umbilical vein endothelial cells (HUVECs) that were treated with 17beta-estradiol for 5 days as 1h pulse or 24h continuous treatment at concentrations such that the 24h exposure (concentration x time) was identical in both conditions. Cell proliferation was studied and gene expression profiling was carried out using the Affymetrix GeneChip microarray analysis. Changes in morphology and apoptosis in HUVECs were examined with electron microscopy. Time-course studies of expression of genes vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed by quantitative PCR. We observed that cell proliferation was significantly decreased over days 3-5 with pulsed estradiol treatment relative to constant exposure. Microarray results showed that after 5 days, 801 genes differed (P<0.05) between continuous versus pulsed estradiol treatment. Functional analysis showed a significant number of genes to be associated with apoptosis and cell cycle pathways. We did not find any evidence of apoptosis from flow cytometry or electron microscopy examination. Our study highlights a large number of significantly different molecular responses to estradiol depending upon the mode of administration of estradiol. Significant changes were observed in genes involved in apoptosis and proliferation including VEGF, IGF receptors, and tumor protein p53. PMID:18562193

  4. The UV-filter benzophenone-1 inhibits 17beta-hydroxysteroid dehydrogenase type 3: Virtual screening as a strategy to identify potential endocrine disrupting chemicals.

    PubMed

    Nashev, Lyubomir G; Schuster, Daniela; Laggner, Christian; Sodha, Seloni; Langer, Thierry; Wolber, Gerhard; Odermatt, Alex

    2010-04-15

    The prevalence of male reproductive disorders and testicular cancer is steadily increasing. Because the exposure to chemicals disrupting natural hormone action has been associated with these diseases, it is important to identify endocrine disrupting chemicals (EDCs) and their targets of action. Here, a 3D-structural database that can be applied for virtual screening approaches to facilitate the identification of EDCs was constructed. The database was screened using pharmacophores of 17beta-hydroxysteroid dehydrogenase type 3 (17beta-HSD3), which catalyzes the last step of testosterone synthesis in testicular Leydig cells and plays an essential role during male sexual development. Among other chemicals, benzophenone (BP) UV-filters were predicted as potential 17beta-HSD3 inhibitors. Biological analyses revealed (2,4-dihydroxyphenyl)-phenylmethanone (also known as benzophenone-1, BP-1) as an inhibitor of human 17beta-HSD3 (IC(50) 1.05microM). BP-1 also efficiently blocked conversion of androstenedione to testosterone by mouse and rat 17beta-HSD3 in whole-organ enzyme assays. Moreover, BP-1 antagonized the testosterone-dependent activation of androgen receptors (IC(50) 5.7microM), suggesting synergistic anti-androgenic effects of BP-1 by preventing testosterone formation and blocking receptor activation. In addition, analyses of several commonly used UV-filters on estrogen- and androgen-metabolizing 17beta-HSD enzymes revealed 3-benzylidene camphor (3-BC) and 4-methylbenzylidene camphor (4-MBC) as low micromolar 17beta-HSD2 inhibitors. In conclusion, screening of virtual chemical structure libraries can facilitate the identification of compounds interfering with hormone action. The potential disruption of 17beta-HSD enzyme function by the UV-filters BP-1, 3-BC and 4-MBC requires further investigation and should be considered for safety assessment of these chemicals. PMID:20005209

  5. THE PATHOBIOLOGY OF 17B-ESTRADIOL IN SUMMER FLOUNDER, PARALICHTYS DENTATUS

    EPA Science Inventory

    Estradiol has been shown to cause increased vitellogenin (VtG) concentrations in male fish. The intent of this study was to evaluate the pathobiology associated with exposure to 17 -estradiol (E2) on liver, gonad, and kidney tissues of summer flounder, Paralichthys dentatus. Juve...

  6. A role for the androgen metabolite, 5alpha androstane 3beta, 17beta diol (3β-diol) in the regulation of the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, Robert J; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary-adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3β-Diol in

  7. A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3β-Diol) in the Regulation of the Hypothalamo-Pituitary–Adrenal Axis

    PubMed Central

    Handa, Robert J.; Sharma, Dharmendra; Uht, Rosalie

    2011-01-01

    Activation of the hypothalamo-pituitary–adrenal (HPA) axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, corticotrophin-releasing hormone (CRH), vasopressin (AVP), and oxytocin (OT) expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2) and testosterone (T) are well known reproductive hormones; however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated adrenocorticotropic hormone (ACTH) and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen dihydrotestosterone (DHT) and its subsequent binding to the androgen receptor, whereas E2 effects were thought to be mediated by estrogen receptors alpha (ERalpha) and beta (ERbeta). However, DHT has been shown to be metabolized to the ERbeta agonist, 5α- androstane 3β, 17β Diol (3β-Diol). The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta-knockout mice. The neurobiological mechanisms underlying the ability of ERbeta to alter HPA reactivity are not currently known. CRH, AVP, and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters has been shown to occur by 3β-Diol binding to ERbeta and this is thought to occur through alternate pathways of gene regulation. Based on available data, a novel and important role of 3

  8. Sorption and degradation of 17ß-estradiol-17sulfate in agricultural soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2) can induce endocrine disruptions at low concentrations. Laboratory studies have indicated low potential for persistence and mobility of E2 in the environment, and yet field studies measure estrogens at concentrations of concern. Humans and animals eliminate E2 primarily as a conju...

  9. Estradiol signaling via sequestrable surface receptors.

    PubMed

    Benten, W P; Stephan, C; Lieberherr, M; Wunderlich, F

    2001-04-01

    Estradiol (E(2))-signaling is widely considered to be exclusively mediated through the transcription-regulating intracellular estrogen receptor (ER) alpha and ERbeta. The aim of this study was to investigate transcription-independent E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC-21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser scanning microscopy. A special feature of this E(2)-receptor is its sequestration upon agonist stimulation. Sequestration depends on energy and temperature, and it proceeds through a clathrin- and caveolin-independent pathway. PMID:11250949

  10. Fate of 17B-estradiol in anaerobic lagoon digesters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate of [14C]17B-estradiol ([14C]E2) was monitored for 42 d in triplicate 10 L anaerobic digesters. Total radioactive residues (TRR) decreased rapidly in the liquid layer of the digesters and reached a steady-state value of 19-24% of the initial dose after 4 days. LC/MS/MS analyses of the liqu...

  11. Fate of estradiol and testosterone in anaerobic lagoon digestors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laboratory-scale lagoon digestors were constructed, and the fate of 14C-labelled 17ß-estradiol (E2) and testosterone (Test) were monitored for 42 d anaerobically under biological and sterile conditions. Hormone levels decreased in the liquid layer and increased in the sludge with time. At 42 d, 16-2...

  12. Drospirenone/ethinyl estradiol.

    PubMed

    Rapkin, Andrea J; Sorger, Shelley N; Winer, Sharon A

    2008-02-01

    Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral contraceptive formulation that combines in a novel dosing regimen the lowest dosage of ethinyl estradiol commonly used today with drospirenone, an innovative progestin. Drospirenone is a compound closely resembling progesterone, but with the antimineralocorticoid and antiandrogenic properties of a related therapeutic agent, the diuretic, antihypertensive and androgen receptor antagonist, 17alpha-spironolactone. The prolongation of hormonally active pills in the monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by 4 days of inactive pills, is an interesting variant of the recently developed extended pill regimens (1). Recent contraceptive research has focused on improving side effect profiles and providing noncontraceptive health and lifestyle advantages. Many of these benefits are now supported with evidence-based medicine (2). Most available oral contraceptives improve cycle regularity, menstrual pain, excessive menstrual flow and acne. However, weight gain, bloating, food cravings, breast tenderness and mood alterations (especially irritability and depression and the complex of affective, behavioral and somatic symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual dysphoric disorder [PMDD]) are not generally improved with the traditional oral contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently the only hormonally based contraceptive regimen with large, randomized, controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and Drug Administration (FDA) indications not only for the prevention of pregnancy but also for PMDD and for moderate acne vulgaris in women who choose oral contraception for birth control (4, 5). PMID:18389090

  13. Nitric oxide concentrations, estradiol-17β progesterone ratio in follicular fluid, and COC quality with respect to perifollicular blood flow in cows.

    PubMed

    Pancarci, S M; Ari, U Ç; Atakisi, O; Güngör, O; Ciğremiş, Y; Bollwein, H

    2012-01-01

    The objectives were to investigate relationships among concentrations of nitric oxide (NO), estradiol 17 beta (E2), and progesterone (P4) in follicular fluids (FF), and quality of cumulus oocyte complexes (COCs) with respect to perifollicular blood flow (FBF). In Experiment I, follicles (138) were classified according to the presence or absence of FBF (assessed with transvaginal Doppler ultrasonography) and diameter of follicles (small, 2-4 mm; medium, 5-8 mm; and large, ≥9 mm). Concentrations of NO in FF did not differ significantly among these size categories. However, NO concentrations in FF with FBF (54.4 ± 7.4 μmol/l) were higher (P<0.05) than in those without FBF (36.6 ± 4.1 μmol/l). There was a positive correlation (r=0.30, P<0.05) between NO concentrations and the E2:P4 in FF. Rate of E2 active (E2:P4 ≥ 1) follicles were numerically 1.2 (0.8-1.8) times higher in follicles with FBF (38.1%) compared to those without FBF (25.0%). Moreover, rates of E2 active follicles were 6.1 (0.7-55.2) and 1.3 (0.1-17.3) times higher (P<0.06) in large (43.3%) and medium (14.3%) compared to small follicles (11.1%), respectively. In Experiment II, quality of COCs from 2 to 8 mm follicles, obtained by transvaginal ovum pick up (OPU), was investigated with respect to FBF. Odds ratio to obtain higher quality COCs from follicles with FBF (47.1%) was 3.3 (1.1-9.6) fold higher (P<0.05) compared to those from follicles without FBF (14.6%). In conclusion, E2:P4, and NO concentrations in FF, as well as FBF, could be used to determine the functionality of ovarian follicles in cows. Moreover, determination of FBF could be useful to predict quality of COCs in cattle. PMID:22281101

  14. [Medication of the month. A new combined oral contraceptive containing estradiol valerate and dienogest (Qlaira)].

    PubMed

    Gaspard, U; Pintiaux, A; Kridelka, F

    2010-12-01

    In combined oral contraception (OC), a drastic reduction of both ethinylestradiol and androgenic progestins mostly derived from 19 NOR testosterone, allowed to moderately reduce the adverse impact of classical combined pills on metabolism and circulation (both arterial and venous). However, the marked hepatic action of ethinylestradiol, even in small dosages, lessens the expected risk reduction. For the first time, an OC has been developed, which contains estradiol valerate (with reduced hepatic action because of lack of a 17alpha ethinyl group) with dienogest, a 19 NOR testosterone-derived nonandrogenic progestin, which powerfully inhibits endometrial proliferation. Thanks to a dynamic modulation of estrogen and progestin doses (26 active days + 2 placebo days), an adequate contraceptive effectiveness, a good cycle control and drug tolerance are achieved, similar to those obtained with a classical low-dose OC. Recent data indicate that this new combination reduces the usually observed metabolic impact. An adequate cycle control (with 20% amenorrhea) is achieved for the first time with estradiol valerate + progestin,, in opposition with prior catastrophic results with other formulations containing 17beta-estradiol. A second combination containing estradiol + nomegestrol acetate (monophasic, 24 active days + 4 placebo days) is under study and seems also to yield promising results. Of course, in-depth study of metabolic and vascular effects of these new combinations is mandatory - and ongoing. PMID:21287768

  15. Superovulation in the cow: comparison of oestradiol-17 beta and progesterone patterns in plasma and milk of cows induced to superovulate; relationships with ovarian responses.

    PubMed

    Saumande, J; Batra, S K

    1985-11-01

    Free oestradiol-17 beta, free + conjugated oestradiol-17 beta (total oestradiol-17 beta) and progesterone in milk, and free oestradiol-17 beta and progesterone in plasma were measured in 16 cyclic cows injected with FSH to induce superovulation during the treatment and periovulatory periods. The patterns of steroid secretion were the same in milk as in plasma but at different concentrations. Among oestrogens, the highest concentrations were measured for total oestradiol-17 beta in milk, followed by free oestradiol in plasma and free oestradiol in milk. Progesterone concentrations in milk were higher than in plasma. The peak concentrations of oestrogens were related to ovulation rate: Spearman Rank Correlation coefficient (r.s.) = 0.87 (P less than 0.001), 0.78 (P less than 0.001) and 0.69 (P less than 0.001) for total oestradiol, free oestradiol in milk and free oestradiol in plasma respectively. The increase in progesterone concentrations in milk between the beginning of treatment and prostaglandin injection was negatively correlated with the percentage of viable embryos among those recovered (r.s. = -0.68; P less than 0.001). This was not observed for progesterone in plasma. These results therefore show that the steroid pattern in milk gives a better indication as to the ovarian response to a superovulatory treatment than does the steroid pattern in plasma. In addition the fact that milk samples are easier to obtain and handle than blood plasma have led us to conclude that, to follow the effect of gonadotrophin stimulation, it would be more informative to assay oestradiol-17 beta and progesterone in milk rather than in plasma. PMID:3934312

  16. Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells1

    PubMed Central

    Hoang, Yvonne D.; Nakamura, Brooke N.; Luderer, Ulrike

    2009-01-01

    Glutathione (GSH), the most abundant intracellular nonprotein thiol, is critical for many cellular functions. The rate-limiting step in GSH synthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimer composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The tissue-specific regulation of GSH synthesis is poorly understood. We showed previously that gonadotropin hormones regulate ovarian GSH synthesis. In the present study, we sought to clarify the ovarian cell type-specific effects of follicle-stimulating hormone (FSH) and estradiol on GSH synthesis. Immature female rats were treated with estradiol to stimulate development of small antral follicles. Granulosa cells (GCs) from these follicles or whole follicles were cultured in serum-free media, with or without FSH and 17beta-estradiol. The GSH and GCLC protein and mRNA levels increased in GCs treated with FSH alone. The effects of FSH on GCLC and GCLM protein and mRNA levels, GCL enzymatic activity, and GSH concentrations in GCs were significantly enhanced by the addition of estradiol. Estradiol alone had no effects on GSH. Dibromo-cAMP mimicked and protein kinase A (PKA) inhibitors prevented FSH stimulation of GCL subunit protein levels. In cultured small antral follicles, FSH stimulated estradiol synthesis and robustly increased GCL subunit mRNA and protein levels and GSH concentrations. The GCL subunit mRNA expression increased in both the granulosa cells and theca cells of follicles with FSH stimulation. These data demonstrate that maximal stimulation of GSH synthesis by FSH in granulosa cells and follicles requires estradiol. Without estradiol, FSH causes lesser increases in GCL subunit expression via a PKA-dependent pathway. PMID:19516019

  17. Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol

    PubMed Central

    Nagata, Yuka; Yoshikawa, Jun; Hashimoto, Atsushi; Yamamoto, Masayuki; Payne, Anita H.; Todokoro, Kazuo

    2003-01-01

    A matured megakaryocyte releases thousands of platelets through a drastic morphological change, proplatelet formation (PPF). The megakaryocyte/erythrocyte-specific transcription factor, p45 NF-E2, is essential for initiating PPF, but the factor regulating PPF has not been identified. Here we report that estradiol synthesized in megakaryocytes triggers PPF. We demonstrate that a key enzyme for steroid hormone biosynthesis, 3β-hydroxysteroid dehydrogenase (3β-HSD), is a target of p45 NF-E2, and rescues PPF of p45 NF-E2-deficient megakaryocytes. We also show that estradiol is synthesized within megakaryocytes, and that extracellular estradiol stimulates PPF, inhibition of 3β-HSD activity blocks PPF, and estrogen receptor antagonists inhibit platelet production in vivo. We conclude that autocrine estradiol action regulates platelet production by triggering PPF. PMID:14665668

  18. The sexually differentiated metabolism of [6,7-3H]17 beta-oestradiol in rats: male-specific 15 alpha- and male-selective 16 alpha-hydroxylation and female-selective catechol formation.

    PubMed

    Maggs, J L; Morgan, P; Park, B K

    1992-03-01

    The oxygenated-metabolite profiles of exogenous 17 beta-oestradiol (E2) in adult male and female Wistar rats have been characterized and major sex-dependent biotransformations observed which correlate with the regioselectivities of known sexually differentiated hepatic P450. [6,7-3H]E2 (27 micrograms/kg) was given i.v. The metabolites of E2 were rapidly and extensively excreted in bile (46 and 78% of the dose over 1 and 6 h, respectively). Female rats metabolized E2 by one major pathway: oxidation to oestrone (E1) followed by C-2 hydroxylation and O-methylation; the principal aglycones (0-1 h bile collections) were E1 (14%), 2-hydroxyE1 (2-OHE1) (42%) and 2-methoxyE1 (24%). Male rats metabolized E2 principally by two parallel composite pathways of E1 hydroxylation which yielded a complex mixture of mono- and di-oxygenated compounds: 15 alpha-OHE1 (33%), 2,15 alpha-diOHE1 (7%), and 2-methoxy-15 alpha OHE1 (14%); 16 alpha-OHE1 (13%), 2,16 alpha-diOHE1 (4%) and 2-methoxy-16 alpha-OHE1 (2%). 15 alpha-Hydroxylation was unique to males. The balance of aromatic and alkyl hydroxylation in males was dose-dependent: at 3 mg/kg, 15 alpha-hydroxylation was decreased approx. 50% in favour of 2-hydroxylation whilst 16 alpha-hydroxylation was largely unaffected. The male-specific 15 alpha-hydroxylation and male-predominant 16 alpha-hydroxylation of E1 derived from E2 in vivo may be ascribable to the male-specific isoforms P450IIC13 and P450IIC11, respectively. PMID:1313694

  19. Comparison of Two Methods of Estradiol Replacement: their Physiological and Behavioral Outcomes

    PubMed Central

    Mosquera, Laurivette; Shepherd, Luz; Torrado, Aranza I; Torres-Diaz, Yvonne M; Miranda, Jorge D; Segarra, Annabell C

    2016-01-01

    Fluctuating sex steroids during the estrous or menstrual cycle of mammalian females make it difficult to determine their role on behaviors and physiology. To avoid this, many investigators ovariectomize their animals and administer progesterone, estradiol or a combination of both. Several different strategies are used to administer estradiol, which confounds interpretation of results. This study compared two methods of estradiol replacement implants: Silastic tubes filled with crystalline estradiol benzoate (E2) and commercially available estradiol benzoate pellets. Implants were placed subcutaneously in adult ovariectomized (OVX) rats and blood samples obtained weekly. Control OVX rats received empty Silastic tubes or placebo pellets. Our data shows that E2 plasma levels from rats with Silastic implants peaked after one week and decreased slowly thereafter. In contrast, plasma E2 from commercial pellets peaked after two weeks, increasing and decreasing over time. To validate hormone release, body weight was monitored. All E2 treated animals maintained a similar body weight over the four weeks period whereas an increase in body weight over time was observed in the OVX group that received empty implants, confirming E2 release and supporting the role of E2 in the regulation of body weight. Furthermore, the effects of E2 on basal locomotor activity were assessed using animal activity cages. Results showed no difference between E2 and control group in several locomotor activities. These results indicate that Silastic implants achieve more stable plasma estradiol levels than pellets and thus are a better alternative for studies of estradiol on brain function and behavior. PMID:26962471

  20. Mammary gland morphology and gene expression signature of prepubertal male and female rats following exposure to exogenous estradiol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to characterize the actions of xenoestrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. We assessed effects of three doses of exogenous estradiol (E2) (0.1, 1.0 and 10 micrograms/kg/day) on the mammary gland morphology and gene expressi...

  1. Estradiol blood test

    MedlinePlus

    E2 test ... temporarily stop taking certain medicines that may affect test results. Be sure to tell your provider about ... helps prevent sperm from dying too early. This test may be ordered to check: How well your ...

  2. The expression of genes encoding zona pellucida glycoproteins in canine cumulus-oocyte complexes cultured in vitro in media supplemented with progesterone and estradiol.

    PubMed

    Kempisty, B; Woźna, M; Piotrowska, H; Bukowska, D; Jackowska, M; Antosik, P; Jaśkowski, J M; Brüssow, K-P

    2012-02-01

    The role of progesterone (P4) and estradiol-17beta (E2) on the efficiency of canine oocyte maturation in vitro is recognized, but little is known about the influence of both steroids on the expression of zona pellucida (ZP) glycoproteins. It has been shown that E2 and P4 used in the IVC significantly influenced canine oocytes meiotic competence, although the effect is specifically related to the combination of hormones used in the experiment. Because both of these steroids may stimulate or inhibit maturation competence of oocytes in a dose-dependent manner, there is a high possibility that they also influence the fertilization ability of canine oocytes. Our study was aimed to analyze whether genes, encoding ZP glycoproteins, are regulated by P4 or E2. Canine cumulus oocyte complexes (COCs) were recovered from anestrous mongrel bitches after ovariohysterectomy and cultured in serum-free tissue culture medium 199. The expression pattern of ZP glycoproteins 2 and 3 (ZP2 and ZP3) mRNAs, using quantitative real-time polymerase chain reaction (RQ-PCR), and of ZP3 and ZP4 proteins, using Western blot analyses, was examined in oocytes after the supplementation of the culture medium with (1) 0.5 μg/mL, 1.0 μg/mL, and 2.0 μg/mL of P4 (experiment 1), or with (2) 2.0 μg/mL E2, and with (3) a combination of E2 (2.0 μg/mL) and P4 (0.5, 1.0, or 2.0 μg/mL, respectively; experiment 2). The analysis revealed an inhibited expression of ZP2 mRNA in oocytes after in vitro maturation (IVM) with different P4 supplementations as compared with oocytes before IVM. The expression of ZP3 mRNA was stimulated (P < 0.01) by the supplementation of 1.0 μg/mL P4. The expression of both ZP3 and ZP4 proteins was also stimulated after the treatment with 1.0 μg/mL P4. On the other hand, the level of ZP2 mRNA was inhibited (P < 0.01) after the supplementation with E2 or with combinations of E2 and P4 as compared with control oocytes. The expression of ZP3 mRNA was significantly higher after the

  3. Localization of neuropeptide-Y immunoreactivity in estradiol-concentrating cells in the hypothalamus

    SciTech Connect

    Sar, M.; Sahu, A.; Crowley, W.R.; Kalra, S.P. )

    1990-12-01

    Considerable evidence shows that gonadal steroids exert a facilitatory influence on levels and release of neuropeptide-Y (NPY) from the hypothalamus. However, it is not known whether gonadal steroids act directly on NPY-producing cells in the arcuate nucleus (ARC) of the hypothalamus to produce these facilitatory effects on NPY or whether they act on other cells that have a modulatory influence via synapses on ARC NPY cells. We applied the combined method of steroid autoradiography and immunocytochemistry to assess the localization of (3H)estradiol in relation to NPY-producing cells in the hypothalamus. Rats (n = 6) were bilaterally ovariectomized and injected intracerebroventricularly with colchicine. Twenty-four hours later each rat received an iv injection of 17 beta-(2,4,6,7,16,17(-3)H)estradiol (SA, 166 Ci/mmol) at a dose of 5.0 micrograms/kg BW. One hour after the injection of (3H)estradiol, the rats were perfused with 4% paraformaldehyde; brains were removed, frozen in isopentane precooled in liquid nitrogen (-190 C), sectioned, and processed for autoradiography. The autoradiograms were then incubated with specific antibodies for NPY immunostaining by the avidin-biotin-peroxidase method. The results revealed NPY-immunopositive cells in the ARC, striatum, hippocampus, amygdala, and cerebral cortex and a few cells in the median eminence. NPY-immunoreactive fibers were also detected in the internal layer of the median eminence. The largest number of neurons showing NPY immunoreactivity in the cytoplasm was detected in the ARC, and only in this nucleus did we observed colocalization of (3H)estradiol and NPY immunoreactivity in neurons. A population of NPY-immunopositive cells in the ARC (10-20%) exhibited nuclear (3H)estradiol; the majority of these cells were located in the lateral and ventral portions of the ARC.

  4. Effects of field-manure applications on stratified 17B-estradiol concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The estrogenic hormone, 17'-estradiol (E2), is a potent endocrine disrupting compound found in animal manures. The objective of this study was to assess the occurrence of manure-borne E2 stratified through soil in fields that receive swine (Sus scrofa domestica) manure slurry as fertilizer. Soil cor...

  5. Sorption and degradation of 17ß-estradiol-17-sulfate in sterilized soil-water systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify abiotic processes that govern the fate of a sulfate conjugated estrogen, 17ß-estradiol-17-sulfate (E2-17S), soil batch experiments were conducted to investigate the dissipation, sorption, and degradation of radiolabeled E2-17S under sterilized conditions. The aqueous dissipation half-liv...

  6. Transport of 17ß-Estradiol and Testosterone in a Field Lysimeter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2) and testosterone (T) are naturally present in manures and have the potential to disrupt aquatic organisms at low concentrations. Laboratory studies have indicated that E2 and T would have limited mobility and would attenuate rapidly in soils; however, these hormones are consistent...

  7. Sorption and Degradation of 17ß-Estradiol-17Sulfate in Agricultural Soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the environment, the natural estrogenic hormone, 17ß-estradiol (E2) can potentially induce endocrine disruptions at low concentrations, i.e. 1-10 ng/L. Laboratory based studies have found low potentials for the persistence and mobility of E2 in the environment due to its high degradation and/or s...

  8. An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest

    PubMed Central

    Fruzzetti, Franca; Trémollieres, Florence; Bitzer, Johannes

    2012-01-01

    Natural estrogens such as estradiol (E2) or its valerate ester (E2V) offer an alternative to ethinyl estradiol (EE). E2-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E2V-containing preparations have been approved to date for contraceptive use: E2V/cypro-terone acetate (CPA) (Femilar®; only approved in Finland and only in women >40 years or women aged 35–40 years in whom a COC containing EE is not appropriate) and E2V/dienogest (DNG; Qlaira®/Natazia®). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E2V/DNG. PMID:22468839

  9. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  10. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  11. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  12. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  13. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  14. β-Estradiol and ethinyl-estradiol contamination in the rivers of the Carpathian Basin.

    PubMed

    Avar, Péter; Zrínyi, Zita; Maász, Gábor; Takátsy, Anikó; Lovas, Sándor; G-Tóth, László; Pirger, Zsolt

    2016-06-01

    17β-Estradiol (E2) and 17α-ethinyl estradiol (EE2), which are environmental estrogens, have been determined with LC-MS in freshwater. Their sensitive analysis needs derivatization and therefore is very hard to achieve in multiresidue screening. We analyzed samples from all the large and some small rivers (River Danube, Drava, Mur, Sava, Tisza, and Zala) of the Carpathian Basin and from Lake Balaton. Freshwater was extracted on solid phase and derivatized using dansyl chloride. Separation was performed on a Kinetex XB-C18 column. Detection was achieved with a benchtop orbitrap mass spectrometer using targeted MS analysis for quantification. Limits of quantification were 0.05 ng/L (MS1) and 0.1 ng/L (MS/MS) for E2, and 0.001 ng/L (MS1) and 0.2 ng/L (MS/MS) for EE2. River samples contained n.d.-5.2 ng/L E2 and n.d.-0.68 ng/L EE2. Average levels of E2 and EE2 were 0.61 and 0.084 ng/L, respectively, in rivers, water courses, and Lake Balaton together, but not counting city canal water. EE2 was less abundant, but it was still present in almost all of the samples. In beach water samples from Lake Balaton, we measured 0.076-0.233 E2 and n.d.-0.133 EE2. A relative high amount of EE2 was found in river Zala (0.68 ng/L) and in Hévíz-Páhoki canal (0.52 ng/L), which are both in the catchment area of Lake Balaton (Hungary). PMID:26936475

  15. Laccase mediated transformation of 17β-estradiol in soil.

    PubMed

    Singh, Rashmi; Cabrera, Miguel L; Radcliffe, David E; Zhang, Hao; Huang, Qingguo

    2015-02-01

    It is known that 17β-estradiol (E2) can be transformed by reactions mediated by some oxidoreductases such as laccase in water. Whether or how such reactions can happen in soil is however unknown although they may significantly impact the environmental fate of E2 that is introduced to soil by land application of animal wastes. We herein studied the reaction of E2 in a model soil mediated by laccase, and found that the reaction behaviors differ significantly from those in water partly because of the dramatic difference in laccase stability. We also examined E2 transformation in soil using (14)C-labeling in combination with soil organic matter extraction and size exclusion chromatography, which indicated that applied (14)C radioactivity was preferably bound to humic acids. The study provides useful information for understanding the environmental fate of E2 and for developing a novel soil remediation strategy via enzyme-enhanced humification reactions. PMID:25489747

  16. Nomegestrol acetate-17b-estradiol for oral contraception

    PubMed Central

    Burke, Anne

    2013-01-01

    Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC) 2.5 mg + 17b-estradiol (E2) 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile. PMID:23836965

  17. Nomegestrol acetate-17b-estradiol for oral contraception.

    PubMed

    Burke, Anne

    2013-01-01

    Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC) 2.5 mg + 17b-estradiol (E2) 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile. PMID:23836965

  18. Estradiol-tethered micropatterned surfaces for the study of estrogenic non-genomic pathways.

    PubMed

    Qi, B; Shimizu, Y; Nakanishi, J; Winnik, F M

    2016-08-21

    Besides its well-known hormonal effects initiated in the nucleus, estradiol (E2) also activates non-nuclear pathways through interactions with receptors located on the cell plasma membrane. Micropatterned substrates consisting of gold dots bearing tethered E2 distributed on a cell-adhesive substrate were prepared and shown to trigger specifically E2 non-genomic effects in cells grown on the substrates. PMID:27451960

  19. Harnessing functional plasticity of enzymes: a fluorogenic probe for imaging 17beta-HSD10 dehydrogenase, an enzyme involved in Alzheimer's and Parkinson's diseases.

    PubMed

    Froemming, Mary K; Sames, Dalibor

    2007-11-21

    In this paper, we describe the development of a fluorogenic substrate for 17beta-hydroxysteroid-dehydrogenase type 10 (17beta-HSD10), which is a multifunctional metabolic enzyme fulfilling several metabolic roles (beta-oxidation of fatty acids, catabolism of isoleucine, and metabolism of steroids). In recent years, it has emerged as an important stress and pathological marker in neurons and glial cells (expression down-regulation in Parkinson's disease, up-regulation and association with beta-amyloid peptide in Alzheimer's disease). Through the iterative molecular design and chemical synthesis described herein, compound 1 was developed, which possesses all required properties for a selective optical reporter substrate: alcohol-ketone optical switching, the ability to function as a good enzyme substrate (expressed in kinetic parameters), cell permeability, and cell retention. Probe 1 provides a blue-to-green/yellow bright switch and enables non-invasive, real-time imaging of 17beta-HSD10 in live human cells. The selectivity of reporter 1 was established by the quantitative correlation of metabolic activity to protein expression in human kidney cell line HEK-293T. PMID:17958419

  20. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    PubMed Central

    Joffe, Hadine; Guthrie, Katherine A.; LaCroix, Andrea Z.; Reed, Susan D.; Ensrud, Kristine E.; Manson, JoAnn E.; Newton, Katherine M.; Freeman, Ellen W.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie; Shifren, Jan; Rexrode, Kathryn M.; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Cohen, Lee

    2014-01-01

    Importance Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine is used widely as a non-hormonal treatment. While clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial. Objective To determine the efficacy and tolerability of low-dose oral 17-beta-estradiol and low-dose venlafaxine XR in alleviating vasomotor symptoms. Design and Participants 339 peri- and postmenopausal women with ≥2 bothersome vasomotor symptoms per day (mean 8.1, SD 5.3/day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites November 2011—October 2012. Interventions Participants were randomized to double-blinded treatment with low-dose oral 17-beta-estradiol 0.5-mg/day (n=97), low-dose venlafaxine XR 75-mg/day (n=96), or placebo (n=146) for 8 weeks. Main Outcomes Primary outcome was the mean daily frequency of vasomotor symptoms after 8 weeks of treatment. Secondary outcomes were vasomotor symptom severity, bother and interference. Intent-to-treat analyses compared change in vasomotor symptom frequency between each active intervention and placebo and between the two active treatments. Results Compared to baseline, mean vasomotor symptom frequency at week 8 decreased by 53% with estradiol, 48% with venlafaxine, and 29% with placebo. Estradiol reduced the frequency of symptoms by 2.3 (95% CI 1.3–3.4) more per day than placebo (p<0.001), and venlafaxine by 1.8 (95% CI 0.8–2.7) more per day than placebo (p=0.005). Results were consistent for VMS severity, bother and interference. Low-dose estradiol reduced symptom frequency by 0.6 more per day than venlafaxine (95% CI, 1.8 more per day to 0.6 fewer per day than

  1. Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta

    PubMed Central

    James, Margaret O.; Li, Wenjun; Summerlot, David P.; Rowland-Faux, Laura; Wood, Charles E.

    2016-01-01

    The personal care product Triclosan, 5-chloro-2(2,4-dichlorophenoxy)-phenol, is widely used in consumer products as an antibacterial agent and is increasingly found in the environment as a contaminant of sewage sludge and wastewater. This compound has been identified in plasma and urine of people in the United States, Sweden and Australia. Triclosan is known to inhibit sulfonation of phenolic xenobiotics and is structurally related to inhibitors of estrogen sulfotransferase, such as polychlorobiphenylols. In pregnancy, the placenta is an important source of estrogen, which is needed for normal fetal development and successful parturition, and estrogen sulfotransferase is thought to play an important role in regulation of estrogen availability. In this study, we examined the effect of Triclosan on sheep placental cytosolic sulfotransferase activity with 17-beta-estradiol and estrone as substrates. For comparison, we studied the effects of 4-hydroxy-3,3′,4′,5-tetrachlorobiphenyl and 2′-hydroxytriclocarban on estradiol sulfonation. The apparent Km for placental cytosolic sulfotransferase activity with estradiol as substrate was 0.27±0.06 nM (mean±S.D., n=3 individuals) and with estrone as substrate was 1.86±0.22 nM. Partial substrate inhibition was observed with estradiol at concentrations higher than 10–20 nM, as is typical of estrogen sulfotransferases (SULT1E1) in other species. Studies of the effect of Triclosan on estrogen sulfotransferase activity were conducted with several concentrations (0.1–6 nM) of estradiol and with 2 nM estrone. Triclosan was a very potent inhibitor of both estradiol and estrone sulfonation. For estradiol the inhibition was shown to be mixed competitive/uncompetitive, with Kic of 0.09±0.01 nM and Kiu of 5.2±2.9 nM. The IC50 for inhibition of estrone sulfonation was 0.60±0.06 nM. At an environmentally relevant concentration of 1 μM, Triclosan was not a substrate for glucuronidation in sheep placental microsomes. Triclosan

  2. Detection of estradiol-17β during a mass coral spawn

    NASA Astrophysics Data System (ADS)

    Atkinson, S.; Atkinson, M. J.

    1992-04-01

    The steroid estradiol-17β (E2) is associated with female gametogenesis in all vertebrates and many invertebrates. This is the first report of estrogens in scleractinian corals. Seawater and egg slicks were collected during a mass coral spawn at Ningaloo reef, Western Australia for the measurement of total phosphate (TP) and E2. Total P in the water column increased 600 times, from 0.5μM to 300μM. Concentrations of E2 increased nearly 8 fold during the spawn, from 55 to 420 pg/100 ml seawater. Coral eggs collected from egg slicks contained 368±40 pg E2/g dry wt of eggs. Estrogen may be a key hormone in a simple endocrine system of scleractinian corals that synchronizes growth and development of coral oocytes. Its potential role in triggering spawning via chemical messengers in the water column warrants further research.

  3. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

    PubMed

    Wisner, Katherine L; Sit, Dorothy K Y; Moses-Kolko, Eydie L; Driscoll, Kara E; Prairie, Beth A; Stika, Catherine S; Eng, Heather F; Dills, John L; Luther, James F; Wisniewski, Stephen R

    2015-08-01

    Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 μg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  4. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot Randomized Trial

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.

    2015-01-01

    Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  5. [Oral combined hormonal contraception containing nomegestrol acetate and 17beta-oestradiol--the statement of Polish Gynecological Society Experts Group].

    PubMed

    Debski, Romuald; Kotarski, Jan; Paszkowski, Tomasz; Pawelczyk, Leszek; Poreba, Ryszard; Skrzypulec-Plinta, Violetta; Tomaszewski, Jacek

    2012-04-01

    Nomegestrol acetate (NOMAC) combined with E2 (Zoely) is a monophasic oral contraceptive (OC) which safety and efficacy was confirmed in a number of level I evidence clinical trials. Zoely is highly effective OC, especially in overweight and obese patients, with good cycle control, safe and well tolerated. NOMAC/E2 combination causes no or minimal weight gain and is characterized by minimal influence on bone mineral density or blood pressure and presence of acne. Moreover lipids profile, carbohydrates metabolism, haemostasis and endocrine glands functioning were not affected. High tolerance and acceptance of NOMAC/E2 combination by women, low adverse event profile, fast recovery of ovarian activity and ovulation is a reasonable treatment tool in everyday practice. PMID:22712267

  6. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    SciTech Connect

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  7. Spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and glutamate transporter 1: benefit of 17 beta-oestradiol treatment.

    PubMed

    Olsen, Michelle L; Campbell, Susan C; McFerrin, Michael B; Floyd, Candace L; Sontheimer, Harald

    2010-04-01

    During neuronal activity astrocytes function to remove extracellular increases in potassium, which are largely mediated by the inwardly-rectifying potassium channel Kir4.1, and to take up excess glutamate via glutamate transporter 1, a glial-specific glutamate transporter. Here we demonstrate that expression of both of these proteins is reduced by nearly 80% following a crush spinal cord injury in adult male rats, 7 days post-injury. This loss extended to spinal segments several millimetres rostral and caudal to the lesion epicentre, and persisted at 4 weeks post-injury. Importantly, we demonstrate that loss of these two proteins is not a direct result of astrocyte loss, as immunohistochemistry at 7 days and western blots at 4 weeks demonstrate a marked up-regulation in glial fibrillary acidic protein expression. Kir4.1 and glutamate transporter 1 expression were partially rescued by post-spinal cord injury administration of physiological levels of 17beta-oestradiol (0.08 mg/kg/day) in vivo. Utilizing an in vitro culture system we demonstrate that 17beta-oestradiol treatment (50 nM) is sufficient to increase glutamate transporter 1 protein expression in spinal cord astrocytes. This increase in glutamate transporter 1 protein expression was reversed and Kir4.1 expression reduced in the presence of an oestrogen receptor antagonist, Fulvestrant 182,780 suggesting a direct translational regulation of Kir4.1 and glutamate transporter 1 via genomic oestrogen receptors. Using whole-cell patch-clamp recordings in cultured spinal cord astrocytes, we show that changes in protein expression following oestrogen application led to functional changes in Kir4.1 mediated currents. These findings suggest that the neuroprotective benefits previously seen with 17beta-oestradiol after spinal cord injury may be in part due to increased Kir4.1 and glutamate transporter 1 expression in astrocytes leading to improved potassium and glutamate homeostasis. PMID:20375134

  8. Modulation of human cytotrophoblastic leptin secretion by interleukin-1alpha and 17beta-oestradiol and its effect on HCG secretion.

    PubMed

    Chardonnens, D; Cameo, P; Aubert, M L; Pralong, F P; Islami, D; Campana, A; Gaillard, R C; Bischof, P

    1999-11-01

    To investigate the role of leptin during pregnancy, we assessed leptin production by pure cultured human cytotrophoblastic cells (CTB), its regulation by cytokines and 17beta-oestradiol and its effects on human chorionic gonadotrophin (HCG) secretion. Purified CTB from first trimester placenta were incubated in duplicates in the presence or absence of cytokines or 17beta-oestradiol. Medium was harvested on day 2 and the culture stopped on day 4. Results were corrected for protein content of each individual well and expressed as percent of controls per day (mean +/- SEM). Basal CTB leptin production was 25.2 +/- 2.6 (ng/mg prot). In comparison with controls, leptin production was stimulated to 320 +/- 16% (P < 0.0001) and 195 +/- 3.2% (P < 0.0004) by 3 and 10 ng/ml of interleukin-1alpha respectively. 17beta-oestradiol 10(-6) to 10(-9) mol/l increased basal leptin production 5-9-fold, while 10(-5) mol/l had no such effect. Basal CTB HCG secretion was 5722 +/- 1055 (mIU/mg prot). There was a dose-dependent leptin-induced increase in HCG secretion (P = 0.0039) reaching a 5-fold increase with a leptin concentration of 1 microg/ml (P < 0.006). Gonadotrophin-releasing hormone (GnRH) 8.5 x 10(-8) mol/l significantly increased HCG secretion to 140 +/- 21% of controls (P = 0.031). Cetrorelix (0.1 microg/ml) inhibited leptin-induced HCG secretion (P = 0.0028). PMID:10541571

  9. Human oestrogenic 17beta-hydroxysteroid dehydrogenase specificity: enzyme regulation through an NADPH-dependent substrate inhibition towards the highly specific oestrone reduction.

    PubMed Central

    Gangloff, A; Garneau, A; Huang, Y W; Yang, F; Lin, S X

    2001-01-01

    Human oestrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1) catalyses the final step in the biosynthesis of all active oestrogens. Here we report the steady-state kinetics for 17beta-HSD1 at 37 degrees C and pH 7.5, using a homogeneous enzyme preparation with oestrone, dehydroepiandrosterone (DHEA) or dihydrotestosterone (DHT) as substrate and NADP(H) as the cofactor. Kinetic studies made over a wide range of oestrone concentrations (10 nM-10 microM) revealed a typical substrate-inhibition phenomenon. Data analysis using the substrate-inhibition equation v=V.[s]/[K(m)+[s](1+[s]/K(i))] gave a K(m) of 0.07+/-0.01 microM, a k(cat) (for the dimer) of 1.5+/-0.1 s(-1), a specificity of 21 microM(-1) x s(-1) and a K(i) of 1.3 microM. When NADH was used instead of NADPH, substrate inhibition was no longer observed and the kinetic constants were significantly modified to 0.42+/-0.07 microM for the K(m), 0.8+/-0.04 s(-1) for the k(cat) and 1.9 microM(-1) x s(-1) for the specificity. The modification of an amino acid in the cofactor-binding site (Leu36Asp) eliminated the substrate inhibition observed in the presence of NADPH, confirming the NADPH-dependence of the phenomenon. The possible formation of an enzyme-NADP(+)-oestrone dead-end complex during the substrate-inhibition process is supported by the competitive inhibition of oestradiol oxidation by oestrone. Kinetic studies performed with either DHEA (K(m)=24+/-4 microM; k(cat)=0.47+/-0.06 s(-1); specificity=0.002 microM(-1) x s(-1)) or DHT (K(m)=26+/-6 microM; k(cat)=0.2+/-0.02 s(-1); specificity=0.0008 microM(-1) x s(-1)) in the presence of NADP(H) resulted in low specificities and no substrate inhibition. Taken together, our results demonstrate that the high specificity of 17beta-HSD1 towards oestrone is coupled with an NADPH-dependent substrate inhibition, suggesting that both the specificity and the enzyme control are provided for the cognate substrate. PMID:11336660

  10. Neuroplastic changes in the hypothalamic arcuate nucleus: the estradiol effect is accompanied by increased exoendocytotic activity of neuronal membranes.

    PubMed

    Párducz, A; Szilágyi, T; Hoyk, S; Naftolin, F; Garcia-Segura, L M

    1996-04-01

    1. In the rat hypothalamic arcuate nucleus, estradiol induces coordinated changes in the number of axosomatic synapses, the amount of glial ensheathing, and the ultrastructure of the membrane of neuronal somas. In the present study we used conventional electron microscopy and freeze-fracture to examine cellular mechanisms responsible for the estradiol-induced changes at the membrane level. 2. In freeze-fracture replicas taken 10-60 min and 24 hr after injection of 17 beta-estradiol to adult ovariectomized females, it was found that there was a rapid increase in the number of exoendocytotic images that reached a plateau by 30 min. 3. In thin sections from animals injected 24 hr earlier we demonstrated a significant increase in coated vesicles in the periphery of the neurons and coated pits in the perikaryal membranes and decreased axosomatic synapses. 4. We conclude that these morphological alterations are signaling estrogen-induced transport and/or turnover of perikaryal membrane constituents and extracellular components which may affect interneuronal and neuroglial interactions. PMID:8743973

  11. Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

    PubMed Central

    Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D.; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R.; Ceda, Gian Paolo; Ferrucci, Luigi

    2015-01-01

    Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = −0.29 ± 0.08, p

  12. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. PMID:27059334

  13. The Papillomavirus E2 proteins

    SciTech Connect

    McBride, Alison A.

    2013-10-15

    The papillomavirus E2 proteins are pivotal to the viral life cycle and have well characterized functions in transcriptional regulation, initiation of DNA replication and partitioning the viral genome. The E2 proteins also function in vegetative DNA replication, post-transcriptional processes and possibly packaging. This review describes structural and functional aspects of the E2 proteins and their binding sites on the viral genome. It is intended to be a reference guide to this viral protein. - Highlights: • Overview of E2 protein functions. • Structural domains of the papillomavirus E2 proteins. • Analysis of E2 binding sites in different genera of papillomaviruses. • Compilation of E2 associated proteins. • Comparison of key mutations in distinct E2 functions.

  14. Effects of liquid swine manure on dissipation of 17ß-estradiol in soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2), an estrogenic hormone, degrades within hours and bind strongly to soils and sediments; however, estrogens are frequently detected in the environment at concentrations that impact water quality. Colloidal (COC) and dissolved (DOC) organic carbon may enhance the persistence and mob...

  15. An On-Farm Survey of Spatial and Temporal Stratifications of 17ß-Estradiol Concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2), a natural estrogenic hormone, may cause endocrine disruption in sensitive organisms. It has been reported to dissipate rapidly in soil laboratory studies, but is frequently detected in the environment leading to question about possible sources and processes that explain the mobil...

  16. Effects of liquid swine manure on sorption of 17ß-estradiol to soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogens are potent endocrine disrupting chemicals and can be found in the environment. Animal manure can contain estrogenic hormones, specifically 17'-estradiol (E2). A common manure management practice is to contain liquid manure in a manure storage ponds or lagoons, which is then applied on or i...

  17. The relationship among vitamin C, beta-carotene, vitamin A, progesterone and oestradiol 17-beta concentrations in plasma and cyst fluid of Holstein cows with ovarian cyst.

    PubMed

    Haliloglu, S; Erdem, H; Serpek, B; Tekeli, T; Bulut, Z

    2008-10-01

    The aims of this study were to determine the concentrations of the progesterone, oestradiol-17-beta, vitamin A, C and beta-carotene in plasma and cyst fluid and to relate these values with cystic diameter and membrane thickness of Holstein cattle with ovarian luteal cyst. 1650 Holstein cows were examined for the presence of the ovarian cyst and luteal and follicular cystic ovaries were obtained following slaughtering in personal slaughterhouse in Konya-Turkey. 15 Luteal and 15 follicular cystic ovaries were distinguished by rectal palpation and by post mortem ultrasonographic examination. Plasma and cyst fluid, hormone and vitamin analyses were carried out by EIA method and spectrophotometric measurement respectively. Although there was no relationship between beta-carotene and vitamin A in plasma and cyst fluid of both cyst type and hormone concentrations, the vitamin C concentration of cyst fluid was found significantly higher in luteal cyst than in follicular cyst. Moreover, there is a positive correlation among values of the vitamin C concentrations of cyst fluid and cystic membrane thickness, plasma and the cyst fluid progesterone concentrations, but there is a negative correlation among the vitamin C concentrations of cystic fluid and oestradiol 17beta levels of plasma and cyst fluid. In conclusion, vitamin C concentration of cyst fluid supported ultrasonographic and endocrinologic findings. Also, it can be postulated that vitamin C is probably effective on progesterone synthesis in the luteal tissue of cyst. PMID:18363607

  18. Regulatory effects of testosterone and 17 beta-oestradiol on the metabolism of dimethylnitrosamine by renal and hepatic microsomal enzymes from BALB/c mice.

    PubMed

    Ampy, F R; Asseffa, A

    1988-01-01

    Previous investigations with BALB/c mice have demonstrated that no sex-related differences exist in the ability of liver microsomal fractions (S-9) to biotransform dimethylnitrosamine (DMN) to its active mutagenic metabolites as evidenced by bacterial screening assays. In contrast, kidney microsomal enzymes from adult male BALB/c mice and not from females, castrates, and immature animals, were capable of activating DMN. The present study was designed to test the effects of testosterone and oestradiol on DMN bioactivation by hepatic or renal microsomal enzymes. Mutagenic assays were performed using liver and kidney microsomal enzymes with the histidine deficient mutant Salmonella typhimurium TA100. Results indicate that testosterone treatment of female BALB/c mice resulted in an increase in the ability of their renal microsomal enzymes to metabolize DMN to its active mutagenic intermediates. Renal microsomal enzymes from female mice treated with 17 beta-oestradiol had no effect on DMN metabolism. However, the ability of the renal microsomal enzymes treated with 17 beta-oestradiol to bioactivate DMN was significantly decreased in males. PMID:3229148

  19. Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice.

    PubMed

    Lai, Shaojuan; Collins, Brittany C; Colson, Brett A; Kararigas, Georgios; Lowe, Dawn A

    2016-05-01

    Impairment of skeletal muscle function has been associated with changes in ovarian hormones, especially estradiol. To elucidate mechanisms of estradiol on skeletal muscle strength, the hormone's effects on phosphorylation of the myosin regulatory light chain (pRLC) and muscle contractility were investigated, hypothesizing an estradiol-specific beneficial impact. In a skeletal muscle cell line, C2C12, pRLC was increased by 17β-estradiol (E2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E2 deficient via ovariectomy (OVX), pRLC was lower than that from ovary-intact, sham-operated mice (Sham). The reduced pRLC in OVX muscle was reversed by in vivo E2 treatment. Posttetanic potentiation (PTP) of muscle from OVX mice was low compared with that from Sham mice, and this decrement was reversed by acute E2 treatment, demonstrating physiological consequence. Western blot of those muscles revealed that low PTP corresponded with low pRLC and higher PTP with greater pRLC. We aimed to elucidate signaling pathways affecting E2-mediated pRLC using a kinase inhibitor library and C2C12 cells as well as a specific myosin light chain kinase inhibitor in muscles. PI3K/Akt, MAPK, and CamKII were identified as candidate kinases sensitive to E2 in terms of phosphorylating RLC. Applying siRNA strategy in C2C12 cells, pRLC triggered by E2 was found to be mediated by estrogen receptor-β and the G protein-coupled estrogen receptor. Together, these results provide evidence that E2 modulates myosin pRLC in skeletal muscle and is one mechanism by which this hormone can affect muscle contractility in females. PMID:26956186

  20. Facial coloration tracks changes in women's estradiol.

    PubMed

    Jones, Benedict C; Hahn, Amanda C; Fisher, Claire I; Wincenciak, Joanna; Kandrik, Michal; Roberts, S Craig; Little, Anthony C; DeBruine, Lisa M

    2015-06-01

    Red facial coloration is an important social cue in many primate species, including humans. In such species, the vasodilatory effects of estradiol may cause red facial coloration to change systematically during females' ovarian cycle. Although increased red facial coloration during estrus has been observed in female mandrills (Mandrillus sphinx) and rhesus macaques (Macaca mulatta), evidence linking primate facial color changes directly to changes in measured estradiol is lacking. Addressing this issue, we used a longitudinal design to demonstrate that red facial coloration tracks within-subject changes in women's estradiol, but not within-subject changes in women's progesterone or estradiol-to-progesterone ratio. Moreover, the relationship between estradiol and facial redness was observed in two independent samples of women (N = 50 and N = 65). Our results suggest that changes in facial coloration may provide cues of women's fertility and present the first evidence for a direct link between estradiol and female facial redness in a primate species. PMID:25796069

  1. Estradiol replacement extends the window of opportunity for hippocampal function

    PubMed Central

    Vedder, LC; Bredemann, TM; McMahon, LL

    2014-01-01

    We previously reported that treating aged female rats, ovariectomized (OVX) as young adults, with acute proestrous levels of 17β estradiol (E2) increases CA1 spine density, NMDAR/AMPAR ratio, GluN2B-mediated NMDAR current, and LTP at CA3-CA1 synapses if administered by 15, but not at 19, months post-OVX, defining the critical window of opportunity. Importantly, when rats are aged with ovaries intact until OVX at 20 months, hippocampal E2 responsiveness is maintained, indicating the deficit at 19 months post-OVX is a consequence of the duration of hormone deprivation and not chronological age. Here, we find the beneficial effect of E2 on novel object recognition in OVX rats was constrained by the same critical window. Furthermore, chronic low level E2 replacement, commenced by 11 months post-OVX using subcutaneous capsules removed 2 weeks prior to acute proestrous E2 treatment, prevents the loss of hippocampal responsiveness at 19 months post-OVX. These data define the dynamic nature of the critical window showing that chronic replacement with physiological E2 levels within a certain period post-OVX can lengthen the window. PMID:24813636

  2. Estradiol replacement extends the window of opportunity for hippocampal function.

    PubMed

    Vedder, Lindsey C; Bredemann, Teruko M; McMahon, Lori L

    2014-10-01

    We previously reported that treating aged female rats, ovariectomized (OVX) as young adults, with acute proestrous levels of 17β estradiol (E2) increases CA1 spine density, NMDAR to AMPAR ratio, GluN2B-mediated NMDAR current, and long-term potentiation at CA3-CA1 synapses if administered by 15, but not at 19-month post-OVX, defining the critical window of opportunity. Importantly, when rats are aged with ovaries intact until OVX at 20 months, hippocampal E2 responsiveness is maintained, indicating the deficit at 19-month post-OVX is a consequence of the duration of hormone deprivation and not chronological age. Here, we find the beneficial effect of E2 on novel object recognition in OVX rats was constrained by the same critical window. Furthermore, chronic low-level E2 replacement, commenced by 11-month post-OVX using subcutaneous capsules removed 2 weeks before acute proestrous E2 treatment, prevents the loss of hippocampal responsiveness at 19-month post-OVX. These data define the dynamic nature of the critical window showing that chronic replacement with physiological E2 levels within a certain period post-OVX can lengthen the window. PMID:24813636

  3. Dynamics of estradiol and testosterone and seminal fluid indexes in smokers and nonsmokers.

    PubMed

    Klaiber, E L; Broverman, D M

    1988-10-01

    The serum levels of estradiol (E2) and testosterone (T), the metabolic clearance rates of estradiol (MCRE2) and testosterone (MCRT), and the production rates of estradiol and testosterone (PRE2) and (PRT) were examined in 22 male smokers and 21 male nonsmokers. Seminal fluid indexes (sperm count, % motility, grade of motility, and % of sperm with abnormal morphology) were also assessed. The mean E2 level and the mean PRE2 were significantly greater in smokers than in nonsmokers (P less than 0.001 and P less than 0.01, respectively); however, the means of MCRE2, MCRT, PRT, and T did not differ significantly in smokers compared to nonsmokers. No significant product-moment correlations were found between the various hormonal measures and the seminal fluid indexes in the overall sample. However, the smokers with sperm counts below the median sperm count of the sample had significantly higher mean levels of E2 and PRE2 than did the smokers with sperm counts above that median. Mechanisms that might mediate the greater PRE2 of smokers and a negative relationship between estradiol and sperm count are discussed. PMID:3169284

  4. 17β-Estradiol induces supernumerary primordial germ cells in embryos of the polychaete Platynereis dumerilii.

    PubMed

    Lidke, Anika K; Bannister, Stephanie; Löwer, Andreas M; Apel, David M; Podleschny, Martina; Kollmann, Martin; Ackermann, Christian F; García-Alonso, Javier; Raible, Florian; Rebscher, Nicole

    2014-01-15

    In the polychaete Platynereis dumerilii exactly four primordial germ cells (PGCs) arise in early development and are subject to a transient mitotic arrest until the animals enter gametogenesis. In order to unravel the mechanisms controlling the number of PGCs in Platynereis, we tested whether the steroid 17β-estradiol (E2) is able to induce PGC proliferation, as it had been described in other species. Our data provide strong support for such a mechanism, showing that E2 significantly increases the occurrence of larvae with supernumerary PGCs in Platynereis in a dose dependent manner. E2 responsiveness is restricted to early developmental stages, when the PGCs are specified. During these stages, embryos exhibit high expression levels of the estradiol receptor (ER). The ER transcript localizes to the yolk-free cytoplasm of unfertilized eggs and segregates into the micromeres during cleavage stages. Nuclear ER protein is found asymmetrically distributed between daughter cells. Neither transcript nor protein is detectable in PGCs at larval stages. Addition of the specific estradiol receptor inhibitor ICI-182,780 (ICI) abolishes the proliferative effect of E2, suggesting that it is mediated by ER signaling. Our study reports for the first time an ER mediated proliferative effect of E2 on PGCs in an invertebrate organism. PMID:24287341

  5. A new contraceptive pill containing 17β-estradiol and nomegestrol acetate.

    PubMed

    Christin-Maitre, Sophie; Laroche, Emmanuelle; Bricaire, Léopoldine

    2013-01-01

    Most combined oral contraceptive pills contain ethinyl estradiol (EE) with progestins. In order to minimize the pill's cardiovascular risks, the concept of using 17β-estradiol (E2), the endogenous estradiol, arose in the 1970s. Many attempts to develop a pill containing 17β-E2 have failed as cycle control was low. The first pill containing 17β-E2 was launched in 2011. This monophasic pill contains 24 pills with 1.5 mg 17β-E2 and 2.5 mg nomegestrol acetate, and four placebo pills. Studies conducted in Europe and the USA demonstrate that its Pearl index is 0.38 and 1.13, respectively. It has less influence on hemostasis, fibrinolysis markers, lipids and carbohydrate metabolism than the combined oral contraceptive levonorgestrel/EE (150 g/30 g and 100 µg/20 µg). Withdrawal bleedings are shorter and lighter as compared with women using drospirenone/EE (3 mg/ 30 µg). The number of women without withdrawal bleeding is approximately 30% after 12 months. Even though its contraindications are identical to other combined oral contraceptives, this nomegestrol acetate/E2 pill should be considered to be of interest for many women. PMID:23241152

  6. Soil temperature and moisture effects on the persistence of synthetic androgen 17alpha-trenbolone, 17beta-trenbolone and trendione.

    PubMed

    Khan, Bushra; Lee, Linda S

    2010-05-01

    Trenbolone acetate (TBA) is a synthetic androgenic steroid hormone administered as a subcutaneous implant for growth promotion in beef cattle. The primary metabolite excreted in manure from implanted cattle is 17alpha-trenbolone with lesser amounts of 17beta-trenbolone and trendione also present. At 22 degrees C and favorable moisture conditions in a controlled laboratory environment, trenbolone degrades to trendione in a few hours; however, these conditions are often not what exist in the field. Therefore, aerobic degradation rates of 17alpha-trenbolone, 17beta-trenbolone and trendione were determined in a sandy soil and silty clay loam under a range of temperature and water availability combinations that may be expected in the field. A first-order exponential decay model was used to estimate rates and generally resulted in good model fits to the data. Degradation rates decreased with decreasing water availability (i.e., more negative soil matric potential) and decreasing temperature. However, when water availability was substantially reduced (-1.0MPa), hotter temperatures (35 degrees C) significantly reduced trenbolone degradation rates. Once temperature was low enough to limit microbial activity, no further changes were observed with decreasing matric potential. Trendione also exhibited similar moisture and temperature dependent degradation, but persisted longer than the parent trenbolone. The latter was discussed in light of extracellular versus intracellular enzymatic degradation and sorption. Half lives at colder temperatures (5 degrees C) even under favorable moisture conditions were 2-3d for the trenbolone isomers and approached 10d for trendione. PMID:20231030

  7. Estradiol rapidly modulates spinogenesis in hippocampal dentate gyrus: Involvement of kinase networks.

    PubMed

    Hojo, Yasushi; Munetomo, Arisa; Mukai, Hideo; Ikeda, Muneki; Sato, Rei; Hatanaka, Yusuke; Murakami, Gen; Komatsuzaki, Yoshimasa; Kimoto, Tetsuya; Kawato, Suguru

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Estradiol (E2) is locally synthesized within the hippocampus and the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. The molecular mechanisms of modulation through the synaptic estrogen receptor (ER) and its downstream signaling, however, are largely unknown in the dentate gyrus (DG). We investigated the E2-induced modulation of dendritic spines in male adult rat hippocampal slices by imaging Lucifer Yellow-injected DG granule cells. Treatments with 1 nM E2 increased the density of spines by approximately 1.4-fold within 2h. Spine head diameter analysis showed that the density of middle-head spines (0.4-0.5 μm) was significantly increased. The E2-induced spine density increase was suppressed by blocking Erk MAPK, PKA, PKC and LIMK. These suppressive effects by kinase inhibitors are not non-specific ones because the GSK-3β antagonist did not inhibit E2-induced spine increase. The ER antagonist ICI 182,780 also blocked the E2-induced spine increase. Taken together, these results suggest that E2 rapidly increases the density of spines through kinase networks that are driven by synaptic ER. PMID:26122288

  8. 17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

    PubMed Central

    Jacobs, Emily G; Holsen, Laura M; Lancaster, Katie; Makris, Nikos; Whitfield-Gabrieli, Sue; Remington, Anne; Weiss, Blair; Buka, Stephen; Klibanski, Anne; Goldstein, Jill M

    2015-01-01

    Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17β-estradiol (E2) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E2 during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E2 conditions were attenuated under high E2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex

  9. In vivo effects of 17-β-estradiol on plasma immunoglobulin levels and leukocyte density in zebrafish Danio rerio

    NASA Astrophysics Data System (ADS)

    Li, Lei; Zhang, Shicui; Tong, Zhou; Liu, Jia

    2010-05-01

    Estradiol, or 17-β-estradiol (E2), the most potent naturally occurring estrogen, is involved in the hormone-immune system interaction in both mammals and fish. However, in vivo studies are largely limited, and little is known about whether E2 exerts similar effects on both female and male zebrafish ( Danio rerio). Here, we show exposure of both sexes of D. rerio to 20 nmol/L E2 resulted in a significant increase in Vg1 expression, but caused little damage to the hepatocytes, suggesting that this is the optimum E2 concentration. Also, exposure to 20 nmol/L E2 for 20 days caused a marked increase in plasma IgM levels, but had little influence on the peripheral leukocyte density, providing the first evidence of a hormone-immune system interaction in this species.

  10. Membrane estradiol signaling in the brain

    PubMed Central

    Micevych, Paul; Dominguez, Reymundo

    2009-01-01

    While the physiology of membrane-initiated estradiol signaling in the nervous system has remained elusive, a great deal of progress has been made toward understanding the activation of cell signaling. Membrane-initiated estradiol signaling activates G proteins and their downstream cascades, but the identity of membrane receptors and the proximal signaling mechanism(s) have been more difficult to elucidate. Mounting evidence suggests that classical intracellular estrogen receptor-α (ERα) and ERβ are trafficked to the membrane to mediate estradiol cell signaling. Moreover, an interaction of membrane ERα and ERβ with metabotropic glutamate receptors has been identified that explains the pleomorphic actions of membrane-initiated estradiol signaling. This review focuses on the mechanism of actions initiated by membrane estradiol receptors and discusses the role of scaffold proteins and signaling cascades involved in the regulation of nociception, sexual receptivity and the synthesis of neuroprogesterone, an important component in the central nervous system signaling. PMID:19416735

  11. 17β-Estradiol modulates huntingtin levels in rat tissues and in human neuroblastoma cell line.

    PubMed

    Nuzzo, Maria Teresa; Fiocchetti, Marco; Servadio, Michela; Trezza, Viviana; Ascenzi, Paolo; Marino, Maria

    2016-02-01

    17β-Estradiol (E2) exerts neurotrophic and neuroprotective functions in the brain. Here, E2-induced increased levels of huntingtin (HTT), a protein involved in several crucial neuronal functions is reported. E2 physiological concentrations up-regulate HTT in hippocampus and striatum of rats as well as in human neuroblastoma cells. This effect requires both nuclear and extra-nuclear estrogen receptor (ER)α activities. Intriguingly, HTT silencing completely prevents E2 protective effects against oxidative stress injury. In conclusion, these data indicate for the first time that HTT is an E2-inducible protein involved in the first steps of E2-induced signaling pathways committed to neuronal protection against oxidative stress. PMID:26264729

  12. Comparison of cytochrome P-450 species which catalyze the hydroxylations of the aromatic ring of estradiol and estradiol 17-sulfate.

    PubMed

    Watanabe, K; Takanashi, K; Imaoka, S; Funae, Y; Kawano, S; Inoue, K; Kamataki, T; Takagi, H; Yoshizawa, I

    1991-06-01

    For identification of microsomal cytochrome P-450 (P-450) enzymes which catalyze 2- or 4-hydroxylations of estrogens in the rat liver, estradiol (E2) and estradiol 17-sulfate (E2-17-S) were selected as the substrates and incubated with various kinds of purified P-450 enzymes: PB-1, PB-2, PB-4 and PB-5 obtained from phenobarbital-treated male rats (Sprague-Dawley); MC-1 and MC-5 from 3-methylcholanthrene-treated male rats; and UT-1, UT-2, UT-4 and UT-5 from untreated animals. The reactions were carried out under the P-450-reconstructed system, and the resulting products were determined by HPLC using electrochemical detection. All the enzymes tested were shown to have varying degrees of catalytic activities for 2-hydroxylation of the two substrates; UT-1 and UT-2 had the highest activity. Of the induced P-450 enzymes, PB-2 and MC-1 showed fairly high catalytic activity for 4-hydroxylation of E2. The P-450 enzymes obtained from the untreated male rats, especially UT-4, showed the highest catalytic activity for 4-hydroxylation of the two substrates. From these results and also from kinetic experiments, the P-450 enzymes which catalyze 2- and 4-hydroxylations of estrogen were considered to be different species. A part of E2 was converted to such metabolites as estrone and those having a hydroxyl group at positions 6 beta, 15 alpha or 16 alpha, each production of which was estimated to be catalyzed by single or multiple P-450s. PMID:2064989

  13. Effect of vinca alkaloids on ERalpha levels and estradiol-induced responses in MCF-7 cells.

    PubMed

    Martínez-Campa, Carlos; Casado, Pedro; Rodríguez, René; Zuazua, Pedro; García-Pedrero, Juana M; Lazo, Pedro S; Ramos, Sofía

    2006-07-01

    Vinca alkaloids (VAs) such as Vincristine, Vinblastine and Vinorelbine are antineoplastic drugs that inhibit tubulin polymerisation into microtubules, induce mitotic G2/M arrest, activate c-Jun N-terminal kinase (JNK) and induce apoptosis. Although there are many studies evaluating the effect of VAs on breast cancer patients, until now little was known about how these compounds and estradiol signaling pathways might interfere. In this report, we show for the first time that VAs decreased ERalpha protein levels in the human breast cancer cell line MCF-7; VAs induced a parallel decrease in estrogen receptor mRNA. All the VAs tested inhibited estradiol (E2) mediated transactivation at ERE-driven promoters. E2 inhibited VAs-induced AP1 stimulation in MCF-7, but this inhibition was not observed when E2 is added 24 h in advance of VAs treatment. In contrast to the reported preventing effect over taxol-mediated apoptosis, E2 did not prevent VAs-induced cell death and interestingly, addition of E2 24 hours in advance of VAs treatment resulted in an increase of the number of cells undergoing apoptosis. Similar results were observed when E2 is replaced by other proliferation signals such as EGF. These results demonstrate that in the breast cancer cell-line MCF-7, E2-induced proliferation before VAs treatment enhances the apoptotical response to VAs which might have important implications in clinica. PMID:16555127

  14. Estradiol in the Preoptic Area Regulates the Dopaminergic Response to Cocaine in the Nucleus Accumbens.

    PubMed

    Tobiansky, Daniel J; Will, Ryan G; Lominac, Kevin D; Turner, Jonathan M; Hattori, Tomoko; Krishnan, Krittika; Martz, Julia R; Nutsch, Victoria L; Dominguez, Juan M

    2016-06-01

    The sex-steroid hormone estradiol (E2) enhances the psychoactive effects of cocaine, as evidenced by clinical and preclinical studies. The medial preoptic area (mPOA), a region in the hypothalamus, is a primary neural locus for neuroendocrine integration, containing one of the richest concentrations of estrogen receptors in the CNS and also has a key role in the regulation of naturally rewarding behaviors. However, whether estradiol enhances the neurochemical response to cocaine by acting in the mPOA is still unclear. Using neurotoxic lesions and microdialysis, we examined whether the mPOA modulates cocaine-induced neurochemical activity in the nucleus accumbens. Tract tracing and immunohistochemical staining were used to determine whether projections from the mPOA to the ventral tegmental area (VTA) are sensitive to estrogen signaling. Finally, estradiol microinjections followed by microdialysis were used to determine whether estrogenic signaling in the mPOA modulates cocaine-induced changes of dopamine in the nucleus accumbens. Results showed that lesions of the mPOA or microinjections of estradiol directly into the mPOA increased cocaine-induced release of dopamine in the nucleus accumbens. Immunohistochemical analyses revealed that the mPOA modulates cocaine responsiveness via projections to both dopaminergic and GABAergic neurons in the VTA, and that these projections are sensitive to estrogenic stimulation. Taken together, these findings point to a novel estradiol-dependent pathway that modulates cocaine-induced neurochemical activity in the mesolimbic system. PMID:26647972

  15. Study on drug release of and biological response to UHMWPE wear debris carrying estradiol

    NASA Astrophysics Data System (ADS)

    Qu, Shuxin; Liu, Aiqin; Liu, Xiaomin; Bai, Yinlong; Weng, Jie

    2012-12-01

    The aim of this study is to investigate in vitro release of 17β-estradiol (E2), the potential drug to treat osteolysis, and the biological response to ultra-high molecular weight polyethylene loaded with E2 (UHMWPE-E2) wear debris. The osteoblasts (MC3T3-E1) and macrophages (RAW264.7) were co-cultured with UHMWPE-E2 wear debris via inversion culture technique, respectively. MTT, ALP and ELISA assay were employed to evaluate the cell proliferation, ALP activity and the expression of interleukin-6 (IL-6). In vitro E2 release included: initial burst release, celerity release and steady release. The E2 released steadily after 40 d and lasted more than 60 d. The E2 in UHMWPE-E2 wear debris promoted the proliferation and ALP activity of MC3T3-E1 cells at the high debris dosages of 8-10 mg. In particular, the UHMWPE-E2 wear debris inhibited the expression of IL-6 of osteoblasts at all dosages in the present study. RAW264.7 cells cultured with UHMWPE-E2 and UHMWPE wear debris exhibited large sizes about 100 μm in diameter. The small size wear debris presented inside of cells indicated that the wear debris activated the phagocytosis of macrophages. The results indicated the E2 in UHMWPE-E2 would play a role in the treatment of the debris induced-osteolysis after artificial hip joint replacement.

  16. Nomegestrol acetate/estradiol: in oral contraception.

    PubMed

    Yang, Lily P H; Plosker, Greg L

    2012-10-01

    Nomegestrol acetate/estradiol is a combined oral contraceptive with approval in many countries. This fixed-dose combination tablet contains nomegestrol acetate, a highly selective progestogen, and estradiol, a natural estrogen. It is the first monophasic combined oral contraceptive to contain estradiol, and is taken in 28-day cycles, consisting of 24 active therapy days with 4 placebo days (i.e. 24/4-day cycles). In two large, 1-year, randomized, open-label, multicentre, phase III trials in healthy adult women (aged 18-50 years), nomegestrol acetate/estradiol was at least as effective as drospirenone/ethinylestradiol as contraceptive therapy, as the pregnancy rates in women aged 18-35 years (primary efficacy population) in terms of the Pearl Index (primary endpoint) were numerically lower with nomegestrol acetate/estradiol, although the between-group difference was not statistically significant. In both trials, nomegestrol acetate/estradiol was given in a 24/4-day cycle, and drospirenone/ethinylestradiol was given in a 21/7-day cycle. The criteria for using condoms in case of forgotten doses were less stringent in the nomegestrol acetate/estradiol group than in the drospirenone/ethinylestradiol group. Nomegestrol acetate/estradiol therapy for up to 1 year was generally well tolerated in healthy adult women, with an acceptable tolerability profile in line with that expected for a combined oral contraceptive. The most commonly reported adverse events were acne and abnormal withdrawal bleeding (most often shorter, lighter or absent periods). Overall, compared with drospirenone/ethinylestradiol, nomegestrol acetate/estradiol appeared to be associated with less favourable acne-related outcomes, and shorter, lighter or absent periods. PMID:22950535

  17. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol and related esters. 556.240 Section 556... Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the...

  18. Prostanoid receptors EP2, EP4, and FP are regulated by estradiol in bovine oviductal smooth muscle.

    PubMed

    Huang, Na; Liu, Bo; Dong, Zhiheng; Mao, Wei; Zhang, Nan; Li, Changyou; Cao, Jinshan

    2015-09-01

    Gamete and embryo transport is an important function of the oviduct. This transport involves both smooth muscle contraction and epithelial cell secretions, the former of which is mediated by prostaglandins (PGs) and their receptors. Our aim was to study the regulation of prostaglandin E2 and prostaglandin F2α receptors (EP2, EP4, and FP receptor) by estradiol in bovine oviduct smooth muscle. EP2, EP4, and FP receptor mRNA and protein expression was investigated using real-time RT-PCR and Western blot analyses, respectively. To evaluate the contraction or relaxation of cultured bovine oviductal smooth muscle tissue, peristalsis was used to assess contractile activity. EP2, EP4, and FP receptor mRNA and protein expression was increased in oviductal smooth muscle tissue after treatment with different concentrations of estradiol for various durations. The expression of all receptors peaked at an estradiol concentration of 10(-11)mol/L after 8h of treatment, whereas no increase in expression was observed after fulvestrant (a selective antagonist of E2 receptor) treatment, indicating that E2 interacts with specific E2 nuclear receptors to regulate EP2, EP4, and FP receptor expression. Although PGF2α and PGE2 induced both contraction and relaxation, no significant differences were found in contractility between the estradiol-treated and control groups, with both groups of cultured smooth muscle strips showing similar vitality. In conclusion, estradiol increases EP2, EP4, and FP receptor mRNA and protein expression in bovine oviductal smooth muscle when added for different periods of time and at different concentrations. Additionally, E2 is transported intracellularly and interacts with specific E2 nuclear receptors to regulate their expression. PMID:26319698

  19. Ethinyl Estradiol and Etonogestrel Vaginal Ring

    MedlinePlus

    ... a class of medications called combination hormonal contraceptives (birth control medications). Etonogestrel is a progestin and ethinyl estradiol ... contraceptive ring is a very effective method of birth control but does not prevent the spread of human ...

  20. Estradiol-induced gene expression in largemouth bass (Micropterus salmoides)

    USGS Publications Warehouse

    Bowman, C.J.; Kroll, K.J.; Gross, T.G.; Denslow, N.D.

    2002-01-01

    Vitellogenin (Vtg) and estrogen receptor (ER) gene expression levels were measured in largemouth bass to evaluate the activation of the ER-mediated pathway by estradiol (E2). Single injections of E2 ranging from 0.0005 to 5 mg/kg up-regulated plasma Vtg in a dose-dependent manner. Vtg and ER mRNAs were measured using partial cDNA sequences corresponding to the C-terminal domain for Vtg and the ligand-binding domain of ER?? sequences. After acute E2-exposures (2 mg/kg), Vtg and ER mRNAs and plasma Vtg levels peaked after 2 days. The rate of ER mRNA accumulation peaked 36-42 h earlier than Vtg mRNA. The expression window for ER defines the primary response to E2 in largemouth bass and that for Vtg a delayed primary response. The specific effect of E2 on other estrogen-regulated genes was tested during these same time windows using differential display RT-PCR. Specific up-regulated genes that are expressed in the same time window as Vtg were ERp72 (a membrane-bound disulfide isomerase) and a gene with homology to an expressed gene identified in zebrafish. Genes that were expressed in a pattern that mimics the ER include the gene for zona radiata protein ZP2, and a gene with homology to an expressed gene found in winter flounder. One gene for fibrinogen ?? was down-regulated and an unidentified gene was transiently up-regulated after 12 h of exposure and returned to basal levels by 48 h. Taken together these studies indicate that the acute molecular response to E2 involves a complex network of responses over time. ?? 2002 Elsevier Science Ireland Ltd. All rights reserved.

  1. 5-Androstene-3{beta},17{beta}-diol Promotes Recovery of Immature Hematopoietic Cells Following Myelosuppressive Radiation and Synergizes With Thrombopoietin

    SciTech Connect

    Aerts-Kaya, Fatima S.F.; Visser, Trudi P.; Arshad, Shazia; Frincke, James; Stickney, Dwight R.; Reading, Chris L.; Wagemaker, Gerard

    2012-11-01

    Purpose: 5-Androstene-3{beta},17{beta}-diol (5-AED) stimulates recovery of hematopoiesis after exposure to radiation. To elucidate its cellular targets, the effects of 5-AED alone and in combination with (pegylated) granulocyte colony-stimulating factor and thrombopoietin (TPO) on immature hematopoietic progenitor cells were evaluated following total body irradiation. Methods and Materials: BALB/c mice were exposed to radiation delivered as a single or as a fractionated dose, and recovery of bone marrow progenitors and peripheral blood parameters was assessed. Results: BALB/c mice treated with 5-AED displayed accelerated multilineage blood cell recovery and elevated bone marrow (BM) cellularity and numbers of progenitor cells. The spleen colony-forming unit (CFU-S) assay, representing the life-saving short-term repopulating cells in BM of irradiated donor mice revealed that combined treatment with 5-AED plus TPO resulted in a 20.1-fold increase in CFU-S relative to that of placebo controls, and a 3.7 and 3.1-fold increase in comparison to 5-AED and TPO, whereas no effect was seen of Peg-G-CSF with or without 5-AED. Contrary to TPO, 5-AED also stimulated reconstitution of the more immature marrow repopulating (MRA) cells. Conclusions: 5-AED potently counteracts the hematopoietic effects of radiation-induced myelosuppression and promotes multilineage reconstitution by stimulating immature bone marrow cells in a pattern distinct from, but synergistic with TPO.

  2. A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival.

    PubMed

    Rauschenberger, Katharina; Schöler, Katja; Sass, Jörn Oliver; Sauer, Sven; Djuric, Zdenka; Rumig, Cordula; Wolf, Nicole I; Okun, Jürgen G; Kölker, Stefan; Schwarz, Heinz; Fischer, Christine; Grziwa, Beate; Runz, Heiko; Nümann, Astrid; Shafqat, Naeem; Kavanagh, Kathryn L; Hämmerling, Günter; Wanders, Ronald J A; Shield, Julian P H; Wendel, Udo; Stern, David; Nawroth, Peter; Hoffmann, Georg F; Bartram, Claus R; Arnold, Bernd; Bierhaus, Angelika; Oppermann, Udo; Steinbeisser, Herbert; Zschocke, Johannes

    2010-02-01

    Deficiency of the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase involved in isoleucine metabolism causes an organic aciduria with atypical neurodegenerative course. The disease-causing gene is HSD17B10 and encodes 17beta-hydroxysteroid dehydrogenase type 10 (HSD10), a protein also implicated in the pathogenesis of Alzheimer's disease. Here we show that clinical symptoms in patients are not correlated with residual enzymatic activity of mutated HSD10. Loss-of-function and rescue experiments in Xenopus embryos and cells derived from conditional Hsd17b10(-/-) mice demonstrate that a property of HSD10 independent of its enzymatic activity is essential for structural and functional integrity of mitochondria. Impairment of this function in neural cells causes apoptotic cell death whilst the enzymatic activity of HSD10 is not required for cell survival. This finding indicates that the symptoms in patients with mutations in the HSD17B10 gene are unrelated to accumulation of toxic metabolites in the isoleucine pathway and, rather, related to defects in general mitochondrial function. Therefore alternative therapeutic approaches to an isoleucine-restricted diet are required. PMID:20077426

  3. Radiation-induced decomposition of trace amounts of 17 β-estradiol in water

    NASA Astrophysics Data System (ADS)

    Kimura, Atsushi; Taguchi, Mitsumasa; Arai, Hidehiko; Hiratsuka, Hiroshi; Namba, Hideki; Kojima, Takuji

    2004-03-01

    The radiation-induced decomposition of trace amounts of 17 β-estradiol (E2) in water was studied as a function of the dose of 60Co γ-rays. The rate constant of the reaction of the OH radicals with E2 was estimated to be 1.6×10 10 mol dm -3 s -1 by a comparison with the known rate constant for the reaction with phenol. Both E2 and E2-equivalent concentrations were estimated by LC-MS and ELISA, and decreased with an increase in γ-rays dose. E2 (1.8 nmol dm -3) in water was degraded almost completely by irradiations up to 10 Gy. The estrogen activity of the same sample solution still remained at a dose of 10 Gy, but decreased at 30 Gy to the lower than the threshold level of contamination to induce some estrogenic effects on the environmental ecology.

  4. Comparing biological effects and potencies of estrone and 17 B-estradiol in mature fathead minnows, Pimephales promelas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of endocrine active compounds such as estrogens in treated wastewater effluent and their effects on aquatic life are causing concern among aquatic resource managers. In contrast to 17B-estradiol (E2), the steroid hormone produced by all vertebrates, the biological effects of estrone (E1...

  5. Different responses to soy and estradiol in the reproductive system of prepubertal male rats and neonatal male pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concerns have been raised regarding the safety of soy infant formula based on phytochemical components such as genistein, structurally similar to estradiol (E2). To examine potential estrogenic actions on male development, we fed weanling male rats casein-based or soy protein isolate (SPI)-based die...

  6. Potential bioactivity and association of 17ß-estradiol with the dissolved and colloidal fractions of manure and soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The dissolved (DF) and colloidal fractions (CF) of soil and manure may play an important role in the environmental fate and transport of steroidal estrogens, therefore, the first objective of this study was to quantify the association of [14C]17ß-estradiol (E2) with the DF and CF isolated from (i) l...

  7. ESTRADIOL-INDUCED ENHANCEMENT OF OBJECT MEMORY CONSOLIDATION INVOLVES HIPPOCAMPAL ERK ACTIVATION AND MEMBRANE-BOUND ESTROGEN RECEPTORS

    PubMed Central

    Fernandez, Stephanie M.; Lewis, Michael C.; Pechenino, Angela S.; Harburger, Lauren L.; Orr, Patrick T.; Gresack, Jodi E.; Schafe, Glenn E.; Frick, Karyn M.

    2009-01-01

    The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen, 17β-estradiol (E2). Here, we asked whether E2 modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we first demonstrate that intraperitoneal (i.p.) injection of 0.2 mg/kg E2 significantly increases dorsal hippocampal levels of phosphorylated ERK protein 1 hour after injection. Second, we show that E2 administered i.p. (0.2 mg/kg) or via intrahippocampal infusion (5.0 μg/side) immediately after training in an object recognition task significantly enhances memory retention, and that the beneficial effect of i.p. E2 is blocked by dorsal hippocampal inhibition of ERK activation. Third, using bovine serum albumin-conjugated 17β-estradiol (BSA-E2), we demonstrate that E2 binding at membrane-bound ERs can increase dorsal hippocampal ERK activation and enhance object memory consolidation in an ERK-dependent manner. Fourth, we show that this effect is independent of nuclear ERs, but is dependent on the dorsal hippocampus. By demonstrating that E2 enhances memory consolidation via dorsal hippocampal ERK activation, this study is the first to identify a specific molecular pathway by which E2 modulates memory and to demonstrate a novel role for membrane-bound ERs in mediating E2-induced improvements in hippocampal memory consolidation. PMID:18753366

  8. Serum estradiol and coronary artery disease.

    PubMed

    Goldberg, R J; Gore, J M; Zive, M; Brady, P; Klaiber, E; Broverman, D; Ockene, I S; Dalen, J E

    1987-01-01

    Serum estradiol levels were measured in 300 men undergoing coronary angiography. Among these men, there were no significant differences in the serum estradiol levels between patients with (mean, 26.4 pg/ml) and those without (mean, 30.9 pg/ml) angiographically confirmed coronary artery disease. There were no significant differences in any of the established coronary risk factors when patients were subdivided according to the presence or absence of coronary artery disease or according to the extent of disease. In addition, no significant correlation was noted between mean serum estradiol levels and the extent of coronary artery disease as classified by the number of obstructed coronary vessels. A matched-pairs analysis was carried out in which patients who had normal coronary arteries were matched with those who had coronary artery disease on the basis of age, cigarette smoking, prior history of myocardial infarction, and body mass index. The mean serum estradiol level in the patients with coronary artery disease was 28.7 pg/ml, and the mean estradiol level was 31.4 pg/ml for the matched patients with normal coronary arteries. In addition, when serial (three) estradiol determinations were carried out in 100 patients, no association was observed between degree of estradiol variability and the occurrence and/or extent of coronary artery disease. The results of this observational study fail to support an association between serum estradiol levels and the presence or degree of coronary artery disease in men as documented by coronary angiography. PMID:3799667

  9. Noncontraceptive benefits of the estradiol valerate/dienogest combined oral contraceptive: a review of the literature

    PubMed Central

    Nappi, Rossella E; Serrani, Marco; Jensen, Jeffrey T

    2014-01-01

    Combined oral contraceptives formulated to include estradiol (E2) have recently become available for the indication of pregnancy prevention. A combined estradiol valerate and dienogest pill (E2V/DNG), designed to be administered using an estrogen step-down and a progestin step-up regimen over 26 days of active treatment followed by 2 days of placebo (26/2-day regimen), has also undergone research to assess the potential for additional noncontraceptive benefits. Randomized, placebo-controlled studies have demonstrated that E2V/DNG is an effective treatment for heavy menstrual bleeding – a reduction in median menstrual blood loss approaching 90% occurs after 6 months of treatment. To date, E2V/DNG is the only oral contraceptive approved for this indication. Comparator studies have also demonstrated a reduction in hormone withdrawal-associated symptoms in users of E2V/DNG compared with a conventional 21/7-day regimen of ethinylestradiol/levonorgestrel. Other potential noncontraceptive benefits associated with E2V/DNG, like improvement in dysmenorrhea, sexual function, and quality of life, are comparable with those associated with other combined oral contraceptives and are discussed further in this review. PMID:25120376

  10. Pituitary self-priming actions of gonadotropin-releasing hormone. Kinetics of estradiol's potentiating effects on gonadotropin-releasing hormone-facilitated luteinizing hormone and follicle-stimulating hormone release in healthy postmenopausal women.

    PubMed

    Veldhuis, J D; Evans, W S; Rogol, A D; Kolp, L; Thorner, M O; Stumpf, P

    1986-06-01

    We examined the kinetically distinct characteristics of estradiol's effects upon pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in response to pulses of exogenous gonadotropin-releasing hormone (GnRH) in healthy postmenopausal individuals. The putative self-priming actions of GnRH on LH and FSH release were tested by intravenous injections of equal paired doses of GnRH (10 micrograms) before and after 1, 5, 10, and 30 d of pure estradiol-17 beta delivery via an intravaginal silastic ring. Self-priming actions of GnRH, as defined by heightened gonadotropin release in response to the second pulse of GnRH compared with the first, were completely absent in the hypoestrogenemic state. However, estradiol administration unmasked GnRH self-priming in a time-dependent fashion, with maximal expression after 5 and 10 d of steroid replacement, followed by attenuation by 30 d. Since estradiol's modulation of GnRH action was expressed differentially on LH and FSH release, we suggest that such facilitation of GnRH-stimulated pituitary LH and FSH release may provide an additional mechanism for dissociated secretion of gonadotropic hormones in health or disease. PMID:3086382

  11. Modeling Sorption and Degradation of 17β-Estradiol-17-Sulfate in Agricultural Soils

    NASA Astrophysics Data System (ADS)

    Bai, X.; Casey, F. X.; Hakk, H.; Shrestha, S. L.; DeSutter, T.; Khan, E.; Oduor, P. G.

    2011-12-01

    The natural steroid hormone, 17β-estradiol (E2), can be an endocrine disruptor at part-per trillion levels. Laboratory studies indicate a low potential for E2 persistence and mobility in the environment; however, field studies consistently indicate the presence of E2 and its primary metabolite, estrone, at levels sufficiently high to impact water quality. To facilitate urine excretion, animals may release E2 as a sulfated conjugate, which would have a higher aqueous solubility than the parent compound. We hypothesize that E2 conjugates contribute to the detection of free estrogens in the environment. The objective of this study was to determine the sorption, degradation, and mobility of a model conjugate, 17β-estradiol-17-sulfate (E2-17S), in agricultural soils. Radiolabeled E2-17S ([14C]E2-17S) was chemically synthesized in a three-step process, and then batch experiments were conducted in natural and sterile soils. Additionally, soil organic carbon (OC) was varied (1.29 and 0.26%) to investigate its effect on the fate of [14C]E2-17S. Liquid scintillation counting (LSC) was used in concert with high performance liquid chromatography (HPLC) to detect and quantitate parent compound and metabolites of E2-17S in the aqueous and bound phases. Residual soil was combusted to determine non-extractable levels of 14C. The E2-17S was relatively stable in the aqueous phase for natural and sterile soils. Mono- and di- hydroxyl E2-17S were detected as metabolites of E2-17S in the aqueous phase above both sterile and natural soil. Deconjugation to form E2 was not observed in aqueous phase; however, E2 and estrone were extracted from both natural and sterile soils. A conceptual model was developed to simulate and identify the fate and transport processes of E2-17S. Organic carbon was found to be an important factor affecting the sorption and degradation of E2-17S in soils.

  12. Simultaneous Degradation of Estrone, 17β-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H₂O₂ System.

    PubMed

    Ma, Xiaoyan; Zhang, Chao; Deng, Jing; Song, Yali; Li, Qingsong; Guo, Yaping; Li, Cong

    2015-10-01

    UV/H₂O₂, which is an advanced treatment technology used to reduce multiple contaminants, is effective in potable water treatment. Simultaneous degradation effects and kinetics of three types of coexisting micropollutant estrogens (steroid estrogens, SEs), including estrone (E1), 17β-estradiol (E2) and 17α-ethinyl estradiol (EE2), in deionized water were studied. Experiments were carried out with ultraviolet-C (UVC) radiation, together with hydrogen peroxide (H₂O₂), in a cylinder photoreactor. The results demonstrated that the degradation processes of all of the estrogens strongly fit first-order kinetics. Single solutions of E1, E2 and EE2 showed higher degradation rates and removal efficiencies under the same reaction conditions compared with those under mixed conditions. Coexisting combinations of estrogens were put into the UV/H₂O₂ system to estimate their possible competitive influences on each other by examining their removal efficiencies and reaction rate constant, k, values. E1 is predominantly reduced rapidly during the competition, while the presence of other estrogens has negligible impacts on E1; however, the degradation of E2 and EE2 is affected by the competitive background, not in relation to the types but to the existing amounts. In the UV/H₂O₂ system, photocatalysis of the estrogens can stably produce an intermediate X, with the highest quantity coming from E1, while considerably lower quantities are obtained from E2 and EE2. PMID:26404330

  13. Simultaneous Degradation of Estrone, 17β-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H2O2 System

    PubMed Central

    Ma, Xiaoyan; Zhang, Chao; Deng, Jing; Song, Yali; Li, Qingsong; Guo, Yaping; Li, Cong

    2015-01-01

    UV/H2O2, which is an advanced treatment technology used to reduce multiple contaminants, is effective in potable water treatment. Simultaneous degradation effects and kinetics of three types of coexisting micropollutant estrogens (steroid estrogens, SEs), including estrone (E1), 17β-estradiol (E2) and 17α-ethinyl estradiol (EE2), in deionized water were studied. Experiments were carried out with ultraviolet-C (UVC) radiation, together with hydrogen peroxide (H2O2), in a cylinder photoreactor. The results demonstrated that the degradation processes of all of the estrogens strongly fit first-order kinetics. Single solutions of E1, E2 and EE2 showed higher degradation rates and removal efficiencies under the same reaction conditions compared with those under mixed conditions. Coexisting combinations of estrogens were put into the UV/H2O2 system to estimate their possible competitive influences on each other by examining their removal efficiencies and reaction rate constant, k, values. E1 is predominantly reduced rapidly during the competition, while the presence of other estrogens has negligible impacts on E1; however, the degradation of E2 and EE2 is affected by the competitive background, not in relation to the types but to the existing amounts. In the UV/H2O2 system, photocatalysis of the estrogens can stably produce an intermediate X, with the highest quantity coming from E1, while considerably lower quantities are obtained from E2 and EE2. PMID:26404330

  14. THE EFFECT OF GONADECTOMY AND ESTRADIOL ON SENSITIVITY TO OXIDATIVE STRESS

    PubMed Central

    Bokov, Alex F.; Ko, Daijin; Richardson, Arlan

    2009-01-01

    The sexual dimorphism of life span and caloric restriction effects in numerous species suggest that estradiol (E2) is protective against oxidative damage. The only direct test of E2's protective effect in mice against in vivo oxidative stress to date may have been confounded by E2's direct chemical action as an antioxidant because it was administered at very high dosages. Therefore, we have identified a low yet physiologically effective dose of E2. We then administered this dose using subcutaneous time-release pellets to ovariectomized mice. Two weeks after E2 pellet implantation, sham-operated, ovariectomized, and ovariectomized E2-supplemented female mice were injected with a lethal dose of paraquat and their survival was followed. It was observed that ovariectomy exacerbates paraquat-induced mortality and is rescued by E2 supplementation. An equivalent experiment was performed on sham-operated, orchidectomized, and E2-supplemented orchidectomized male mice. The survival of male mice was improved by orchidectomy, and E2 gave no further benefit. We interpret the results to mean that E2 is protective against oxidative stress through its regulatory role and that testosterone diminishes protection against oxidative stress. PMID:19557590

  15. Biomechanical properties of osteoporotic rat femurs after different hormonal treatments: genistein, estradiol, and estradiol/progesterone

    PubMed Central

    Azboy, İbrahim; Özkaya, Mustafa; Demir, Teyfik; Demirtaş, Abdullah; Kağan Arslan, Arslan; Özkul, Emin; Akcan, Adnan; Tolunay, Tolga

    2016-01-01

    Introduction: The purpose of the study is to compare the effects of genistein, estradiol, estradiol/progesterone combination on the bone mineral density and biomechanical properties of ovariectomized rats’ bone. Methods: 50 female adult Sprague-Dawley rats were divided into five groups. Bilaterally ovaeriectomy were performed in all groups except the sham-operated group. Groups were a sham-operated group and a control group (water was given), estradiol treated group (17-β estradiol 0.015 mg/kg per day), genistein treated group (genistein 10 mg/kg per day), and an estradiol/progesterone combination group (17-β estradiol 0.015 mg/kg plus drosperinone 0.028 mg/kg per day). The water or hormones were implemented in relevant groups for eight weeks by orogasthric catheter. The bone mineral density and biomechanical properties of the femur were analyzed. Results: Genistein, estradiol, and estradiol/progesterone groups increased bone mineral density significantly compared to the control group. In diaphysis and metaphysis bending test, all groups had higher peak load values than the control group. There were statistically significant differences between the estrogen/progesterone group and control group in diaphysis bending with regard to peak load. There were statistically significant differences between the estradiol and control groups in metaphysis bending with regard to peak load. In axial rotation test, all groups had higher peak torque values than the control groups. Conclusions: Genistein, estradiol and estrogen/progesterone combination improved the biomechanical properties of the ovariectomized rat bone. Genistein which has less side effects may be considered as an alternative in the treatment of postmenopausal osteoporosis. PMID:27194109

  16. Promoter Methylation Status of Breast Cancer Susceptibility Gene 1 and 17 Beta Hydroxysteroid Dehydrogenase Type 1 Gene in Sporadic Breast Cancer Patients

    PubMed Central

    Hosny, Marwa M.; Sabek, Nagwan A.; El-Abaseri, Taghrid B.; Hassan, Fathalla M.; Farrag, Sherif H.

    2016-01-01

    Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17βHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17βHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (p < 0.001). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype “luminal A” (p = 0.048, p = 0.042, p = 0.007, and p = 0.049, resp.). Methylation of BRCA1 and 17βHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17βHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies. PMID:27413552

  17. A role for the androgen metabolite, 5alpha-androstane-3beta,17beta-diol, in modulating oestrogen receptor beta-mediated regulation of hormonal stress reactivity.

    PubMed

    Handa, R J; Weiser, M J; Zuloaga, D G

    2009-03-01

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a basic response of animals to environmental perturbations that threaten homeostasis. These responses are regulated by neurones in the paraventricular nucleus of the hypothalamus (PVN) that synthesise and secrete corticotrophin-releasing hormone (CRH). Other PVN neuropeptides, such as arginine vasopressin and oxytocin, can also modulate activity of CRH neurones in the PVN and enhance CRH secretagogue activity of the anterior pituitary gland. In rodents, sex differences in HPA reactivity are well established; females exhibit a more robust activation of the HPA axis after stress than do males. These sex differences primarily result from opposing actions of sex steroids, testosterone and oestrogen, on HPA function. Ostreogen enhances stress activated adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) secretion, whereas testosterone decreases the gain of the HPA axis and inhibits ACTH and CORT responses to stress. Data show that androgens can act directly on PVN neurones in the male rat through a novel pathway involving oestrogen receptor (ER)beta, whereas oestrogen acts predominantly through ERalpha. Thus, we examined the hypothesis that, in males, testosterone suppresses HPA function via an androgen metabolite that binds ERbeta. Clues to the neurobiological mechanisms underlying such a novel action can be gleaned from studies showing extensive colocalisation of ERbeta in oxytocin-containing cells of the PVN. Hence, in this review, we address the possibility that testosterone inhibits HPA reactivity by metabolising to 5alpha-androstane-3beta,17beta-diol, a compound that binds ERbeta and regulates oxytocin containing neurones of the PVN. These findings suggest a re-evaluation of studies examining pathways for androgen receptor signalling. PMID:19207807

  18. Serum estradiol levels in male cigarette smokers.

    PubMed

    Klaiber, E L; Broverman, D M; Dalen, J E

    1984-11-01

    Serum estradiol levels were compared in smoking and nonsmoking men in two separate samples. Sample I consisted of 41 young adult male volunteers ranging in age from 18 to 24 years. Twenty-three men smoked an average of 24.5 +/- 6.9 cigarettes daily. The duration of smoking averaged 5.2 +/- 2.2 years. Sample II consisted of 35 husbands who had been evaluated for infertility; they ranged in age from 19 to 49 years. Eighteen men smoked an average of 21.6 +/- 7.9 cigarettes daily. The duration of smoking averaged 11.5 +/- 4.5 years. Age, height, and weight did not differ significantly between smokers and nonsmokers within either group. Serum estradiol levels were significantly elevated in smokers compared with nonsmokers in both groups (p less than 0.001 and p less than 0.0001 in Samples I and II, respectively). No significant correlations were found between serum estradiol levels and the number of cigarettes smoked daily, or with the duration of smoking in either sample. The differences in serum estradiol levels between smokers and nonsmokers could not be attributed to the differences in marijuana and alcohol use that existed between the smokers and nonsmokers in each sample. The recent reports of elevated serum estradiol levels as a possible risk factor in coronary heart disease are discussed in view of the known relationship of cigarette smoking to coronary heart disease. PMID:6496540

  19. Identification of 5alpha-androst-1-ene-3beta,17beta-diol in the fat of Sus scrofa L.: a "nutritional supplement" not found previously in the food supply.

    PubMed

    McGregor, Stephen J; Erickson, Andrew J

    2003-09-01

    5alpha-Androst-1-ene-3beta,17beta-diol (1) was detected in extracts from fat of Sus scrofa L. (pig) by comparison with the commercially available synthetic compound, using gas chromatography-mass spectrometry. This observation is unprecedented because 1 is currently sold as a nutritional supplement, yet has not been previously reported as naturally occurring in the food supply. PMID:14510586

  20. Isolation and Bioaugmentation of an Estradiol-Degrading Bacterium and Its Integration into a Mature Biofilm▿

    PubMed Central

    Iasur-Kruh, Lilach; Hadar, Yitzhak; Minz, Dror

    2011-01-01

    Bioaugmentation can alter the potential activity as well as the composition of the naturally occurring microbial biota during bioremediation of a contaminated site. The focus of the current study is the pollutant 17β-estradiol (E2), which can cause endocrine effects and is potentially harmful to aquatic biota and to public health. The community composition and function of biofilms, originating from a wetland system, as affected by augmentation of an estradiol-degrading bacterium (EDB-LI1) under different conditions, were investigated. EDB-LI1 inoculation into biofilm from two wetland ponds representing early and advanced water treatment stages, respectively, yielded three significant observations, as follows: (i) EDB-LI1, enriched from a biofilm of a constructed wetland wastewater treatment system, was detected (by quantitative PCR [qPCR] analysis) in this environment in the augmented biofilm only; (ii) the augmented biofilm acquired the ability to remove estradiol; and (iii) the bacterial community composition (analyzed by PCR-denaturing gradient gel electrophoresis [DGGE]) of the augmented biofilm differed from that of the control biofilm. Furthermore, EDB-LI1 bioaugmentation showed a higher level of removal of estradiol with biofilms that originated from the advanced-treatment-stage wetland pond than those from the early-treatment-stage pond. Hence, the bioaugmentation efficiency of EDB-LI1 depends on both the quality of the feed water and the microbial community composition in the pond. PMID:21478310

  1. Estrogens and development of pulmonary hypertension - Interaction of estradiol metabolism and pulmonary vascular disease

    PubMed Central

    Tofovic, Stevan P.

    2010-01-01

    Severe pulmonary arterial hypertension (PAH) is characterized by clustered proliferation of endothelial cells in the lumina of small size pulmonary arteries resulting in concentric obliteration of the lumina and formation of complex vascular structures known as plexiform lesions. This debilitating disease occurs more frequently in women, yet both animal studies in classical models of PAH and limited clinical data suggest protective effects of estrogens: the estrogen paradox in pulmonary hypertension. Little is known about the role of estrogens in PAH, but one line of evidence strongly suggests that the vascular protective effects of 17β-estradiol (estradiol; E2) are mediated largely by its downstream metabolites. Estradiol is metabolized to 2-hydroxyestradiol (2HE) by CYP1A1/CYP1B1, and 2HE is converted to 2-methoxyestradiol (2ME) by catechol-O-methyl transferase. 2ME is extensively metabolized to 2-methoxyestrone, a metabolite that lacks biologic activity but which may be converted back to 2ME. 2ME has no estrogenic activity and its effects are mediated by estrogen receptors-independent mechanism(s). Notably, in systemic and pulmonary vascular endothelial cells, smooth muscle cells, and fibroblasts 2ME exerts stronger anti-mitotic effects than E2 itself. E2 and 2ME, despite having similar effects on other cardiovascular cells, have opposing effects on endothelial cells; that is, in endothelial cells, E2 is pro-mitogenic, pro-angiogenic and anti- apoptotic, whereas 2ME is antimitogenic, anti-angiogenic and pro-apoptotic. This may have significant ramifications in severe PAH that involves uncontrolled proliferation of monoclonal, apoptosis resistant endothelial cells. Based on its cellular effects, 2ME should be expected to attenuate the progression of disease and provide protection in severe PAH. In contrast, E2, due to its mitogenic, angiogenic, and anti-apoptotic effects (otherwise desirable in normal, quiescent endothelial cells), may even adversely affect

  2. Review of the safety, efficacy and patient acceptability of the combined dienogest/estradiol valerate contraceptive pill.

    PubMed

    Guida, Maurizio; Bifulco, Giuseppe; Di Spiezio Sardo, Attilio; Scala, Mariamaddalena; Fernandez, Loredana Maria Sosa; Nappi, Carmine

    2010-01-01

    The aim of this review is to define the role of the combined dienogest (DNG)/estradiol valerate (E2V) contraceptive pill, in terms of biochemistry, metabolic and pharmacological effects and clinical application as well. E2V is the esterified form of 17β-estradiol (E2), while dienogest is a fourth-generation progestin with a partial antiandrogenic effect. The cycle stability is achieved with 2 to 3 mg DNG, supporting contraceptive efficacy. In this new oral contraceptive, E2V is combined with DNG in a four-phasic dose regimen (the first two tablets contain 3 mg E2V; the next five tablets include 2 mg E2V + 2 mg DNG, followed by 17 tablets with 2 mg E2V + 3 mg DNG; followed by two tablets with 1 mg E2V only, and finally two placebo tablets). Duration and intensity of scheduled withdrawal bleeding are lower with this contraceptive pill, whereas the incidence and the intensity of intra-cyclic bleeding are similar to the other oral contraceptive. With this new pill the levels of high density lipoprotein increased, while the levels of prothrombin fragment 1 + 2 and D-dimer remained relatively unchanged; the levels of sex hormone binding globulin, cortisol binding globulin, thyroxine binding globulin increased. The most frequently reported adverse events are: breast pain, headache, acne, alopecia, migraine, increase of bodyweight. The satisfaction rate is about 79.4%. PMID:21151673

  3. Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation

    SciTech Connect

    Zhu, Liangliang; Xiao, Ling; Xia, Yangliu; Zhou, Kun; Wang, Huili; Huang, Minyi; Ge, Guangbo; Wu, Yan; Wu, Ganlin; Yang, Ling

    2015-03-01

    This in vitro study investigates the effects of diethylstilbestrol (DES), a widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O) glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP-glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O-glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the Ki value of 2.1 ± 0.3 μM, which is less than the possible in vivo level. In contrast to the inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O-glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In the presence of DES (0–6.25 μM), K{sub m} values for E2-17-O-glucuronidation are located in the range of 7.2–7.4 μM, while V{sub max} values range from 0.38 to 1.54 nmol/min/mg. The mechanism behind the activation in HLM is further demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4 in catalyzing E2-17-O-glucuronidation. The presence of DES (2 μM) can elevate V{sub max} from 0.016 to 0.81 nmol/min/mg, while lifting K{sub m} in a much lesser extent from 4.4 to 11 μM. Activation of E2-17-O-glucuronidation is well described by a two binding site model, with K{sub A}, α, and β values of 0.077 ± 0.18 μM, 3.3 ± 1.1 and 104 ± 56, respectively. However, diverse effects of DES towards E2-3/17-O-glucuronidation are not observed in liver microsomes from several common experimental animals. In summary, this study issues new potential toxic mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. - Highlights: • E2-3-O-glucuronidation in HLM is inhibited when co-incubated with DES. • E2-17-O-glucuronidation in HLM is stimulated when co-incubated with DES. • Acceleration of E2-17-O-glucuronidationin in HLM by DES is via activating the

  4. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

    PubMed Central

    Krumenacker, Joshua S.; Hyder, Salman M.; Murad, Ferid

    2001-01-01

    Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17β-estradiol (E2) regulates the α1 and β1 subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC α1 10% and sGC β1 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression. PMID:11209068

  5. Estradiol rapidly modulates synaptic plasticity of hippocampal neurons: Involvement of kinase networks.

    PubMed

    Hasegawa, Yoshitaka; Hojo, Yasushi; Kojima, Hiroki; Ikeda, Muneki; Hotta, Keisuke; Sato, Rei; Ooishi, Yuuki; Yoshiya, Miyuki; Chung, Bon-Chu; Yamazaki, Takeshi; Kawato, Suguru

    2015-09-24

    Estradiol (E2) is locally synthesized within the hippocampus in addition to the gonads. Rapid modulation of hippocampal synaptic plasticity by E2 is essential for synaptic regulation. Molecular mechanisms of modulation through synaptic estrogen receptor (ER) and its downstream signaling, however, have been still unknown. We investigated induction of LTP by the presence of E2 upon weak theta burst stimulation (weak-TBS) in CA1 region of adult male hippocampus. Since only weak-TBS did not induce full-LTP, weak-TBS was sub-threshold stimulation. We observed LTP induction by the presence of E2, after incubation of hippocampal slices with 10nM E2 for 30 min, upon weak-TBS. This E2-induced LTP was blocked by ICI, an ER antagonist. This E2-LTP induction was inhibited by blocking Erk MAPK, PKA, PKC, PI3K, NR2B and CaMKII, individually, suggesting that Erk MAPK, PKA, PKC, PI3K and CaMKII may be involved in downstream signaling for activation of NMDA receptors. Interestingly, dihydrotestosterone suppressed the E2-LTP. We also investigated rapid changes of dendritic spines (=postsynapses) in response to E2, using hippocampal slices from adult male rats. We found 1nM E2 increased the density of spines by approximately 1.3-fold within 2h by imaging Lucifer Yellow-injected CA1 pyramidal neurons. The E2-induced spine increase was blocked by ICI. The increase in spines was suppressed by blocking PI3K, Erk MAPK, p38 MAPK, PKA, PKC, LIMK, CaMKII or calcineurin, individually. On the other hand, blocking JNK did not inhibit the E2-induced spine increase. Taken together, these results suggest that E2 rapidly induced LTP and also increased the spine density through kinase networks that are driven by synaptic ER. This article is part of a Special Issue entitled SI: Brain and Memory. PMID:25595055

  6. Serum Estradiol Levels Are Inversely Associated With Cortical Porosity in Older Men

    PubMed Central

    Vandenput, Liesbeth; Lorentzon, Mattias; Sundh, Daniel; Nilsson, Maria E.; Karlsson, Magnus K.; Mellström, Dan

    2014-01-01

    Context: The key role of serum estradiol (E2) for bone health in men is well established. The effect of serum sex steroids on bone microstructure, measured by high-resolution peripheral quantitative computed tomography, remains unknown in elderly men. Objective: The objective of the study was to examine the associations between serum sex steroids and bone microstructural parameters in older men. Methods: Trabecular and cortical bone microstructure at the tibia was measured by high-resolution peripheral quantitative computed tomography in 440 men (mean 80 y of age) participating in the population-based Osteoporotic Fractures in Men Sweden cohort. Serum levels of E2 and T were analyzed with mass spectrometry and free E2 and free T levels were calculated using law-of-mass-action equations. Results: Age-adjusted models demonstrated that E2 and free E2 but not T or free T associated significantly inversely with cortical porosity. The associations between E2 and free E2 and cortical porosity remained significant after further adjustment for height, weight, physical activity, calcium intake, and smoking. Models including both serum E2 and T demonstrated that E2 (standardized β = −.12, P < .05) but not T associated independently with cortical porosity. A similar independent association was found for free E2 (standardized β = −.12, P < .05) but not free T. Free E2 associated significantly with trabecular bone volume fraction in the age-adjusted models, but this association did not remain significant after further adjustment. Conclusions: Serum E2 levels associated inversely with cortical porosity in 80-year-old men. We propose that low serum E2 may reduce cortical bone strength, at least partly, by increasing cortical porosity and thereby increase fracture risk in older men. PMID:24694340

  7. EFFECTS OF 17B ESTRADIOL AND ETHINYL ESTRADIOL ON REPRODUCTIVE INDICATORS IN LABORATORY-EXPOSED CUNNER, TAUTOGOLABRUS ADPERSUS

    EPA Science Inventory

    Cunner (Tautogolabrus adspersus) are being studied in our laboratory to evaluate how 17 - estradiol and ethinyl estradiol affect their reproductive success. Cunner was selected because this species spawns daily, is common in estuarine areas, is easily obtainable, and is amenable ...

  8. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  9. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  10. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  11. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  12. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  13. Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

  14. Effects of biodegradation and sorption by humic acid on the estrogenicity of 17β-estradiol.

    PubMed

    Lee, Ji Ho; Zhou, John L; Kim, Sang Don

    2011-11-01

    The removal of 17β-estradiol (E2) by biodegradation and sorption onto humic acid (HA) was examined at various HA concentrations. Subsequently, estrogenicity associated with E2 removal was estimated using E-screen bioassay. Results showed that E2 biodegradation and its subsequent transformation to estrone (E1) were significantly reduced with increasing HA concentration. In addition, the presence of nutrients enhanced the biodegradation of E2. Overall, E2 biodegradation was the dominating contributor to its removal, which demonstrated a significantly negative correlation with E2 sorption at various HA concentrations. The sorption of E2 by HA was significantly enhanced with increasing HA concentration. Estrogenicity associated with residual E2 showed that there existed a significant difference among various HA concentrations, with the lowest value in the absence of HA. The findings suggest that the presence of HA and nutrients in natural waters should be considered in assessing estrogenicity of environmental samples due to complex sorption and biodegradation processes. PMID:21872903

  15. 17β-Estradiol Modulates Gene Expression in the Female Mouse Cerebral Cortex

    PubMed Central

    Humphreys, Gwendolyn I.; Ziegler, Yvonne S.; Nardulli, Ann M.

    2014-01-01

    17β-estradiol (E2) plays critical roles in a number of target tissues including the mammary gland, reproductive tract, bone, and brain. Although it is clear that E2 reduces inflammation and ischemia-induced damage in the cerebral cortex, the molecular mechanisms mediating the effects of E2 in this brain region are lacking. Thus, we examined the cortical transcriptome using a mouse model system. Female adult mice were ovariectomized and implanted with silastic tubing containing oil or E2. After 7 days, the cerebral cortices were dissected and RNA was isolated and analyzed using RNA-sequencing. Analysis of the transcriptomes of control and E2-treated animals revealed that E2 treatment significantly altered the transcript levels of 88 genes. These genes were associated with long term synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen activated protein kinase, and phosphatidylinositol 3-kinase signaling. E2 also altered the expression of genes linked to lipid synthesis and metabolism, vasoconstriction and vasodilation, cell-cell communication, and histone modification. These results demonstrate the far-reaching and diverse effects of E2 in the cerebral cortex and provide valuable insight to begin to understand cortical processes that may fluctuate in a dynamic hormonal environment. PMID:25372139

  16. Neuroprotective Effects of 17β-Estradiol Rely on Estrogen Receptor Membrane Initiated Signals

    PubMed Central

    Fiocchetti, Marco; Ascenzi, Paolo; Marino, Maria

    2012-01-01

    Besides its crucial role in many physiological events, 17β-estradiol (E2) exerts protective effects in the central nervous system. The E2 effects are not restricted to the brain areas related with the control of reproductive function, but rather are widespread throughout the developing and the adult brain. E2 actions are mediated through estrogen receptors (i.e., ERα and ERβ) belonging to the nuclear receptor super-family. As members of the ligand-regulated transcription factor family, classically, the actions of ERs in the brain were thought to mediate only the E2 long-term transcriptional effects. However, a growing body of evidence highlighted rapid, membrane initiated E2 effects in the brain that are independent of ER transcriptional activities and are involved in E2-induced neuroprotection. The aim of this review is to focus on the rapid effects of E2 in the brain highlighting the specific role of the signaling pathway(s) of the ERβ subtype in the neuroprotective actions of E2. PMID:22493583

  17. Estradiol protective role in atherogenesis through LDL structure modification

    NASA Astrophysics Data System (ADS)

    Papi, Massimiliano; Brunelli, Roberto; Ciasca, Gabriele; Maiorana, Alessandro; Maulucci, Giuseppe; Palmieri, Valentina; Parasassi, Tiziana; De Spirito, Marco

    2016-07-01

    Relevant physiological functions are exerted by circulating low density lipoprotein (LDL) as well as eventual pathological processes triggering atherogenesis. Modulation of these functions can well be founded on modifications of LDL structure. Given its large dimension, multicomponent organization and strong interactions between the protein apoB-100 and lipids, determining LDL 3D structure remains a challenge. We propose a novel quantitative physical approach to this complex biological problem. We introduce a three-component model, fitted to small angle x-ray scattering data on LDL maintained in physiological conditions, able to achieve a consistent 3D structure. Unexpected features include three distinct protein domains protruding out of a sphere, quite rough in its surface, where several core lipid areas are exposed. All LDL components are affected by 17-β-estradiol (E2) binding to apoB-100. Mostly one of the three protruding protein domains, dramatically reducing its presence on the surface and with a consequent increase of core lipids’ exposure. This result suggests a structural basis for some E2 protecting roles and LDL physiological modifications.

  18. ELEVATION OF SERUM 17-B-ESTRADIOL IN CHANNEL CATFISH FOLLOWING INJECTION OF 17-B-ESTRADIOL, ETHYNYL ESTRADIOL, ESTRONE, ESTRIOL, AND ESTRADIOL-17B- GLUCURONIDE

    EPA Science Inventory

    17-b-Estradiol is naturally converted in numerous organisms to various derivatives/metabolites, which may be excreted from the organism into its immediate external environment. There is a paucity of data regarding the biological effects of the derivatives/metabolites on aquatic o...

  19. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

    PubMed

    McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

    2015-02-01

    Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. PMID:25555360

  20. Transcriptomics of the fetal hypothalamic response to brachiocephalic occlusion and estradiol treatment.

    PubMed

    Wood, Charles E; Rabaglino, Maria Belen; Richards, Elaine; Denslow, Nancy; Zarate, Miguel A; Chang, Eileen I; Keller-Wood, Maureen

    2014-07-15

    Estradiol (E2) is a well-known modulator of fetal neuroendocrine activity and has been proposed as a critical endocrine signal readying the fetus for birth and postnatal life. To investigate the modulatory role of E2 on fetal stress responsiveness and the response of the fetal brain to asphyxic stress, we subjected chronically catheterized fetal sheep to a transient (10 min) brachiocephalic artery occlusion (BCO) or sham occlusion. Half of the fetuses received subcutaneous pellets that increased plasma E2 concentrations within the physiological range. Hypothalamic mRNA was analyzed using the Agilent 8x15k ovine array (019921), processed and annotated as previously reported by our laboratory. Analysis of the data by ANOVA revealed that E2 differentially regulated (DR) 561 genes, and BCO DR 894 genes compared with control and E2+BCO DR 1,153 genes compared with BCO alone (all P < 0.05). E2 upregulated epigenetic pathways and downregulated local steroid biosynthesis but did not significantly involve genes known to directly respond to the estrogen receptor. Brachiocephalic occlusion upregulated kinase pathways as well as genes associated with lymphocyte infiltration into the brain and downregulated neuropeptide synthesis. E2 upregulated immune- and apoptosis-related pathways after BCO and reduced kinase and epigenetic pathway responses to the BCO. Responses to BCO are different from responses to hypoxic hypoxia suggesting that mechanisms of responses to these two forms of brain hypoxia are distinct. We conclude that cerebral ischemia caused by BCO might stimulate lymphocyte infiltration into the brain and that this response appears to be modified by estradiol. PMID:24824211

  1. β-Arrestin Regulates Estradiol Membrane-Initiated Signaling in Hypothalamic Neurons

    PubMed Central

    Wong, Angela M.; Abrams, Matthew C.; Micevych, Paul E.

    2015-01-01

    Estradiol (E2) action in the nervous system is the result of both direct nuclear and membrane-initiated signaling (EMS). E2 regulates membrane estrogen receptor-α (ERα) levels through opposing mechanisms of EMS-mediated trafficking and internalization. While ß-arrestin-mediated mERα internalization has been described in the cortex, a role of ß-arrestin in EMS, which underlies multiple physiological processes, remains undefined. In the arcuate nucleus of the hypothalamus (ARH), membrane-initiated E2 signaling modulates lordosis behavior, a measure of female sexually receptivity. To better understand EMS and regulation of ERα membrane levels, we examined the role of ß-arrestin, a molecule associated with internalization following agonist stimulation. In the present study, we used an immortalized neuronal cell line derived from embryonic hypothalamic neurons, the N-38 line, to examine whether ß-arrestins mediate internalization of mERα. β-arrestin-1 (Arrb1) was found in the ARH and in N-38 neurons. In vitro, E2 increased trafficking and internalization of full-length ERα and ERαΔ4, an alternatively spliced isoform of ERα, which predominates in the membrane. Treatment with E2 also increased phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2) in N-38 neurons. Arrb1 siRNA knockdown prevented E2-induced ERαΔ4 internalization and ERK1/2 phosphorylation. In vivo, microinfusions of Arrb1 antisense oligodeoxynucleotides (ODN) into female rat ARH knocked down Arrb1 and prevented estradiol benzoate-induced lordosis behavior compared with nonsense scrambled ODN (lordosis quotient: 3 ± 2.1 vs. 85.0 ± 6.0; p < 0.0001). These results indicate a role for Arrb1 in both EMS and internalization of mERα, which are required for the E2-induction of female sexual receptivity. PMID:25803606

  2. Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep.

    PubMed

    Puttabyatappa, Muraly; Cardoso, Rodolfo C; Herkimer, Carol; Veiga-Lopez, Almudena; Padmanabhan, Vasantha

    2016-08-01

    Gestational testosterone (TS) excess, acting via both the androgenic and estrogenic pathways, advances puberty and disrupts the neuroendocrine estradiol (E2) feedback and periovulatory hormonal dynamics in female sheep. These prenatally programmed defects may be subject to postnatal modifications by continued organizational and/or activational effects of steroids. This study investigated (1) the organizational contribution of prenatal estrogen excess and (2) the impact of postnatal exposure to E2 in modulating the effects of prenatal androgen excess (TS and dihydrotestosterone (DHT)) on puberty, neuroendocrine feedback mechanisms, and periovulatory hormonal dynamics in sheep. Pregnant Suffolk sheep were treated with TS, DHT, E2, or E2 plus DHT (ED) from days 30 to 90 of gestation. A subset of the control (C), TS, and DHT female offspring received a constant-release E2 implant postnatally. Findings revealed that (1) prenatal E2-treatment failed to reproduce the neuroendocrine disruptions predicted to be programmed by the estrogenic pathway and (2) prenatal E2D-treatment did not adequately replicate the reproductive neuroendocrine defects induced by prenatal TS excess. More importantly, continuous postnatal E2-treatment, while delaying the onset of puberty and reducing the inhibitory effects of E2 on tonic luteinizing hormone (LH) release, failed to amplify the E2-positive feedback and periovulatory defects induced by prenatal TS-treatment. Our results indicate that disruptions in E2-positive feedback mechanisms and periovulatory gonadotropin secretion induced by prenatal TS-treatment are programmed predominantly during the prenatal life with postnatal exposure to E2 excess not contributing further to these disruptions. PMID:27222598

  3. Steroid sex hormone dynamics during estradiol-17β induced gonadal differentiation in Paralichthys olivaceus (Teleostei)

    NASA Astrophysics Data System (ADS)

    Sun, Peng; You, Feng; Liu, Mengxia; Wu, Zhihao; Wen, Aiyun; Li, Jun; Xu, Yongli; Zhang, Peijun

    2010-03-01

    Steroid sex hormones, such as estradiol-17β (E2) and testosterone (T), are important regulators of sex change in fish. In this study, we examined the effects of E2 treatment on the dynamics of E2 and T during gonadal differentiation in the olive flounder Paralichthys olivaceus using histology and radioimmunoassay (RIA). Flounder larvae were divided into five groups (G0-G4), and fed with 0 (control), 0.2, 2, 20 and 100 mg E2/kg feed from 35 to 110 day post hatching (dph). Fish growth in the G1 and G2 groups was not significantly different from that of the control group ( P>0.05), while fish in the G3 and G4 groups were less active and showed growth depression and high mortality. The gonads of fish in the G3 and G4 groups were smaller and surrounded by hyperplastic connective tissue. The frequency of females in the G0-G4 groups was 54.5%, 75.0%, 100%, 100% and 93.3%, respectively. The RIA analyses of E2 and T showed that T levels decreased during gonadal differentiation, and increased slightly at the onset of ovarian differentiation, while E2 levels increased gradually and peaked at the onset of ovarian differentiation in the control group. In the E2-treated groups, T levels decreased before the onset of ovarian differentiation. E2 levels were high on the 48 dph, but declined to a lower level on the 54 dph, and then increased gradually during gonadal differentiation. And a sharp increase of E2 levels were observed in all E2-treated groups at the onset of ovarian differentiation. The data suggest that T and E2 play important roles during gonadal differentiation, and an E2 dose of 2 mg/kg feed could induce sex reversal in P. olivaceus.

  4. Characterization of the Estradiol-Binding Site Structure of Human Protein Disulfide Isomerase (PDI)

    PubMed Central

    Fu, Xin-Miao; Wang, Pan; Zhu, Bao Ting

    2011-01-01

    Background Earlier studies showed that 17β-estradiol (E2), an endogenous female sex hormone, can bind to human protein disulfide isomerase (PDI), a protein folding catalyst for disulfide bond formation and rearrangement. This binding interaction can modulate the intracellular levels of E2 and its biological actions. However, the structure of PDI's E2-binding site is still unclear at present, which is the focus of this study. Methodology/Principal Findings The E2-binding site structure of human PDI was studied by using various biochemical approaches coupled with radiometric receptor-binding assays, site-directed mutagenesis, and molecular computational modeling. Analysis of various PDI protein fragments showed that the [3H]E2-binding activity is not associated with the single b or b' domain but is associated with the b-b' domain combination. Computational docking analyses predicted that the E2-binding site is located in a hydrophobic pocket composed mainly of the b' domain and partially of the b domain. A hydrogen bond, formed between the 3-hydroxyl group of E2 and His256 of PDI is critical for the binding interaction. This binding model was jointly confirmed by a series of detailed experiments, including site-directed mutagenesis of the His256 residue coupled with selective modifications of the ligand structures to alter the binding interaction. Conclusions/Significance The results of this study elucidated the structural basis for the PDI–E2 binding interaction and the reservoir role of PDI in modulating the intracellular E2 levels. The identified PDI E2-binding site is quite different from its known peptide binding sites. Given that PDI is a potential therapeutic target for cancer chemotherapy and HIV prevention and that E2 can inhibit PDI activity in vitro, the E2-binding site structure of human PDI determined here offers structural insights which may aid in the rational design of novel PDI inhibitors. PMID:22073283

  5. Prostaglandin H synthase catalyzes regiospecific release of tritium from labeled estradiol

    SciTech Connect

    Degen, G.H.; Jellinck, P.H.; Hershcopf, R.J.

    1987-06-01

    Prostaglandin H synthase (PHS) from ram seminal vesicle microsomes was found to catalyze the release of tritium (3H) from estradiol (E2) regiospecifically labeled in position C-2 or C-4 of ring A but not from positions C-17 alpha, C-16 alpha, or C-6,7. Formation of 3H2O from ring A of E2 is dependent upon native enzyme supplemented with either arachidonic acid, eicosapentaenoic acid, or hydrogen peroxide and proceeds very rapidly as do other cooxidation reactions catalyzed by PHS-peroxidase. The 3H-loss from ring A of E2 reflecting oxidative displacement of this isotope by PHS increases linearly up to 100 microM under our conditions (8-45 nmol/mg x 5 min). Loss of tritium in various blanks is negligible by comparison. Indomethacin (0.07 and 0.2 mM) inhibited the PHS-dependent release of 3H2O from estradiol but less efficiently than it inhibited DES-cooxidation measured in parallel incubations under similar conditions. Addition of EDTA (0.5 mM) had no effect on the regiospecific transfer of 3H from E2 or on DES-oxidation; ascorbic acid (0.5 mM) or NADH (0.33 mM) clearly inhibited both reactions and to a similar extent. These data suggest that estradiol-2/4-hydroxylation can be catalyzed by PHS in vitro probably via its peroxidase activity and point to PHS as an enzyme that could contribute to catechol estrogen formation in vitro by tissue preparations in the presence of unsaturated fatty acids or peroxides.

  6. The effect of progesterone and 17-β estradiol on membrane-bound HLA-G in adipose derived stem cells.

    PubMed

    Moslehi, Akram; Hashemi-Beni, Batool; Moslehi, Azam; Akbari, Maryam Ali; Adib, Minoo

    2016-07-01

    Membrane-bound HLA-G (mHLA-G) discovery on adipose derived stem cells (ADSCs) as a tolerogenic and immunosuppressive molecule was very important. Many documents have shown that HLA-G expression can be controlled via some hormones such as progesterone (P4) and estradiol (E2). Therefore, this study was designed to evaluate progesterone and estradiol effects on mHLA-G in ADSCs at restricted and combination concentrations. Three independent cell lines were cultured in complete free phenol red DMEM and subcultured to achieve suffi cient cells. These cells were treated with P4, E2 and P4 plus E2 at physiologic and pregnancy concentrations for 3 days in cell culture conditions. The HLA-G positive ADSCs was measured via monoclonal anti HLA-G-FITC/MEMG-09 by means of flow cytometry in nine groups. Data were analyzed by one way ANOVA and Tukey's post hoc tests. There were no signifi cant values of the mean percentage of HLA-G positive cells in E2-treated and the combination of P4 plus E2-treated ADSCs compared to control cells (p value>0.05) but P4 had a signifi cant increase on mHLA-G in ADSCs (p value<0.05). High P4 concentration increased mHLA-G but E2 and the combination of P4 plus E2 could not change mHLA-G on ADSCs. PMID:27382350

  7. The effect of progesterone and 17-β estradiol on membrane-bound HLA-G in adipose derived stem cells

    PubMed Central

    Moslehi, Akram; Hashemi-beni, Batool; Moslehi, Azam; Akbari, Maryam Ali

    2016-01-01

    Membrane-bound HLA-G (mHLA-G) discovery on adipose derived stem cells (ADSCs) as a tolerogenic and immunosuppressive molecule was very important. Many documents have shown that HLA-G expression can be controlled via some hormones such as progesterone (P4) and estradiol (E2). Therefore, this study was designed to evaluate progesterone and estradiol effects on mHLA-G in ADSCs at restricted and combination concentrations. Three independent cell lines were cultured in complete free phenol red DMEM and subcultured to achieve suffi cient cells. These cells were treated with P4, E2 and P4 plus E2 at physiologic and pregnancy concentrations for 3 days in cell culture conditions. The HLA-G positive ADSCs was measured via monoclonal anti HLA-G-FITC/MEMG-09 by means of flow cytometry in nine groups. Data were analyzed by one way ANOVA and Tukey's post hoc tests. There were no signifi cant values of the mean percentage of HLA-G positive cells in E2-treated and the combination of P4 plus E2-treated ADSCs compared to control cells (p value>0.05) but P4 had a signifi cant increase on mHLA-G in ADSCs (p value<0.05). High P4 concentration increased mHLA-G but E2 and the combination of P4 plus E2 could not change mHLA-G on ADSCs. PMID:27382350

  8. Neuroprotective effect of estradiol-loaded poly(lactic-co-glycolic acid) nanoparticles on glutamate-induced excitotoxic neuronal death.

    PubMed

    Kim, Jeong Hwan; Kim, Gyu Hyun; Jeong, Ji Heun; Lee, In Ho; Lee, Ye Ji; Lee, Nam Seob; Jeong, Young Gil; Lee, Je Hun; Yu, Kwang Sik; Lee, Shin Hye; Hong, Seul Ki; Kang, Seong Hee; Kang, Bo Sun; Kim, Do Kyung; Han, Seung Yun

    2014-11-01

    Different concentrations of estradiol (E2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (E2-PLGA-NPs) were synthesized using the emulsion-diffusion method. Transmission electron microscopy results showed that the average particle size of E2-PLGA-NPs was 98 ± 1.9 nm when stabilized with polyvinyl alcohol and 103 ± 4.9 nm when stabilized with Tween-80. Fourier transform-infrared spectroscopy with diamond attenuated total reflectance was used to identify the presence or absence of E2 molecules in PLGA nanocapsules. Cell proliferation was assessed after treating SH-SY5Y neuroblastoma cells with 1 nM-1 μM of E2 and E2-PLGA-NPs. The neuroprotective efficacy against glutamate-induced excitotoxicity was also investigated in SH-SY5Y neuroblastoma cells. Neuroprotection was greater in E2-PLGA-NP-treated cells than in cells treated with the same concentration of E2. Furthermore, E2- and E2-PLGA-NP-treated cells expressed more p-ERK1/2 and p-CREB than cells treated with glutamate only. Moreover, the expression of p-ERK1/2 was higher than that of p-CREB. In this study, p-ERK1/2 had a greater influence on the neuroprotective effect of E2 and E2-PLGA-NPs than p-CREB. PMID:25958534

  9. Inhibition of estradiol synthesis impairs fear extinction in male rats.

    PubMed

    Graham, Bronwyn M; Milad, Mohammed R

    2014-07-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole, significantly impairs extinction recall in male rats. This deficit in extinction recall is not due to state-dependent memory formation and is completely abolished by coadministration of estradiol. Our data suggest that estradiol may be just as important in the regulation of fear extinction in males as it is in females. PMID:24939838

  10. Inhibition of estradiol synthesis impairs fear extinction in male rats

    PubMed Central

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole, significantly impairs extinction recall in male rats. This deficit in extinction recall is not due to state-dependent memory formation and is completely abolished by coadministration of estradiol. Our data suggest that estradiol may be just as important in the regulation of fear extinction in males as it is in females. PMID:24939838

  11. Interaction of [3H] estradiol - and [3H] monohydroxytamoxifen-estrogen receptor complexes with a monoclonal antibody.

    PubMed

    Tate, A C; DeSombre, E R; Greene, G L; Jensen, E V; Jordan, V C

    1983-01-01

    The aim of this study was to compare and contrast the interaction of estrogen [( 3H]17 beta-estradiol)- or antiestrogen [( 3H]monohydroxytamoxifen)-receptor complexes from human breast tumor cytosols with monoclonal antibodies raised to the human breast tumor estrogen receptor. Breast tumor cytosols containing estrogen receptor which sedimented as radiolabeled peaks in either the 8S, 8S and 4S, or 4S regions of sucrose density gradients, interacted with the monoclonal antibody D547 to produce a broad 9-10S peak, a broad 8S-10S peak, or a more discrete 8S peak, respectively. On high salt (0.4M KC1) sucrose density gradients the 4S ligand-receptor complex plus antibody produced a binding peak at approximately the 8S region of the gradient. These sedimentation studies with the monoclonal antibody D547, and similar studies with the monoclonal antibody D58, could detect no differences in the cytosolic estrogen receptor whether complexed with [3H]estradiol or with [3H]monohydroxytamoxifen. These observations were confirmed by Scatchard equilibrium saturation analysis and sucrose density gradient analysis of cytosols from the MCF-7 human breast cancer cell line. The antibody D547 interacted with 8S ER from these cytosols to produce a broad 8S-10S peak, but the antibody produced no change in the affinity or number of binding sites present in these cytosols. It seems, therefore, that the antigenic determinants recognized by these particular antibodies on the breast tumor cytosolic receptor are not significantly altered by the binding of either an estrogen or an antiestrogen to the receptor. PMID:6671136

  12. 17β-Estradiol modulates the prolactin secretion induced by TRH through membrane estrogen receptors via PI3K/Akt in female rat anterior pituitary cell culture.

    PubMed

    Sosa, Liliana d V; Gutiérrez, Silvina; Petiti, Juan P; Palmeri, Claudia M; Mascanfroni, Iván D; Soaje, Marta; De Paul, Ana L; Torres, Alicia I

    2012-05-01

    Considering that estradiol is a major modulator of prolactin (PRL) secretion, the aim of the present study was to analyze the role of membrane estradiol receptor-α (mERα) in the regulatory effect of this hormone on the PRL secretion induced by thyrotropin-releasing hormone (TRH) by focusing on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway activation. Anterior pituitary cell cultures from female rats were treated with 17β-estradiol (E(2), 10 nM) and its membrane-impermeable conjugated estradiol (E(2)-BSA, 10 nM) alone or coincubated with TRH (10 nM) for 30 min, with PRL levels being determined by RIA. Although E(2), E(2)-BSA, TRH, and E(2)/TRH differentially increased the PRL secretion, the highest levels were achieved with E(2)-BSA/TRH. ICI-182,780 did not modify the TRH-induced PRL release but significantly inhibited the PRL secretion promoted by E(2) or E(2)-BSA alone or in coincubation with TRH. The PI3K inhibitors LY-294002 and wortmannin partially inhibited the PRL release induced by E(2)-BSA, TRH, and E(2)/TRH and totally inhibited the PRL levels stimulated by E(2)-BSA/TRH, suggesting that the mER mediated the cooperative effect of E(2) on TRH-induced PRL release through the PI3K pathway. Also, the involvement of this kinase was supported by the translocation of its regulatory subunit p85α from the cytoplasm to the plasma membrane in the lactotroph cells treated with E(2)-BSA and TRH alone or in coincubation. A significant increase of phosphorylated Akt was induced by E(2)-BSA/TRH. Finally, the changes of ERα expression in the plasmalemma of pituitary cells were examined by confocal microscopy and flow cytometry, which revealed that the mobilization of intracellular ERα to the plasma membrane of lactotroph cells was only induced by E(2). These finding showed that E(2) may act as a modulator of the secretory response of lactotrophs induced by TRH through mER, with the contribution by PI3K/Akt pathway activation providing a new

  13. Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

    SciTech Connect

    Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Hernandez-Ochoa, Isabel Paulose, Tessie Leslie, Traci C. Flaws, Jodi A.

    2011-06-15

    The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E{sub 2}) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24 h for 96 h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E{sub 2} metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E{sub 2}, testosterone, androstenedione, and progesterone (P{sub 4}) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17{beta}-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17{alpha}-hydroxylase/17,20-lyase (Cyp17a1), 3{beta} hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels. - Highlights: > MXC inhibits steroidogenesis > MXC inhibits steroidogenic enzymes > MXC induces metabolic enzymes

  14. Plasma fluctuation in estradiol-17β and bone resorption markers around parturition in dairy cows

    PubMed Central

    DEVKOTA, Bhuminad; TAKAHASHI, Masahiro; SATO, Saori; SASAKI, Kouya; UEKI, Atsushi; OSAWA, Takeshi; TAKAHASHI, Masahiro; YAMAGISHI, Norio

    2015-01-01

    Blood samples were obtained sequentially from 10 dairy cows around the time of parturition to assess plasma fluctuations in estradiol-17β (E2) levels in association with those of several bone resorption markers. Plasma E2 concentration increased sharply a few days prepartum and decreased quickly after parturition. In terms of bone resorption markers, the plasma level of tartrate-resistant acid phosphatase isoform 5b (TRAP5b) rose significantly, commencing 1 week prepartum, and was maintained at this level to a few days postpartum. The plasma concentration of carboxyterminal collagen cross-links of type-I collagen (CTx) increased significantly after parturition. These observations suggest that osteoclast-mediated bone resorption was activated after parturition when plasma E2 concentrations decreased. PMID:25755022

  15. Estradiol improves pulmonary hemodynamics and vascular remodeling in perinatal pulmonary hypertension.

    PubMed

    Parker, T A; Ivy, D D; Galan, H L; Grover, T R; Kinsella, J P; Abman, S H

    2000-02-01

    Partial ligation of the ductus arteriosus (DA) in the fetal lamb causes sustained elevation of pulmonary vascular resistance (PVR) and hypertensive structural changes in small pulmonary arteries, providing an animal model for persistent pulmonary hypertension of the newborn. Based on its vasodilator and antimitogenic properties in other experimental studies, we hypothesized that estradiol (E(2)) would attenuate the pulmonary vascular structural and hemodynamic changes caused by pulmonary hypertension in utero. To test our hypothesis, we treated chronically instrumented fetal lambs (128 days, term = 147 days) with daily infusions of E(2) (10 microg; E(2) group, n = 6) or saline (control group, n = 5) after partial ligation of the DA. We measured intrauterine pulmonary and systemic artery pressures in both groups throughout the study period. After 8 days, we delivered the study animals by cesarean section to measure their hemodynamic responses to birth-related stimuli. Although pulmonary and systemic arterial pressures were not different in utero, fetal PVR immediately before ventilation was reduced in the E(2)-treated group (2.43 +/- 0.79 vs. 1.48 +/- 0.26 mmHg. ml(-1). min, control vs. E(2), P < 0.05). During the subsequent delivery study, PVR was lower in the E(2)-treated group in response to ventilation with hypoxic gas but was not different between groups with ventilation with 100% O(2). During mechanical ventilation after delivery, arterial partial O(2) pressure was higher in E(2) animals than controls (41 +/- 11 vs. 80 +/- 35 Torr, control vs. E(2), P < 0. 05). Morphometric studies of hypertensive vascular changes revealed that E(2) treatment decreased wall thickness of small pulmonary arteries (59 +/- 1 vs. 48 +/- 1%, control vs. E(2), P < 0.01). We conclude that chronic E(2) treatment in utero attenuates the pulmonary hemodynamic and histological changes caused by DA ligation in fetal lambs. PMID:10666122

  16. Reduction of estrone to 17 β-estradiol in the presence of swine manure colloids.

    PubMed

    Prater, Jacob R; Horton, Robert; Thompson, Michael L

    2015-01-01

    Land application of animal manure and municipal biosolids to improve soil fertility carries the risk of adding to aquatic ecosystems contaminants that can disrupt the endocrine systems of aquatic organisms. This study explored the fate of two estrogens, 17 β-estradiol (E2) and estrone (E1), in the presence of organic colloids derived from swine manure. Most reports concerning environmental estrogens indicate a degradation/transformation pathway that leads to decreased estrogenicity, that is, E2 is transformed to E1 and potentially to other daughter products. However, in this study we found that within 24 h the reverse reaction was possible (E1 transforming to E2) in a swine manure colloidal suspension closed to the atmosphere. The reaction occurred after approximately the same 24-h period in separate colloidal suspensions of swine manure that had been initially incubated with E2 or with E1. In the experiment with E2, there was an apparent complete reversal of the solution estrogen form, from E2 to E1 and then back to E2. Our observations support the concern that environmentally relevant estrogens have the potential to increase in estrogenicity and/or to persist under reducing conditions. PMID:25150467

  17. Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation

    PubMed Central

    Totta, Pierangela; Busonero, Claudia; Leone, Stefano; Marino, Maria; Acconcia, Filippo

    2016-01-01

    17β-estradiol (E2) regulates diverse physiological effects, including cell proliferation, by binding to estrogen receptor α (ERα). ERα is both a transcription factor that drives E2-sensitive gene expression and an extra-nuclear localized receptor that triggers the activation of diverse kinase cascades. While E2 triggers cell proliferation, it also induces ERα degradation in a typical hormone-dependent feedback loop. Although ERα breakdown proceeds through the 26S proteasome, a role for lysosomes and for some endocytic proteins in controlling ERα degradation has been reported. Here, we studied the role of the endocytic protein dynamin II in E2-dependent ERα signaling and degradation. The results indicate that dynamin II siRNA-mediated knock-down partially prevents E2-induced ERα degradation through the inhibition of an autophagy-based pathway and impairs E2-induced cell proliferation signaling. Altogether, these data demonstrate that dynamin II is required for the E2:ERα signaling of physiological functions and uncovers a role for autophagy in the control of ERα turnover. PMID:27009360

  18. Dynamin II is required for 17β-estradiol signaling and autophagy-based ERα degradation.

    PubMed

    Totta, Pierangela; Busonero, Claudia; Leone, Stefano; Marino, Maria; Acconcia, Filippo

    2016-01-01

    17β-estradiol (E2) regulates diverse physiological effects, including cell proliferation, by binding to estrogen receptor α (ERα). ERα is both a transcription factor that drives E2-sensitive gene expression and an extra-nuclear localized receptor that triggers the activation of diverse kinase cascades. While E2 triggers cell proliferation, it also induces ERα degradation in a typical hormone-dependent feedback loop. Although ERα breakdown proceeds through the 26S proteasome, a role for lysosomes and for some endocytic proteins in controlling ERα degradation has been reported. Here, we studied the role of the endocytic protein dynamin II in E2-dependent ERα signaling and degradation. The results indicate that dynamin II siRNA-mediated knock-down partially prevents E2-induced ERα degradation through the inhibition of an autophagy-based pathway and impairs E2-induced cell proliferation signaling. Altogether, these data demonstrate that dynamin II is required for the E2:ERα signaling of physiological functions and uncovers a role for autophagy in the control of ERα turnover. PMID:27009360

  19. Glial response to 17β-estradiol in neonatal rats with excitotoxic brain injury.

    PubMed

    Pansiot, Julien; Pham, Hoa; Dalous, Jeremie; Chevenne, Didier; Colella, Marina; Schwendimann, Leslie; Fafouri, Assia; Mairesse, Jérôme; Moretti, Raffaella; Schang, Anne-Laure; Charriaut-Marlangue, Christiane; Gressens, Pierre; Baud, Olivier

    2016-08-01

    White-matter injury is the most common cause of the adverse neurodevelopmental outcomes observed in preterm infants. Only few options exist to prevent perinatal brain injury associated to preterm delivery. 17β-estradiol (E2) is the predominant estrogen in circulation and has been shown to be neuroprotective in vitro and in vivo. However, while E2 has been found to modulate inflammation in adult models of brain damage, how estrogens influence glial cells response in the developing brain needs further investigations. Using a model of ibotenate-induced brain injury, we have refined the effects of E2 in the developing brain. E2 provides significant neuroprotection both in the cortical plate and the white matter in neonatal rats subjected to excitotoxic insult mimicking white matter and cortical damages frequently observed in very preterm infants. E2 promotes significant changes in microglial phenotypes balance in response to brain injury and the acceleration of oligodendrocyte maturation. Maturational effects of E2 on myelination process were observed both in vivo and in vitro. Altogether, these data demonstrate that response of glial cells to E2 could be responsible for its neuroprotective properties in neonatal excitotoxic brain injury. PMID:27222132

  20. Update on the effect of estradiol in postmenopause women with Alzheimer's disease: a systematic review.

    PubMed

    Lan, Yu-Long; Zou, Shuang; Zhang, Changfu; Li, Jun; Xu, Yinghui; Li, Shao

    2016-09-01

    Estradiol (E2) has been used in the treatment of Alzheimer's disease (AD) for many years but with various responses. Evidence from clinical studies, randomized clinical trials (RCTs), and observational studies further underscores the importance of E2 in postmenopause women diagnosed with AD. The purpose of this article is to review all clinical trials to date focusing on the E2 in AD patients to explore the evidence regarding use of E2 in AD treatments. To achieve this objective, clinical studies regarding E2 levels in AD patients and RCTs assessing AD treatment in postmenopause women were identified through searches of MEDLINE, The Cochrane Library, EMBASE, Web of Science, Ovid, and Google Scholar. E2 has demonstrated good therapeutic effectiveness in AD patients, however, further larger scale, double-blind RCTs are required before a definitive conclusion can be reached and the results need to be compared with other drugs. This update reviews the newest clinical information regarding the role of E2 in postmenopause women with AD. To our knowledge, this is the only systematic review of this area. PMID:26931740

  1. Variation in plasma concentrations of oestradiol-17 beta and their relationship to those of progesterone, 13,14-dihydro-15-keto-prostaglandin F-2 alpha and oxytocin across pregnancy and at parturition in pony mares.

    PubMed

    Haluska, G J; Currie, W B

    1988-11-01

    Concentrations of plasma progesterone were similar to values reported in the literature except that a significant decrease in progesterone during the last day, but before parturition, was detected by systematic, high-intensity blood sampling. Mean concentrations of oestradiol-17 beta increased sharply and significantly, plateaued for 132.8 +/- 1.5 days (mean +/- s.e.m., N = 9), then declined sharply in each mare. There was obvious variation between the mares in when these increases and decreases in oestradiol-17 beta occurred, with the events being related closely to ambient photoperiod conditions rather than to the stage of pregnancy. Concentration of 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) remained at low levels (less than 400 pg/ml) until Day 200 then increased to peak pregnancy levels (greater than 2000 pg/ml) by Day 300 and remained at this value until parturition. The concentrations of oxytocin remained basal (less than 15 microU/ml) throughout pregnancy and increased only at the beginning of the expulsive stage of labour. There was an increase, although not statistically significant, in the relative concentrations of oestradiol-17 beta to progesterone beginning 3 days before parturition, with the highest value of the ratio occurring at fetal delivery. Far more striking were acute changes in PGFM and oxytocin during parturition. Maximal concentrations of PGFM (approximately 30 ng/ml) and oxytocin (greater than 200 microU/ml) were measured between rupture of the chorioallantois and the completion of delivery. Closely timed samples from one animal showed that oxytocin increased (more than 10 standard deviations of the mean levels during late pregnancy for this animal) before any change in PGFM. In another dystocic mare, both oxytocin and PGFM peaked in the initial stages of delivery but only oxytocin remained elevated until the dystocia was remedied. The results suggest that an abrupt increase in oxytocin secretion precipitates the expulsive phase

  2. Multigenerational Exposure of the Estuarine Sheepshead Minnow (Cyprinodon variegatus) to 17β-estradiol. I. Organism-Level Effects Over Three GenerationsLife Cycles

    EPA Science Inventory

    This study reports the effects of 17β-estradiol (E2) on reproductive processes through two complete generations of the sheepshead minnow, Cyprinodon variegatus, and determined the need for multiple generation exposure testing for assessing the risks of endocrine disrupting chemic...

  3. VITELLOGENIN MRNA REGULATION AND PLASMA CLEARANCE IN MALE SHEEPSHEAD MINNOWS, CYPRINODON VARIEGATUS AFTER CESSATION OF EXPOSURE TO 17B-ESTRADIOL AND P-NONYLPHENOL

    EPA Science Inventory

    Research was conducted to determine the kinetics of hepatic vitellogenin (VTG) mRNA regulation and plasma VTG accumulation and clearance in male sheepshead minnows (Cyprinodon variegatus) during and after cessation of exposure to either 17b-estradiol (E2) or para-nonylphenol (NP)...

  4. Specific Roles for 17ß-Estradiol versus Gonad Development in Nutrient Partitioning and Regulation of Nutrient- and Growth-Related Mechanisms During Sexual Maturation in Rainbow Trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of sex steroids to nutrient partitioning and energy balance during gonad development was studied in rainbow trout (Oncorhynchus mykiss). Nineteen month old triploid (3N) female rainbow trout were fed a diet supplemented with 17ß-estradiol (E2) at 30 mg steroid/kg diet for a 1 month...

  5. Haemostatic effects of a new combined oral contraceptive, nomegestrol acetate/17β-estradiol, compared with those of levonorgestrel/ethinyl estradiol. A double-blind, randomised study.

    PubMed

    Gaussem, Pascale; Alhenc-Gelas, Martine; Thomas, Jean-Louis; Bachelot-Loza, Christilla; Remones, Veronique; Ali, Fouad Dali; Aiach, Martine; Scarabin, Pierre-Yves

    2011-03-01

    Use of oral contraceptives (OC) that combine a progestogen with synthetic ethinyl estradiol (EE) is associated with increased risk of venous thromboembolism. NOMAC/E2 is a new monophasic OC that combines nomegestrol acetate (NOMAC), a highly selective progestogen, with 17β-estradiol (E2). The study objective was to compare the effects on markers of haemostasis of NOMAC/E2 (2.5 mg/1.5 mg) versus the second-generation OC, levonorgestrel (LNG)/EE (100 μg/20 μg). Healthy women (age 18-38 years) received once-daily treatment for three consecutive 28-day cycles in a double-blind, randomised study: either NOMAC/E2 for 24 days with a four-day placebo interval (n=45) or LNG/EE for 21 days with a seven-day placebo interval (n=45) per cycle. Mean changes from baseline to end-of-treatment in coagulation markers, including prothrombin fragment 1+2 (primary endpoint), fibrinolysis markers and platelet functions were assessed. Mean prothrombin fragment 1+2 levels (primary endpoint) did not increase with NOMAC/E2 compared with LNG/EE ( -0.02 vs. +0.08 nM, p<0.01). Other significant differences between NOMAC/E2 and LNG/EE were mean changes in antithrombin (+0.3% vs. -4.4%, p<0.001), activated protein C resistance - normalised ratio (+0.20 vs. +0.46, p<0.01), D-dimer ( -53 vs. +43 ng/ml, p<0.001), plasminogen (+6% vs. +30%, p<0.0001) and plasminogen activator inhibitor-1 ( -3.1 vs. -8.0 ng/ml, p<0.001). There was no effect of either treatment on platelet aggregation. The NOMAC/E2 pill regimen has fewer adverse effects on blood biological coagulation and fibrinolysis markers than LNG/EE. This suggests that NOMAC/E2 could have a more favourable venous thromboembolism risk profile than LNG/EE; further epidemiological data are required to confirm this. PMID:21225090

  6. 26 CFR 1.367(e)-2 - Distributions described in section 367(e)(2).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 4 2012-04-01 2012-04-01 false Distributions described in section 367(e)(2). 1.367(e)-2 Section 1.367(e)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (Continued) Effects on Corporation § 1.367(e)-2 Distributions described in section 367(e)(2)....

  7. Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive.

    PubMed

    Recio, R; Garza-Flores, J; Schiavon, R; Reyes, A; Diaz-Sanchez, V; Valles, V; Luz de la Cruz, D; Oropeza, G; Perez-Palacios, G

    1986-06-01

    The pharmacodynamics of the combination of dihydroxyprogesterone acetophenide (DHPA) and estradiol enanthate (E2-EN) following its intramuscular administration at two doses were studied in 16 healthy women of reproductive age. Subjects were randomly allocated in two groups: group I (n = 9) received the combination DHPA 150 mg + E2-EN 10 mg on three consecutive monthly injections, while group II (n = 7) received half-dose of the same formulation. Ovarian function and endometrial bleeding patterns were investigated in all participants for one pre-treatment cycle, three treatment intervals and two post-treatment cycles. The results disclosed that ovulation was inhibited for at least 30 days following DHPA/E2-EN administration in all participants from both groups. The circulating estradiol levels 30 days after last injection were slightly elevated as compared with those observed in normal early follicular phase. Return to ovulatory cycles was documented within 90 days after treatment. The length of the bleeding-free intervals during treatment was shortened in both groups, particularly in group II. No significant changes in HDL-cholesterol levels were observed throughout the study. It is envisaged however, that large modification of the formulation and additional long-term safety studies will be required prior to its recommendation. PMID:3769482

  8. Bisphenol A exposure reduces the estradiol response to gonadotropin stimulation during in vitro fertilization

    PubMed Central

    Bloom, Michael S.; Kim, Dongsul; vom Saal, Frederick S.; Taylor, Julia A.; Cheng, Gloria; Lamb, Julie D.; Fujimoto, Victor Y.

    2011-01-01

    Objective Investigate associations between serum BPA concentrations and follicular response to exogenous ovary stimulation. Design Fasting serum was prospectively collected on the day of oocyte retrieval and assessed for unconjugated BPA using high-performance liquid chromatography (HPLC) with Coularray detection. Multivariable linear regression and negative binomial regression were used to assess associations between concentrations of BPA and outcome measures. Models were adjusted for race/ethnicity, antral follicle count at baseline, and cigarette smoking. Setting A reproductive health center. Patients Forty-four women undergoing in vitro fertilization (IVF). Main outcome measures Peak-estradiol level (E2) and the number of oocytes retrieved during IVF. Results The median unconjugated serum BPA concentration is 2.53 ng/ml (range 0.3–67.36 ng/ml). Bisphenol A is inversely associated with E2 (β=−0.16; 95% confidence interval (CI) −0.32, 0.01), as well as with E2 normalized to the number of mature-sized follicles at the hCG trigger (β=−0.14; 95%CI −0.24, −0.03). No association is observed for BPA and the number of oocytes retrieved (adjusted risk ratio=0.95; 95%CI 0.82, 1.10). Conclusions Bisphenol A is associated with a reduced estradiol response during IVF. Although limited by the preliminary nature of this study, these results merit confirmation in a future comprehensive investigation. PMID:21813122

  9. Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels.

    PubMed

    Pluchino, N; Genazzani, A D; Bernardi, F; Casarosa, E; Pieri, M; Palumbo, M; Picciarelli, G; Gabbanini, M; Luisi, M; Genazzani, A R

    2005-03-01

    The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the

  10. Selective Aptamers for Detection of Estradiol and Ethynylestradiol in Natural Waters.

    PubMed

    Akki, Spurti U; Werth, Charles J; Silverman, Scott K

    2015-08-18

    We used in vitro selection to identify new DNA aptamers for two endocrine-disrupting compounds often found in treated and natural waters, 17β-estradiol (E2) and 17α-ethynylestradiol (EE). We used equilibrium filtration to determine aptamer sensitivity/selectivity and dimethyl sulfate (DMS) probing to explore aptamer binding sites. The new E2 aptamers are at least 74-fold more sensitive for E2 than is a previously reported DNA aptamer, with dissociation constants (Kd values) of 0.6 μM. Similarly, the EE aptamers are highly sensitive for EE, with Kd of 0.5-1.0 μM. Selectivity values indicate that the E2 aptamers bind E2 and a structural analogue, estrone (E1), equally well and are up to 74-fold selective over EE. One EE aptamer is 53-fold more selective for EE over E2 or E1, but the other binds EE, E2, and E1 with similar affinity. The new aptamers do not lose sensitivity or selectivity in natural water from a local lake, despite the presence of natural organic matter (∼4 mg/L TOC). DMS probing suggests that E2 binding occurs in relatively flexible single-stranded DNA regions, an important finding for rational redesign of aptamers and their incorporation into sensing platforms. This is the first report of aptamers with strong selectivity for E2 and E1 over EE, or with strong selectivity for EE over E2 and E1. Such selectivity is important for achieving the goal of creating practically useful DNA-based sensors that can distinguish structurally similar estrogenic compounds in natural waters. PMID:26182235

  11. Pathogenic infection confounds induction of the estrogenic biomarker vitellogenin in rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine the behavior of the estrogenic biomarker vitellogenin (VTG) under the combined impact of estrogens and pathogens, parasite-infected or noninfected rainbow trout were exposed to two doses of 17 beta-estradiol (E2). Infected and E2-exposed fish showed significantly lower hepatic VTG mRNA le...

  12. Patient acceptability and satisfaction with Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension).

    PubMed

    Shulman, L P; Oleen-Burkey, M; Willke, R J

    1999-10-01

    The results from a User Satisfaction Questionnaire, Treatment Assessment Questionnaire, and Global Well-Being Schedule questionnaire administered to women participating in an open-labeled, nonrandomized, parallel, controlled study comparing a new monthly injectable contraceptive containing 25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate (E2C) (MPA/E2C) (Lunelle Monthly Contraceptive Injection) and a triphasic norethindrone (0.5, 0.75, 1.0 mg)/0.035 mg ethinyl estradiol (NET/EE) oral contraceptive (Ortho-Novum 7/7/7) are reviewed. Approximately 85% of all 1103 women enrolled in the comparative trial completed their initial and final questionnaires. To better assess the comparison of a new and extant method of contraception, outcome data were divided among MPA/E2C users and new and previous oral contraceptive (OC) users. Despite the inherent inequalities in comparing an injectable to an oral method of contraception, few treatment assessment and satisfaction outcomes were significantly different when comparing MPA/E2C users to new OC (NET/EE) users. More women in the MPA/E2C study group reported discomfort with their method than women in either NET/EE study group; however, only 19.4% of MPA/E2C users rated the administration of their contraceptive to be moderately uncomfortable or worse, compared to 11.7% of new NET/EE users and 13.4% of previous OC users. Among MPA/E2C users, 86.3% reported no interference with social activities compared with 90.4% of new NET/EE users. MPA/E2C and new NET/EE users were also similar in their responses recommending their respective contraceptive method to friends, with > 90% of both groups stating that they had a very favorable experience and would definitely recommend their method to a friend. In general, MPA/E2C was well accepted by women in the study group. Their attitudes and perceptions are similar to those of women who were starting OCs for the first time. These data support the premise that MPA/E2C may

  13. The Effects of 17β-estradiol in Cancer are Mediated by Estrogen Receptor Signaling at the Plasma Membrane

    PubMed Central

    Acconcia, Filippo; Marino, Maria

    2011-01-01

    Two different isoforms of the estrogen receptors (i.e., ERα and ERβ) mediate pleiotropic 17β-estradiol (E2)-induced cellular effects. The ERs are principally localized in the nucleus where they act by globally modifying the expression of the E2-target genes. The premise that E2 effects are exclusively mediated through the nuclear localized ERs has been rendered obsolete by research over the last 15 years demonstrating that ERα and ERβ proteins are also localized at the plasma membranes and in other extra-nuclear organelles. The E2 modulation of cancer cell proliferation represents a good example of the impact of membrane-initiated signals on E2 effects. In fact, E2 via ERα elicits rapid signals driving cancer cells to proliferation (e.g., in breast cancer cells), while E2-induced ERβ rapid signaling inhibits proliferation (e.g., in colon cancer cells). In this review we provide with an overview of the complex system of E2-induced signal transduction pathways, their impact on E2-induced cancer cell proliferation, and the participation of E2-induced membrane-initiated signals in tumor environment. PMID:21747767

  14. Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats.

    PubMed

    Sárvári, Miklós; Deli, Levente; Kocsis, Pál; Márk, László; Maász, Gábor; Hrabovszky, Erik; Kalló, Imre; Gajári, Dávid; Vastagh, Csaba; Sümegi, Balázs; Tihanyi, Károly; Liposits, Zsolt

    2014-10-01

    The mesocortical dopaminergic pathway projecting from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) contributes to the processing of reward signals. This pathway is regulated by gonadal steroids including estradiol. To address the putative role of estradiol and isotype-selective estrogen receptor (ER) agonists in the regulation of the rodent mesocortical system, we combined fMRI, HPLC-MS and qRT-PCR techniques. In fMRI experiments adult, chronically ovariectomized rats, treated with either vehicle, estradiol, ERα agonist 16α-lactone-estradiol (LE2) or ERβ agonist diarylpropionitrile (DPN), received a single dose of d-amphetamine-sulphate (10mg/kg, i.p.) and BOLD responses were monitored in the VTA and the PFC. Ovariectomized rats showed no significant response to amphetamine. In contrast, the VTA of ER agonist-substituted ovariectomized rats showed robust amphetamine-evoked BOLD increases. The PFC of estradiol-replaced animals was also responsive to amphetamine. Mass spectroscopic analysis of dopamine and its metabolites revealed a two-fold increase in both dopamine and 3,4-dihydroxyphenylacetic acid content of the PFC in estradiol-replaced animals compared to ovariectomized controls. qRT-PCR studies revealed upregulation of dopamine transporter and dopamine receptor in the VTA and PFC, respectively, of ER agonist-treated ovariectomized animals. Collectively, the results indicate that E2 and isotype-selective ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopamine content of the PFC. In a broader sense, the findings support the concept that the manifestation of reward signals in the PFC is dependent on the actual estrogen milieu of the brain. PMID:24976584

  15. The association between supra-physiological levels of estradiol and response patterns to experimental pain.

    PubMed

    Nisenblat, Vicki; Engel-Yeger, Batya; Ohel, Gonen; Aronson, Doron; Granot, Michal

    2010-09-01

    The precise mechanism by which gonadal hormones influence pain perception is still obscure. However, no studies have examined experimental pain responses at supra-physiological hormone levels. This study explored the influence of pharmacological estradiol (E2) levels on the stability of pain perception obtained via quantitative sensory testing. A repeated measures design was used with 31 women, treated by a same In Vitro Fertilization (IVF) protocol. Patterns of experimental pain response were assessed in three different sessions (baseline, down regulation, maximal ovarian stimulation). Correlations between hormonal levels (E2, progesterone, luteinizing hormone (LH)) and pain perceptions were assessed at each session. While in the entire sample the pattern of response to pain stimulations remained unchanged regardless of hormonal manipulations, a greater pain sensitivity was associated with supra-physiological levels of E2 during the maximal ovarian stimulation session (for 47 degrees C stimulation: r=.383, p=0.044). Mixed model repeated measures ANOVA indicated that participants who over-responded to the ovarian stimulation session (E2 > 10,500 pmol/l) showed significant enhanced pain responses under this condition (p=0.004). No correlations between progesterone, LH and experimental pain perception were found in any of the study sessions. Although pain perceptions at different E2 levels remained constant, the enhancement of pain scoring at supra-physiological E2 levels, underscore the possible role of sex hormones in pain modulation and experience. PMID:20194038

  16. Biodegradation of 17β-estradiol, estrone and testosterone in stream sediments

    USGS Publications Warehouse

    Bradley, Paul M.; Barber, Larry B.; Chapelle, Francis H.; Gray, James L.; Kolpin, Dana W.; McMahon, Peter B.

    2009-01-01

    Biodegradation of 17β-estradiol (E2), estrone (E1), and testosterone (T) was investigated in three wastewater treatment plant (WWTP) affected streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing saturated sediment or water-only from locations upstream and downstream of the WWTP outfall in each system. Upstream sediment demonstrated significant mineralization of the “A” ring of E2, E1, and T, with biodegradation of T consistently greater than that of E2 and no systematic difference in E2 and E1 biodegradation. “A” ring mineralization also was observed in downstream sediment, with E1 and T mineralization being substantially depressed relative to upstream samples. In marked contrast, E2 mineralization in sediment immediately downstream from the WWTP outfalls was more than double that in upstream sediment. E2 mineralization was observed in water, albeit at insufficient rate to prevent substantial downstream transport. The results indicate that, in combination with sediment sorption processes which effectively scavenge hydrophobic contaminants from the water column and immobilize them in the vicinity of the WWTP outfall, aerobic biodegradation of reproductive hormones can be an environmentally important mechanism for nonconservative (destructive) attenuation of hormonal endocrine disruptors in effluent-affected streams.

  17. Removal mechanisms of 17β-estradiol and 17α-ethinylestradiol in membrane bioreactors.

    PubMed

    Yang, W; Zhou, H; Cicek, N

    2012-01-01

    The fate and behavior of natural and synthetic estrogens in wastewater treatment processes is currently of increasing concern all over the world. In this study, the removal mechanisms of a natural estrogen, 17β-estradiol (E2), and a synthetic estrogen, 17α-ethinylestradiol (EE2) were investigated in membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition. The experimental results showed that the average removal rates of E2 and EE2 by the MBR without PAC addition were 89.0 and 70.9%; PAC addition in the MBR increased the removal rate of E2 and EE2 by 3.4 and 15.8%, respectively. The greater impact of PAC dosing on EE2 removal was due to its greater hydrophobic property. Adsorption played a more important role in the removal mechanisms of EE2 than E2. Biodegradation was the dominant mechanism for the removal of E2 and EE2 in MBRs. Unlike their adsorption behavior, the biodegradation rates of both E2 and EE2 were not significantly different between the MBRs with and without PAC addition. PMID:22828304

  18. 17β-estradiol regulates the differentiation of cementoblasts via Notch signaling cascade.

    PubMed

    Liao, Jing; Zhou, Zeyuan; Huang, Li; Li, Yuyu; Li, Jingtao; Zou, Shujuan

    2016-08-12

    Estrogen has been well recognized as a key factor in the homeostasis of bone and periodontal tissue, but the way it regulates the activities of cementoblasts, the cell population maintaining cementum has not been fully understood. In this study, we examined the expression of estrogen receptor in OCCM-30 cells and the effect of 17β-estradiol (E2) on the proliferation and differentiation of OCCM-30 cells. We found that both estrogen receptor α and β were expressed in OCCM-30 cells. E2 exerted no significant influence on the proliferation of OCCM-30 cells, but inhibited the transcription and translation of BSP and Runx2 in the early phase of osteogenic induction except the BSP mRNA. Afterwards in the late phase of osteogenic induction, E2 enhanced the transcription and translation of BSP and Runx2 and promoted the calcium deposition. In addition, the expression level of Notch1, NICD and Hey1 mRNAs responded to exogenous E2 in a pattern similar to that of the osteoblastic markers. DAPT could attenuate the effect of E2 on the expression of osteoblastic markers. These findings indicated that E2 might regulate the differentiation of cementoblasts via Notch signaling. PMID:27289020

  19. Capillary electrophoresis characterization of molecularly imprinted polymer particles in fast binding with 17β-estradiol.

    PubMed

    DeMaleki, Zack; Lai, Edward P C; Dabek-Zlotorzynska, Ewa

    2010-09-01

    Molecularly imprinted polymer (MIP) submicron particles were synthesized, using either ethylene glycol dimethacrylate or trimethylolpropane trimethacrylate as a cross-linker, specifically for recognition of 17β-estradiol (E2). HPLC with fluorescence detection (HPLC-FD) results showed that 90(±5)% of E2 bound onto these particles after 2 min of incubation, and 96(±3)% after long equilibrium. The binding capacity was 8(±3) μmol/g for MIP particles prepared using ethylene glycol dimethacrylate, and 33-43(±8) μmol/g for using trimethylolpropane trimethacrylate. CE separation of MIP and non-imprinted polymer particles was successful when 50 mM borate buffer (pH 8.5) containing 0.005% w/v EOTrol™ LN in reverse polarity (-30 kV) was used. The electrophoretic mobilities of MIP and non-imprinted polymer particles, together with dynamic light scattering measurement of particle sizes, allowed for an estimation of their surface charges. Automated injection of E2 and particles in mixture set a lower limit of 20(±1) s on incubation time for the study of fast binding kinetics. The presence of E2 and bisphenol A (BPA) together tested the selectivity of MIP particles, when the two compounds competed for available binding cavities or sites. Addition of E2 after BPA confirmed E2 occupation of the specific binding cavities, via displacement of BPA. PMID:20658488

  20. 17-β-estradiol up-regulates apolipoprotein genes expression during osteoblast differentiation in vitro.

    PubMed

    Gui, Yuyan; Chu, Nan; Qiu, Xuemin; Tang, Wei; Gober, Hans-Jürgen; Li, Dajin; Wang, Ling

    2016-05-23

    Apolipoproteins are of great physiological importance and are associated with different diseases. Many independent studies of patterns of gene expression during osteoblast differentiation have been described, and some apolipoproteins have been induced during this process. 17-β-estradiol (E2) may enhance osteoblast physiological function. However, no studies have indicated whether E2 can modulate the expression of apolipoproteins during osteoblast differentiation in vitro. The aim of the current study was to observe the regulation of apolipoprotein mRNA expression by E2 during this process. Primary osteoblasts were collected from the calvaria of newborn mice and were subjected to osteoblast differentiation in vitro with serial concentrations of E2. RNA was isolated on days 0, 5, and 25 of differentiation. Real-time PCR was performed to analyze the levels of apolipoprotein mRNA. Results showed that during osteoblast differentiation all of the apolipoprotein genes were up-regulated by E2 in a dose-dependent manner. Moreover, only ApoE was strongly induced during the mineralization of cultured osteoblasts. This result suggests that ApoE might be involved in osteoblast differentiation. The hypothesis is that E2 promotes osteoblast differentiation by up-regulating ApoE gene expression, though further study is needed to confirm this hypothesis. PMID:27074899

  1. Estradiol treatment, physical activity, and muscle function in ovarian-senescent mice.

    PubMed

    Greising, Sarah M; Carey, Ryan S; Blackford, Jennifer E; Dalton, Laurin E; Kosir, Allison M; Lowe, Dawn A

    2011-08-01

    Estradiol (E(2)) treatment in young adult, ovariectomized mice increases physical activity and reverses deleterious effects on skeletal muscle. Here we test the hypothesis that E(2) treatment improves muscle function and physical activity in aged, ovarian-senescent mice. Plasma E(2) levels and vaginal cytology confirmed ovarian senescence in 20-month-old C57BL/6 mice. Mice were then randomly divided into activity groups, having access to a running wheel or not, and further into those receiving E(2) or placebo. Placebo-treated mice wheel ran more than E(2)-treated mice (P=0.03), with no difference between treatment groups in cage activities such as time spent being active and ambulation distance (P≥0.55). Soleus muscles from aged mice that wheel ran adapted by getting larger and stronger, irrespective of E(2) status (P≤0.02). Soleus muscle fatigue resistance was greater in mice treated with E(2) (P=0.02), but maximal isometric tetanic force was not affected (P≥0.79). Because E(2) treatment did not improve physical activity or overall muscle function in the aged, ovarian-senescent mice as predicted, a second study was initiated to examine E(2) treatment of young adult mice prematurely ovarian senescent from exposure to the chemical, 4-vinylcyclohexene diepoxide (VCD). Four-month-old C57BL/6 female mice were dosed with oil (control) or VCD. Vaginal cytology confirmed ovarian senescence in all mice treated with VCD 63 days after the onset of dosing, and then a subset of the VCD mice received E(2) (VCD+E(2)). Wheel running distance did not differ among control, VCD, and VCD+E(2) mice (P≥0.34). Soleus muscle concentric, isometric, and eccentric in vitro forces were greater in VCD+E(2) than in VCD mice (P<0.04), indicating beneficial estrogenic effects on muscle function. In general, aged and young mice with senescent ovaries were less responsive to E(2) treatment, in terms of physical activities and muscle function, than what has previously been shown for young

  2. Estradiol treatment, physical activity, and muscle function in ovarian-senescent mice

    PubMed Central

    Greising, Sarah M.; Carey, Ryan S.; Blackford, Jennifer E.; Dalton, Laurin E.; Kosir, Allison M.; Lowe, Dawn A.

    2011-01-01

    Estradiol (E2) treatment in young adult, ovariectomized mice increases physical activity and reverses deleterious effects on skeletal muscle. Here we test the hypothesis that E2 treatment improves muscle function and physical activity in aged, ovarian-senescent mice. Plasma E2 levels and vaginal cytology confirmed ovarian senescence in 20-month-old C57BL/6 mice. Mice were then randomly divided into activity groups, having access to a running wheel or not, and further into those receiving E2 or placebo. Placebo-treated mice wheel ran more than E2-treated mice (P=0.03), with no difference between treatment groups in cage activities such as time spent being active and ambulation distance (P≥0.55). Soleus muscles from aged mice that wheel ran adapted by getting larger and stronger, irrespective of E2 status (P≤0.02). Soleus muscle fatigue resistance was greater in mice treated with E2 (P=0.02), but maximal isometric tetanic force was not affected (P≥0.79). Because E2 treatment did not improve physical activity or overall muscle function in the aged, ovarian-senescent mice as predicted, a second study was initiated to examine E2 treatment of young adult mice prematurely ovarian senescent from exposure to the chemical, 4-vinylcyclohexene diepoxide (VCD). 4-month-old C57BL/6 female mice were dosed with oil (control) or VCD. Vaginal cytology confirmed ovarian senescence in all mice treated with VCD 63 days after the onset of dosing, and then a subset of the VCD mice received E2 (VCD+E2). Wheel running distance did not differ among control, VCD, and VCD+E2 mice (P≥0.34). Soleus muscle concentric, isometric, and eccentric in vitro forces were greater in VCD+E2 than VCD mice (P<0.04), indicating beneficial estrogenic effects on muscle function. In general, aged and young mice with senescent ovaries were less responsive to E2 treatment, in terms of physical activities and muscle function, than what has previously been shown for young, ovariectomized mice. These results

  3. TCF7L2 involvement in estradiol- and progesterone-modulated islet and hepatic glucose homeostasis

    PubMed Central

    Dong, Fengqin; Ling, Qi; Ye, Dan; Zhang, Zhe; Shu, Jing; Chen, Guoping; Fei, Yang; Li, Chengjiang

    2016-01-01

    To evaluate the role of TCF7L2, a key regulator of glucose homeostasis, in estradiol (E2) and progesterone (P4)-modulated glucose metabolism, mouse insulinoma cells (MIN6) and human liver cancer cells (hepG2 and HUH7) were treated with physiological concentrations of E2 or P4 in the up- and down-regulation of TCF7L2. Insulin/proinsulin secretion was measured in MIN6 cells, while glucose uptake and production were evaluated in liver cancer cells. E2 increased insulin/proinsulin secretion under both basal and stimulated conditions, whereas P4 increased insulin/proinsulin secretion only under glucose-stimulated conditions. An antagonistic effect, possibly concentration-dependent, of E2 and P4 on the regulation of islet glucose metabolism was observed. After E2 or P4 treatment, secretion of insulin/proinsulin was positively correlated with TCF7L2 protein expression. When TCF7L2 was silenced, E2- or P4-promoted insulin/proinsulin secretion was significantly weakened. Under glucotoxicity conditions, overexpression of TCF7L2 increased insulin secretion and processing. In liver cancer cells, E2 or P4 exposure elevated TCF7L2 expression, enhanced the activity of insulin signaling (pAKT/pGSK), reduced PEPCK expression, subsequently increased insulin-stimulated glucose uptake, and decreased glucose production. Silencing TCF7L2 eliminated effects of E2 or P4. In conclusion, TCF7L2 regulates E2- or P4-modulated islet and hepatic glucose metabolism. The results have implications for glucose homeostasis in pregnancy. PMID:27108846

  4. TCF7L2 involvement in estradiol- and progesterone-modulated islet and hepatic glucose homeostasis.

    PubMed

    Dong, Fengqin; Ling, Qi; Ye, Dan; Zhang, Zhe; Shu, Jing; Chen, Guoping; Fei, Yang; Li, Chengjiang

    2016-01-01

    To evaluate the role of TCF7L2, a key regulator of glucose homeostasis, in estradiol (E2) and progesterone (P4)-modulated glucose metabolism, mouse insulinoma cells (MIN6) and human liver cancer cells (hepG2 and HUH7) were treated with physiological concentrations of E2 or P4 in the up- and down-regulation of TCF7L2. Insulin/proinsulin secretion was measured in MIN6 cells, while glucose uptake and production were evaluated in liver cancer cells. E2 increased insulin/proinsulin secretion under both basal and stimulated conditions, whereas P4 increased insulin/proinsulin secretion only under glucose-stimulated conditions. An antagonistic effect, possibly concentration-dependent, of E2 and P4 on the regulation of islet glucose metabolism was observed. After E2 or P4 treatment, secretion of insulin/proinsulin was positively correlated with TCF7L2 protein expression. When TCF7L2 was silenced, E2- or P4-promoted insulin/proinsulin secretion was significantly weakened. Under glucotoxicity conditions, overexpression of TCF7L2 increased insulin secretion and processing. In liver cancer cells, E2 or P4 exposure elevated TCF7L2 expression, enhanced the activity of insulin signaling (pAKT/pGSK), reduced PEPCK expression, subsequently increased insulin-stimulated glucose uptake, and decreased glucose production. Silencing TCF7L2 eliminated effects of E2 or P4. In conclusion, TCF7L2 regulates E2- or P4-modulated islet and hepatic glucose metabolism. The results have implications for glucose homeostasis in pregnancy. PMID:27108846

  5. Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol

    PubMed Central

    Wu, Y W C; Du, X; van den Buuse, M; Hill, R A

    2015-01-01

    The recent use of estrogen-based therapies as adjunctive treatments for the cognitive impairments of schizophrenia has produced promising results; however the mechanism behind estrogen-based cognitive enhancement is relatively unknown. Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its expression is highly responsive to estradiol. We recently found that estradiol modulates the expression of hippocampal parvalbumin-positive GABAergic interneurons, known to regulate neuronal synchrony and cognitive function. What is unknown is whether disruptions to the aforementioned estradiol–parvalbumin pathway alter learning and memory, and whether BDNF may mediate these events. Wild-type (WT) and BDNF heterozygous (+/−) mice were ovariectomized (OVX) at 5 weeks of age and simultaneously received empty, estradiol- or progesterone-filled implants for 7 weeks. At young adulthood, mice were tested for spatial and recognition memory in the Y-maze and novel-object recognition test, respectively. Hippocampal protein expression of BDNF and GABAergic interneuron markers, including parvalbumin, were assessed. WT OVX mice show impaired performance on Y-maze and novel-object recognition test. Estradiol replacement in OVX mice prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by OVX in WT mice, while E2 replacement prevented these deficits. In contrast, BDNF+/− mice showed either no response or an opposite response to hormone manipulation in both behavioral and molecular indices. Our data suggest that BDNF status is an important biomarker for predicting responsiveness to estrogenic compounds which have emerged as promising adjunctive therapeutics for schizophrenia patients. PMID:25603414

  6. 26 CFR 1.367(e)-2 - Distributions described in section 367(e)(2).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 4 2014-04-01 2014-04-01 false Distributions described in section 367(e)(2). 1.367(e)-2 Section 1.367(e)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Effects on Corporation § 1.367(e)-2...

  7. 26 CFR 1.367(e)-2 - Distributions described in section 367(e)(2).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 4 2013-04-01 2013-04-01 false Distributions described in section 367(e)(2). 1.367(e)-2 Section 1.367(e)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Effects on Corporation § 1.367(e)-2...

  8. The Binding Constant of Estradiol to Bovine Serum Albumin: An Upper-Level Experiment Utilizing Tritium-Labeled Estradiol and Liquid Scintillation Counting

    ERIC Educational Resources Information Center

    Peihong Liang; Adhyaru, Bhavin; Pearson, Wright L.; Williams, Kathryn R.

    2006-01-01

    The experiment used [to the third power]H-labeled estradiol to determine the binding constant of estradiol to bovine serum albumin. Estradiol must complex with serum proteins for the transport in the blood stream because of its low solubility in aqueous systems and estradiol-protein binding constant, where K[subscript B] is important to understand…

  9. Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver

    PubMed Central

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; de Mirecki-Garrido, Mercedes; García, Irma; Guerra, Borja; Mateo-Díaz, Carlos; Iglesias-Gato, Diego; Díaz-Chico, Juan Carlos; Flores-Morales, Amilcar; Díaz, Mario

    2014-01-01

    17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on

  10. Anti-Inflammatory and Antimicrobial Effects of Estradiol in Bovine Mammary Epithelial Cells during Staphylococcus aureus Internalization

    PubMed Central

    Medina-Estrada, Ivan; López-Meza, Joel E.

    2016-01-01

    17β-Estradiol (E2), the predominant sexual hormone in females, is associated with the modulation of the innate immune response (IIR), and changes in its levels at parturition are related to intramammary infections, such as mastitis. In bovine mammary epithelial cells (bMECs), E2 regulates differentiation and proliferation, but its immunomodulatory functions have not been explored. Staphylococcus aureus is the predominant pathogen causing mastitis, which can persist intracellularly in bMECs. The aim of this work was to analyze whether E2 modulates the IIR of bMECs during S. aureus internalization. bMECs treated with E2 (50 pg/mL, 24 h) reduced bacteria internalization (~50%). The host receptors α5β1 and TLR2 do not participate in this reduction. However, E2 activates ERα and modulates the IIR reducing the S. aureus induced-mRNA expression of TNF-α (~50%) and IL-1β (90%). E2 also decreased the secretion of these cytokines as well as IL-6 production; however, in infected bMECs, E2 induced the secretion of IL-1β. Furthermore, E2 upregulates the expression of the antimicrobial peptides DEFB1, BNBD5, and psoriasin S100A7 (~5-, 3-, and 6-fold, resp.). In addition, E2 induced the production of antimicrobial compounds in bMEC culture medium, which, together with the modulation of the IIR, could be related to the reduction of S. aureus internalization. PMID:27034592

  11. Bleeding patterns of women using Lunelle monthly contraceptive injections (medroxyprogesterone acetate and estradiol cypionate injectable suspension) compared with those of women using Ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol triphasic) or other oral contraceptives.

    PubMed

    Garceau, R J; Wajszczuk, C J; Kaunitz, A M

    2000-12-01

    Persistent and/or unpredictable bleeding is a common reason for discontinuation of hormonal contraceptive methods. An open-label, nonrandomized, parallel, controlled study compared the efficacy, safety, and cycle control of the new, highly efficacious monthly injectable contraceptive containing 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate (E(2)C) (MPA/E(2)C) (Lunelle Monthly Contraceptive Injection) with that of the frequently used norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum 7/7/7). This report directly compares the bleeding patterns of women on MPA/E(2)C to those of women on NET/EE and untreated women. Overall, breakthrough bleeding occurred less frequently in women using MPA/E(2)C than in women using NET/EE (p < or =0.01). However, more women using MPA/E(2)C experienced amenorrhea/missed periods than those on NET/EE (p < or =0.01). In addition, the percentage of women experiencing breakthrough bleeding or amenorrhea while using other oral contraceptives is compared to that of women using MPA/E(2)C. A rapidly reversible method, MPA/E(2)C, combines the high contraceptive efficacy of surgical sterilization with the convenience of monthly administration. These data suggest that, for a large proportion of women, MPA/E(2)C offers predictability in bleeding patterns comparable to or greater than that experienced by ovulatory untreated women or those using combination oral contraceptives. PMID:11239615

  12. 26 CFR 1.367(e)-2 - Distributions described in section 367(e)(2).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Distributions described in section 367(e)(2). 1.367(e)-2 Section 1.367(e)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.367(e)-2 Distributions described in section 367(e)(2). (a) Purpose and...

  13. 17β-Estradiol Induces Sulfotransferase 2A1 Expression through Estrogen Receptor α

    PubMed Central

    Li, Wei; Ning, Miaoran; Koh, Kwi Hye; Kim, Heesue

    2014-01-01

    Sulfotransferase (SULT) 2A1 catalyzes sulfonation of drugs and endogenous compounds and plays an important role in xenobiotic metabolism as well as in the maintenance of steroid and lipid homeostasis. A recent study showed that 17β-estradiol (E2) increases the mRNA levels of SULT2A1 in human hepatocytes. Here we report the underlying molecular mechanisms. E2 enhanced SULT2A1 expression in human hepatocytes and HepG2-ER cells (HepG2 stably expressing ERα). SULT2A1 induction by E2 was abrogated by antiestrogen ICI 182,780, indicating a key role of ERα in the induction. Results from deletion and mutation assays of SULT2A1 promoter revealed three cis-elements located within –257/+140 region of SULT2A1 that are potentially responsible for the induction. Chromatin immunoprecipitation assay verified the recruitment of ERα to the promoter region. Electrophoretic mobility shift assays revealed that AP-1 proteins bind to one of the cis-elements. Interestingly, SULT2A1 promoter assays using ERα mutants revealed that the DNA-binding domain of ERα is indispensable for SULT2A1 induction by E2, suggesting that direct ERα binding to the SULT2A1 promoter is also necessary for the induction. Taken together, our results indicate that E2 enhances SULT2A1 expression by both the classical and nonclassical mechanisms of ERα action. PMID:24492894

  14. A syndrome of functional hypogonadotropic hypogonadism and sterility in a male with elevated serum estradiol.

    PubMed

    Valenta, L J

    1977-08-01

    A 36-year-old male complaining of impotence was examined. He was a genotypic male. Phenotypically, he exhibited signs of long-standing estrogen excess, such as feminine body build, gynecomastia, and varicose veins. His testes were soft and borderline small, and his prostate was small and soft. However, he had a normal-sized penis, normal male hair distribution, normal sense of smell, and normal intelligence. The laboratory data were compatible with mild hypogonadotropic hypogonadism. Serum estradiol (E2) levels were consistently elevated. The patient had azoospermia and a decreased semen volume. Inappropriately low levels of luteinizing hormone and follicle-stimulating hormone responded normally to gonadotropin-releasing hormone and clomiphene citrate. Levels of both testosterone (T) and E2 increased dramatically after prolonged clomiphene medication and in response to human chorionic gonadotropin. There was no change in either T or E2 levels in response to manipulations of the pituitary-adrenal axis. It is concluded that the elevated E2 level was responsible for suppression of gonadotropins which, in turn, caused mild hypogonadism and sterility in this patient. According to the stimulation tests, the source of the elevated E2 levels was testicular. PMID:69556

  15. Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

    PubMed Central

    Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

    2009-01-01

    While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

  16. Dissipation of 17B-estradiol in composted poultry litter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of heated composting and ambient temperature poultry waste decomposition on the fate of 17ß-estradiol and testosterone were determined in separate experiments. A mixture of poultry litter, wood chips and straw was amended with [14C]17ß-estradiol or [14C]testosterone and allowed to under...

  17. Estradiol release kinetics determine tissue response in ovariectomized rats.

    PubMed

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women. PMID:22334713

  18. Centrally Synthesized Estradiol Is a Potent Anti-Inflammatory in the Injured Zebra Finch Brain.

    PubMed

    Pedersen, Alyssa L; Nelson, Lars H; Saldanha, Colin J

    2016-05-01

    In homeotherms, injury to the brain, such as a penetrating wound, increases microglial cytokine expression and astroglial aromatase (estrogen synthase). In songbirds, injury-induced synthesis of estrogens is neuroprotective as aromatase inhibition and replacement with estradiol (E2) exacerbates and mitigates the extent of damage, respectively. The influence of induced aromatization on inflammation, however, remains unstudied. We hypothesized that injury-induced aromatization, via E2 synthesis, may affect neuroinflammation after a penetrating brain injury. Using adult zebra finches, we first documented an increase in the transcription of cytokines but not aromatase, 2 hours after the injury. Twenty-four hours after the injury, however, aromatase was dramatically elevated and cytokine expression had returned to baseline, suggesting that aromatization may be involved in the decrease of cytokines and neuroinflammation. In two subsequent experiments, we tested the influence of the inhibition of induced aromatization and aromatase inhibition with concomitant central E2 replacement on the transcription of the cytokines TNF-α, IL-1β, and IL-6, the enzyme cyclooxygenase-2 (cox-2), and its product prostaglandin E2 (PGE2). Administration of fadrozole, an aromatase inhibitor, caused a sustained elevation of IL-1β in females and TNF-α, cox-2, and PGE2 in both sexes. This prolonged neuroinflammation appears to be due to a failure to synthesize E2 locally because intracranial E2 replacement lowered IL-1β in females, TNF-α in males, and cox-2 and PGE2 in both sexes. IL-6 was not affected by injury, aromatase inhibition, or E2 replacement in either sex. These data suggest that E2 synthesis after a penetrating brain injury is a potent and inducible anti-inflammatory signal, with specific modulation of discrete cytokine signaling. PMID:26963472

  19. Determination of serum delta 5-3 beta-hydroxysteroid sulphates by combined high-performance liquid chromatography and immobilized 3 beta,17 beta-hydroxysteroid dehydrogenase in column form.

    PubMed

    Wu, M C; Takagi, K; Okuyama, S; Ohsawa, M; Masahashi, T; Narita, O; Tomoda, Y

    1986-04-25

    We studied the use of an immobilized enzyme, covalently bound to aminopropyl-CPG, in the analysis of individual delta 5-3 beta-hydroxysteroid sulphates. A microcolumn with immobilized 3 beta,17 beta-hydroxysteroid dehydrogenase was prepared and used together with high-performance liquid chromatography (HPLC). The reduced nicotinamide-adenine dinucleotide produced from delta 5-3 beta-hydroxysteroids by this enzyme was fluorimetrically determined. The immobilized enzyme was sufficiently stable for at least one month or for 180 tests when used repeatedly. A clinical trial demonstrated that this HPLC-immobilized enzyme method is superior to the soluble enzyme method, giving reliable and reproducible results at a low cost. PMID:2940254

  20. Effects of exposure to estradiol and estradiol plus testosterone on the Mongolian gerbil (Meriones unguiculatus) female prostate.

    PubMed

    Da Silva, Diego Augusto Lopes; Zanatelli, Marianna; Shinohara, Filipe Zardini; Góes, Rejane Maira; Dos Santos, Fernanda Cristina Alcântara; Vilamaior, Patricia Simone Leite; Taboga, Sebastião Roberto

    2013-05-01

    The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol + testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol + testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric-estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol + testosterone. However, these hormones were not able to re-establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER-α, ER-β, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones. PMID:23529937

  1. DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

    EPA Science Inventory

    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

    ABSTRACT
    Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

  2. Fathead minnow and bluegill sunfish life-stage responses to 17β-estradiol exposure in outdoor mesocosms

    USGS Publications Warehouse

    Elliott, Sarah M.; Kiesling, Richard L.; Jorgenson, Zachary G.; Rearick, Daniel C.; Schoenfuss, Heiko L.; Fredricks, Kim T.; Gaikowski, Mark P.

    2014-01-01

    Developmental and reproductive effects of 17β-estradiol (E2) exposure on two generations of fathead minnows and one generation of bluegill sunfish were assessed. Fish were exposed to E2 for six continuous weeks in outdoor mesocosms simulating natural lake environments. First generation fish were exposed while sexually mature. Second generation fathead minnows were exposed either during early development, sexual maturity, or both stages. Multiple endpoints were measured to assess effects of E2 exposure on fecundity and fish health and development. Plasma vitellogenin concentrations were highly variable in all fish. Differences in egg production timing for both species indicate differences in fecundity between females exposed to E2 and controls. First generation fathead minnows exposed to E2 had lower body condition factors and reduced secondary sexual characteristic expression by males. Only a difference in relative liver weight was observed in second generation fathead minnows. First generation bluegill males exposed to E2 had significantly smaller testes compared to controls. Although fish response was highly variable, results indicate that exposure to E2 at environmentally relevant concentrations affect fathead minnow and bluegill sunfish health and development, which may have implications for the health and sustainability of fish populations. Furthermore, exposure timing and environmental factors affect fish response to E2 exposure.

  3. Biodegradation of 17β-estradiol, estrone, and testosterone in stream sediments

    USGS Publications Warehouse

    Bradley, P.M.; Chapelle, F.H.; Barber, L.B.; McMahon, P.B.; Gray, J.L.; Kolpin, D.W.

    2009-01-01

    The release of endocrine-disrupting chemicals (EDCs) in wastewater treatment plant (WWTP) effluent poses a significant threat to the ecology of surface water receptors, due to impacts on the hormonal control, sexual development, reproductive success and community structure of the indigenous aquatic organisms and associated wildlife. Among the EDCs commonly observed in WWTP effluent, the natural [e.g., 17??-estradiol (E2) and estrone (E1)] and synthetic [e.g., ethynylestradiol (EE2)] estrogens are particular concerns owing to their high endocrine reactivity in both in vitro and in vivo laboratory models. These reproductive hormones have been identified as the primary cause of estrogenic effects in wastewater effluent, with greater than 95% of the estrogen receptor agonist activity in effluent attributed to this contaminant group. The potentials for in situ biodegradation of 17??-estradiol (E2), estrone (E1), and testosterone (T) were investigated in three, hydrologically-distinct, WWTP-impacted streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing sediment or water-only from locations upstream and downstream of the WWTP outfall in each system. Upstream samples provided insight into the biodegradative potential of sediment microbial communities that were not under the immediate impact of WWTP effluent. Upstream sediment from all three systems demonstrated significant mineralization of the "A" ring of E2, E1 and T, with the potential of T biodegradation consistently greater than of E2 and no systematic difference in the potentials of E2 and E1. Downstream samples provided insight into the impacts of effluent on reproductive hormone biodegradation. Significant "A" ring mineralization was also observed in downstream sediment, with the potentials for E1 and T mineralization being substantially depressed relative to upstream samples. In marked contrast, the potentials for E2

  4. 17ß-Estradiol Regulates mTORC2 Sensitivity to Rapamycin in Adaptive Cardiac Remodeling

    PubMed Central

    Kusch, Angelika; Schmidt, Maria; Gürgen, Dennis; Postpieszala, Daniel; Catar, Rusan; Hegner, Björn; Davidson, Merci M.; Mahmoodzadeh, Shokoufeh; Dragun, Duska

    2015-01-01

    Adaptive cardiac remodeling is characterized by enhanced signaling of mTORC2 downstream kinase Akt. In females, 17ß-estradiol (E2), as well as Akt contribute essentially to sex-related premenopausal cardioprotection. Pharmacologic mTOR targeting with rapamycin is increasingly used for various clinical indications, yet burdened with clinical heterogeneity in therapy responses. The drug inhibits mTORC1 and less-so mTORC2. In male rodents, rapamycin decreases maladaptive cardiac hypertrophy whereas it leads to detrimental dilative cardiomyopathy in females. We hypothesized that mTOR inhibition could interfere with 17β-estradiol (E2)-mediated sexual dimorphism and adaptive cell growth and tested responses in murine female hearts and cultured female cardiomyocytes. Under physiological in vivo conditions, rapamycin compromised mTORC2 function only in female, but not in male murine hearts. In cultured female cardiomyocytes, rapamycin impaired simultaneously IGF-1 induced activation of both mTOR signaling branches, mTORC1 and mTORC2 only in presence of E2. Use of specific estrogen receptor (ER)α- and ERβ-agonists indicated involvement of both estrogen receptors (ER) in rapamycin effects on mTORC1 and mTORC2. Classical feedback mechanisms common in tumour cells with upregulation of PI3K signaling were not involved. E2 effect on Akt-pS473 downregulation by rapamycin was independent of ERK as shown by sequential mTOR and MEK-inhibition. Furthermore, regulatory mTORC2 complex defining component rictor phosphorylation at Ser1235, known to interfere with Akt-substrate binding to mTORC2, was not altered. Functionally, rapamycin significantly reduced trophic effect of E2 on cell size. In addition, cardiomyocytes with reduced Akt-pS473 under rapamycin treatment displayed decreased SERCA2A mRNA and protein expression suggesting negative functional consequences on cardiomyocyte contractility. Rictor silencing confirmed regulation of SERCA2A expression by mTORC2 in E2-cultured

  5. The effects of high fat diet and estradiol on hypothalamic prepro-QRFP mRNA expression in female rats.

    PubMed

    Schreiber, Allyson L; Arceneaux, Kenneth P; Malbrue, Raphael A; Mouton, Alan J; Chen, Christina S; Bench, Elias M; Braymer, H Douglas; Primeaux, Stefany D

    2016-08-01

    Estradiol (E2) is a potent regulator of feeding behavior, body weight and adiposity in females. The hypothalamic neuropeptide, QRFP, is an orexigenic peptide that increases the consumption of high fat diet (HFD) in intact female rats. Therefore, the goal of the current series of studies was to elucidate the effects of E2 on the expression of hypothalamic QRFP and its receptors, QRFP-r1 and QRFP-r2, in female rats fed a HFD. Alterations in prepro-QRFP, QRFP-r1, and QRFP-r2 expression across the estrous cycle, following ovariectomy (OVX) and following estradiol benzoate (EB) treatment were assessed in the ventral medial nucleus of the hypothalamus/arcuate nucleus (VMH/ARC) and the lateral hypothalamus. In intact females, consumption of HFD increased prepro-QRFP and QRFP-r1 mRNA levels in the VMH/ARC during diestrus, a phase associated with increased food intake and low levels of E2. To assess the effects of diminished endogenous E2, rats were ovariectomized. HFD consumption and OVX increased prepro-QRFP mRNA in the VMH/ARC. Ovariectomized rats consuming HFD expressed the highest levels of QRFP. In the third experiment, all rats received EB replacement every 4days following OVX to examine the effects of E2 on QRFP expression. Prepro-QRFP, QRFP-r1 and QRFP-r2 mRNA were assessed prior to and following EB administration. EB replacement significantly reduced prepro-QRFP mRNA expression in the VMH/ARC. Overall these studies support a role for E2 in the regulation of prepro-QRFP mRNA in the VMH/ARC and suggest that E2's effects on food intake may be via a direct effect on the orexigenic peptide, QRFP. PMID:26823127

  6. Long-term effects of intraperitoneal injection of estradiol-17β on the growth and physiology of juvenile stellate sturgeon Acipenser stellatus.

    PubMed

    Falahatkar, Bahram; Poursaeid, Samaneh; Meknatkhah, Bahman; Khara, Hossein; Efatpanah, Iraj

    2014-04-01

    Juvenile stellate sturgeon Acipenser stellatus were intraperitoneally injected with estradiol-17β (E2; 0 and 5 mg/kg fish) to investigate the possibility of sex reversal and also determine the changes in biochemical parameters. Five-month-old fish (40.9 ± 1.1 g) were injected every 3-week interval during a 190-day trial. At the termination of the experiment, final weight and other growth parameters including weight gain and specific growth rate, hepatosomatic and viscerosomatic indices were not affected by repetitive injection of E2. Hematological features of E2-treated fish showed significant reductions in number of red blood cells, hemoglobin concentration, hematocrit value and mean corpuscular hemoglobin (P < 0.05), but no significant changes were observed in number of white blood cells, mean corpuscular volume and mean corpuscular hemoglobin concentration (P > 0.05). Calcium, phosphorus, glucose, triacylglycerol, cholesterol, total protein and estradiol concentrations were significantly increased in fish injected with E2 (P < 0.001). Plasma progesterone and testosterone levels were noticeably lower in fish injected with 5 mg/kg E2 rather than the control fish (P < 0.001). Histological observations of gonads showed that all fish injected with 5 mg/kg E2 apparently feminized, while 66.6 % of the control group was female. These results revealed that the injection of E2 is an effective method for feminization of stellate sturgeon without having significant inhibitory effects on growth and survival. PMID:23990284

  7. Epidermal growth factor receptor is required for estradiol-stimulated bovine satellite cell proliferation.

    PubMed

    Reiter, B C; Kamanga-Sollo, E; Pampusch, M S; White, M E; Dayton, W R

    2014-07-01

    The objective of this study was to assess the role of the epidermal growth factor receptor (EGFR) in estradiol-17β (E2)-stimulated proliferation of cultured bovine satellite cells (BSCs). Treatment of BSC cultures with AG1478 (a specific inhibitor of EGFR tyrosine kinase activity) suppresses E2-stimulated BSC proliferation (P < 0.05). In addition, E2-stimulated proliferation is completely suppressed (P < 0.05) in BSCs in which EGFR expression is silenced by treatment with EGFR small interfering RNA (siRNA). These results indicate that EGFR is required for E2 to stimulate proliferation in BSC cultures. Both AG1478 treatment and EGFR silencing also suppress proliferation stimulated by LR3-IGF-1 (an IGF1 analogue that binds normally to the insulin-like growth factor receptor (IGFR)-1 but has little or no affinity for IGF binding proteins) in cultured BSCs (P < 0.05). Even though EGFR siRNA treatment has no effect on IGFR-1β mRNA expression in cultured BSCs, IGFR-1β protein level is substantially reduced in BSCs treated with EGFR siRNA. These data suggest that EGFR silencing results in post-transcriptional modifications that result in decreased IGFR-1β protein levels. Although it is clear that functional EGFR is necessary for E2-stimulated proliferation of BSCs, the role of EGFR is not clear. Transactivation of EGFR may directly stimulate proliferation, or EGFR may function to maintain the level of IGFR-1β which is necessary for E2-stimulated proliferation. It also is possible that the role of EGFR in E2-stimulated BSC proliferation may involve both of these mechanisms. PMID:24906928

  8. 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis.

    PubMed

    Khan, Khaleque Newaz; Kitajima, Michio; Inoue, Tsuneo; Fujishita, Akira; Nakashima, Masahiro; Masuzaki, Hideaki

    2015-05-01

    Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E2) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E2 and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E2 (10(-8) mol/L) compared to nontreated Mφ. This effect of E2 was abrogated after pretreatment of cells with ICI 182720 (10(-6) mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E2 and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E2 + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E2 and LPS on promoting proinflammatory response in pelvis and growth of endometriosis. PMID:25355803

  9. Xenoestrogens challenge 17β-estradiol protective effects in colon cancer.

    PubMed

    Marino, Maria

    2014-03-15

    Several epidemiological, cellular, and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities, typical of Westernized societies, in the pathogenesis of numerous diseases including cancer. Nonetheless this information, the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing, they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages. These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol (E2) actions in that this hormone is crucial determinant of sex-related differences in anatomical, physiological, and behavioral traits which characterize male and female physiology. Moreover, E2 is also involved in carcinogenesis. The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment. Little is known about the E2 preventive signalling in colorectal cancer, although this disease is more common in men than women, the difference being more striking amongst pre-menopausal women and age-matched men. This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors (i.e., xenoestrogens) in impair these E2 actions. Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2 signals important for colorectal cancer prevention. PMID:24653796

  10. Estradiol and G1 Reduce Infarct Size and Improve Immunosuppression after Experimental Stroke

    PubMed Central

    Zhang, Bing; Subramanian, Sandhya; Dziennis, Suzan; Jia, Jia; Uchida, Masayoshi; Akiyoshi, Kozaburo; Migliati, Elton; Lewis, Anne D.; Vandenbark, Arthur A.; Offner, Halina; Hurn, Patricia D.

    2011-01-01

    Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke-induced immunosuppression has not been evaluated in female mice. To test the hypothesis that estradiol (E2) deficiency exacerbates immunosuppression after focal stroke in females, we evaluated the effect of middle cerebral artery occlusion on infarct size and peripheral and CNS immune responses in ovariectomized mice with or without sustained, controlled levels of 17-β–E2 administered by s.c. implant or the putative membrane estrogen receptor agonist, G1. Both E2- and G1-replacement decreased infarct volume and partially restored splenocyte numbers. Moreover, E2-replacement increased splenocyte proliferation in response to stimulation with anti-CD3/CD28 Abs and normalized aberrant mRNA expression for cytokines, chemokines, and chemokine receptors and percentage of CD4+CD25+FoxP3+ T regulatory cells observed in E2-deficient animals. These beneficial changes in peripheral immunity after E2 replacement were accompanied by a profound reduction in expression of the chemokine, MIP-2, and a 40-fold increased expression of CCR7 in the lesioned brain hemisphere. These results demonstrate for the first time that E2 replacement in ovariectomized female mice improves stroke-induced peripheral immunosuppression. PMID:20304826

  11. Body weight decreases induced by estradiol in female rhesus monkeys are dependent upon social status

    PubMed Central

    Michopoulos, Vasiliki; Wilson, Mark E.

    2010-01-01

    Gonadal steroids regulate appetite and thus body weight. In addition, continuous exposure to stressors negatively influences appetite through circuits likely distinct from those of gonadal steroids. The occurrence of adverse metabolic consequences due to chronic exposure to psychosocial stressors is twice as frequent in women as men, implicating a role for ovarian hormones, estradiol (E2) and progesterone (P4), in modulating stress-induced changes in appetite. Using social subordination in female macaques as a model of social stress, the current study tested the hypothesis that subordinate females would lose more weight during E2 treatment and gain less weight during P4 administration than dominant females. Because polymorphisms in the gene encoding the serotonin transporter (5HTT; SCL6A4) are known to alter responsivity to stress, we hypothesized that weight loss during E2 administration would be greatest in females with the short variant (s-variant) allele of 5HTT. Dominant females were significantly heavier than subordinate animals throughout the study, a result consistent with previous accounts of food intake when animals are fed a low-fat, high-fiber diet. Females with the s-variant 5HTT genotype weighed significantly less than l/l animals. Dominant animals lost significantly more weight than subordinate animals during E2 treatment. Administration of P4 blocked the weight-reducing effects of E2 in all females, regardless of social status. These data provide evidence that social subordination modulates the influence of ovarian steroid hormones on body weight in female rhesus monkeys independent of 5HTT genotype. Given the prosocial effects of these steroids, future studies are necessary to determine whether status differences in E2-induced weight loss are due to diminished food intake and or increases in energy expenditure and how the change in energy availability during E2 treatments relates to a female’s motivation to interact with conspecifics. PMID

  12. Estradiol Restrains Prepubertal Gonadotropin Secretion in Female Mice via Activation of ERα in Kisspeptin Neurons.

    PubMed

    Dubois, Sharon L; Wolfe, Andrew; Radovick, Sally; Boehm, Ulrich; Levine, Jon E

    2016-04-01

    Elimination of estrogen receptorα (ERα) from kisspeptin (Kiss1) neurons results in premature LH release and pubertal onset, implicating these receptors in 17β-estradiol (E2)-mediated negative feedback regulation of GnRH release during the prepubertal period. Here, we tested the dependency of prepubertal negative feedback on ERα in Kiss1 neurons. Prepubertal (postnatal d 14) and peripubertal (postnatal d 34) wild-type (WT) and Kiss1 cell-specific ERα knockout (KERαKO) female mice were sham operated or ovariectomized and treated with either vehicle- or E2-containing capsules. Plasma and tissues were collected 2 days after surgery for analysis. Ovariectomy increased LH and FSH levels, and E2 treatments completely prevented these increases in WT mice of both ages. However, in prepubertal KERαKO mice, basal LH levels were elevated vs WT, and both LH and FSH levels were not further increased by ovariectomy or affected by E2 treatment. Similarly, Kiss1 mRNA levels in the medial basal hypothalamus, which includes the arcuate nucleus, were suppressed with E2 treatment in ovariectomized prepubertal WT mice but remained unaffected by any treatment in KERαKO mice. In peripubertal KERαKO mice, basal LH and FSH levels were not elevated vs WT and were unaffected by ovariectomy or E2. In contrast to our previous findings in adult animals, these results demonstrate that suppression of gonadotropins and Kiss1 mRNA by E2 in prepubertal animals depends upon ERα activation in Kiss1 neurons. Our observations are consistent with the hypothesis that these receptors play a critical role in restraining GnRH release before the onset and completion of puberty. PMID:26824364

  13. Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines

    PubMed Central

    Moinfar, Zahra; Dambach, Hannes; Schoenebeck, Bodo; Förster, Eckart; Prochnow, Nora; Faustmann, Pedro Michael

    2016-01-01

    Introduction Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43) and estrogen receptors (ERs). Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2) on Cx43 expression in two glioma cell lines with variable native expression of Cx43. Materials and Methods F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique. Results E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells. Discussion These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma. PMID:26919293

  14. Estradiol and tamoxifen interaction at receptor sites at 37 C.

    PubMed

    Fishman, J H

    1983-09-01

    Mature rat uterine cytosol was pretreated with dextran-coated charcoal at 0 C for 2 h. This renders the subsequently formed estradiol-receptor complex thermostable at 37 C and also uncovers antiestrogen binding sites, possibly by removing an endogenous ligand. A sharp distinction is found between tamoxifen and estradiol as receptor ligands in pretreated cytosols in that tamoxifen will inhibit estradiol binding, on incubation at 37 C, only if dithiothreitol (DTT) had been included in the pretreatment solution. The presence of tamoxifen as the sole ligand in cytosol pretreated in the presence of DTT does not protect the estradiol receptor from thermal inactivation and following 37 C incubation tamoxifen is found bound exclusively to antiestrogen binding sites. Incubating the cytosol at 37 C with an equimolar mixture of estradiol and tamoxifen results in a very large increase in receptor-bound estradiol. This effect is attributed to the presence of tamoxifen complexed with antiestrogen sites. Tamoxifen in such equimolar ligand mixture binds to antiestrogen sites and is excluded from receptor sites by the estradiol, whose affinity for these sites is much greater than that of tamoxifen. PMID:6191968

  15. Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

    SciTech Connect

    Werner Fürst, Rainer; Pistek, Veronika Leopoldine; Kliem, Heike; Skurk, Thomas; Hauner, Hans; Meyer, Heinrich Herman Dietrich; Ulbrich, Susanne Ernestine

    2012-09-15

    Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

  16. Estradiol agonists inhibit human LoVo colorectal-cancer cell proliferation and migration through p53

    PubMed Central

    Hsu, Hsi-Hsien; Kuo, Wei-Wen; Ju, Da-Tong; Yeh, Yu-Lan; Tu, Chuan-Chou; Tsai, Ying-Lan; Shen, Chia-Yao; Chang, Sheng-Huang; Chung, Li-Chin; Huang, Chih-Yang

    2014-01-01

    AIM: To investigate the effects of 17β-estradiol via estrogen receptors (ER) or direct administration of ER agonists on human colorectal cancer. METHODS: LoVo cells were established from the Bioresource Collection and Research Center and cultured in phenol red-free DMEM (Sigma, United States). To investigate the effects of E2 and/or ER selective agonists on cellular proliferation, LoVo colorectal cells were treated with E2 or ER-selective agonists for 24 h and 48 h and subjected to the MTT (Sigma) assay to find the concentration. And investigate the effects of E2 and/or ER selective agonists on cell used western immunoblotting to find out the diversification of signaling pathways. In order to observe motility and migration the wound healing assay and a transwell chamber (Neuro Probe) plate were tased. For a quantitative measure, we counted the number of migrating cells to the wound area post-wounding for 24 h. We further examined the cellular migration-regulating factors urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and matrix metalloproteinase (MMP)-9 in human LoVo cells so gelatin zymography that we used and gelatinolytic activity was visualized by Coomassie blue staining. And these results are presented as means ± SE, and statistical comparisons were made using Student’s t-test. RESULTS: The structure was first compared with E2 and ER agonists. We then treated the LoVo cells with E2 and ER agonists (10-8 mol/L) for 24 h and 48 h and subsequently measured the cell viability using MTT assay. Our results showed that treatment with 17β-estradiol and/or ER agonists in human LoVo colorectal cancer cells activated p53 and then up-regulated p21 and p27 protein levels, subsequently inhibiting the downstream target gene, cyclin D1, which regulates cell proliferation. Taken together, our findings demonstrate the anti-tumorigenesis effects of 17β-estradiol and/or ER agonists and suggest that these compounds may prove to be a

  17. RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17β-estradiol and casein

    PubMed Central

    Ronis, Martin J.; Gomez-Acevedo, Horacio; Blackburn, Michael L.; Cleves, Mario A.; Singhal, Rohit; Badger, Thomas M.

    2016-01-01

    This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 μg/kg/d estradiol and relative to rats treated with estradiol and also fed soy protein isolate. Complete raw data files were deposited in the gene Expression Omnibus (GEO) at NCBI (http:/www.ncbi.nlm.nih.gov.geo/) under the GEO accession number GEO: GSE69819. Data presented here incudes a summary of the differential expression analysis with top 30 genes up- and down-regulated by soy protein isolate (SPI), estradiol (E2) and SPI+E2. Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article “Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats” Ronis et al. (2016) [1]. PMID:27182546

  18. RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17β-estradiol and casein.

    PubMed

    Ronis, Martin J; Gomez-Acevedo, Horacio; Blackburn, Michael L; Cleves, Mario A; Singhal, Rohit; Badger, Thomas M

    2016-06-01

    This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 μg/kg/d estradiol and relative to rats treated with estradiol and also fed soy protein isolate. Complete raw data files were deposited in the gene Expression Omnibus (GEO) at NCBI (http:/www.ncbi.nlm.nih.gov.geo/) under the GEO accession number GEO: GSE69819. Data presented here incudes a summary of the differential expression analysis with top 30 genes up- and down-regulated by soy protein isolate (SPI), estradiol (E2) and SPI+E2. Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article "Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats" Ronis et al. (2016) [1]. PMID:27182546

  19. Pattern recognition of estradiol, testosterone and dihydrotestosterone in children's saliva samples using stochastic microsensors

    PubMed Central

    Staden, Raluca-Ioana Stefan-van; Gugoaşă, Livia Alexandra; Calenic, Bogdan; Legler, Juliette

    2014-01-01

    Stochastic microsensors based on diamond paste and three types of electroactive materials (maltodextrin (MD), α-cyclodextrin (α-CD) and 5,10,15,20-tetraphenyl-21H,23H porphyrin (P)) were developed for the assay of estradiol (E2), testosterone (T2) and dihydrotestosterone (DHT) in children's saliva. The main advantage of utilization of such tools is the possibility to identify and quantify all three hormones within minutes in small volumes of childen's saliva. The limits of quantification obtained for DHT, T2, and E2 (1 fmol/L for DHT, 1 pmol/L for T2, and 66 fmol/L for E2) determined using the proposed tools allows the utilization of these new methods with high reliability for the screening of saliva samples from children. This new method proposed for the assay of the three hormones overcomes the limitations (regarding limits of determination) of ELISA method which is the standard method used in clinical laboratories for the assay of DHT, T2, and E2 in saliva samples. The main feature of its utilization for children's saliva is to identify earlier problems related to early puberty and obesity. PMID:24993181

  20. CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer.

    PubMed

    Thompson, Deborah J; O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Michailidou, Kyriaki; Tyrer, Jonathan P; Maranian, Mel J; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Zhao, Hui; Depreeuw, Jeroen; Schrauwen, Stefanie; Amant, Frederic; Goode, Ellen L; Fridley, Brooke L; Dowdy, Sean C; Winham, Stacey J; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Carvajal-Carmona, Luis; Tham, Emma; Liu, Tao; Mints, Miriam; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth G; Montgomery, Grant W; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Hopper, John L; Traficante, Nadia; Ruebner, Matthias; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Lambrechts, Diether; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Bolla, Manjeet K; Wang, Qin; Bojesen, Stig E; Shah, Mitul; Luben, Robert; Khaw, Kay-Tee; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Dowsett, Mitch; Easton, Douglas F; Spurdle, Amanda B

    2016-02-01

    Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction. PMID:26574572

  1. Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk.

    PubMed

    Del Pup, Lino; Berretta, Massimiliano; Di Francia, Raffaele; Cavaliere, Carla; Di Napoli, Marilena; Facchini, Gaetano; Fiorica, Francesco; Mileto, Mario; Schindler, Adolf E

    2014-08-01

    Combined hormonal contraceptives (CHCs) contain estrogen and progestin, which can stimulate estrogen-sensitive and/or progesterone-sensitive breast cancer growth. Until recently, ethinylestradiol had been almost the only estrogen used for decades, and its dose has been greatly reduced over time. The first generations of birth control pills contained approximately five times more estrogen and four times more progestin than the latest contraceptives. Newer CHCs also contain steroids that more closely mimic the physiological estradiol (E2) and progesterone effects. The newer CHC formulations are thus expected to have less influence on the breast, although it is very difficult to demonstrate any difference among the recent available preparations in human studies. Recently, nomegestrol acetate (NOMAC), a neutral, nonandrogenic, progesterone-like profile progestin, has become available in combination with the 'natural' estrogen, E2. According to the literature, NOMAC/E2 is expected to have either a lesser stimulating effect or a neutral effect on estrogen-sensitive breast cancers. We performed an analysis of the available studies and a bibliographical review. The endocrine and metabolic effects of NOMAC/E2 formulation might lead to a lesser breast tissue stimulation. The data reported, confirmed through clinical studies, should be considered when choosing a hormonal contraceptive, especially when breast stimulation is a concern. PMID:24346139

  2. Pattern recognition of estradiol, testosterone and dihydrotestosterone in children's saliva samples using stochastic microsensors

    NASA Astrophysics Data System (ADS)

    Staden, Raluca-Ioana Stefan-Van; Gugoaşă, Livia Alexandra; Calenic, Bogdan; Legler, Juliette

    2014-07-01

    Stochastic microsensors based on diamond paste and three types of electroactive materials (maltodextrin (MD), α-cyclodextrin (α-CD) and 5,10,15,20-tetraphenyl-21H,23H porphyrin (P)) were developed for the assay of estradiol (E2), testosterone (T2) and dihydrotestosterone (DHT) in children's saliva. The main advantage of utilization of such tools is the possibility to identify and quantify all three hormones within minutes in small volumes of childen's saliva. The limits of quantification obtained for DHT, T2, and E2 (1 fmol/L for DHT, 1 pmol/L for T2, and 66 fmol/L for E2) determined using the proposed tools allows the utilization of these new methods with high reliability for the screening of saliva samples from children. This new method proposed for the assay of the three hormones overcomes the limitations (regarding limits of determination) of ELISA method which is the standard method used in clinical laboratories for the assay of DHT, T2, and E2 in saliva samples. The main feature of its utilization for children's saliva is to identify earlier problems related to early puberty and obesity.

  3. Simultaneous determination of environmental estrogens: Diethylstilbestrol and estradiol using Cu-BTC frameworks-sensitized electrode.

    PubMed

    Ji, Liudi; Wang, Yanying; Wu, Kangbing; Zhang, Weikang

    2016-10-01

    It is quite important to monitor environmental estrogens in a rapid, sensitive, simple and cost-effective manner due to their wide existence and high toxicity. Using 1,3,5-Benzenetricarboxylic acid (H3BTC) as the ligand and copper ions as the center, Cu-BTC frameworks with surface area of 654.6m(2)/g were prepared, and then used to construct a novel electrochemical sensing platform for diethylstilbestrol (DES) and estradiol (E2). On the surface of Cu-BTC frameworks, two oxidation waves at 0.26V and 0.45V are observed for DES and E2, and the oxidation signals are improved greatly. The prepared Cu-BTC frameworks not only enhance the accumulation efficiency of DES and E2, but also improve their electron transfer ability. The influences of pH value, modification amount of Cu-BTC and accumulation time were examined. As a result, a highly-sensitive, rapid and convenient electrochemical method was developed for the simultaneous determination of DES and E2, with detection limit of 2.7nM and 1.1nM. The practical applications manifest this new sensing system is accurate and feasible. PMID:27474301

  4. Ovarian Hormones and Borderline Personality Disorder Features: Preliminary Evidence for Interactive Effects of Estradiol and Progesterone

    PubMed Central

    Eisenlohr-Moul, Tory A.; DeWall, C. Nathan; Girdler, Susan S.; Segerstrom, Suzanne C.

    2015-01-01

    Cyclical fluctuations in the ovarian hormones 17β-estradiol (E2; estrogen) and progesterone (P4) predict emotions, cognitive processes, and behaviors relevant to Borderline Personality Disorder (BPD); however, there are individual differences in sensitivity to normal hormone shifts. This study examined associations of naturally occurring hormonal changes with concurrent BPD feature expression. Forty women sampled for a flat distribution of the PAI-BOR (n=10 where T<50, n=10 where 5070) provided 4 weekly saliva samples and psychological assessments. Across most outcomes (e.g., BPD features, felt rejection, anger rumination, negative urgency) P4 deviation (from one’s person mean) moderated the effect of current E2 deviation (from one’s person mean) among women high (+1 SD) in trait BPD features such that E2 deviation was negatively associated with symptoms only when P4 was higher-than-usual. Cyclical hormone changes (e.g., higher P4 in the luteal phase; E2 fluctuations at ovulation and in the luteal phase) may impact BPD feature expression among at-risk women. PMID:25837710

  5. CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer

    PubMed Central

    Thompson, Deborah J; O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Michailidou, Kyriaki; Tyrer, Jonathan P; Maranian, Mel J; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Zhao, Hui; Depreeuw, Jeroen; Schrauwen, Stefanie; Amant, Frederic; Goode, Ellen L; Fridley, Brooke L; Dowdy, Sean C; Winham, Stacey J; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Carvajal-Carmona, Luis; Tham, Emma; Liu, Tao; Mints, Miriam; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth G; Montgomery, Grant W; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Hopper, John L; Traficante, Nadia; Ruebner, Matthias; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Lambrechts, Diether; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Bolla, Manjeet K; Wang, Qin; Bojesen, Stig E; Shah, Mitul; Luben, Robert; Khaw, Kay-Tee; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Dowsett, Mitch; Easton, Douglas F; Spurdle, Amanda B

    2016-01-01

    Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10−11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10−8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11–1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03–1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction. PMID:26574572

  6. Ovarian hormones and borderline personality disorder features: Preliminary evidence for interactive effects of estradiol and progesterone.

    PubMed

    Eisenlohr-Moul, Tory A; DeWall, C Nathan; Girdler, Susan S; Segerstrom, Suzanne C

    2015-07-01

    Cyclical fluctuations in the ovarian hormones 17β-estradiol (E2; estrogen) and progesterone (P4) predict emotions, cognitive processes, and behaviors relevant to Borderline Personality Disorder (BPD); however, there are individual differences in sensitivity to normal hormone shifts. This study examined associations of naturally occurring hormonal changes with concurrent BPD feature expression. Forty women sampled for a flat distribution of the PAI-BOR (n=10 where T<50, n=10 where 5070) provided four weekly saliva samples and psychological assessments. Across most outcomes (e.g., BPD features, felt rejection, anger rumination, negative urgency) P4 deviation (from one's person mean) moderated the effect of current E2 deviation (from one's person mean) among women high (+1 SD) in trait BPD features such that E2 deviation was negatively associated with symptoms only when P4 was higher-than-usual. Cyclical hormone changes (e.g., higher P4 in the luteal phase; E2 fluctuations at ovulation and in the luteal phase) may impact BPD feature expression among at-risk women. PMID:25837710

  7. Evolutionary variation of papillomavirus E2 protein and E2 binding sites

    PubMed Central

    2011-01-01

    Background In an effort to identify the evolutionary changes relevant to E2 function, within and between papillomavirus genera, we evaluated the E2 binding sites (E2BS)s inside the long-control-region (LCR), and throughout the genomes. We identified E2BSs in the six largest genera of papillomaviruses: Alpha, Beta, Gamma, Delta, Lambda, and Xi-papillomaviruses (128 genomes), by comparing the sequences with a model consensus we created from known functional E2BSs (HPV16, HPV18, BPV1). We analyzed the sequence conservation and nucleotide content of the 4-nucleotide spacer within E2BSs. We determined that there is a statistically significant difference in GC content of the four-nucleotide E2BS spacer, between Alpha and Delta-papillomaviruses, as compared to each of the other groups. Additionally, we performed multiple alignments of E2 protein sequences using members of each genus in order to identify evolutionary changes within the E2 protein. Results When a phylogenetic tree was generated from E2 amino acid sequences, it was discovered that the alpha-papillomavirus genera segregates into two distinct subgroups (α1 and α2). When these subgroups were individually analyzed, it was determined that the subgroup α1 consensus E2BS favored a spacer of AAAA, whereas subgroup α2 favored the opposite orientation of the same spacer; TTTT. This observation suggests that these conserved inverted linkers could have functional importance. PMID:21806797

  8. Alterations in opioid parameters in the hypothalamus of rats with estradiol-induced polycystic ovarian disease

    SciTech Connect

    Desjardins, G.C.; Beaudet, A.; Brawer, J.R. )

    1990-12-01

    The distribution and density of selectively labeled mu-, delta-, and kappa-opioid binding sites were examined by in vitro radioautography in the hypothalamus of normal, estradiol valerate (EV)-injected, and estradiol (E2)-implanted female rats. Hypothalamic beta-endorphin concentration was also examined by RIA in these three groups of animals. Quantitative analysis of film radioautographs demonstrated a selective increase in mu-opioid binding in the medial preoptic area of EV-treated, but not of E2-implanted rats. However, both these estrogenized groups exhibited a reduction in the density of delta-opioid binding in the suprachiasmatic nucleus. Statistically significant changes between either estrogenized groups were not observed for kappa-opioid binding. Results on the hypothalamic concentration of beta-endorphin indicated a marked reduction in EV-injected animals with respect to controls. In contrast, the E2-implanted animals exhibited beta-endorphin concentrations similar to controls. The present results confirm the increase in opioid receptor binding previously reported in the hypothalamus of EV-treated rats and further demonstrate that this increase is confined to the medial preoptic area and exclusively concerns mu-opioid receptors. The concomitant reduction in beta-endorphin levels observed in the same group of animals suggests that the observed increase in mu-opioid binding could reflect a chronic up-regulation of the receptor in response to compromised beta-endorphin input. Given the restriction of this effect to the site of origin of LHRH neurons and the demonstrated inhibitory role of opioids on LHRH release, it is tempting to postulate that such up-regulation could lead to the suppression of the plasma LH pattern that characterizes polycystic ovarian disease in the EV-treated rat.

  9. Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats.

    PubMed

    Ronis, Martin J; Gomez-Acevedo, Horacio; Blackburn, Michael L; Cleves, Mario A; Singhal, Rohit; Badger, Thomas M

    2016-04-15

    There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens. PMID:26945725

  10. 17β-Estradiol influent and effluent concentrations in wastewater: demographic influences and the risk to environmental health.

    PubMed

    Heffron, K T; Gaines, K F; Novak, J M; Canam, T; Collard, D A

    2016-05-01

    The concentration of 17β-estradiol (E2) was measured through stages of wastewater treatment at a central Illinois wastewater treatment plant (WWTP). E2 concentration was quantified using a competitive enzyme-linked immunosorbent assay (ELISA). The concentration of E2 was compared with demographic effects of a university; physical parameters of the wastewater (dissolved oxygen, pH, and temperature); and daily influent and effluent flow rates. Effluent concentrations ranged from 0 to 25.3 ng L(-1) with an average discharge of 3.6 ng L(-1). E2 concentration was shown to increase at the start of each university semester; however, this trend was not observed in the summer sessions. Low influent and effluent flow rates, which correspond to increased water retention time at the WWTP, were correlated to increased removal efficiency of E2, where low flow was linked to 91 % removal efficiency and high flow with 58 % removal efficiency. This study concludes that E2 was being discharged at concentrations known to cause ecological risk, and that the demographic changes in a university student body had a significant effect on E2 concentration throughout the treatment process. PMID:27075313

  11. Estradiol, TGF-β1 and hypoxia promote breast cancer stemness and EMT-mediated breast cancer migration

    PubMed Central

    PARK, SEONG-JOON; KIM, JOONG-GOOK; KIM, NAM DEUK; YANG, KWANGMO; SHIM, JAE WOONG; HEO, KYU

    2016-01-01

    Breast cancer is one of the most common cancer types among women, acting as a distinct cause of mortality, and has a high incidence of recurrence. External stimuli, including 17β-estradiol (E2), transforming growth factor (TGF)-β1 and hypoxia, may be important in breast cancer growth and metastasis. However, the effects of these stimuli on breast cancer stem cell (CSC) regulation have not been fully investigated. In the present study, the proportion of cluster of differentiation (CD)44+/CD24−/low cells increased following treatment with E2, TGF-β1 and hypoxia in MCF-7 cells. The expression of CSC markers, including SOX2, KLF4 and ABCG2, was upregulated continually by E2, TGF-β1 and hypoxia. In addition, the expression levels of epithelial-mesenchymal transition-associated factors increased following treatment with E2, TGF-β1 and hypoxia. Therefore, the migration ability of E2-, TGF-β1- and hypoxia-treated MCF-7 cells was enhanced compared with control cells. In addition, the enhancement of apoptosis by 5-flurouracil or radiation was abolished following treatment with E2, TGF-β1 and hypoxia. These results indicate that E2, TGF-β1 and hypoxia are important for regulating breast CSCs, and that the modulation of the microenvironment in tumors may improve the efficiency of breast cancer therapy. PMID:26998096

  12. Microalgae cultivation on wastewater digestate: β-estradiol and 17α-ethynylestradiol degradation and transformation products identification.

    PubMed

    Hom-Diaz, Andrea; Llorca, Marta; Rodríguez-Mozaz, Sara; Vicent, Teresa; Barceló, Damià; Blánquez, Paqui

    2015-05-15

    Selenastrum capricornutum and Chlamydomonas reinhardtii were tested for possible biodegradation of the hormones β-estradiol (E2) and 17α-ethinylestradiol (EE2) when cultured in anaerobic digester centrate (ADC). Neither ADC nor the hormones had a negative or toxic effect on the microalgae growth but enhanced it. E2 and EE2 biodegradation was evaluated under different culture conditions. After 7 days of treatment, between 88% and 100% of E2 was removed by S. capricornutum. Overall, 42 and 54% of the removal was attributed to biodegradation processes, while the rest of the removal was due to adsorption onto the algae biomass. For EE2, removals between 60 and 95%, depending on the culture conditions, were achieved, with biodegradation accounting for 20-54% of the removal. E2 and EE2 were completely removed in the experiments performed with C. reinhardtii, except for EE2 in the presence of ADC, which decreased to 76%. However, C. reinhardtii presented higher adsorption percentages: 86% and 71% after 7 days for E2 and EE2, respectively. Transformation products (TPs) of E2 and EE2 generated in each treatment were also monitored. Two TPs were tentatively proposed as degradation products of E2 and EE2 by the algae. In addition, the removal of 26 endocrine disruptors and related pollutants present in the centrate was also monitored: bisphenol A was completely removed, whereas tris(2-butoxyethyl)phosphate was only removed in the absence of hormones. PMID:25785785

  13. High Maternal Serum Estradiol Levels Induce Dyslipidemia in Human Newborns via a Hepatic HMGCR Estrogen Response Element

    PubMed Central

    Meng, Ye; Lv, Ping-Ping; Ding, Guo-Lian; Yu, Tian-Tian; Liu, Ye; Shen, Yan; Hu, Xiao-Ling; Lin, Xian-Hua; Tian, Shen; Lv, Min; Song, Yang; Guo, Meng-Xi; Ke, Zhang-Hong; Xu, Hong; Sheng, Jian-Zhong; Shi, Feng-Tao; Huang, He-Feng

    2015-01-01

    While the intrauterine environment is essential for the health of offspring, the impact of high maternal serum estradiol (E2) on lipid metabolism in offspring and the mechanisms are unknown. We found that ovarian stimulation (OS) could result in high E2 levels in women throughout pregnancy. Strikingly, their newborns showed elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels that were positively related with E2 in newborns. In vitro, E2 dose-dependently stimulated TC and LDL-C secretion, and increased expression of the cholesterol synthesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in HepG2 cells and mouse fetal hepatocytes. In vivo, high maternal E2 was detected and fetal livers also showed significantly higher HMGCR expression in an OS mouse model. Notably, an estrogen response element (ERE) was identified in the HMGCR promoter, indicating that high maternal serum E2 could up-regulate HMGCR expression in fetal hepatocytes via an ERE that in turn induces elevated levels of TC and LDL-C in offspring. Conclusion: OS can induce a high maternal E2 environment, which up-regulates HMGCR expression in fetal hepatocytes via an ERE in the promoter, and induces elevated levels of TC and LDL-C in newborns that may be related to increased risk of metabolic disease in adulthood. PMID:25961186

  14. Hindbrain Administration of Estradiol Inhibits Feeding and Activates Estrogen Receptor-α-Expressing Cells in the Nucleus Tractus Solitarius of Ovariectomized Rats

    PubMed Central

    Thammacharoen, Sumpun; Lutz, Thomas A.; Geary, Nori; Asarian, Lori

    2008-01-01

    17β-Estradiol (E2), acting via estrogen receptor (ER)-α, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERα-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 μg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of 3H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERα-positive cells in the cNTS after ip injection of 4 μg/kg CCK-8. We conclude that E2, acting via ERα in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding. PMID:18096668

  15. Bisphenol A and 17β-Estradiol Promote Arrhythmia in the Female Heart via Alteration of Calcium Handling

    PubMed Central

    Yan, Sujuan; Chen, Yamei; Dong, Min; Song, Weizhong; Belcher, Scott M.; Wang, Hong-Sheng

    2011-01-01

    Background There is wide-spread human exposure to bisphenol A (BPA), a ubiquitous estrogenic endocrine disruptor that has been implicated as having potentially harmful effects on human heart health. Higher urine BPA concentrations have been shown to be associated with cardiovascular diseases in humans. However, neither the nature nor the mechanism(s) of BPA action on the heart are understood. Methodology/Principal Findings The rapid (<7 min) effects of BPA and 17β-estradiol (E2) in the heart and ventricular myocytes from rodents were investigated in the present study. In isolated ventricular myocytes from young adult females, but not males, physiological concentrations of BPA or E2 (10−9 M) rapidly induced arrhythmogenic triggered activities. The effects of BPA were particularly pronounced when combined with estradiol. Under conditions of catecholamine stimulation, E2 and BPA promoted ventricular arrhythmias in female, but not male, hearts. The cellular mechanism of the female-specific pro-arrhythmic effects of BPA and E2 were investigated. Exposure to E2 and/or BPA rapidly altered myocyte Ca2+ handling; in particular, estrogens markedly increased sarcoplasmic reticulum (SR) Ca2+ leak, and increased SR Ca2+ load. Ryanodine (10−7 M) inhibition of SR Ca2+ leak suppressed estrogen-induced triggered activities. The rapid response of female myocytes to estrogens was abolished in an estrogen receptor (ER) β knockout mouse model. Conclusions/Significance Physiologically-relevant concentrations of BPA and E2 promote arrhythmias in a female-specific manner in rat hearts; the pro-arrhythmic actions of estrogens are mediated by ERβ-signaling through alterations of myocyte Ca2+ handling, particularly increases in SR Ca2+ leak. Our study provides the first experimental evidence suggesting that exposure to estrogenic endocrine disrupting chemicals and the unique sensitivity of female hearts to estrogens may play a role in arrhythmogenesis in the female heart. PMID

  16. 3D model of amphioxus steroid receptor complexed with estradiol

    SciTech Connect

    Baker, Michael E.; Chang, David J.

    2009-08-28

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  17. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  18. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  19. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  20. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  1. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  2. Puerarin Suppresses Invasion and Vascularization of Endometriosis Tissue Stimulated by 17β-Estradiol

    PubMed Central

    Han, Jie; Zai, Dongxia; Ji, Mei; Cheng, Wen; Xu, Ling; Yang, Luxi; He, Miaoxia; Ni, Jian; Cai, Zailong; Yu, Chaoqin

    2011-01-01

    Background Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17β-estradiol (E2) and producing an anti-estrogenic effect. This study was to investigate whether puerarin could suppress the invasion and vascularization of E2-stimulated endometriotic tissue. Methodology/Principal Findings The endometriotic stromal cells (ESCs) were successfully established and their invasive ability under different treatments was assessed through a Transwell Assay. Simultaneously, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by western blotting. Vascularization of endometriotic tissues was observed by chicken chorioallantoic membrane (CAM) assay. The staining of MMP-9, intercellular adhesion molecule 1 (ICAM-1), TIMP-1, and vascular endothelial growth factor (VEGF) in grafted endometriotic tissues was examined using immunohistochemistry analysis. The purity of ESCs in isolated cells was >95%, as determined by the fluoroimmunoassay of vimentin. E2 (10−8 mol/L) promoted the invasiveness of ESCs by increasing MMP-9 accumulation and decreasing TIMP-1 accumulation. Interestingly, puerarin (10−9 mol/L) significantly reversed these effects (P<0.01). The CAM assay indicated that puerarin (10−9 mol/L) also inhibited the angiopoiesis of endometriotic tissue stimulated by the E2 (10−8 mol/L) treatment (P<0.05). Accordingly, immunohistochemistry showed that the accumulation of MMP-9, ICAM-1, and VEGF was reduced whereas that of TIMP-1 increased in the combination treatment group compared with the E2 treatment group. Conclusions/Significance This study demonstrated that puerarin could suppress the tissue invasion by ESCs and the vascularization of ectopic endometrial tissues stimulated by E2, suggesting that puerarin may be a potential drug for the treatment of endometriosis. PMID:21949833

  3. Effect of low doses of estradiol and tamoxifen on breast cancer cell karyotypes.

    PubMed

    Rondón-Lagos, Milena; Rangel, Nelson; Di Cantogno, Ludovica Verdun; Annaratone, Laura; Castellano, Isabella; Russo, Rosalia; Manetta, Tilde; Marchiò, Caterina; Sapino, Anna

    2016-08-01

    Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. The nature of E2- or TAM-induced chromosomal damage has been explored using relatively high concentrations of these agents, and only some numerical aberrations and chromosomal breaks have been analyzed. This study aimed to determine the effects of low doses of E2 and TAM (10(&8 )mol L(&1) and 10(&6 )mol L(&1) respectively) on karyotypes of MCF7, T47D, BT474, and SKBR3 breast cancer cells by comparing the results of conventional karyotyping and multi-FISH painting with cell proliferation. Estrogen receptor (ER)-positive (+) cells showed an increase in cell proliferation after E2 treatment (MCF7, T47D, and BT474) and a decrease after TAM treatment (MCF7 and T47D), whereas in ER& cells (SKBR3), no alterations in cell proliferation were observed, except for a small increase at 96 h. Karyotypes of both ER+ and ER& breast cancer cells increased in complexity after treatments with E2 and TAM leading to specific chromosomal abnormalities, some of which were consistent throughout the treatment duration. This genotoxic effect was higher in HER2+ cells. The ER&/HER2+ SKBR3 cells were found to be sensitive to TAM, exhibiting an increase in chromosomal aberrations. These in vitro results provide insights into the potential role of low doses of E2 and TAM in inducing chromosomal rearrangements in breast cancer cells. PMID:27357940

  4. Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus.

    PubMed

    Rabaglino, Maria Belen; Richards, Elaine; Denslow, Nancy; Keller-Wood, Maureen; Wood, Charles E

    2012-07-01

    In fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40-100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E(2)S) action in the ovine fetal brain. The hypothesis was that E(2)S stimulates genes involved in the neuroendocrine pathways that direct or facilitate fetal development at the end of gestation. Four sets of chronically catheterized ovine twin fetuses were studied (gestational age: 120-127 days gestation) with one infused with E(2)S intracerebroventricularly (1 mg/day) and the other remaining untreated (control). After euthanasia, mRNA samples were extracted from fetal brains. Only hypothalamic samples were employed for this study given the important function of this brain region in the control of the hypothalamus-pituitary-adrenal axis. Microarray analysis was performed following the Agilent protocol for one-color 8 × 15 microarrays, designed for Ovis aries. A total of 363 known genes were significantly upregulated by the E(2)S treatment (P < 0.05). Network and enrichment analyses were performed using the Cytoscape/Bingo software, and the results validated by quantitative real-time PCR. The main overrepresented biological processes resulting from this analysis were feeding behavior, hypoxia response, and transforming growth factor signaling. Notably, the genes involved in the feeding behavior (neuropeptide Y and agouti-related protein) were the most strongly induced by the E(2)S treatment. In conclusion, E(2)S may be an important component of the mechanism for activating orexigenic, hypoxia responsiveness and neuroprotective pathways in the lamb as it approaches postnatal life. PMID:22570439

  5. Relationship between Estradiol and Progesterone Concentrations and Cognitive Performance in Normally Cycling Female Cynomolgus Monkeys

    PubMed Central

    Kromrey, Sarah A.; Czoty, Paul W.; Nader, Michael A.

    2015-01-01

    Preclinical studies have demonstrated that cognitive function may be influenced by estradiol (E2) and progesterone (P4) concentrations, although few cognition studies involve normally cycling females. The present study examined cognitive performance in normally cycling female cynomolgus macaques (n=14), a species with similarities to humans in brain organization and a nearly identical menstrual cycle to women. Initial assessments compared cognitive measures to circulating concentrations of E2 and P4 (n=12). Once a relationship was characterized between hormones and cognitive performance, the menstrual cycle was divided into 4 distinct phases: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL), verified by the onset of menses and serum concentrations of E2 and P4. Concentrations of E2 were highest during the LF phase and P4 concentrations peaked during the EL phase. All monkeys were trained on two cognitive tasks: reversal learning, involving simple discrimination (SD) and reversal (SDR), which measured associative learning and behavioral flexibility, respectively (n=3–4 per phase) and a delayed match-to-sample (DMS) task which assessed working memory (n=11). P4 concentrations were positively correlated with number of trials and errors during SD performance, but not during acquisition of the SDR task or maintenance of the reversal-learning task. Across the menstrual cycle, significantly fewer errors were made in the SDR task during the LF phase, when E2 concentrations were high and P4 concentrations low. Working memory, assessed with the DMS task, was not consistently altered based on previously characterized menstrual cycle phases. These findings demonstrate a relationship between P4, E2 and cognitive performance in normally cycling cynomolgus monkeys that is task dependent. Knowledge of these interactions may lead to a better understanding of sex-specific cognitive performance. PMID:25921587

  6. Cytochrome P450 1A2 Metabolizes 17β-Estradiol to Suppress Hepatocellular Carcinoma

    PubMed Central

    Ren, Jianwai; Chen, George G.; Liu, Yi; Su, Xianwei; Hu, Baoguang; Leung, Billy C. S.; Wang, Y.; Ho, Rocky L. K.; Yang, Shengli; Lu, Gang; Lee, C. G.; Lai, Paul B. S.

    2016-01-01

    Hepatocellular carcinoma (HCC) occurs more frequently in men than in women. It is commonly agreed that estrogen plays important roles in suppressing HCC development, however, the underlying mechanism remains largely unknown. Since estrogen is mainly metabolized in liver and its metabolites affect cell proliferation, we sought to investigate if the liver-specific cytochrome P450 1A2 (CYP1A2) mediated the inhibitory effect of estrogen on HCC. In this study, the expression of estrogen-metabolizing enzyme CYP1A2 was determined in HCC tissues and cell lines. Cell proliferation and apoptosis were assessed in cells with or without CYP1A2 overexpression. The levels of 17β-estradiol (E2) and its metabolite 2-methoxyestradiol (2-ME) were determined. A xenograft tumor model in mice was established to confirm the findings. It was found that CYP1A2 expression was greatly repressed in HCC. E2 suppressed HCC cell proliferation and xenograft tumor development by inducing apoptosis. The inhibitory effect was significantly enhanced in cells with CYP1A2 overexpression, which effectively conversed E2 to the cytotoxic 2-ME. E2 in combination with sorafenib showed an additive effect on HCC. The anti-HCC effect of E2 was not associated with estrogen receptors ERα and ERβ as well as tumor suppressor P53 but enhanced by the approved anti-HCC drug sorafenib. In addition, HDAC inhibitors greatly induced CYP1A2 promoter activities in cancer cells, especially liver cancer cells, but not in non-tumorigenic cells. Collectively, CYP1A2 metabolizes E2 to generate the potent anti-tumor agent 2-ME in HCC. The reduction of CYP1A2 significantly disrupts this metabolic pathway, contributing the progression and growth of HCC and the gender disparity of this malignancy. PMID:27093553

  7. Cytochrome P450 1A2 Metabolizes 17β-Estradiol to Suppress Hepatocellular Carcinoma.

    PubMed

    Ren, Jianwai; Chen, George G; Liu, Yi; Su, Xianwei; Hu, Baoguang; Leung, Billy C S; Wang, Y; Ho, Rocky L K; Yang, Shengli; Lu, Gang; Lee, C G; Lai, Paul B S

    2016-01-01

    Hepatocellular carcinoma (HCC) occurs more frequently in men than in women. It is commonly agreed that estrogen plays important roles in suppressing HCC development, however, the underlying mechanism remains largely unknown. Since estrogen is mainly metabolized in liver and its metabolites affect cell proliferation, we sought to investigate if the liver-specific cytochrome P450 1A2 (CYP1A2) mediated the inhibitory effect of estrogen on HCC. In this study, the expression of estrogen-metabolizing enzyme CYP1A2 was determined in HCC tissues and cell lines. Cell proliferation and apoptosis were assessed in cells with or without CYP1A2 overexpression. The levels of 17β-estradiol (E2) and its metabolite 2-methoxyestradiol (2-ME) were determined. A xenograft tumor model in mice was established to confirm the findings. It was found that CYP1A2 expression was greatly repressed in HCC. E2 suppressed HCC cell proliferation and xenograft tumor development by inducing apoptosis. The inhibitory effect was significantly enhanced in cells with CYP1A2 overexpression, which effectively conversed E2 to the cytotoxic 2-ME. E2 in combination with sorafenib showed an additive effect on HCC. The anti-HCC effect of E2 was not associated with estrogen receptors ERα and ERβ as well as tumor suppressor P53 but enhanced by the approved anti-HCC drug sorafenib. In addition, HDAC inhibitors greatly induced CYP1A2 promoter activities in cancer cells, especially liver cancer cells, but not in non-tumorigenic cells. Collectively, CYP1A2 metabolizes E2 to generate the potent anti-tumor agent 2-ME in HCC. The reduction of CYP1A2 significantly disrupts this metabolic pathway, contributing the progression and growth of HCC and the gender disparity of this malignancy. PMID:27093553

  8. Modulation of 17β-Estradiol Signaling on Cellular Proliferation by Caveolin-2.

    PubMed

    Totta, Pierangela; Gionfra, Fabio; Busonero, Claudia; Acconcia, Filippo

    2016-06-01

    The sex hormone 17β-estradiol (E2) exerts pleiotropic effects by binding to the ligand-activated transcription factor estrogen receptor α (ERα). The E2:ERα complex regulates several physiological processes, including cell survival and proliferation, through transcriptional effects (i.e., estrogen responsive element [ERE]-based gene transcription) and non-transcriptional membrane-initiated effects (i.e., the activation of extra-nuclear signaling cascades), which derive from the activation of the pool of ERα that is localized to plasma membrane caveolae. Caveolae are ω-shaped membrane sub-domains that are composed of scaffold proteins named caveolins (i.e., caveolin-1, caveolin-2, and caveolin-3). Although caveolin-3 is exclusively expressed in muscles, caveolin-1 and caveolin-2 are co-expressed in all human tissues. From a functional point of view, caveolin-2 can operate both dependently on and independently of caveolin-1, which is the main coat component of caveolae. Interestingly, while a functional interplay between caveolin-1 and ERα has been reported in the control of E2-induced physiological effects, the role of caveolin-2 in E2:ERα signaling within the cell remains poorly understood. This study shows that siRNA-mediated caveolin-2 depletion in breast ductal carcinoma cells (MCF-7) reduces E2-induced ERα phosphorylation at serine residue 118 (S118), controls intracellular receptor levels, precludes ERα-mediated extra-nuclear activation of signaling pathways, reduces ERα transcriptional activity, and prevents cellular proliferation. Meanwhile, the impact of caveolin-1 depletion on ERα signaling in MCF-7 cells is shown to be similar to that elicited by siRNA-mediated caveolin-2 depletion. Altogether, these data demonstrate that caveolin-2 expression is necessary for the control of E2-dependent cellular proliferation. PMID:26480297

  9. Biodegradation of 17β-Estradiol, Estrone and Testosterone in Stream Sediments

    NASA Astrophysics Data System (ADS)

    Bradley, P. M.; Chapelle, F. H.; Barber, L. B.; McMahon, P. B.; Gray, J. L.; Kolpin, D. W.

    2009-12-01

    The potentials for in situ biodegradation of 17β-estradiol (E2), estrone (E1), and testosterone (T) were investigated in three, hydrologically-distinct, WWTP-impacted streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing sediment or water-only from locations upstream and downstream of the WWTP outfall in each system. Upstream samples provided insight into the biodegradative potential of sediment microbial communities that were not under the immediate impact of WWTP effluent. Upstream sediment from all three systems demonstrated significant mineralization of the “A” ring of E2, E1 and T, with the potential of T biodegradation consistently greater than of E2 and no systematic difference in the potentials of E2 and E1. Downstream samples provided insight into the impacts of effluent on reproductive hormone biodegradation. Significant “A” ring mineralization was also observed in downstream sediment, with the potentials for E1 and T mineralization being substantially depressed relative to upstream samples. In marked contrast, the potentials for E2 mineralization immediately downstream of the WWTP outfalls were more than double that of upstream samples. E2 mineralization was also observed in water, albeit at insufficient rate to prevent substantial downstream transport in the water column. The results of this study indicate that, in combination with sediment sorption processes which effectively scavenge hydrophobic contaminants from the water column and immobilize them in the vicinity of the WWTP outfall, aerobic biodegradation of reproductive hormones can be an environmentally important mechanism for non-conservative (destructive) attenuation of hormonal endocrine disruptors in effluent-impacted streams.

  10. The Astro-E2 Mission

    NASA Technical Reports Server (NTRS)

    Kelley, Richard L.

    2004-01-01

    The Astro-E2 observatory is a rebuild of the original Astro-E observatory that was lost during launch in February 2000. It is scheduled for launch into low earth orbit on a Japanese M-V rocket in early 2005. The Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, is developing the observatory with major contributions from the US. The three instruments on the observatory are the high-resolution x-ray spectrometer (the XRS) featuring a 30-pixel x-ray microcalorimeter array, a set of four CCD cameras (the XIS) and a combination photo-diode/scintillator detector system (the HXD) that will extend the band pass up to nearly 700 keV. A significant feature of Astro-E2 is that all of the instruments are coaligned and operated simultaneously. With its high spectral resolution and collecting area for spectroscopy above 1 keV, Astro-E2 should enable major discovery space and pioneer new technology for use in space. Prime areas for investigation are supernova remnants, active galaxies and the measurement of black hole properties via relativistically-broadened Fe-K emission galaxies. A number of enhancements have been made for the Astro-E2/XRS, including a higher resolution microcalorimeter array, ii mechanical cooler for longer cryogen life, and an improved in-flight calibration system. The Astro-E2/XIS has also been improved to include two back-side-illuminated CCDs to enhance the low energy response. Improvements have also been made to the x-ray mirrors used for both the XRS and XIS to sharpen the point spread function and reduce the effects of stray light. In this talk we will present the essential features of Astro-E2, paying particular attention to the enhancements, and describe the major scientific strengths of the observatory.

  11. Differential effects of short term feeding of a soy protein isolate diet and estrogen treatment on bone in the pre-pubertal rat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beneficial effects of a soy diet on bone quality have been assumed to be due to the putative estrogenic actions of isoflavones. We studied the effects of soy protein isolate (SPI) on bone quality and compared these effects to 17 beta-estradiol (E2) in pre-pubertal rats. Female rats were weaned to a ...

  12. Sorption, fate, and transport of endogenous steroid hormones in soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The natural hormones 17 beta-estradiol (E2) and testosterone (T) are present in animal manures that are applied to agricultural land as fertilizer and, potentially, may act as endocrine disruptors. Laboratory incubation, batch, and column experiments have been conducted on a series of soils and wer...

  13. EFFECT OF 17B-ESTRADIOL, O,P'-DDT, OCTYLPHENOL AND P,P'-DDE ON GONADAL DEVELOPMENT AND LIVER AND KIDNEY PATHOLOGY IN JUVENILE MALE SUMMER FLOUNDER (PARALICHTYS DENTATUS)

    EPA Science Inventory

    The intent of this study was to compare histopathologically the effect of 17 -estradiol (E2), o,p' DDT, octylphenol and p,p' DDE on gonadal development and liver and kidney condition in sexually immature (juvenile) summer flounder (Paralichthys dentatus). The dorsal sinus of 2-...

  14. EFFECT OF ACUTE STRESS ON PLASMA B-CORTICOSTERONE, ESTRADIOL-17B AND TESTOSTERONE CONCENTRATIONS IN JUVENILE AMERICAN ALLIGATORS COLLECTED FROM THREE SITES WITHIN THE KISSIMMEE-EVERGLADES DRAINAGE BASIN IN FLORIDA (USA)

    EPA Science Inventory

    The effect of acute stress on plasma b-corticosterone (B), testosterone (T) and estradiol-17b (E2), concentrations in juvenile alligators collected from sites with varying sediment contaminants was examined in this study. Dramatic increases in plasma B concentrations were observe...

  15. Association Between Preovulatory Concentrations of Estradiol and Expression of Uterine Milk Protein Precursor, Inhibin Beta A, Period 1, Proenkephalin, and Receptors for Oxytocin, Progesterone, and Estradiol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eliminating the preovulatory surge of estradiol decreased uterine weight, uterine protein, RNA to DNA ratio, rate of protein synthesis, and embryo survival following embryo transfer in sheep. Furthermore, cows that did not exhibit standing estrus (decreased preovulatory concentrations of estradiol) ...

  16. Estradiol rapidly modulates odor responses in mouse vomeronasal sensory neurons.

    PubMed

    Cherian, S; Wai Lam, Y; McDaniels, I; Struziak, M; Delay, R J

    2014-06-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  17. Electron emission from photo-excited testosterone in water-ethanol solution.

    PubMed

    Getoff, Nikola; Schittl, Heike; Hartmann, Johannes; Quint, Ruth Maria

    2009-03-01

    Testosterone (TES; 4-androstene-17beta-ol-3-on) is found for the first time to eject electrons from its singlet excited state in water-ethanol solvent mixture. This ability was very recently also observed for 17beta-estradiol (17betaE2) and progesterone (PRG)/1/. With increasing TES-concentration, the yield of solvated electrons (e(s)(-)) is decreasing, because of "associate" formation. At higher absorbed UV-doses (lambda=254 nm) the e(s)(-) yield is passing a sharp maximum by formation of TES-ethanol adducts, which are able likewise to emit electrons when excited. At prolonged irradiation the resulting photolytic products of TES-ethanol adducts are also able to emit electrons. The capability of the hormones: 17betaE2, PRG and TES to eject electrons and the resulting metabolites, some of which can induce cancer, is discussed. PMID:19124256

  18. 17β-Estradiol infusions into the dorsal striatum rapidly increase dorsal striatal dopamine release in vivo.

    PubMed

    Shams, Waqqas M; Sanio, Christian; Quinlan, Matthew G; Brake, Wayne G

    2016-08-25

    Systemic injections of 17β-estradiol (E2) in ovariectomized (OVX) female rats rapidly enhance dorsal striatal dopamine (DA) release in response to amphetamine (AMPH). Additionally, a single injection of E2 rapidly (within 30min) enhances amphetamine-induced DA release. In situ studies show that this rapid effect of E2 occurs specifically within the dorsal striatum (DS). The present study investigated the in vivo effects of E2 infused into the DS, medial prefrontal cortex (mPFC) or the substantia nigra (SN) on dorsal striatal DA release. Rats were OVX and implanted with a silastic tube containing 5% E2 in cholesterol, previously shown to mimic low physiological serum concentrations of 18-32pg/ml. Single-probe microdialysis was used to measure extracellular DA levels in the DS. In addition, DA release was measured subsequent to systemic injections of the indirect DA agonist, AMPH (0.5mg/kg SC), administered simultaneously with E2 (0.544μg/100μl) or its vehicle, cyclodextrin (VEH) (0.520μg/100μl). Local infusions of E2 into the DS resulted in a greater amphetamine-induced dorsal striatal DA release in comparison to vehicle. Local infusions of E2 into the mPFC or the SN did not result in an enhancement of amphetamine-induced DA levels in the DS. These studies suggest that increases in dorsal striatal DA release in response to systemic E2 are a consequence of E2 actions within the DS itself. PMID:27256507

  19. 17β-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level

    SciTech Connect

    Zhao, Ziyi; Chen, Changjin; Liu, Yu; Wu, Chuanfang

    2014-03-07

    Highlights: • E2 affects not only estrogen-receptor α positive breast cells but also negative ones. • 100 nM E2 treatment affects breast cells proliferation, migration. • 100 nM E2 treatment functions in an estrogen-receptor α-independent way. • E2 treatment decreases MALAT-1 RNA level by post-transcriptional regulation. - Abstract: Breast cancer cells, which express estrogen receptor α (ERα), respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. But breast cancer cells without ERα show no effect on low concentration of estrogen treatment. Proliferation, migration and invasion of MCF10a, MCF7 and MB231 cells treated with low (1 nM) or high (100 nM) dose of 17β-Estradiol (E2) was performed. We identified the effects of E2 on these breast cell lines, and looked for the difference in the presence and absence of ERα. Specifically, we looked for the changes of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), which is found extensively and highly expressed in several kinds of tumor cells, including breast carcinoma. It was observed that proliferation, migration and invasion of breast cells were greatly affected by high concentration E2 treatment and were not affected by low concentration E2 treatment in an ERα independent way. We found that the high concentration E2 treatment largely decreased MALAT-1 RNA level. Interestingly, MALAT-1 decreasing by knocking down showed similar effects on proliferation, migration and invasion. E2 treatment affects breast tumor or non-tumor cells proliferation, migration and invasion in an ERα -independent, but a dose-dependent way by decreasing the MALAT-1 RNA level.

  20. 17β-estradiol activates mTOR in chondrocytes by AKT-dependent and AKT-independent signaling pathways

    PubMed Central

    Tao, Yulei; Sun, Haibiao; Sun, Hongyan; Qiu, Xianxing; Xu, Changbo; Shi, Changxiu; Du, Jiahui

    2015-01-01

    To confirm whether 17β-estradiol (E2) activates mammalian target of rapamycin (mTOR) signaling pathway in chondrocytes and in what way activates mTOR. Human immortalized chondrocytes cell lines TC28a2 and C28/I2 were subjected to incubate with or without E2, LY294002 (the inhibitor of PI3K), rapamycin (the inhibitor of mTOR), or E2 in combination with LY294002 or rapamycin. Thereafter, protein levels of S6K1, p-S6K1, protein kinase B (AKT), and p-AKT were determined by Western blot analysis. Matrix metallopeptidase (MMP) 3 or MMP13 mRNA levels were evaluated by quantitative real-time PCR (qRT-PCR). Co-immunoprecipitation and Western blot analysis were performed to verify the interaction between ERα and mTOR. Both p-S6K1 and p-AKT protein levels in TC28a2 and C28/I2E2 cells were significantly increased by incubation with E2 (0.5 h and 1 h) (P < 0.05). Rapamycin did not affect the levels of p-AKT, but were significantly reduced by LY294002 or E2 in combination with LY294002. The levels of p-S6K1 were significantly decreased by incubation with LY294002, but the effect could be reversed by E2 in combination with LY294002. Rabbit anti-mTOR antibody was able to immunoprecipitate ERα after incubation with E2. Moreover, E2 inhibited the mRNA levels of MMP3 and MMP13 by mTOR pathway. E2 actives mTOR in chondrocytes through AKT-dependent and independent ways. PMID:26884863

  1. A point mutation in the putative TATA box, detected in nondiseased individuals and patients with hereditary breast cancer, decreases promoter activity of the 17{beta}-hydroxysteroid dehydrogenase type 1 gene 2 (EDH17B2) in vitro

    SciTech Connect

    Peltoketo, H.; Piao, Y.; Isomaa, V.

    1994-09-01

    EDH17B2, the gene encoding 17{beta}-hydroxysteroid dehydrogenase type 1, has been suggested as a candidate for the familial breast cancer gene, BRCA1, located on 17q12-q21. We analyzed the promoter region of EDH17B2 in DNA from 20 control individuals and 40 patients with familial breast cancer. Two frequent (designated vI and vIII) and two rare (vII and vIV) nucleotide variations were present in both the breast cancer patients and the controls, except the alteration vII, which was found only in one patient. Although the data do not support the identification of EDH17B2 as the BRCA1 gene, it is of interest that point mutation vIV (A {yields} C) was located in the putative TATA box of the EDH17B2 gene. Reporter gene analysis showed that the mutation vIV decreases EDH17B2 promoter activity by an average of 45% in in vitro assays, suggesting that nucleotide A at position -27 is significant for efficient transcription. 12 refs., 2 figs., 1 tab.

  2. CYP21-catalyzed production of the long-term urinary metandienone metabolite 17beta-hydroxymethyl-17 alpha-methyl-18-norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping.

    PubMed

    Zöllner, Andy; Parr, Maria Kristina; Drăgan, Călin-Aurel; Dräs, Stefan; Schlörer, Nils; Peters, Frank T; Maurer, Hans H; Schänzer, Wilhelm; Bureik, Matthias

    2010-01-01

    Anabolic-androgenic steroids are some of the most frequently misused drugs in human sports. Recently, a previously unknown urinary metabolite of metandienone, 17beta-hydroxymethyl-17 alpha-methyl-18-norandrosta-1,4,13-trien-3-one (20OH-NorMD), was discovered via LC-MS/MS and GC-MS. This metabolite was reported to be detected in urine samples up to 19 days after administration of metandienone. However, so far it was not possible to obtain purified reference material of this metabolite and to confirm its structure via NMR. Eleven recombinant strains of the fission yeast Schizosaccharomyces pombe that express different human hepatic or steroidogenic cytochrome P450 enzymes were screened for production of this metabolite in a whole-cell biotransformation reaction. 17,17-Dimethyl-18-norandrosta-1,4,13-trien-3-one, chemically derived from metandienone, was used as substrate for the bioconversion, because it could be converted to the final product in a single hydroxylation step. The obtained results demonstrate that CYP21 and to a lesser extent also CYP3A4 expressing strains can catalyze this steroid hydroxylation. Subsequent 5 l-scale fermentation resulted in the production and purification of 10 mg of metabolite and its unequivocal structure determination via NMR. The synthesis of this urinary metandienone metabolite via S. pombe-based whole-cell biotransformation now allows its use as a reference substance in doping control assays. PMID:19919183

  3. 17 beta-(N-tert-butylcarbamoyl)-4-aza-5 alpha-androstan-1-en-3-one is an active site-directed slow time-dependent inhibitor of human steroid 5 alpha-reductase 1.

    PubMed

    Tian, G; Stuart, J D; Moss, M L; Domanico, P L; Bramson, H N; Patel, I R; Kadwell, S H; Overton, L K; Kost, T A; Mook, R A

    1994-03-01

    17 beta-(N-tert-butylcarbamoyl)-4-aza-5 alpha-androstan-1-en-3-one (finasteride), which has been approved for treatment of benign prostatic hyperplasia, is shown here to be a slow time-dependent inhibitor of human steroid 5 alpha-reductase isozyme 1. This inhibition is characterized by an initial, fast step where the inhibitor binds to the enzyme followed by a slow step that leads to a final enzyme-inhibitor complex (EI*). No recovery of activity from this EI* complex was observed after dialysis for 3 days. The formation of EI* is diminished in the presence of a competitive, reversible inhibitor, indicating that the inhibition is active site-directed. At 37 degrees C and pH 7.0, the rate constant for the second, slow inhibition step, k3, is (1.40 +/- 0.04) x 10(-3) s-1 and the pseudo-bimolecular rate constant, k3/Ki, is (4.0 +/- 0.3) x 10(3) M-1 s-1. This latter rate constant is less than the value of 2.7 x 10(5) M-1 s-1 determined for the inhibition of 5 alpha-reductase 2 by finasteride [Faller, B., Farley, D., & Nick, H. (1993) Biochemistry 32, 5705-5710].(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8117686

  4. The presence of high-affinity, low-capacity estradiol-17β binding in rainbow trout scale indicates a possible endocrine route for the regulation of scale resorption

    USGS Publications Warehouse

    Persson, Petra; Shrimpton, J.M.; McCormick, S.D.; Bjornsson, Bjorn Thrandur

    2000-01-01

    High-affinity, low-capacity estradiol-17β (E2) binding is present in rainbow trout scale. The Kd and Bmax of the scale E2 binding are similar to those of the liver E2 receptor (Kd is 1.6 ± 0.1 and 1.4 ± 0.1 nM, and Bmax is 9.1 ± 1.2 and 23.1 ± 2.2 fmol x mg protein-1, for scale and liver, respectively), but different from those of the high-affinity, low-capacity E2 binding in plasma (Kd is 4.0 ± 0.4 nM and Bmax is 625.4 ± 63.1 fmol x mg protein-1). The E2 binding in scale was displaced by testosterone, but not by diethylstilbestrol. Hence, the ligand binding specificity is different from that of the previously characterized liver E2 receptor, where E2 is displaced by diethylstilbestrol, but not by testosterone. The putative scale E2 receptor thus appears to bind both E2 and testosterone, and it is proposed that the increased scale resorption observed during sexual maturation in both sexes of several salmonid species may be mediated by this receptor. No high-affinity, low-capacity E2 binding could be detected in rainbow trout gill or skin.

  5. Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology.

    PubMed

    Cover, K K; Maeng, L Y; Lebrón-Milad, K; Milad, M R

    2014-01-01

    Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders. PMID:25093600

  6. Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology

    PubMed Central

    Cover, K K; Maeng, L Y; Lebrón-Milad, K; Milad, M R

    2014-01-01

    Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders. PMID:25093600

  7. Aging and Loss of Circulating 17β-Estradiol Alters the Alternative Splicing of ERβ in the Female Rat Brain.

    PubMed

    Shults, Cody L; Pinceti, Elena; Rao, Yathindar S; Pak, Toni R

    2015-11-01

    Loss of circulating 17β-estradiol (E2) that occurs during menopause can have detrimental effects on cognitive function. The efficacy of hormone replacement therapy declines as women become farther removed from the menopausal transition, yet the molecular mechanisms underlying this age-related switch in E2 efficacy are unknown. We hypothesized that aging and varying lengths of E2 deprivation alters the ratio of alternatively spliced estrogen receptor (ER)β isoforms in the brain of female rats. Further, we tested whether changes in global transcriptional activity and splicing kinetics regulate the alternative splicing of ERβ. Our results revealed brain region-specific changes in ERβ alternative splicing in both aging and E2-deprivation paradigms and showed that ERβ could mediate E2-induced alternative splicing. Global transcriptional activity, as measured by phosphorylated RNA polymerase II, was also regulated by age and E2 in specific brain regions. Finally, we show that inhibition of topoisomerase I resulted in increased ERβ2 splice variant expression. PMID:26295370

  8. 17β-Estradiol alters oxidative damage and oxidative stress response protein expression in the mouse mammary gland.

    PubMed

    Yuan, Lisi; Dietrich, Alicia K; Ziegler, Yvonne S; Nardulli, Ann M

    2016-05-01

    Although substantial evidence has demonstrated that parity and 17β-estradiol (E2) reduce mammary carcinogenesis, it is not clear how this protection is conferred. Thus, we examined the effects of parity and E2 treatment in the mammary glands of ovariectomized 15 week-old virgin mice, 15 week-old primiparous mice, and 9 month-old retired breeders. E2 treatment significantly increased lipid peroxidation, protein carbonylation, and protein nitrosylation in the virgin mice, but not in the age-matched primiparous mice or retired breeders. Mammary gland expression of the oxidative stress response protein Cu/Zn superoxide dismutase was consistently reduced in all of the E2-treated mice regardless of parity. Expression of the oxidative stress and DNA repair protein apurinic endonuclease (Ape1) was significantly increased only in the mammary glands of the E2-treated retired breeders. These findings suggest that E2 and parity help to reduce mammary oncogenesis by maintaining the structure and function of proteins, lipids, and DNA. PMID:26872614

  9. Proteome-Wide Effect of 17-β-Estradiol and Lipoxin A4 in an Endometriotic Epithelial Cell Line

    PubMed Central

    Sobel, Jonathan A.; Waridel, Patrice; Gori, Ilaria; Quadroni, Manfredo; Canny, Geraldine O.

    2016-01-01

    Endometriosis affects approximately 10% of women of reproductive age. This chronic, gynecological inflammatory disease results in a decreased quality of life for patients, with the main symptoms including chronic pelvic pain and infertility. The steroid hormone 17-β Estradiol (E2) plays a key role in the pathology. Our previous studies showed that the anti-inflammatory lipid Lipoxin A4 (LXA4) acts as an estrogen receptor-alpha agonist in endometrial epithelial cells, inhibiting certain E2-mediated effects. LXA4 also prevents the progression of endometriosis in a mouse model via anti-proliferative mechanisms and by impacting mediators downstream of ER signaling. The aim of the present study was therefore to examine global proteomic changes evoked by E2 and LXA4 in endometriotic epithelial cells. E2 impacted a greater number of proteins in endometriotic epithelial cells than LXA4. Interestingly, the combination of E2 and LXA4 resulted in a reduced number of regulated proteins, with LXA4 mediating a suppressive effect on E2-mediated signaling. These proteins are involved in diverse pathways of relevance to endometriosis pathology and metabolism, including mRNA translation, growth, proliferation, proteolysis, and immune responses. In summary, this study sheds light on novel pathways involved in endometriosis pathology and further understanding of signaling pathways activated by estrogenic molecules in endometriotic epithelial cells. PMID:26779118

  10. A comparative adsorption study: 17β-estradiol onto aerobic granular sludge and activated sludge.

    PubMed

    Zheng, Xiao-ying; He, Yu-jie; Chen, Wei; Wang, Ming-yang; Cao, Su-lan; Ni, Ming; Chen, Yu

    2016-01-01

    Adsorption plays a significant role in removing hydrophobic 17β-estradiol (E2) from wastewater. Batch experiments were conducted to compare the adsorption of E2 onto activated aerobic granular sludge (AGS) and activated sludge (AS), and features evaluated included the adsorption kinetics, thermodynamics, and influence of other environmental factors. By using a non-chemical wet-heat technique, both AGS and AS were treated to inactivated status. Then, after loading E2, the adsorption equilibrium capacity of the AGS was found to be greater than that of the AS at the same initial concentration of E2. Moreover, both the adsorption processes corresponded to a pseudo-second-order kinetic model; the adsorption rate constant of AGS was found to be higher and the half-adsorption time was shorter than that of AS. Next, evaluations of adsorption isotherms and thermodynamics indicated that the adsorption process was mainly a physical process. Lower temperatures facilitated a higher equilibrium adsorption capacity. However, the adsorption binding sites of AGS were distributed more uniformly at higher temperature, in contrast to the distribution found for AS. Finally, acidic conditions and an appropriate ionic strength (0.4 mol/L) were found to be particularly conducive to the adsorption process. Overall, the results showed that AGS has the potential to adsorb E2 with significant efficiency, thereby offering a new and more efficient means of treating E2 and trace oestrogens in wastewater. PMID:26209151

  11. E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle.

    PubMed Central

    Sardet, C; Vidal, M; Cobrinik, D; Geng, Y; Onufryk, C; Chen, A; Weinberg, R A

    1995-01-01

    The E2F transcription factors play a role in regulating the expression of genes required for cell proliferation. Their activity appears to be regulated by association with the retinoblastoma protein (pRb) and the pRb-related proteins p107 and p130. In vivo, pRb is found in complex with a subset of E2F components--namely, E2F-1, E2F-2, and E2F-3. Here we describe the characterization of cDNAs encoding two unusual E2Fs, E2F-4 and E2F-5, each identified by the ability of their gene product to interact with p130 in a yeast two-hybrid system. E2F-4 and -5 share common sequences with E2F-1, E2F-2, and E2F-3 and, like these other E2Fs, the ability to heterodimerize with DP-1, thereby acquiring the ability to bind an E2F DNA recognition sequence with high affinity. However, in contrast to E2F-1, E2F-4 and E2F-5 fail to bind pRb in a two-hybrid assay. Moreover, they show a unique pattern of expression in synchronized human keratinocytes: E2F-4 and E2F-5 mRNA expression is maximal in mid-G1 phase before E2F-1 expression is detectable. These findings suggest that E2F-4 and E2F-5 may contribute to the regulation of early G1 events including the G0/G1 transition. Images Fig. 2 Fig. 3 Fig. 4 PMID:7892279

  12. E2 Regulates Epigenetic Signature on Neuroglobin Enhancer-Promoter in Neuronal Cells

    PubMed Central

    Guglielmotto, Michela; Reineri, Stefania; Iannello, Andrea; Ferrero, Giulio; Vanzan, Ludovica; Miano, Valentina; Ricci, Laura; Tamagno, Elena; De Bortoli, Michele; Cutrupi, Santina

    2016-01-01

    Estrogens are neuroprotective factors in several neurological diseases. Neuroglobin (NGB) is one of the estrogen target genes involved in neuroprotection, but little is known about its transcriptional regulation. Estrogen genomic pathway in gene expression regulation is mediated by estrogen receptors (ERα and ERβ) that bind to specific regulatory genomic regions. We focused our attention on 17β-estradiol (E2)-induced NGB expression in human differentiated neuronal cell lines (SK-N-BE and NT-2). Previously, using bioinformatics analysis we identified a putative enhancer in the first intron of NGB locus. Therefore, we observed that E2 increased the enrichment of the H3K4me3 epigenetic marks at the promoter and of the H3K4me1 and H3K27Ac at the intron enhancer. In these NGB regulatory regions, we found estrogen receptor alpha (ERα) binding suggesting that ERα may mediate chromatin remodeling to induce NGB expression upon E2 treatment. Altogether our data show that NGB expression is regulated by ERα binding on genomic regulatory regions supporting hormone therapy applications for the neuroprotection against neurodegenerative diseases. PMID:27313512

  13. [Postpartum ovarian physiology. Pituitary gonadotropins, estradiol and prolactin during 12 months of postpartum physiology].

    PubMed

    Hernández Horta, J L; Alonso Uriarte, Q; Cortés Gallegos, V

    1994-06-01

    In order to establish a relationship between hyperprolactinemia and FSH-LH associated to the ovarian physiology postpartum, a clinical/endocrinological follow-up was performed during a period of twelve months in a cohorte of seventeen women beginning pregnancy resolution. The study had two phases: Lactancy (LAC) and Post-lactancy (LAC) and Post-lactancy (POST-LAC). In both phases blood samples were obtained every week from the first one through the 52nd, to quantitate FSH, LH, prolactin (PRL) and estradiol (E-2). PRL levels were significantly higher during LAC as compared to POST-LAC: an inverse relationship in E-2/PRL was seen through the study. No significant changes for LH and FSH were attained in both phases. Concentrations of these gonadotropins were at the physiological levels and no differences in either one of the two phases were shown when compared to a nonlactating subject. There was a negative association in prolactin levels and the weeks postpartum, and on the contrary, a positive one for E-2. Thus, ovarian follicular development apparently is independent to the gonadotropic-hypophysis stimulus. PMID:8056364

  14. 17 β-estradiol Protects Male Mice from Cuprizone-induced Demyelination and Oligodendrocyte Loss

    PubMed Central

    Taylor, Lorelei C; Puranam, Kasturi; Gilmore, Wendy; Ting, Jenny P-Y.; Matsushima, G.K.

    2010-01-01

    In addition to regulating reproductive functions in the brain and periphery, estrogen has trophic and neuroprotective functions in the central nervous system (CNS). Estrogen administration has been demonstrated to provide protection in several animal models of CNS disorders, including stroke, brain injury, epilepsy, Parkinson’s disease, Alzheimer’s disease, age-related cognitive decline and multiple sclerosis. Here, we use a model of toxin-induced oligodendrocyte death which results in demyelination, reactive gliosis, recruitment of oligodendrocyte precursor cells and subsequent remyelination to study the potential benefit of 17β-estradiol (E2) administration in male mice. The results indicate that E2 partially ameliorates loss of oligodendrocytes and demyelination in the corpus callosum. This protection is accompanied by a delay in microglia accumulation as well as reduced mRNA expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), and insulin-like growth factor-1 (IGF-1). E2 did not significantly alter the accumulation of astrocytes or oligodendrocyte precursor cells, or remyelination. These data obtained from a toxin-induced, T cell-independent model using male mice provide an expanded view of the beneficial effects of estrogen on oligodendrocyte and myelin preservation. PMID:20347981

  15. Transient Effect of 17β-estradiol on Osteoporosis in Ovariectomized Rats Accompanied with Unilateral Disuse in the Early Phase

    PubMed Central

    Sun, Xiaodi; Liang, Jin; Wang, Chune; Cao, Sensen; Hu, Yingwei; Xu, Xin

    2015-01-01

    Purpose: It is clinically important to determine the efficacy of estrogen replacement for postmenopausal women combined with mobility difficulties, due to the potential risks of estradiol. The objective of the current study was to investigate the effect of estradiol replacement on osteoporosis induced by the ovariectomy (OVX) combined with unilateral sciatic neurectomy (SN) in a rat model. Method: Female Sprague-Dawley rats were subjected to OVX and unilateral SN on the right hindlimb (OVX+SN) or sham surgery (CTRL). 17β-estradiol (E2) or vehicle was administrated to the rats immediately, and followed by every other day. Bone mass and trabecular microarchitecture were analyzed using micro-Computed Tomography (micro-CT) and histology at days 3, 7, 14, and 28 post-surgery. The local expressions of sclerostin/SOST, secreted exclusively by osteocytes, and tartrate-resistant acid phosphatase 5b (TRAP 5b), produced mostly by osteoclasts, were examined by immunohistochemistry and TRAP staining, respectively. Serum markers of bone resorption, including C-terminal telopeptides of type I collagen (CTx), receptor activator for nuclear factor κB ligand (RANKL), and TRAP 5b, were quantified by enzyme linked immunosorbent assay (ELISA). Result: Based on micro-CT analysis, E2 treatment of OVX+SN rats improved the preservation of the bone volume fraction (BV/TV) and trabecular number (Tb.N) in the tibias at day 14 post-surgery, which were 43% and 46% higher in OVX+SN+E2 rats than those in OVX+SN rats, respectively. However, the impact of E2 was transient and disappeared at day 28. Expression of sclerostin in the tibias of OVX+SN rats was significantly elevated at day 7 post-surgery compared with the CTRL, but was suppressed until day 14 with E2 replacement. Conclusion: Our results showed that estrogen replacement could transiently protect against bone loss in OVX rats combined with mechanical unloading. The up-regulation of sclerostin expression appears to be transiently delayed

  16. Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol.

    PubMed

    Miousse, Isabelle R; Gomez-Acevedo, Horacio; Sharma, Neha; Vantrease, Jamie; Hennings, Leah; Shankar, Kartik; Cleves, Mario A; Badger, Thomas M; Ronis, Martin Jj

    2013-09-01

    In order to characterize the actions of xenoestrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. We assessed effects of three doses of exogenous estradiol (E2) (0.1, 1.0 and 10 µg/kg/day) given between postnatal days 21 and 33 on the mammary gland morphology and gene expression profiles of male and female rats compared to vehicle-treated controls. The male mammary gland was more responsive to E2 treatment than in females, with 509 genes regulated >2-fold in a dose-dependent manner in males and only 174 in females. In males, E2 treatment significantly (P < 0.01) increased the number of terminal end buds (TEBs) and the expression of proliferating cell nuclear antigen (PCNA) protein (P < 0.05), both of which are indicators of proliferation. This change was linked to a significant increase (P < 0.05) in the expression of the gene encoding amphiregulin, which is known to induce TEB formation. There was also a dose-dependent increase (P < 0.001) in the estrogen-regulated gene encoding the progesterone receptor. In intact females, despite lack of changes in mammary morphology, we observed a dose-dependent increase (P < 0.05) in the expression of genes encoding three milk proteins: whey acidic protein, casein beta and casein kappa. There was a significant (P < 0.05) downregulation of both estrogen receptors in response to E2 treatment. These results suggest that mammary glands of male rats are very sensitive to exogenous E2 during development post-weaning. The dose-dependent increase observed in amphiregulin and progesterone receptor gene expression was linked to morphological changes and represents a reliable and sensitive tool to evaluate estrogenicity. In contrast, intact weanling female rats were less responsive. PMID:23925648

  17. Comparative safety, efficacy, and cycle control of Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) and Ortho-Novum 7/7/7 oral contraceptive (norethindrone/ethinyl estradiol triphasic). Lunelle Study Group.

    PubMed

    Kaunitz, A M; Garceau, R J; Cromie, M A

    1999-10-01

    An open-label, nonrandomized, parallel, controlled study compared the efficacy, safety, and cycle control of a new monthly injectable contraceptive containing 25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate (E2C) (MPA/E2C) (Lunelle Monthly Contraceptive Injection) with that of a norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum 7/7/7). At study enrollment, women chose either the injections or the oral contraceptive. A higher proportion of women in the NET/EE group (65.1%) than in the MPA/E2C group (48.7%) had used hormonal contraception during the month before the study (p < 0.01). Overall, 55.5% (434/782) of MPA/E2C users and 67.6% (217/321) of NET/EE users completed the 60-week trial. One-year contraceptive efficacy (13 cycles of 28 days) for MPA/E2C and NET/EE was based on 8008 and 3434 woman-cycles of use, respectively. During the first year, one pregnancy occurred in an NET/EE user for a life table rate of 0.3; no pregnancies occurred in users of MPA/E2C. One additional pregnancy in the NET/EE group occurred during the 15th treatment cycle. After the first treatment cycle, women in both groups experienced regular menses, with an average cycle length of 28 days in MPA/E2C users and 27 days in NET/EE users. Although MPA/E2C users were more likely to experience bleeding irregularities, only 2.5% (19/775) cited metrorrhagia as a reason for discontinuing treatment. The adverse events reported in both treatment groups are consistent with those expected with the use of combined hormonal contraceptives. Overall, the results of this first Phase III US clinical trial of MPA/E2C confirm this method's high contraceptive efficacy and safety, as shown in previous studies by the World Health Organization. These results suggest that a monthly combination injectable would represent a welcome new contraceptive option for women in the US. PMID:10640164

  18. Estradiol and Estrogen Receptor Agonists Oppose Oncogenic Actions of Leptin in HepG2 Cells.

    PubMed

    Shen, Minqian; Shi, Haifei

    2016-01-01

    Obesity is a significant risk factor for certain cancers, including hepatocellular carcinoma (HCC). Leptin, a hormone secreted by white adipose tissue, precipitates HCC development. Epidemiology data show that men have a much higher incidence of HCC than women, suggesting that estrogens and its receptors may inhibit HCC development and progression. Whether estrogens antagonize oncogenic action of leptin is uncertain. To investigate potential inhibitory effects of estrogens on leptin-induced HCC development, HCC cell line HepG2 cells were treated with leptin in combination with 17 β-estradiol (E2), estrogen receptor-α (ER-α) selective agonist PPT, ER-β selective agonist DPN, or G protein-coupled ER (GPER) selective agonist G-1. Cell number, proliferation, and apoptosis were determined, and leptin- and estrogen-related intracellular signaling pathways were analyzed. HepG2 cells expressed a low level of ER-β mRNA, and leptin treatment increased ER-β expression. E2 suppressed leptin-induced HepG2 cell proliferation and promoted cell apoptosis in a dose-dependent manner. Additionally E2 reversed leptin-induced STAT3 and leptin-suppressed SOCS3, which was mainly achieved by activation of ER-β. E2 also enhanced ERK via activating ER-α and GPER and activated p38/MAPK via activating ER-β. To conclude, E2 and its receptors antagonize the oncogenic actions of leptin in HepG2 cells by inhibiting cell proliferation and stimulating cell apoptosis, which was associated with reversing leptin-induced changes in SOCS3/STAT3 and increasing p38/MAPK by activating ER-β, and increasing ERK by activating ER-α and GPER. Identifying roles of different estrogen receptors would provide comprehensive understanding of estrogenic mechanisms in HCC development and shed light on potential treatment for HCC patients. PMID:26982332

  19. 17β-Estradiol Ameliorates Tight Junction Disruption via Repression of MMP Transcription.

    PubMed

    Na, Wonho; Lee, Jee Youn; Kim, Won-Sun; Yune, Tae Young; Ju, Bong-Gun

    2015-09-01

    The blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB) formed by capillary endothelial cells provides a physical wall between the central nervous system (CNS) and circulating blood with highly selective permeability. BBB/BSCB disruption by activation of matrix metalloproteinases (MMPs) has been shown to result in further neurological damage after CNS injury. Recently it has been discovered that estrogen attenuates BBB/BSCB disruption in in vitro and in vivo models. However, the molecular mechanism underlying the estrogen-mediated attenuation of BBB/BSCB disruption has not been elucidated fully. In the present study, we found that 17β-estradiol (E2) suppresses nuclear factor-κB-dependent MMP-1b, MMP-2, MMP-3, MMP-9, MMP-10, and MMP-13 gene activation in microvessel endothelial bEnd.3 cells subjected to oxygen and glucose deprivation/reperfusion injury. E2 induced the recruitment of ERα and nuclear receptor corepressor to the nuclear factor-κB binding site on the MMPs' gene promoters. Consistently, ER antagonist ICI 182.780 showed opposite effects of E2. We further found that E2 attenuates tight junction disruption through the decreased degradation of tight junction proteins in bEnd.3 cells subjected to oxygen and glucose deprivation-reperfusion injury. In addition, E2 suppressed the up-regulation of MMP expression, leading to a decreased BSCB disruption in the injured spinal cord. In conclusion, we discovered the molecular mechanism underlying the protective role of estrogenin BBB/BSCB disruption using an in vitro and in vivo model. Our study suggests that estrogens may provide a potential therapeutic intervention for preserving BBB/BSCB integrity after CNS injury. PMID:26168035

  20. Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

    PubMed Central

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W.; Saunders, Philippa T.K.

    2016-01-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1–differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. PMID:26073038

  1. Rescue from Sexually Dimorphic Neuronal Cell Death by Estradiol and PI3 Kinase Activity.

    PubMed

    Cheng, Hui-Yun; Hung, Shin-Hui; Chu, Po-Ju

    2016-07-01

    Responses of primary hippocampal and cortical neurons derived from male and female rats to cellular stressors were studied. It is demonstrated that 17β-estradiol (E2), a potent neuroprotectant, protected the female neurons but had no effects on the male neurons from CoCl2- and glutamate-induced toxicity. Agonists of the estrogen receptor (ER) subtypes ERα and ERβ, DPN and PPT, respectively, had similar effects to E2. By contrast, effects of E2 were abolished by the ER antagonist ICI-182780, further corroborating the neuroprotective role of ERs. In male neurons, CoCl2 predominately activated the apoptosis-inducing factor (AIF)-dependent pathway and AIF translocation from the cytosol to the nucleus. In comparison, CoCl2 activated the caspase pathway and cytochrome c release in female neurons. The inhibitors of these pathways, namely DiQ for AIF and zVAD for caspase, specifically rescued CoCl2-induced cell death in male and female neurons, respectively. When zVAD and ICI-182780, and E2 were applied in combination, it was demonstrated E2 acted on the caspase pathway leading to female-specific neuroprotection. Furthermore, the PI3 kinase (PI3K) inhibitor blocked the rescue effects of DiQ and zVAD on the male and female neurons, respectively, suggesting that PI3K is a common upstream regulator for both pathways. The present study suggested that both sex-specific and nonspecific mechanisms played a role in neuronal responses to stressors and protective reagents. PMID:26369912

  2. Proteomic study of periovarian adipose tissue in 17β-estradiol-treated and untreated ovariectomized rats.

    PubMed

    Amengual-Cladera, Emilia; Capllonch-Amer, Gabriela; Lladó, Isabel; Gianotti, Magdalena; Proenza, Ana M

    2016-04-01

    Taking into account the sexual dimorphism previously found in white adipose tissue (WAT) regarding mitochondrial function and biogenesis, as well as insulin sensitivity, the aim of this study was to go further into the role of sex hormones in this dimorphism. To achieve this objective, we used ovariectomized rats and performed a screening by means of proteomic analyses of the periovarian WAT, combined with a study of the protein levels of specific factors involved in mitochondrial function. Rats were ovariectomized at 5 weeks of age and subcutaneously injected every 48 h with corn-oil (OVX group) or with 17β-estradiol (E2, 10 μg/kg body mass; OVX + E2 group) for 4 weeks prior to sacrifice. Beside proteomic analysis, protein levels of Transcription Factor A, Mitochondrial (TFAM), cytochrome oxidase (COX)II, and COXIV were determined by Western blot, and mRNA levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, ERα, ERβ, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ), and adiponectin were quantified by real-time PCR. Our results show that ovariectomy leads to an increase in anabolic processes and inflammatory protein levels as well as to a decrease in some of the markers of mitochondrial function, which are restored, at least in part, by E2 supplementation. Indeed, this E2 supplementation seems to be counteracted by a decline in ERα and in the ERα to ERβ ratio values that could be directed to avoid an over-stimulation of the E2 signaling pathway, given the possibility of an activation of extra-gonadal steroid biosynthetic pathways. PMID:26914441

  3. Estradiol and Estrogen Receptor Agonists Oppose Oncogenic Actions of Leptin in HepG2 Cells

    PubMed Central

    Shen, Minqian; Shi, Haifei

    2016-01-01

    Obesity is a significant risk factor for certain cancers, including hepatocellular carcinoma (HCC). Leptin, a hormone secreted by white adipose tissue, precipitates HCC development. Epidemiology data show that men have a much higher incidence of HCC than women, suggesting that estrogens and its receptors may inhibit HCC development and progression. Whether estrogens antagonize oncogenic action of leptin is uncertain. To investigate potential inhibitory effects of estrogens on leptin-induced HCC development, HCC cell line HepG2 cells were treated with leptin in combination with 17 β-estradiol (E2), estrogen receptor-α (ER-α) selective agonist PPT, ER-β selective agonist DPN, or G protein-coupled ER (GPER) selective agonist G-1. Cell number, proliferation, and apoptosis were determined, and leptin- and estrogen-related intracellular signaling pathways were analyzed. HepG2 cells expressed a low level of ER-β mRNA, and leptin treatment increased ER-β expression. E2 suppressed leptin-induced HepG2 cell proliferation and promoted cell apoptosis in a dose-dependent manner. Additionally E2 reversed leptin-induced STAT3 and leptin-suppressed SOCS3, which was mainly achieved by activation of ER-β. E2 also enhanced ERK via activating ER-α and GPER and activated p38/MAPK via activating ER-β. To conclude, E2 and its receptors antagonize the oncogenic actions of leptin in HepG2 cells by inhibiting cell proliferation and stimulating cell apoptosis, which was associated with reversing leptin-induced changes in SOCS3/STAT3 and increasing p38/MAPK by activating ER-β, and increasing ERK by activating ER-α and GPER. Identifying roles of different estrogen receptors would provide comprehensive understanding of estrogenic mechanisms in HCC development and shed light on potential treatment for HCC patients. PMID:26982332

  4. Estradiol differentially affects auditory recognition and learning according to photoperiodic state in the adult male songbird, European starling (Sturnus vulgaris)

    PubMed Central

    Knudsen, Daniel P.; Krause, Jesse S.; Wingfield, John C.; Gentner, Timothy Q.

    2013-01-01

    Changes in hormones can affect many types of learning in vertebrates. Adults experience fluctuations in a multitude of hormones over a temporal scale, from local, rapid action to more long-term, seasonal changes. Endocrine changes during development can affect behavioral outcomes in adulthood, but how learning is affected in adults by hormone fluctuations experienced during adulthood is less understood. Previous reports have implicated the sex steroid hormone estradiol (E2) in both male and female vertebrate cognitive functioning. Here, we examined the effects of E2 on auditory recognition and learning in male European starlings (Sturnus vulgaris). European starlings are photoperiodic, seasonally breeding songbirds that undergo different periods of reproductive activity according to annual changes in day length. We simulated these reproductive periods, specifically 1. photosensitivity, 2. photostimulation, and 3. photorefractoriness in captive birds by altering day length. During each period, we manipulated circulating E2 and examined multiple measures of learning. To manipulate circulating E2, we used subcutaneous implants containing either 17-β E2 and/or fadrozole (FAD), a highly specific aromatase inhibitor that suppresses E2 production in the body and the brain, and measured the latency for birds to learn and respond to short, male conspecific song segments (motifs). We report that photostimulated birds given E2 had higher response rates and responded with better accuracy than those given saline controls or FAD. Conversely, photosensitive, animals treated with E2 responded with less accuracy than those given FAD. These results demonstrate how circulating E2 and photoperiod can interact to shape auditory recognition and learning in adults, driving it in opposite directions in different states. PMID:24058881

  5. Transdermal estradiol for postpartum depression: A promising treatment option

    PubMed Central

    Moses-Kolko, Eydie L.; Berga, Sarah L.; Kalro, Brinda; Sit, Dorothy K.Y.; Wisner, Katherine L.

    2009-01-01

    Postpartum depression (PPD) is the most common complication of childbirth and affects one out of seven childbearing women. While conventional pharmacological and psychotherapeutic antidepressant treatments are effective for PPD, a natural alternative may be preferred by postpartum women, especially those who breastfeed their infants. The treatment of PPD with synthetic forms of naturally occurring estrogen is mechanistically appealing because PPD occurs in the context of estrogen withdrawal at parturition. Preliminary evidence suggests that PPD is a disorder of hormone-related mood dysregulation (similar to perimenopausal depression) that can be effectively treated with estrogen. This review provides the basic science and clinical background as well as safety considerations to support the application of transdermal estradiol as a treatment for PPD. We conclude that estradiol treatment for PPD requires confirmation of efficacy in a randomized clinical trial prior to routine clinical use as monotherapy. Additional data regarding maternal tolerability of cyclic progestins, long-term safety of estradiol treatment, estradiol passage into breastmilk and infants, and interdisciplinary collaboration among psychiatrists and gynecologists is also needed before estradiol is used in women who decline or fail to respond to first-line antidepressant treatments, or as an augmentation of conventional antidepressant treatment. PMID:19661765

  6. The role of estradiol in male reproductive function.

    PubMed

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  7. The role of estradiol in male reproductive function

    PubMed Central

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  8. Comparative effects of Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension) and ortho-Novum 7/7/7 oral contraceptive (norethindrone/ethinyl estradiol triphasic) on lipid profiles. Investigators from the Lunelle Study Group.

    PubMed

    Cromie, M A; Maile, M H; Wajszczuk, C P

    2000-01-01

    As part of a 60-week, open-label, nonrandomized, parallel, controlled study comparing a monthly contraceptive injection containing medroxyprogesterone acetate (MPA) 25 mg and estradiol cypionate (E(2)C) 5 mg (Lunelle Monthly Contraceptive Injection) and a norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum(R) 7/7/7), a longitudinal examination of lipid profiles was conducted. Lipid parameters were assessed at screening and at weeks 20, 40, and 60 (or the final visit) in 114 women using MPA/E(2)C and 93 using NET/EE (lipid analysis population). Extra blood samples were obtained at weeks 21, 22, and 23 in 61 MPA/E(2)C users and 51 NET/EE users (index-cycle analysis population) to investigate lipid changes during one cycle of use. In the index-cycle population, median changes from screening to week 60 showed a decrease in apolipoprotein (apo) A-I and apo A-II in both groups. MPA/E(2)C users had a decrease in total cholesterol (C), total triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with maintenance of the total C/HDL-C ratio. NET/EE users showed an increase in total C and LDL-C, with no change in HDL-C or the total C/HDL-C ratio. Within the index cycle (weeks 20 to 23), median changes in lipid values in both MPA/E(2)C and NET/EE users were generally greatest during the first week after the injection or the start of the pill pack. The results of this first longitudinal examination of serum lipids in US women using MPA/E(2)C confirm earlier findings in women in other countries. However, a direct comparison of the effects of MPA/E(2)C and NET/EE on lipid profiles was not possible in this study because of its design and because of the baseline and pharmacokinetic/pharmacodynamic differences between the two contraceptive groups. The results of this analysis showed that, although overall lipid values decreased, including a significant decrease in HDL

  9. A highly-efficient imprinted magnetic nanoparticle for selective separation and detection of 17β-estradiol in milk.

    PubMed

    Gao, Ruixia; Cui, Xihui; Hao, Yi; Zhang, Lili; Liu, Dechun; Tang, Yuhai

    2016-03-01

    In this work, we prepared molecularly imprinted polymers (MIPs) combining surface molecular imprinting technique and magnetic separation for separation and determination of 17β-estradiol (E2) from milk. During the synthesis process, the acryloyl chloride was specially used to graft double bonds on Fe3O4 nanoparticles and served as co-functional monomer cooperating with acrylamide. The morphology, structure proper