Role of Steroids in Hyperexcitatory Adverse and Anesthetic Effects of Sevoflurane in Neonatal Rats.

PubMed

Zhang, Jiaqiang; Xu, Changqing; Puentes, Dyanet L; Seubert, Christoph N; Gravenstein, Nikolaus; Martynyuk, Anatoly E

2016-01-01

Recent studies have demonstrated that long-term developmental effects of neonatal anesthesia were more prominent in males. We tested whether steroids, in general, and sex steroids, in particular, are involved in the mediation of sevoflurane-caused paradoxical cortical seizures during the early postnatal period. Cortical electroencephalograms, hippocampal synaptic activity, serum levels of steroids and the loss of the righting reflex (LORR), a marker of anesthetic effect, were measured on postnatal days 4-6 in Sprague Dawley rats of both genders exposed to 2.1% sevoflurane. Episodes of seizures, persistent spikes in electroencephalograms and increases in serum corticosterone were similar in both genders. In the order of increasing potency, the corticosteroid receptor antagonist RU 28318, the estradiol receptor antagonist ICI 182780 and the estradiol synthesis inhibitor formestane decreased sevoflurane-induced seizures. Exogenous estradiol increased sevoflurane-caused seizures, spikes and serum levels of corticosterone. These estradiol-enhanced seizures and spikes were depressed by ICI 182780 and the NKCC1 inhibitor, bumetanide, while RU 28318 decreased seizures only. In hippocampal CA1 neurons, estradiol increased the amplitude, rise time and area under the curve of gamma-aminobutyric acid type A receptor (GABAAR)-mediated miniature postsynaptic currents. Exogenous estradiol shortened, while ICI 182780 and formestane lengthened the time needed for sevoflurane to induce LORR. These findings provide evidence for gender-independent acute electroencephalographic effects of sevoflurane at this age. Corticosterone and estradiol are involved in the mediation of sevoflurane-induced seizures. Estradiol, but not corticosterone, also contributes to sevoflurane-caused spikes, by enhancing GABAAR-mediated excitation in the cortex. By increasing GABAAR-mediated inhibition in more mature caudal regions of the brain, estradiol contributes to sevoflurane-induced LORR. © 2015 S. Karger AG, Basel.

Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats

NASA Astrophysics Data System (ADS)

Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying

2015-10-01

The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.

Estradiol alters body temperature regulation in the female mouse.

PubMed

Krajewski-Hall, Sally J; Blackmore, Elise M; McMinn, Jessi R; Rance, Naomi E

2018-01-01

Hot flushes are due to estrogen withdrawal and characterized by the episodic activation of heat dissipation effectors. Recent studies (in humans and rats) have implicated neurokinin 3 (NK 3 ) receptor signaling in the genesis of hot flushes. Although transgenic mice are increasingly used for biomedical research, there is limited information on how 17β-estradiol and NK 3 receptor signaling alters thermoregulation in the mouse. In this study, a method was developed to measure tail skin temperature (T SKIN ) using a small data-logger attached to the surface of the tail, which, when combined with a telemetry probe for core temperature (T CORE ), allowed us to monitor thermoregulation in freely-moving mice over long durations. We report that estradiol treatment of ovariectomized mice reduced T CORE during the light phase (but not the dark phase) while having no effect on T SKIN or activity. Estradiol also lowered T CORE in mice exposed to ambient temperatures ranging from 20 to 36°C. Unlike previous studies in the rat, estradiol treatment of ovariectomized mice did not reduce T SKIN during the dark phase. Subcutaneous injections of an NK 3 receptor agonist (senktide) in ovariectomized mice caused an acute increase in T SKIN and a reduction in T CORE , consistent with the activation of heat dissipation effectors. These changes were reduced by estradiol, suggesting that estradiol lowers the sensitivity of central thermoregulatory pathways to NK 3 receptor activation. Overall, we show that estradiol treatment of ovariectomized mice decreases T CORE during the light phase, reduces the thermoregulatory effects of senktide and modulates thermoregulation differently than previously described in the rat.

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells.

PubMed

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-04-19

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin.

Metformin inhibits 17β-estradiol-induced epithelial-to-mesenchymal transition via βKlotho-related ERK1/2 signaling and AMPKα signaling in endometrial adenocarcinoma cells

PubMed Central

Liu, Zhao; Qi, Shasha; Zhao, Xingbo; Li, Mingjiang; Ding, Sentai; Lu, Jiaju; Zhang, Hui

2016-01-01

The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17β-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17β-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17β-estradiol-induced cell proliferation and reversed 17β-estradiol-induced EMT in Ishikawa cells. In addition, metformin increased the expression of βKlotho, a fibroblast growth factors (FGFs) coreceptor, and decreased ERK1/2 phosphorylation in both Ishikawa and KLE cells. Decreased expression of βKlotho was noted in human endometrial adenocarcinomas, and plasmid-driven expression of βKlotho in Ishikawa cells abolished 17β-estradiol-induced EMT via inhibiting ERK1/2 signaling. βKlotho expression and metformin show synergetic effects on the proliferation and the EMT in Ishikawa cells. Furthermore, we demonstrated that the anti-EMT effects of metformin could be partly abolished by introducing Compound C, a specific AMPKα signaling inhibitor. In conclusion, metformin abolishes 17β-estradiol-induced cell proliferation and EMT in endometrial adenocarcinoma cells by upregulating βKlotho expression, inhibiting ERK1/2 signaling, and activating AMPKα signaling. Our study provides novel mechanistic insight into the anti-tumor effects of metformin. PMID:26824324

Estradiol-modified prolactin secretion independently of action potentials and Ca2+ and blockade of outward potassium currents in GH3 cells.

PubMed

Sánchez, Manuel; Suárez, Lorena; Cantabrana, Begoña; Bordallo, Javier

2017-01-01

Estrogens facilitate prolactin (PRL) secretion acting on pituitary cells. In GH 3 cells, estradiol induces acute action potentials and oscillations of intracellular Ca 2+ associated with the secretagogue function. Estradiol modulates several ion channels which may affect the action potential rate and the release of PRL in lactotroph cells, which might depend on its concentration. The aims were to characterize the acute effect of supraphysiological concentrations of estradiol on Ca 2+ and noninactivating K + currents and measure the effect on the spontaneous action potentials and PRL release in the somatolactotroph cell line, GH 3 . Electrophysiological studies were carried out by voltage- and current-clamp techniques and ELISA determination of PRL secretion. Pharmacological concentrations of estradiol (above 1 μM), without a latency period, blocked Ca 2+ channels and noninactivating K + currents, including the large-conductance voltage- and Ca 2+ -activated K + channels (BK), studied in whole-cell nystatin perforated and in excided inside-out patches of GH 3 and CHO cells, transiently transfected with the human α-pore forming subunit of BK. The effect on BK was contrary to the agonist effect associated with the regulatory β 1 -subunits of the BK, which GH 3 cells lack, but its transient transfection did not modify the noninactivating current blockade, suggesting a different mechanism of regulation. Estradiol, at the same concentration range, acutely decreased the frequency of action potentials, an expected effect as consequence of the Ca 2+ channel blockade. Despite this, PRL secretion initially increased, followed by a decrease in long-term incubations. This suggests that, in GH 3 cells, supraphysiological concentrations of estradiol modulating PRL secretion are partially independent of extracellular Ca 2+ influx.

Estradiol regulates the insulin-like growth factor-I (IGF-I) signalling pathway: A crucial role of phosphatidylinositol 3-kinase (PI 3-kinase) in estrogens requirement for growth of MCF-7 human breast carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Laurence; Legay, Christine; Adriaenssens, Eric

2006-12-01

Estrogens can stimulate the proliferation of estrogen-responsive breast cancer cells by increasing their proliferative response to insulin-like growth factors. With a view to investigating the molecular mechanisms implicated, we studied the effect of estradiol on the expression of proteins implicated in the insulin-like growth factor signalling pathway. Estradiol dose- and time-dependently increased the expression of insulin receptor substrate-1 and the p85/p110 subunits of phosphatidylinositol 3-kinase but did not change those of ERK2 and Akt/PKB. ICI 182,780 did not inhibit estradiol-induced IRS-1 and p85 expression. Moreover, two distinct estradiol-BSA conjugate compounds were as effective as estradiol in inducing IRS-1 and p85/p110more » expression indicating the possible implication of an estradiol membrane receptor. Comparative analysis of steroids-depleted and steroids-treated cells showed that IGF-I only stimulates cell growth in the latter condition. Nevertheless, expression of a constitutively active form of PI 3-kinase in steroid-depleted cells triggers proliferation. These results demonstrate that estradiol positively regulates essential proteins of the IGF signalling pathway and put in evidence that phosphatidylinositol 3-kinase plays a central role in the synergistic pro-proliferative action of estradiol and IGF-I.« less

Aromatase inhibitor (anastrozole) affects growth of endometrioma cells in culture.

PubMed

Badawy, Shawky Z A; Brown, Shereene; Kaufman, Lydia; Wojtowycz, Martha A

2015-05-01

To study the effects of aromatase inhibitor (anastrozole) on the growth and estradiol secretion of endometrioma cells in culture. Endometrioma cells are grown in vitro until maximum growth before used in this study. This was done in the research laboratory for tissue culture, in an academic hospital. Testosterone at a concentration of 10 μg/mL was added as a substrate for the intracellular aromatase. In addition, aromatase inhibitor was added at a concentration of 200 and 300 μg/mL. The effect on cell growth and estradiol secretion is evaluated using Student's t-test. The use of testosterone increased estradiol secretion by endometrioma cells in culture. The use of aromatase inhibitor significantly inhibited the growth of endometrioma cells, and estradiol secretion. Aromatase inhibitor (anastrozole) may be an effective treatment for endometriosis due to inhibition of cellular aromatase. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sex hormones affect language lateralisation but not cognitive control in normally cycling women.

PubMed

Hodgetts, Sophie; Weis, Susanne; Hausmann, Markus

2015-08-01

This article is part of a Special Issue "Estradiol and Cognition". Natural fluctuations of sex hormones during the menstrual cycle have been shown to modulate language lateralisation. Using the dichotic listening (DL) paradigm, a well-established measurement of language lateralisation, several studies revealed that the left hemispheric language dominance was stronger when levels of estradiol were high. A recent study (Hjelmervik et al., 2012) showed, however, that high levels of follicular estradiol increased lateralisation only in a condition that required participants to cognitively control (top-down) the stimulus-driven (bottom-up) response. This finding suggested that sex hormones modulate lateralisation only if cognitive control demands are high. The present study investigated language lateralisation in 73 normally cycling women under three attention conditions that differed in cognitive control demands. Saliva estradiol and progesterone levels were determined by luminescence immunoassays. Women were allocated to a high or low estradiol group. The results showed a reduced language lateralisation when estradiol and progesterone levels were high. The effect was independent of the attention condition indicating that estradiol marginally affected cognitive control. The findings might suggest that high levels of estradiol especially reduce the stimulus-driven (bottom-up) aspect of lateralisation rather than top-down cognitive control. Copyright © 2015 Elsevier Inc. All rights reserved.

High estradiol levels improve false memory rates and meta-memory in highly schizotypal women.

PubMed

Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

2015-10-30

Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 μg/levonorgestrel 100 μg + ethinyl estradiol 10 μg.

PubMed

Krishnan, Sheila; Kiley, Jessica

2010-08-10

Extended-cycle oral contraceptives (OCs) are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE) and levonorgestrel (LNG) + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 μg and ethinyl estradiol 20 μg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 μg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.

Exogenous application of estradiol to eggs unexpectedly induces male development in two turtle species with temperature-dependent sex determination.

PubMed

Warner, Daniel A; Addis, Elizabeth; Du, Wei-guo; Wibbels, Thane; Janzen, Fredric J

2014-09-15

Steroid hormones affect sex determination in a variety of vertebrates. The feminizing effects of exposure to estradiol and the masculinizing effects of aromatase inhibition during development are well established in a broad range of vertebrate taxa, but paradoxical findings are occasionally reported. Four independent experiments were conducted on two turtle species with temperature-dependent sex determination (Chrysemys picta and Chelydra serpentina) to quantify the effects of egg incubation temperature, estradiol, and an aromatase inhibitor on offspring sex ratios. As expected, the warmer incubation temperatures induced female development and the cooler temperatures produced primarily males. However, application of an aromatase inhibitor had no effect on offspring sex ratios, and exogenous applications of estradiol to eggs produced male offspring across all incubation temperatures. These unexpected results were remarkably consistent across all four experiments and both study species. Elevated concentrations of estradiol could interact with androgen receptors or inhibit aromatase expression, which might result in relatively high testosterone concentrations that lead to testis development. These findings add to a short list of studies that report paradoxical effects of steroid hormones, which addresses the need for a more comprehensive understanding of the role of sex steroids in sexual development. Copyright © 2014 Elsevier Inc. All rights reserved.

Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory.

PubMed

Herrera, Alexandra Ycaza; Hodis, Howard N; Mack, Wendy J; Mather, Mara

2017-12-01

Postmenopausal estradiol therapy (ET) can reduce the stress response. However, it remains unclear whether such reductions can mitigate effects of stress on cognition. Investigate effects of ET on cortisol response to a physical stressor, cold pressor test (CPT), and whether ET attenuates stress effects on working memory. Women completed the CPT or control condition across two sessions and subsequently completed a sentence span task. General community: Participants were recruited from the Early vs Late Intervention Trial with Estradiol (ELITE). ELITE participants (mean age = 66, standard deviation age = 6.8) in this study did not suffer from any major chronic illness or use medications known to affect the stress response or cognition. Participants had received a median of randomized 4.7 years of estradiol (n = 21) or placebo (n = 21) treatment at time of participation in this study. Salivary cortisol and sentence span task performance. Women assigned to estradiol exhibited blunted cortisol responses to CPT compared with placebo (P = 0.017) and lesser negative effects of stress on working memory (P = 0.048). We present evidence suggesting ET may protect certain types of cognition in the presence of stress. Such estrogenic protection against stress hormone exposure may prove beneficial to both cognition and the neural circuitry that maintains and propagates cognitive faculties. Copyright © 2017 Endocrine Society

Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

PubMed

Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

2000-04-03

To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

Preparation and characterization of marine sponge collagen nanoparticles and employment for the transdermal delivery of 17beta-estradiol-hemihydrate.

PubMed

Nicklas, Martina; Schatton, Wolfgang; Heinemann, Sascha; Hanke, Thomas; Kreuter, Jörg

2009-09-01

Transdermal administration of estradiol offers advantages over oral estrogens for hormone replacement therapy regarding side effects by bypassing the hepatic presystemic metabolism. The objective of this study was to develop nanoparticles of Chondrosia reniformis sponge collagen as penetration enhancers for the transdermal drug delivery of 17beta-estradiol-hemihydrate in hormone replacement therapy. Collagen nanoparticles were prepared by controlled alkaline hydrolysis and characterized using atomic force microscopy and photon correlation spectroscopy. Estradiol-hemihydrate was loaded to the nanoparticles by adsorption to their surface, whereupon a drug loading up to 13.1% of sponge collagen particle mass was found. After incorporation of drug-loaded nanoparticles in a hydrogel, the estradiol transdermal delivery from the gel was compared with that from a commercial gel that did not contain nanoparticles. Saliva samples in postmenopausal patients showed significantly higher estradiol levels after application of the gel with nanoparticles. The area under the curve (AUC) for estradiol time-concentration curves over 24 hours was 2.3- to 3.4-fold higher and estradiol levels 24 hours after administration of estradiol were at least twofold higher with the nanoparticle gel. The hydrogel with estradiol-loaded collagen nanoparticles enabled a prolonged estradiol release compared to a commercial gel and yielded a considerably enhanced estradiol absorption. Consequently, sponge collagen nanoparticles represent promising carriers for transdermal drug delivery.

Voluntary Exercise Impairs Initial Delayed Spatial Alternation Performance in Estradiol Treated Ovariectomized Middle-Aged Rats

PubMed Central

Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

2013-01-01

Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradiol induced deficits on DSA performance. OVX 12-month old Long- Evans rats were implanted with a Silastic capsule containing 17β-estradiol (10% in cholesterol: low physiological range) or with a blank capsule. A subset of the 17β-estradiol and OVX untreated rats were given free access to a running wheel in their home cage. All rats were tested for 40 sessions on the DSA task. Surprisingly, we found running wheel access to impair initial acquisition of the DSA task in 17β-estradiol treated rats, an effect not seen in OVX untreated rats given running wheel access. This deficit was driven by an increase in perseverative responding on a lever no longer associated with reinforcement. We also report for the first time a 17β-estradiol induced impairment on the DSA task following a long intertrial delay (18-sec), an effect revealed following more extended testing than in our previous studies (15 additional sessions). Overall, running wheel access increased initial error rate on the DSA task in 17β-estradiol treated middle-aged OVX rats, and failed to prevent the 17β-estradiol induced deficits in performance of the operant DSA task in later testing sessions. PMID:24013039

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PubMed

Check, J H; Amui, J; Choe, J K; Cohen, R

2015-01-01

To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

Estradiol concentrations and working memory performance in women of reproductive age.

PubMed

Hampson, Elizabeth; Morley, Erin E

2013-12-01

Estrogen has been proposed to exert a regulatory influence on the working memory system via actions in the female prefrontal cortex. Tests of this hypothesis have been limited almost exclusively to postmenopausal women and pharmacological interventions. We explored whether estradiol discernibly influences working memory within the natural range of variation in concentrations characteristic of the menstrual cycle. The performance of healthy women (n=39) not using hormonal contraceptives, and a control group of age- and education-matched men (n=31), was compared on a spatial working memory task. Cognitive testing was done blind to ovarian status. Women were retrospectively classified into low- or high-estradiol groups based on the results of radioimmunoassays of saliva collected immediately before and after the cognitive testing. Women with higher levels of circulating estradiol made significantly fewer errors on the working memory task than women tested under low estradiol. Pearson's correlations showed that the level of salivary estradiol but not progesterone was correlated inversely with the number of working memory errors produced. Women tested at high levels of circulating estradiol tended to be more accurate than men. Superior performance by the high estradiol group was seen on the working memory task but not on two control tasks, indicating selectivity of the effects. Consistent with previous studies of postmenopausal women, higher levels of circulating estradiol were associated with better working memory performance. These results add further support to the hypothesis that the working memory system is modulated by estradiol in women, and show that the effects can be observed under non-pharmacological conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat.

PubMed

Russell, Ashley L; Grimes, Jamie Moran; Cruthirds, Danette F; Westerfield, Joanna; Wooten, Lawren; Keil, Margaret; Weiser, Michael J; Landauer, Michael R; Handa, Robert J; Wu, T John; Larco, Darwin O

2017-06-01

17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin levels (p<0.05) compared to animals fed an isoflavone-free diet. Estradiol replacement resulted in decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin (p<0.05). Current literature suggests the involvement of cytokines in the inflammatory response of body weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (p<0.05) diet-dependent increases in inflammatory cytokines (keratinocyte-derived chemokine). The isoflavone-free diet in OVX rats resulted in the regulation of the following cytokines and chemokines: interleukin-10, interleukin-18, serum regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 (p<0.05). Overall, these results reveal that estradiol treatment can have differential effects on energy metabolism and body weight regulation depending on the presence of isoflavones in rodent chow. © Georg Thieme Verlag KG Stuttgart · New York.

Developmental Programming: Contribution of Prenatal Androgen and Estrogen to Estradiol Feedback Systems and Periovulatory Hormonal Dynamics in Sheep1

PubMed Central

Veiga-Lopez, Almudena; Astapova, Olga I.; Aizenberg, Esther F.; Lee, James S.; Padmanabhan, Vasantha

2009-01-01

Prenatal testosterone excess leads to neuroendocrine and periovulatory disruptions in the offspring culminating in progressive loss of cyclicity. It is unknown whether the mediary of these disruptions is androgen or estrogen, because testosterone can be aromatized to estrogen. Taking a reproductive life span approach of studying control, prenatal testosterone, and dihydrotestosterone-treated offspring, this study tested the hypothesis that disruptions in estradiol-negative but not -positive feedback effects are programmed by androgenic actions of testosterone and that these disruptions in turn will have an impact on the periovulatory hormonal dynamics. The approach was to test estradiol-negative and -positive feedback responses of all three groups of ovary-intact females during prepubertal age and then compare the periovulatory dynamics of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone during the first breeding season. The findings show that estradiol-negative but not estradiol-positive feedback disruptions in prenatal testosterone-treated females are programmed by androgenic actions of prenatal testosterone excess and that follicular phase estradiol and gonadotropins surge disruptions during reproductive life are consistent with estrogenic programming. Additional studies carried out testing estradiol-positive feedback response over time found progressive deterioration of estradiol-positive feedback in prenatal testosterone-treated sheep until the time of puberty. Together, these findings provide insight into the mechanisms by which prenatal testosterone disrupts the reproductive axis. The findings may be of translational relevance since daughters of mothers with hyperandrogenism are at risk of increased exposure to androgens. PMID:19122183

Developmental programming: contribution of prenatal androgen and estrogen to estradiol feedback systems and periovulatory hormonal dynamics in sheep.

PubMed

Veiga-Lopez, Almudena; Astapova, Olga I; Aizenberg, Esther F; Lee, James S; Padmanabhan, Vasantha

2009-04-01

Prenatal testosterone excess leads to neuroendocrine and periovulatory disruptions in the offspring culminating in progressive loss of cyclicity. It is unknown whether the mediary of these disruptions is androgen or estrogen, because testosterone can be aromatized to estrogen. Taking a reproductive life span approach of studying control, prenatal testosterone, and dihydrotestosterone-treated offspring, this study tested the hypothesis that disruptions in estradiol-negative but not -positive feedback effects are programmed by androgenic actions of testosterone and that these disruptions in turn will have an impact on the periovulatory hormonal dynamics. The approach was to test estradiol-negative and -positive feedback responses of all three groups of ovary-intact females during prepubertal age and then compare the periovulatory dynamics of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone during the first breeding season. The findings show that estradiol-negative but not estradiol-positive feedback disruptions in prenatal testosterone-treated females are programmed by androgenic actions of prenatal testosterone excess and that follicular phase estradiol and gonadotropins surge disruptions during reproductive life are consistent with estrogenic programming. Additional studies carried out testing estradiol-positive feedback response over time found progressive deterioration of estradiol-positive feedback in prenatal testosterone-treated sheep until the time of puberty. Together, these findings provide insight into the mechanisms by which prenatal testosterone disrupts the reproductive axis. The findings may be of translational relevance since daughters of mothers with hyperandrogenism are at risk of increased exposure to androgens.

EFFECTS OF ETHINYL ESTRADIOL ON GONDAL DEVELOPMENT AND PATHOLOGY IN CUNNER, TAUTOGOLABRUS ADSPERSUS

EPA Science Inventory

The intent of this study was to determine histopathologically the effect of ethinyl estradiol (EE2) on gonadal development, liver and kidney condition in reproductively active cunner, Tautogolabrus adspersus. Reproductively active cunner were treated by implanting EE2 in a slow r...

Estradiol shows anti-skin cancer activities through decreasing MDM2 expression.

PubMed

Li, Li; Feng, Jianguo; Chen, Ying; Li, Shun; Ou, Mengting; Sun, Weichao; Tang, Liling

2017-01-31

Estradiol plays important roles in many biological responses inducing tumor genesis and cancer treatment. However, the effects of estradiol on tumors were inconsistent among a lot of researches and the mechanism is not fully understood. Our previous study indicated that splicing factor hnRNPA1 could bind to the human homologue of mouse double minute (MDM2), an oncogene which has been observed to be over-expressed in numerous types of cancers. In this research, we investigated whether and how estradiol correlate to cancer cell behaviors through heterogeneous nuclear ribonucleoprotein (hnRNPA1) and MDM2. Results showed that 10×10-13Mestradiol elevated the expression of hnRNPA1 regardless ER expression in cells, and then down-regulated the expression of MDM2. At the same time, estradiol inhibited cell proliferation, migration and epithelial-mesenchymal transition progression of A375 and GLL19 cells. While, knocking down hnRNPA1 through the transfection of hnRNPA1 siRNA led to the increase of MDM2 at both protein level and gene level In vivo experiment, subcutaneous injection with estradiol every two days near the tumor at doses of 2.5mg/kg/d suppressed tumor growth and reduced MDM2 expression. In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas. We confirmed therapeutic effect of estradiol, as well as a new way for estradiol to resist skin cancer.

Leptin Signaling Is Not Required for Anorexigenic Estradiol Effects in Female Mice.

PubMed

Kim, Joon S; Rizwan, Mohammed Z; Clegg, Deborah J; Anderson, Greg M

2016-05-01

Estradiol and leptin are critical hormones in the regulation of body weight. The aim of this study was to determine whether this cross talk between leptin receptor (LepRb) and estrogen receptor-α (ERα) signaling is critical for estradiol's anorexigenic effects. Leprb-Cre mice were crossed with Cre-dependent Tau-green fluorescent protein (GFP) reporter, Stat3-flox or Erα-flox mice to generate female mice with GFP expression, signal transducer and activator of transcription 3 (STAT3) knockout (KO), or ERα KO, specifically in LepRb-expressing cells. The proportion of Leprb-GFP cells colocalizing ERα was high (∼80%) in the preoptic area but low (∼10%) in the mediobasal hypothalamus, suggesting that intracellular cross talk between these receptors is minimal for metabolic regulation. To test whether estradiol enhanced arcuate leptin sensitivity, ovarectomized mice received varying levels of estradiol replacement. Increasing estrogenic states did not increase the degree of leptin-induced STAT3 phosphorylation. LepRb-specific STAT3 KO mice and controls were ovarectomized and given either chronic estradiol or vehicle treatment to test whether STAT3 is required for estrogen-induced body weight suppression. Both groups of estradiol-treated mice showed an equivalent reduction in body weight and fat content compared with vehicle controls. Finally, mice lacking ERα specifically in LepRb-expressing neurons also showed no increase in body weight or impairments in metabolic function compared with controls, indicating that estradiol acts independently of leptin-responsive cells to regulate body weight. However, fecundity was impaired in in Leprb-ERα KO females. Contrary to the current dogma, we report that estradiol has minimal direct actions on LepRb cells in the mediodasal hypothalamus and that its anorexigenic effects can occur entirely independently of LepRb-STAT3 signaling in female mice.

The effects on ovarian activity of a monophasic oral contraceptive with 100 microg levonorgestrel and 20 microg ethinyl estradiol.

PubMed

Coney, P; DelConte, A

1999-11-01

An open-label, single-center, noncomparative study was conducted to determine the effects of a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol on ovarian activity. The subjects were 26 healthy women 20 to 35 years of age who had normal ovulatory cycles and were not at risk for becoming pregnant. For 3 treatment cycles, they took 1 tablet of active drug daily for 21 days followed by placebo tablets for 7 days. Follicle diameters and serum progesterone and 17beta-estradiol levels were measured before, during, and after treatment. In 2 (2.7%) of 73 cycles, luteinized unruptured follicles were present and in another 2 (2.7%) cycles, ovulation was confirmed by the disappearance of the enlarged follicle. Ovarian activity, as reflected by mean serum progesterone levels, was restored after treatment. The results of this study are in agreement with those of other studies that showed suppression of ovarian activity in women treated with a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. These results indicate that low-dose 100 microg levonorgestrel and 20 microg ethinyl estradiol given for 21 days is effective in suppressing ovarian activity and they confirm the contraceptive efficacy observed in clinical trials (Pearl index of 0.8).

Differential effects of raloxifene and estrogen on body composition in growth hormone-replaced hypopituitary women.

PubMed

Birzniece, Vita; Meinhardt, Udo J; Gibney, James; Johannsson, Gudmundur; Armstrong, Nicola; Baxter, Robert C; Ho, Ken K Y

2012-03-01

GH deficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuated more markedly by raloxifene, a selective estrogen receptor modulator, compared with 17β-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown. Our objective was to compare the effects of 17β-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement. This was an open-label randomized crossover study. Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17β-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months; the other received the reversed sequence. Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects. GH therapy significantly increased mean IGF-I during 17β-estradiol and raloxifene cotreatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17β-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene. In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17β-estradiol. Raloxifene has no metabolic advantage over 17β-estradiol during GH replacement.

Estradiol, dopamine and motivation.

PubMed

Yoest, Katie E; Cummings, Jennifer A; Becker, Jill B

2014-01-01

The gonadal hormone estradiol modulates mesolimbic dopamine systems in the female rat. This modulatory effect is thought to be responsible for the observed effects of estradiol on motivated behaviors. Dopamine acting in the nucleus accumbens is thought to be important for the attribution of incentive motivational properties to cues that predict reward delivery, while dopamine in the striatum is associated with the expression of repetitive or stereotyped behaviors. Elevated concentrations of estradiol are associated with increased motivation for sex or cues associated with access to a mate, while simultaneously attenuating motivation for food. This shift in motivational salience is important for adaptive choice behavior in the natural environment. Additionally, estradiol's adaptive effects on motivation can be maladaptive when increasing motivation for non-natural reinforcers, such as drugs of abuse. Here we discuss the effect of estradiol on mesotelencephalic dopamine transmission and subsequent effects on motivated behaviors.

Estradiol modulates neural response to conspecific and heterospecific song in female house sparrows: An in vivo positron emission tomography study

PubMed Central

Stabile, Frank A.; Carson, Richard E.

2017-01-01

Although there is growing evidence that estradiol modulates female perception of male sexual signals, relatively little research has focused on female auditory processing. We used in vivo 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the neuronal effects of estradiol and conspecific song in female house sparrows (Passer domesticus). We assessed brain glucose metabolism, a measure of neuronal activity, in females with empty implants, estradiol implants, and empty implants ~1 month after estradiol implant removal. Females were exposed to conspecific or heterospecific songs immediately prior to imaging. The activity of brain regions involved in auditory perception did not differ between females with empty implants exposed to conspecific vs. heterospecific song, but neuronal activity was significantly reduced in females with estradiol implants exposed to heterospecific song. Furthermore, our within-individual design revealed that changes in brain activity due to high estradiol were actually greater several weeks after peak hormone exposure. Overall, this study demonstrates that PET imaging is a powerful tool for assessing large-scale changes in brain activity in living songbirds, and suggests that after breeding is done, specific environmental and physiological cues are necessary for estradiol-stimulated females to lose the selectivity they display in neural response to conspecific song. PMID:28832614

The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.

PubMed

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2014-09-01

There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P < 0.05; 30 mg/kg, P < 0.05) reduced immobility by increasing swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P < 0.05) reduced immobility by increasing swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.

Estradiol increases choice of cocaine over food in male rats.

PubMed

Bagley, Jared R; Adams, Julia; Bozadjian, Rachel V; Bubalo, Lana; Ploense, Kyle L; Kippin, Tod E

2017-10-19

Estradiol modulates the rewarding and reinforcing properties of cocaine in females, including an increase in selection of cocaine over alternative reinforcers. However, the effects of estradiol on male cocaine self-administration behavior are less studied despite equivalent levels of estradiol in the brains of adult males and females, estradiol effects on motivated behaviors in males that share underlying neural substrates with cocaine reinforcement as well as expression of estrogen receptors in the male brain. Therefore, we sought to characterize the effects of estradiol in males on choice between concurrently-available cocaine and food reinforcement as well as responding for cocaine or food in isolation. Male castrated rats (n=46) were treated daily with estradiol benzoate (EB) (5μg/0.1, S.C.) or vehicle (peanut oil) throughout operant acquisition of cocaine (1mg/kg, IV; FI20 sec) and food (3×45mg; FI20 sec) responding, choice during concurrent access and cocaine and food reinforcement under progressive ratio (PR) schedules. EB increased cocaine choice, both in terms of percent of trials on which cocaine was selected and the proportion of rats exhibiting a cocaine preference as well as increased cocaine, but not food, intake under PR. Additionally, within the EB treated group, cocaine-preferring rats exhibited enhanced acquisition of cocaine, but not food, reinforcement whereas no acquisition differences were observed across preferences in the vehicle treated group. These findings demonstrate that estradiol increases cocaine choice in males similarly to what is observed in females. Copyright © 2017 Elsevier Inc. All rights reserved.

Estrogen-withdrawal migraine. I. Duration of exposure required and attempted prophylaxis by premenstrual estrogen administration.

PubMed

Somerville, B W

1975-03-01

The minimum exposure to estrogen required to cause estrogen-withdrawal migraine has been studied by giving long-acting estradiol valerate to four women and short-acting estradiol benzoate to two women. It was found that several days of exposure to high estrogen levels were needed to cause migraine on estrogen withdrawal. Oral administration of estrogen supplements in the form of estradiol valerate or as conjugated equine estrogens during the premenstrual phase in four women did not significantly affect plasma levels of estradiol, nor was it effective in preventing menstrual migraine.

Effects of different varieties of Maca (Lepidium meyenii) on bone structure in ovariectomized rats.

PubMed

Gonzales, Carla; Cárdenas-Valencia, Isaias; Leiva-Revilla, Johanna; Anza-Ramirez, Cecilia; Rubio, Julio; Gonzales, Gustavo F

2010-01-01

This study was designed to determine the effect of different varieties of maca (Lepidium meyenii) on bone structure in ovariectomized (OVX) rats. 36 female rats were randomly divided into 6 groups: sham and OVX rats treated with vehicle, estradiol (40 microg/kg), black, yellow or red maca (63 mg/ml) for 4 weeks. At the end of the treatment, uterine weight, femoral bone and lumbar vertebra histomorphology were assessed. Ovariectomy reduced weight, diameter and width of the femoral bone. Estradiol, black and red maca treatment reduced the effect of ovariectomy on these variables. Histological analyses revealed that estradiol, black and red maca treatments reversed the effect of ovariectomy by increasing the trabecular bone area in the second lumbar vertebra. Uterine weight was reduced in OVX rats, and estradiol but neither black nor red maca increased uterine weight. Red and black maca have protective effects on bone architecture in OVX rats without showing estrogenic effects on uterine weight. 2010 S. Karger AG, Basel.

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

PubMed

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did not. The results suggest rapid effects of estradiol on amphetamine sensitization consistent with rapid effects of estradiol reported for other behaviours. Copyright © 2017. Published by Elsevier Inc.

G protein-coupled estrogen receptor is required for the neuritogenic mechanism of 17β-estradiol in developing hippocampal neurons.

PubMed

Ruiz-Palmero, Isabel; Hernando, Maria; Garcia-Segura, Luis M; Arevalo, Maria-Angeles

2013-06-15

Estradiol promotes neuritogenesis in developing hippocampal neurons by a mechanism involving the upregulation of neurogenin 3, a Notch-regulated transcription factor. In this study we have explored whether G-protein coupled estrogen receptor 1 (GPER) participates in this hormonal action. GPER agonists (17β-estradiol, G1, ICI 182,780) increased neurogenin 3 expression and neuritogenesis in mouse primary hippocampal neurons and this effect was blocked by the GPER antagonist G15 and by a siRNA for GPER. In addition, GPER agonists increased Akt phosphorylation in ser473, which is indicative of the activation of phosphoinositide-3-kinase (PI3K). G15 or GPER silencing prevented the estrogenic induction of Akt phosphorylation. Furthermore, the PI3K inhibitor wortmannin prevented the effect of G1 and estradiol on neurogenin 3 expression and the effect of estradiol on neuritogenesis. These findings suggest that GPER participates in the control of hippocampal neuritogenesis by a mechanism involving the activation of PI3K signaling. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Rainfall timing effect on concentrations of testosterone and estradiol in surface runoff from broiler litter applied to grassed plots

USDA-ARS?s Scientific Manuscript database

Broiler litter contains the sex hormones testosterone and estradiol, which may contaminate surface runoff following litter application to grasslands. This study was conducted to evaluate the effect of runoff occurring at different times after litter application and under different environmental con...

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...

Estradiol and Progesterone Administration After pMCAO Stimulates the Neurological Recovery and Reduces the Detrimental Effect of Ischemia Mainly in Hippocampus.

PubMed

Perez-Alvarez, Maria Jose; Mateos, Laura; Alonso, Alvaro; Wandosell, Francisco

2015-12-01

Epidemiological studies have suggested a differential response, males versus female, in stroke incidence and prognosis. These divergences in brain response after damage are based mostly on hormonal differences. To date, estradiol and progesterone administered independently have demonstrated neuroprotection after ischemia in animal models. Nonetheless, contradictory results were revealed using a combined administration. In order to evaluate the effects of combinatorial treatment administered after ischemia induction, we used two different approaches: in vivo and in vitro models. Male rats which underwent permanent middle cerebral artery occlusion were treated with a combination of estradiol/progesterone at 6, 24 and 48 h after injury and sacrificed at 54 h post-ischemia. The rat brains were evaluated for reactive gliosis, NeuN-positive neurons, levels of synapse-associated proteins and activity levels of PI3K/Akt/GSK3/β-catenin survival pathway. Also, primary cortical neurons were subjected to oxygen and glucose deprivation for 17 h and returned to a normal environment in the presence of estradiol or estradiol/progesterone. Cell viability was evaluated, and activity levels of the PI3K/Akt/GSK3/β-catenin pathway. Our results indicate that some beneficial effects of estradiol were abolished in the presence of progesterone, particularly in the cerebral cortex (core). However, the combinatorial treatment showed positive effects in the hippocampus.

G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol.

PubMed

Otto, Christiane; Rohde-Schulz, Beate; Schwarz, Gilda; Fuchs, Iris; Klewer, Mario; Brittain, Dominic; Langer, Gernot; Bader, Benjamin; Prelle, Katja; Nubbemeyer, Reinhard; Fritzemeier, Karl-Heinrich

2008-10-01

The classical estrogen receptor (ER) mediates genomic as well as rapid nongenomic estradiol responses. In case of genomic responses, the ER acts as a ligand-dependent transcription factor that regulates gene expression in estrogen target tissues. In contrast, nongenomic effects are initiated at the plasma membrane and lead to rapid activation of cytoplasmic signal transduction pathways. Recently, an orphan G protein-coupled receptor, GPR30, has been claimed to bind to and to signal in response to estradiol. GPR30 therefore might mediate some of the nongenomic estradiol effects. The present study was performed to clarify the controversy about the subcellular localization of GPR30 and to gain insight into the in vivo function of this receptor. In transiently transfected cells as well as cells endogenously expressing GPR30, we confirmed that the receptor localized to the endoplasmic reticulum. However, using radioactive estradiol, we observed only saturable, specific binding to the classical ER but not to GPR30. Estradiol stimulation of cells expressing GPR30 had no impact on intracellular cAMP or calcium levels. To elucidate the physiological role of GPR30, we performed in vivo experiments with estradiol and G1, a compound that has been claimed to act as selective GPR30 agonist. In two classical estrogen target organs, the uterus and the mammary gland, G1 did not show any estrogenic effect. Taken together, we draw the conclusion that GPR30 is still an orphan receptor.

Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

PubMed Central

Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

2016-01-01

The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

17β-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway.

PubMed

Hoffmann, Marta; Fiedor, Elżbieta; Ptak, Anna

2016-11-01

Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17β-estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17β-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17β-estradiol and leptin, we observed antagonistic effects of 17β-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17β-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR + /ER + , 17β-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway. © The Author(s) 2016.

Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus.

PubMed

Davis, Angela M; Mao, Jiude; Naz, Bushra; Kohl, Jessica A; Rosenfeld, Cheryl S

2008-10-01

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.

Effect of diet on oxidation of 17 beta-estradiol in vivo.

PubMed

Musey, P I; Collins, D C; Bradlow, H L; Gould, K G; Preedy, J R

1987-10-01

The effect of a high fat, low carbohydrate, low protein diet on the in vivo oxidation of 17 beta-estradiol was studied using radiometric methods. Five male chimpanzees were fed a normal (13%) fat diet or a high (65%) fat diet for 8 weeks. After a 4-week rest period, the animals were fed the alternative diet. The mean percent oxidation of 16 alpha-[3H]estradiol-17 beta 24 h after injection was 3.8 +/- 1.3% (+/- SD) on the normal diet vs. 18.4 +/- 4.7% on the high fat diet (P less than 0.01). In contrast, the mean percent oxidation of 2-[3H]estradiol 24 h after injection was 31.6 +/- 3.8% (+/- SD) on the normal diet vs. 20.0 +/- 3.5% on the high fat diet (P less than 0.05). These results suggest that the oxidation of 17 beta-estradiol to estriols relative to that to catechol estrogens is increased by a high fat diet.

Hormonal Treatment of Transgender Women with Oral Estradiol.

PubMed

Leinung, Matthew C; Feustel, Paul J; Joseph, Jalaja

2018-01-01

Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.

Synchronization of follicular wave emergence in the seasonally anestrous ewe: the effects of estradiol with or without medroxyprogesterone acetate.

PubMed

Barrett, D M W; Bartlewski, P M; Duggavathi, R; Davies, K L; Huchkowsky, S L; Epp, T; Rawlings, N C

2008-04-15

Fertility is often lower in anestrous compared to cyclic ewes, after conventional estrus synchronization. We hypothesized that synchronization of ovarian follicular waves and ovulation could improve fertility at controlled breeding in anestrous ewes. Estradiol-17beta synchronizes follicular waves in cattle. The objectives of the present experiments were to study the effect of an estradiol injection, with or without a 12-d medroxyprogesterone acetate (MAP) sponge treatment, on synchronization of follicular waves and ovulation in anestrous ewes. Twenty ewes received sesame oil (n=8) or estradiol-17beta (350 microg; n=12). Eleven ewes received MAP sponges for 12d and were treated with oil (n=5) or estradiol-17beta (n=6) 6d before sponge removal. Saline (n=6) or eCG (n=6) was subsequently given to separate groups of ewes at sponge removal in the MAP/estradiol-17beta protocol. Estradiol treatment alone produced a peak in serum FSH concentrations (4.73+/-0.53 vs. 2.36+/-0.39 ng/mL for treatment vs. control; mean+/-S.E.M.) after a short-lived (6 h) suppression. Six of twelve ewes given estradiol missed a follicular wave around the time of estradiol injection. Medroxyprogesterone acetate-treated ewes given estradiol had more prolonged suppression of serum FSH concentrations (6-18 h) and a delay in the induced FSH peak (32.3+/-3.3 vs. 17.5+/-0.5 h). Wave emergence was delayed (5.7+/-0.3 vs. 1.4+/-0.7d from the time of estradiol injection), synchronized, and occurred at a predictable time (5-7 vs. 0-4d) compared to ewes given MAP alone. All ewes given eCG ovulated 3-4d after injection; this predictable time of ovulation may be efficacious for AI and embryo transfer.

A multicenter randomized comparison of cycle control and laboratory findings with oral contraceptive agents containing 100 microg levonorgestrel with 20 microg ethinyl estradiol or triphasic norethindrone with ethinyl estradiol.

PubMed

Reisman, H; Martin, D; Gast, M J

1999-11-01

This study was undertaken to compare the effects of 2 oral contraceptive regimens on menstrual cycle control and laboratory findings. In a multicenter randomized study 100 microg levonorgestrel with 20 microg ethinyl estradiol (Alesse or Loette) was given to 155 healthy women. A triphasic preparation of 500, 750, and 1000 microg norethindrone with 35 microg ethinyl estradiol (Ortho-Novum 7/7/7 or TriNovum) was given to 167 women for 1 to 4 cycles of treatment. Overall, the percentages of normal menstrual cycles and the percentages of cycles with intermenstrual and withdrawal bleeding were similar between the 2 treatment groups. In the levonorgestrel with ethinyl estradiol group, there was a statistically significantly longer latent period and a statistically significantly shorter withdrawal bleeding episode. Adverse events were similar between treatment groups, and none were serious. Most mean changes from baseline laboratory values were comparable between groups, although the mean increase in cholesterol concentration was statistically significantly lower in the levonorgestrel with ethinyl estradiol group. Changes in triglyceride and glucose concentrations were not statistically significantly different between groups. Levonorgestrel (100 microg) with ethinyl estradiol (20 microg) provides menstrual cycle control equivalent to that obtained with triphasic norethindrone with ethinyl estradiol (75% higher estrogen dose) with similar safety and tolerability.

Cognitive Performance in Healthy Women During Induced Hypogonadism and Ovarian Steroid Addback

PubMed Central

Schmidt, Peter J.; Keenan, PA; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn; Rubinow, David R.

2012-01-01

Background Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman’s symptomatic experience during the menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Methods Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were re-introduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. Results With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. Conclusions In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short term changes in gonadal steroids have a limited effect on cognition in young, healthy, women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause. Key Words: estradiol, hypogonadism, progesterone, cognition. PMID:23188540

Combined effects of sex hormone-binding globulin and sex hormones on risk of incident type 2 diabetes.

PubMed

Hu, Jinbo; Zhang, Aiping; Yang, Shumin; Wang, Yue; Goswami, Richa; Zhou, Huang; Zhang, Yi; Wang, Zhihong; Li, Rong; Cheng, Qingfeng; Zhen, Qianna; Li, Qifu

2016-07-01

The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008-13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62-51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21-4.53], 0.14 [95% CI 0.10-0.74]; Ptrend  = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Altered functional brain asymmetry for mental rotation: effect of estradiol changes across the menstrual cycle.

PubMed

Zhu, Xun; Kelly, Thomas H; Curry, Thomas E; Lal, Chitra; Joseph, Jane E

2015-09-30

Mental rotation is a visuospatial task associated with pronounced sex differences. Performance is also affected by gonadal hormones such as testosterone and estradiol. To better understand hormonal modulation of the neural substrates of mental rotation, the present study examined the influence of estradiol using functional MRI. Ten premenopausal women were tested on a 3D mental rotation task during the early follicular and late follicular phases of the menstrual cycle. Change in estradiol between the two phases was confirmed by hormone assays. Brain activation patterns were similar across the two phases, but the change in estradiol had different associations with the two hemispheres. Better performance in the late follicular than the early follicular phase was associated with a pattern of reduced recruitment of the right hemisphere and increased recruitment of the left hemisphere. The increased recruitment of the left hemisphere was directly associated with greater changes in estradiol. Given that the right hemisphere is the dominant hemisphere in visuospatial processing, our results suggest that estradiol is associated with reduced functional asymmetry, consistent with recent accounts of hormonal modulation of neurocognitive function.

Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

PubMed

Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo

2011-06-01

Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

Differential effects of acute and chronic estrogen treatment on thermogenic and metabolic pathways in ovariectomized sheep.

PubMed

Clarke, Scott D; Clarke, Iain J; Rao, Alexandra; Evans, Roger G; Henry, Belinda A

2013-01-01

Estrogen is protective against weight gain, but the underlying mechanisms are not fully elucidated. We sought to characterize the effects of estrogen on energy expenditure in skeletal muscle and adipose tissue in ovariectomized sheep. Temperature probes were implanted into sc (gluteal) and visceral (retroperitoneal) fat depots and skeletal muscle of the hind limb (vastus lateralis). Food was available from 1100-1600 h to entrain postprandial thermogenesis. We characterized the effects of single (50 μg estradiol benzoate, im) and repeated (25 μg estradiol-17β, iv) injections as well as chronic (3 × 3 cm estradiol-17β implants for 7 d) treatment on heat production. A single injection of estrogen increased heat production in visceral fat and skeletal muscle, without an effect on food intake. Increased heat production in skeletal muscle was sustained by repeated estradiol-17β injections. On the other hand, continuous treatment reduced food intake but had no effect on thermogenesis. To determine possible mechanisms that underpin estradiol-17β-induced heat production, we measured femoral artery blood flow, the expression of uncoupling protein (UCP) mRNA and the phosphorylation of AMP-activated protein kinase and Akt in fat and muscle. There was little effect of either single or repeated injections of estradiol-17β on the expression of UCP1, -2, or -3 mRNA in visceral fat or skeletal muscle. Acute injection of estradiol-17β increased the phosphorylation of AMP-activated protein kinase and Akt in muscle only. Estradiol-17β treatment did not alter femoral artery blood flow. Thus, the stimulatory effect of estradiol-17β on thermogenesis in female sheep is dependent upon a pulsatile pattern of treatment and not constant continuous exposure.

[Co-administration of RJR-2403 with low dose of 17beta-estradiol on spatial learning in ovariectomized rats].

PubMed

Fedotova, Yu O

2013-01-01

The aim of this work was to study the influence of stimulation or blockade Nalpha7-cholinoreceptors on dynamics of spatial learning in water Morris maze and on behavior in the "open field" test in adult ovariectomized (OVX) females given with a low dose of 17beta-estradiol. Agonist of Nalpha7-cholinoreceptors - RJR-2403 (1.0 mg/kg, i.p.) or antagonist of Nalpha7-cholinoreceptors - mecamylamine (1.0 mg/kg, i.p.) treated chronically (14 days) alone and in a combination with low dose of 17beta-estradiol (0.5 micro/rat, s.c.) to OVX rats. Co-administration of RJR-2403 with low dose of 17beta-estradiol completely restored impaired spatial learning in water Morris maze in OVX females. Moreover, OVX rats treated with RJR-2403 and low dose of 17beta-estradiol demonstrated increased exploratory and grooming behavior in the "open field" test. Both mecamylamine alone and in combination with low dose of 17beta-estradiol failed to influence on spatial learning and failed to modify behavior in the "open field" test in OVX rats. The results of the present study suggest a positive effect of RJR-2403 in combination with low dose of 17beta-estradiol on spatial learning at estrogen deficiency.

Interaction of estradiol and high density lipoproteins on proliferation of the human breast cancer cell line MCF-7 adapted to grow in serum free conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jozan, S.; Faye, J.C.; Tournier, J.F.

1985-11-27

The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combinedmore » treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation.« less

Quantifying the Role of Circulating Unconjugated Estradiol in Mediating the Body Mass Index-Breast Cancer Association.

PubMed

Schairer, Catherine; Fuhrman, Barbara J; Boyd-Morin, Jennifer; Genkinger, Jeanine M; Gail, Mitchell H; Hoover, Robert N; Ziegler, Regina G

2016-01-01

Higher body mass index (BMI) and circulating estrogen levels each increase postmenopausal breast cancer risk, particularly estrogen receptor-positive (ER(+)) tumors. Higher BMI also increases estrogen production. We estimated the proportion of the BMI-ER(+) breast cancer association mediated through estrogen in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants included 143 women with invasive ER(+) breast cancer and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 estrogens and estrogen metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated estradiol on the BMI-ER(+) breast cancer association using Aalen additive hazards and Cox regression models. All estrogens and estrogen metabolites were statistically significantly correlated with BMI, with unconjugated estradiol most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of obesity, and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER(+) breast cancer risk was mediated through unconjugated estradiol. The BMI-breast cancer association, once adjusted for unconjugated estradiol, was not modified by further adjustment for two metabolic ratios statistically significantly associated with both breast cancer and BMI. Circulating unconjugated estradiol levels partially mediate the BMI-breast cancer association, but other potentially important estrogen mediators (e.g., bioavailable estradiol) were not evaluated. Further research is required to identify mechanisms underlying the BMI-breast cancer association. ©2015 American Association for Cancer Research.

Interdependence of Platelet-Derived Growth Factor and Estrogen-Signaling Pathways in Inducing Neonatal Rat Testicular Gonocytes Proliferation1

PubMed Central

Thuillier, Raphael; Mazer, Monty; Manku, Gurpreet; Boisvert, Annie; Wang, Yan; Culty, Martine

2010-01-01

We previously found that platelet-derived growth factor (PDGF) and 17beta-estradiol stimulate gonocyte proliferation in a dose-dependent, nonadditive manner. In the present study, we report that gonocytes express RAF1, MAP2K1, and MAPK1/3. Inhibition of RAF1 and MAP2K1/2, but not phosphoinositide-3-kinase, blocked PDGF-induced proliferation. AG-370, an inhibitor of PDGF receptor kinase activity, suppressed not only PDGF-induced proliferation but also that induced by 17beta-estradiol. In addition, RAF1 and MAP2K1/2 inhibitors blocked 17beta-estradiol-activated proliferation. The estrogen receptor antagonist ICI 182780 inhibited both the effects of 17beta-estradiol and PDGF. PDGF lost its stimulatory effect when steroid-depleted serum or no serum was used. Similarly, 17beta-estradiol did not induce gonocyte proliferation in the absence of PDGF. The xenoestrogens genistein, bisphenol A, and DES, but not coumestrol, stimulated gonocyte proliferation in a dose-dependent and PDGF-dependent manner similarly to 17beta-estradiol. Their effects were blocked by ICI 182780, suggesting that they act via the estrogen receptor. AG-370 blocked genistein and bisphenol A effects, demonstrating their requirement of PDGF receptor activation in a manner similar to 17beta-estradiol. These results demonstrate the interdependence of PDGF and estrogen pathways in stimulating in vitro gonocyte proliferation, suggesting that this critical step in gonocyte development might be regulated in vivo by the coordinated action of PDGF and estrogen. Thus, the inappropriate exposure of gonocytes to xenoestrogens might disrupt the crosstalk between the two pathways and potentially interfere with gonocyte development. PMID:20089883

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Enduring influences of peripubertal/adolescent stressors on behavioral response to estradiol and progesterone in adult female mice.

PubMed

Laroche, Julie; Gasbarro, Lauren; Herman, James P; Blaustein, Jeffrey D

2009-08-01

Exposure to stressors during particular stages of development leads to acute and long-term physiological and behavioral changes. We have reported that shipping mice during the peripubertal/adolescent period results in decreased induction of feminine sexual behavior by estradiol and progesterone in adult female mice. To study further the factors involved in this decreased behavioral response, female mice were exposed to a variety of experimental stressors when 6 wk old. Effects of peripubertal/adolescent exposure to these stressors on acute plasma corticosterone levels and changes in body weight and adult behavioral response to estradiol and progesterone were assessed. Although restraint for three daily 3-h periods, 36-h food deprivation, or a multiple stressor regimen acutely increased plasma corticosterone levels and reduced body weight, only exposure to particular doses of the bacterial endotoxin lipopolysaccharide (LPS; 1-1.5 mg/kg body weight, doses that induced moderate levels of sickness behavior in these studies) resulted in reduced behavioral response to estradiol and progesterone in adulthood. Like the effects of shipping, the effects of LPS on adult feminine sexual behavior appear most robust when injected at 6 wk old and are limited to exposure during a vulnerable period at approximately 4-6 wk of age. Therefore, an immune stressor during the peripubertal/adolescent period, but not restraint, food restriction, or a combined stressor, has an enduring influence on behavioral response to estradiol and progesterone. This demonstrates that the decreased response to estradiol and progesterone is not a general response to all stressors during this developmental stage.

Estradiol, progesterone and genistein differentially regulate levels of aquaporin (AQP)-1, 2, 5 and 7 expression in the uteri of ovariectomized, sex-steroid deficient rats.

PubMed

Chinigarzadeh, Asma; Muniandy, Sekaran; Salleh, Naguib

2016-11-01

In this study, effects of estradiol, progesterone and genistein on uterine aquaporin (AQP)-1, 2, 5 and 7 expression were investigated in sex-steroid deficient state which could help to elucidate the mechanisms underlying uterine fluid volume changes that were reported under these hormone and hormone-like compound influences. Uteri from ovariectomized, female Sprague-Dawley rats receiving seven days estradiol, progesterone or genistein (25, 50 and 100mg/kg/day) were harvested and levels of AQP-1, 2, 5 and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR (qPCR) respectively. Distribution of these proteins in uterus was observed by immunohistochemistry. Genistein caused a dose-dependent increase in uterine AQP-1, 2, 5 and 7 protein and mRNA expression, however at the levels lower than following estradiol or progesterone stimulations. Effects of genistein were antagonized by estradiol receptor blocker, ICI 182780. Estradiol caused the highest AQP-2 protein and mRNA expression while progesterone caused the highest AQP-1, 5 and 7 protein and mRNA expression in uterus. AQP-1, 2, 5 and 7 protein were found to be distributed in the myometrium as well as in uterine luminal and glandular epithelia and endometrial blood vessels. In conclusion, the observed effects of estradiol, progesterone and genistein on uterine AQP-1, 2, 5 and 7 expression could help to explain the differences in the amount of fluid accumulated in the uterus under these different conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation by steroid hormones of a "sexy" acoustic signal in an Oscine species, the Common Canary Serinus canaria.

PubMed

Rybak, Fanny; Gahr, Manfred

2004-06-01

The respective influence of testosterone and estradiol on the structure of the Common Canary Serinus canaria song was studied by experimentally controlling blood levels of steroid hormones in males and analyzing the consequent effects on acoustic parameters. A detailed acoustic analysis of the songs produced before and after hormonal manipulation revealed that testosterone and estradiol seem to control distinct song parameters independently. The presence of receptors for testosterone and estradiol in the brain neural pathway controlling song production strongly suggests that the observed effects are mediated by a steroid action at the neuronal level.

Efficacy of a new oral contraceptive containing drospirenone and ethinyl estradiol in the long-term treatment of hirsutism.

PubMed

Batukan, Cem; Muderris, Iptisam Ipek

2006-02-01

This study represents long term clinical and biochemical results and the response of different body parts to medical therapy with oral ethinyl estradiol/drospirenone combination in hirsute patients with or without polycystic ovary syndrome (PCOS). Prospective, open, controlled clinical study. Outpatients at Erciyes University Medical School. Fifty women with moderate to severe hirsutism were recruited. Two women were lost to follow-up. Women were treated with 3 mg of drospirenone and 30 microg of ethinyl estradiol for 12 cycles. Hirsutism was assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system. Serum FSH, LH, total and free testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), and sex-hormone binding globulin (SHBG) levels at 6 and 12 months of therapy were compared with baseline values. Total mean FG score declined by 67% and 78% after 6 and 12 months, respectively. Improvement was most prominent on the chest and abdomen, followed by the upper lip and chin. The lowest effect was observed on the back and arms. Serum levels of total and free T and A decreased, whereas SHBG levels increased significantly after 6 and 12 months when compared with baseline levels. Drospirenone/ethinyl estradiol combination exerts significant antiandrogenic activity and is effective in improving facial hirsutism. The beneficial effect is most obvious after six cycles and continues thereafter at a slower rate.

EFFECTS OF ETHYNYL ESTRADIOL EXPOSURE ON REPRODUCTIVE PARAMETERS IN AN ESTUARINE FISH

EPA Science Inventory

This study investigated the impact of ethynyl estradiol (EE2) on reproductive success of cunner, Tautogolabrus adspersus. EE2 is the estrogen used in human contraceptives and is released into the aquatic environment in sewage treatment effluent. Reproductively active male and fem...

Influence of different estrogens on neuroplasticity and cognition in the hippocampus.

PubMed

Barha, Cindy K; Galea, Liisa A M

2010-10-01

Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain. This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats. Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning. Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females. Copyright © 2010 Elsevier B.V. All rights reserved.

Estradiol treatment in preadolescent females enhances adolescent spatial memory and differentially modulates hippocampal region-specific phosphorylated ERK labeling.

PubMed

Wartman, Brianne C; Keeley, Robin J; Holahan, Matthew R

2012-10-24

Estrogen levels in rats are positively correlated with enhanced memory function and hippocampal dendritic spine density. There is much less work on the long-term effects of estradiol manipulation in preadolescent rats. The present work examined how injections of estradiol during postnatal days 19-22 (p19-22; preadolescence) affected water maze performance and hippocampal phosphorylated ERK labeling. To investigate this, half of the estradiol- and vehicle-treated female rats were trained on a water maze task 24h after the end of estradiol treatment (p23-27) while the other half was not trained. All female rats were tested on the water maze from p40 to p44 (adolescence) and hippocampal pERK1/2 labeling was assessed as a putative marker of neuronal plasticity. During adolescence, preadolescent-trained groups showed lower latencies than groups without preadolescent training. Retention data revealed lower latencies in both estradiol groups, whether preadolescent trained or not. Immunohistochemical detection of hippocampal pERK1/2 revealed elevations in granule cell labeling associated with the preadolescent trained groups and reductions in CA1 labeling associated with estradiol treatment. These results show a latent beneficial effect of preadolescent estradiol treatment on adolescent spatial performance and suggest an organizational effect of prepubescent exogenously applied estradiol. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Differential regulation of gonadotropin-releasing hormone (GnRH) neuron activity and membrane properties by acutely-applied estradiol: dependence on dose and estrogen receptor subtype

PubMed Central

Chu, Zhiguo; Andrade, Josefa; Shupnik, Margaret A.; Moenter, Suzanne M.

2009-01-01

GnRH neurons are critical to controlling fertility. In vivo, estradiol can inhibit or stimulate GnRH release depending on concentration and physiological state. We examined rapid, non-genomic effects of estradiol. Whole-cell recordings were made of GnRH neurons in brain slices from ovariectomized mice with ionotropic GABA and glutamate receptors blocked. Estradiol was bath-applied and measurements completed within 15 min. Estradiol from high physiological (preovulatory) concentrations (100pM) to 100nM enhanced action potential firing, reduced afterhyperpolarizing potential (AHP) and increased slow afterdepolarization (sADP) amplitudes, and reduced IAHP and enhanced IADP. The reduction of IAHP was occluded by prior blockade of calcium-activated potassium channels. These effects were mimicked by an estrogen receptor (ER) β-specific agonist and were blocked by the classical receptor antagonist ICI182780. ERα or GPR30 agonists had no effect. The acute stimulatory effect of high physiological estradiol on firing rate was dependent on signaling via protein kinase A. In contrast, low physiological levels of estradiol (10pM) did not affect intrinsic properties. Without blockade of ionotropic GABA and glutamate receptors, however, 10pM estradiol reduced firing of GnRH neurons; this was mimicked by an ERα agonist. ERα agonists reduced the frequency of GABA transmission to GnRH neurons; GABA can excite to these cells. In contrast, ERβ agonists increased GABA transmission and postsynaptic response. These data suggest rapid intrinsic and network modulation of GnRH neurons by estradiol is dependent upon both dose and receptor subtype. In cooperation with genomic actions, non-genomic effects may play a role in feedback regulation of GnRH secretion. PMID:19403828

The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

PubMed

Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

2013-11-01

The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. © 2013.

Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

PubMed

Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

2014-11-01

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats

PubMed Central

Pisani, Samantha L.; Neese, Steven L.; Doerge, Daniel R.; Helferich, William G.; Schantz, Susan L.; Korol, Donna L.

2012-01-01

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatum function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for two days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5 μg/kg) but not high dose (45 μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4 mg of genistein over two days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both the low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor β and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ERβ subtype and affinity for GPER. PMID:22944517

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...

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-...

Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women.

PubMed

Smith, Gordon I; Reeds, Dominic N; Okunade, Adewole L; Patterson, Bruce W; Mittendorfer, Bettina

2014-07-01

Sexual dimorphism in plasma triglyceride (TG) metabolism is well established but it is unclear to what extent it is driven by differences in the sex hormone milieu. RESULTS from previous studies evaluating the effects of sex steroids on plasma TG homeostasis are inconclusive because they relied on orally administered synthetic hormone preparations or evaluated only plasma lipid concentrations but not kinetics. The purpose of this study was to evaluate the effects of systemically delivered 17β-estradiol, progesterone, and T on very low density lipoprotein-triglyceride (VLDL-TG) concentration and kinetics in postmenopausal women. VLDL-TG concentration and kinetics were evaluated by using stable isotope-labeled tracer techniques in four groups of postmenopausal women (n = 27 total) who were studied before and after treatment with either 17β-estradiol (0.1 mg/d via continuous delivery skin patch), progesterone (100 mg/d via vaginal insert) and T (12.5 mg/d via skin gel), or no intervention (control group). VLDL-TG concentration and kinetics were unchanged in the control group and not altered by T and progesterone administration. Estradiol treatment, in contrast, reduced VLDL-TG concentration by approximately 30% due to accelerated VLDL-TG plasma clearance (25.1 ± 2.5 vs. 17.4 ± 2.7 mL/min; P < .01). Estradiol, but not progesterone or T, is a major regulator of VLDL-TG metabolism.

DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory.

PubMed

Tunur, Tumay; Stelly, Claire E; Schrader, Laura Ann

2013-11-18

Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K⁺ channel interacting protein 3 (KChIP3) is a multifunctional Ca²⁺-binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of DR/C/K3 expression in female mice. Fluctuating hormones that occur during the estrous cycle may affect these results. In this study, we hypothesized that DR/C/K3 interacts with 17β-estradiol, the primary estrogen produced by the ovaries, to play a role in hippocampus function. We investigated the role of estradiol and DR/C/K3 in learning strategy in ovariectomized (OVX) female mice. OVX WT and DR/C/K3 knockout (KO) mice were given three injections of vehicle (sesame oil) or 17β-estradiol benzoate (0.25 mg in 100 mL sesame oil) 48, 24, and 2 h before training and testing. DR/C/K3 and estradiol had a time-dependent effect on strategy use in the female mice. Male KO mice exhibited enhanced place strategy relative to WT 24 h after pre-exposure. Fear memory formation was significantly reduced in intact female KO mice relative to intact WT mice, and OVX reduced fear memory formation in the WT, but had no effect in the KO mice. Long-term potentiation in hippocampus slices from female mice was enhanced by circulating ovarian hormones in both WT and DR/C/K3 KO mice. Paired-pulse depression was not affected by ovarian hormones but was reduced in DR/C/K3 KO mice. These results provide the first evidence that DR/C/K3 plays a timing-dependent role in estradiol regulation of learning, memory, and plasticity.

17β-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

PubMed

Mukai, Kanae; Nakajima, Yukari; Urai, Tamae; Komatsu, Emi; Nasruddin; Sugama, Junko; Nakatani, Toshio

2016-10-01

This study investigated the effect of 17β-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17β-estradiol after ovariectomy (OVX + 17β-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17β-estradiol group was administered 17β-estradiol at 0·01 g/day until healing. In the OVX + 17β-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17β-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17β-estradiol administration. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Reproductive failure of the red shiner (Cyprinella lutrensis) after exposure to an exogenous estrogen

USGS Publications Warehouse

McGree, M.M.; Winkelman, D.L.; Vieira, N.K.M.; Vajda, A.M.

2010-01-01

Endocrine disrupting chemicals (EDCs) have been detected in surface waters worldwide and can lead to developmental and reproductive disruption in exposed fishes. In the US Great Plains, EDCs are impacting streams and rivers and may be causing adverse reproductive effects. To examine how estrogenic EDCs might affect reproductive success of plains fishes, we experimentally exposed male red shiners (Cyprinella lutrensis) to exogenous 17b-estradiol. We characterized the effects of estradiol on male gonadal histology and secondary sexual characteristics, determined whether exposure reduced reproductive success, and examined the effects of depuration. Adults were exposed to a mean concentration of 70 ng L-1 estradiol, a solvent control, or a water control for at least 83 days. Male exposure to estradiol resulted in elevated plasma vitellogenin concentrations, changes in spermatogenesis, reduced mating coloration and tubercles, altered mating behaviors, and reduced reproductive success with no viable progeny produced. Reproductive endpoints improved upon depuration (28 days). Exposure to estradiol had significant adverse effects on red shiners, indicating that wild populations may face developmental and reproductive difficulties if they are chronically exposed to estradiol.

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

PubMed

Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

2016-01-01

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.

PubMed

Almey, Anne; Arena, Lauren; Oliel, Joshua; Shams, Waqqas M; Hafez, Nada; Mancinelli, Cynthia; Henning, Lukas; Tsanev, Aleks; Brake, Wayne G

2017-03-01

There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

PubMed

Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanism of the Rapid Effect of 17β -Estradiol on Medial Amygdala Neurons

NASA Astrophysics Data System (ADS)

Nabekura, Junichi; Oomura, Yutaka; Minami, Taketsugu; Mizuno, Yuji; Fukuda, Atsuo

1986-07-01

The mechanism by which sex steroids rapidly modulate the excitability of neurons was investigated by intracellular recording of neurons in rat medial amygdala brain slices. Brief hyperpolarization and increased potassium conductance were produced by 17β - estradiol. This effect persisted after elimination of synaptic input and after suppression of protein synthesis. Thus, 17β -estradiol directly changes the ionic conductance of the postsynaptic membrane of medial amygdala neurons. In addition, a greater proportion of the neurons from females than from males responded to 17β -estradiol.

Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

PubMed

Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

2017-11-01

Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

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

PubMed

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

2011-03-30

Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

The effects of chronic testosterone administration on body weight, food intake, and adipose tissue are changed by estrogen treatment in female rats.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yano, Kiyohito; Yanagihara, Rie; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Mayila, Yiliyasi; Kuwahara, Akira; Irahara, Minoru

2017-07-01

In females, estrogens play pivotal roles in preventing excess body weight (BW) gain. On the other hand, the roles of androgens in female BW, appetite, and energy metabolism have not been fully examined. We hypothesized that androgens' effects on food intake (FI) and BW regulation change according to the estrogens' levels. To evaluate this hypothesis, the effects of chronic testosterone administration in ovariectomized (OVX) female rats with or without estradiol supplementation were examined in this study. Chronic testosterone administration decreased BW, FI, white adipose tissue (WAT) weight, and adipocyte size in OVX rats, whereas it increased BW, WAT weight, and adipocyte size in OVX with estradiol-administered rats. In addition, chronic testosterone administration increased hypothalamic CYP19a1 mRNA levels in OVX rats, whereas it did not alter CYP19a1 mRNA levels in OVX with estradiol-administered rats, indicating that conversion of testosterone to estrogens in the hypothalamus may be activated in testosterone-administered OVX rats. Furthermore, chronic testosterone administration decreased hypothalamic TNF-α mRNA levels in OVX rats, whereas it increased hypothalamic IL-1β mRNA levels in OVX with estradiol-administered rats. On the other hand, IL-1β and TNF-α mRNA levels in visceral and subcutaneous WAT and liver were not changed by chronic testosterone administration in both groups. These data indicate that the effects of chronic testosterone administration on BW, FI, WAT weight, and adipocyte size were changed by estradiol treatment in female rats. Testosterone has facilitative effects on BW gain, FI, and adiposity under the estradiol-supplemented condition, whereas it has inhibitory effects in the non-supplemented condition. Differences in the responses of hypothalamic factors, such as aromatase and inflammatory cytokines, to testosterone might underlie these opposite effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Why use of dienogest for the first contraceptive pill with estradiol?

PubMed

Mueck, Alfred O; Seeger, Harald; Bühling, Kai J

2010-02-01

Dienogest (DNG) has the essential properties of an effective progestogen for use in a new contraceptive pill using estradiol valerate as estrogenic component -- it inhibits ovulation and protects against endometrial proliferation. DNG is a derivative of norethisterone (NET), but has a cyanomethyl- instead of an ethinyl-group in C17 position which may offer a variety of benefits regarding hepatic effects. The similarity to NET is reflected in the high endometriotropy and in similar pharmacokinetics like short plasma half-live and high bioavailability. However, DNG also elicits properties of progesterone derivatives like neutrality in metabolic and cardiovascular system and considerable antiandrogenic activity, the latter increased by lack of binding to SHBG as specific property of DNG. It has no glucocorticoid and antimineralocorticoid activity and has no antiestrogenic activity with the consequence that possible beneficial estradiol effects should not be antagonized. This may be of special importance for the tolerability and safety of the first pill with estradiol valerate instead of ethinylestradiol, although well-designed postmarketing studies are still ongoing to demonstrate what can be expected on the basis of pharmacology.

Estradiol-dependent modulation of auditory processing and selectivity in songbirds

PubMed Central

Maney, Donna; Pinaud, Raphael

2011-01-01

The steroid hormone estradiol plays an important role in reproductive development and behavior and modulates a wide array of physiological and cognitive processes. Recently, reports from several research groups have converged to show that estradiol also powerfully modulates sensory processing, specifically, the physiology of central auditory circuits in songbirds. These investigators have discovered that (1) behaviorally-relevant auditory experience rapidly increases estradiol levels in the auditory forebrain; (2) estradiol instantaneously enhances the responsiveness and coding efficiency of auditory neurons; (3) these changes are mediated by a non-genomic effect of brain-generated estradiol on the strength of inhibitory neurotransmission; and (4) estradiol regulates biochemical cascades that induce the expression of genes involved in synaptic plasticity. Together, these findings have established estradiol as a central regulator of auditory function and intensified the need to consider brain-based mechanisms, in addition to peripheral organ dysfunction, in hearing pathologies associated with estrogen deficiency. PMID:21146556

Estradiol and Progesterone Modulate Spontaneous Sleep Patterns and Recovery from Sleep Deprivation in Ovariectomized Rats

PubMed Central

Deurveilher, Samüel; Rusak, Benjamin; Semba, Kazue

2009-01-01

Study Objectives: Women undergo hormonal changes both naturally during their lives and as a result of sex hormone treatments. The objective of this study was to gain more knowledge about how these hormones affect sleep and responses to sleep loss. Design: Rats were ovariectomized and implanted subcutaneously with Silastic capsules containing oil vehicle, 17β-estradiol and/or progesterone. After 2 weeks, sleep/wake states were recorded during a 24-h baseline period, 6 h of total sleep deprivation induced by gentle handling during the light phase, and an 18-h recovery period. Measurements and Results: At baseline and particularly in the dark phase, ovariectomized rats treated with estradiol or estradiol plus progesterone spent more time awake at the expense of non-rapid eye movement sleep (NREMS) and/or REMS, whereas those given progesterone alone spent less time in REMS than ovariectomized rats receiving no hormones. Following sleep deprivation, all rats showed rebound increases in NREMS and REMS, but the relative increase in REMS was larger in females receiving hormones, especially high estradiol. In contrast, the normal increase in NREMS EEG delta power (an index of NREMS intensity) during recovery was attenuated by all hormone treatments. Conclusions: Estradiol promotes arousal in the active phase in sleep-satiated rats, but after sleep loss, both estradiol and progesterone selectively facilitate REMS rebound while reducing NREMS intensity. These results indicate that effects of ovarian hormones on recovery sleep differ from those on spontaneous sleep. The hormonal modulation of recovery sleep architecture may affect recovery of sleep related functions after sleep loss. Citation: Deurveilher S; Rusak B; Semba K. Estradiol and progesterone modulate spontaneous sleep patterns and recovery from sleep deprivation in ovariectomized rats. SLEEP 2009;32(7):865-877. PMID:19639749

Role of adiponectin in delayed embryonic development of the short-nosed fruit bat, Cynopterus sphinx.

PubMed

Anuradha; Krishna, Amitabh

2014-12-01

The aim of this study was to evaluate the role of adiponectin in the delayed embryonic development of Cynopterus sphinx. Adiponectin receptor (ADIPOR1) abundance was first observed to be lower during the delayed versus non-delayed periods of utero-embryonic unit development. The effects of adiponectin treatment on embryonic development were then evaluated during the period of delayed development. Exogenous treatment increased the in vivo rate of embryonic development, as indicated by an increase in weight, ADIPOR1 levels in the utero-embryonic unit, and histological changes in embryonic development. Treatment with adiponectin during embryonic diapause showed a significant increase in circulating progesterone and estradiol concentrations, and in production of their receptors in the utero-embryonic unit. The adiponectin-induced increase in estradiol synthesis was correlated with increased cell survival (BCL2 protein levels) and cell proliferation (PCNA protein levels) in the utero-embryonic unit, suggesting an indirect effect of adiponectin via estradiol synthesis by the ovary. An in vitro study further confirmed the in vivo findings that adiponectin treatment increases PCNA levels together with increased uptake of glucose by increasing the abundance of glucose transporter 8 (GLUT8) in the utero-embryonic unit. The in vitro study also revealed that adiponectin, together with estradiol but not alone, significantly increased ADIPOR1 protein levels. Thus, adiponectin works in concert with estradiol to increase glucose transport to the utero-embryonic unit and promote cell proliferation, which together accelerate embryonic development. © 2014 Wiley Periodicals, Inc.

Estrogens facilitate memory processing through membrane mediated mechanisms and alterations in spine density

PubMed Central

Luine, Victoria N.; Frankfurt, Maya

2012-01-01

Estrogens exert sustained, genomically mediated effects on memory throughout the female life cycle, but here we review new studies documenting rapid effects of estradiol on memory, which are exerted through membrane-mediated mechanisms. Use of recognition memory tasks in rats, shows that estrogens enhance memory consolidation within one hour. 17α-estradiol is more potent than 17β-estradiol, and the dose response relationship between estrogens and memory is an inverted U shape. Use of specific estrogen receptor (ER) agonists suggests mediation by an ERβ-like membrane receptor. Enhanced memory is associated with increased spine density and altered noradrenergic activity in the medial prefrontal cortex and hippocampus within 30 min. of administration. The environmental chemical, bisphenol-A, rapidly antagonizes enhancements in memory in both sexes possibly through actions on spines. Thus, estradiol and related compounds exert rapid alterations in cognition through non-genomic mechanisms, a finding which may provide a basis for better understanding and treating memory impairments. PMID:22981654

Baseline Serum Estradiol and Fracture Reduction During Treatment With Hormone Therapy: The Women’s Health Initiative Randomized Trial

PubMed Central

Cauley, Jane A.; LaCroix, Andrea Z.; Robbins, John A.; Larson, Joseph; Wallace, Robert; Wactawski-Wende, Jean; Chen, Zhao; Bauer, Douglas C.; Cummings, Steven R.; Jackson, Rebecca

2009-01-01

Purpose To test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels. Methods We conducted a nested case-control study within the Women’s Health Initiative HT Trials. The sample included 231 hip fracture case-control pairs and a random sample of 519 all fracture case-control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture identified over an average follow-up of 6.53 years. Results There was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture including hip fracture, compared to placebo. Conclusion The effect of HT on fracture reduction is independent of estradiol and SHBG levels. PMID:19436934

Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen.

PubMed

Huang, Weiren; Chen, Yuanbin; Liu, Yuchen; Zhang, Qiaoxia; Yu, Zhou; Mou, Lisha; Wu, Hanwei; Zhao, Li; Long, Ting; Qin, Danian; Gui, Yaoting

2015-01-01

Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB) is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1) were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats.

PubMed

Fujitani, Mina; Mizushige, Takafumi; Bhattarai, Keshab; Iwahara, Asami; Aida, Ryojiro; Kishida, Taro

2015-01-01

We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats.

PubMed

Mora, S; Dussaubat, N; Díaz-Véliz, G

1996-10-01

The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased open-arm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.

Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Sahin, Cagdas; Majidi-Zolbin, Masoumeh; Ge, Guanghao; Mani, Arya; Taylor, Hugh S

2018-02-01

The contributions of estradiol and testosterone to atherosclerotic lesion progression are not entirely understood. Cross-sex hormone therapy (XHT) for transgender individuals dramatically alters estrogen and testosterone levels and consequently could have widespread consequences for cardiovascular health. Yet, no preclinical research has assessed atherosclerosis risk after XHT. We examined the effects of testosterone XHT after ovariectomy on atherosclerosis plaque formation in female mice and evaluated whether adding low-dose estradiol to cross-sex testosterone treatments after ovariectomy reduced lesion formation. Six-week-old female ApoE-/- C57BL/6 mice underwent ovariectomy and began treatments with testosterone, estradiol, testosterone with low-dose estradiol, or vehicle alone until euthanized at 23 weeks of age. Atherosclerosis lesion progression was measured by Oil Red O stain and confirmed histologically. We found reduced atherosclerosis in the estradiol- and combined testosterone/estradiol-treated mice compared with those treated with testosterone or vehicle only in the whole aorta (-75%), aortic arch (-80%), and thoracic aorta (-80%). Plaque size was similarly reduced in the aortic sinus. These reductions in lesion size after combined testosterone/estradiol treatment were comparable to those obtained with estrogen alone. Testosterone/estradiol combined therapy resulted in less atherosclerosis plaque formation than either vehicle or testosterone alone after ovariectomy. Testosterone/estradiol therapy was comparable to estradiol replacement alone, whereas mice treated with testosterone only fared no better than untreated controls after ovariectomy. Adding low-dose estrogen to cross-sex testosterone therapy after oophorectomy could improve cardiovascular outcomes for transgender patients. Additionally, these results contribute to understanding of the effects of estrogen and testosterone on atherosclerosis progression. Copyright © 2018 Endocrine Society.

Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH.

PubMed

Allen, J J; Herrick, S L; Fortune, J E

2016-11-01

In cattle, primordial follicles form before birth. Fetal ovarian capacity to produce progesterone and estradiol is high before follicle formation begins and decreases around the time follicles first appear (around 90 days of gestation). However, mechanisms that regulate steroid production during this time remain unclear. We hypothesized that LH stimulates progesterone and androgen production and that FSH stimulates aromatization of androgens to estradiol. To test this, we cultured pieces from fetal bovine ovaries for 10 days without or with exogenous hormones and then measured the accumulation of steroids in the culture medium by RIA. LH (100 ng/mL) alone increased the accumulation of progesterone, androstenedione, testosterone and estradiol. FSH (100 ng/mL) alone increased both progesterone and estradiol accumulation, but had no effect on androgens. Exogenous testosterone (0.5 µM) alone greatly increased estradiol accumulation and the combination of testosterone + FSH, but not testosterone + LH, increased estradiol relative to testosterone alone. Interestingly, exogenous testosterone and estradiol decreased progesterone accumulation in a dose-dependent manner. Because the highest dose of estradiol (0.5 µM) decreased progesterone accumulation, but increased both pregnenolone and androstenedione in the same cultures, endogenous estradiol may be a paracrine regulator of steroid synthesis. Together, these results confirm our initial hypotheses and indicate that LH stimulates androgen production in fetal bovine ovaries via the Δ 5 pathway, whereas FSH stimulates aromatization of androgens to estradiol. These results are consistent with the two-cell, two-gonadotropin model of estradiol production by bovine preovulatory follicles, which suggests that the mechanisms regulating ovarian steroid production are established during fetal life. © 2016 Society for Endocrinology.

The Effect of Estradiol on the Growth Plate Chondrocytes of Limb and Spine from Postnatal Mice in vitro: The Role of Estrogen-Receptor and Estradiol Concentration.

PubMed

Shi, Sheng; Zheng, Shuang; Li, Xin-Feng; Liu, Zu-De

2017-01-01

Objectives: Skeletal development is a complex process. Little is known about the different response of limb or spine growth plate chondrocytes (LGP or SGP) to the estrogen level and the role of estrogen receptor (ER) during postnatal stage. Methods: LGP and SGP chondrocytes were isolated from 50 one-week mice and treated with different concentrations of 17β-estradiol. Cell viability was measured by cell counting kit-8 (CCK-8). The expression of collagen II and X were evaluated by real-time PCR and Western blotting. Then, the response of LGP or SGP chondrocyte after with or without estradiol and specific ER antagonists to block the effect of ERs were also measured by Western blotting and immunofluorescence. Results: Estradiol promoted the chondrogensis of the chondrocytes in vitro and achieved the maximal expression of type II collagen at the dose of 10 -7 M. Additionally, the regulatory effect of estradiol on the chondrogenesis can be mainly relied on ERα. The LGP chondrocytes were more sensitive to the estradiol treatment than SGP in the expression of type II collagen. Conclusions: Estrogen at a pharmacological concentration (10 -7 M) could stimulate the maximal production of type II collagen in the growth plate chondrocytes in vitro, which exerts its activity mainly through ERα in the chondrogenesis. Furthermore, the LGP chondrocytes were more sensitive to the estradiol treatment than SGP in the chondrogenesis.

Estradiol therapy in adulthood reverses glial and neuronal alterations caused by perinatal asphyxia.

PubMed

Saraceno, Gustavo Ezequiel; Bertolino, María Laura Aón; Galeano, Pablo; Romero, Juan Ignacio; Garcia-Segura, Luis Miguel; Capani, Francisco

2010-06-01

The capacity of the ovarian hormone 17beta-estradiol to prevent neurodegeneration has been characterized in several animal models of brain and spinal cord pathology. However, the potential reparative activity of the hormone under chronic neurodegenerative conditions has received less attention. In this study we have assessed the effect of estradiol therapy in adulthood on chronic glial and neuronal alterations caused by perinatal asphyxia (PA) in rats. Four-month-old male Sprague-Dawley rats submitted to PA just after delivery, and their control littermates, were injected for 3 consecutive days with 17beta estradiol or vehicle. Animals subjected to PA and treated with vehicle showed an increased astrogliosis, focal swelling and fragmented appearance of MAP-2 immunoreactive dendrites, decreased MAP-2 immunoreactivity and decreased phosphorylation of high and medium molecular weight neurofilaments in the hippocampus, compared to control animals. Estradiol therapy reversed these alterations. These findings indicate that estradiol is able to reduce, in adult animals, chronic reactive astrogliosis and neuronal alterations caused by an early developmental neurodegenerative event, suggesting that the hormone might induce reparative actions in the Central Nervous System (CNS). Copyright (c) 2009 Elsevier Inc. All rights reserved.

The effects of a low-dose monophasic preparation of levonorgestrel and ethinyl estradiol on coagulation and other hemostatic factors.

PubMed

Archer, D F; Mammen, E F; Grubb, G S

1999-11-01

This study was undertaken to evaluate the effects on hemostatic factors of a low-dose preparation of levonorgestrel and ethinyl estradiol in a 12-cycle study. Thirty healthy women began taking 100 microg levonorgestrel and 20 microg ethinyl estradiol on the first day of the menstrual cycle, continued to take the preparation for the next 21 days, and then took placebo for 7 days. Mean changes in prothrombin time, partial thromboplastin time, and levels of factors VII and X, antithrombin, plasminogen, fibrinogen, protein S, thrombin-antithrombin complexes, and D-dimer were analyzed at baseline and at cycles 3, 6, and 12 with paired Student t tests. Factor X, plasminogen antigen and activity, and D-dimer levels were significantly increased (P

Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study.

PubMed

Barzegar, Mohammad Hossein; Khazali, Homayoun; Kalantar, Seyyed Mehdi; Khoradmehr, Arezoo

2017-10-01

Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model. 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS.

Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study

PubMed Central

Barzegar, Mohammad Hossein; Khazali, Homayoun; Kalantar, Seyyed Mehdi; Khoradmehr, Arezoo

2017-01-01

Background: Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. Objective: We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats’ model. Materials and Methods: 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. Results: There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Conclusion: Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS. PMID:29387832

Short-term estradiol administration in aging ovariectomized rats provides lasting benefits for memory and the hippocampus: a role for insulin-like growth factor-I.

PubMed

Witty, Christine F; Gardella, Layne P; Perez, Maria C; Daniel, Jill M

2013-02-01

We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle age exhibited enhanced spatial memory and increased levels of estrogen receptor (ER)-α in the hippocampus long after estradiol treatment was terminated. The implication for cognition of increased levels of ERα resulting from prior estradiol exposure is unknown. In the absence of estrogens, growth factors, including IGF-I, can induce ERα-mediated transcription through ligand-independent mechanisms. Our current goal was to determine whether IGF-I mediates the ability of short-term exposure to estradiol to exert long-term effects on cognition and the hippocampus of aging females. Ovariectomized middle-aged rats were implanted with estradiol or cholesterol vehicle capsules. After 40 days, all capsules were removed and drug treatments were initiated. Half of each hormone treatment group received chronic intracerebroventricular delivery of the IGF-I receptor antagonist JB1, and the other half received artificial cerebrospinal fluid vehicle. Rats were tested on a spatial memory radial-arm maze task and hippocampi were immunostained for proteins of interest by Western blotting. As expected, previous treatment with estradiol enhanced spatial memory and increased levels of ERα in the hippocampus. JB1 reversed these effects. Previous treatment with estradiol resulted in lasting increases in levels of IGF-I receptors and phosphorylation of ERK/MAPK, a downstream signaling molecule of both ERα and IGF-I receptors, and increased levels of the ERα-regulated protein, choline acetyltransferase. JB1 blocked effects on ERK/MAPK and choline acetyltransferase. Results indicate that activation of IGF-I receptors is necessary for prior estradiol exposure to exert lasting impact on the hippocampus and memory.

Physiological and biochemical effects of 17β estradiol in aging female rat brain.

PubMed

Kumar, Pardeep; Taha, Asia; Kale, R K; Cowsik, S M; Baquer, Najma Zaheer

2011-07-01

Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

High-dose estradiol improves cognition for women with AD: results of a randomized study.

PubMed

Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

2001-08-28

To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

Effects of melatonin and dexpanthenol on antioxidant parameters when combined with estrogen treatment in ovariectomized rats.

PubMed

Turgut, Ozan; Ay, Aybala Agac; Turgut, Hulya; Ay, Ahmet; Kafkas, Samet; Dost, Turhan

2013-12-01

The purpose of the study was to assess whether it is possible to reduce the oxidative damage using antioxidant agents combined with hormone replacement therapy after menopause. In this prospective experimental study, 50 mature female Wistar albino rats weighing 270-310 g were used. Rats were divided into the following six groups: (1) Ovx group (n = 7): the animals underwent bilateral ovariectomy. No drug was administered following bilateral ovariectomy. (2) Ovx + E 2 group (n = 7): bilateral ovariectomy + 17β-estradiol (100 μg/kg/day); (3) Ovx + E 2 + MT5 group (n = 7): bilateral ovariectomy + 17β-estradiol (100 μg/kg/day) + melatonin (5 mg/kg/day); (4) Ovx + E 2 + MT20 group (n = 7): bilateral ovariectomy + 17β-estradiol (100 μg/kg/day) + melatonin (20 mg/kg/day); (5) Ovx + E 2 + Dxp250 group (n = 7): bilateral ovariectomy + 17β-estradiol (100 μg/kg/day) + dexpanthenol (250 mg/kg/day); (6) Ovx + E 2 + Dxp500 group (n = 7): bilateral ovariectomy + 17β-estradiol (100 μg/kg/day) + dexpanthenol (500 mg/kg/day), and the activity of these antioxidative enzymes and oxidative stress products were measured. Enzymatic activity levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase(GSH-Px), and glutathione reductase and levels of free radicals (malondialdehyde (MDA) and nitric oxide) were both analyzed. We observed an increase in the level of GSH activity, but no significant differences in levels of CAT, SOD, and GSH-Px enzymatic activity and in levels of free radical MDA following 17β-estradiol or additional antioxidant treatment (melatonin or dexpanthenol). Despite the present study indicating that the addition of melatonin and dexpanthenol into the hormone replacement therapy regimen may contribute to the antioxidant effect of estrogen, the existence of limited data in this field indicates that further studies are warranted.

The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

PubMed

Olsson, B; Landgren, B M

2001-11-01

Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

A comparative evaluation of treatments with 17β-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease.

PubMed

Tschiffely, Anna E; Schuh, Rosemary A; Prokai-Tatrai, Katalin; Prokai, Laszlo; Ottinger, Mary Ann

2016-07-01

Estrogens are neuroprotective and, thus, potentially useful for the therapy of Alzheimer's disease; however, clinical use of hormone therapy remains controversial due to adverse peripheral effects. The goal of this study was to investigate the benefits of treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective prodrug of 17β-estradiol, in comparison with the parent hormone using APPswe/PS1dE9 double transgenic mice to model the pathology of the disease. Ovariectomized and intact females were continuously treated with vehicle, 17β-estradiol, or DHED via subcutaneous osmotic pumps from 6 to 8months of age. We confirmed that this prolonged treatment with DHED did not stimulate uterine tissue, whereas 17β-estradiol treatment increased uterine weight. Amyloid precursor protein decreased in both treatment groups of intact, but not in ovariectomized double transgenic females in which ovariectomy already decreased the expression of this protein significantly. However, reduced brain amyloid-β peptide levels could be observed for both treatments. Consequently, double-transgenic ovariectomized and intact mice had higher cognitive performance compared to untreated control animals in response to both estradiol and DHED administrations. Overall, the tested brain-selective 17β-estradiol prodrug proved to be an effective early-stage intervention in an Alzheimer's disease-relevant mouse model without showing systemic impact and, thus, warrants further evaluation as a potential therapeutic candidate. Copyright © 2016 Elsevier Inc. All rights reserved.

17β-estradiol in runoff as affected by various poultry litter application strategies.

PubMed

Delaune, P B; Moore, P A

2013-02-01

Steroidal hormones, which are excreted by all mammalian species, have received increasing attention in recent years due to potential environmental implications. The objective of this study was to evaluate 17β-estradiol concentrations in runoff water from plots receiving poultry litter applications using various management strategies. Treatments included the effects of 1) aluminum sulfate (alum) application rates to poultry litter; 2) time until the first runoff event occurs after poultry litter application; 3) poultry litter application rate; 4) fertilizer type; and 5) litter from birds fed modified diets. Rainfall simulators were used to cause continuous runoff from fertilized plots. Runoff samples were collected and analyzed for 17β-estradiol concentrations. Results showed that increasing alum additions to poultry litter decreased 17β-estradiol concentrations in runoff water. A significant exponential decline in 17β-estradiol runoff was also observed with increasing time until the first runoff event after litter application. Concentrations of 17β-estradiol in runoff water increased with increasing litter application rate and remained above background concentrations after three runoff events at higher application rates. Management practices such as diet modification and selection of fertilizer type were also shown to affect 17β-estradiol concentrations in runoff water. Although results from these experiments typically represented a worst case scenario since runoff events generally occurred immediately after litter application, the contaminant loss from pastures fertilized with poultry litter can be expected to be much lower than continual estradiol loadings observed from waste water treatment plants. Management practices such as alum amendment and application timing can significantly reduce the risk of 17β-estradiol losses in the environment. Copyright © 2012 Elsevier B.V. All rights reserved.

Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an `interface' nucleus

PubMed Central

Pawlisch, Benjamin A.; Remage-Healey, Luke

2014-01-01

Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher-order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity. PMID:25453773

Neuroestrogen signaling in the songbird auditory cortex propagates into a sensorimotor network via an 'interface' nucleus.

PubMed

Pawlisch, B A; Remage-Healey, L

2015-01-22

Neuromodulators rapidly alter activity of neural circuits and can therefore shape higher order functions, such as sensorimotor integration. Increasing evidence suggests that brain-derived estrogens, such as 17-β-estradiol, can act rapidly to modulate sensory processing. However, less is known about how rapid estrogen signaling can impact downstream circuits. Past studies have demonstrated that estradiol levels increase within the songbird auditory cortex (the caudomedial nidopallium, NCM) during social interactions. Local estradiol signaling enhances the auditory-evoked firing rate of neurons in NCM to a variety of stimuli, while also enhancing the selectivity of auditory-evoked responses of neurons in a downstream sensorimotor brain region, HVC (proper name). Since these two brain regions are not directly connected, we employed dual extracellular recordings in HVC and the upstream nucleus interfacialis of the nidopallium (NIf) during manipulations of estradiol within NCM to better understand the pathway by which estradiol signaling propagates to downstream circuits. NIf has direct input into HVC, passing auditory information into the vocal motor output pathway, and is a possible source of the neural selectivity within HVC. Here, during acute estradiol administration in NCM, NIf neurons showed increases in baseline firing rates and auditory-evoked firing rates to all stimuli. Furthermore, when estradiol synthesis was blocked in NCM, we observed simultaneous decreases in the selectivity of NIf and HVC neurons. These effects were not due to direct estradiol actions because NIf has little to no capability for local estrogen synthesis or estrogen receptors, and these effects were specific to NIf because other neurons immediately surrounding NIf did not show these changes. Our results demonstrate that transsynaptic, rapid fluctuations in neuroestrogens are transmitted into NIf and subsequently HVC, both regions important for sensorimotor integration. Overall, these findings support the hypothesis that acute neurosteroid actions can propagate within and between neural circuits to modulate their functional connectivity. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Divergent effects of estradiol and the estrogen receptor-alpha agonist PPT on eating and activation of PVN CRH neurons in ovariectomized rats and mice.

PubMed

Thammacharoen, Sumpun; Geary, Nori; Lutz, Thomas A; Ogawa, Sonoko; Asarian, Lori

2009-05-01

Eating is modulated by estradiol in females of many species and in women. To further investigate the estrogen receptor mechanism mediating this effect, ovariectomized rats and mice were treated with estradiol benzoate or the estrogen receptor-alpha (ER-alpha)-selective agonist PPT. PPT inhibited eating in rats much more rapidly than estradiol (approximately 2-6 h versus >24 h). In contrast, the latencies to vaginal estrus after PPT and estradiol were similar (>24 h). PPT also inhibited eating within a few hours in wild-type mice, but failed to inhibit eating in transgenic mice deficient in ER-alpha (ERalphaKO mice). PPT, but not estradiol, induced the expression of c-Fos in corticotrophin-releasing hormone (CRH)-expressing cells of the paraventricular nucleus (PVN) of the hypothalamus within 90-180 min in rats. Both PPT and estradiol reduced c-Fos expression in an ER-alpha-containing area of the nucleus of the solitary tract. The anomalously rapid eating-inhibitory effect of PPT suggests that PPT's neuropharmacological effect differs from estradiol's, perhaps because PPT differentially activates membrane versus nuclear ER-alpha or because PPT activates non-ER-alpha membrane estrogen receptors in addition to ER-alpha. The failure of PPT to inhibit eating in ERalphaKO mice, however, indicates that ER-alpha is necessary for PPT's eating-inhibitory action and that any PPT-induced activation of non-ER-alpha estrogen receptors is not sufficient to inhibit eating. Finally, the rapid induction of c-Fos in CRH-expressing cells in the PVN by PPT suggests that PPT elicits a neural response that is similar to that elicited by stress or aversive emotional stimuli.

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

USDA-ARS?s Scientific Manuscript database

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...

Habitual physical activity and estradiol levels in women of reproductive age.

PubMed

Jasienska, Grazyna; Ziomkiewicz, Anna; Thune, Inger; Lipson, Susan F; Ellison, Peter T

2006-10-01

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

Estrogen-cholinergic interactions: Implications for cognitive aging.

PubMed

Newhouse, Paul; Dumas, Julie

2015-08-01

This article is part of a Special Issue "Estradiol and Cognition". While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects. Published by Elsevier Inc.

Effects of preovulatory estradiol on embryo survival and pregnancy establishment in beef cows

USDA-ARS?s Scientific Manuscript database

The role of preovulatory estradiol on embryo survival and pregnancy establishment has not been well characterized in beef cows. We hypothesized that preovulatory estradiol is important for embryo survival and pregnancy establishment in beef cows. Twenty-four ovariectomized multiparous cows were use...

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.

Alteration in G Proteins and Prolactin Levels in Pituitary After Ethanol and Estrogen Treatment

PubMed Central

Chaturvedi, Kirti; Sarkar, Dipak K.

2010-01-01

Background Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol’s mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine the changes in the pituitary levels of G proteins during the tumor development following alcohol and ethanol treatments. Methods Using ovariectomized Fischer-344 female rats, we have determined ethanol and estradiol actions at 2 and 4 weeks on pituitary weight and pituitary cell contents of prolactin, Gs. Gq11, Gi1, Gi2, and Gi3 proteins. Western blots were employed to measure protein contents. Results Ethanol increased basal and estradiol-enhanced wet weight and the prolactin content in the pituitary in a time-dependent manner. Chronic exposure of estradiol increased the levels of Gs protein in the pituitary. Unlike estradiol, ethanol exposure did not show significant effect on the basal level of Gs protein, but moderately increased the estradiol-induced levels of this protein. Estradiol exposure enhanced Gq11 protein levels in the pituitary after 2 and 4 weeks, while ethanol treatment failed to alter these protein levels in the pituitary in control-treated or estradioltreated ovariectomized rats. In the case of Gi1, estradiol but not ethanol increased the level of this protein at 4 weeks of treatment. However, estradiol and ethanol alone reduced the levels of both Gi2 and Gi3 proteins at 2 and 4 weeks of treatment. Ethanol also significantly reduced the estradiol-induced Gi2 levels at 4 weeks and Gi3 level at 2 and 4 weeks. Conclusions These results confirm ethanol’s and estradiol’s growth-promoting and prolactin stimulating actions on lactotropes of the pituitary and further provide evidence that ethanol and estradiol may control lactotropic cell functions by altering expression of specific group of G proteins in the pituitary. PMID:18336630

Dissipation of 17B-estradiol in composted poultry litter

USDA-ARS?s Scientific Manuscript database

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...

Effects of preovulatory estradiol concentration on embryo survival and pregnancy establishment in beef cows

USDA-ARS?s Scientific Manuscript database

The role of estradiol during the preovulatory period on embryo survival and pregnancy establishment has not been characterized in beef cows. We hypothesized that preovulatory estradiol is important for embryo survival and pregnancy establishment in beef cows. In order to establish the importance o...

Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus)

NASA Astrophysics Data System (ADS)

Saino, N.; Rubolini, D.; Romano, M.; Boncoraglio, G.

2007-03-01

The length ratio between individual digits differs between males and females in humans, other mammals, lizards, and one bird species. Sexual dimorphism in digit ratios and variation among individuals of the same sex may depend on differential exposure to androgens and estrogens during embryonic life. Organizational effects of sex hormones could cause the observed correlations between digit ratios and diverse phenotypic traits in humans. However, no study has investigated experimentally the effect of prenatal estrogens on digit ratios. We analyzed the effect of estradiol injection in ring-necked pheasant (Phasianus colchicus) eggs on digit ratios. Males from control eggs had higher ratios between the second or third and the fourth digit of the right foot compared to females. Estradiol-treated eggs produced males with lower (feminized) right foot second to fourth digit ratio. Thus, we provided the first experimental evidence that prenatal exposure to physiologically high estrogen levels affects bird digit ratios.

Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study.

PubMed

Jasuja, Guneet Kaur; Travison, Thomas G; Davda, Maithili; Murabito, Joanne M; Basaria, Shehzad; Zhang, Anqi; Kushnir, Mark M; Rockwood, Alan L; Meikle, Wayne; Pencina, Michael J; Coviello, Andrea; Rose, Adam J; D'Agostino, Ralph; Vasan, Ramachandran S; Bhasin, Shalender

2013-06-01

Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study. Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation. There were 1,461 eligible men (mean age [±SD] 61.1±9.5 years and body mass index [BMI] 28.8±4.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others. Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.

Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.

PubMed

Simone, Jean; Bogue, Elizabeth A; Bhatti, Dionnet L; Day, Laura E; Farr, Nathan A; Grossman, Anna M; Holmes, Philip V

2015-12-01

In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation

PubMed Central

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong

2017-01-01

Background A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. Objective This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Methods Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Results Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil (p<0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. Conclusion A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL. PMID:28566902

Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

PubMed

Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

2012-06-07

Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation.

PubMed

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong; Lee, Won-Soo

2017-06-01

A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil ( p <0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL.

To Modulate and Be Modulated: Estrogenic Influences on Auditory Processing of Communication Signals within a Socio-Neuro-Endocrine Framework

PubMed Central

Yoder, Kathleen M.; Vicario, David S.

2012-01-01

Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1. Local estradiol action within an auditory area is necessary for socially-relevant sounds to induce normal physiological responses in the brains of both sexes; 2. These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3. Estradiol action within the auditory forebrain enables behavioral discrimination among socially-relevant sounds in males; and 4. Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. Keywords: Estrogens, Songbird, Social Context, Auditory Perception PMID:22201281

Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.

PubMed

Gan, Lu; Jiang, Xuemin; Mendonza, Anisha; Swan, Therese; Reynolds, Christine; Nguyen, Joanne; Pal, Parasar; Neelakantham, Srikanth; Dahlke, Marion; Langenickel, Thomas; Rajman, Iris; Akahori, Mizuki; Zhou, Wei; Rebello, Sam; Sunkara, Gangadhar

2016-01-01

LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions. © 2015, The American College of Clinical Pharmacology.

Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

PubMed

Guevara-Guzmán, R; Arriaga, V; Kendrick, K M; Bernal, C; Vega, X; Mercado-Gómez, O F; Rivas-Arancibia, S

2009-03-31

There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue.

PubMed

Ramakrishnan, Gopalakrishnan; Rana, Anita; Das, Chandana; Chandra, Nimai Chand

2007-10-01

The aim of this study was to compare in vitro the role of two oral contraceptives, desogestrel (a less androgenic derivative of levonorgestrel) and levonorgestrel--alone and in combination with ethinyl estradiol--on low-density lipoprotein (LDL) receptor regulation by assessing receptor protein expression and functional effectiveness. Placental tissue and cultured placental cells (JEG-3) were used to study the expression and endocytotic activity of LDL receptor protein. The expression of the receptor was assessed by immunocytochemistry and immunoblot assays with and without contraceptive challenge. Functioning activity of LDL receptor was studied by measuring the rate of uptake of LDL by placental cells. Quantification of LDL was based on the total cholesterol content of the lipoprotein. A combination of desogestrel (20 ng/mL of incubation medium) and ethinyl estradiol (10 ng/mL of incubation medium) maintained the LDL receptor at high level of expression and functioning mode. In contrast, the double-blind preparation of levonorgestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL) had shown much lower expression as well as receptor-mediated LDL uptake. The concentration of contraceptives used in this study was similar to the prevailing concentration of oral contraceptives in clinical use. Higher expression of LDL receptor and enhanced rate of LDL uptake by the receptor protein projects the possibility that there might be less atherosclerosis-related disorders from the combination of desogestrol and ethinyl estradiol.

The effect of oral contraception on cardiometabolic risk factors in women with elevated androgen levels.

PubMed

Krysiak, Robert; Gilowska, Małgorzata; Okopień, Bogusław

2017-02-01

In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30μg) and drospirenone (3mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

PubMed

Peplonska, Beata; Bukowska, Agnieszka; Lie, Jenny Anne; Gromadzinska, Jolanta; Zienolddiny, Shanbeh

2016-09-01

The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (P<0.05 when compared to night work duration <5 years). Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm

PubMed Central

2011-01-01

Background The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha-zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from their structural similarity to 17beta-estradiol, 17beta-estradiol was used as a positive control for 'estrogen-like' effects. Methods Stallion spermatozoa were exposed in vitro to zearalenone, alpha-zearalenol, beta-zearalenol or 17beta-estradiol at concentrations ranging from 1 pM - 0.1 mM. After 2 hours exposure, motility parameters were evaluated by computer-assisted analysis, and acrosome integrity was examined by flow cytometry after staining with fluoroscein-conjugated peanut agglutinin. Results Mycotoxins affected sperm parameters only at the highest concentration tested (0.1 mM) after 2 hours exposure. In this respect, all of the compounds reduced the average path velocity, but only alpha-zearalenol reduced percentages of motile and progressively motile sperm. Induction of motility patterns consistent with hyperactivation was stimulated according to the following rank of potency: alpha-zearalenol >17beta-estradiol > zearalenone = beta-zearalenol. The hyperactivity-associated changes observed included reductions in straight-line velocity and linearity of movement, and an increase in the amplitude of lateral head displacement, while curvilinear velocity was unchanged. In addition, whereas alpha- and beta- zearalenol increased the percentages of live acrosome-reacted sperm, zearalenone and 17beta-estradiol had no apparent effect on acrosome status. In short, alpha-zearalenol inhibited normal sperm motility, but stimulated hyperactive motility in the remaining motile cells and simultaneously induced the acrosome reaction. Beta-zearalenol induced the acrosome reaction without altering motility. Conversely, zearalenone and 17beta-estradiol did not induce the acrosome reaction but induced hyperactive motility albeit to a different extent. Conclusions Apparently, the mycotoxin zearalenone has 17beta-estradiol-like estrogenic activity that enables it to induce hyperactivated motility of equine sperm cells, whereas the zearalenol derivatives induce premature completion of the acrosome reaction and thereby adversely affect stallion sperm physiology. The alpha form of zearalenol still possessed the estrogenic ability to induce hyperactivated motility, whereas its beta stereo-isomere had lost this property. PMID:21970729

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soverchia, L.; Ruggeri, B.; Palermo, F.

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. auratusmore » 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 rate through interaction with the ER{beta}-1 subtype. The present study also suggests that 4-NP at the concentration of 10{sup -6} M bioaccumulates in the liver.« less

Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial.

PubMed

Maloney, J Michael; Dietze, Peter; Watson, David; Niknian, Minoo; Lee-Rugh, Sooji; Sampson-Landers, Carole; Korner, Paul

2008-10-01

To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris. Healthy females aged 14-45 years with moderate acne were randomized in this double-blind study to 3-mg drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six cycles of 28 days. The primary outcome measures of acne lesion counts and Investigator Static Global Assessment scale ratings were assessed at baseline and during cycles 1, 3, and 6. The percentage reduction from baseline to endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95% confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated. The low-dose combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen significantly reduced acne lesion counts more effectively than placebo and demonstrated greater improvement in the Investigator Static Global Assessment rating of acne. The safety profile was consistent with low-dose combined oral contraceptive use.

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

PubMed

de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

ESTIMATING SYSTEMIC EXPOSURE TO ETHINYL ESTRADIOL FROM AN ORAL CONTRACEPTIVE

PubMed Central

WESTHOFF, Carolyn L.; PIKE, Malcolm C.; TANG, Rosalind; DINAPOLI, Marianne N.; SULL, Monica; CREMERS, Serge

2015-01-01

Objectives This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive to steady-state values, and to assess whether any simpler measures could provide an adequate proxy of the ‘gold standard’ 24-hour steady-state area-under-the-curve. Identifying a simple, less expensive, measure of systemic ethinyl estradiol exposure would be useful for larger studies designed to assess the relationship between an individual’s ethinyl estradiol exposure and her side effects. Study Design We conducted a 13 samples over 24 hours pharmacokinetic analysis on day 1 and day 21 of the first cycle of a monophasic oral contraceptive containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel in 17 non-obese healthy white women. We also conducted an abbreviated single dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of full 13-sample steady-state pharmacokinetic analysis with results calculated using fewer samples (9 or 5) and following the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. Results The area-under-the-curve, maximum (Cmax), and 24-hour (C24) values were similar following the two single oral contraceptive doses (area-under-the-curve, r = 0.92). The steady-state 13-sample 24-hour area-under-the-curve was highly correlated with the average 9-sample area-under-the-curve after the two single doses (r = 0.81, p = 0.0002). This correlation remained the same if the number of samples was reduced to 4, taken at time 1, 2.5, 4 and 24 hours. The C24 at steady-state was highly correlated with the 24-hour steady-state area-under-the-curve (r = 0.92, p < 0.0001). The average of the C24 values following the two single doses was also quite highly correlated with the steady-state area-under-the-curve (r = 0.72, p = 0.0026). Conclusions Limited blood sampling, including results from two single doses, gave highly correlated estimates of an oral contraceptive user’s steady-state ethinyl estradiol exposure. PMID:25511238

The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium.

PubMed

Rapkin, Rachel B; Creinin, Mitchell D

2011-10-01

Neural tube defects are the second most common congenital anomaly in the United States, although their incidence may be decreased by periconception folic acid supplementation. A new oral contraceptive containing drospirenone and ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk of neural tube defects in pregnancies conceived while taking or shortly after discontinuing this pill. Because of its novelty, very few studies have been performed to evaluate the efficacy, side effects and safety related to contraception, premenstrual dysphoric disorder and acne; therefore, literature evaluating similar contraceptives without levomefolate is reviewed. Additionally, we review studies evaluating the addition of levomefolate calcium to oral contraceptives containing 3 mg drospirenone and either 20 or 30 μg ethinyl estradiol. To date, no study has been performed to evaluate the effect this new oral contraceptive has on reducing the incidence of neural tube defects. This new pill has similar contraceptive efficacy, side effect, safety and benefits profile to other drospirenone-containing contraceptives. While also approved to prevent neural tube defects, no studies validate this claim and physician time is better spent counseling women, regardless of contraceptive choice, on the importance of folic acid supplementation during the child-bearing years.

Estradiol or fluoxetine alters depressive behavior and tryptophan hydroxylase in rat raphe.

PubMed

Yang, Fu-Zhong; Wu, Yan; Zhang, Wei-Guo; Cai, Yi-Yun; Shi, Shen-Xun

2010-03-10

The effects of 17beta-estradiol and fluoxetine on behavior of ovariectomized rats subjected to the forced swimming test and the expression of tryptophan hydroxylase (TPH) in dorsal and median raphe were investigated, respectively through time sampling technique of behavior scoring and immunohistochemistry. Both estradiol and fluoxetine increased swimming and decreased immobility in the forced swimming test. The forced swimming stress decreased integrated optical density of TPH-positive regions in dorsal and median raphe. Both estradiol and fluoxetine administration prevented integrated optical density of TPH-positive regions from being decreased by forced swimming stress. These observations suggest that both estradiol and fluoxetine have protective bearing on ovariectomized rats enduring forced swimming stress.

Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes.

PubMed

Ensrud, Kristine E; Guthrie, Katherine A; Hohensee, Chancellor; Caan, Bette; Carpenter, Janet S; Freeman, Ellen W; LaCroix, Andrea Z; Landis, Carol A; Manson, JoAnn; Newton, Katherine M; Otte, Julie; Reed, Susan D; Shifren, Jan L; Sternfeld, Barbara; Woods, Nancy F; Joffe, Hadine

2015-01-01

Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks. Academic research centers. 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day. Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine). Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality. NCT01418209 at www.clinicaltrials.gov. © 2014 Associated Professional Sleep Societies, LLC.

No compelling positive association between ovarian hormones and wearing red clothing when using multinomial analyses.

PubMed

Blake, Khandis R; Dixson, Barnaby J W; O'Dean, Siobhan M; Denson, Thomas F

2017-04-01

Several studies report that wearing red clothing enhances women's attractiveness and signals sexual proceptivity to men. The associated hypothesis that women will choose to wear red clothing when fertility is highest, however, has received mixed support from empirical studies. One possible cause of these mixed findings may be methodological. The current study aimed to replicate recent findings suggesting a positive association between hormonal profiles associated with high fertility (high estradiol to progesterone ratios) and the likelihood of wearing red. We compared the effect of the estradiol to progesterone ratio on the probability of wearing: red versus non-red (binary logistic regression); red versus neutral, black, blue, green, orange, multi-color, and gray (multinomial logistic regression); and each of these same colors in separate binary models (e.g., green versus non-green). Red versus non-red analyses showed a positive trend between a high estradiol to progesterone ratio and wearing red, but the effect only arose for younger women and was not robust across samples. We found no compelling evidence for ovarian hormones increasing the probability of wearing red in the other analyses. However, we did find that the probability of wearing neutral was positively associated with the estradiol to progesterone ratio, though the effect did not reach conventional levels of statistical significance. Findings suggest that although ovarian hormones may affect younger women's preference for red clothing under some conditions, the effect is not robust when differentiating amongst other colors of clothing. In addition, the effect of ovarian hormones on clothing color preference may not be specific to the color red. Copyright © 2017 Elsevier Inc. All rights reserved.

Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats.

PubMed

Duarte-Guterman, Paula; Lieblich, Stephanie E; Chow, Carmen; Galea, Liisa A M

2015-01-01

Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol's effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus.

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro

PubMed Central

Weingartshofer, Sigrid; Grunt, Thomas W.; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F.

2017-01-01

Background Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Materials and methods Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. Results In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). Conclusion We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status. PMID:28945801

Estradiol impairs the antiproliferative and proapoptotic effect of Zoledronic acid in hormone sensitive breast cancer cells in vitro.

PubMed

Gschwantler-Kaulich, Daphne; Weingartshofer, Sigrid; Grunt, Thomas W; Mairhofer, Mario; Tan, Yen; Gamper, Jutta; Singer, Christian F

2017-01-01

Zoledronic acid (ZA) has antiresorptive effects and protects from bone metastasis in women with early breast cancer. In addition, in postmenopausal women with endocrine responsive breast cancer ZA prolongs DFS. The exact mechanism is still unclear. We have therefore investigated the effect of increasing concentrations of ZA in breast cancer cell lines in the absence or presence of estradiol to mimic the hormonal environment in vitro. Using assays for cell proliferation (EZ4U, BrdU) and cell death (Annexin/PI), we have analyzed the dose-dependent antiproliferative and pro-apoptotic effects of ZA in two hormone sensitive cell lines (MCF-7 and T47D) and a hormone insensitive, triple negative cell line (MDA-MB-231) in the presence of 0, 1 and 10 nM estradiol. In the absence of estradiol, ZA exerts dose-dependent antiproliferative and pro-apoptotic antitumor effects in both, hormone sensitive (MCF-7, T47D) and -insensitive (MDA-MB-231) breast cancer cell lines (p<0.0001). In the presence of estradiol, the antitumoral effect of ZA was significantly decreased only in the hormone sensitive MCF-7 and T47D cell lines (p = 0.0008 and p = 0.0008, respectively). We have demonstrated that estradiol impairs the antiproliferative and proapoptotic effect of ZA in hormone sensitive, but not in hormone insensitive breast cancer cell lines. Our findings provide a possible explanation for the differential effect of ZA on DFS in pre- and postmenopausal patients with hormone sensitive early breast cancer, which has been demonstrated clinically. We further hypothesize that endocrine insensitive tumors such as triple negative breast cancer (TNBC) should benefit from ZA irrespective of their menopausal status.

Estradiol and progesterone influence on influenza infection and immune response in a mouse model.

PubMed

Davis, Sarah M; Sweet, Leigh M; Oppenheimer, Karen H; Suratt, Benjamin T; Phillippe, Mark

2017-10-01

Influenza infection severity may be mediated by estradiol and/or progesterone. An exploratory study was designed to evaluate 17-β-estradiol and progesterone on influenza infection and examine immune-mediated response in a mouse model. Inoculation with placebo or mouse-adapted H1N1 influenza virus occurred. Treatment groups included 17-β-estradiol, progesterone, ovariectomy, and pregnancy. Mice were assessed for morbidity and mortality. Toll-like receptor gene studies and airspace cell differentials were performed. Onset of morbidity was earlier and morbidity duration greater for progesterone. Absence of morbidity/mortality and overall survival was greater for 17-β-estradiol. Airspace cell differentials suggest improved immune cell recruitment for 17-β-estradiol. Pregnant mouse data demonstrate significant mortality during the period of increased progesterone. Select immune cell markers demonstrate patterns of regulation that may promote proper immune response to influenza infection for 17-β-estradiol. Estradiol may play a protective and progesterone a detrimental role in the pathophysiology of influenza infection. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An Antiprogestin, CDB4124, Blocks Progesterone’s Attenuation of the Negative Effects of a Mild Stress on Sexual Behavior

PubMed Central

Uphouse, Lynda; Hiegel, Cindy

2012-01-01

These experiments were designed to test the hypothesis that a progesterone receptor antagonist would block progesterone’s ability to reduce the negative effects of a 5 min restraint on female rat sexual behavior. Ovariectomized Fisher rats were injected with 10 μg estradiol benzoate. Two days later, rats were injected subcutaneously (sc) with the progesterone receptor antagonist, CDB4124 (17 α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione) (60 mg/kg), or vehicle (20% DMSO + propylene glycol). One hr later, rats were injected sc with 500 μg progesterone or vehicle (sesame seed oil). Rats were assigned to one of three different treatment conditions: (1) (ECV) estradiol benzoate, CDB4124, sesame seed oil vehicle, (2) (ECP) estradiol benzoate, CDB4124, progesterone, and (3) (EVP) estradiol benzoate, DMSO/propylene glycol vehicle, progesterone. That afternoon sexual behavior was examined before and after a 5 min restraint experience. Before restraint, lordosis behavior was comparable across treatment conditions but only progesterone-treated rats exhibited proceptive behavior. CDB4124 did not block progesterone’s induction of proceptivity. However, after restraint, CDB4124 attenuated the positive effects of progesterone on all sexual behaviors examined. The restraint experience inhibited sexual behavior in rats treated with estradiol benzoate and CDB4124 and in rats treated with estradiol benzoate, CDB4124, and progesterone but not in rats given estradiol benzoate and progesterone without CDB4124. These findings are consistent with the hypothesis that progesterone receptors mediate progesterone’s ability to reduce the negative sexual behavioral effects of a mild stressor. PMID:23153933

An antiprogestin, CDB4124, blocks progesterone's attenuation of the negative effects of a mild stress on sexual behavior.

PubMed

Uphouse, Lynda; Hiegel, Cindy

2013-03-01

These experiments were designed to test the hypothesis that a progesterone receptor antagonist would block progesterone's ability to reduce the negative effects of a 5 min restraint on female rat sexual behavior. Ovariectomized Fischer rats were injected with 10 μg estradiol benzoate. Two days later, rats were injected subcutaneously (sc) with the progesterone receptor antagonist, CDB4124 (17α-acetoxy-21-methoxy-11β-[4-N,N-dimethyaminopheny]-19-norpregna-4,9-dione-3,20-dione) (60 mg/kg), or vehicle (20% DMSO+propylene glycol). One hour later, rats were injected sc with 500 μg progesterone or vehicle (sesame seed oil). Rats were assigned to one of three different treatment conditions: (1) (ECV) estradiol benzoate, CDB4124, sesame seed oil vehicle, (2) (ECP) estradiol benzoate, CDB4124, progesterone, and (3) (EVP) estradiol benzoate, DMSO/propylene glycol vehicle, progesterone. That afternoon sexual behavior was examined before and after a 5 min restraint experience. Before restraint, lordosis behavior was comparable across treatment conditions but only progesterone-treated rats exhibited proceptive behavior. CDB4124 did not block progesterone's induction of proceptivity. However, after restraint, CDB4124 attenuated the positive effects of progesterone on all sexual behaviors examined. The restraint experience inhibited sexual behavior in rats treated with estradiol benzoate and CDB4124 and in rats treated with estradiol benzoate, CDB4124, and progesterone but not in rats given estradiol benzoate and progesterone without CDB4124. These findings are consistent with the hypothesis that progesterone receptors mediate progesterone's ability to reduce the negative sexual behavioral effects of a mild stressor. Copyright © 2012 Elsevier B.V. All rights reserved.

The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes.

PubMed

Pereira, Alécio Matos; de Souza Júnior, Antônio; Machado, Fernanda Brandão; Gonçalves, Gleisy Kelly Neves; Feitosa, Lauro César Soares; Reis, Adelina Martha; Santos, Robson Augusto Souza; Honorato-Sampaio, Kinulpe; Costa, Amilton Raposo

2015-12-01

Many studies identified new components of the renin–angiotensin system (RAS), such as Angiotensin-(1-7) [Ang-(1–7)] and Angiotensin-converting enzyme type 2 (ACE2), in mammalian ovaries.We previously showed Angiotensin-Converting Enzyme (ACE) inhibition, which increases the level of Ang-(1–7), stimulated ovarian estradiol output in ewe after estrous synchronization. Considering that Ang-(1–7) stimulates ovarian function and elevated estradiol before ovulation is associated with increased chance of achieving pregnancy, the present study investigated whether ACE inhibition throughout a superovulation protocol in ewe might improve ovulation outcome. At first, immunohistochemistry in ovaries of nonpregnant ewes revealed localization of Angiotensin II (Ang II), Ang-(1–7) and ACE2 in theca cells of antral follicles and in corpus luteum. Ang II and Ang-(1–7)were also detected in follicular fluid (FF) by Radioimmunoassay (RIA). Enalapril treatment throughout the superovulation protocol decreased 17β-estradiol (E2) output and raised progesterone:estradiol (P4:E2) ratio without a direct influence on ovulation and quality of embryos.

Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

PubMed

Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

2014-06-01

Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS.

PubMed

Wang, Yuan; Zhu, Qinling; Dang, Xuan; He, Yaqiong; Li, Xiaoxue; Sun, Yun

2017-01-01

Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50 ± 63.70 pg/ml) was significantly higher than that from non-PCOS patients (338.00 ± 57.88 pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1 μM for 24 h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.

Testosterone and 17β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice

PubMed Central

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Periera-Simon, Simone; Xia, Xiaomei; Korach, Ken; Berho, Mariana; Elliot, Sharon J.; Karl, Michael

2016-01-01

Podocyte damage and apoptosis are thought to be important if not essential in the development of glomerulosclerosis. Female estrogen receptor knockout mice develop glomerulosclerosis at 9 months of age due to excessive ovarian testosterone production and secretion. Here, we studied the pathogenesis of glomerulosclerosis in this mouse model to determine whether testosterone and/or 17β-estradiol directly affect the function and survival of podocytes. Glomerulosclerosis in these mice was associated with the expression of desmin and the loss of nephrin, markers of podocyte damage and apoptosis. Ovariectomy preserved the function and survival of podocytes by eliminating the source of endogenous testosterone production. In contrast, testosterone supplementation induced podocyte apoptosis in ovariectomized wild-type mice. Importantly, podocytes express functional androgen and estrogen receptors, which, upon stimulation by their respective ligands, have opposing effects. Testosterone induced podocyte apoptosis in vitro by androgen receptor activation, but independent of the TGF-β1 signaling pathway. Pretreatment with 17β-estradiol prevented testosterone-induced podocyte apoptosis, an estrogen receptor-dependent effect mediated by activation of the ERK signaling pathway, and protected podocytes from TGF-β1- or TNF-α-induced apoptosis. Thus, podocytes are target cells for testosterone and 17β-estradiol. These hormones modulate podocyte damage and apoptosis. PMID:20962747

Testosterone and 17β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice.

PubMed

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Periera-Simon, Simone; Xia, Xiaomei; Korach, Ken; Berho, Mariana; Elliot, Sharon J; Karl, Michael

2011-02-01

Podocyte damage and apoptosis are thought to be important if not essential in the development of glomerulosclerosis. Female estrogen receptor knockout mice develop glomerulosclerosis at 9 months of age due to excessive ovarian testosterone production and secretion. Here, we studied the pathogenesis of glomerulosclerosis in this mouse model to determine whether testosterone and/or 17β-estradiol directly affect the function and survival of podocytes. Glomerulosclerosis in these mice was associated with the expression of desmin and the loss of nephrin, markers of podocyte damage and apoptosis. Ovariectomy preserved the function and survival of podocytes by eliminating the source of endogenous testosterone production. In contrast, testosterone supplementation induced podocyte apoptosis in ovariectomized wild-type mice. Importantly, podocytes express functional androgen and estrogen receptors, which, upon stimulation by their respective ligands, have opposing effects. Testosterone induced podocyte apoptosis in vitro by androgen receptor activation, but independent of the TGF-β1 signaling pathway. Pretreatment with 17β-estradiol prevented testosterone-induced podocyte apoptosis, an estrogen receptor-dependent effect mediated by activation of the ERK signaling pathway, and protected podocytes from TGF-β1- or TNF-α-induced apoptosis. Thus, podocytes are target cells for testosterone and 17β-estradiol. These hormones modulate podocyte damage and apoptosis.

17β-estradiol regulates the differentiation of cementoblasts via Notch signaling cascade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Jing; Zhou, Zeyuan; Huang, Li

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 osteogenicmore » 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. - Highlights: • 17β-estradiol showed no significant effect on the proliferation of cementoblasts. • 17β-estradiol promoted the osteoblastic differentiation of cementoblasts despite of an early transient inhibition. • Notch signaling was regulated by 17β-estradiol and was responsible for mediating the effect of E2 on cementoblasts. • Hey1 might display an opposite expression pattern to Notch signaling in certain circumstances.« less

Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model.

PubMed

Chaloner, Aaron; Greenwood-Van Meerveld, Beverley

2013-03-01

Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. Copyright © 2013 American Pain Society. All rights reserved.

Influence of estradiol and androstenedione on ACTH and cortisol secretion in the ovine fetus.

PubMed

Wood, C E; Saoud, C J

1997-01-01

To test the hypothesis that physiologic increases in fetal plasma 17 beta-estradiol and androstenedione modulate the activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Seventeen pregnant ewes and their fetuses were chronically catheterized. At the time of surgery, the fetuses received implants that released 17 beta-estradiol (n = 5) alone or 17 beta-estradiol and androstenedione (n = 6), each at a rate of approximately 250 micrograms/day for each steroid. The control group (n = 6) received either no pellet (n = 2) or a "placebo" pellet, which contained no steroid (n = 4). Fetal blood samples were drawn for hormone and blood gas analysis at 1-3-day intervals until the time of spontaneous parturition. Fetal plasma ACTH and cortisol concentrations were fit to semilogarithmic equations and analyzed by stepwise multiple linear regression analysis for statistically significant effects of 17 beta-estradiol and androstenedione. Estradiol significantly increased and androstenedione significantly decreased the ACTH and cortisol concentrations. Treatment with both 17 beta-estradiol and androstenedione resulted in parturition approximately 4 days earlier than in the other groups (P < .05). Physiologic increases in fetal plasma estradiol and androstenedione modify the activity of the HPA axis.

In vitro effects of diethylstilbestrol, genistein, 4-tert-butylphenol, and 4-tert-octylphenol on steroidogenic activity of isolated immature rat ovarian follicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myllymaeki, Sari; Haavisto, Tapio; Vainio, Minna

2005-04-01

Isolated rat ovarian follicles grow and produce steroid hormones in vitro and so provide a good model for studying the effects of hormonally active compounds on follicular steroidogenesis. We have evaluated the effects of diethylstilbestrol (DES), genistein (GEN) and two alkylphenols, 4-tert-butylphenol (BP) and 4-tert-octylphenol (OP) on the growth, survival, and steroid hormone and cAMP production by isolated 14-day-old rat (Sprague-Dawley) ovarian follicles. During a 5-day culture, FSH was obligatory for follicle growth and increased estradiol and testosterone secretion in a dose-dependent manner. DES (10{sup -6} M) caused the strongest decline in estradiol and testosterone levels but did not havemore » detectable effects on either cAMP production or aromatase enzyme activity. GEN caused a prominent decrease in cAMP and testosterone levels without significant changes in secreted estradiol. The latter, apparently, was due to a dose-dependent stimulation of aromatase enzyme activity in the presence of genistein. Both BP and OP decreased estradiol and testosterone secretion in a dose-dependent manner while no effect on aromatase activity was observed. OP, unlike BP, decreased forskolin-induced cAMP levels. Xenoestrogens at the used concentrations did not interfere with the growth and survival of the follicles. The results indicate that isolated ovarian follicles representing intact morphological and functional units offer a sensitive model system for elucidating the female-specific reproductive effects of environmental chemicals.« less

Transport of estradiol-17β-glucuronide, estrone-3-sulfate and taurocholate across the endoplasmic reticulum membrane: evidence for different transport systems☆

PubMed Central

Wlcek, Katrin; Hofstetter, Lia; Stieger, Bruno

2014-01-01

Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. Consequently, UGT generated glucuronides, like estradiol-17β-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis. Based on their physicochemical properties such compounds are not favored for passive diffusion and therefore likely necessitate transport system(s) to cross the ER membrane in either direction. The current study aims to investigate the transport of taurocholate, estradiol-17β-glucuronide, and estrone-3-sulfate in smooth (SER) and rough (RER) endoplasmic reticulum membrane vesicles isolated from Wistar and TR− rat liver. Time-dependent and bidirectional transport was demonstrated for taurocholate, showing higher uptake rates in SER than RER vesicles. For estradiol-17β-glucuronide a fast time-dependent efflux with similar efficiencies from SER and RER but no clear protein-mediated uptake was shown, indicating an asymmetric transport system for this substrate. Estrone-3-sulfate uptake was time-dependent and higher in SER than in RER vesicles. Inhibition of steroidsulfatase mediated estrone-3-sulfate hydrolysis decreased estrone-3-sulfate uptake but had no effect on taurocholate or estradiol-17β-glucuronide transport. Based on inhibition studies and transport characteristics, three different transport mechanisms are suggested to be involved in the transport of taurocholate, estrone-3-sulfate and estradiol-17β-glucuronide across the ER membrane. PMID:24406246

Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses

PubMed Central

Saal, Frederick S. vom; Timms, Barry G.; Montano, Monica M.; Palanza, Paola; Thayer, Kristina A.; Nagel, Susan C.; Dhar, Minati D.; Ganjam, V. K.; Parmigiani, Stefano; Welshons, Wade V.

1997-01-01

On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship. PMID:9050904

The folic acid combined with 17-β estradiol produces antidepressant-like actions in ovariectomized rats forced to swim.

PubMed

Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

2011-01-15

Folic acid or 17-β estradiol produces antidepressant effects, either alone or combined with several antidepressants. However, the antidepressant-like actions of folic acid combined with 17-β estradiol in the forced swimming test (FST) have not been tested before. Thus, in the present study, ovariectomized female rats received folic acid (5.0 nmol/i.c.v., P<0.05; 10.0 nmol/ i.c.v., P<0.05; or 50mg/kg, P<0.05, p.o.; 75.0; mg/kg, P<0.05, p.o.), or fluoxetine (20.0mg/kg, P<0.05; 25.0mg/kg, P<0.05) or 17-β estradiol (10.0 μg/rat, P<0.05; 20.0 μg/rat, P<0.05) and they displayed reduced immobility by increasing swimming behavior when they were tested in the FST. Combination of subthreshold doses of folic acid (2.5 nmol/i.c.v.; or 25.0mg/kg, p.o.) with subthreshold doses of 17-β estradiol (5.0 μg/rat, P<0.05) or with subthreshold doses of fluoxetine (15.0mg/kg, P<0.05) produced antidepressant-like actions. Ketanserin was used to evaluate the participation of the drugs used in the serotonergic pathway; ketanserin cancelled the antidepressant-like actions of the several combinations used. In conclusion, folic acid alone or combined with estradiol or fluoxetine in the FST reduced immobility in the FST. These antidepressant-like actions probably were due to modifications of the serotonergic system since swimming behavior was increased and these effects were cancelled by ketanserin. Copyright © 2010 Elsevier Inc. All rights reserved.

G protein-coupled estrogen receptor and estrogen receptor ligands regulate colonic motility and visceral pain.

PubMed

Zielińska, M; Fichna, J; Bashashati, M; Habibi, S; Sibaev, A; Timmermans, J-P; Storr, M

2017-07-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal (GI) disorder, which occurs more frequently in women than men. The aim of our study was to determine the role of activation of classical estrogen receptors (ER) and novel membrane receptor, G protein-coupled estrogen receptor (GPER) in human and mouse tissue and to assess the possible cross talk between these receptors in the GI tract. Immunohistochemistry was used to determine the expression of GPER in human and mouse intestines. The effect of G-1, a GPER selective agonist, and estradiol, a non-selective ER agonist, on muscle contractility was characterized in isolated preparations of the human and mouse colon. To characterize the effect of G-1 and estradiol in vivo, colonic bead expulsion test was performed. G-1 and estradiol activity on the visceral pain signaling was assessed in the mustard oil-induced abdominal pain model. GPER is expressed in the human colon and in the mouse colon and ileum. G-1 and estradiol inhibited muscle contractility in vitro in human and mouse colon. G-1 or estradiol administered intravenously at the dose of 20 mg/kg significantly prolonged the time to bead expulsion in females. Moreover, G-1 prolonged the time to bead expulsion and inhibited GI hypermotility in both genders. The injection of G-1 or estradiol resulted in a significant reduction in the number of pain-induced behaviors in mice. GPER and ER receptors are involved in the regulation of GI motility and visceral pain. Both may thus constitute an important pharmacological target in the IBS-D therapy. © 2017 John Wiley & Sons Ltd.

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women

PubMed Central

Klump, Kelly L.; O’Connor, Shannon M.; Hildebrandt, Britny A.; Keel, Pamela K.; Neale, Michael; Sisk, Cheryl L.; Boker, Steven; Burt, S. Alexandra

2016-01-01

Recent data show shifts in genetic and environmental influences on emotional eating across the menstrual cycle, with significant shared environmental influences during pre-ovulation, and primarily genetic effects during post-ovulation. Factors driving differential effects are unknown, although increased estradiol during pre-ovulation and increased progesterone during post-ovulation are thought to play a role. We indirectly investigated this possibility by examining whether overall levels of estradiol and progesterone differentially impact genetic and environmental risk for emotional eating in adult female twins (N = 571) drawn from the MSU Twin Registry. Emotional eating, estradiol levels, and progesterone levels were assessed daily and then averaged to create aggregate measures for analysis. As predicted, shared environmental influences were significantly greater in twins with high estradiol levels, whereas additive genetic effects increased substantially across low versus high progesterone groups. Results highlight significant and differential effects of ovarian hormones on etiologic risk for emotional eating in adulthood. PMID:27747142

The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

PubMed

Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

2016-01-01

Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P < 0.05). GABA significantly decreased the aforementioned parameters (P < 0.05). The uterus weight increased significantly in rats that received estradiol (P < 0.05). Serum and kidney levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P < 0.05). It seems that GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

Modulation of hepatocyte growth factor secretion in human female reproductive tract stromal fibroblasts by poly (I:C) and estradiol.

PubMed

Coleman, Kimberly D; Ghosh, Mimi; Crist, Sarah G; Wright, Jacqueline A; Rossoll, Richard M; Wira, Charles R; Fahey, John V

2012-01-01

Hepatocyte Growth Factor (HGF) secretion facilitates epithelial cell growth and development in the female reproductive tract (FRT) and may contribute to pathological conditions such as cancer and endometriosis. We hypothesized that estradiol and poly (I:C), a synthetic RNA mimic, may have a regulatory effect on HGF secretion by stromal fibroblasts from FRT tissues. Following hysterectomies, normal tissue from the uterus, endocervix, and ectocervix were dispersed into stromal cell fractions by enzymatic digestion and differential filtering. Stromal fibroblasts were cultured and treated with estradiol and/or poly (I:C), and conditioned media were analyzed for HGF via enzyme-linked immunosorbent assay. Treating uterine fibroblasts with estradiol or poly (I:C) significantly increased HGF secretion. When uterine fibroblasts were co-treated with estradiol and poly (I:C), the effect on HGF secretion was additive. In contrast, stromal fibroblasts from endo- and ecto-cervix were unresponsive to estradiol, but were stimulated to secrete HGF by poly (I:C). HGF secretion is uniquely regulated in the uterus, but not in ecto- and endo-cervix, by estradiol. Moreover, potential viral pathogens further induce HGF. These findings have potential applications in understanding both hormonal regulation of normal tissue as well as the role of HGF in tumorogenesis, endometriosis, and human immunodeficiency virus infection. © 2011 John Wiley & Sons A/S.

Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Sukhdeep; Mukherjee, Tapan K.; Guptasarma, Purnananda, E-mail: guptasarma@iisermohali.ac.in

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 {sup 1}H and {sup 13}C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl {sup 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 agemore » 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. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters {sup 1}H and {sup 13}C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C{sub 18} reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.« less

Evaluation of performance with small and scale-up rotating and flat reactors; photocatalytic degradation of bisphenol A, 17β-estradiol, and 17α-ethynyl estradiol under solar irradiation.

PubMed

Kim, Saewon; Cho, Hyekyung; Joo, Hyunku; Her, Namguk; Han, Jonghun; Yi, Kwangbok; Kim, Jong-Oh; Yoon, Jaekyung

2017-08-15

In this study, the performances of photocatalytic reactors of the small and scale-up rotating and flat types were evaluated to investigate the treatment of new emerging contaminants such as bisphenol A (BPA), 17α-ethynyl estradiol (EE2), and 17β-estradiol (E2) that are known as endocrine disrupting compounds (EDCs). In the laboratory tests with the small-scale rotating and flat reactors, the degradation efficiencies of the mixed EDCs were significantly influenced by the change of the hydraulic retention time (HRT). In particular, considering the effective two-dimensional reaction area with light and nanotubular TiO 2 (NTT) on a Ti substrate, the rotating reactors showed the more effective performance than the flat reactor because the degradation efficiencies are similar in the small effective area. In addition, the major parameters affecting the photocatalytic activities of the NTT were evaluated for the rotating reactors according to the effects of single and mixed EDCs, the initial concentrations of the EDCs, the UV intensity, and dissolved oxygen. In the extended outdoor tests with the scale-up photocatalytic reactors and NTT, it was confirmed from the four representative demonstrations that an excellent rotating-reactor performance is consistently shown in terms of the degradation of the target pollutants under solar irradiation. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Peri-pubertal high caffeine exposure increases ovarian estradiol production in immature rats.

PubMed

Kwak, Yoojin; Choi, Hyeonhae; Bae, Jaeman; Choi, Yun-Young; Roh, Jaesook

2017-04-01

Chronic caffeine consumption exerts a negligible effect on the reproductive organs of normal adult females, but it is not known whether this is also true for children and adolescents. Here, we investigated the effects of high caffeine exposure on sexual maturation and ovarian estradiol production in immature female rats. Immature female SD rats were divided into controls and caffeine groups fed 120 and 180mg/kg/day for 4 or 8 weeks. There was a significant delay in vaginal opening in the caffeine-fed groups. In addition, serum estradiol levels were elevated in the caffeine-fed animals after 2 and 4 weeks of exposure. Estradiol secretion as well as aromatase expression also increased significantly in the ovarian cells in response to caffeine. These results demonstrate that peripubertal exposure to high caffeine increases estradiol production in the ovary; this may disturb the coordinated regulation of the hypothalamo-pituitary-ovarian axis, thereby interfering with sexual maturation. Copyright © 2017 Elsevier Inc. All rights reserved.

Sexual characteristics of male guppies Poecilia reticulata serve as effect biomarkers of estrogens

NASA Astrophysics Data System (ADS)

Tian, Hua; Li, Yun; Wang, Wei; Zhao, Fei; Gao, Su; Ru, Shaoguo

2017-10-01

Guppies (Poecilia reticulata) are considered a candidate model species for the identification and testing of endocrine-disrupting chemicals. Male guppies may be used to address the challenge of making potential linkages between alterations of biomarkers, both at the cellular and organ level, and adverse outcomes. In the present study, a predictive relationship between sex characteristics and reproductive output was observed in male guppies that underwent a long-term toxicity test with 0.5 μg/L 17β-estradiol administered during the juvenile period. Radioimmunoassay and western blot analyses demonstrated that 17β-estradiol exposure caused a significant increase in testicular 17β-estradiol levels as well as the induction of exposure biomarkers, namely hepatic vitellogenin. Exposure to 17β-estradiol also caused a significant decrease in testosterone levels, which consequently reduced the gonadosomatic index, sperm counts, and the coloration index. These changes of male sexual characteristics further translated into adverse influences on reproduction, as measured by a decrease in off spring production and survival rate. Our results suggest that the above-mentioned sexual characteristics of male guppies may be considered potential in vivo biomarkers of estrogen effects on reproduction.

The effect of Escherichia coli lipopolysaccharide and Tumor Necrosis Factor alpha on ovarian function

PubMed Central

Williams, Erin J.; Sibley, Kelly; Miller, Aleisha N.; Lane, Elizabeth A.; Fishwick, John; Nash, Deborah M.; Herath, Shan; England, Gary CW; Dobson, Hilary; Sheldon, I. Martin

2009-01-01

Problem Pelvic inflammatory disease and metritis are important causes of infertility in humans and domestic animals. Uterine infection with Escherichia coli in cattle is associated with reduced ovarian follicle growth and decreased estradiol secretion. We hypothesized that this effect could be mediated by the bacterial lipopolysaccharide (LPS) or cytokines such as tumor necrosis factor alpha (TNFα). Method of study In vitro, bovine ovarian theca and granulosa cells were treated with LPS or TNFα and steroid secretion measured. In vivo, the effect of LPS or TNFα intrauterine infusion was determined by ovarian ultrasonography and measurement of hormones in cattle. Results LPS reduced granulosa cell estradiol secretion, whilst TNFα decreased theca and granulosa cell androstenedione and estradiol production, respectively. In vivo, fewer animals ovulated following intrauterine infusion with LPS or TNFα. Conclusion LPS and TNFα suppress ovarian cell function, supporting the concept that pelvic inflammatory disease and metritis are detrimental for bovine ovarian health. PMID:19238751

Effect of Urinary Bisphenol A on Androgenic Hormones and Insulin Resistance in Preadolescent Girls: A Pilot Study from the Ewha Birth & Growth Cohort

PubMed Central

Lee, Hye Ah; Kim, Young Ju; Lee, Hwayoung; Gwak, Hye Sun; Park, Eun Ae; Cho, Su Jin; Kim, Hae Soon; Ha, Eun Hee; Park, Hyesook

2013-01-01

To assess the effect of urinary bisphenol A (BPA) on repeated measurements of androgenic hormones and metabolic indices, we used multivariate analysis of variance (MANOVA) adjusted for potential confounders at baseline. During July to August 2011, 80 preadolescent girls enrolled in the Ewha Birth & Growth Cohort study participated in a follow-up study and then forty-eight of them (60.0%) came back one year later. Baseline levels of estradiol and androstenedione were higher in the BPA group than in the non-BPA group. One year later, girls in the high BPA exposure group showed higher levels of androstenedione, testosterone, estradiol, and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index, than those in the other groups (p < 0.05). In MANOVA, estradiol and androstenedione showed significant differences among groups, while dehydroepiandrosterone, insulin, and HOMA-IR showed marginally significant differences. Exposure to BPA may affect endocrine metabolism in preadolescents. However, further investigation is required to elucidate the mechanisms linking BPA with regulation of androgenic hormones. PMID:24189184

Elsevier Trophoblast Research Award lecture: Molecular mechanisms underlying estrogen functions in trophoblastic cells--focus on leptin expression.

PubMed

Gambino, Y P; Maymó, J L; Pérez Pérez, A; Calvo, J C; Sánchez-Margalet, V; Varone, C L

2012-02-01

The steroid hormone 17β-estradiol is an estrogen that influences multiple aspects of placental function and fetal development in humans. During early pregnancy it plays a role in the regulation of blastocyst implantation, trophoblast differentiation and invasiveness, remodeling of uterine arteries, immunology and trophoblast production of hormones such as leptin. Estradiol exerts some effects through the action of classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors and regulate gene expression. In addition, estradiol can elicit rapid responses from membrane-associated receptors, like activation of protein-kinase pathways. Thus, the cellular effects of estradiol will depend on the specific receptors expressed and the integration of their signaling events. Leptin, the 16,000MW protein product of the obese gene, was originally considered an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy. The leptin gene is expressed in placenta, where leptin promotes proliferation and survival of trophoblastic cells. Expression of leptin in placenta is highly regulated by key pregnancy molecules as hCG and estradiol. The aim of this paper is to review the molecular mechanisms underlying estrogen functions in trophoblastic cells; focusing on mechanisms involved in estradiol regulation of placental leptin expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Effect of Feeding Purified versus Chow Diet on Bone Changes Produced by Hindlimb Suspension of Female Rats

NASA Technical Reports Server (NTRS)

Tou, Janet; Arnaud, Sara B.; Grindeland, Richard; Wade, Charles

2004-01-01

Spaceflight simulation studies use chow diets while spaceflight studies use a semi-purified &et. To determine whether the differences in these diets would affect the changes in unweighted bone, we compared the effects of purified vs chow diet on bone parameters, urinary calcium, plasma estradiol, and urinary corticosterone (CORT) in sexually mature female Sprague-Dawley rats. Rats fed purified AIN-93G or chow diet were kept ambulatory (AMB) or subjected to a spaceflight simulation model of unweighted hindlimbs (HLS) for 38 days. Body mass of treatment groups was similar although food intake and caloric density of the diets differed. Both HLS diet groups showed similar decreases in bone mineral content and mechanical strength in unweighted femurs compared to AMB (p<0.05). However, femur length was lower (p<0.05) in the chow-fed than AIN-93G fed groups. Urinary calcium excretion was greater in chow than AIN-93G fed rats, consistent with the higher level of calcium in the diet. Plasma estradiol was lower in HLS than in AMB fed AIN-93G, but similar in HLS and AMB chow fed groups. Femur mineral content was related to plasma estradiol (r(sup 2) =0.91, p<0.00l). Urinary CORT excretion was increased during initial HLS and elevated in HLS/chow-fed rats. Diets did not appear to affect the osteopenia induced by unweighting, but effects on bone growth, calcium excretion, plasma estradiol and urinary CORT do not support the view that these diets can by used interchangeably in bone studies.

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

2015-05-01

This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Non-Genomic Estrogen Regulation of Ion Transport and Airway Surface Liquid Dynamics in Cystic Fibrosis Bronchial Epithelium

PubMed Central

Saint-Criq, Vinciane; Kim, Sung Hoon; Katzenellenbogen, John A.; Harvey, Brian J.

2013-01-01

Male cystic fibrosis (CF) patients survive longer than females and lung exacerbations in CF females vary during the estrous cycle. Estrogen has been reported to reduce the height of the airway surface liquid (ASL) in female CF bronchial epithelium. Here we investigated the effect of 17β-estradiol on the airway surface liquid height and ion transport in normal (NuLi-1) and CF (CuFi-1) bronchial epithelial monolayers. Live cell imaging using confocal microscopy revealed that airway surface liquid height was significantly higher in the non-CF cells compared to the CF cells. 17β-estradiol (0.1–10 nM) reduced the airway surface liquid height in non-CF and CF cells after 30 min treatment. Treatment with the nuclear-impeded Estrogen Dendrimer Conjugate mimicked the effect of free estrogen by reducing significantly the airway surface liquid height in CF and non-CF cells. Inhibition of chloride transport or basolateral potassium recycling decreased the airway surface liquid height and 17β-estradiol had no additive effect in the presence of these ion transporter inhibitors. 17β-estradiol decreased bumetanide-sensitive transepithelial short-circuit current in non-CF cells and prevented the forskolin-induced increase in ASL height. 17β-estradiol stimulated an amiloride-sensitive transepithelial current and increased ouabain-sensitive basolateral short-circuit current in CF cells. 17β-estradiol increased PKCδ activity in CF and non-CF cells. These results demonstrate that estrogen dehydrates CF and non-CF ASL, and these responses to 17β-estradiol are non-genomic rather than involving the classical nuclear estrogen receptor pathway. 17β-estradiol acts on the airway surface liquid by inhibiting cAMP-mediated chloride secretion in non-CF cells and increasing sodium absorption via the stimulation of PKCδ, ENaC and the Na+/K+ATPase in CF cells. PMID:24223826

Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix

PubMed Central

Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P.

2009-01-01

Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Objective: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. Design: This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Participants: Fifty-five healthy, regularly cycling premenopausal women participated. Interventions: Subjects were administered a single oral dose of 25–400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (±1) after onset of menses. Main Outcome Measures: Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Results: Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50–200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 ± 3 to 68 ± 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Conclusions: Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states. PMID:19033369

Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix.

PubMed

Struthers, R Scott; Nicholls, Andrew J; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S C; Bozigian, Haig P

2009-02-01

Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist. Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women. This was a first-in-human, double-blind, placebo-controlled, single- and multiple-dose study with sequential dose escalation. Fifty-five healthy, regularly cycling premenopausal women participated. Subjects were administered a single oral dose of 25-400 mg or placebo. In a second arm of the study, subjects received placebo or 50, 100, or 200 mg once daily or 100 mg twice daily for 7 d. Treatment was initiated on d 7 (+/-1) after onset of menses. Safety, tolerability, pharmacokinetics, and serum LH, FSH, and estradiol concentrations were assessed. Elagolix was well tolerated and rapidly bioavailable after oral administration. Serum gonadotropins declined rapidly. Estradiol was suppressed by 24 h in subjects receiving at least 50 mg/d. Daily (50-200 mg) or twice-daily (100 mg) administration for 7 d maintained low estradiol levels (17 +/- 3 to 68 +/- 46 pg/ml) in most subjects during late follicular phase. Effects of the compound were rapidly reversed after discontinuation. Oral administration of a nonpeptide GnRH antagonist, elagolix, suppressed the reproductive endocrine axis in healthy premenopausal women. These results suggest that elagolix may enable dose-related pituitary and gonadal suppression in premenopausal women as part of treatment strategies for reproductive hormone-dependent disease states.

Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

PubMed

Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

2016-07-01

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

PubMed

Day, Danielle S; Gozansky, Wendolyn S; Bell, Christopher; Kohrt, Wendy M

2011-10-01

Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA. MSNA was measured in 9 women (30±2 years; mean±SE) on three separate occasions: during the mid-luteal menstrual cycle phase, on the fifth day of gonadotropin-releasing hormone antagonist (GnRHant) administration, and after 5 days add-back of either estradiol (n=4) or progesterone (n=3) during continued GnRHant administration. In response to GnRHant, there were significant reductions in serum estradiol and progesterone (both p<0.01) and MSNA (25.0±1.9 vs. 19.2±2.4 bursts/min, p=0.04). Continued GnRHant plus add-back estradiol or progesterone resulted in a nonsignificant decrease (19.2±1.7 vs. 12.1±1.9 bursts/min, p=0.07) or increase (16.2±1.7 vs. 21.0±6.0 bursts/min, p=0.39), respectively, in MSNA when compared with GnRHant alone. The findings of this preliminary study suggest that short-term ovarian hormone suppression attenuates MSNA and that this may be related to the suppression of progesterone rather than estradiol.

Estradiol Activates PI3K/Akt/GSK3 Pathway Under Chronic Neurodegenerative Conditions Triggered by Perinatal Asphyxia

PubMed Central

Saraceno, G. Ezequiel; Bellini, Maria J.; Garcia-Segura, Luis M.; Capani, Francisco

2018-01-01

Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) α and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERα and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA. PMID:29686616

Fluctuations of estradiol during women's menstrual cycle: Influences on reactivity towards erotic stimuli in the late positive potential.

PubMed

Munk, Aisha J L; Zoeller, Aaron C; Hennig, Juergen

2018-05-01

While several studies examined the reactivity towards negative emotional stimuli across women's menstrual cycle, only few investigated responses to positive emotional cues in association with sexual hormones on a neural level. Therefore, the aim of the current EEG-experiment was to study the differential reactivity towards positive (erotic) words during the menstrual cycle (i.e. with fluctuations in the steroids estradiol and progesterone) in the late positive potential (LPP). Regarding reactivity towards erotic stimuli, the LPP is seen as the most relevant ERP-component, as more positive amplitudes in the LPP reflect larger incentive salience and higher arousal. The LPP towards erotic words was expected to be more pronounced during fertile phases of the menstrual cycle (around ovulation). Furthermore, associations with hormonal concentrations of estradiol and progesterone were investigated. 19 young, free cycling women were tested in an Erotic Stroop paradigm during the follicular phase, ovulation, and the luteal phase in a balanced cross-over design, while electroencephalogram (EEG) was recorded. LPPs in reaction to erotic compared to neutral words were larger in every phase. During the follicular phase and ovulation, higher estradiol-concentrations were associated with more positive LPP-amplitudes towards erotic- than to neutral words. No effects of progesterone, as well as no effects of cycle phase, were evident. Results are being discussed regarding implications for further research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Estradiol Activates PI3K/Akt/GSK3 Pathway Under Chronic Neurodegenerative Conditions Triggered by Perinatal Asphyxia.

PubMed

Saraceno, G Ezequiel; Bellini, Maria J; Garcia-Segura, Luis M; Capani, Francisco

2018-01-01

Perinatal asphyxia (PA) remains as one of the most important causes of short-term mortality, psychiatric and neurological disorders in children, without an effective treatment. In previous studies we have observed that the expression of different neurodegenerative markers increases in CA1 hippocampal area of 4-months-old male rats born by cesarean section and exposed for 19 min to PA. We have also shown that a late treatment with 17β estradiol (daily dose of 250 μg/kg for 3 days) was able to revert the brain alterations observed in those animals. Based on these previous results, the main aim of the present study was to explore the mechanism by which the estrogenic treatment is involved in the reversion of the chronic neurodegenerative conditions induced by PA. We demonstrated that estradiol treatment of adult PA exposed animals induced an increase in estrogen receptor (ER) α and insulin-like growth factor receptor (IGF-1R) protein levels, an activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta/β-catenin signaling pathway and an increase in Bcl-2/Bax ratio in the hippocampus in comparison to PA exposed animals treated with vehicle. Taking together, our data suggest that the interaction between ERα and IGF-IR, with the subsequent downstream activation, underlies the beneficial effects of estradiol observed in late treatment of PA.

Human uterine and placental arteries exhibit tissue-specific acute responses to 17β-estradiol and estrogen-receptor-specific agonists.

PubMed

Corcoran, Jemma J; Nicholson, Christopher; Sweeney, Michèle; Charnock, Jayne C; Robson, Stephen C; Westwood, Melissa; Taggart, Michael J

2014-05-01

The discrete regulation of vascular tone in the human uterine and placental circulations is a key determinant of appropriate uteroplacental blood perfusion and pregnancy success. Humoral factors such as estrogen, which increases in the placenta and maternal circulation throughout human pregnancy, may regulate these vascular beds as studies of animal arteries have shown that 17β-estradiol, or agonists of estrogen receptors (ER), can exert acute vasodilatory actions. The aim of this study was to compare how acute exposure to ER-specific agonists, and 17β-estradiol, altered human placental and uterine arterial tone in vitro. Uterine and placental arteries were isolated from biopsies obtained from women with uncomplicated pregnancy delivering a singleton infant at term. Vessels were mounted on a wire myograph, exposed to the thromboxane receptor agonist U46619 (10(-6) M), and then incubated with incremental doses (5 min, 0.03-30 µM) of either 17β-estradiol or agonists specific for the ERs ERα (PPT), ERβ (DPN) or the G-protein-coupled estrogen receptor GPER-1 (G1). ERα and ERβ mRNA expression was assessed. 17β-estradiol, PPT and DPN each relaxed myometrial arteries (P < 0.05) in a manner that was partly endothelium-dependent. In contrast, 17β-estradiol or DPN relaxed placental arteries (maximum relaxation to 42 ± 1.1 or 47.6 ± 6.53% of preconstriction, respectively) to a lesser extent than myometrial arteries (to 0.03 ± 0.03 or 8.0 ± 1.0%) and in an endothelial-independent manner whereas PPT was without effect. G1 exposure did not inhibit the constriction of myometrial nor placenta arteries. mRNA expression of ERα and ERβ was greater in myometrial arteries than placental arteries. ER-specific agonists, and 17β-estradiol, differentially modulate the tone of uterine versus placental arteries highlighting that estrogen may regulate human uteroplacental blood flow in a tissue-specific manner.

Effect of calcium soaps of fatty acids and administration of somatotropin on milk production, preovulatory follicular development, and plasma and follicular fluid lipid composition in high yielding dairy cows.

PubMed

Moallem, U; Folman, Y; Bor, A; Arav, A; Sklan, D

1999-11-01

The effect of fat and bovine somatotropin (bST) on preovulatory follicular hormones and lipids was evaluated by feeding cows for 150 d from parturition a control diet, a control diet plus 0.55 kg/d of calcium soaps of fatty acids, or a control diet with 500 mg of bST injected every 14 d. Fourteen days after a synchronized or natural estrus, cows were injected with a PGF2 alpha analogue; 48 h later, follicular fluid from all ovarian follicles > 8 mm was aspirated. Cows fed fat or injected with bST produced more milk and milk solids than did control cows, and cows on the bST treatment lost more body condition after calving than did cows on the other treatments. Both treatments changed the proportion of estradiol-active follicles (> 400 ng of estradiol/ml of follicular fluid) and the correlation between follicular fluid estradiol concentration and the total number large follicles per cow. In follicles aspirated between 60 and 90 DIM the percentage of estradiol-active follicles was 67, 40, and 0 for cows on the control, calcium soaps of fatty acids, and bST treatments, respectively. After 90 DIM, no differences existed between treatments in the percentage of estradiol-active follicles. Estradiol concentration in follicular fluid was correlated with DIM at follicle aspiration (r = 0.51). The proportion of oleic acid in free fatty acids in plasma at 50 DIM was lower in control cows and was lower in follicular fluid of estradiol-active follicles. Both calcium soaps of fatty acids and bST had a considerable effect on follicular development and activity and the composition of fatty acids in follicles.

Sex differences in analgesic, reinforcing, discriminative, and motoric effects of opioids.

PubMed

Craft, Rebecca M

2008-10-01

This review summarizes evidence for sex differences in behavioral effects of opioids, primarily in rats. Whereas micro agonists have been found to be more potent and in some cases more efficacious in producing analgesia and sedation in males than females, females are more sensitive than males to reinforcing and locomotor stimulant effects of opioids. Sex differences in motoric effects of opioids may contribute to sex differences in other behavioral effects of opioids; for example, sex differences in rats' ability to discriminate morphine from saline can be attributed entirely to greater morphine-induced sedation in males. Chronic estradiol blunts females' sensitivity to morphine's analgesic and sedative effects, but enhances females' sensitivity to the reinforcing and locomotor stimulant effects of micro opioids. The neurobiological basis for sex differences in and estradiol modulation of behavioral effects of opioids includes brain opioid receptor density (greater in males and under low-estradiol conditions in females) and dopaminergic function (greater in females and under high-estradiol conditions). Given the significant and growing use of opioids by women, both medicinally and recreationally, understanding how female biology influences analgesic and other effects of opioids is crucial. Copyright (c) 2008 APA, all rights reserved.

Estradiol and GPER Activation Differentially Affect Cell Proliferation but Not GPER Expression in the Hippocampus of Adult Female Rats

PubMed Central

Duarte-Guterman, Paula; Lieblich, Stephanie E.; Chow, Carmen; Galea, Liisa A. M.

2015-01-01

Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol’s effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus. PMID:26075609

Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin, estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1.

PubMed

Weiss, J M; Polack, S; Treeck, O; Diedrich, K; Ortmann, O

2006-08-01

The secretion of luteinizing hormone (LH) and the GnRH receptor (GnRH-R) concentration are modulated by ovarian steroids and GnRH. To elucidate whether this regulation is due to alterations at the transcriptional level, we examined the GnRH I-R mRNA expression in the gonadotroph-derived cell line alphaT3-1 treated with different estradiol and progesterone paradigms and the GnRH I agonist triptorelin. alphaT3-1 cells were treated with different steroid paradigms: 1 nM estradiol or 100 nM progesterone for 48 h alone or in combination. Cells were exposed to 10 nM or 100 pM triptorelin for 30 min, 3 h, 9 h, or, in pulsatile way, with a 5-min pulse per hour. The GnRH I-R mRNA was determined by Northern blot analysis. GnRH I-R mRNA from cells treated with continuous triptorelin decreased in a time- and concentration-dependent manner. Pulsatile triptorelin increased GnRH I-R gene expression. Progesterone alone further enhanced this effect, whereas estradiol and its combination with progesterone diminished it. Continuous combined treatment with estradiol and progesterone lead to a significant decrease of GnRH I-R mRNA by 30% and by 35% for estradiol alone. The addition of 10 nM triptorelin for 30 min or 3 h could not influence that steroid effect. In conclusion, estradiol and progesterone exclusively decreased GnRH I-R mRNA in alphaT3-1 cells no matter whether they are treated additionally with the GnRH I agonist triptorelin. The enhanced sensitivity of gonadotrophs and GnRH I-R upregulation by estradiol is not due to increased GnRH I gene expression because GnRH I-R mRNA is downregulated by estradiol and progesterone. Other pathways of the GnRH I-R signal transduction might be involved.

Effects of low-dose monophasic levonorgestrel with ethinyl estradiol preparation on serum lipid levels: A twenty-four month clinical trial.

PubMed

Young, R L; DelConte, A

1999-11-01

The aim of this 24-cycle study was to evaluate the effects on serum lipid concentrations of an oral contraceptive preparation containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Forty-two healthy women were enrolled in a study designed to evaluate the effects on serum lipid concentrations of an oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Lipid data were evaluated for 28 women who completed 24 cycles of treatment with a preparation of 100 microg levonorgestrel with 20 microg ethinyl estradiol for 21 days followed by placebo for 7 days. Concentrations of triglycerides, total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol subfractions 2 and 3, low-density lipoprotein cholesterol, and apolipoproteins A-I and B were analyzed. Mean percentage changes from baseline were tested for significance by means of paired Student t tests. Total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein subfraction 2, and apolipoprotein A-I concentrations were not significantly changed from baseline. Neither was the ratio of high-density lipoprotein subfraction 2 to high-density lipoprotein subfraction 3. Mean percentage increases in concentrations of triglyceride, high-density lipoprotein subfraction 3, apolipoprotein B, and low-density lipoprotein cholesterol and increases in the ratios of total cholesterol to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and apolipoprotein B to apolipoprotein A-I were significant (P <.05) at >/=1 cycle. By cycle 24, however, only the concentration of high-density lipoprotein subfraction 3 remained significantly elevated. Changes in the plasma lipid profiles among women receiving monophasic 100 microg levonorgestrel with 20 microg ethinyl estradiol were similar to those seen with other low-dose oral contraceptives, but by cycle 24 only 1 of 7 mean values remained significantly different from baseline.

The Effect of Supraphysiological Estradiol on Pregnancy Outcomes Differs between Women with PCOS and Ovulatory Women.

PubMed

Wei, Daimin; Yu, Yunhai; Sun, Mei; Shi, Yuhua; Sun, Yun; Deng, Xiaohui; Li, Jing; Wang, Ze; Zhao, Shigang; Zhang, Heping; Legro, Richard S; Chen, Zi-Jiang

2018-04-27

Supra-physiological estradiol exposure after ovarian stimulation may disrupt embryo implantation after fresh embryo transfer, compared with physiological estradiol exposure during frozen embryo transfer(FET). Women with polycystic ovary syndrome (PCOS) who usually over-respond to ovarian stimulation have a better live birth rate after elective FET than fresh embryo transfer; however ovulatory women don't. To evaluate whether the discrepancy in live birth rate after fresh versus FET between women with PCOS and ovulatory women was due to the variation in ovarian response, i.e. peak estradiol level or oocyte number. This was a secondary analysis of data from two multicenter randomized trials with similar study designs. A total of 1508 women with PCOS in the first trial and 2157 ovulatory women in the second trial were randomized to undergo either fresh or frozen embryo transfer. The primary outcome was live birth. Compared with fresh embryo transfer, FET resulted in a higher live birth rate(51.9% vs. 40.7%, OR: 1.57, 95%CI: 1.22-2.03) in PCOS women with peak estradiol level >3000pg/ml but not in those with estradiol level ≤3000pg/ml. In PCOS women with oocyte number ≥16, FET yielded a higher live birth rate(54.8% vs. 42.1%, OR: 1.67, 95%CI: 1.20-2.31), but not in those with oocyte number <16. However, in ovulatory women, the pregnancy outcomes were comparable after fresh and FET in all subgroups. Supra-physiological level of estradiol after ovarian stimulation may adversely affect pregnancy outcomes in women with PCOS; but not in ovulatory women.

Pregnancy-induced gingivitis and OMICS in dentistry: in silico modeling and in vivo prospective validation of estradiol-modulated inflammatory biomarkers.

PubMed

Gürsoy, Mervi; Zeidán-Chuliá, Fares; Könönen, Eija; Moreira, José C F; Liukkonen, Joonas; Sorsa, Timo; Gürsoy, Ulvi K

2014-09-01

Pregnancy-associated gingivitis is a bacterial-induced inflammatory disease with a remarkably high prevalence ranging from 35% to 100% across studies. Yet little is known about the attendant mechanisms or diagnostic biomarkers that can help predict individual susceptibility for rational personalized medicine. We aimed to define inflammatory proteins in saliva, induced or inhibited by estradiol, as early diagnostic biomarkers or target proteins in relation to pregnancy-associated gingivitis. An in silico gene/protein interaction network model was developed by using the STITCH 3.1 with "experiments" and "databases" as input options and a confidence score of 0.700 (high confidence). Salivary estradiol, interleukin (IL)-1β and -8, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-2, -8, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 levels from 30 women were measured prospectively three times during pregnancy and twice during postpartum. In silico analysis revealed that estradiol interacts with IL-1β and -8 by an activation link when the "actions view" was consulted. In saliva, estradiol concentrations associated positively with TIMP-1 and negatively with MPO and MMP-8 concentrations. When the gingival bleeding on probing percentage (BOP%) was included in the model as an effect modifier, the only association, a negative one, was found between estradiol and MMP-8. Throughout gestation, estradiol modulates the inflammatory response by inhibiting neutrophilic enzymes, such as MMP-8. The interactions between salivary degradative enzymes and proinflammatory cytokines during pregnancy suggest promising ways to identify candidate biomarkers for pregnancy-associated gingivitis, and for personalized medicine in the field of dentistry. Finally, we call for greater investments in, and action for biomarker research in periodontology and dentistry that have surprisingly lagged behind in personalized medicine compared to other fields, such as cancer research.

Transport of estradiol-17β-glucuronide, estrone-3-sulfate and taurocholate across the endoplasmic reticulum membrane: evidence for different transport systems.

PubMed

Wlcek, Katrin; Hofstetter, Lia; Stieger, Bruno

2014-03-01

Important reactions of drug metabolism, including UGT mediated glucuronidation and steroidsulfatase mediated hydrolysis of sulfates, take place in the endoplasmic reticulum (ER) of hepatocytes. Consequently, UGT generated glucuronides, like estradiol-17β-glucuronide, have to be translocated back into the cytoplasm to reach their site of excretion. Also steroidsulfatase substrates, including estrone-3-sulfate, have to cross the ER membrane to reach their site of hydrolysis. Based on their physicochemical properties such compounds are not favored for passive diffusion and therefore likely necessitate transport system(s) to cross the ER membrane in either direction. The current study aims to investigate the transport of taurocholate, estradiol-17β-glucuronide, and estrone-3-sulfate in smooth (SER) and rough (RER) endoplasmic reticulum membrane vesicles isolated from Wistar and TR(-) rat liver. Time-dependent and bidirectional transport was demonstrated for taurocholate, showing higher uptake rates in SER than RER vesicles. For estradiol-17β-glucuronide a fast time-dependent efflux with similar efficiencies from SER and RER but no clear protein-mediated uptake was shown, indicating an asymmetric transport system for this substrate. Estrone-3-sulfate uptake was time-dependent and higher in SER than in RER vesicles. Inhibition of steroidsulfatase mediated estrone-3-sulfate hydrolysis decreased estrone-3-sulfate uptake but had no effect on taurocholate or estradiol-17β-glucuronide transport. Based on inhibition studies and transport characteristics, three different transport mechanisms are suggested to be involved in the transport of taurocholate, estrone-3-sulfate and estradiol-17β-glucuronide across the ER membrane. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Basal and dynamic relationships between implicit power motivation and estradiol in women.

PubMed

Stanton, Steven J; Schultheiss, Oliver C

2007-12-01

This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

Treatment with liraglutide--a once-daily GLP-1 analog--does not reduce the bioavailability of ethinyl estradiol/levonorgestrel taken as an oral combination contraceptive drug.

PubMed

Jacobsen, Lisbeth V; Vouis, Jan; Hindsberger, Charlotte; Zdravkovic, Milan

2011-12-01

Liraglutide is a once-daily human GLP-1 analog for treatment of type 2 diabetes. Like other GLP-1 analogs, liraglutide delays gastric emptying, which could potentially affect absorption of concomitantly administered oral drugs. This study investigated the effect of liraglutide on the pharmacokinetics of the components of an oral contraceptive (ethinyl estradiol/levonorgestrel). Postmeno-pausal healthy women (n = 21) were included. A single dose of this contraceptive was administered. Blood samples for ethinyl estradiol/levonorgestrel measurements were drawn until 74 hours post dosing of the contraceptive during liraglutide and placebo treatments. The 90% confidence interval (CI) of the ratio of the area under the curve (AUC) (1.06; 90% CI, 0.99-1.13) for ethinyl estradiol (during liraglutide and placebo) was within defined limits, demonstrating equivalence. The 90% CI for the ratio of AUC for levonorgestrel was not fully contained within the limits (1.18; 90% CI, 1.04-1.34) (levonorgestrel AUC was 18% greater with liraglutide vs placebo). However, equivalence was demonstrated for levonorgestrel AUC(0-t) (1.15; 90% CI, 1.06-1.24). Equivalence was not demonstrated for maximum concentration (C(max)); values for ethinyl estradiol and levonorgestrel C(max) were 12% and 13% lower with liraglutide versus placebo, respectively. Both reached C(max) ~1.5 hours later with liraglutide. No clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel occurred.

The regulation of progesterone receptor by 17 beta estradiol and tamoxifen in the Zr-75-1 human breast cancer cell line in defined medium.

PubMed

Allegra, J C; Korat, O; Do, H M; Lippman, M

1981-01-01

The regulation of progesterone receptor by 17 beta estradiol and tamoxifen in the ZR-75-1 human breast cancer cell line in defined medium is described. ZR-75-1 cells maintained in serum free hormone supplemented medium minus estradiol lack progesterone receptor activity. Readdition of estradiol to these cells leads to a marked stimulation of progesterone receptor activity (0 to greater than 100 fmols of specifically bound progesterone per million cells). Tamoxifen (10(-6)M-10(-8)M) does not stimulate progesterone receptor activity in this cell line. The presence of progesterone receptor activity is not directly related to growth. Withdrawal of insulin in the continued presence of estradiol has no effect on progesterone receptor concentration although net cell growth ceases. Conversely, withdrawal of estradiol in the continued presence of insulin induces a cessation of net cell growth accompanied by a loss of all progesterone receptor activity within 3-5 days.

Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol.

PubMed

Torgrimson, Britta N; Meendering, Jessica R; Kaplan, Paul F; Minson, Christopher T

2007-06-01

Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n=7) active pills contained 150 microg levonorgestrel/30 microg ethinyl estradiol versus Group very low dose (VLD) (n=8) with 100 microg levonorgestrel/20 microg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 +/- 1.77% vs. 7.23 +/- 2.60%; P=0.024). This phase difference was not observed in Group LD (8.00 +/- 0.970% vs. 7.61 +/- 1.07%; P=0.647). Endothelium-independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 microg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 +/- 2.34% vs. 6.97 +/- 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women.

Reduction of post injury neointima formation due to 17β-estradiol and phytoestrogen treatment is not influenced by the pure synthetic estrogen receptor antagonist ICI 182,780 in vitro

PubMed Central

Finking, Gerald; Lenz, Christina; Schochat, Thomas; Hanke, Hartmut

2002-01-01

Background Animal and organ culture experiments have shown beneficial inhibitory estrogen effects on post injury neointima development. The purpose of this study was to investigate whether such estrogen effects are influenced by the estrogen receptor antagonist ICI 182,780. Different concentrations of 17β-estradiol and the phytoestrogens genistein and daidzein were tested. Methods F emale New Zealand White rabbits were benumbed. In situ vascular injury of the thoracic and abdominal aorta was performed by a 3F Fogarty catheter. Segments of 5 mm were randomised and held in culture for 21 days. Three test series were performed: 1) control group – 20 μM ICI – 30 μM ICI – 40 μM ICI. 2) control group – 20 μM ICI – 40 μM 17β-estradiol – 40 μM 17β-estradiol + 20 μM ICI. 3) control group – 20 μM ICI – 40 μM daidzein – 40 μM daidzein + 20 μM ICI – 20 μM genistein – 20 μM genistein + 20 μM ICI. After 21 days the neointima-media-ratio was evaluated. Results 1) Treatment with ICI 182,780 did not reduce neointima formation significantly (p = 0.05). 2) 40 μM 17β-estradiol alone (p < 0.0001) and in combination with 20 μM ICI (p < 0.0001) reduced neointima formation significantly. 3) 20 μM genistein alone (p = 0.0083) and combined with 20 μM ICI (p = 0.0053) reduced neointima formation significantly. 40 μM daidzein did not have a significant (p = 0.0637) effect. Conclusions The estrogen receptor antagonist ICI 182,780 did not modulate the inhibitory estrogen effects on post injury neointima formation. These results do not support the idea that such effects are mediated by vascular estrogen receptors. PMID:12162794

Effect of physical activity on sex hormones in women: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Ennour-Idrissi, Kaoutar; Maunsell, Elizabeth; Diorio, Caroline

2015-11-05

Exposure to high levels of endogenous estrogens is a main risk factor for breast cancer in women, and in observational studies was found to be inversely associated with physical activity. The objective of the present study is to determine the effect of physical activity interventions on sex hormone levels in healthy women. Electronic databases (MEDLINE, EMBASE, CENTRAL), from inception to December 2014, and reference lists of relevant reviews and clinical trials were searched, with no language restrictions applied. Randomized controlled trials (RCTs) were included if they compared any type of exercise intervention to no intervention or other interventions, and assessed the effects on estrogens, androgens or the sex hormone binding globulin (SHBG) in cancer-free women. Following the method described in the Cochrane Handbook for Systematic Reviews of Interventions, data on populations, interventions, and outcomes were extracted, and combined using the inverse-variance method and a random-effects model. A pre-established protocol was drawn up, in which the primary outcome was the difference in circulating estradiol concentrations between the physical activity (experimental) and the control groups after intervention. Pre-specified subgroup analyses and sensitivity analysis according to the risk of bias were conducted. Data suitable for quantitative synthesis were available from 18 RCTs (1994 participants) for total estradiol and from 5 RCTs (1245 participants) for free estradiol. The overall effect of physical activity was a statistically significant decrease of both total estradiol (standardized mean difference [SMD] -0.12; 95 % confidence interval [CI] -0.20 to -0.03; P = 0.01; I (2) = 0 %) and free estradiol (SMD -0.20; 95 % CI -0.31 to -0.09; P = 0.0005; I (2) = 0 %). Subgroup analyses suggest that this effect is independent of menopausal status and is more noticeable for non-obese women and for high intensity exercise. Meta-analysis for secondary outcomes found that physical activity induces a statistically significant decline of free testosterone, androstenedione, dehydroepiandrosterone-sulfate and adiposity markers, while a significant increase of SHBG was observed. Although the effect is relatively modest, physical activity induces a decrease in circulating sex hormones and this effect is not entirely explained by weight loss. The findings emphasize the benefits of physical activity for women.

Estradiol causes the rapid accumulation of cAMP in human prostate.

PubMed Central

Nakhla, A M; Khan, M S; Romas, N P; Rosner, W

1994-01-01

Androgens are widely acknowledged to be central to the pathogenesis of benign prostatic hypertrophy (BPH). However, BPH increases in prevalence as men age, at precisely the stage of life when plasma androgens are decreasing. The decrease in total plasma androgens is amplified by an age-related increase in plasma sex hormone-binding globulin (SHBG) that results in a relatively greater decrease in free androgens than in total androgens. In addition, estrogens have long been suspected to be important in BPH, but a direct effect on the human prostate has never been demonstrated. We present data that are consistent with a role for estradiol, and for a decrease in androgens and an increase in SHBG, in the pathogenesis of BPH. We show that estradiol, but not dihydrotestosterone, acts in concert with SHBG to produce an 8-fold increase in intracellular cAMP in human BPH tissue. This increase is not blocked by an antiestrogen and is not provoked by an estrogen (diethylstilbestrol) that does not bind to SHBG, thus excluding the classic estrogen receptor as being operative in these events. Conversely, dihydrotestosterone, which blocks the binding of estradiol to SHBG, completely negates the effect of estradiol. Finally, we demonstrate that the SHBG-steroid-responsive second-messenger system is primarily localized to the prostatic stromal cells and not to the prostatic epithelial cells. Thus, we have shown a cell-specific, powerful, nontranscriptional effect of estradiol on the human prostate. PMID:7515502

Laser spectroscopic study of β-estradiol and its monohydrated clusters in a supersonic jet.

PubMed

Morishima, Fumiya; Inokuchi, Yoshiya; Ebata, Takayuki

2012-08-09

The structures of 17β-estradiol (estradiol) and its 1:1 cluster with water have been investigated in supersonic jets. The S(1)-S(0) electronic spectrum of estradiol monomer shows four strong sharp bands in the 35050-35200 cm(-1) region. Ultraviolet-ultraviolet hole-burning (UV-UV HB) and infrared-ultraviolet double-resonance (IR-UV DR) spectra of these bands indicate that they are due to four different conformers of estradiol originating from the different orientation of the OH groups in the A- and D-rings. The addition of water vapor to the sample gas generates four new bands in the 34700-34800 cm(-1) region, which are assigned to the estradiol-H(2)O 1:1 cluster with the A-ring (phenyl ring) OH acting as a hydrogen(H)-bond donor. In addition, we found very weak bands near the origin bands of bare estradiol upon the addition of water vapor. These bands are assigned to the isomers of estradiol-H(2)O 1:1 cluster having an H-bond at the D-ring OH. We determine the conformation of bare estradiol and the structures of its monohydrated clusters with the aid of density functional theory calculation and discuss the relationship between the stability of hydrated clusters and the conformation of estradiol.

DIBROMOACETIC ACID-INDUCED ELEVATIONS IN CIRCULATING ESTRADIOL: EFFECTS IN BOTH CYCLING AND OVARIECTOMIZED/STEROID-PRIMED FEMALE RATS

EPA Science Inventory

RTD-03-031
Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations in Circulating Estradiol: Effects in Both Cycling and Ovariectomized/Steroid-primed Female Rats. Reproductive Toxicology (in press).

Abstract

Oral exposures to high concentrations of th...

Effects of phytoestrogens on indices of protein turnover in rainbow trout (Oncorhynchus mykiss) primary myocytes

USDA-ARS?s Scientific Manuscript database

Soybeans and other legumes investigated as alternative ingredients in aquafeeds contain phytoestrogens that act as endocrine disruptors, capable of binding to and activating estrogen receptors, although at a much lower level of estrogenicity compared to estradiol. Estradiol has catabolic effects on...

The Anxiolytic and Antidepressant-like Effects of Testosterone and Estrogen in Gonadectomized Male Rats

PubMed Central

Carrier, Nicole; Saland, Samantha K.; Duclot, Florian; He, Huan; Mercer, Roger; Kabbaj, Mohamed

2015-01-01

Background While the influence of testosterone levels on vulnerability to affective disorders is not straightforward, research suggests this hormone may confer some degree of resiliency in men. We recently demonstrated a role for the dentate gyrus in mediating testosterone’s protective effects on depressive-like behavior in gonadectomized male rats. Here, testosterone may exert its effects through androgen receptor-mediated mechanisms or via local aromatization to estradiol. Methods Gonadectomized male rats were implanted with a placebo, testosterone, or estradiol pellet, and subsequent protective anxiolytic- and antidepressant-like effects of testosterone and its aromatized metabolite, estradiol, were then investigated in the open field and sucrose preference tests, respectively. Moreover, their influence on gene expression in the hippocampus was analyzed by genome-wide cDNA microarray analysis. Finally, the contribution of testosterone’s aromatization within the dentate gyrus was assessed by local infusion of the aromatase inhibitor, fadrozole, whose efficacy was confirmed by LC-MS/MS. Results Both hormones had antidepressant-like effects associated with a substantial overlap in transcriptional regulation, particularly in synaptic plasticity- and mitogen-activated protein kinase pathway-related genes. Further, chronic aromatase inhibition within the dentate gyrus blocked the protective effects of testosterone. Conclusions Both testosterone and estradiol exhibit anxiolytic- and antidepressant-like effects in gonadectomized male rats, while similarly regulating critical mediators of these behaviors, suggesting common underlying mechanisms. Accordingly, we demonstrated that testosterone’s protective effects are mediated, in part, by its aromatization in the dentate gyrus. These findings thus provide further insight into a role for estradiol in mediating the protective anxiolytic- and antidepressant-like effects of testosterone. PMID:25683735

Effects of estrogen coadministration on epoxiconazole toxicity in rats.

PubMed

Stinchcombe, Stefan; Schneider, Steffen; Fegert, Ivana; Rey Moreno, Maria Cecilia; Strauss, Volker; Gröters, Sibylle; Fabian, Eric; Fussell, Karma C; Pigott, Geoffrey H; van Ravenzwaay, Bennard

2013-06-01

Epoxiconazole (EPX; CAS-No. 133855-98-8) is a triazole class-active substance of plant protection products. At a dose level of 50 mg/kg bw/day, it causes a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (gestation day [GD] 7-18 or 21), as reported previously (Taxvig et al., 2007, 2008) and confirmed in these studies. Late fetal resorptions occurred in the presence of significant maternal toxicity such as clear reduction of corrected body weight gain, signs of anemia, and, critically, a marked reduction of maternal estradiol plasma levels. Furthermore, estradiol supplementation at dose levels of 0.5 or 1.0 μg/animal/day of estradiol cyclopentylpropionate abolished the EPX-mediated late fetal resorptions. No increased incidences of external malformations were found in rats cotreated with 50 mg/kg bw/day EPX and estradiol cyclopentylpropionate, indicating that the occurrence of malformations was not masked by fetal mortality under the study conditions. Overall, the study data indicate that fetal mortality observed in rat studies with EPX is not the result of direct fetal toxicity but occurs indirectly via depletion of maternal estradiol levels. The clarification of the human relevance of the estrogen-related mechanism behind EPX-mediated late fetal resorptions in rats warrants further studies. In particular, this should involve investigation of the placenta (Rey Moreno et al., 2013), since it is the materno-fetal interface and crucial for fetal maintenance. The human relevance is best addressed in a species which is closer to humans with reference to placentation and hormonal regulation of pregnancy, such as the guinea pig (Schneider et al., 2013). © 2013 Wiley Periodicals, Inc.

Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer

PubMed Central

Rock, Cheryl L.; Flatt, Shirley W.; Laughlin, Gail A.; Gold, Ellen B.; Thomson, Cynthia A.; Natarajan, Loki; Jones, Lovell A.; Caan, Bette J.; Stefanick, Marcia L.; Hajek, Richard A.; Al-Delaimy, Wael K.; Stanczyk, Frank Z.; Pierce, John P.

2008-01-01

Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01−1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03−1.53), and free estradiol (HR, 1.31; 95% CI, 1.03−1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer. PMID:18323413

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.

PubMed

Hodis, Howard N; Mack, Wendy J; Henderson, Victor W; Shoupe, Donna; Budoff, Matthew J; Hwang-Levine, Juliana; Li, Yanjie; Feng, Mei; Dustin, Laurie; Kono, Naoko; Stanczyk, Frank Z; Selzer, Robert H; Azen, Stanley P

2016-03-31

Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).

Sclerostin Levels and Bone Turnover Markers in Adolescents with Anorexia Nervosa and Healthy Adolescent Girls

PubMed Central

Faje, Alexander T.; Fazeli, Pouneh K.; Katzman, Debra K.; Miller, Karen K.; Breggia, Anne; Rosen, Clifford J.; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita

2012-01-01

Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study objectives were to (i) assess associations of sclerostin with surrogate bone turnover markers in girls with AN and controls and (ii) examine effects of transdermal estradiol on sclerostin in AN. 69 girls (44 with AN and 25 normal-weight controls) 13–18 years old were studied at baseline. 22 AN girls were randomized to transdermal estradiol (plus cyclic medroxyprogesterone) or placebo in a double-blind study for 12 months. Sclerostin correlated positively with P1NP and CTX in controls (r = 0. 67 and 0. 53, p = 0. 0002 and 0. 005, respectively) but not in AN despite comparable levels at baseline. Changes in sclerostin over twelve months did not differ in girls randomized to estradiol or placebo. The relationship between sclerostin and bone turnover markers is disrupted in adolescent girls with AN. Despite an increase in BMD with estradiol administration in AN, estrogen does not impact sclerostin levels in this group. PMID:22728230

New estradiol-linked nitrosoureas: can the pharmacokinetic properties help to explain the pharmacodynamic activities?

PubMed

Betsch, B; Berger, M R; Spiegelhalder, B; Eisenbrand, G; Schmähl, D

1989-01-01

The pharmacokinetics of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) a new estradiol-linked anticancer drug and the unlinked DNA-crosslinking agent 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-alanine) have been studied in methylnitrosourea-induced female Sprague-Dawley rats after equimolar intravenous and oral administration. In comparison with the unlinked single agent, the CNC-alanine-estradiol-17-ester showed a 3-fold longer halflife in plasma and a three times larger volume of distribution. The distribution after intravenous administration was nearly three times faster. The absorption after peroral administration was likewise two times faster. The bioavailability of the estradiol-linked drug was determined to be 52%. After application of CNC-alanine-estradiol-17-ester the cytostatic metabolite CNC-alanine was found, indicating the cleavage of the ester bond. CNC-alanine generated from CNC-alanine-estradiol-17-ester showed a 50% longer halflife than when applied directly. The results indicate that linking 2-chloroethyl-nitrosoureas to estradiol can result in new anticancer agents with modified properties in comparison to the unlinked single agent. The higher antineoplastic activity of the hormone-linked drug can mainly be attributed to differences in the pharmacokinetic behaviour.

Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction.

PubMed

Hwang, Moon Jung; Zsido, Rachel G; Song, Huijin; Pace-Schott, Edward F; Miller, Karen Klahr; Lebron-Milad, Kelimer; Marin, Marie-France; Milad, Mohammed R

2015-11-18

Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group (n = 16) and a low estradiol (LE) group (n = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. Our data further support the important contribution of estradiol levels in the activation of brain regions underlying fear learning and extinction. The results highlight the need to document gonadal hormonal levels, menstrual cycle phase as well as oral contraceptive use in women in order to avoid overlooking sex differences when investigating the neurobiology of emotional regulation.

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.

Bioavailable serum estradiol may alter radiation risk of postmenopausal breast cancer: a nested case-control study.

PubMed

Grant, Eric J; Cologne, John B; Sharp, Gerald B; Eguchi, Hidetaka; Stevens, Richard G; Izumi, Shizue; Kim, Young-Min; Berrington de González, Amy; Ohishi, Waka; Nakachi, Kei

2018-02-01

Ionizing radiation and high levels of circulating estradiol are known breast cancer carcinogens. We investigated the risk of first primary postmenopausal breast cancer in relation to the combined effects of whole-body ionizing radiation exposure and prediagnostic levels of postmenopausal sex hormones, particularly bioavailable estradiol (bE 2 ). A nested case-control study of 57 incident breast cancer cases matched with 110 controls among atomic bomb survivors. Joint effects of breast radiation dose and circulating levels of sex hormones were assessed using binary regression and path analysis. Radiation exposure, higher levels of bE 2 , testosterone and progesterone, and established reproductive risk factors were positively associated with postmenopausal breast cancer risk. A test for mediation of the effect of radiation via bE 2 level suggested a small (14%) but significant mediation (p = 0.004). The estimated interaction between radiation and bE 2 was large but not significant (interaction = 3.86; p = 0.32). There is accumulating evidence that ionizing radiation not only damages DNA but also alters other organ systems. While caution is needed, some portion of the radiation risk of postmenopausal breast cancer appeared to be mediated through bE 2 levels, which may be evidence for cancer risks due to both direct and indirect effects of radiation.

Studies of the hormonal control of postnatal testicular descent in the rat.

PubMed

Spencer, J R; Vaughan, E D; Imperato-McGinley, J

1993-03-01

Dihydrotestosterone is believed to control the transinguinal phase of testicular descent based on hormonal manipulation studies performed in postnatal rats. In the present study, these hormonal manipulation experiments were repeated, and the results were compared with those obtained using the antiandrogens flutamide and cyproterone acetate. 17 beta-estradiol completely blocked testicular descent, but testosterone and dihydrotestosterone were equally effective in reversing this inhibition. Neither flutamide nor cyproterone acetate prevented testicular descent in postnatal rats despite marked peripheral antiandrogenic action. Further analysis of the data revealed a correlation between testicular size and descent. Androgen receptor blockade did not produce a marked reduction in testicular size and consequently did not prevent testicular descent, whereas estradiol alone caused marked testicular atrophy and testicular maldescent. Reduction of the estradiol dosage or concomitant administration of androgens or human chorionic gonadotropin resulted in both increased testicular size and degree of descent. These data suggest that growth of the neonatal rat testis may contribute to its passage into the scrotum.

Experimental study on the estrogen-like effect of boric Acid.

PubMed

Wang, Yadong; Zhao, Yingzheng; Chen, Xiaoyu

2008-02-01

There are now considerable evidences that boric acid has reproductive and developmental toxicity, but it is uncertain whether such toxicity is caused by estrogen-like effect. Our objective is to determine the estrogen-like effect of boric acid. Proliferation assay of MCF-7 human breast cancer cells, uterotrophic assay, measure assay of the estradiol (E2), proliferation assay of mucous membrane cells, and assay of estrogen receptor were conducted in this study. Boric acid could increase the weight of uterus of ovariectomized SD rats and the height of epithelium cells of mucous membrane, enhance the expression of the proliferating cell nucleus antigen, and reduce the density of estrogen receptors. However, boric acid could not affect the level of estradiol in serum and stimulate the proliferation of MCF-7 human breast cancer cells. In this study, boric acid exhibited the estrogen-like effect in vivo.

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

PubMed Central

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Individual differences in risk taking and endogeneous levels of testosterone, estradiol, and cortisol: A systematic literature search and three independent meta-analyses.

PubMed

Kurath, Jennifer; Mata, Rui

2018-05-03

Hormonal levels have been hypothesized to serve as proximal biological mechanisms underlying individual differences in risk taking. We conducted a systematic literature search and independent meta-analyses to assess the link between endogenous testosterone, estradiol, and cortisol levels and risk-taking related constructs (i.e., risk-taking propensity, impulsivity, sensation seeking, novelty seeking). We found small correlations between risk-taking constructs and testosterone (r = 0.12, 95% CI = 0.08, 0.16, 108 effect sizes, k = 49, N = 9112) as well as estradiol (r = 0.10, 95% CI = 0.02, 0.18, 48 effect sizes, k = 17, N = 2900), but not cortisol (r = -0.01, 95% CI = -0.11, 0.09, 60 effect sizes, k = 27, N = 3880). Overall, these results suggest a biological foundation for individual differences in risk taking. We point out some limitations of past studies and make recommendations for future work investigating the hormonal basis of individual differences in risk taking. Copyright © 2018 Elsevier Ltd. All rights reserved.

Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

NASA Technical Reports Server (NTRS)

Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

2002-01-01

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

Effects of leuprolide acetate on selected blood and fecal sex hormones in Hispaniolan Amazon parrots (Amazona ventrais).

PubMed

Klaphake, Eric; Fecteau, Kellie; DeWit, Martine; Greenacre, Cheryl; Grizzle, Judith; Jones, Michael; Zagaya, Nancy; Abney, L Kim; Oliver, Jack

2009-12-01

The luteinizing hormone-releasing hormone agonist leuprolide acetate is used commonly to anage reproductive problems in pet birds. To determine the effect of leuprolide acetate on plas a and fecal hormone levels in a psittacine species, a single 800 microg/kg dose of the 30-day depot form of leuprolide acetate was administered IM in 11 healthy, nonbreeding adult Hispaniolan Amazon parrots (Amazona ventralis), and plasma and fecal hormone levels were measured before and after leuprolide administration. At pooled baseline to 21 days postleuprolide acetate administration, sample collection day was significantly associated with plasma 17beta-estradiol and androstenedione levels and fecal 17beta-estradiol levels (evaluated in females only). Both plasma androstenedione and plasma 17beta-estradiol levels decreased significantly from baseline to a nadir at 7 days postleuprolide acetate administration but did not differ significantly 14 days later from that nadir or from pooled baseline samples, suggesting that the effect of leuprolide on hormone levels remained about 2 weeks. Fecal 17beta-estradiol levels increased significantly from the nadir at 7 days postleuprolide to 21 days postleuprolide administration, with trends of the level at 21 days postleuprolide being higher than the pooled baseline level and of decreasing levels from pooled baseline to 7 days postleuprolide administration. Plasma luteinizing hormone and fecal testosterone levels did not change significantly from baseline levels after leuprolide administration over the 2-day period. No significant correlations were found between plasma hormone and fecal hormone levels. These results suggest that measurement of plasma androstenedione, plasma 17beta-estradiol, and fecal 17beta-estradiol levels might be useful in assessing the effects of 30-day depot leuprolide acetate in Hispaniolan Amazon parrots.

Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

NASA Astrophysics Data System (ADS)

Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

1983-01-01

A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat

EPA Science Inventory

Triclosan (TCS), a broad-spectrum antimicrobial agent found in many personal care products, has been detected in humans and has been shown to interact with endocrine systems in rats. We previously reported that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on u...

Bisphenol A and estradiol impede myoblast differentiation through down-regulating Akt signaling pathway.

PubMed

Go, Ga-Yeon; Lee, Sang-Jin; Jo, Ayoung; Lee, Jae-Rin; Kang, Jong-Sun; Yang, Mihi; Bae, Gyu-Un

2018-04-20

Bisphenol A (BPA), one of the most widespread endocrine disrupting chemicals, is known as an artificial estrogen, which interacts with estrogen receptor (ER). In this study, we investigated the effects of BPA and estradiol on myoblast differentiation and the underlying signaling mechanism. Exposure to BPA (0.01-1 μM) in mouse myoblast C2C12 cells attenuated myogenic differentiation via the reduced expression of muscle-specific genes, such as myosin heavy chain (MHC), MyoD, and Myogenin, without the alteration of cell proliferation and viability. BPA-exposed C2C12 myoblasts also showed a reduction of Akt phosphorylation ((37-61) %, p < 0.001), a key event for myogenesis. Similarly to BPA, estradiol (0.01-1 μM) reduced the expression of muscle-specific proteins and the formation of multinucleated myotubes, and attenuated the muscle differentiation-specific phosphorylation of Akt ((42-59) %, p < 0.001). We conclude that BPA and estradiol suppress myogenic differentiation through the inhibition of Akt signaling. Copyright © 2018 Elsevier B.V. All rights reserved.

The vibrational spectroscopic studies and molecular property analysis of Estradiol, Tamoxifen and their interaction by density functional theory

NASA Astrophysics Data System (ADS)

Borah, Mukunda Madhab; Gomti Devi, Th.

2018-07-01

In the present work Tamoxifen, Estradiol and their interaction are studied using the experimental and theoretical methodologies. The spectral characterization was made by using Raman, FTIR, DFT and VEDA calculation. The optimization of the molecules have been studied using basis set B3LYP/6-31 G(d,p). Complete vibrational assignment of Tamoxifen, Estradiol and Estradiol + Tamoxifen have been attempted and the potential energy distribution and normal mode analysis had also been carried out to determine the contributions of bond oscillators in each normal mode. We have optimized several binding modes of Estradiol and Tamoxifen and taken the lowest energy conformer in our interest. The molecular geometry, HOMO-LUMO energy gap, molecular hardness (η), ionization energy (IE), electron affinity (EA), total energy and dipole moment were analyzed. The observed experimental and the scaled theoretical results were found in good agreement.

The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle

PubMed Central

Santollo, Jessica; Eckel, Lisa A.

2008-01-01

Recently, it was shown that that the orexigenic effect of melanin concentrating hormone (MCH) is attenuated by estradiol treatment in ovariectomized (OVX) rats. This suggests that female rats may be less responsive than male rats to the behavioral effects of MCH. To investigate this hypothesis, the effects of lateral ventricular infusions of MCH on food intake, water intake, meal patterns, and running wheel activity were examined in male and female rats. To further characterize the impact of estradiol on MCH-induced food intake, female rats were OVX and tested with and without 17-β-estradiol benzoate (EB) replacement. In support of our hypothesis, food and water intakes following MCH treatment were greater in male rats, relative to female rats. Specifically, the orexigenic effect of MCH was maximal in male rats and minimal in EB-treated OVX rats. In both sexes, the orexigenic effect of MCH was mediated by a selective increase in meal size, which was attenuated in EB-treated OVX rats. MCH induced a short-term (2 h) decrease in wheel running that, unlike its effects on ingestive behavior, was similar in males and females. Thus, estradiol decreases some, but not all, of the behavioral effects of MCH. To examine the influence of endogenous estradiol, food intake was monitored following MCH treatment in ovarian-intact, cycling rats. As predicted by our findings in OVX rats, the orexigenic effect of MCH was attenuated in estrous rats, relative to diestrous rats. We conclude that the female rat’s reduced sensitivity to the orexigenic effect of MCH may contribute to sex- and estrous cycle-related differences in food intake. PMID:18191424

Role of an estradiol regulatory factor-hydroxysteroid dehydrogenase (HSD) in Toxoplasma gondii infection and pathogenicity.

PubMed

Zhang, Xiao; Liu, Jing; Li, Muzi; Fu, Yong; Zhang, Taotao; Han, Qian; Liu, Qun

2017-11-01

Toxoplasma gondii is an apicomplexan parasite that infects most species of warm-blooded animals, including humans, and causes abortions and severe damage to the fetal central nervous system. During pregnancy, the prevalence of toxoplasmosis increases throughout the second and third quarter of gestation, while the hormones progesterone and estradiol simultaneously increase. Thus, it has been suggested that these hormones could affect parasite reproduction. This study was mainly focused on an estradiol regulatory factor-Hydroxysteroid dehydrogenase (HSD) gene in T. gondii. Our data showed that estradiol promoted Pru (Type II) and VEG (Type III) infection and thus significantly contributed to the pathogenicity of T. gondii in mice. Subsequently, we found that this phenomenon may relate to the interplay of T. gondii and estradiol. We reported that estradiol can enter T. gondii tachyzoites. Bioinformatics analysis showed that T. gondii may have a residual estradiol metabolism-related gene HSD. To verify the gene function, HEK293T cells were transiently transfected with Tg-HSD and gene expression was induced. Then, HPLC (high-performance liquid chromatography) analysis showed that Tg-HSD can efficiently transform estrone into estradiol. Moreover, Tg-HSD -overexpressing parasites showed significantly enhanced pathogenicity and upregulation of estradiol levels in mice. In conclusion, estradiol can promote T. gondii infection in vitro and in vivo, and this may be related to its Tg- HSD gene. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells.

PubMed

Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla; Hansson, Stefan; Casslén, Bertil

2009-02-01

Epidermal growth factor (EGF) stimulates proliferation and migration in ovarian cancer cells, and high tumor expression of the EGF system correlates with poor prognosis. Epidermal growth factor upregulates urokinase plasminogen activator receptor (uPAR) on the cell surface via 3 distinct mechanisms: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression and cell migration in ovarian cancer cells and further to identify the ER involved.We used 7 ovarian cancer cell lines, cell migration assay, cellular binding of (125)I-uPA, cellular degradation of (125)I-uPA/PAI-1 complex, enzyme-linked immunosorbent assay for uPAR, solid-phase enzyme immunoassay for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents mobilization of uPAR from detergent-resistant domains such as lipid rafts. Estradiol influenced neither the amount of uPAR mRNA nor the rate of uPAR degradation or solubilization. The nuclear ER antagonists ICI 182780 and tamoxifen, which are GPR30 agonists, as well as the specifically constructed GPR30 agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates that this effect is mediated via the membrane ER GPR30.

Gonadal Steroids: Effects on Excitability of Hippocampal Pyramidal Cells

NASA Astrophysics Data System (ADS)

Teyler, Timothy J.; Vardaris, Richard M.; Lewis, Deborah; Rawitch, Allen B.

1980-08-01

Electrophysiological field potentials from hippocampal slices of rat brain show sex-linked differences in response to 1 × 10-10M concentrations of estradiol and testosterone added to the incubation medium. Slices from male rats show increased excitability to estradiol and not to testosterone. Slices from female rats are not affected by estradiol, but slices from female rats in diestrus show increased excitability in response to testosterone whereas slices from females in proestrus show decreased excitability.

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.

Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsurugizawa, Tomokazu; Core Research for Evolutional Science and Technology Project of Japan Science and Technology Agency, Graduate School of Arts and Sciences, University of Tokyo at Komaba, 3-8-1 Meguro, Tokyo 153; Mukai, Hideo

2005-12-02

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but notmore » by MK-801 (NMDA receptor antagonist). ER{alpha} agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ER{beta} agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ER{alpha} was performed using purified RC-19 antibody. The localization of ER{alpha} (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ER{alpha} and MAP kinase.« less

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...

Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Reichert, L.E. Jr.

1990-08-01

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+more » influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.« less

Exposure to increased levels of estradiol during development can have long-term effects on the response to undernutrition in female rats.

PubMed

Carrillo, B; Collado, P; Díaz, F; Chowen, J A; Pinos, H

2016-11-01

Undernutrition during development alters the expression of peptides that control energy expenditure and feeding behavior. Estrogens can also modulate these peptides. Here, we analyze whether the early postnatal administration of estradiol modulates the effects of undernutrition on neuroendocrine parameters in adult female Wistar rats. Control rats were fed a control diet. Undernourished pups were submitted to a restricted diet with half of the undernourished rats receiving 0.4 mg/kg s.c. of estradiol benzoate (EB) from postnatal day (P) 6 until P13. Quantitative real-time polymerase chain reaction was performed to determine expression in the hypothalamus of agouti-related peptide (AgRP), proopiomelanocortin (POMC), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript. Plasma estradiol, testosterone, and adiponectin levels were measured by enzyme-linked immunosorbent assay. Total and acylated ghrelin levels were measured in plasma by radioimmunoassay. Insulin and leptin were measured by mulitplex immunoassays. Undernourishment decreased body weight, fat mass, plasma leptin and insulin levels, and hypothalamic POMC mRNA levels. An increase in orexigenic signals AgRP and NPY mRNA levels, and in plasma adiponectin levels were found in undernourished animals. Early postnatal treatment with EB to undernourished female rats reversed the effects of undernutrition on adult hypothalamic POMC mRNA levels. In addition, neonatal EB treatment to undernourished females significantly decreased adult plasma testosterone, estradiol, and acylated ghrelin levels. Our results suggest that increased estradiol during a critical period of development has the capacity to modulate the alterations that undernutrition produces on energy metabolism.

Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

PubMed

Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

2013-02-01

To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

Estrogen-Cholinergic Interactions: Implications for Cognitive Aging

PubMed Central

Newhouse, Paul; Dumas, Julie

2015-01-01

While many studies in humans have investigated the effects of estrogen and hormone therapy on cognition, potential neurobiological correlates of these effects have been less well studied. An important site of action for estrogen in the brain is the cholinergic system. Several decades of research support the critical role of CNS cholinergic systems in cognition in humans, particularly in learning and memory formation and attention. In humans, the cholinergic system has been implicated in many aspects of cognition including the partitioning of attentional resources, working memory, inhibition of irrelevant information, and improved performance on effort-demanding tasks. Studies support the hypothesis that estradiol helps to maintain aspects of attention and verbal and visual memory. Such cognitive domains are exactly those modulated by cholinergic systems and extensive basic and preclinical work over the past several decades has clearly shown that basal forebrain cholinergic systems are dependent on estradiol support for adequate functioning. This paper will review recent human studies from our laboratories and others that have extended preclinical research examining estrogen-cholinergic interactions to humans. Studies examined include estradiol and cholinergic antagonist reversal studies in normal older women, examinations of the neural representations of estrogen-cholinergic interactions using functional brain imaging, and studies of the ability of selective estrogen receptor modulators such as tamoxifen to interact with cholinergic-mediated cognitive performance. We also discuss the implications of these studies for the underlying hypotheses of cholinergic-estrogen interactions and cognitive aging, and indications for prophylactic and therapeutic potential that may exploit these effects. PMID:26187712

A new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis by means of high-pressure liquid chromatography for pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites.

PubMed

Betsch, B; Berger, M R; Spiegelhalder, B

1990-09-01

Estradiol-linked nitrosoureas are offering new perspectives in the antineoplastic chemotherapy of estradiol-receptor positive mammary carcinomas. In such a molecule estradiol has the function of a carrier which brings about a specific accumulation of the anticancer drug in estradiol-receptor containing tumor cells. However, there is only little knowledge about the pharmacokinetic behavior of this new group of anticancer agents. For that reason a new comprehensive technique of catheterisation, blood sampling, sample preparation and sample analysis with high-pressure liquid chromatography (HPLC) for preclinical pharmacokinetic studies with estradiol-linked nitrosoureas and their metabolites has been developed. N-(2-Chloroethyl)-N-nitroso-carbamoyl-L-alanine-estradiol-17-ester (CNC-alanine-estradiol-17-ester) and N-(2-chloroethyl)-N-nitroso-carbamoyl-L-alanine (CNC-alanine) were used as test compounds. The drugs were tested in female Sprague-Dawley rats with chemically induced mammary carcinomas. The laboratory animals were supplied with two catheters prior to the pharmacokinetic experiments. The blood samples were drawn from the vena cava catheter after the drug had been applied through a vena jugularis catheter. The compounds were extracted from plasma with C18 silicagel reversed phase cartridges. The clean-up technique delivered clear samples only slightly contaminated with the biological matrix. The recovery from plasma was 75 +/- 5% for the hormone-linked CNC-alanine-estradiol-17-ester and 70 +/- 5% for the unlinked CNC-alanine. The analysis was carried out by means of HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Estradiol on Post-Traumatic Stress Disorder Symptoms

DTIC Science & Technology

2010-03-01

Steroid Metabolism pathways 34 Figure 6. HPG Axis 35 Chapter 3 Figure 1. Effect of 7, 14, and 22 Days of...87 Treatment on Plasma CORT in OVX Sprague-Dawley Rats that were also Immobilization Stressed for 22 -days Figure 3. Effect of Early...for 22 -days Figure 5. Effect of Estradiol, Selective ERα Agonist, and ERβ Agonist 90 Treatment on Pre-Pulse Inhibition in OVX Sprague-Dawley

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

PubMed

Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Leonetti, Donna L; Page, Stephanie T

The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. This is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m 2 ). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively). Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. Copyright © 2015 Asia Oceania Association for the Study of Obesity. All rights reserved.

Interactions of trans-acting factor(s) with the estradiol response element and nuclear factor 1 of the vitellogenin II gene of Japanese quail.

PubMed

Gupta, S; Upadhayay, R; Kanungo, M S

1996-08-01

This study was directed at achieving an understanding of the mechanisms by which steroid hormones control the synthesis of vitellogenin (VTG) protein in the liver of the Japanese quail. Northern hybridization shows that administration of estradiol alone or with progesterone stimulates the synthesis of VTG mRNA. Gel mobility shift assay of DNA fragments containing the ERE and NF 1 shows that estradiol alone or with progesterone increases the levels of nuclear proteins that bind to these cis-acting elements of the promoter of the VTG gene. The cooperative effect of the two hormones seen at the level of expression of the VTG gene may be due to protein-protein interactions of trans-acting factors that bind to ERE and NF 1.

The biological effects of sex hormones on rabbit articular chondrocytes from different genders.

PubMed

Chang, Shwu Jen; Kuo, Shyh Ming; Lin, Yen Ting; Yang, Shan-Wei

2014-01-01

The aim of this study was to investigate the biological effects of sex hormones (17β-estradiol and testosterone) on rabbit articular chondrocytes from different genders. We cultured primary rabbit articular chondrocytes from both genders with varying concentration of sex hormones. We evaluate cell proliferation and biochemical functions by MTT and GAG assay. The chondrocyte function and phenotypes were analyzed by mRNA level using RT-PCR. Immunocytochemical staining was also used to evaluate the generation of collagen-II. This study demonstrated that 17β-estradiol had greater positive regulation on the biological function and gene expressions of articular chondrocytes than testosterone, with the optimal concentrations of 10(-6) and 10(-7) M, particularly for female chondrocytes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg)more » subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening.« less

Effects of dietary traditional fermented soybean on reproductive hormones, lipids, and glucose among postmenopausal women in northern Thailand.

PubMed

Sapbamrer, Ratana; Visavarungroj, Nuwat; Suttajit, Maitree

2013-01-01

Isoflavone in soybean and its products have numerous beneficial health effects. A number of clinical studies have demonstrated that dietary soy isoflavone can relieve menopausal symptoms, lower risks of breast cancer, and lower cholesterol and glucose. Among the various effects of isoflavone, the role of cholesterol and glucose reduction seems to be well documented; however, other effects such as reproductive hormones were inconclusive and inconsistent. The main objective of the present study was to investigate the effects of six-month dietary traditional fermented soybean intake on BMI, reproductive hormones, lipids, and glucose among postmenopausal women. Subjects were women with their last menstrual period occurring at least 12 months prior to selection by interview and health screening from Baan Tham Village, Phayao Province, Thailand. A total of 60 women were divided into 2 groups: experimental group (n=31) and reference group (n=29). The experimental group was permitted to continue their usual diet, and supplemented with fermented soybean for 6 months. The fermented soybean provided approximately 60 mg of isoflavone per day. The remarkable findings were that dietary fermented soybean had favorable effects on progesterone and cholesterol, but had no effects on estradiol, glucose, and triglycerides. Although estradiol and glucose in the experimental group did not change, a decrease of estradiol and an increase of glucose were found in the reference group. Our results, therefore, suggest that fermented soybean may have beneficial effects on reproductive hormones and cholesterol, and they would be warrant further detail investigations.

Estradiol Increases Mucus Synthesis in Bronchial Epithelial Cells

PubMed Central

Tam, Anthony; Wadsworth, Samuel; Dorscheid, Delbert; Man, Shu-Fan Paul; Sin, Don D.

2014-01-01

Airway epithelial mucus hypersecretion and mucus plugging are prominent pathologic features of chronic inflammatory conditions of the airway (e.g. asthma and cystic fibrosis) and in most of these conditions, women have worse prognosis compared with male patients. We thus investigated the effects of estradiol on mucus expression in primary normal human bronchial epithelial cells from female donors grown at an air liquid interface (ALI). Treatment with estradiol in physiological ranges for 2 weeks caused a concentration-dependent increase in the number of PAS-positive cells (confirmed to be goblet cells by MUC5AC immunostaining) in ALI cultures, and this action was attenuated by estrogen receptor beta (ER-β) antagonist. Protein microarray data showed that nuclear factor of activated T-cell (NFAT) in the nuclear fraction of NHBE cells was increased with estradiol treatment. Estradiol increased NFATc1 mRNA and protein in ALI cultures. In a human airway epithelial (1HAE0) cell line, NFATc1 was required for the regulation of MUC5AC mRNA and protein. Estradiol also induced post-translational modification of mucins by increasing total fucose residues and fucosyltransferase (FUT-4, -5, -6) mRNA expression. Together, these data indicate a novel mechanism by which estradiol increases mucus synthesis in the human bronchial epithelium. PMID:24964096

Vocal Acoustic and Auditory-Perceptual Characteristics During Fluctuations in Estradiol Levels During the Menstrual Cycle: A Longitudinal Study.

PubMed

Arruda, Polyanna; Diniz da Rosa, Marine Raquel; Almeida, Larissa Nadjara Alves; de Araujo Pernambuco, Leandro; Almeida, Anna Alice

2018-03-07

Estradiol production varies cyclically, changes in levels are hypothesized to affect the voice. The main objective of this study was to investigate vocal acoustic and auditory-perceptual characteristics during fluctuations in the levels of the hormone estradiol during the menstrual cycle. A total of 44 volunteers aged between 18 and 45 were selected. Of these, 27 women with regular menstrual cycles comprised the test group (TG) and 17 combined oral contraceptive users comprised the control group (CG). The study was performed in two phases. In phase 1, anamnesis was performed. Subsequently, the TG underwent blood sample collection for measurement of estradiol levels and voice recording for later acoustic and auditory-perceptual analysis. The CG underwent only voice recording. Phase 2 involved the same measurements as phase 1 for each group. Variables were evaluated using descriptive and inferential analysis to compare groups and phases and to determine relationships between variables. Voice changes were found during the menstrual cycle, and such changes were determined to be related to variations in estradiol levels. Impaired voice quality was observed to be associated with decreased levels of estradiol. The CG did not demonstrate significant vocal changes during phases 1 and 2. The TG showed significant increases in vocal parameters of roughness, tension, and instability during phase 2 (the period of low estradiol levels) when compared with the CG. Low estradiol levels were also found to be negatively correlated with the parameters of tension, instability, and jitter and positively correlated with fundamental voice frequency. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Effect of a chronic treatment with 17β-estradiol on striatal dopamine neurotransmission and the Akt/GSK3 signaling pathway in the brain of ovariectomized monkeys.

PubMed

Sánchez, Maria Gabriela; Morissette, Marc; Di Paolo, Thérèse

2012-02-01

The present experiments sought the effect of chronic treatment with 17β-estradiol on striatal dopaminergic activity and the Akt/GSK3 signaling pathway in the brain of monkeys. Eight female monkeys (Macacca fascicularis) were ovariectomized (OVX) and a month later, half received a month treatment with 17β-estradiol and the other with vehicle. The DA transporter (DAT) was measured by autoradiography with [(125)I]RTI-121 and the vesicular DA transporter (VMAT(2)) with [(3)H]TBZ-OH at three rostro-caudal levels (anterior, middle and posterior) of the caudate nucleus and putamen subdivided in their lateral/medial, ventral/dorsal sub-regions. Specific binding to DAT was increased in all sub-regions of the caudate nucleus and the putamen of 17β-estradiol-treated compared to vehicle-treated monkeys whereas specific binding to VMAT(2) remained unchanged. We measured by Western blot the phosphorylated forms of Akt at serine 473 and threonine 308, GSK3β at serine 9 and tyrosine 216 and GSK3α at serine 21 in anterior, middle and posterior caudate nucleus and putamen. 17β-Estradiol treatment increased in all the caudate nucleus and putamen pAkt (Ser473)/βIII-tubulin, pGSK3β (Ser9)/βIII-tubulin and in putamen Akt/βIII-tubulin compared to vehicle-treated monkeys. In anterior and middle putamen, pAkt (Thr308)/βIII-tubulin was also increased in monkeys treated with 17β-estradiol. pGSK3β (Tyr216)/βIII-tubulin and pGSK3α (Ser21)/βIII-tubulin remained unchanged by the 17β-estradiol treatment. These results suggest that 17β-estradiol activates striatal DA neurotransmission in primates as reflected with increased DAT specific binding and downstream activation of Akt/GSK3 signaling. This supports a beneficial role of a chronic treatment with 17β-estradiol by increasing the activity of signaling pathways implicated in cell survival. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats.

PubMed

Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; Maclusky, Neil J; Leranth, Csaba; Duman, Ronald S

2010-01-15

Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in female subjects is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant desipramine. Considering that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life might influence behavioral and synaptic responses to stress and depression. With electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n = 70), under different conditions of estradiol exposure. Stress induced an acute and persistent loss of hippocampal spine synapses, whereas subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either before stress or before escape testing of nonstressed animals increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. These findings suggest that hippocampal spine synapse remodeling might be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression.

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...

Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

PubMed

Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

2010-04-01

Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

Differential effects of selective estrogen receptor modulators on the vagina and its supportive tissues.

PubMed

Liang, Rui; Knight, Katrina; Nolfi, Alexis; Abramowitch, Steven; Moalli, Pamela A

2016-02-01

Some selective estrogen receptor modulators (SERMs) have been associated with increased incidence of urinary incontinence and pelvic organ prolapse. This study explored the effects of five SERMs on the function and matrix components of the vagina and its supportive tissues. Fifty-six rats were administered SERMs by oral gavage for 8 weeks (n = 8 for each SERM): raloxifene, tamoxifen, idoxifene, bazedoxifene at three different doses, and bazedoxifene with conjugated estrogens. Thirty-two rats were used as controls (n = 8 per group): sham operation (no ovariectomy), ovariectomy only, ovariectomy with vehicle gavage, and 17β-estradiol (subcutaneous). Vaginal supportive tissue complex was tested by uniaxial tensile testing. Total collagen content (hydroxyproline) and glycosaminoglycan content (Blyscan) were measured. Ovariectomy significantly decreased the mechanical integrity of the vagina and its supportive tissue complex, with a decrease in ultimate load and stiffness (all P < 0.05). Although 17β-estradiol supplementation maintained these properties similarly to sham operation, none of the SERMs was as effective--particularly idoxifene, bazedoxifene at higher doses, and bazedoxifene with conjugated estrogens (all P < 0.05). In addition, idoxifene and bazedoxifene induced increased total collagen content compared with sham or 17β-estradiol treatment (all P < 0.05). Glycosaminoglycan content did not change significantly. Unlike 17β-estradiol, SERM supplementation does not fully prevent ovariectomy-induced deterioration in the biomechanical properties of the vagina and its supportive tissues, with the effects of idoxifene and bazedoxifene being the least. The paradoxically increased collagen content in these two groups may be related to increased formation of nonfunctional collagen.

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

Estrogen receptors and biologic response in rat parathyroid tissue and C cells.

PubMed Central

Naveh-Many, T; Almogi, G; Livni, N; Silver, J

1992-01-01

The expression of the PTH and calcitonin genes is dramatically decreased by 1,25(OH)2D3 in vivo, and the PTH gene expression is increased by hypocalcemia. We have now studied the effect of estrogens on the expression of these genes in vivo. 17 beta-Estradiol, given to ovariectomized rats, led to a fourfold increase in PTH mRNA and calcitonin mRNA levels. These effects occurred 24 h after single injections of 37-145 nmol estradiol, or after constant infusions of 12 pmol/d for 1 or 2 wk, where there was no effect on serum calcium levels. The estrogen receptor mRNA was demonstrated in the thyroparathyroid tissue by polymerase chain reaction. The estrogen binding was localized to the parathyroid and C cells by immunohistochemistry. Uterus weight was increased by repeated larger doses (73 nmol/d x 7) of estradiol, but not by the small doses (12 pmol/d for 1 or 2 wk) which were effective on the PTH and calcitonin genes, suggesting a sensitive endocrine effect. These results confirm that the parathyroid and C cells are target organs for estrogen, leading to an increased expression of PTH and calcitonin, which by their combined anabolic effect on bone would help prevent osteoporosis. Images PMID:1469095

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.

A comparison between monophasic levonorgestrel-ethinyl estradiol 150/30 and triphasic levonorgestrel-ethinyl estradiol 50-75-125/30-40-30 contraceptive pills for side effects and patient satisfaction: a study in Iran.

PubMed

Kashanian, Maryam; Shahpourian, Farangis; Zare, Omolbanin

2010-05-01

Oral contraceptive pills (OCPs) are one of the most effective reversible and accessible contraceptives, and patient acceptance for their use depends partly on the unfavorable adverse effects. The present study compared the two kinds of OCPs (monophasic; levonorgestrel (LNG)-ethinyl estradiol (EE) 150/30 versus triphasic; LNG-EE 50-75-125/30-40-30) for adverse effects and patient satisfaction. A randomized clinical trial was performed on 314 women who used OCPs for the first time, as their contraception, for 6 months. Overall, 1884 cycles were studied. In the monophasic group (n=159 who finally finished the study), monophasic pills LNG-EE 150/30mcg, and in the triphasic group (n=155 who finally finished the study), triphasic pills LNG-EE 50-75-125/30-40-30 mcg were used. Statistical analysis was performed using SPSS 10: Chi square test, Fisher exact test and Student's t-test were used. There were no significant differences between the two groups for common side effects, including nausea, headache, nervousness, facial hyperpigmentation (chloasma), and body weight (increase or decrease) but breakthrough bleeding and spotting (BTB/S) were less in the triphasic group, occurring in 30 cycles (18.86%) versus 10 cycles (6.45%), P=0.009*. Patient satisfaction for the two OCPs was similar and high. The rates of side effects were low. It seems that the monophasic and triphasic pills are similar according to patient satisfaction and side effects; therefore there is no benefit of one over the other except for BTB/S, for which triphasic is superior. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Biometry of the hypospadic penis after hormone therapy (testosterone and estrogen): A randomized, double-blind controlled trial.

PubMed

Paiva, Kelly Christina de Castro; Bastos, André Netto; Miana, Laura Pimenta; Barros, Eveline de Souza; Ramos, Plínio Santos; Miranda, Lara Meneguelli; Faria, Natália Maia; Avarese de Figueiredo, André; de Bessa, José; Netto, José Murillo B

2016-08-01

The use of preoperative hormonal stimulation before hypospadias surgery aims to increase penile size and achieve better surgical results; however, the rules are not clear in the literature. We evaluated the effects of topical testosterone and estrogen in the hypospadic penis regarding biometric measures, side effects, and serum hormonal levels. To our knowledge, this is the first study using estradiol prior to hypospadias surgery. Sixty-nine children with hypospadias were randomly divided into three study groups: a control group (CG) of 17 children given placebo cream; a testosterone group (TG) of 28 children who used 1% testosterone propionate; and an estradiol group (EG) of 24 children using 0.01% estradiol. All subjects applied the topical ointment on the entire penis, twice daily for 30 days before surgical correction. Biometric evaluation of the penis included penile length and diameter, glans diameter, distance from the urethral meatus to the tip, and the width of the urethral plate. These measurements as well as serum hormone level, and side effects were evaluated prior to hormone use, and 30 and 90 days after. After 30 days an increase in penile diameter and length and diameter of the glans were observed in TG (p < 0.05). The width of the urethral plate and distance from meatus to the tip increased in TG, although not significantly. The most frequent side effects were appearance of pubic hair and darkening of the genital skin, mainly in TG, but these were transient and disappeared after 90 days of treatment. No significant variations were seen in serum hormonal levels (Table). As in previous studies, an increase in penile length and diameter, and glans diameter was observed with the use of testosterone. Proximal urethral plate width and distance from the meatus to the tip of the penis had a tendency to increase also in TG. Estradiol did not change biometric measure of the penis. Few side effects occurred after both hormones, and any that did improved after 90 days follow-up and did not change hormone serum levels. Preoperative use of topical testosterone increases penile size, diameter of the penis and glans. The use of estradiol does not change penile biometry. Side effects occur mainly with the use of testosterone and are transient. No significant and persistent hormonal changes were observed. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study.

PubMed

Isotton, Ana Lúcia; Wender, Maria Celeste Osorio; Casagrande, Alessandra; Rollin, Guilherme; Czepielewski, Mauro Antônio

2012-02-01

To evaluate the effects of oral estradiol and transdermal 17β-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. Prospective, comparative study. Eleven patients with hypopituitarism were randomly allocated to receive 2 mg oral estradiol (n=6) or 50 μg/day of transdermal 17β-estradiol (n=5) for 3 months. The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%±41.4, P=0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%±230.9, P=0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8±9.3, P=0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

PubMed

Shahid, Adangam Purath; Salini, Sasidharan; Sasidharan, Nanu; Padikkala, Jose; Raghavamenon, Achuthan Chathrattil; Babu, Thekkekara Devassy

2015-09-01

Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

How medical treatment affects mean platelet volume as a cardiovascular risk marker in polycystic ovary syndrome?

PubMed

Kabil Kucur, Suna; Gozukara, Ilay; Aksoy, Aysenur; Uludag, Eda U; Keskin, Havva; Kamalak, Zeynep; Carlioglu, Ayse

2015-12-01

Polycystic ovary syndrome (PCOS) is a prevalent disease with many potential long-term metabolic and cardiovascular risks if not managed appropriately. Mean platelet volume (MPV) is a marker associated with adverse cardiovascular events. In this study, we aimed to investigate MPV levels under ethinyl estradiol/cyproterone acetate or metformin therapy for the previous 6 months in PCOS. A total of 114 individuals [metformin treatment (n = 18), ethinyl estradiol/cyproterone acetate treatment (n = 29), newly diagnosed PCOS patient with no treatment (n = 35), and control group of eumenorrheic healthy individuals (n = 32)] were included in the current study. Hematologic parameters other than MPV were similar in all groups. The MPV value was significantly higher in the newly diagnosed PCOS patients compared with the other three groups independent of age, BMI, and C-reactive protein level in multiple regression analysis (P < 0.01). The MPV value of control group was comparable to the groups under ethinyl estradiol/cyproterone acetate or metformin therapy (P = 1.0). There was no statistically significant difference in the white blood cell count among the groups. The MPV values were positively correlated with the homeostatic model assessment-insulin resistance and Ferriman-Gallwey Score (P = 0.044, r = 0.261; P = 0.037, r = 0.229, respectively). Ethinyl estradiol/cyproterone acetate and metformin similarly appear to decrease MPV, a marker of cardiovascular risk. Therefore, a possible beneficial effect of ethinyl estradiol/cyproterone acetate and metformin on long-term cardiovascular morbidities in PCOS may be suggested.

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

PubMed

Klein, Karen Oerter

2015-07-01

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

17β-Estradiol on the Expression of G-Protein Coupled Estrogen Receptor (GPER/GPR30) Mitophagy, and the PI3K/Akt Signaling Pathway in ATDC5 Chondrocytes In Vitro

PubMed Central

Fan, Dong-xiao; Yang, Xu-hao; Li, Yi-nan

2018-01-01

Background Osteoarthritis is a progressive inflammatory joint disease resulting in damage to articular cartilage. G-protein coupled estrogen receptor (GPER/GPR30) activates cell signaling in response to 17β-estradiol, which can be blocked by the GPR30 agonist, G15, an analog of G-1. The aims of this study were to investigate the effects of 17β-estradiol on the expression of G-protein coupled estrogen receptor (GPER/GPR30) on mitophagy and the PI3K/Akt signaling pathway in ATDC5 chondrocytes in vitro. Material/Methods Cultured ATDC5 chondrocytes were treated with increasing concentrations of 17β-estradiol with and without G15, p38 inhibitor (SB203580), JNK inhibitor (SP600125), PI3K inhibitor (LY294002, S1737), and mTOR inhibitor (S1842). Expression of GPER/GPR30 and components of the PI3K/Akt pathway in cultured ATDC5 chondrocytes were detected by immunofluorescence (IF) staining, Western blot, and real-time polymerase chain reaction (RT-PCR). Transmission electron microscopy (TEM) and IF were used to detect mitophagosomes. Expression of LC-3, LAMP2, TOM20, Hsp60, p-Akt, p-mTOR, p-p38, and p-JNK was investigated by Western blot. Proliferation and viability of the ATDC5 chondrocytes were determined using BrdU and MTT assays. Results In 17β-estradiol-treated ATDC5 chondrocytes, increased expression of GPER/GPR30 was found, but fewer mitophagosomes were observed, and decreased numbers of TOM20-positive granules were co-localized with decreased LAMP2 and increased expression levels of TOM20, Hsp60, p-Akt, and p-mTOR, and reduced expression of LC3-II, were found. In 17β-estradiol-treated ATDC5 chondrocytes, the proliferation and viability of the 17β-estradiol-treated ATDC5 chondrocytes were significantly elevated. Conclusions Treatment with 17β-estradiol protected ATDC5 chondrocytes against mitophagy via the GPER/GPR30 and the PI3K/Akt signaling pathway. PMID:29608013

Aging and estradiol effects on gene expression in the medial preoptic area, bed nucleus of the stria terminalis, and posterodorsal medial amygdala of male rats

PubMed Central

Nutsch, Victoria L.; Bell, Margaret R.; Will, Ryan G.; Yin, Weiling; Wolfe, Andrew; Gillette, Ross; Dominguez, Juan M.; Gore, Andrea C.

2017-01-01

Studies on the role of hormones in male reproductive aging have traditionally focused on testosterone, but estradiol also plays important roles in the control of masculine physiology and behavior. Our goal was to examine the effects of E2 on the expression of genes selected for E2-sensitivity, involvement in behavioral neuroendocrine functions, and impairments with aging. Mature adult (MAT, 5 mo.) and aged (AG, 18 mo.) Sprague-Dawley male rats were castrated, implanted with either vehicle or estradiol (E2) subcutaneous capsules, and euthanized one month later. Bilateral punches were taken from the bed nucleus of the stria terminalis (BnST), posterodorsal medial amygdala (MePD) and the preoptic area (POA). RNA was extracted, and expression of 48 genes analyzed by qPCR using Taqman low-density arrays. Results showed that effects of age and E2 were age- and region-specific. In the POA, 5 genes were increased with E2 compared to vehicle, and there were no age effects. By contrast the BnST showed primarily age-related changes, with 6 genes decreasing with age. The MePD had 5 genes that were higher in aged than mature males, and 17 genes with significant interactions between age and E2. Gene families identified in the MePD included nuclear hormone receptors, neurotransmitters and neuropeptides and their receptors. Ten serum hormones were assayed in these same males, with results revealing both age- and E2-effects, in several cases quite profound. These results support the idea that the male brain continues to be highly sensitive to estradiol even with aging, but the nature of the response can be substantially different in mature and aging animals. PMID:28007657

Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakami, Gen; Mukai, Hideo; Hojo, Yasushi

2006-12-15

Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17{beta}-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosum-moleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1 nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2 h. This increase by estradiol was blocked by Erkmore » MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ER{alpha} agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol.« less

Pregnancy-Induced Gingivitis and OMICS in Dentistry: In Silico Modeling and in Vivo Prospective Validation of Estradiol-Modulated Inflammatory Biomarkers

PubMed Central

Zeidán-Chuliá, Fares; Könönen, Eija; Moreira, José C. F.; Liukkonen, Joonas; Sorsa, Timo; Gürsoy, Ulvi K.

2014-01-01

Abstract Pregnancy-associated gingivitis is a bacterial-induced inflammatory disease with a remarkably high prevalence ranging from 35% to 100% across studies. Yet little is known about the attendant mechanisms or diagnostic biomarkers that can help predict individual susceptibility for rational personalized medicine. We aimed to define inflammatory proteins in saliva, induced or inhibited by estradiol, as early diagnostic biomarkers or target proteins in relation to pregnancy-associated gingivitis. An in silico gene/protein interaction network model was developed by using the STITCH 3.1 with “experiments” and “databases” as input options and a confidence score of 0.700 (high confidence). Salivary estradiol, interleukin (IL)-1β and -8, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-2, -8, and -9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 levels from 30 women were measured prospectively three times during pregnancy and twice during postpartum. In silico analysis revealed that estradiol interacts with IL-1β and -8 by an activation link when the “actions view” was consulted. In saliva, estradiol concentrations associated positively with TIMP-1 and negatively with MPO and MMP-8 concentrations. When the gingival bleeding on probing percentage (BOP%) was included in the model as an effect modifier, the only association, a negative one, was found between estradiol and MMP-8. Throughout gestation, estradiol modulates the inflammatory response by inhibiting neutrophilic enzymes, such as MMP-8. The interactions between salivary degradative enzymes and proinflammatory cytokines during pregnancy suggest promising ways to identify candidate biomarkers for pregnancy-associated gingivitis, and for personalized medicine in the field of dentistry. Finally, we call for greater investments in, and action for biomarker research in periodontology and dentistry that have surprisingly lagged behind in personalized medicine compared to other fields, such as cancer research. PMID:24983467

Estradiol targets T cell signaling pathways in human systemic lupus.

PubMed

Walters, Emily; Rider, Virginia; Abdou, Nabih I; Greenwell, Cindy; Svojanovsky, Stan; Smith, Peter; Kimler, Bruce F

2009-12-01

The major risk factor for developing systemic lupus erythematosus (SLE) is being female. The present study utilized gene profiles of activated T cells from females with SLE and healthy controls to identify signaling pathways uniquely regulated by estradiol that could contribute to SLE pathogenesis. Selected downstream pathway genes (+/- estradiol) were measured by real time polymerase chain amplification. Estradiol uniquely upregulated six pathways in SLE T cells that control T cell function including interferon-alpha signaling. Measurement of interferon-alpha pathway target gene expression revealed significant differences (p= 0.043) in DRIP150 (+/- estradiol) in SLE T cell samples while IFIT1 expression was bimodal and correlated moderately (r= 0.55) with disease activity. The results indicate that estradiol alters signaling pathways in activated SLE T cells that control T cell function. Differential expression of transcriptional coactivators could influence estrogen-dependent gene regulation in T cell signaling and contribute to SLE onset and disease pathogenesis.

Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

NASA Astrophysics Data System (ADS)

Kusuma, R.; Siregar, Y.; Mardianto

2018-03-01

Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

Relationship of QT dispersion with sex hormones and insulin in young women with polycystic ovary syndrome: an observational study.

PubMed

Gazi, Emine; Gencer, Meryem; Hancı, Volkan; Temiz, Ahmet; Altun, Burak; Cakır Güngör, Ayşe Nur; Oztürk, Ufuk; Kırılmaz, Bahadır

2013-12-01

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in reproductive women. Cardiovascular disease risk factors are more frequent in this population. We aimed in this study to investigate presence of QT dispersion and effects of sex hormones and insulin on QT duration in young PCOS patients. This present study was cross-sectional observational study. A total of 47 women, 25 patients with PCOS and 22 healthy, were included. Serum testosterone, estradiol and insulin levels were studied and electrocardiography was performed at 2nd or 3th days of menstrual cycle. The study population was divided into groups according to serum testosterone and estradiol levels. Sub-groups and pairwise groups were compared by Mann-Whitney U or student t-test. The associations of QTc durations with hormone levels were calculated using Spearman rank correlation analysis. The results were evaluated at the p<0.05 significance level. No differences found between groups regarding to demographic parameters. Estradiol and testosterone levels were higher in patients with PCOS (41.12 ± 13.59 vs. 35.57 ± 19.29 pg/mL, p=0.09 and 105 ± 58.5 vs. 17.6 ± 10.9 ng/dL, p=0.01, respectively). QT dispersion was significantly longer in PCOS patients (47.1 vs. 32.7 ms, p=0.01). A positive correlation was found between the serum insulin level and QTc min, QTc max, and QTc mean (r=0.402, p=0.011; r=0.341, p=0.033; r=0.337, p=0.036; respectively). QT dispersion with serum testosterone and estradiol levels were positively correlated (r=0.525, p=0.001 and r=0.326, p=0.046; respectively). Our results suggest that QT dispersion is prolonged and testosterone, estradiol and insulin are associated with QT duration in young PCOS patients.

Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

PubMed

Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

2015-07-28

The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100μg/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100μg/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100μg/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100μg/day. Published by Elsevier B.V.

Sex steroid receptors in male human bladder: expression and biological function.

PubMed

Chavalmane, Aravinda K; Comeglio, Paolo; Morelli, Annamaria; Filippi, Sandra; Fibbi, Benedetta; Vignozzi, Linda; Sarchielli, Erica; Marchetta, Matilde; Failli, Paola; Sandner, Peter; Saad, Farid; Gacci, Mauro; Vannelli, Gabriella B; Maggi, Mario

2010-08-01

In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens. Within the bladder, LUTS are linked to RhoA/Rho-kinase (ROCK) pathway overactivity. To investigate the effects of changing sex steroids on bladder smooth muscle. ER α, ER β, GPR30/GPER1 and aromatase mRNA expression was analyzed in male genitourinary tract tissues, and cells isolated from bladder, prostate, and urethra. Estrogen and G1 effect on RhoA/ROCK signaling output like cell migration, gene expression, and cytoskeletal remodeling, and [Ca(2+) ](i) was also studied in hB cells. Contractile studies on bladder strips from castrated male rats supplemented with estradiol and testosterone was also performed. The effects of classical (ER α, ER β) and nonclassical (GPR30/GPER1) estrogen receptor ligands (17 β-estradiol and G1, respectively) and androgens on RhoA/ROCK-.mediated cell functions were studied in hB cells. Contractility studies were also performed in bladder strips from castrated male rats supplemented with testosterone or estradiol. Aromatase and sex steroid receptors, including GPR30, were expressed in human bladder and mediates several biological functions. Both 17 β-estradiol and G1 activated calcium transients and induced RhoA/ROCK signaling (cell migration, cytoskeleton remodeling and smooth muscle gene expression). RhoA/ROCK inhibitors blunted these effects. Estrogen-, but not androgen-supplementation to castrated rats increased sensitivity to the ROCK inhibitor, Y-27632 in isolated bladder strips. In hB cells, testosterone elicited effects similar to estrogen, which were abrogated by blocking its aromatization through letrozole. Our data indicate for the first time that estrogen-more than androgen-receptors up-regulate RhoA/ROCK signaling. Since an altered estrogen/androgen ratio characterizes conditions, such as aging, obesity and metabolic syndrome, often associated to LUTS, we speculate that a relative hyperestrogenism may induce bladder overactivity through the up-regulation of RhoA/ROCK pathway. © 2010 International Society for Sexual Medicine.

The tolerability of a triphasic norgestimate/EE-containing OC: results from a double-blind, placebo-controlled trial.

PubMed

Lippman; Godwin; Olson

1998-07-01

Objective: To compare adverse event data collected during administration of a triphasic norgestimate ethinyl estradiol (EE) containing oral contraceptive (OC) [ORTHO TRI-CYCLEN(R)] or placebo.Methods: Four-hundred fifty-two females between the ages of 15 and 49 years were enrolled in two multicenter, double-blind, randomized, placebo-controlled studies. These studies were conducted to evaluate the effectiveness of triphasic norgestimate/EE in the treatment of acne vulgaris (Redmond G, Olson W, Lippman J, et al. Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a randomized placebo-controlled trial. Obstet Gynecol 1997;89:X-X; Lucky A, Henderson T, Olson W, et al. The effectiveness of norgestimate and ethinyl estradiol in treating acne vulgaris. J Am Acad Dermatol, in press). Participants returned to the study centers monthly for evaluation. At each visit, interviews were conducted to elicit and record the occurrence of adverse events. Reports were derived by nondirected questioning.Results: The table below describes the number and percentage of subjects reporting the event during the 6-month period. Note that, over the range of percentages observed, the differences detectable with a power of 0.80 range from approximately 4% to 12%.Conclusion: Excellent tolerability for the triphasic norgestimate/EE OC is demonstrated by a low rate of side effects that did not differ in a statistically significant manner from placebo.

Neurodevelopmental Low-dose Bisphenol A Exposure Leads to Early Life-stage Hyperactivity and Learning Deficits in Adult Zebrafish

PubMed Central

Saili, Katerine S.; Corvi, Margaret M.; Weber, Daniel N.; Patel, Ami U.; Das, Siba R.; Przybyla, Jennifer; Anderson, Kim A.; Tanguay, Robert L.

2011-01-01

Developmental bisphenol A (BPA) exposure has been implicated in adverse behavior and learning deficits. The mode of action underlying these effects is unclear. The zebrafish model was employed to investigate the neurobehavioral effects of developmental bisphenol A (BPA) exposure. The objectives of this study were to identify whether low-dose, developmental BPA exposure affects larval zebrafish locomotor behavior and whether learning deficits occur in adults exposed during development. Two control compounds, 17β-estradiol (an estrogen receptor ligand) and GSK4716 (a synthetic estrogen related receptor gamma ligand), were included. Larval toxicity assays were used to determine appropriate BPA, 17β-estradiol, and GSK4716 concentrations for behavior testing. BPA tissue uptake was analyzed using HPLC and lower doses were extrapolated using a linear regression analysis. Larval behavior tests were conducted using a ViewPoint Zebrabox. Adult learning tests were conducted using a custom-built T-maze. BPA exposure to ≤30 μM was nonteratogenic in zebrafish. Neurodevelopmental BPA exposure to 0.01, 0.1, or 1 μM led to larval hyperactivity or learning deficits in adult zebrafish. Exposure to 0.1 μM 17β-estradiol or GSK4716 also led to larval hyperactivity. This study demonstrates the efficacy of using the larval zebrafish model for studying the neurobehavioral effects of low-dose developmental BPA exposure. PMID:22108044

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years

PubMed Central

Kocarnik, Beverly M.; Boyko, Edward J.; Matsumoto, Alvin M.; Fujimoto, Wilfred Y.; Hayashi, Tomoshige; Leonetti, Donna L.; Page, Stephanie T.

2016-01-01

Summary Problem The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. Methods This is a longitudinal observational study in community-dwelling Japanese-American men (n = 215, mean age 52 years, BMI 25.4 kg/m2). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Results Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r = −0.05 for both time points, p = 0.45 and p = 0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p = 0.52 and p = 0.55, respectively). Conclusions Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. PMID:26747209

Circulating Estrogen Levels and Self-Reported Health and Mobility Limitation in Community-Dwelling Men of the Framingham Heart Study.

PubMed

Jasuja, Guneet Kaur; Travison, Thomas G; Murabito, Joanne M; Davda, Maithili N; Rose, Adam J; Basaria, Shehzad; Coviello, Andrea; Vasan, Ramachandran S; D'Agostino, Ralph; Bhasin, Shalender

2017-08-01

Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men. The cross-sectional sample included 1,148 men, who attended Framingham Offspring Study Examinations 7 and 8. Estrone and estradiol levels were measured using liquid chromatography tandem mass spectrometry at Examination 7. Self-reported mobility limitation and self-rated health were assessed at Examinations 7 and 8. Additionally, short physical performance battery, usual walking speed, and grip strength were assessed at Examination 7. In incident analysis, estradiol levels at Examination 7 were associated with increased odds of fair or poor self-rated health at Examination 8, after adjusting for age, body mass index, comorbidities, and testosterone levels; in an individual with 50% greater estradiol than other, the odds of reporting "fair or poor" self-rated health increased by 1.78 (95% confidence interval: 1.25-2.55; p = .001). Neither estrone nor estradiol levels were associated with any physical performance measure at baseline. Higher circulating levels of estradiol are associated with increased risk of incident fair/poor self-rated health in community-dwelling men. The mechanisms by which circulating levels of estradiol are related to self-rated health in men need further investigation. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

NEONATAL LOW- AND HIGH-DOSE EXPOSURE TO ESTRADIOL BENZOATE IN THE MALE RAT: I. EFFECTS ON THE PROSTATE GLAND

EPA Science Inventory

Neonatal Low- And High-Dose Exposure To Estradiol Benzoate In The Male Rat: 1. Effects On The Prostate Gland. Oliver Putz, Christian B. Schwartz, Steve Kim, Gerald A. LeBlanc Ralph L. Cooper, Gail S. Prins

ABSTRACT
Brief exposure of rats to high doses of natural estro...

Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets.

PubMed

Panay, Nick; Maamari, Ricardo

2012-03-01

Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.

Pituitary, ovarian and additional contraceptive effects of an estradiol-based combined oral contraceptive: results of a randomized, open-label study.

PubMed

Endrikat, Jan; Parke, Susanne; Trummer, Dietmar; Serrani, Marco; Duijkers, Ingrid; Klipping, Christine

2013-02-01

The estrogen step-down/progestogen step-up 28-day estradiol valerate/dienogest (E(2)V/DNG) oral contraceptive effectively inhibits ovulation; however, limited data are available regarding its effects on estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or its additional extraovarian contraceptive effects. In this secondary analysis, 100 women received E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26 and placebo on days 27-28 for one treatment cycle. Measures included the presence/absence of cervical mucus; endometrial thickness; and serum E2, progesterone, and gonadotropin levels. E2, progesterone, LH and FSH levels did not exhibit the typical ovulatory increase and remained relatively stable during the cycle. E(2)V/DNG reduced mean maximal endometrial thickness and proportion of women with visible cervical mucus. All parameters returned to pretreatment levels during the posttreatment cycle. E(2)V/DNG provides extraovarian contraceptive effects (reducing endometrial thickness and cervical mucus production) in addition to inhibiting ovulation, assuring contraceptive efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis.

PubMed

Farris, Manuela; Bastianelli, Carlo; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-10-01

The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range.

Glassy carbon electrode modified with carbon black for sensitive estradiol determination by means of voltammetry and flow injection analysis with amperometric detection.

PubMed

Smajdor, Joanna; Piech, Robert; Ławrywianiec, Martyna; Paczosa-Bator, Beata

2018-03-01

A voltammetric method for fast and sensitive estradiol determination using carbon black modified glassy carbon electrode (CBGC) is proposed. The use of carbon black as a modifying layer led to obtain low detection limit (9.2·10 -8  mol L -1 for a preconcentration time of 60 s) and stability of registered signals (measured as RSD is 1.3%, n = 7, estradiol concentration 0.5·10 -6  mol L -1 ). Cyclic voltammetry study revealed that in phosphate media estradiol suffers irreversible one-proton and one-electron oxidation process. Under the optimum conditions, estradiol calibration curve was linear in the concentration range from 0.15·10 -6 to 3.5·10 -6  mol L -1 . The proposed method enable to determine estradiol content in different pharmaceutical formulation with good recovery. Amperometric measurements of estradiol were performed as well to indicate the possibility of its fast and accurate determination under the flow conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood.

PubMed

Ambrosetti, Valery; Guerra, Marcelo; Ramírez, Luisa A; Reyes, Aldo; Álvarez, Daniela; Olguín, Sofía; González-Mañan, Daniel; Fernandois, Daniela; Sotomayor-Zárate, Ramón; Cruz, Gonzalo

2016-07-01

Maternal obesity during pregnancy has been related with several pathological states in offspring. However, the impact of maternal obesity on reproductive system on the progeny is beginning to be elucidated. In this work, we characterize the effect of maternal obesity on puberty onset and follicular development in adult offspring in rats. We also propose that alterations in ovarian physiology observed in offspring of obese mothers are due to increased levels of estradiol during early development. Offspring of control dams and offspring of dams exposed to a high-fat diet (HF) were studied at postnatal days (PND) 1, 7, 14, 30, 60, and 120. Body weight and onset of puberty were measured. Counting of ovarian follicles was performed at PND 60 and 120. Serum estradiol, estriol, androstenedione, FSH, LH, and insulin levels were measured by ELISA. Hepatic CYP3A2 expression was determined by Western blot. HF rats had a higher weight than controls at all ages and they also had a precocious puberty. Estradiol levels were increased while CYP3A2 expression was reduced from PND 1 until PND 60 in HF rats compared to controls. Estriol was decreased at PND60 in HF rats. Ovaries from HF rats had a decrease in antral follicles at PND60 and PND120 and an increase in follicular cysts at PND60 and PND120. In this work, we demonstrated that maternal obesity in rats alters follicular development and induces follicular cysts generation in the adult offspring. We observed that maternal obesity produces an endocrine disruption through increasing endogenous estradiol in early life. A programmed failure in hepatic metabolism of estradiol is probably the cause of its increase.

Ovarian and uterine alterations following forced swimming: An immunohistochemical study.

PubMed

Seyed Saadat, Seyedeh Nazanin; Mohammadghasemi, Fahimeh; Ebrahimi, Hannan; Rafati Sajedi, Hanieh; Chatrnour, Gelayol

2016-10-01

Physical exercise is known to be a stressor stimulus that leads to reproductive disruption. The aim of this study was to evaluate the effect of forced swimming on the uterus and ovaries in mice. Adult mice (N=24) were divided into the following three groups: A, control; B, swimming in water (10 o C); and C, swimming in water (23 o C). Swimmers swam for 5 min daily for 5 consecutive days/ wk during 2 wks. An enzyme linked immunosorbent assay was used to determine serum estradiol, follicle stimulating hormone (FSH) and testosterone levels. Immunohistochemistry was performed to study apoptotic cells or estrogen receptor (ER) expression in uterine epithelial cells and ovaries. ANOVA was used for statistical analysis. Swimming in both groups reduced the serum FSH and estradiol levels (p<0.01) without having a significant effect on the serum testosterone level or percentage of apoptosis in ovarian and uterine tissues (p<0.01) compared with controls. A significant reduction in the number of ERs in the uterus and ovaries, and secondary and graafian follicles were observed in groups B and C compared with controls (p<0.01); however the number of primordial and primary follicles were not significantly changed in the ovaries. Forced swimming of 2 wks duration reduces the serum levels of FSH and estradiol without having effects on apoptosis in the ovaries or uteri of mice. Over a long period of time, forced swimming may have an adverse effect on fertility.

Ovarian and uterine alterations following forced swimming: An immunohistochemical study

PubMed Central

Seyed Saadat, Seyedeh Nazanin; Mohammadghasemi, Fahimeh; Ebrahimi, Hannan; Rafati Sajedi, Hanieh; Chatrnour, Gelayol

2016-01-01

Background: Physical exercise is known to be a stressor stimulus that leads to reproductive disruption. Objective: The aim of this study was to evaluate the effect of forced swimming on the uterus and ovaries in mice. Materials and Methods: Adult mice (N=24) were divided into the following three groups: A, control; B, swimming in water (10oC); and C, swimming in water (23oC). Swimmers swam for 5 min daily for 5 consecutive days/ wk during 2 wks. An enzyme linked immunosorbent assay was used to determine serum estradiol, follicle stimulating hormone (FSH) and testosterone levels. Immunohistochemistry was performed to study apoptotic cells or estrogen receptor (ER) expression in uterine epithelial cells and ovaries. ANOVA was used for statistical analysis. Results: Swimming in both groups reduced the serum FSH and estradiol levels (p<0.01) without having a significant effect on the serum testosterone level or percentage of apoptosis in ovarian and uterine tissues (p<0.01) compared with controls. A significant reduction in the number of ERs in the uterus and ovaries, and secondary and graafian follicles were observed in groups B and C compared with controls (p<0.01); however the number of primordial and primary follicles were not significantly changed in the ovaries. Conclusion: Forced swimming of 2 wks duration reduces the serum levels of FSH and estradiol without having effects on apoptosis in the ovaries or uteri of mice. Over a long period of time, forced swimming may have an adverse effect on fertility. PMID:27921086

Changes in ovarian function associated with circulating concentrations of estradiol before a GnRH-induced ovulation in beef cows

USDA-ARS?s Scientific Manuscript database

These studies were conducted to evaluate causes for differences in circulating concentrations of estradiol prior to a GnRH-induced ovulation and to determine if exogenous GnRH administration could alter LH secretion and subsequent follicular estradiol production. Beef cows (Experiment 1; n = 32, Ex...

Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

PubMed

Phumsatitpong, Chayarndorn; Moenter, Suzanne M

2018-01-01

Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

The influence of chronic exposure to low frequency pulsating magnetic fields on concentrations of FSH, LH, prolactin, testosterone and estradiol in men with back pain.

PubMed

Woldanska-Okonska, Marta; Karasek, Michal; Czernicki, Jan

2004-06-01

There is widespread public concern that electromagnetic fields might be hazardous. However, studies on the biological effects of magnetic fields (MFs) have not always been consistent. Influence of extremely-low frequency MFs used in physiotherapy on endocrine system was rarely examined. Therefore, the aim of the present study was to investigate the concentrations of some pituitary (FSH, LH, prolactin) and sex (testosterone, estradiol) hormones in men with back pain exposed to magnetic fields applied during magnetotherapy or magnetostimulation over the period of three weeks. The study was performed on 20 men aged 28-62 years (mean+/-SEM: 46.4+/-2.0 years) suffering from chronic low back pain who underwent magnetotherapy (10 patients, mean age+/-SEM: 48.4 years, range: 28-62 years) or subjected to magnetostimulation (10 patients, mean age+/-SEM: 44.3 years, range: 34-52 years) for 15 days (daily at 10:00 h, with weekend breaks). Blood samples were collected at 08:00 before magnetic field application, one day and one month following the application. Concentrations of hormones were measured by micromethod of chemiluminescence. Both magnetotherapy and magnetostimulation lowered levels of prolactin. The levels of LH decreased significantly one month after magnetotherapy in comparison with the baseline whereas following magnetostimulation slight but insignificant increase was observed. Estradiol concentrations were significantly lower one day and one month following magnetosimulation in comparison to the baseline and did not change after magnetotherapy. No statistically significant changes were observed in levels of FSH and testosterone after either magnetotherapy or magnetosimulation at any time examined. Magnetic fields applied in physiotherapy exert no or very subtle effect on concentrations of FSH, LH, prolactin, testosterone, and estradiol in men.

Simultaneous total occlusion of two coronary arteries associated with use of drospirenone-ethinyl estradiol (oral contraceptive).

PubMed

Atmaca, Hüsnü; Köprülü, Diyar; Kiriş, Tuncay; Zeren, Gönül; Şahin, İrfan

2018-01-01

Although the use of oral contraceptives is associated with an increased risk of venous thromboembolic disease, the risk of myocardial infarction (MI) is unclear. A new, third-generation contraceptive agent, drospirenone-ethinyl estradiol, which contains less estrogen and a new progestogen, drospirenone, in a different combination, has been considered more reliable in terms of risk of MI. However, there have been some cases of MI associated with the use of drospirenone-ethinyl estradiol, despite the protective effects of this oral contraceptive. In this report, a 33-year-old woman who had used drospirenone-ethinyl estradiol for 6 months was admitted with MI and symptoms of cardiogenic shock. Coronary angiography revealed the total occlusion of 2 coronary arteries and so percutaneous coronary intervention was performed. To the best of our knowledge, this is the first case report of simultaneous total occlusion of 2 coronary arteries associated with the use of drospirenone-ethinyl estradiol in the English-language medical literature.

Increased impact of a contraceptive vaginal ring with ethinyl estradiol and nestorone on C-reactive protein.

PubMed

Rad, Mandana; Burggraaf, Jacobus; Sitruk-Ware, Regine L; de Kam, Marieke L; Cohen, Adam F; Kluft, Cornelis

2012-11-01

OBJECTIVE & STUDY DESIGN: In a parallel design, 23 and 22 healthy pre-menopausal women were randomly administered a contraceptive vaginal ring (CVR) delivering 150/15 μg Nestorone®/ethinyl estradiol (EE) daily or an oral contraceptive (OC) containing levonorgestrel and EE (150/30 μg) for three cycles, to compare the effects on C-reactive protein and other markers of inflammation. ANCOVA was performed with baseline values as covariate. The CVR caused [estimate of difference (95% CI), 109% (16-275%)] higher levels of CRP than the OC, while no difference was observed for leukocyte 1% (-13/+17%) and monocyte counts 6% (-9/+23%). The greater increase in CRP was confined to CVR recipients exhibiting low pre-treatment CRP-levels, whereas no difference was observed in the increases for recipients in the highest tertile of pre-treatment CRP levels. The difference in CRP rise in CVR and OC users does not correspond with the effects on other markers of inflammation and is most likely due to a specific difference in the effect of ethinyl-estradiol combined with nestorone in cases with low CRP. Copyright © 2012 Elsevier Inc. All rights reserved.

Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation.

PubMed

Sehmisch, S; Boeckhoff, J; Wille, J; Seidlova-Wuttke, D; Rack, T; Tezval, M; Wuttke, W; Stuermer, K M; Stuermer, E K

2009-06-01

Osteoporosis research undertaken in males is rare and there are only a few therapeutic options. Phytoestrogens might be a safe alternative for prophylaxis. Sixty 3-month-old male rats were orchidectomized and divided into five groups. The groups either received soy-free food (C), estradiol (E), testosterone (T) or Vitex agnus castus in different concentrations (AC high/AC low) for 12 weeks. The tibia metaphysis was tested biomechanically and histomorphometrically. The AC high group reached 87% of the biomechanical values of the estradiol group and was significantly superior to the control group. Testosterone supplementation resulted in poor biomechanical properties. The cortical bone parameters of the AC group were similar to the control group, while supplementation with estradiol and testosterone demonstrated a reduction of cortical bone. The AC high group reached 88.4% of trabecular bone area, 80.7% of trabecular number and 66.9% of the number of trabecular nodes compared with estradiol supplementation. Vitex agnus castus demonstrated osteoprotective effects in males. It preserves the cortical as well as the trabecular bone and might be a safe alternative for HRT. Testosterone supplementation has positive effects on trabecular bone, which are concurrently counteracted by the loss of cortical bone. (c) 2008 John Wiley & Sons, Ltd.

Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

PubMed Central

Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

2009-01-01

Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

Overlapping but distinct effects of genistein and ethinyl estradiol (EE2) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies

PubMed Central

Delclos, K. Barry; Weis, Constance C.; Bucci, Thomas J.; Olson, Greg; Mellick, Paul; Sadovova, Natalya; Latendresse, John R.; Thorn, Brett; Newbold, Retha R.

2009-01-01

Genistein and ethinyl estradiol (EE2) were examined in multigenerational reproductive and chronic toxicity studies that had different treatment intervals among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm) or EE2 (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE2 at 50 ppb produced similar effects in continuously exposed rats, including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals. At the high dose, anogenital distance was subtly affected by both compounds, and a reduction in litter size was evident in genistein-treated animals. Genistein at 500 ppm induced an early onset of aberrant cycles relative to controls in the chronic studies. EE2 significantly increased the incidence of uterine lesions (atypical focal hyperplasia and squamous metaplasia). These compound-specific effects appeared to be enhanced in the offspring of prior exposed generations. PMID:19159674

Estrogen regulation of microcephaly genes and evolution of brain sexual dimorphism in primates.

PubMed

Shi, Lei; Lin, Qiang; Su, Bing

2015-06-30

Sexual dimorphism in brain size is common among primates, including humans, apes and some Old World monkeys. In these species, the brain size of males is generally larger than that of females. Curiously, this dimorphism has persisted over the course of primate evolution and human origin, but there is no explanation for the underlying genetic controls that have maintained this disparity in brain size. In the present study, we tested the effect of the female hormone (estradiol) on seven genes known to be related to brain size in both humans and nonhuman primates, and we identified half estrogen responsive elements (half EREs) in the promoter regions of four genes (MCPH1, ASPM, CDK5RAP2 and WDR62). Likewise, at sequence level, it appears that these half EREs are generally conserved across primates. Later testing via a reporter gene assay and cell-based endogenous expression measurement revealed that estradiol could significantly suppress the expression of the four affected genes involved in brain size. More intriguingly, when the half EREs were deleted from the promoters, the suppression effect disappeared, suggesting that the half EREs mediate the regulation of estradiol on the brain size genes. We next replicated these experiments using promoter sequences from chimpanzees and rhesus macaques, and observed a similar suppressive effect of estradiol on gene expression, suggesting that this mechanism is conserved among primate species that exhibit brain size dimorphism. Brain size dimorphism among certain primates, including humans, is likely regulated by estrogen through its sex-dependent suppression of brain size genes during development.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats.

PubMed

Hawley, Wayne R; Grissom, Elin M; Moody, Nicole M; Dohanich, Gary P; Vasudevan, Nandini

2014-04-01

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the α or β isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1 μg) of estradiol 48 h and 24 h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48 h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25 μg) 48 h and 24 h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol. Copyright © 2014 Elsevier B.V. All rights reserved.

Ovarian Lipid Metabolism Modulates Circulating Lipids in Premenopausal Women.

PubMed

Jensen, Jeffrey T; Addis, Ilana B; Hennebold, Jon D; Bogan, Randy L

2017-09-01

The premenopausal circulating lipid profile may be linked to the hormonal profile and ovarian lipid metabolism. Assess how estradiol, progesterone, and ovarian lipid metabolism contributes to the premenopausal lipid profile; and evaluate the acute effects of a common hormonal oral contraceptive (OC) on circulating lipids. Experimental crossover with repeated measures. Academic hospitals. Eight healthy, regularly menstruating women. Participants underwent periodic serum sampling during a normal menstrual cycle; a standard 21-day, monophasic combined hormonal OC cycle (30 µg of ethinyl estradiol and 150 µg of levonorgestrel per day); menopause simulated by leuprolide acetate (22.5-mg depot); and an artificial menstrual cycle achieved via transdermal estradiol (50 to 300 µg/d) and vaginal micronized progesterone (100 to 300 mg/d). Primary outcomes included evaluation of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, triglycerides, and the total cholesterol to HDL cholesterol ratio. To estimate the effect of estradiol, progesterone, and ovarian lipid metabolism, all specimens except those from the OC cycle were analyzed. Subgroup analysis was conducted on the follicular and luteal phases. In a separate analysis, the effect of the OC was evaluated relative to the normal menstrual cycle. Estradiol was significantly associated with increased levels of HDL cholesterol throughout the menstrual cycle and in the follicular phase. Ovarian effects were associated with reduced lipid levels, especially during the luteal phase. The OC was associated with an increased total cholesterol to HDL cholesterol ratio and triglycerides. Previously unappreciated factors including ovarian lipid metabolism may contribute to the premenopausal lipid profile. Copyright © 2017 by the Endocrine Society

A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.

PubMed

Koninckx, P R; Spielmann, D

2005-08-01

To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen. This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28. Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium. The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.

A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol.

PubMed

Kluft, Cornelis; Endrikat, Jan; Mulder, Simone M; Gerlinger, Christoph; Heithecker, Renate

2006-04-01

In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.

Histopathologic Effects of Estrogens on Marine Fishes

EPA Science Inventory

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

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

PubMed

Bray, M J; Vick, T M; Shah, N; Anderson, S M; Rice, L W; Iranmanesh, A; Evans, W S; Veldhuis, J D

2001-07-01

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.

Sex Steroids Effects on the Molting Process of the Helminth Human Parasite Trichinella spiralis

PubMed Central

Hernández-Bello, Romel; Ramirez-Nieto, Ricardo; Muñiz-Hernández, Saé; Nava-Castro, Karen; Pavón, Lenin; Sánchez-Acosta, Ana Gabriela; Morales-Montor, Jorge

2011-01-01

We evaluated the in vitro effects of estradiol, progesterone, and testosterone on the molting process, which is the initial and crucial step in the development of the muscular larvae (ML or L1) to adult worm. Testosterone had no significative effect on the molting rate of the parasite, however, progesterone decreased the molting rate about a 50% in a concentration- and time-independent pattern, while estradiol had a slight effect (10%). The gene expression of caveolin-1, a specific gene used as a marker of parasite development, showed that progesterone and estradiol downregulated its expression, while protein expression was unaffected. By using flow citometry, a possible protein that is recognized by a commercial antiprogesterone receptor antibody was detected. These findings may have strong implications in the host-parasite coevolution, in the sex-associated susceptibility to this infection and could point out to possibilities to use antihormones to inhibit parasite development. PMID:22162638

High-dose anabolic implants are not all the same for growth and carcass traits of feedlot steers: a meta-analysis.

PubMed

Reinhardt, C D; Wagner, J J

2014-10-01

A meta-analysis of studies evaluating feedlot steer implant programs was conducted to evaluate the differential effects of anabolic implant dosage on feedlot performance and carcass traits. The effect sizes of the implant dosage of interest vs. negative controls and vs. other implant dosages on various dependent variables (ADG, F:G, DMI, dressing percentage [DP], HCW, yield grade, percentage Choice or higher, and marbling score) were calculated. Treatments used for comparisons included no implant, EST (20 mg estradiol benzoate + 200 mg progesterone, 36 mg zeranol, or 72 mg zeranol), ET120 (24 mg estradiol 17β + 120 mg trenbolone acetate [TBA]), and ET200 (28 mg estradiol benzoate + 200 mg TBA or 20 mg estradiol-17β + 200 mg TBA). In the first analysis, the 3 implant dosages were compared to negative control. A second analysis was conducted to compare ET120 vs. ET200 using only studies that included a direct comparison of these 2 dosages. The number of studies included in the analysis for each implant dosage and response variable ranged from 34 to 7. A mixed model was used to evaluate individual implant treatments; implant dosage was a fixed effect, and individual study was included as a random effect. All dosages had greater ADG, DMI, and HCW and lower F:G, percentage Choice, and marbling score vs. negative controls (P < 0.05) In the second direct comparison analysis, ET200 tended to have greater ADG (P = 0.10) and HCW (P = 0.07) and had lower F:G (P < 0.01) and percentage of carcasses grading Choice or greater (P < 0.01) vs. ET120. Differences in HCW between ET120 and ET200 diminished numerically with increasing days of implant activity (P < 0.01). All dosages of implants evaluated herein increased performance and decreased quality grade vs. negative controls. Combination implants containing estrogen (E) and 200 mg TBA have greater potency for growth promotion than implants containing E+120 mg TBA resulting in slightly greater performance.

Neonatal exposure to estradiol valerate increases dopamine content in nigrostriatal pathway during adulthood in the rat.

PubMed

Cruz, G; Riquelme, R; Espinosa, P; Jara, P; Dagnino-Subiabre, A; Renard, G M; Sotomayor-Zárate, R

2014-05-01

Research in programming has focused in the study of stimuli that affect sensitive periods of development such as prenatal and neonatal stage. We previously showed that exposure to estradiol valerate to female rats during the first 12 h of life increased catecholamine content in ventromedial-arcuatus hypothalamus of the adult rat. However, changes in others dopaminergic circuits have not been studied. The purpose of this work was to determine the neurotransmitters changes induced by neonatal estradiol valerate (0.1 mg/50 μl s. c. per rat) administration on nigrostriatal pathway of adult female rats. Sesame oil (50 μl s. c. per rat) was administered in a control parallel group. EV-1 adult rats presented effective markers of long-term estrogenization as decreased serum levels of progesterone and a reduction in the size of estrogen-sensitive organs. In the brain, neonatal estradiol valerate administration led to a significant increase in dopamine content in striatum, substantia nigra and ventral tegmental area. With respect to the contents of dopamine metabolites, only 3-methoxytyramine content increased in substantia nigra and ventral tegmental area. In addition, the content of noradrenaline increased only in striatum. Interestingly, estrogenized rats lacked locomotor activity induced by acute dose of amphetamine (1 mg/kg i. p.). Altogether, these results show that neonatal exposure to estradiol valerate permanently modified the content of monoamine neurotransmitters in nigrostriatal pathway and amphetamine-induced locomotor activity of adult female rats. This might imply that estrogenized rats could have changes in the expression of key proteins in dopaminergic regulation, as tyrosine hydroxylase and dopamine transporter. © Georg Thieme Verlag KG Stuttgart · New York.

Bisphenol A Impairs Follicle Growth, Inhibits Steroidogenesis, and Downregulates Rate-Limiting Enzymes in the Estradiol Biosynthesis Pathway

PubMed Central

Peretz, Jackye; Gupta, Rupesh K.; Singh, Jeffrey; Hernández-Ochoa, Isabel; Flaws, Jodi A.

2011-01-01

Bisphenol A (BPA) is used as the backbone for plastics and epoxy resins, including various food and beverage containers. BPA has also been detected in 95% of random urine samples and ovarian follicular fluid of adult women. Few studies have investigated the effects of BPA on antral follicles, the main producers of sex steroid hormones and the only follicles capable of ovulation. Thus, this study tested the hypothesis that postnatal BPA exposure inhibits antral follicle growth and steroidogenesis. To test this hypothesis, antral follicles isolated from 32-day-old FVB mice were cultured with vehicle control (dimethyl sulfoxide [DMSO]), BPA (4.4–440μM), pregnenolone (10 μg/ml), pregnenolone + BPA 44μM, and pregnenolone + BPA 440μM. During the culture, follicles were measured for growth daily. After the culture, media was subjected to ELISA for hormones in the estradiol biosynthesis pathway, and follicles were processed for quantitative real-time PCR of steroidogenic enzymes. The results indicate that BPA (440μM) inhibits follicle growth and that pregnenolone cotreatment was unable to restore/maintain growth. Furthermore, BPA 44 and 440μM inhibit progesterone, dehydroepiandrosterone, androstenedione, estrone, testosterone, and estradiol production. Pregnenolone cotreatment was able to increase production of pregnenolone, progesterone, and dehydroepiandrosterone and maintain androstenedione and estrone levels in BPA-treated follicles compared with DMSO controls but was unable to protect testosterone or estradiol levels. Furthermore, pregnenolone was unable to protect follicles from BPA-(44–440 μM) induced inhibition of steroidogenic enzymes compared with the DMSO control. Collectively, these data show that BPA targets the estradiol biosynthesis pathway in the ovary. PMID:20956811

Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells.

PubMed

Sun, Y; Gu, X; Zhang, E; Park, M-A; Pereira, A M; Wang, S; Morrison, T; Li, C; Blenis, J; Gerbaudo, V H; Henske, E P; Yu, J J

2014-05-15

Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. (18)F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms.

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2014 CFR

2014-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2013 CFR

2013-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2011 CFR

2011-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

Code of Federal Regulations, 2012 CFR

2012-04-01

...; not for use in dairy or beef replacement heifers. Safety and effectiveness have not been established... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... dairy or beef replacement heifers. Safety and effectiveness have not been established in veal calves. A... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Trenbolone acetate and estradiol benzoate. 522.2478 Section 522.2478 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Data describing lack of effects of 17α-ethinyl estradiol on mammary gland morphology in female mice exposed during pregnancy and lactation.

PubMed

LaPlante, Charlotte D; Vandenberg, Laura N

2017-10-01

Ethinyl estradiol (EE) is a synthetic estrogen used in pharmaceutical contraceptives. In many studies evaluating estrogenic endocrine disruptors, EE is used as a positive control for estrogenicity. However, the effects of EE often differ from the effects of other xenoestrogens, suggesting that these other compounds might act via distinct mechanisms. Reported here are data describing the effect of low doses of EE during pregnancy and lactation on the morphology of the lactating mammary gland in CD-1 mice. The data suggest that these low doses have few if any discernable effects on mammary gland morphology. Alterations to cell proliferation and the expression of estrogen receptor (ER)α were also not observed. These companion data were collected from the same females analyzed for effects of EE on maternal behavior and brain recently published in Reproductive Toxicology (Catanese & Vandenberg, 2017).

A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism

PubMed Central

2014-01-01

Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure. Study design 20 prepubertal adolescent females with ovarian failure, ages 12–18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test. Results Mean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone. Conclusions Treatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required. Trial registration Clinical Trials Identifier: NCT01023178. PMID:24982681

Changes in salivary estradiol predict changes in women's preferences for vocal masculinity.

PubMed

Pisanski, Katarzyna; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Feinberg, David R; Jones, Benedict C

2014-08-01

Although many studies have reported that women's preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women's masculinity preferences tested only judgments of men's facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men's faces were related to either women's estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women's salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men's voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women's preferences for vocal masculinity. These results complement other recent research implicating estradiol in women's mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women's voice preferences directly to measured hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Social regulation of plasma estradiol concentration in a female anuran

PubMed Central

Lynch, Kathleen S.; Wilczynski, Walter

2008-01-01

The behavior of an individual within a social aggregation profoundly influences behavior and physiology of other animals within the aggregation in such a way that these social interactions can enhance reproductive success, survival and fitness. This phenomenon is particularly important during the breeding season when males and female must synchronize their reproductive efforts. We examined whether exposure to conspecific social cues can elevate sex steroid levels, specifically estradiol and androgens, in female túngara frogs (Physalaemus pustulosus). We compared plasma estradiol and androgen concentrations in wild-caught females before and after exposure to either natural mate choruses or random tones. After exposure to mate choruses for 10 consecutive nights, estradiol concentrations were significantly elevated whereas there was no significant elevation in estradiol concentrations in the group of females exposed to random tones for 10 nights. Plasma androgen concentrations were not significantly changed after exposure to either natural mate choruses or random tones for 10 consecutive nights. Social modulation of estradiol concentrations may be important in maintaining a female’s reproductive state while males are chorusing. To our knowledge, this is the first study to demonstrate social regulation of estradiol concentration in female anurans. PMID:16545384

Development of molecularly imprinted column-on line-two dimensional liquid chromatography for rapidly and selectively monitoring estradiol in cosmetics.

PubMed

Guo, Pengqi; Xu, Xinya; Xian, Liang; Ge, Yanhui; Luo, Zhimin; Du, Wei; Jing, Wanghui; Zeng, Aiguo; Chang, Chun; Fu, Qiang

2016-12-01

Nowadays, the illegal use of estradiol in cosmetics has caused a series of events which endangering public health seriously. Therefore, it is imperative to establish a simple, fast and specific method for monitoring the illegal use of estradiol in cosmetics. In current study, we developed a molecular imprinted monolithic column two dimensional liquid chromatography method (MIMC-2D-LC) for rapid and selective determination of estradiol in various cosmetic samples. The best polymerization, morphology, structure property, surface groups, and the adsorption performance of the prepared material were investigated. The MIMC-2D-LC was validated and successfully used for detecting estradiol in cosmetic samples with good selectivity, sensitivity, efficiency and reproducibility. The linear range of the MIMC-2D-LC for estradiol was 0.5-50μgg -1 with the limit of detection of 0.08μgg -1 . Finally, six batches of cosmetic samples obtained from local markets were tested by the proposed method. The test results showed that the illegal use of estradiol still existed in the commercially available samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Norelgestromin/ethinyl estradiol intravenous infusion formulation optimization, stability and compatibility testing: A case study to overcome polysorbate 80 interference in chromatographic analysis.

PubMed

Abdallah, Inas A; Hammell, Dana C; Hassan, Hazem E; Stinchcomb, Audra L

2016-06-05

Norelgestromin/ethinyl estradiol is a progestin/estrogen combination hormonal contraceptive indicated for the prevention of pregnancy in women. The very poor solubility and wettability of these drugs, along with their high potency (adsorption issues), give rise to difficulties in designing intravenous (IV) formulations to assess absolute bioavailability of products containing both drugs. The purpose of this study was to develop an IV formulation, evaluate its stability under different conditions and evaluate its compatibility with IV sets for potential use in absolute bioavailability studies in humans. Also, a selective high-performance liquid chromatography (HPLC) method for quantification of ethinyl estradiol and norelgestromin in polysorbate 80 matrix was developed and validated. Norelgestromin/ethinyl estradiol IV solution was prepared using sterile water for injection with 2.5% ethanol and 2.5% polysorbate 80 as a cosolvent/surfactant system to obtain a final drug solution of 25μg ethinyl estradiol and 252μg norelgestromin from a concentrated stock drug solution. The stabilities of the concentrated stock and IV solutions were assessed after storing them in the refrigerator (3.7±0.6°C) and at room temperature (19.5±0.5°C), respectively. Additional studies were conducted to examine the stability of the IV solution using an Alarias(®) low sorbing IV administration set with and without an inline filter. The solution was allowed to drip at 1mL/min over a 60min period. Samples were obtained at the beginning, middle and end of the 60min duration. The chemical stability was evaluated for up to 10 days. Norelgestromin and ethinyl estradiol concentration, purity, and degradant levels were determined using the HPLC method. The norelgestromin/ethinyl estradiol IV formulation met the chemical stability criteria when tested on day 1 through day 9 (216h). Norelgestromin concentrations assayed in stock and IV solutions were in the range of 90.0-98.5% and 90.9-98.8% after 9 days, respectively. As for ethinyl estradiol, the assayed concentrations were in the range of 91.8-100.9% and 92.7-100.8% for the stock and IV solutions, respectively. The administration set was found to be compatible with both drugs; the assayed concentrations were in the range of 99.2-100.3% for norelgestromin and 96.3-102.7% for ethinyl estradiol, but the inline filter showed some adsorption of ethinyl estradiol; where the assayed concentrations were in the range of 98.1-99.8% for norelgestromin and 95.9-97.4% for ethinyl estradiol. The present study provided evidence supporting the suitability of an intravenous formulation for norelgestromin/ethinyl estradiol using ethanol/polysorbate 80 as a cosolvent/surfactant system. Both IV and concentrated stock solutions when stored at room temperature and refrigeration, respectively, were found to be chemically stable up to 9 days. These results indicated that this formulation is chemically stable and can be used over the time period tested. This IV formulation can be used to evaluate the absolute bioavailability of products containing norelgestromin and ethinyl estradiol provided that microbial testing of the IV formulation is performed. Copyright © 2016. Published by Elsevier B.V.

Pentagastrin-induced hemoconcentration in healthy volunteers and patients with panic disorder: effect of pretreatment with ethinyl estradiol.

PubMed

Le Melledo, Jean Michel; Perez-Parada, Jorge; Morrow, Jarret; Bellavance, Francois; Lara, Nathalie; Jahandar, Farideh; Granger, Robert; Tait, Glendon; McManus, Karen

2011-01-01

Panic disorder has been associated with both an increased risk of coronary events as well as an increased risk of stroke. Hemoconcentration, with both a decrease in plasma volume and an increase in plasma viscosity, is a possible contributor to the risk of acute ischemic events. Our objectives were to demonstrate the process of hemoconcentration in response to induced panic symptoms and to assess the effect of pretreatment with ethinyl estradiol on panic-induced hemoconcentration. Fifteen male patients with panic disorder and 10 male healthy volunteers were included in a double-blind cross-over placebo-controlled design consisting of two injections of pentagastrin following randomized pretreatment with placebo and ethinyl estradiol. Plasma levels of hematocrit and hemoglobin were assessed at baseline and post-injections, and used to calculate an indirect estimation of the change in plasma volume. Pentagastrin-induced panic symptoms were associated with a mean decrease in plasma volume of 4.8% in the placebo pretreatment condition. Pretreatment with ethinyl estradiol attenuated this effect. The acute hemoconcentration observed in relation to pentagastrin-induced panic symptoms may be relevant to the increased risk of stroke and acute coronary events found in patients with panic disorder.

Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development.

PubMed

Carrillo, Beatriz; Collado, Paloma; Díaz, Francisca; Chowen, Julie A; Pérez-Izquierdo, Mª Ángeles; Pinos, Helena

2017-07-11

Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.

Methoxsalen supplementation attenuates bone loss and inflammatory response in ovariectomized mice.

PubMed

Ham, Ju Ri; Choi, Ra-Yeong; Yee, Sung-Tae; Hwang, Yun-Ho; Kim, Myung-Joo; Lee, Mi-Kyung

2017-12-25

Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants that has many known biofunctions; however, its effects on osteoporosis and related mechanisms are not clear. This study examined whether MTS exhibited preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet), and OVX with estradiol (0.03 μg/day, s.c). After 6 weeks, MTS supplementation significantly increased femur bone mineral density and bone surface along with bone surface/total volume. MTS significantly elevated the levels of serum formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that MTS suppressed osteoclast numbers and formation in femur tissues compared with the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis-related genes (Runx-2, osterix, osteocalcin, and Alp) expression, whereas it significantly down-regulated inflammatory genes (Nfκb and Il6) expression in femur tissue compared with the OVX group. These results indicate that MTS supplementation effectively prevented OVX-induced osteoporosis via enhancement of bone formation and suppression of inflammatory response in OVX mice. Our study provides valid scientific information regarding the development and application of MTS as a food ingredient, a food supplement or an alternative agent for preventing postmenopausal osteoporosis. Copyright © 2017 Elsevier B.V. All rights reserved.

A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism.

PubMed

Shah, Sejal; Forghani, Nikta; Durham, Eileen; Neely, E Kirk

2014-01-01

Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure. 20 prepubertal adolescent females with ovarian failure, ages 12-18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test. Mean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone. Treatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients. OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls, but larger prospective randomized trials are required. NCT01023178.

Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells.

PubMed

Sharma, Geetanjali; Prossnitz, Eric R

2011-08-01

Sexual dimorphism and supplementation studies suggest an important role for estrogens in the amelioration of glucose intolerance and diabetes. Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. The results of this study suggest that the activation of downstream signaling pathways by the GPER-selective ligand G-1 could represent a novel therapeutic strategy in the treatment of diabetes.

Progesterone and estradiol profiles in different reproductive stages of captive collared peccary (Pecari tajacu) females assessed by fecal metabolites.

PubMed

Ahuja-Aguirre, Concepción; López-deBuen, Lorena; Rojas-Maya, Susana; Hernández-Cruz, Bertha C

2017-05-01

The study determined the fecal progesterone and estradiol profiles in different reproductive stages of captive collared peccary (Pecari tajacu) females from eastern Mexico. Fifteen adult females were included. At the start of the study the females were either pregnant (early, mid, or late pregnancy), lactating, or non-lactating of unknown pregnancy status. Feces from each female were collected once a week during nine consecutive months to determine concentrations of fecal progesterone and estradiol metabolites using ELISA. Progesterone was similar in early (2048±285ng/g), mid (2254±274ng/g), and late pregnancy (2491±374ng/g), and in early-pregnant and non-lactating females (1154±274ng/g). Progesterone in lactating females (442±255ng/g) was lower than in females at any stage of pregnancy, but was similar to non-lactating females. Overall progesterone in pregnant females (2229±173ng/g) was higher than in lactating and non-lactating females together (772±189ng/g). Estradiol was similar in early (66±8ng/g), mid (83±9ng/g), late pregnant (109±15ng/g), and non-lactating females (64±9ng/g). Estradiol in lactating females (34±8ng/g) was similar to estradiol in early-pregnant and non-lactating females, but was lower than in females in late and mid pregnancy. Overall estradiol in pregnant females (79±6ng/g) was similar to non-lactating females, but higher than in lactating females. The progesterone and estradiol profiles of captive collared peccary females at different reproductive stages were determined by assessing concentrations of fecal hormone metabolites. Copyright © 2017 Elsevier B.V. All rights reserved.

The mechanism of Cordyceps sinensis and strontium in prevention of osteoporosis in rats.

PubMed

Qi, Wei; Wang, Pu-jie; Guo, Wen-jun; Yan, Ya-bo; Zhang, Yang; Lei, Wei

2011-10-01

The effects of Cordyceps sinensis (Caterpillar fungus) and strontium ranelate on ovariectomized osteopenic rats was studied in this paper. After the rats were treated orally with C. sinensis, strontium, and C. sinensis rich in strontium ranelate (CSS) respectively, serum alkaline phosphatase (ALP), tartarate-resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine, C-terminal crosslinked telopeptides of collagen type I (CTX), estradiol, and interferon-gamma (IFN-γ) level were examined. The beneficial effects of CSS on improvement of osteoporosis in rats were attributable mainly to decrease ALP activity, TRAP activity, CTX level, and IFN-γ level. At the same time, CSS also increase the OC and estradiol level in ovariectomized osteopenic rats. This study demonstrates the value of C. sinensis rich in strontium ranelate in the management of postmenopausal osteoporosis in humans.

Estrogenic plant consumption predicts red colobus monkey (Procolobus rufomitratus) hormonal state and behavior

PubMed Central

Wasserman, Michael D.; Chapman, Colin A.; Milton, Katharine; Gogarten, Jan F.; Wittwer, Dan J.; Ziegler, Toni E.

2012-01-01

Numerous studies have examined the effects of anthropogenic endocrine disrupting compounds; however, very little is known about the effects of naturally occurring plant-produced estrogenic compounds (i.e., phytoestrogens) on vertebrates. To examine the seasonal pattern of phytoestrogen consumption and its relationship to hormone levels (407 fecal samples analyzed for estradiol and cortisol) and social behavior (aggression, mating, and grooming) in a primate, we conducted an 11-month field study of red colobus (Procolobus rufomitratus) in Kibale National Park, Uganda. The percent of diet from estrogenic plants averaged 10.7% (n = 45 weeks; range: 0.7 – 32.4%). Red colobus fed more heavily on estrogenic Millettia dura young leaves during weeks of higher rainfall, and the consumption of this estrogenic item was positively correlated to both their fecal estradiol and cortisol levels. Social behaviors were related to estradiol and cortisol levels, as well as the consumption of estrogenic plants and rainfall. The more the red colobus consumed estrogenic plants the higher their rates of aggression and copulation and the lower their time spent grooming. Our results suggest that the consumption of estrogenic plants has important implications for primate health and fitness through interactions with the endocrine system and changes in hormone levels and social behaviors. PMID:23010620

ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

PubMed Central

Frick, Karyn M.

2009-01-01

The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

17β-Estradiol induces cyto-genotoxicity on blood cells of common carp (Cyprinus carpio).

PubMed

Orozco-Hernández, Luis; Gutiérrez-Gómez, Adriana Andrea; SanJuan-Reyes, Nely; Islas-Flores, Hariz; García-Medina, Sandra; Galar-Martínez, Marcela; Dublán-García, Octavio; Natividad, Reyna; Gómez-Oliván, Leobardo Manuel

2018-01-01

17β-Estradiol, a natural hormone present at high concentrations in aquatic ecosystems, affects and modifies endocrine function in animals. In recent years research workers have expressed concern over its potential effects on aquatic organisms; however, little is known about its capacity to induce genetic damage or the pro-apoptotic effects of such damage on fish. Therefore, this study aimed to evaluate 17β-estradiol-induced cyto-genotoxicity in blood cells of the common carp Cyprinus carpio exposed to different concentrations (1 ng, 1 μg and 1 mg L -1 ). Peripheral blood samples were collected and evaluated by comet assay, micronucleus test, determination of caspase-3 activity and TUNEL assay at 12, 24, 48, 72 and 96 h of exposure. Increases in frequency of micronuclei, TUNEL-positive cells and caspase-3 activity were observed, particularly at the highest concentration. In contrast, the comet assay detected significant increases at 24 and 96 h with the 1 μg and 1 ng L -1 concentrations respectively. The set of assays used in the present study constitutes a reliable early warning biomarker for evaluating the toxicity induced by this type of emerging contaminants on aquatic species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypothalamic interaction with the mesolimbic DA system in the control of the maternal and sexual behaviors in rats.

PubMed

Stolzenberg, Danielle S; Numan, Michael

2011-01-01

The medial preoptic area (MPOA) of the hypothalamus regulates maternal behavior, male sexual behavior, and female sexual behavior. Functional neuroanatomical evidence indicates that the appetitive aspects of maternal behavior are regulated through MPOA interactions with the mesolimbic dopamine (DA) system; a major focus of this review is to explore whether or not the MPOA participates in the appetitive aspects of sexual behavior via its interaction with the mesolimbic DA system. A second focus of this review is to examine the extent to which estradiol interactions with DA within this circuit regulate all three reproductive behaviors. One mechanism through which estradiol activates male sexual behavior is through the potentiation of DA activity in the MPOA. In the hypothalamus, estradiol has also been found to act in concert with DA, through the activation of similar intracellular signaling pathways, in order to stimulate female sexual behavior. Finally, recent evidence suggests that some effects of estradiol are mediated by direct action of estradiol on the mesolimbic DA system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison of desogestrel/ethinyl estradiol plus spironolactone versus cyproterone acetate/ethinyl estradiol in the treatment of polycystic ovary syndrome: a randomized controlled trial.

PubMed

Leelaphiwat, Supatra; Jongwutiwes, Theerayut; Lertvikool, Srithean; Tabcharoen, Chotika; Sukprasert, Matchuporn; Rattanasiri, Sasivimol; Weerakiet, Sawaek

2015-03-01

To compare the effects of ethinyl estradiol (EE) 30 mcg/desogestrel 150 mcg plus spironolactone 25 mg/day (group A) versus EE 35 mcg/cyproterone acetate 2 mg (group B) on hyperandrogenism and metabolism in PCOS. This was a randomized clinical study. Eighteen women in groups A and B received medications for three cycles. Acne score, androgens and metabolic parameters were assessed before and after treatment. One and two women in groups A and B, respectively, were excluded from the study. Both groups had significantly decreased acne score and free androgen index, and increased sex hormone-binding globulin levels. Cholesterol and high-density lipoprotein were significantly increased in group B, and androstenedione was significantly decreased in group A. The regular withdrawal bleeding was obtained in both groups. Both regimens had quite similar efficacy on hyperandrogenism after three cycles of therapy and without any changes in metabolic parameters. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Effects of estradiol on incorporation of new cells in the developing zebra finch song system: potential relationship to expression of ribosomal proteins L17 and L37.

PubMed

Tang, Yu Ping; Wade, Juli

2009-06-01

Mechanisms regulating masculinization of the zebra finch song system are unclear; both estradiol and sex-specific genes may be important. This study was designed to investigate relationships between estrogen and ribosomal proteins (RPL17 and RPL37; sex-linked genes) that exhibit greater expression in song control nuclei in juvenile males than females. Four studies on zebra finches were conducted using bromodeoxyuridine (BrdU) injections on posthatching days 6-10 with immunohistochemistry for the ribosomal proteins and the neuronal marker HuC/D at day 25. Volumes of brain regions were also assessed in Nissl-stained tissue. Most BrdU+ cells expressed RPL17 and RPL37. The density and percentage of cells co-expressing BrdU and HuC/D was greatest in Area X. The density of BrdU+ cells in Area X (or its equivalent) and the percentage of these cells that were neurons were greater in males than females. In RA and HVC, total BrdU+ cells were increased in males. A variety of effects of estradiol were also detected, including inducing an Area X in females with a masculine total number of BrdU+ cells, and increasing the volume and percentage of new neurons in the HVC of females. The same manipulation in males decreased the density of BrdU+ cells in Area X, total number of BrdU+ cells in RA, and density of new neurons in HVC and RA. These data are consistent with the idea that RPL17, RPL37, and estradiol might all influence sexual differentiation, perhaps with the hormone and proteins interacting, such that an appropriate balance is required for normal development.

Effects of Estradiol on Incorporation of New Cells in the Developing Zebra Finch Song System: Potential Relationship to Expression of Ribosomal Proteins L17 and L37

PubMed Central

Tang, Yu Ping; Wade, Juli

2009-01-01

Mechanisms regulating masculinization of the zebra finch song system are unclear; both estradiol and sex-specific genes may be important. This study was designed to investigate relationships between estrogen and ribosomal proteins (RPL17 and RPL37; sex-linked genes) that exhibit greater expression in song control nuclei in juvenile males than females. Four studies on zebra finches were conducted using bromodeoxyuridine (BrdU) injections on posthatching days 6-10 with immunohistochemistry for the ribosomal proteins and the neuronal marker HuC/D at day 25. Volumes of brain regions were also assessed in Nissl-stained tissue. Most BrdU+ cells expressed RPL17 and RPL37. The density and percentage of cells co-expressing BrdU and HuC/D was greatest in Area X. The density of BrdU+ cells in Area X (or its equivalent) and the percentage of these cells that were neurons were greater in males than females. In RA and HVC, total BrdU+ cells were increased in males. A variety of effects of estradiol were also detected, including inducing an Area X in females with a masculine total number of BrdU+ cells, and increasing the volume and percentage of new neurons in the HVC of females. The same manipulation in males decreased the density of BrdU+ cells in Area X, total number of BrdU+ cells in RA, and density of new neurons in HVC and RA. These data are consistent with the ideas that RPL17, RPL37, and estradiol might all influence sexual differentiation, perhaps with the hormone and proteins interacting, such that an appropriate balance is required for normal development. PMID:19373862

Estradiol regulates expression of miRNAs associated with myogenesis in rainbow trout

USDA-ARS?s Scientific Manuscript database

17-Estradiol (E2) is a steroid hormone that negatively affects muscle growth in rainbow trout, but the mechanism associated with this response is not fully understood. To better characterize the effects of E2 on muscle, we identified differentially regulated microRNAs (miRNAs) and muscle atrophy-rel...

COMPARATIVE ESTROGENICITY OF ESTRADIOL, ETHYNYL ESTRADIOL AND DIETHYLSTILBESTROL IN AN IN VIVO, MALE SHEEPSHEAD MINNOW (CYPRINODON VARIEGATUS), VITELLOGENIN BIOASSAY

EPA Science Inventory

An in vivo bioassay for vitellogenin (VTG) synthesis was developed to screen individual chemicals or mixtures of chemicals for potentially estrogenic effects in a marine teleost model. An enzyme-linked immunosorbent assay (ELISA) was used to quantitate VTG synthesis in male sheep...

Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions.

PubMed

Piccinato, Carla A; Montrezor, Luis H; Collares, Cristhianna A V; Vireque, Alessandra A; Rosa e Silva, Alzira A M

2012-11-22

Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE) in the steroid hormone profile of a serum-free granulosa cell (GC) culture system in the context of follicular development and dominance. Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose-response study. The highest tested concentration of NE (10 (-7) M) resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone production was further investigated by incubating GCs with propranolol (10 (-8) M), a non-selective beta-adrenergic antagonist. The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation.

Local oestrogen for vaginal atrophy in postmenopausal women.

PubMed

Suckling, J; Lethaby, A; Kennedy, R

2003-01-01

Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the estradiol releasing ring). The objective of this review is to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy. We searched the Cochrane Menstrual Disorders and Subfertility Group register of trials (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966-January 2003), EMBASE (1980-January 2003), Current Contents (1993-January 2003), Biological Abstracts (1969-2002), Social Sciences Index (1980-January 2003), PsycINFO (1972-February 2003), CINAHL (1982-January 2003) and reference list of articles. We also contacted manufacturers and researchers in the field. The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis. Twenty nine trials were identified, of these 13 were excluded. Trials were assessed for quality and two reviewers extracted data independently. Ratios for dichotomous and means for continuous outcomes were estimated. Outcomes analysed were included under the headings of efficacy, safety and acceptability. Sixteen trials with 2129 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy with various outcome measures. When comparing efficacy of oestrogenic preparations (in the form of creams, pessaries, tablets and the estradiol releasing vaginal ring) with each other in relieving the symptoms of vaginal atrophy, results indicated significant differences favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and six looked at adverse effects. One trial showed significant adverse effects of cream (conjugated equine oestrogen) when compared to tablets (estradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by progestagen challenge test in the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (estradiol). Nine studies compared acceptability to the participants by comparing comfort of product, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the estradiol releasing vaginal ring. Creams, pessaries, tablets and the estradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects noted following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the estradiol releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing-Part 2.

PubMed

Brufani, Mario; Rizzi, Nicoletta; Meda, Clara; Filocamo, Luigi; Ceccacci, Francesca; D'Aiuto, Virginia; Bartoli, Gabriele; Bella, Angela La; Migneco, Luisa M; Bettolo, Rinaldo Marini; Leonelli, Francesca; Ciana, Paolo; Maggi, Adriana

2017-05-31

Estrogen deprivation is associated with delayed healing, while estrogen replacement therapy (ERT) accelerates acute wound healing and protects against development of chronic wounds. However, current estrogenic molecules have undesired systemic effects, thus the aim of our studies is to generate new molecules for topic administration that are devoid of systemic effects. Following a preliminary study, the new 17β-estradiol derivatives 1 were synthesized. The estrogenic activity of these novel compounds was evaluated in vitro using the cell line ERE-Luc B17 stably transfected with an ERE-Luc reporter. Among the 17β-estradiol derivatives synthesized, compounds 1e and 1f showed the highest transactivation potency and were therefore selected for the study of their systemic estrogenic activity. The study of these compounds in the ERE-Luc mouse model demonstrated that both compounds lack systemic effects when administered in the wound area. Furthermore, wound-healing experiments showed that 1e displays a significant regenerative and anti-inflammatory activity. It is therefore confirmed that this class of compounds are suitable for topical administration and have a clear beneficial effect on wound healing.

Predictive value of repeated measurements of luteal progesterone and estradiol levels in patients with intrauterine insemination and controlled ovarian stimulation.

PubMed

Bakas, Panagiotis; Simopoulou, Maria; Giner, Maria; Drakakis, Petros; Panagopoulos, Perikles; Vlahos, Nikolaos

2017-10-01

The objective of this study is to assess if the difference of repeated measurements of estradiol and progesterone during luteal phase predict the outcome of intrauterine insemination. Prospective study. Reproductive clinic. 126 patients with infertility. Patients underwent controlled ovarian stimulation with recombinant FSH (50-150 IU/d). The day of IUI patients were given p.o natural micronized progesterone in a dose of 100 mg/tds. The area under the receiver characteristic operating curve (ROC curve) in predicting clinical pregnancy for % change of estradiol level on days 6 and 10 was 0.892 with 95% CI: 0.82-0.94. A cutoff value of change > -29.5% had a sensitivity of 85.7 with a specificity of 90.2. The corresponding ROC curve for % change of progesterone level was 0.839 with 95% CI: 0.76-0.90. A cutoff value of change > -33% had a sensitivity of 85 with a specificity of 75. The % change of estradiol and progesterone between days 6 and 10 has a predictive ability of pregnancy after IUI with COS of 89.2% and 83.4%, respectively. The addition of % of progesterone to % change of estradiol does not improve the predictive ability of % estradiol and should not be used.

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.

Effects of ethinyl estradiol and ibuprofen compared to placebo on endometrial bleeding, cervical mucus and the postcoital test in levonorgestrel subcutaneous implant users.

PubMed

Archer, David F; Philput, Christine B; Levine, Adam S; Cullins, Vanessa; Stovall, Thomas G; Bacon, Janice; Weber, Margaret E

2008-08-01

The study was conducted to evaluate ethinyl estradiol (EE) or ibuprofen (IBU) compared to placebo (PL) on spotting and bleeding (S/B) and a postcoital test (PCT) in women using the levonorgestrel subcutaneous implant. Women experiencing excessive S/B were enrolled in a multicenter prospective randomized study using EE, IBU or PL. Duration of S/B and a PCT were evaluated. Statistical analysis used a general linear model procedure with Duncan's multiple range tests for individual variables. One hundred seven women were evaluated, and there was no difference in the duration of bleeding among the three therapies, while the mean number of spotting days were 1.8 for EE and 2.8 for PL (p=.04). There was no effect of IBU on S/B. No effect on cervical mucus or sperm was found between treatments. There was a decrease in spotting but no effect on bleeding with EE compared to PL.

Effectiveness, tolerability and acceptance of an oral estradiol/levonorgestrel formulation for the treatment of menopausal complaints: a non-interventional observational study over six cycles of 28 days.

PubMed

Rouskova, Daniela; Mittmann, Katrin; Schumacher, Ulrike; Dietrich, Horst; Zimmermann, Thomas

2014-10-01

Use of hormone therapy for menopausal complaints is a subject of controversy and increased uncertainty and concerns. This non-interventional study aimed to investigate a marketed oral formulation containing 1 mg estradiol and 0.04 mg levonorgestrel for continuous treatment of menopausal symptoms for approximately 6 months in women visiting gynecological practices in Germany. Changes in the menopause rating scale (MRS) total and sub-domain scores after three and six 28-d cycles served as primary endpoint. Skin- and hair-related complaints, quality of sexual life and subjective satisfaction with the treatment were assessed. Adverse drug reactions (ADRs), adverse events (AEs) and vaginal bleeding were evaluated. MRS scores improved significantly above 5 points of clinical relevance as compared to baseline (n = 736, p < 0.0001). Skin- and hair-related symptoms abated; quality of sexual life improved. AEs were registered in 9.9% of the participants. No unexpected ADRs were reported. Bleeding episodes consistently decreased; >75% of the subjects were amenorrheic throughout the study. Medication's effectiveness and tolerability was rated very good/good by >80% of the participants, who also continued treatment. This estradiol/low-dose levonorgestrel formulation safely alleviates menopausal symptoms in peri- and postmenopausal women with add-on benefits regarding dermatological and sexual life complaints.

Bulk derivatization and direct injection of human cerebrospinal fluid for trace-level quantification of endogenous estrogens using trap-and-elute liquid chromatography with tandem mass spectrometry.

PubMed

Fan, Hui; Papouskova, Barbora; Lemr, Karel; Wigginton, Jane G; Schug, Kevin A

2014-08-01

Although there are existing methods for determining estrogen in human bodily fluids including blood plasma and serum, very little information is available regarding estrogen levels in human cerebrospinal fluid (CSF), which is critical to assess in studies of neuroprotective functions and diffusion of neuroprotective estrogens across the blood-brain barrier. To address this problem, a liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of four endogenous estrogens (estrone, 17α-estradiol, 17β-estradiol, and estriol) in human CSF was developed. An aliquot (300 μL) of human CSF was bulk derivatized using dansyl chloride in the sample and 10 μL was directly injected onto a restricted-access media trap column for protein removal. No off-line sample extraction or cleanup was needed. The limits of detection of estrone, 17α-estradiol, 17β-estradiol, and estriol were 17, 28, 13, and 30 pg/mL, respectively, which is in the parts-per-trillion regime. The method was then applied to human CSF collected from ischemic trauma patients. Endogenous estrogens were detected and quantified, demonstrating the effectiveness of this method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice.

PubMed

Desroziers, Elodie; Brock, Olivier; Bakker, Julie

2017-04-01

We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during development, inducing both a male-and female-typical pattern of PR expression in the mouse hypothalamus. In the present study, we took advantage of a newly developed PR antagonist (ZK 137316) to determine whether PR contributes to either male- or female-typical sexual differentiation. Thus groups of male and female C57Bl/6j mice were treated with ZK 137316 or OIL as control: males were treated neonatally (P0-P10), during the critical period for male sexual differentiation, and females were treated prepubertally (P15-P25), during the critical period for female sexual differentiation. In adulthood, mice were tested for sexual behavior. In males, some minor effects of neonatal ZK treatment on sexual behavior were observed: latencies to the first mount, intromission and ejaculation were decreased in neonatally ZK treated males; however, this effect disappeared by the second mating test. By contrast, female mice treated with ZK during the prepubertal period showed significantly less lordosis than OIL-treated females. Mate preferences were not affected in either males or females treated with ZK during development. Taken together, these results suggest a role for PR and thus perhaps progesterone in the development of lordosis behavior in female mice. By contrast, no obvious role for PR can be discerned in the development of male sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

Proliferative effects of estradiol- or ethinylestradiol-progestogen combinations on human breast cancer cells in an intermitted and a long-term regimen.

PubMed

Merki-Feld, G S; Seeger, H; Mueck, A O

2012-06-01

Currently the use of natural estradiol as estrogenic component in oral contraceptives is more and more extended. It is unknown whether the application of this estrogen is associated with a different breast cancer risk as compared to the common use of the synthetic ethinylestradiol. In addition with the intention to reduce menstruation associated symptoms and bleeding periods an extended-cycle regimen is currently considered. In the present in vitro work, we have compared the effect of these different estrogenic compounds and the different treatment regimens on breast cancer risk. Human breast cancer cells (ZR75-1 and HCC1500) were incubated with equimolar concentrations of estradiol or ethinylestradiol combined with various progestogens, dienogest, drospirenone, keto-desogestrel, levonorgestrel, and nomegestrel. Usual and extended cycle was mimicked by incubation periods of 3 days with 1 day hormones off and 4 days, respectively. Molecular markers for proliferation and apoptosis were investigated by Western blot. In both cell lines estradiol and ethinylestradiol elicited a significant increase in the proliferation rate without difference between the 2 estrogens. The effect in the long-term cycle tended to be more pronounced than in the intermitted cycle. Progestogen addition most significantly reduced the estrogen-induced proliferation rate. The molecular markers were influenced by the progestogens mostly in the same manner, reducing the proliferation/apoptosis rate. Our results indicate that both estrogenic based combinations with progestogens may not increase breast cancer risk independent from the regimen, intermitted or long-term cycle. However clinical studies are necessary to prove these in vitro results. © Georg Thieme Verlag KG Stuttgart · New York.

Do changes in sex steroid hormones precede or follow increases in body weight during the menopause transition? Results from the Study of Women's Health Across the Nation.

PubMed

Wildman, Rachel P; Tepper, Ping G; Crawford, Sybil; Finkelstein, Joel S; Sutton-Tyrrell, Kim; Thurston, Rebecca C; Santoro, Nanette; Sternfeld, Barbara; Greendale, Gail A

2012-09-01

Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. The objective of the study was to characterize the potential reciprocal nature of the associations between sex hormones and their binding protein with waist circumference in midlife women. The study included 1528 women (mean age 46 yr) with 9 yr of follow-up across the menopause transition from the observational Study of Women's Health Across the Nation. Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. Current waist circumference predicted future SHBG, testosterone, and FSH but not vice versa. For each SD higher current waist circumference, at the subsequent visit SHBG was lower by 0.04-0.15 SD, testosterone was higher by 0.08-0.13 SD, and log(2) FSH was lower by 0.15-0.26 SD. Estradiol results were distinct from those above, changing direction across the menopause transition. Estradiol and waist circumference were negatively associated in early menopausal transition stages and positively associated in later transition stages (for each SD higher current waist circumference, future estradiol was lower by 0.15 SD in pre- and early perimenopause and higher by 0.38 SD in late peri- and postmenopause; P for interaction <0.001). In addition, they appeared to be reciprocal, with current waist circumference associated with future estradiol and current estradiol associated with future waist circumference. However, associations in the direction of current waist circumference predicting future estradiol levels were of considerably larger magnitude than the reverse. These Study of Women's Health Across the Nation data suggest that the predominant temporal sequence is that weight gain leads to changes in sex steroids rather than vice versa.

Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

PubMed

Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

2017-11-01

Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

Gender Differences in Subjective and Physiological Responses to Caffeine and the Role of Steroid Hormones

PubMed Central

Ziegler, Amanda M.

2011-01-01

Background We have shown previously that male and female adolescents differ in their responses to caffeine, but to date, the mechanisms underlying these gender differences are unknown. Objective The purpose of this study was to test the hypothesis that differences in circulating steroid hormones mediate gender differences in response to caffeine. Methods Subjective and physiological responses to caffeine were tested in adolescents using a double-blind, placebo controlled, crossover design. Participants were tested every 2 weeks for 8 weeks and received placebo and caffeine (2 mg/kg) twice each. Females were tested with placebo and caffeine in each phase of their menstrual cycle. Salivary concentrations of testosterone, estradiol, and progesterone were also measured. Results Males showed greater positive subjective effects than females. In females, higher levels of estradiol were associated with little or no subjective responses to caffeine, but lower levels of estradiol were associated with negative subjective responses to caffeine relative to placebo. There were gender differences in cardiovascular responses to caffeine, with males showing greater decreases in heart rate after caffeine administration than females, but females showing greater increases in diastolic blood pressure than males after caffeine administration. These gender differences may be related to steroid hormone concentrations. Blood pressure responses to caffeine were lower in males when estradiol was high, but higher in females when estradiol was high. Conclusions When taken together, these findings suggest that males and females differ in their responses to caffeine and that these differences may be mediated by changes in circulating steroid hormones. PMID:24761262

Interactive Effects of Dopamine Baseline Levels and Cycle Phase on Executive Functions: The Role of Progesterone.

PubMed

Hidalgo-Lopez, Esmeralda; Pletzer, Belinda

2017-01-01

Estradiol and progesterone levels vary along the menstrual cycle and have multiple neuroactive effects, including on the dopaminergic system. Dopamine relates to executive functions in an "inverted U-shaped" manner and its levels are increased by estradiol. Accordingly, dopamine dependent changes in executive functions along the menstrual cycle have been previously studied in the pre-ovulatory phase, when estradiol levels peak. Specifically it has been demonstrated that working memory is enhanced during the pre-ovulatory phase in women with low dopamine baseline levels, but impaired in women with high dopamine baseline levels. However, the role of progesterone, which peaks in the luteal cycle phase, has not been taken into account previously. Therefore, the main goals of the present study were to extend these findings (i) to the luteal cycle phase and (ii) to other executive functions. Furthermore, the usefulness of the eye blink rate (EBR) as an indicator of dopamine baseline levels in menstrual cycle research was explored. 36 naturally cycling women were tested during three cycle phases (menses-low sex hormones; pre-ovulatory-high estradiol; luteal-high progesterone and estradiol). During each session, women performed a verbal N-back task, as measure of working memory, and a single trial version of the Stroop task, as measure of response inhibition and cognitive flexibility. Hormone levels were assessed from saliva samples and spontaneous eye blink rate was recorded during menses. In the N-back task, women were faster during the luteal phase the higher their progesterone levels, irrespective of their dopamine baseline levels. In the Stroop task, we found a dopamine-cycle interaction, which was also driven by the luteal phase and progesterone levels. For women with higher EBR performance decreased during the luteal phase, whereas for women with lower EBR performance improved during the luteal phase. These findings suggest an important role of progesterone in modulating dopamine-cycle interactions. Additionally, we identified the eye blink rate as a non-invasive indicator of baseline dopamine function in menstrual cycle research.

Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

PubMed Central

Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

2011-01-01

Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process. PMID:21464994

Dopamine-induced apoptosis of lactotropes is mediated by the short isoform of D2 receptor.

PubMed

Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

2011-03-25

Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

Vinclozolin modulates hepatic cytochrome P450 isoforms during pregnancy.

PubMed

de Oca, Félix Genoveva García-Montes; López-González, Ma de Lourdes; Escobar-Wilches, Derly Constanza; Chavira-Ramírez, Roberto; Sierra-Santoyo, Adolfo

2015-06-01

Vinclozolin (V) is classified as a potent endocrine disruptor. The aim of the present study was to determine the effects of V on rat liver CYP regulation and on serum levels of testosterone and estradiol during pregnancy. Pregnancy decreased the liver total CYP content by 65%, enzyme activities of MROD, PROD, and PNPH, and testosterone hydroxylation activities, as well as the protein content of CYP2A and 3A. V exposure remarkably induced the protein content and enzyme activities of CYP1A, 2A, 2B and 3A subfamilies. Testosterone and estradiol were affected in an opposite manner, provoking a 3.5-fold increase in the estradiol/testosterone ratio. These results suggest that V could regulate the hepatic CYP expression through interaction with receptors and coactivators involved in its expression and may play an important role in hormonal balance during pregnancy. In addition, the results may also contribute to understanding the toxicity of V by in utero exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines.

PubMed

Yang, Lingyun; Huang, Feng; Mei, Jiandong; Wang, Xun; Zhang, Qiuyang; Wang, Hongjing; Xi, Mingrong; You, Zongbing

2017-02-01

Estrogen is a well-known oncogenic driver in endometrial (ECs) and breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1 Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in EC and BC cell lines. 17β-Estradiol (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in EC and BC cells. Coculture of T cells and cancer cells with E2 stimulation was performed to assess the functions of T cells. We found that E2 increased expression of PD-L1, but not PD-L2, protein via activation of phosphoinositide 3-kinase (PI3K)/Akt pathway in Ishikawa and Michigan Cancer Foundation-7 (MCF-7) cells. Phosphoinositide 3-kinase and Akt inhibitors could block E2's effects. 17β-Estradiol did not increase PD-L1 mRNA transcription, but stabilized PD-L1 mRNA. 17β-Estradiol's effects were only observed in estrogen receptor α (ERα)-positive Ishikawa and MCF-7 cells, but not in ERα-negative MDA-MB-231 cells. Coculture of Ishikawa or MCF-7 cells with T cells inhibited expression of interferon-γ and interleukin-2 and increased BCL-2-interacting mediator of cell death expression in the presence of E2. This study provides the first evidence that estrogen upregulates PD-L1 protein expression in ERα-positive EC and BC cells to suppress immune functions of T cells in the tumor microenvironment, demonstrating a new mechanism of how estrogen drives cancer progression.

Progesterone and estradiol synergistically promote the lung metastasis of tuberin-deficient cells in a preclinical model of lymphangioleiomyomatosis

PubMed Central

Sun, Yang; Zhang, Erik; Lao, Taotao; Pereira, Ana M.; Li, Chenggang; Xiong, Li; Morrison, Tasha; Haley, Kathleen J.; Zhou, Xiaobo; Yu, Jane J.

2014-01-01

Lymphangioleiomyomatosis (LAM) is a female-predominant lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 hyperactivation. The gender specificity of LAM suggests that female hormones contribute to disease progression. Clinical findings indicate that estradiol exacerbates LAM behaviors and symptoms. Although hormonal therapy with progesterone has been employed, the benefit in LAM improvement has not been achieved. We have previously found that estradiol promotes the survival and lung metastasis of cells lacking tuberin in a preclinical model of LAM. In this study, we hypothesize that progesterone alone or in combination with estradiol promote metastatic behaviors of TSC2-deficient cells. In cell culture models of TSC2-deficient LAM patient-derived and rat uterine leiomyoma-derived cells, we found that progesterone treatment or progesterone plus estradiol resulted in increased phosphorylation of Akt and ERK1/2, induced the proliferation, and enhanced the migration and invasiveness. In addition, treatment of progesterone plus estradiol synergistically decreased the levels of reactive oxygen species, and enhanced cell survival under oxidative stress. In a murine model of LAM, treatment of progesterone plus estradiol promoted the growth of xenograft tumors; however, progesterone treatment did not affect the development of xenograft tumors of Tsc2-deficient cells. Importantly, treatment of progesterone plus estradiol resulted in alteration of lung morphology, and significantly increased the number of lung micrometastases of Tsc2-deficient cells compared with estradiol treatment alone. Collectively, these data indicate that progesterone increases the metastatic potential of TSC2-deficient LAM patient-derived cells in vitro and lung metastasis in vivo. Thus, targeting progesterone-mediated signaling events may have therapeutic benefit for LAM and possibly other hormonally dependent cancers. PMID:25069840

Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism.

PubMed

Klipping, Christine; Marr, Joachim

2005-06-01

To compare the effect of ethinyl estradiol 20 microg/drospirenone 3 mg (EE 20 microg/DRSP 3 mg) administered according to a 24/4 regimen with ethinyl estradiol 20 microg/desogestrel 150 microg (EE 20 microg/DSG 150 microg) administered according to the conventional 21/7 regimen on lipid, carbohydrate and hemostatic parameters. In this open-label study, healthy women were randomized to EE 20 microg/DRSP 3 mg or EE 20 microg/DSG 150 microg for seven cycles. Mean differences in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels at cycle 7 compared to baseline were assessed. Secondary variables included changes in other lipid, hemostatic and carbohydrate parameters. Both treatments increased HDL-cholesterol, but decreased LDL-cholesterol by a comparable extent. Although slightly elevated in both groups, blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7. Overall, the differences in lipid, hemostatic or carbohydrate parameters were not significant between the two treatments. EE 20 microg/DRSP 3 mg has a good safety profile comparable with EE 20 microg/DSG 150 microg.

Preclinical and clinical properties of trimegestone: a potent and selective progestin.

PubMed

Sitruk-Ware, Regine; Bossemeyer, Ronald; Bouchard, Phillipe

2007-06-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin with potent and selective properties. In preclinical studies, TMG has been shown to provide high endometrial selectivity. Further, TMG has high affinity and selectivity for the progesterone receptor and lacks the agonist effects of other steroid hormones. In clinical studies, TMG has been shown to have high endometrial safety and an improved bleeding profile along with improved tolerability compared with other progestins. In addition, TMG also does not impede the beneficial effects of estrogen, especially on bone, and does not compromise quality of life. The preclinical findings of lack of mineralocorticoid activity of TMG were supported in clinical findings, with neutral effect on body weight. Similarly, the smaller effect of TMG on the GABA-ergic (gamma-aminobutyric acid) system in preclinical studies is consistent with the improvement of central nervous system-related effects on depressed mood and sleep quality in clinical studies. Low-dose estradiol/TMG regimens provide rapid relief from menopausal symptoms, reducing the number and severity of hot flushes as effectively as 2 mg 17beta-estradiol/1 mg norethisterone acetate. Therefore, it may be concluded that TMG provides a clinically proven option in hormone therapy for both clinicians and patients.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nintasen, Rungrat; Multidisciplinary Cardiovascular Research Center; Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University

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 protectivemore » 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 was no modulation by E2 in either cell-type. In conclusion, TNF-{alpha} induced SV neointima formation, increased SMC proliferation and migration, impaired SV-EC migration and increased expression of adhesion molecules. E2 exerted distinct cell-type and function-specific modulation, the mechanisms underlying which are worthy of further detailed study.« less

Estradiol promotes pentose phosphate pathway addiction and cell survival via reactivation of Akt in mTORC1 hyperactive cells

PubMed Central

Sun, Y; Gu, X; Zhang, E; Park, M-A; Pereira, A M; Wang, S; Morrison, T; Li, C; Blenis, J; Gerbaudo, V H; Henske, E P; Yu, J J

2014-01-01

Lymphangioleiomyomatosis (LAM) is a female-predominant interstitial lung disease that can lead to respiratory failure. LAM cells typically have inactivating TSC2 mutations, leading to mTORC1 activation. The gender specificity of LAM suggests that estradiol contributes to disease development, yet the underlying pathogenic mechanisms are not completely understood. Using metabolomic profiling, we identified an estradiol-enhanced pentose phosphate pathway signature in Tsc2-deficient cells. Estradiol increased levels of cellular NADPH, decreased levels of reactive oxygen species, and enhanced cell survival under oxidative stress. Mechanistically, estradiol reactivated Akt in TSC2-deficient cells in vitro and in vivo, induced membrane translocation of glucose transporters (GLUT1 or GLUT4), and increased glucose uptake in an Akt-dependent manner. 18F-FDG-PET imaging demonstrated enhanced glucose uptake in xenograft tumors of Tsc2-deficient cells from estradiol-treated mice. Expression array study identified estradiol-enhanced transcript levels of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway. Consistent with this, G6PD was abundant in xenograft tumors and lung metastatic lesions of Tsc2-deficient cells from estradiol-treated mice. Molecular depletion of G6PD attenuated estradiol-enhanced survival in vitro, and treatment with 6-aminonicotinamide, a competitive inhibitor of G6PD, reduced lung colonization of Tsc2-deficient cells. Collectively, these data indicate that estradiol promotes glucose metabolism in mTORC1 hyperactive cells through the pentose phosphate pathway via Akt reactivation and G6PD upregulation, thereby enhancing cell survival under oxidative stress. Interestingly, a strong correlation between estrogen exposure and G6PD was also found in breast cancer cells. Targeting the pentose phosphate pathway may have therapeutic benefit for LAM and possibly other hormonally dependent neoplasms. PMID:24832603

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…

Arsenic abrogates the estrogen-signaling pathway in the rat uterus

PubMed Central

2010-01-01

Background Arsenic, a major pollutant of water as well as soil, is a known endocrine disruptor, and shows adverse effects on the female reproductive physiology. However, the exact molecular events leading to reproductive dysfunctions as a result of arsenic exposure are yet to be ascertained. This report evaluates the effect and mode of action of chronic oral arsenic exposure on the uterine physiology of mature female albino rats. Methods The effect of chronic oral exposure to arsenic at the dose of 4 microg/ml for 28 days was evaluated on adult female albino rats. Hematoxylin-eosin double staining method evaluated the changes in the histological architecture of the uterus. Circulating levels of gonadotropins and estradiol were assayed by enzyme-linked immunosorbent assay. Expression of the estrogen receptor and estrogen-induced genes was studied at the mRNA level by RT-PCR and at the protein level by immunohistochemistry and western blot analysis. Results Sodium arsenite treatment decreased circulating levels of estradiol in a dose and time-dependent manner, along with decrease in the levels of both LH and FSH. Histological evaluation revealed degeneration of luminal epithelial cells and endometrial glands in response to arsenic treatment, along with reduction in thickness of the longitudinal muscle layer. Concomitantly, downregulation of estrogen receptor (ER alpha), the estrogen-responsive gene - vascular endothelial growth factor (VEGF), and G1 cell cycle proteins, cyclin D1 and CDK4, was also observed. Conclusion Together, the results indicate that arsenic disrupted the circulating levels of gonadotropins and estradiol, led to degeneration of luminal epithelial, stromal and myometrial cells of the rat uterus and downregulated the downstream components of the estrogen signaling pathway. Since development and functional maintenance of the uterus is under the influence of estradiol, arsenic-induced structural degeneration may be attributed to the reduction in circulating estradiol levels. Downregulation of the estrogen receptor and estrogen-responsive genes in response to arsenic indicates a mechanism of suppression of female reproductive functions by an environmental toxicant that is contra-mechanistic to that of estrogen. PMID:20598115

G-protein-coupled receptor 30 mediates the effects of estrogen on endothelial cell tube formation in vitro.

PubMed

Zhou, Liyuan; Chen, Hong; Mao, Xun; Qi, Hongbo; Baker, Philip N; Zhang, Hua

2017-06-01

The placenta is the exchange organ between the mother and the fetus. The inadequate function of this organ is associated with a number of pregnancy disorders. Hypoxia and oxidative stress during placental development may induce endothelial dysfunction, resulting in the reduction in the perfusion of the placenta. During pregnancy, the levels of estrogen are increased. Decreased estrogen levels have been reported in women with preeclampsia. However, whether estrogen is involved in placental angiogenesis remains unclear. In this study, we aimed to investigate the effects of estrogen on endothelial cell tube formation and to elucidate the underlying mechanisms. For this purpose, human umbilical vein endothelial cells (HUVECs) were cultured with 17‑β‑estradiol under conditions of hypoxia/reoxygenation (H/R). The total pipe length of the tube‑like structure on endothelial cells was measured. The expression levels of G‑protein‑coupled receptor 30 (GPR30) and endothelial nitric oxide synthase (eNOS) and Akt were also measured in the endothelial cells following treatment with 17‑β‑estradiol under H/R conditions by western blot analysis and immunostaining. We found that the total pipe length of the tube‑like structure on endothelial cells was significantly reduced. This reduction was reversed by treatment with 17‑β‑estradiol. The expression of GPR30 in endothelial cells was significantly increased following treatment with 17‑β‑estradiol under H/R conditions. Furthermore, the levels of eNOS and Akt in endothelial cells were also significantly increased following treatment with 17-β-estradiol under H/R conditions. The activation of eNOS was inhibited by wortmannin, an inhibitor of PI3K/Akt. Our data thus demonstrate that estrogen prevents the failure of endothelial cell tube formation induced by H/R. GPR30 plays an important role in these protective effects through the activation of eNOS and Akt in endothelial cells. Our data suggest that increased levels of estrogen are important for placental angiogenesis.

17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

ERIC Educational Resources Information Center

Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

2013-01-01

Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…

Post-weaning performance and carcass characteristics of steers implanted during the suckling phase with a combination of estradiol benzoate and trenbolone acetate

USDA-ARS?s Scientific Manuscript database

An experiment was conducted to examine the effects of administering an extended release, estradiol benzoate and trenbolone acetate combination implant to suckling steer calves on post-weaning performance and carcass characteristics. In early May, suckling steer calves were either not implanted (NONE...

17beta-Estradiol and testosterone in drainage and runoff from poultry litter applications to tilled and no-till crop land under irrigation.

PubMed

Jenkins, Michael B; Endale, Dinku M; Schomberg, Harry H; Hartel, Peter G; Cabrera, Miguel L

2009-06-01

Thirteen million [corrected] metric tons of poultry litter are produced annually by poultry producers in the U.S. Poultry litter contains the sex hormones estradiol and testosterone, endocrine disruptors that have been detected in surface waters. The objective of this study was to evaluate the potential impact of poultry litter applications on estradiol and testosterone concentrations in subsurface drainage and surface runoff in irrigated crop land under no-till and conventional-till management. We conducted an irrigation study in fall of 2001 and spring of 2002. Four treatments, no-till plus poultry litter, conventional-till plus poultry litter, no-till plus conventional fertilizer, and conventional-till plus conventional fertilizer, were evaluated. Flow-weighted concentration and load ha(-1) of the two hormones were measured in drainage and runoff. Soil concentrations of estradiol and testosterone were measured. Based on comparisons to the conventional fertilizer (and control) treatments, poultry litter did not add to the flow-weighted concentration or load ha(-1) of either estradiol or testosterone in subsurface drainage or surface runoff. Significant differences were, however, observed between tillage treatments: flow-weighted concentrations of estradiol were greater for no-till than conventional-till plots of the June irrigation; and runoff loads of both estradiol and testosterone were less from no-till than conventional-till plots for the November irrigation. Although the differences between no-till and conventional-tillage appeared to affect the hydrologic transport of both hormones, the differences appeared to have inconsequential environmental impact.

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

PubMed

Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

2009-06-01

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

Quantitative three-dimensional reconstruction: feasibility for studies of sexually dimorphic hypothalamic development in rats.

PubMed

Scallet, Andrew C; Meredith, John M

2002-01-01

The adult rat brain develops through an interplay of neuronal proliferation with programmed cell death. Sensory stimulation, as well as growth factors and steroids, may alter the balance between these competing processes. "Endocrine disrupters" (EDs) may do the same by mimicry or modulation of endogenous hormones. The sexually dimorphic nucleus (SDN) of the medial preoptic hypothalamus contains a high concentration of estrogen receptors (ERs). The SDN develops to a final adult volume, which may be used as an indication of the hormonal conditions during perinatal development. Although male rats have been repeatedly observed to have a greater adult SDN volume than female rats, variability between the actual measurements reported (both within and between laboratories) have been rather large. Exposure of female rats to testosterone (or excessive estradiol, beyond the binding capacity of alpha-fetoprotein) has been shown to masculinize them through a P450 aromatase that converts testosterone to estrogen in the SDN. Exposure of males to estradiol may feminize them at low doses through interference with the synthesis of their endogenous testosterone, which normally acts on SDN ERs following aromatization. We have employed computer-assisted reconstruction methods in order to render the SDN within the surrounding hypothalamus in 3-D for computation of its volume. Ongoing studies are investigating whether exposure through the diet to estrogenic endocrine disruptors such as genistein, nonylphenol, and ethinyl estradiol might produce effects similar to those of estradiol itself on the adult SDN.

Effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis.

PubMed

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kamińska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17 β -estradiol, it can mimic estradiol's effect and therefore is considered as a "phytoestrogen." The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development.

Effect of Formononetin on Mechanical Properties and Chemical Composition of Bones in Rats with Ovariectomy-Induced Osteoporosis

PubMed Central

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kamińska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17β-estradiol, it can mimic estradiol's effect and therefore is considered as a “phytoestrogen.” The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development. PMID:23762138

Developmental estrogen exposures and disruptions to maternal behavior and brain: Effects of ethinyl estradiol, a common positive control.

PubMed

Catanese, Mary C; Vandenberg, Laura N

2017-11-07

Due of its structural similarity to the endogenous estrogen 17β-estradiol (E2), the synthetic estrogen 17α-ethinyl estradiol (EE2) is widely used to study the effects of estrogenic substances on sensitive organs at multiple stages of development. Here, we investigated the effects of EE2 on maternal behavior and the maternal brain in females exposed during gestation and the perinatal period. We assessed several components of maternal behavior including nesting behavior and pup retrieval; characterized the expression of estrogen receptor (ER)α in the medial preoptic area (MPOA), a brain region critical for the display of maternal behavior; and measured expression of tyrosine hydroxylase, a marker for dopaminergic cells, in the ventral tegmental area (VTA), a brain region important in maternal motivation. We found that developmental exposure to EE2 induces subtle effects on several aspects of maternal behavior including time building the nest and time spent engaged in self-care. Developmental exposure to EE2 also altered ERα expression in the central MPOA during both early and late lactation and led to significantly reduced tyrosine hydroxylase immunoreactivity in the VTA. Our results demonstrate both dose- and postpartum stage-related effects of developmental exposure to EE2 on behavior and brain that manifest later in adulthood, during the maternal period. These findings provide further evidence for effects of exposure to exogenous estrogenic compounds during the critical periods of fetal and perinatal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk

PubMed Central

Brinton, Louise A.; Key, Tim J.; Kolonel, Laurence N.; Michels, Karin B.; Sesso, Howard D.; Ursin, Giske; Van Den Eeden, Stephen K.; Wood, Shannon N.; Falk, Roni T.; Parisi, Dominick; Guillemette, Chantal; Caron, Patrick; Turcotte, Véronique; Habel, Laurel A.; Isaacs, Claudine J.; Riboli, Elio; Weiderpass, Elisabete; Cook, Michael B.

2015-01-01

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers. PMID:25964249

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).” ...

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).” ...

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).” ...

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).” ...

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).” ...

Effect of estradiol and hydrocortisone on the process of peroxidation of mitochondrial membrane lipids in irradiated rat liver. [/sup 60/Co. gamma. rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saksonov, N.P.

Experiments were conducted on male, mongrel albino rats. They were exposed to /sup 60/Co ..gamma.. radiation once, in a dosage of 600 R. Estradiol and hydrocortisone were given intraperitoneally at the rate of 1 mg/kg, 2 h before irradiation or 2, 24 and 72 h after exposure. The animals were sacrificed 5 days after irradiation. These studies established that single exposure of animals to radiation in a dosage of 600 R leads to activation of processes of peroxidation of membrane lipids of the hepatic mitochondria. When estradiol is given 2 and 4 days before sacrificing, one observes acceleration of processesmore » of peroxidation of lipids without reliable change in malonic dialdehyde content. Administration of estrogen 5 days prior to sacrificing leads to a drop of malonic dialdehyde level, which is indicative of attenuation of the process of lipid peroxidation. Administration of hydrocortisone is associated with elevation of the latency period and level of peroxidation after 5 days, as compared to intact animals. Injection of this hormone 2 days before sacrificing the animals leads to attenuation and decrease in rate of peroxidation. The obtained data indicate that there are different mechanisms involved in the inhibitory effects of estradiol and hydrocortisone on peroxidation of lipids of mitochondrial membranes of the rat liver, activated by irradiation. Thus, it may be assumed that steroid hormones are actively involved in regulation of lipid peroxidation when mammals are exposed to radiation. (ERB)« less

Influence of night-shift and napping at work on urinary melatonin, 17-β-estradiol and clock gene expression in pre-menopausal nurses.

PubMed

Bracci, M; Copertaro, A; Manzella, N; Staffolani, S; Strafella, E; Nocchi, L; Barbaresi, M; Copertaro, B; Rapisarda, V; Valentino, M; Santarelli, L

2013-01-01

Night-workers experience disruption of the sleep-wake cycle and light at night which may increase breast cancer risk by suppressing the nocturnal melatonin surge, resulting in higher levels of circulating estrogens. Night-work may also deregulate peripheral clock genes which have been found to be altered in breast cancer. This study investigated urinary 6-sulfatoxymelatonin (aMT6s), serum 17-beta-estradiol levels in premenopausal shift nurses at the end of the night-shift compared to a control group of daytime nurses. Peripheral clock gene expression in lymphocytes were also investigated. All participants were sampled in the follicular phase of the menstrual cycle. The effect of nurses’ ability to take a short nap during the night-shift was also explored. The shift-work group had significantly lower aMT6s levels than daytime nurses independently of a nap. Night-shift napping significantly influences 17-beta-estradiol levels resulting in higher outcomes in nurses who do not take a nap compared to napping group and daytime workers. Peripheral clock genes expression investigated was not significantly different among the groups. Our findings suggest that shift nurses experience changes in aMT6s levels after a night-shift. Napping habits influence 17-beta-estradiol levels at the end of a night-shift. These findings might be related to the increased cancer risk reported in night-shift workers and suggest that a short nap during night-shifts may exert a positive effect.

THE HISTOLOGY OF FITC AND FITC-17B ESTRADIOL IN CUNNER, TAUTOGOLABRUS ADSPERSUS, AFTER SUBCUTANEOUS IMPLANTATION IN A CONTROLLED RELEASE MATRIX

EPA Science Inventory

To mimic environmental exposures in studying the effects of estrogenic chemicals on fish reproduction, a slow-release mechanism is needed to deliver a continuous dosing of chemicals over the course of a long-term study. The effects of slow-release chemical exposures via a subcuta...

Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1-44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states.

PubMed

Evans, W S; Anderson, S M; Hull, L T; Azimi, P P; Bowers, C Y; Veldhuis, J D

2001-02-01

How estrogen amplifies GH secretion in the human is not known. The present study tests the clinical hypothesis that estradiol modulates the stimulatory actions of a primary GH feedforward signal, GHRH. To this end, we investigated the ability of short-term (7- to 12-day) supplementation with oral estradiol vs. placebo to modulate basal, pulsatile, entropic, and 24-h rhythmic GH secretion driven by a continuous iv infusion of recombinant human GHRH-(1--44)-amide vs. saline in nine healthy postmenopausal women. Volunteers underwent concurrent blood sampling every 10 min for 24 h on four occasions in a prospectively randomized, single blind, within-subject cross-over design (placebo/saline, placebo/GHRH, estradiol/saline, estradiol/GHRH). Intensively sampled serum GH concentrations were quantitated by ultrasensitive chemiluminescence assay. Basal, pulsatile, entropic (feedback-sensitive), and 24-h rhythmic modes of GH secretion were appraised by deconvolution analysis, the approximate entropy (ApEn) statistic, and cosine regression, respectively. ANOVA revealed that continuous iv infusion of GHRH in the estrogen-withdrawn (control) milieu 1) amplified individual basal (P = 0.00011) and pulsatile (P < 10(-13)) GH secretion rates by 12- and 11-fold, respectively; 2) augmented GH secretory burst mass and amplitude each by 10-fold (P < 10(-11)), without altering GH secretory burst frequency, duration, or half-life; 3) increased the disorderliness (ApEn) of GH release patterns (P = 0.0000002); 4) elevated the mesor (cosine mean) and amplitude of the 24-h rhythm in serum GH concentrations by nearly 30-fold (both P < 10(-12)); 5) induced a phase advance in the clocktime of the GH zenith (P = 0.021); and 6) evoked a new 24-h rhythm in GH secretory burst mass with a maximum at 0018 h GH (P < 10(-3)), while damping the mesor of the 24-h rhythm in GH interpulse intervals (P < 0.025). Estradiol supplementation alone 1) increased the 24-h mean and integrated serum GH concentration (P = 0.047); 2) augmented GH secretory burst mass (P: = 0.025) without influencing pulse frequency, duration, half-life, or basal secretion; 2) stimulated more irregular patterns of GH release (higher ApEn; P = 0.012); and 3) elevated the 24-h rhythmic GH mesor (P = 0.0005), but not amplitude. Notably, combined stimulation of the GH axis with GHRH-(1--44)-amide and estradiol exerted no further effect beyond that evoked by GHRH alone, except for normalizing the acrophase of 24-h GH rhythmic release and elevating the postinfusion plasma insulin-like growth factor I concentration (P = 0.016). Unexpectedly, the two GHRH-infused serum GH concentration profiles monitored after placebo and estradiol pretreatment showed strongly nonrandom synchrony with a 20- to 30-min lag (P < 0.001). In summary, the present clinical investigations unmask a 3-fold (pulsatile, entropic, and daily rhythmic) similitude between the neuroregulatory actions of estradiol and GHRH in healthy postmenopausal women. However, GHRH infusion was multifold more effectual than estradiol, and only GHRH elevated nonpulsatile (basal) GH secretion, shifted the GH acrophase, and synchronized GH profiles. Given the nonadditive nature of the joint effects of estradiol and GHRH on pulsatile and entropic GH release, we hypothesize that estrogen amplifies GH secretion in part by enhancing endogenous GHRH release or actions. In addition, the distinctive ability of GHRH (but not estradiol) to increase basal (nonpulsatile) GH secretion, shift the GH acrophase and synchronize GH output patterns identifies certain divergent hypothalamo-pituitary actions of these two major GH secretagogues.

In vitro and in vivo effects of phytoestrogens on protein turnover in rainbow trout (Oncorhynchus mykiss) white muscle

USDA-ARS?s Scientific Manuscript database

Soybeans and other legumes investigated as fishmeal replacements in aquafeeds contain phytoestrogens capable of binding to and activating estrogen receptors. Estradiol has catabolic effects in salmonid white muscle, partially through increases in protein turnover. The current study determines whet...

Clitoral vascularization and sexual behavior in young patients treated with drospirenone-ethinyl estradiol or contraceptive vaginal ring: a prospective, randomized, pilot study.

PubMed

Battaglia, Cesare; Morotti, Elena; Persico, Nicola; Battaglia, Bruno; Busacchi, Paolo; Casadio, Paolo; Paradisi, Roberto; Venturoli, Stefano

2014-02-01

Oral contraceptives (OC) are effective for birth control and have good cycle control and tolerability. However, the hormonal components could modify mood and libido. The aim of this study is to evaluate the genital vascular effects and sexual behavior of an OC containing 30 μg ethinyl estradiol and 3 mg drospirenone in comparison with a flexible combined contraceptive vaginal ring. Forty women underwent a sonographic assessment of the clitoral anatomy and vascularization and were administered the McCoy Female Sexuality Questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). Estradiol, androstenedione, testosterone, and SHBG were assayed. Free Androgen Index (FAI) and Free Estrogen Index (FEI) were calculated. The patients were randomly submitted to OC (group I; n = 21) or vaginal ring (group II; n = 19). Ultrasonographic clitoral volume, pulsatility index (PI) of dorsal clitoral arteries, MFSQ, BDI, and hormonal and biochemical assays were analyzed. After therapy, the testosterone levels were reduced in both groups, whereas estradiol decreased only in group I women. The SHBG increased in all the subjects, and both FAI and FEI decreased. The clitoral volume decreased in all the women. The PI of the dorsal clitoral artery increased only in patients on OC. The hormonal contraception was associated, in both studied groups, with a significant decrease of the two-factor Italian MFSQ score, which was more marked in OC users. In group I subjects, there was a reduction of the number of intercourse/week and a reduction of orgasm frequency during intercourse. The pain during intercourse worsened after OC use. The vaginal ring users reported a vaginal wetness. Six-month treatment with hormonal contraception is associated with a diminished MFSQ score. However, the frequency of sexual intercourse and orgasm was reduced only by the use of OC. The OC use was associated with increased pain during intercourse. © 2013 International Society for Sexual Medicine.

Mechanisms of Estradiol-Induced Insulin Secretion by the G Protein-Coupled Estrogen Receptor GPR30/GPER in Pancreatic β-Cells

PubMed Central

Sharma, Geetanjali

2011-01-01

Sexual dimorphism and supplementation studies suggest an important role for estrogens in the amelioration of glucose intolerance and diabetes. Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. The results of this study suggest that the activation of downstream signaling pathways by the GPER-selective ligand G-1 could represent a novel therapeutic strategy in the treatment of diabetes. PMID:21673097

Changes in estradiol and testosterone levels in postmenopausal women after changes in body mass index.

PubMed

Jones, Michael E; Schoemaker, Minouk; Rae, Megan; Folkerd, Elizabeth J; Dowsett, Mitch; Ashworth, Alan; Swerdlow, Anthony J

2013-07-01

Endogenous sex hormones are risk factors for postmenopausal breast cancer. A potential route for favorable hormonal modification is weight loss. The objective of the study was to measure change in plasma estradiol and testosterone levels in postmenopausal women in relation to change in body mass index (BMI) and plasma leptin. The setting was a cohort study of over 100,000 female volunteers from the general population, United Kingdom. The participants were a sample of 177 postmenopausal women aged over 45 years who provided blood samples during 2004-2005 and again during 2010-2011. Outcomes were percentage change in plasma estradiol and testosterone levels per 1 kg/m² change in BMI and per 1 ng/mL change in plasma leptin. Among women with reduction in BMI, estradiol decreased 12.7% (95% confidence interval: [6.4%, 19.5%]; P < .0001) per kg/m² and among women with increased BMI estradiol increased 6.4% [0.2%, 12.9%] (P = .042). The corresponding figures for testosterone were 10.7% [3.0%, 19.0%] (P = .006) and 1.9% [-5.4%, 9.7%] (P = .61) per kg/m². For women with decreases and increases in leptin, estradiol decreased by 3.6% [1.3%, 6.0%] (P = .003) per ng/mL and increased by 1.7% [-0.3%, 3.6%] (P = .094), respectively. The corresponding figures for testosterone were 4.8% [2.0%, 7.8%] (P = .009) and 0.3% [-2.0%, 2.6%] (P = .82) per ng/mL. In postmenopausal women, changes in BMI and plasma leptin occurring over several years are associated with changes in estradiol and testosterone levels. The results suggest that fat loss by an individual can result in substantial decreases in postmenopausal estradiol and testosterone levels and provides support for weight management to lessen breast cancer risk.

A novel mutation in the human aromatase gene: insights on the relationship among serum estradiol, longitudinal growth and bone mineral density in an adult man under estrogen replacement treatment.

PubMed

Lanfranco, Fabio; Zirilli, Lucia; Baldi, Matteo; Pignatti, Elisa; Corneli, Ginevra; Ghigo, Ezio; Aimaretti, Gianluca; Carani, Cesare; Rochira, Vincenzo

2008-09-01

Here we report on a new case of human aromatase deficiency in a man of 26 years of age and present the results of five year follow-up during trandermal estradiol (tE2) substitution, focusing on bone growth and mineralization. The lack of patient's compliance to tE2 treatment, resulting in low but detectable serum estradiol levels, provides helpful information about the physiological estradiol needed in serum to guarantee a complete bone maturation and mineralization. Clinical case report study. Genetic, biochemical and hormonal evaluations and the study of bone health were performed before and during estrogen treatment. Eunuchoid body proportions, unfused epiphyses, tall stature, osteopenia, increase fasting insulin, mild astenozoospermia and a history of right cryptorchidism were present. Baseline serum FSH was slightly above the normal range and estradiol was undetectable. Genetic analysis revealed a pattern of compound heterozygosity due to 23 bp deletion in exon IV and a point mutation in the first nucleotide of intron IX of the CYP19A1 gene, respectively. The closure of epiphyseal cartilage, the normalization of bone BMD and bone turnover markers, and the improvement of insulin levels were reached during tE2 only when serum estradiol raised above 73 pmol/L. Sperm parameters and overweight did not improve with substitutive therapy. This new case of aromatase deficiency underlines the role of estrogen on skeletal maturation, BMD, metabolic abnormalities and gonadal axis. It provides evidence on the need not only of a continuous estrogen replacement, but also of ensuring adequate estradiol levels in serum in order to ensure a complete bone maturation and mineralization and to prevent the worsening of body skeletal proportions. The comprehension of this physiological aspect has relevant clinical significance especially for the development of new therapeutic strategies useful to treat growth disorders by targeting serum estradiol in men.

[Influence of the high peak serum estradiol on the outcome of in vitro fertilization cycles].

PubMed

Carmona-Ruiz, Israel Obed; Galache-Vega, Pedro; Santos-Haliscak, Roberto; Díaz-Spíndola, Pablo; Batiza-Reséndiz, Víctor Alfonso; Hernández-Ayup, Samuel

2010-10-01

For the use of assisted reproductive technologies of high complexity (IVF-ET and ICSI) is essential to proper ovarian stimulation with recombinant FSH drugs menotropins, as well as the use of GnRH analogues. To correlate serum estradiol level on day 10th with the outcome of in vitro fertilization cycles. Retrospective study of 523 IVF cycles, selected and analyzed from 2005 to 2009. Patients underwent individualized stimulation protocols with gonadotropins and agonist (late luteal phase). The patients were divided into three groups according with the serum level of estradiol on day 10th of stimulation: Group I, patients with serum level of Estradiol below 1,000 pg/mL; Group II, with levels between 1,000-4,000 pg/mL; and Group III, with levels above 4,000 pg/mL. Peak serum estradiol levels, oocyte number, fertilization rates, implantation rates, and pregnancy rates were compared among groups. The fertilization rate was 62.8 in Group I; 60.6% in Group II, and 54.2% in Group III. The pregnancy rate in Group I was 29.8%; in Group II, 37.3%; and 24% for Group III. The implantation rates were 14, 22 and 14% for each group respectively (I, II and III). There is an inverse relationship between high peak serum estradiol levels and pregnancy rate; the implantation rate seems affected by the extreme levels of serum estradiol. The percent of total mature oocytes and fertilization rate improve with serum levels of estradiol at physiologic values.

Comprehensive analysis of lncRNAs and mRNAs in skeletal muscle of rainbow trout (Oncorhynchus mykiss) exposed to estradiol

USDA-ARS?s Scientific Manuscript database

Estradiol (E2) is a steroid hormone that negatively affects muscle growth in rainbow trout, but the mechanisms directing with this response are not fully understood. To better characterize the effects of E2 in muscle, we identified differentially regulated mRNAs and lncRNAs in juvenile rainbow trout...

RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate,17B-estradiol and casein

USDA-ARS?s Scientific Manuscript database

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 ug/kg/d estradiol and relative to rats treated with e...

Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action.

PubMed

Riordan, Alexander J; Schaler, Ari W; Fried, Jenny; Paine, Tracie A; Thornton, Janice E

2018-05-01

The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP. To modulate E and LH, animals received estradiol capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task (NORT). Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABA A agonist, GABA A antagonist, or GAD inhibitor before behavioral testing. We found that PCP reduced hippocampal GAD67 and abolished recognition memory. Antide restored hippocampal GAD67 and rescued recognition memory in PCP-treated animals. Estradiol prevented PCP's amnesic effect in NORT but failed to restore hippocampal GAD67. PCP did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABA A agonist restored recognition memory in PCP-treated rats. Blocking hippocampal GAD or GABA A receptors in ovx animals reproduced recognition memory loss similar to PCP and inhibited estradiol's protection of recognition memory in PCP-treated animals. In summary, decreasing LH or increasing E can lessen short-term episodic memory loss, as measured by novel object recognition, in a PCP model of schizophrenia. Alterations in hippocampal GABA may contribute to both PCP's effects on recognition memory and the hormones' ability to prevent or reverse them. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hormone effects on fMRI and cognitive measures of encoding: importance of hormone preparation.

PubMed

Gleason, C E; Schmitz, T W; Hess, T; Koscik, R L; Trivedi, M A; Ries, M L; Carlsson, C M; Sager, M A; Asthana, S; Johnson, S C

2006-12-12

We compared fMRI and cognitive data from nine hormone therapy (HT)-naive women with data from women exposed to either opposed conjugated equine estrogens (CEE) (n = 10) or opposed estradiol (n = 4). Exposure to either form of HT was associated with healthier fMRI response; however, CEE-exposed women exhibited poorer memory performance than either HT-naive or estradiol-exposed subjects. These preliminary findings emphasize the need to characterize differential neural effects of various HTs.

Effects of melatonin implants in pony mares. 1. Acute effects.

PubMed

Peltier, M R; Robinson, G; Sharp, D C

1998-04-15

The effects of melatonin implant treatment over a four week period on LH, estradiol (E2) and progesterone (P4) secretion during the breeding season were studied in ovary-intact and ovariectomized pony mares. Mares with melatonin implants had significantly higher daytime melatonin concentrations than mares with sharm implants (P = 0.0065). In ovariectomized mares, LH secretion did not differ between mares with melatonin and sham implants. In ovary-intact mares, melatonin implants altered the pattern of LH secretion (P = 0.0023) in such a way that an increase in LH secretion was observed during the periovulatory period. Estradiol and P4 secretion were unaffected by melatonin implants. These results suggest that constant administration of melatonin may enhance the secretion of LH during the periovulatory surge but does not adversely affect E2, P4 or basal LH secretion in mares during the breeding season.

Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women.

PubMed

Mason, Caitlin; De Dieu Tapsoba, Jean; Duggan, Catherine; Imayama, Ikuyo; Wang, Ching-Yun; Korde, Larissa A; Stanczyk, Frank; McTiernan, Anne

2016-06-01

The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program. Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL ("insufficient") were randomized to either weight loss + 2,000 IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend = 0.01), and larger decreases in free and bioavailable estradiol (Ptrend = 0.04, Ptrend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D ≥32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7 pg/mL), free testosterone (-0.8 vs -0.3 pg/mL), and bioavailable testosterone (-1.8 vs -0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss. Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.

Effect of mono-(2-ethylhexyl) phthalate on steroid production of human granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinsberg, Jochen; Wegener-Toper, Petra; Ven, Katrin van der

2009-08-15

The phthalate ester mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of di-(2-ethylhexyl) phthalate, a high-production-volume chemical used as a plasticizer and solvent in numerous consumer products. MEHP has been demonstrated to be a reproductive toxicant in rodents decreasing estradiol and progesterone production in preovulatory granulosa cells. In the present study, we examined the effect of MEHP on steroid production of human granulosa-lutein (GL) cells. Human GL cells collected from women undergoing in vitro fertilization were cultured in medium containing FSH, hCG and 8-Br-cAMP, respectively, together with various concentrations of MEHP (0-500 {mu}mol L{sup -1}). After incubation for 48 h estradiolmore » and progesterone were assayed in the spent culture medium. Furthermore, aromatase activity and mRNA levels of GL cells were determined. Basal as well as FSH-, hCG- and 8-Br-cAMP-stimulated estradiol production of GL cells was suppressed by MEHP in a dose-dependent manner (IC{sub 50} = 105 {mu}mol L{sup -1}, 138 {mu}mol L{sup -1}, 49 {mu}mol L{sup -1} and 78 {mu}mol L{sup -1}). Furthermore aromatase activity and mRNA levels were reduced in GL cells cultured with MEHP. In contrast, MEHP did not alter the production of progesterone up to a concentration of 167 {mu}mol L{sup -1}. The present data indicate that MEHP is a specific inhibitor of estradiol production in human GL cells with a post-cAMP site of action. The inhibition of estradiol production obviously results from a reduction of aromatase activity on the transcript level. As the in vitro effective doses of MEHP are within the range of real environmental exposure levels an inhibitory effect on estrogen production in vivo seems to be possi0009b.« less

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

PubMed

Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

2001-05-15

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females. Copyright 2001 Academic Press.

Higher than expected estradiol levels in aromatase inhibitor-treated, postmenopausal breast cancer patients.

PubMed

Kunovac Kallak, T; Baumgart, J; Stavreus Evers, A; Sundström Poromaa, I; Moby, L; Kask, K; Norjavaara, E; Kushnir, M M; Bergquist, J; Nilsson, K

2012-10-01

Vaginal estradiol is considered contraindicated in aromatase inhibitor (AI)-treated patients because of the risk of elevated estrogen levels. This leaves limited treatment options for patients experiencing gynecological symptoms. However, in clinical practice, no precise estimation has been performed of circulating estrogens and aromatase index in postmenopausal breast cancer patients on long-lasting AI or tamoxifen treatment. Steroid hormones were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) and extraction radioimmunoassay (RIA). Postmenopausal AI-treated patients (n =33) were compared with tamoxifen-treated patients (n =34) and controls without vaginal treatment (n =56), with vaginal estradiol (n =25), or with estriol (n =11) treatment. By use of LC-MS/MS, median (range) estradiol plasma concentrations were 16.7 (2.4-162.6), 31.0 (13.4-77.1), 27.2 (7.8-115.8) and 33.3 (20.3-340.1) pmol/l in AI-treated breast cancer patients, tamoxifen-treated breast cancer patients, postmenopausal controls and postmenopausal controls on vaginal estradiol, respectively. The AI-treated group and subgroups had significantly lower estradiol and estrone concentrations than all other groups (p <0.05). There was extensive interindividual variation in estradiol concentration within the AI-treated group, measured using both LC-MS/MS (2.3-182.0 pmol/l) and extraction RIA (2.4-162.6 pmol/l). The AI-treated group had lower aromatase index compared to all other groups (p <0.05-0.001). Circulating estrogen levels may have been underestimated in previous longitudinal studies of AI-treated breast cancer patients. Additional studies are required to further evaluate the role of circulating estrogens in breast cancer patients suffering from gynecological symptoms.

Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition.

PubMed

Kantarci, Kejal; Lowe, Val J; Lesnick, Timothy G; Tosakulwong, Nirubol; Bailey, Kent R; Fields, Julie A; Shuster, Lynne T; Zuk, Samantha M; Senjem, Matthew L; Mielke, Michelle M; Gleason, Carey; Jack, Clifford R; Rocca, Walter A; Miller, Virginia M

2016-05-07

It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer's disease (AD). To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women. Participants within 5-36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated. Women (age = 52-65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11-0.83)]. In the APOEɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004-0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006-0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOEɛ4 non-carriers. In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOEɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample.

Estradiol increases the expression of TNF-α and TNF receptor 1 in lactotropes.

PubMed

Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

2011-01-01

Estrogens are recognized modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that plays an important role in tissue homeostasis modulating cell proliferation, differentiation and death. We previously demonstrated that TNF-α-induced apoptosis of anterior pituitary cells from female rats is estrogen-dependent and predominant in cells from rats at proestrus when estradiol levels are the highest. Considering that one of the mechanisms involved in the apoptotic action of estrogens can result from increased expression of cytokines and/or their receptors, the aim of the present study was to evaluate the effect of estrogens on the expression of TNF-α and its receptor, TNF receptor 1 (TNFR1), in anterior pituitary cells. TNFR1 expression, determined by Western blot, was higher in anterior pituitary glands from rats at proestrus than at diestrus. Incubation of anterior pituitary cells from ovariectomized rats with 17β-estradiol enhanced TNFR1 protein expression. As determined by double immunocytochemistry, the expression of TNF-α and TNFR1 was detected in prolactin-, GH-, LH- and ACTH-bearing cells. 17β-estradiol increased the percentage of TNF-α and TNFR1-immunoreactive lactotropes but did not modify the number of GH-bearing cells expressing TNF-α or TNFR1. Our results demonstrate that estradiol increases the expression of TNF-α and TNFR1 in anterior pituitary cells, especially in lactotropes. The sensitizing action of estrogens to proapoptotic stimuli at proestrus in the anterior pituitary gland may involve changes in the expression of the TNF-α/TNFR1 system. Copyright © 2011 S. Karger AG, Basel.

Mouse strain-dependent differences in estrogen sensitivity during vaginal candidiasis.

PubMed

Mosci, Paolo; Pietrella, Donatella; Ricci, Giovanni; Pandey, Neelam; Monari, Claudia; Pericolini, Eva; Gabrielli, Elena; Perito, Stefano; Bistoni, Francesco; Vecchiarelli, Anna

2013-02-01

The animal models available for studying the immune response to genital tract infection require induction of a pseudo estrous state, usually achieved by administration of 17-β-estradiol. In our experimental model of vaginal candidiasis, under pseudo estrus, different strains of mice were used. We observed major differences in the clearance of Candida albicans infection among the different strains, ascribable to differing susceptibility to estradiol treatment. In the early phase of infection CD1, BALB/c, C57BL/6 albino and C57BL/6 mice were colonized to similar levels, while in the late phase of infection, BALB/c mice, which are considered genetically resistant to C. albicans infection, exhibited greater susceptibility to vaginal candidiasis than CD1 and C57BL/6 albino strains of mice. This was because estradiol induced "per se" enlarged and fluid-filled uteri, more pronounced in infected mice and consistently more evident in BALB/c and C57BL/6 mice than in CD1 mice. Unlike CD1, BALB/c and C57BL/6 mice showed a heavy fungal colonization of the uterus, even though C57BL/6 mice apparently cleared C. albicans from the vagina. The presence of C. albicans in the vagina and uterus was accompanied by a heavy bacterial load. Collectively these observations prompted us to carry out a careful analysis of estradiol effects in a mouse model of vaginal infection.

A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.

PubMed

Sierralta, Walter D; Epuñan, Maria J; Reyes, José M; Valladares, Luis E; Andersen, Thomas T; Bennett, James A; Jacobson, Herbert I; Pino, Ana M

2008-01-01

This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.

A critical review of fundamental controversies in the field of GPR30 research.

PubMed

Langer, Gernot; Bader, Benjamin; Meoli, Luca; Isensee, Jörg; Delbeck, Martina; Noppinger, Patricia Ruiz; Otto, Christiane

2010-01-01

The female sex hormone estradiol plays an important role in reproduction, mammary gland development, bone turnover, metabolism, and cardiovascular function. The effects of estradiol are mediated by two classical nuclear receptors, estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). In 2005, G-protein-coupled receptor 30 (GPR30) was claimed to act as a non-classical estrogen receptor that was also activated by the ERalpha and ERbeta antagonists tamoxifen and fulvestrant (ICI 182780). Despite many conflicting results regarding the potential role of GPR30 as an estrogen receptor, the official nomenclature was changed to GPER (G-protein-coupled estrogen receptor). This review revisits the inconsistencies that still exist in the literature and focuses on selected publications that basically address the following two questions: what is the evidence for and against the hypothesis that GPR30 acts as an estrogen receptor? What is the potential in vivo role of GPR30? Thus, in the first part we focus on conflicting results from in vitro studies analysing the subcellular localization of GPR30, its ability to bind (or not to bind) estradiol and to signal (or not to signal) in response to estradiol. In the second part, we discuss the strengths and limitations of four available GPR30 mouse models. We elucidate the potential impact of different targeting strategies on phenotypic diversity. Copyright 2010 Elsevier Inc. All rights reserved.

Transfer of estradiol to human milk. [Radioimmunoassay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nilsson, S.; Nygren, K.G.; Johansson, E.D.B.

1978-11-15

A radioimmunoassay for the measurement of estradiol in human milk is evaluated. The detection limit was found to be 25 pg of estradiol per milliliter of milk. In milk samples collected from four lactating women during three to four months and from one pregnant and lactating woman, the concentration of estradiol was found to be below the detection limit of the assay. When six lactating women were given vaginal suppositories containing 50 or 100 mg of estradiol, it was possible to estimate the estradiol concentration in milk. A ratio of transfer of estradiol from plasma to milk during physiologic conditionsmore » is calculated to be less than 100 : 10.« less

Endogenous hormones, muscle strength, and risk of fall-related fractures in older women.

PubMed

Sipilä, Sarianna; Heikkinen, Eino; Cheng, Sulin; Suominen, Harri; Saari, Päivi; Kovanen, Vuokko; Alén, Markku; Rantanen, Taina

2006-01-01

Among older people, fracture-causing fall often leads to health deterioration. The role of endogenous hormone status and muscle strength on fall-related fracture risk is unclear. This study investigates if, after adjustment for bone density, endogenous hormones and muscle strength would predict fall-related limb fracture incidence in older community-dwelling women followed-up over 10 years. As a part of a prospective population-based study, 187 75-year-old women were investigated. Serum estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate concentrations were analyzed, and isometric muscle strength and bone mineral density were assessed. Fall-related limb fractures were gathered from patient records. Serum estradiol concentration was a significant predictor of fall-related limb fractures. Women with serum estradiol concentrations less than 0.022 nmol/L had a 3-fold risk (relative risk 3.05; 95% confidence interval, 1.26-7.36), and women with estradiol concentrations between 0.022 and 0.066 nmol/L doubled the risk (relative risk 2.24; 95% confidence interval, 0.97-5.19) of fall-related limb fracture compared to the women with estradiol concentrations ()above 0.066 nmol/L. Adjustment for muscle strength and bone mineral density did not materially change the risk estimates. High muscle strength was associated with a low incidence of fall-related limb fractures. This study showed that in 75-year-old women higher serum estradiol concentration and greater muscle strength were independently associated with a low incidence of fall-related limb fractures even after adjustment for bone density. Our results suggest that hormonal status and muscle strength have their own separate mechanisms protecting from fall-related fractures. This finding is of importance in developing preventive strategies, but calls for further study.

Impact of Aromatase Genetic Variation on Hormone Levels and Global Outcome after Severe TBI

PubMed Central

Garringer, Julie A.; Niyonkuru, Christian; McCullough, Emily H.; Loucks, Tammy; Dixon, C. Edward; Conley, Yvette P.; Berga, Sarah

2013-01-01

Abstract Although experimental traumatic brain injury (TBI) studies support estradiol as a neuroprotectant and potent stimulator of neuroplasticity, clinical studies suggest a negative association between endogenous estradiol profiles and mortality/poor outcomes. However, no studies have evaluated associations with cerebral spinal fluid (CSF) hormone profiles and aromatase gene (cytochrome P450 [CYP]19A1) variability on clinical TBI outcomes. We evaluated 110 adults with severe TBI. Average and daily estradiol, testosterone, and estradiol/testosterone ratios (E2:T) were measured using CSF and serum samples and compared to healthy controls. Eighteen tagging and four functional single-nucleotide polymorphisms (SNPs) for CYP19A1 were genotyped and compared to hormones, acute mortality, and Glasgow Outcome Scale (GOS) scores 6 months post-TBI. TBI subjects had lower CSF estradiol over time versus controls. CSF testosterone was initially high, but declined over time. E2/T ratios were initially low, compared to controls, but rose over time. Higher mean E2/T ratio in bivariate analysis was associated with lower mortality (p=0.019) and better GOS-6 scores (p=0.030). rs2470152 influenced CSF E2/T ratio and also serum and CSF testosterone (p≤0.05 all comparisons). Multiple-risk SNPs rs2470152, rs4646, and rs2470144 were associated with worse GOS-6 scores (p≤0.05, all comparisons), and those with>1 risk SNP variant had a higher risk for poor outcome, compared with those with ≤1 risk variant. TBI results in low CSF estradiol and dynamic CSF testosterone and E2/T ratio. In contrast to clinical serum hormone studies, higher CSF E2/T ratio was associated with better outcome. Further, genetic variation in CYP19A1 influences both hormone dynamics and outcome post-TBI. PMID:23540392

Effects on body weight and body composition of a low-dose oral estroprogestin containing ethinyl estradiol 20 microg plus levonorgestrel 100 microg.

PubMed

Lello, Stefano; Vittori, Giorgio; Paoletti, Anna Maria; Sorge, Roberto; Guardianelli, Francesca; Melis, Gian Benedetto

2007-11-01

Weight gain is a common problem reported by users of estroprogestins (EPs) and is a frequent reason for EP discontinuation, even if this problem is not confirmed in several clinical studies. We studied the impact of a EP containing ethinyl estradiol (EE) 20 microg plus levonorgestrel (LNG) 100 microg on body weight (BW) and body composition in 47 treated women and 31 women as controls. Also, we studied the effect of this association on metabolic parameters (glycemia, lipid profile). EE20/LNG100 had no significant impact on body weight, body composition (fat mass, fat-free mass, total body water, intracellular water, extracellular water) or metabolic profile in comparison with no treatment. Thus, the use of EE20/LNG100 showed no impact on metabolic parameters, body weight and body composition. This could be important not only for the safety profile of this combination, but also in increasing patient compliance.

A Mouse Model of Hypospadias Induced by Estradiol Benzoate.

PubMed

He, Hou-Guang; Han, Cong-Hui; Zhang, Wei

2015-12-01

We wished to establish a mouse model of hypospadias using injections of estradiol benzoate for investigating the molecular mechanisms of hypospadias. Fifty timed pregnant mice were randomly divided into five study groups: A, B, C, D, and E. These groups were injected subcutaneously with estradiol benzoate mixed with sesame oil at, respectively, the doses of 0, 0.1, 0.5, 2.5, or 12.5 mg kg(-1) days(-1) from gestation day (GD) 12 to GD 16. The pups' mortality was recorded on the day of delivery. Urethras and positions of testes were examined on postnatal day 28. The numbers of live pups were significantly lower in the study groups D and E compared to study group A (p < 0.01). Hypospadias was seen in groups C (3.3 %; 1/30), D (18.2 %; 4/22), and E (21.4 %; 3/14), while cryptorchidism was observed in groups C (10 %; 3/30), D (31.8 %; 7/22), and E (57.1 %; 8/14) on postnatal day 28. The experimental model of hypospadias induced by estradiol benzoate in the group D (2.5 mg kg(-1) days(-1)) was more reliable considering high mortality of the study group E. The dose of estradiol benzoate used in the group D is suitable for establishing mouse model of hypospadias.

In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

PubMed

Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

2017-08-01

Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P < 0.001) higher than that with product-C, product-A, gel, and spray. However, products-A and C, gel, and spray showed almost the same (P > 0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P < 0.001) higher than those with products-A and B, gel, and spray. The in vitro study results indicate a high potential of skin-to-skin drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol for contraception and control of menstrual symptoms.

PubMed

Jensen, Jeffrey T; Archer, David F

2008-02-01

Considerable recent interest has focused on new methods of delivery of oral contraceptives that reduce or eliminate the hormone-free interval in order to improve convenience and acceptability, but maintain contraceptive efficacy, minimize side effects and reduce or eliminate the frequency of withdrawal bleeding episodes. Studies in several countries, including the US, have documented that many women would prefer to have no episodes of withdrawal bleeding when using oral contraceptives. This review focuses on a unique oral contraceptive formulation containing levonogestrel 90 microg and ethinyl estradiol 20 microg, approved for use in a continuous dosing regimen designed to eliminate withdrawal bleeding throughout the entire year.

The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells

PubMed Central

2016-01-01

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and 17β-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer. PMID:27188280

Premenstrual flares of pyoderma gangrenosum controlled with use of a combined oral contraceptive and antiandrogen (ethinyl estradiol/drospirenone).

PubMed

Jourabchi, N; Rhee, S M; Lazarus, G S

2016-05-01

The effect of sex hormones on pyoderma gangrenosum (PG) has not been reported. We report the case of a 34-year-old woman with chronic PG leg ulcers who was found to have recurring, premenstrual flares of PG. Her PG flares were controlled with the use of ethinyl estradiol/drospirenone. © 2015 British Association of Dermatologists.

Can Measurement of Progesterone, Estradiol, and Prolactin by Immunoassay be Interchanged? A Comparison of the Roche Cobas e601 vs. Abbott Architect i2000sr.

PubMed

Yin, Lianli; Chen, Xiang; Tang, Yinghua; Sun, Yifan

2017-03-01

Progesterone is a reliable indicator of either natural or induced ovulation, and it plays an important role in preparing for implantation in the uterus and maintaining pregnancy. Estradiol is the most powerful natural estrogen in humans. It adjusts reproductive function in females and, with progesterone, maintains a pregnancy. Prolactin is also an important indicator, and its major physiological action is the initiation and maintenance of lactation in women. Architect i2000sr and Cobas e601 are automated immunoassay systems that are widely used to measure progesterone, estradiol, and prolactin concentrations in the blood. However, there is a dearth of confidence in these methods for comparative research. Therefore, the aim of this study is to investigate the correlation of serum progesterone, estradiol, and prolactin results measured with Architect i2000sr and Cobas e601. Two hundred venous blood samples from routine serum progesterone, estradiol, and prolactin tests were analyzed on the Cobas e601 and the Architect i2000sr in our laboratory within the same day. Passing-Bablok regression analysis and a Bland-Altman plot were used to compare methods. According to the concordance correlation coefficient, the correlation was strong in estradiol, but the correlation of prolactin and progesterone was poor between the two systems. The Bland-Altman plots showed that the measured value of progesterone, estradiol, and prolactin detected by Cobas e601 were about 1.30, 1.24, and 1.10 times higher, respectively, than that measured using Architect i2000sr. The results of progesterone, estradiol, and prolactin of one method should not be directly transferable to the other.

The association between estradiol levels, hormonal contraceptive use, and responsiveness to one-session-treatment for spider phobia in women.

PubMed

Graham, Bronwyn M; Li, Sophie H; Black, Melissa J; Öst, Lars-Göran

2018-04-01

Preclinical studies have demonstrated that conditioned fear extinction is impaired in females with low endogenous levels of the sex hormone estradiol, due to menstrual fluctuations or hormonal contraceptive use. As fear extinction is a laboratory model of exposure therapy for anxiety and trauma disorders, here we assessed the hypothesis that treatment outcomes may be diminished when exposure therapy occurs during periods of low estradiol. 90 women with spider phobia (60 cycling and 30 using hormonal contraceptives) underwent a one-session exposure treatment for spider phobia, following which, serum estradiol levels were assessed. A median split in estradiol level was used to divide cycling participants into two groups; lower and higher estradiol. Behavioral avoidance and self-reported fear of spiders were measured pre-treatment, post-treatment, and at a 12 week follow-up assessment. Women using hormonal contraceptives exhibited a significantly slower rate of improvement across treatment, greater behavioral avoidance at post-treatment and follow-up, and fewer self-initiated post-treatment exposure tasks, relative to both groups of cycling women, who did not differ. No group differences in self-reported fear were evident. Correlational analyses revealed that across the whole sample, lower estradiol levels were associated with slower rates of improvement across treatment, and greater self-reported fear and behavioral avoidance at post-treatment, but not follow-up. These results provide the first evidence of an association between endogenous estradiol, hormonal contraceptive use, and exposure therapy outcomes in spider phobic women. Hormonal profile may partly account for variability in responsiveness to psychological treatments for anxiety and trauma disorders in women. Copyright © 2018 Elsevier Ltd. All rights reserved.

Serum estradiol does not differentiate stress, mixed and urge incontinent women around menopause. A report from the Women's Health in the Lund Area (WHILA) study.

PubMed

Hamer, Maria Andrada; Källén, Karin; Lidfeldt, Jonas; Samsioe, Göran; Teleman, Pia

2011-11-01

To outline serum estradiol levels in perimenopausal women with stress, mixed or urge incontinence. We believe the majority of urgency symptoms in perimenopausal women to be caused by a pelvic floor dysfunction and a hypermobility of the bladder neck. If this is the case, there would be no difference in estradiol levels between the groups. University hospital. In the observational Women's Health in the Lund Area study, a subset of 400/2221 women reporting urinary incontinence completed a detailed questionnaire regarding lower urinary tract symptoms and had their serum steroid hormone levels measured. Statistical analyses were made by Chi-square test, nonparametrical tests, ANOVA, multi- and univariate logistic regression analysis. Stress incontinence was reported by 196, mixed incontinence by 153 and urge incontinence by 43 women; in 369, serumestradiol values were available. Serum estradiol did not differ significantly between stress incontinent (median 49.5 pmo/l, range 2.63-875.4), urge incontinent (median 31.6 pmol/l, range 2.63-460.7) or mixed incontinent women (median 35.5 pmol/l, range 2.63-787.9, p=0.62). Logistic regression analysis correcting for age, parity, hormonal status, smoking, hysterectomy and BMI also failed to show any difference in estradiol levels between the groups (p=0.41-0.58). No significant differences in serum estradiol levels between stress, mixed or urge incontinent perimenopausal women could be demonstrated. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A study of estrogen metabolic clearance rates and transfer factors

PubMed Central

Hembree, W. C.; Bardin, C. W.; Lipsett, M. B.

1969-01-01

We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E2) and estrone (E1) during 2-hr and 12-hr infusions. When estradiol-3H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-3H levels increased slowly throughout the infusion. When estrone-3H was infused, constancy of estrone-3H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios CE1E2 and CE2E1 continually changed and transfer factors could not be calculated. The apparent “MCR'S” calculated on the basis of the 2-hr studies expressed as liters/24 hr per m2 ±SD were: “MCRE1” (women) 980 ±94, (men) 1170 ±95; “MCRE2” (women) 615 ±17, (men) 830 ±30. The estradiol “MCR's” differed significantly between men and women. “MCRE2” was the same using either estradiol-14C or -3H and was unchanged by the infusion of 170 μg of estradiol daily. Postmenopausal women had estrogen “MCR's” in the same range as premenopausal women. Excess glucocorticoids increased the “MCRE2.” PMID:5822587

Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ali, Imran; Engström, Annette; Vahter, Marie

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), inmore » 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.« less

Human sperm liver receptor homolog-1 (LRH-1) acts as a downstream target of the estrogen signaling pathway

PubMed Central

Montanaro, Daniela; Santoro, Marta; Carpino, Amalia; Perrotta, Ida; De Amicis, Francesca; Sirianni, Rosa; Rago, Vittoria; Gervasi, Serena; Aquila, Saveria

2015-01-01

In the last decade, the study of human sperm anatomy, at molecular level, has revealed the presence of several nuclear protein receptors. In this work, we examined the expression profile and the ultrastructural localization of liver receptor homolog-1 (LRH-1) in human spermatozoa. We evidenced the presence of the receptor by Western blotting and real time-RT-PCR. Furthermore, we used immunogold electron microscopy to investigate the sperm anatomical regions containing LRH-1. The receptor was mainly located in the sperm head, whereas its expression was reduced in the neck and across the tail. Interestingly, we observed the presence of LRH-1 in different stages of testicular germ cell development by immunohistochemistry. In somatic cells, it has been suggested that the LRH-1 pathway is tightly linked with estrogen signaling and the important role of estradiol has been widely studied in sperm cells. To assess the significance of LRH-1 in male gametes and to deepen understanding of the role of estrogens in these cells, we investigated important sperm features such as motility, survival and capacitation. Spermatozoa were treated with 10 nm estradiol and the inhibition of LRH-1 reversed the estradiol stimulatory action. From our data, we discovered that human spermatozoa can be considered a new site of expression for LRH-1, evidencing its role in sperm motility, survival and cholesterol efflux. Furthermore, we may presume that in spermatozoa the LRH-1 effects are closely integrated with the estrogen signaling, supporting LRH-1 as a downstream effector of the estradiol pathway on some sperm functions. PMID:26241668

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow.

PubMed

Bateman, Marjorie E; Strong, Amy L; Hunter, Ryan S; Bratton, Melyssa R; Komati, Rajesh; Sridhar, Jayalakshmi; Riley, Kevin E; Wang, Guangdi; Hayes, Daniel J; Boue, Stephen M; Burow, Matthew E; Bunnell, Bruce A

2017-04-15

While current therapies for osteoporosis focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs). To investigate the effects of glyceollins, structural derivatives of daidzein, on osteogenesis of ASCs and BMSCs. Herein, the osteoinductive effects of glyceollin I and glyceollin II were assessed and compared to estradiol in ASCs and BMSCs. The mechanism by which glyceollin II induces osteogenesis was further examined. The ability of glyceollins to promote osteogenesis of ASCs and BMSCs was evaluated in adherent and scaffold cultures. Relative deposition of calcium was analyzed using Alizarin Red staining, Bichinchoninic acid Protein Assay, and Alamar Blue Assay. To further explore the mechanism by which glyceollin II exerts its osteoinductive effects, docking studies of glyceollin II, RNA isolation, cDNA synthesis, and quantitative RT-PCR (qPCR) were performed. In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, or glyceollin II demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol and glyceollin I. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation. The ability of glyceollin II to induce osteogenic differentiation in ASCs and BMSCs indicates that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

PubMed

Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

2015-10-01

This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

PubMed

Fteita, Dareen; Könönen, Eija; Gürsoy, Mervi; Söderling, Eva; Gürsoy, Ulvi Kahraman

2015-12-01

Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relaxin's induction of metalloproteinases is associated with the loss of collagen and glycosaminoglycans in synovial joint fibrocartilaginous explants

PubMed Central

Naqvi, Tabassum; Duong, Trang T; Hashem, Gihan; Shiga, Momotoshi; Zhang, Qin; Kapila, Sunil

2005-01-01

Diseases of specific fibrocartilaginous joints are especially common in women of reproductive age, suggesting that female hormones contribute to their etiopathogenesis. Previously, we showed that relaxin dose-dependently induces matrix metalloproteinase (MMP) expression in isolated joint fibrocartilaginous cells. Here we determined the effects of relaxin with or without β-estradiol on the modulation of MMPs in joint fibrocartilaginous explants, and assessed the contribution of these proteinases to the loss of collagen and glycosaminoglycan (GAG) in this tissue. Fibrocartilaginous discs from temporomandibular joints of female rabbits were cultured in medium alone or in medium containing relaxin (0.1 ng/ml) or β-estradiol (20 ng/ml) or relaxin plus β-estradiol. Additional experiments were done in the presence of the MMP inhibitor GM6001 or its control analog. After 48 hours of culture, the medium was assayed for MMPs and the discs were analyzed for collagen and GAG concentrations. Relaxin and β-estradiol plus relaxin induced the MMPs collagenase-1 and stromelysin-1 in fibrocartilaginous explants – a finding similar to that which we observed in pubic symphysis fibrocartilage, but not in articular cartilage explants. The induction of these proteinases by relaxin or β-estradiol plus relaxin was accompanied by a loss of GAGs and collagen in joint fibrocartilage. None of the hormone treatments altered the synthesis of GAGs, suggesting that the loss of this matrix molecule probably resulted from increased matrix degradation. Indeed, fibrocartilaginous explants cultured in the presence of GM6001 showed an inhibition of relaxin-induced and β-estradiol plus relaxin-induced collagenase and stromelysin activities to control baseline levels that were accompanied by the maintenance of collagen or GAG content at control levels. These findings show for the first time that relaxin has degradative effects on non-reproductive synovial joint fibrocartilaginous tissue and provide evidence for a link between relaxin, MMPs, and matrix degradation. PMID:15642129

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1. Effects on metabolism.

PubMed

Bastianelli, Carlo; Farris, Manuela; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-03-01

The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease. Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral contraceptives (COC) has substantially changed, with new combinations, dosages and mode of administration appearing on the market. Area covered: In a series of articles, recent information on the complex issue of COC risks and benefits will be reviewed in the hope of providing an updated picture. The present article reviews metabolic changes occurring during use of modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), often compared to classic compounds, such as levonorgestrel. Three categories of metabolic effects in healthy women are detailed: on carbohydrates, lipid and bone mineral content. Expert commentary: Overall, the picture is reassuring: the new generations of progestins are basically devoid of androgenic, estrogenic or glucocorticoid related side-effects. This should result in an improved safety profile, although past history teaches us that that large comparative and surveillance studies are required before firm conclusions can be drawn. At any rate, available evidence indicates that metabolic effects of third and fourth generation progestins, especially when they are combined with natural estrogens, are minimal and, if used in healthy women, should not cause concern.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression.

PubMed

Tian, J-M; Ran, B; Zhang, C-L; Yan, D-M; Li, X-H

2018-01-23

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

Estrogen attenuates the cardiovascular and ventilatory responses to central command in cats.

PubMed

Hayes, Shawn G; Moya Del Pino, Nicolas B; Kaufman, Marc P

2002-04-01

Static exercise is well known to increase heart rate, arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has been attributed to an effect of estrogen on neuronal function. In decerebrate male cats, we examined the effect of estrogen (17beta-estradiol; 0.001, 0.01, 0.1, and 1.0 microg/kg iv) on the cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17beta-estradiol, in each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17beta-estradiol had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps surae muscles. We conclude that, in decerebrate male cats, estrogen injected intravenously attenuates cardiovascular and ventilatory responses to central command but has no effect on responses to the exercise pressor reflex.

17β-Estradiol Induced Effects on Anterior Cruciate Ligament Laxness and Neuromuscular Activation Patterns in Female Runners.

PubMed

Khowailed, Iman Akef; Petrofsky, Jerrold; Lohman, Everett; Daher, Noha; Mohamed, Olfat

2015-08-01

We investigate the effects of 17β-Estradiol across phases of menstrual cycle on the laxness of the anterior cruciate ligament (ACL) and the neuromuscular control patterns around the knee joint in female runners. Twelve healthy female runners who reported normal menstrual cycles for the previous 6 months were tested twice across one complete menstrual cycle for serum levels of 17β-estradiol, and knee joint laxity (KJL). Electromyographic (EMG) activity of the quadriceps and hamstrings muscles was also recorded during running on a treadmill. The changes in the EMG activity, KJL, and hormonal concentrations were recorded for each subject during the follicular and the ovulatory phases across the menstrual cycle. An observed increase in KJL in response to peak estradiol during the ovulatory phase was associated with increased preactivity of the hamstring muscle before foot impact (p<0.001). A consistent pattern was also observed in the firing of the quadriceps muscle recruitment pattern throughout the follicular phase associated with decreased hamstring recruitment pattern during weight acceptance phase of running (p=0.02). Additionally, a low ratio of medial to lateral quadriceps recruitment was associated with a significant reduction of the quadriceps to hamstring co-contraction ratio during the follicular phase. Changes in KJL during the menstrual cycle in response to 17β-estradiol fluctuations changes the neuromuscular control around the knee during running. Female runners utilize different neuromuscular control strategies during different phases of the menstrual cycle, which may contribute to increased ACL injury risk.

Genes in the GABA pathway increase in the lateral thalamus of Sprague Dawley rats during the proestrus/estrus phase

PubMed Central

Umorin, Mikhail; Stinson, Crystal; Bellinger, Larry L.; Kramer, Phillip

2015-01-01

Pain can vary over the estrous cycle as a result of changes in estradiol concentration but the mechanism causing this variation is unclear. Because the thalamus is important in pain control, gene expression in the lateral thalamus (ventral posteromedial, ventral posterolateral, reticular thalamic nuclei) was screened at different phases of the estrous cycle. Gene expression changes in Sprague-Dawley rats were further analyzed by real-time PCR and ELISA and plasma estradiol levels were measured by RIAs at different phases of the estrous cycle. Our results indicated that both the RNA and protein expression of glutamate decarboxylase 1 and 2 (GAD1, GAD2), GABA(A) receptor-associated protein like 1 (GABARAPL1) and vesicular GABA transporter (VGAT) significantly increased in the lateral thalamus when plasma estradiol levels were elevated. Estradiol levels were elevated during the proestrus and estrus phases of the estrous cycle. Estrogen receptor α (ERα) was observed to be co-localized in thalamic cells and thalamic infusion of an ERα antagonist significantly reduced GAD1 and VGAT transcript. GAD1, GAD2 GABARAPL1 and VGAT have been shown to effect neuronal responses suggesting that modulation of pain during the estrous cycle can be dependent, in part, through estradiol induced changes in thalamic gene expression. PMID:26388520

Phenols and Parabens in relation to Reproductive and Thyroid Hormones in Pregnant Women

PubMed Central

Aker, Amira M; Watkins, Deborah J; Johns, Lauren E; Ferguson, Kelly K; Soldin, Offie P; Del Toro, Liza V Anzalota; Alshawabkeh, Akram N; Cordero, José F; Meeker, John D

2016-01-01

Introduction Phenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)”. Methods Urinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16–20 weeks and 24–28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression. Results An IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI −18.31, −0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16–20 weeks), and suggestively positively associated with estradiol at the second time point (24–28 weeks). Conclusions Within this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required. PMID:27448730

Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women.

PubMed

Aker, Amira M; Watkins, Deborah J; Johns, Lauren E; Ferguson, Kelly K; Soldin, Offie P; Anzalota Del Toro, Liza V; Alshawabkeh, Akram N; Cordero, José F; Meeker, John D

2016-11-01

Phenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, "Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)". Urinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16-20 weeks and 24-28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression. An IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI -18.31,-0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16-20 weeks), and suggestively positively associated with estradiol at the second time point (24-28 weeks). Within this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required. Copyright © 2016 Elsevier Inc. All rights reserved.

A BIOLOGICALLY BASED MODEL FOR THE HORMONAL CONTROL OF THE MENSTRUAL CYCLE

EPA Science Inventory

Recent studies suggest that environmental substances that mimic endogenous estrogens (eg. estradiol) may disrupt the endocrine system. While high-level exposures to estrogenic substances are believed to contribute to such adverse effects as cancer, developmental disorders, and fe...

COULD ETHINYL ESTRADIOL AFFECT THE POPULATION BIOLOGY OF CUNNER, TAUTOGOLABRUS ADSPERSUS

EPA Science Inventory

Endocrine disrupting chemicals in the environment may disturb the population dynamics of wildlife by affecting reproductive output and embryonic development of organisms. This study used a population model to evaluate whether ethinyl estradiol (EE2 could affect cunner Tautogolabr...

A novel 17β-hydroxysteroid dehydrogenase in Rhodococcus sp. P14 for transforming 17β-estradiol to estrone.

PubMed

Ye, Xueying; Wang, Hui; Kan, Jie; Li, Jin; Huang, Tongwang; Xiong, Guangming; Hu, Zhong

2017-10-01

17β-hydroxysteroid dehydrogenases (17β-HSD) are a group of oxidoreductase enzymes that exhibit high specificity for 17C reduction/oxidation. However, the mechanism of 17β-HSD in oxidizing steroid hormone 17β-estradiol to estrone in bacterium is still unclear. In this work, a functional bacterium Rhodococcus sp. P14 was identified having rapid ability to oxidize estradiol into estrone in mineral salt medium (MSM) within 6 h. The functional genes encoding NADH-dependent oxidoreductase were successfully detected with the help of bioinformatics, and it was identified that it contained two consensus regions affiliated to the short-chain dehydrogenase/reductase (SDR) superfamily. Expression of 17β-HSD could be induced by estradiol in strain P14. The 17β-HSD gene from Rhodococcus sp. P14 was expressed in Escherichia coli strain BL21. Furthermore, recombinant 17β-HSD-expressing BL21 cells showed a high transformation rate, they are capable of transforming estradiol to estrone up to 94%. The purified His-17β-HSD protein also exhibited high catalyzing efficiency. In conclusion, this study provides the first evidence that a novel 17β-HSD in Rhodococcus sp. P14 can catalyze the oxidation of estradiol. Copyright © 2017 Elsevier B.V. All rights reserved.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, I; Bhattacharya, S; McNeil, A; van Rumste, M M E

2008-04-16

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model.

PubMed

Pezeshki, Zahra; Nematbakhsh, Mehdi; Nasri, Hamid; Talebi, Ardeshir; Pilehvarian, Ali-Asghar; Safari, Tahereh; Eshraghi-Jazi, Fatemeh; Haghighi, Maryam; Ashrafi, Farzaneh

2013-01-01

Cisplatin (CP) is an effective drug in cancer therapy to treat the solid tumors, but it is accompanied with nephrotoxicity. The protective effect of estrogen in cardiovascular diseases is well-documented; but its nephron-protective effect against CP-induced nephrotoxicity is not completely understood. Thirty ovarectomized Wistar rats were divided in to five groups. Groups 1-3 received different doses of estradiol valerate (0.5, 2.5 and 10 mg/kg/week) in sesame oil for 4 weeks, and at the end of week 3, a single dose of CP (7 mg/kg, intraperitoneal [IP]) was administrated. Group 4 (positive control) received the same regimen as group 1-3 without estradiol without vehicle. The negative control group (Group 5) received sesame oil during the study. The animals were sacrificed 1 week after CP injection for histopathological studies. The serum level of blood urea nitrogen and creatinine, kidney tissue damage score (KTDS), kidney weight and percentage of body weight change in CP-treated groups significantly increased (P < 0.05), however, there were no significant differences detected between the estrogen-treated groups (Groups 1-3) and the positive control group (Group 4). Although, estradiol administration enhanced the serum level of nitrite, it was not affected by CP. Finally, significant correlation between KTDS and kidney weight was detected (r (2) = 0.63, P < 0.01). Estrogen is not nephron-protective against CP-induced nephrotoxicity. Moreover, it seems that the mechanism may be related to estrogen-induced oxidative stress in the kidney, which may promote the nephrotoxicity.

Short-term improvement of erectile dysfunction by viewing humorous films in patients with atopic dermatitis.

PubMed

Kimata, Hajime

2008-09-01

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczema, pruritus and cutaneous hyperreactivity to allergic triggers. We and others have reported that psychogenic stress aggravates these symptoms, while viewing humorous films alleviates them. We have also found that many AD patients suffer from erectile dysfunction (ED). ED exhibits multifactorial etiologies, including psychogenic stress and reduction of serum testosterone levels. This study assessed the effects of viewing humorous films on ED in patients with AD. The effects of viewing humorous films on International Index Erectile Function (IIEF) domain (erectile function, orgasmic function, sexual desire, intercourse satisfaction, overall satisfaction) were studied. Subjects comprised 36 AD patients with ED and their healthy wives. Randomly assigned 18 patients and their healthy wives first viewed humorous films on three consecutive days (Days 1-3). After 2 weeks, they viewed control nonhumorous weather information films on three consecutive days (Days 1-3). Alternatively, other 18 patients and their wives first viewed control films on three consecutive days, and after 2 weeks they viewed humorous films on three consecutive days. Severity of ED and serum testosterone and estradiol levels were assessed 1 day before viewing (Day -1) and 1-4 days after viewing (Days 4-7). Viewing humorous films significantly improved the IIEF domain in association with increased serum testosterone levels and decreased serum estradiol levels on Day 4, while viewing control films failed to do so. However, this effect was short-term. After 4 days of viewing (Day 7), no improvement in ED or modulation of serum sex hormone levels was observed. Viewing humorous films improved ED in AD patients in association with increased serum testosterone levels and decreased serum estradiol levels. These results may be useful for the study and treatment of ED.

Alleviation of ischaemia-reperfusion injury by endogenous estrogen involves maintaining Bcl-2 expression via the ERα signalling pathway.

PubMed

Zhang, Zeng-Li; Qin, Pei; Liu, Yuhong; Zhang, Li-Xia; Guo, Hang; Deng, You-Liang; Yizhao-Liu; Hou, Yu-Shu; Wang, Li-Yang; Miao, Yi; Ma, Yu-Long; Hou, Wu-Gang

2017-04-15

The neuroprotective effects of estrogen against cerebral ischaemia have been confirmed by multiple basic and clinical studies. However, most of these studies used exogenous estrogen administered via different injection methods, and the neuroprotective effects of endogenous estrogen produced by ovaries during different phases of estrous cycle and the underlying mechanisms involved have rarely been explored. In this study, we first identified the stage of estrous cycle via vaginal smears and then measured serum estradiol levels at each phase via radioimmunoassay. We found that the estradiol level was highest in the proestrous and lowest in the diestrous. However, ovariectomy or treatment with the aromatase inhibitor letrozole significantly decreased estradiol levels compared to that of rats in diestrous. Western blotting showed that ovariectomy or letrozole treatment significantly decreased ERα and Bcl-2 protein expression and dramatically increased Bax protein expression compared with the rats in diestrous or proestrous. Rats also underwent 2h of ischaemia via middle cerebral artery occlusion followed by a 24-h reperfusion. Ovariectomy or letrozole treatment significantly decreased the neurological scores and the number of intact neurons detected via Nissl staining and dramatically increased the infarct volume detected via TTC staining and the extent of apoptosis detected via TUNEL staining and Western blotting for cleaved-caspase 3 protein expression. These results demonstrate that endogenous estrogen alleviates ischaemia-reperfusion injury by maintaining Bcl-2 expression via ERα signalling pathway and highlight the neuroprotective effects of endogenous estrogen during different stages of the estrous cycle, providing preliminary information on the underlying mechanism of this process. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of male and female sex steroids on the development of normal and the transient Froriep's dorsal root ganglia of the chick embryo.

PubMed

Liu, Jiali; Chen, Dawei; Goldstein, Ronald S; Cui, Sheng

2005-03-22

Sex steroids can influence developmental processes and support the survival of neurons in the embryonic central nervous system. Recent studies have shown that estrogen receptors are also expressed in the peripheral nervous system, in the dorsal root ganglia (DRG) of chick embryos. However, no studies have examined the effects of sex steroids on development of embryonic DRG. In the present study, 0.2 microg, 1.0 microg, 5.0 microg 10 microg, 20 microg, 25 microg, and 40 microg doses of testosterone or estradiol were delivered to chick embryos at Hamburger and Hamilton stage 18 (E3). The actions of these doses of sex steroids on the development of the C5DRG (fifth cervical ganglion, a "normal" DRG) and C2DRG (a transient ganglion known as a "Froriep's DRG") were then evaluated by quantifying ganglionic volumes, cell number, proliferation, and apoptosis after 1 day of growth to stage 23. We found that both testosterone and estradiol promoted proliferation of cells in both normal DRG and the Froriep's ganglia. By contrast, estradiol significantly increased the number of apoptotic cells, while testosterone strongly inhibited apoptosis. These actions of sex steroids on DRG development were dose-dependent, and C5DRG and C2DRG showed different sensitivities to the applied sex steroids. In addition, the present results demonstrated that specific ER and AR inhibitors (tamoxifen and flutamide) did not influence the effects of 5 microg E2 and 5 microg T on C2 and C5DRG significantly. These results demonstrate that male and female sex steroids can modulate DRG development through an epigenetic mechanism, as had been shown for the central nervous system.

Estradiol production by preimplantation blastocysts and increased serum progesterone following estradiol treatment in llamas.

PubMed

Powell, Susan A; Smith, Bradford B; Timm, Karen I; Menino, Alfred R

2007-11-01

Estradiol is a potential candidate for the blastocyst signal responsible for maternal recognition of pregnancy in the llama (Lama glama). Two experiments were conducted to determine if the llama blastocyst produces estradiol during the presumed period of maternal recognition of pregnancy and if exogenous estradiol can extend the luteal phase. In Experiment 1, llamas were superovulated with eCG and mated 7 days later (Day 0=day of mating). Blastocysts were collected nonsurgically on Days 7, 9, or 11 or at necropsy on Days 13 and 15 post-mating and cultured for 48h. Conditioned medium was recovered, replaced with fresh medium at 24-h intervals, and assayed for estradiol-17beta. Estradiol production (pg/blastocyst) over the 48-h culture increased (P<0.05) by day of gestation where more estradiol (P<0.05) was produced by Day 11 compared to Day 7 blastocysts, Day 13 compared to Days 7-11 blastocysts, and Day 15 compared to Days 7-13 blastocysts. A dramatic increase was observed between Days 11 and 13 when estradiol production by Day 13 blastocysts increased (P<0.05) more than 50-fold. In Experiment 2, 30 females were induced to ovulate with hCG (Day 0=day of hCG injection). Starting on Day 7 and continuing through Day 15, animals received daily injections i.m. of 0 (n=11), 5 (n=7), or 10mg (n=12) estradiol benzoate (EB) dissolved in isopropylmyristate. Sera were collected immediately prior to each injection and on Days 16, 17, 18, 20, and 22 and analyzed for progesterone. Progesterone concentrations were greater (P<0.05) on Days 14, 15, 16, and 17 in llamas treated with 10mg EB compared to llamas treated with 0mg EB. These results demonstrate that llama blastocysts produce estradiol and exogenous estradiol can enhance and transiently extend luteal progesterone production. Estradiol produced by the preimplantation llama blastocyst may play a role in maternal recognition of pregnancy and early luteal support.

Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

PubMed

Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

2018-06-01

Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

Fructose-rich diet and insulin action in female rat heart: Estradiol friend or foe?

PubMed

Bundalo, Maja; Romic, Snjezana; Tepavcevic, Snezana; Stojiljkovic, Mojca; Stankovic, Aleksandra; Zivkovic, Maja; Koricanac, Goran

2017-09-15

Increased intake of fructose in humans and laboratory animals is demonstrated to be a risk factor for development of metabolic disorders (insulin resistance, metabolic syndrome, type 2 diabetes) and cardiovascular diseases. On the other hand, estradiol is emphasized as a cardioprotective agent. The main goal of this review is to summarize recent findings on damaging cardiac effects of fructose-rich diet in females, mostly experimental animals, and to evaluate protective capacity of estradiol. Published results of our and other research groups indicate mostly detrimental effects of fructose-rich diet on cardiac insulin signaling molecules, glucose and fatty acid metabolism, nitric oxide production and ion transport, as well as renin-angiotensin system and inflammation. Some of these processes are involved in cardiac insulin signal transmission, others are regulated by insulin or have an influence on insulin action. Administration of estradiol to ovariectomized female rats, exposed to increased intake of fructose, was mostly beneficial to the heart, but sometimes it was ineffective or even detrimental, depending on the particular processes. We believe that these data, carefully translated to human population, could be useful for clinicians dealing with postmenopausal women susceptible to metabolic diseases and hormone replacement therapy. Copyright © 2017. Published by Elsevier B.V.

Effects of steroid hormones on nuclear membrane and membrane-bound heterochromatin from breast cancer cells evaluated by fractal morphometry.

PubMed

Losa, G A; Graber, R; Baumann, G; Nonnenmacher, T F

1999-10-01

To evaluate the effect of steroid hormones on the ultrastructure of nuclear heterochromatin and perinuclear membranes in human MCF-7 breast cancer cells. MCF-7 cells were cultured briefly (five minutes) in the presence of 10(-9) M estrogen 17 beta-estradiol, a stimulator of cell proliferation and/or 10(-9) M glucocorticoid dexamethasone. Changes in the morphologic complexity of nuclear membrane-bound heterochromatin (NMBHC) and nuclear membranes (ENM) were assessed by means of the fractal capacity dimension, D, a noneuclidean geometric descriptor of complex, irregular bodies. 17 beta-estradiol (10(-9) M) enhanced the ultrastructural irregularity of NMBHC, as documented by the increased value of D, whereas dexamethasone (10(-9) M) reduced it when compared to NMBHC from untreated MCF-7 control cells. In contrast, neither steroid modified ENM ultrastructure. Changes in the nuclear heterochromatin complexity induced by estrogen 17 beta-estradiol occurred concomitantly with functional changes at the cell periphery, such as activation of the phospholipase C, a cell membrane-associated enzyme involved in signal transduction. Dexamethasone reduced the ultrastructural complexity of NMBHC without affecting functional processes. Fractal morphometry proved its usefulness in quantifying early ultrastructural changes in nuclear components induced in MCF-7 cells by steroid hormones, 17 beta-estradiol and dexamethasone.

Estradiol increases body weight loss and gut-peptide satiation after Roux-en-Y gastric bypass in ovariectomized rats.

PubMed

Asarian, Lori; Abegg, Kathrin; Geary, Nori; Schiesser, Marc; Lutz, Thomas A; Bueter, Marco

2012-08-01

Despite the fact that ∼85% of bariatric operations are performed in women, the effects of the reproductive axis function on outcome of bariatric surgery remain to be determined. Here we developed the first published model of Roux-en-Y gastric bypass (RYGB) in female rats. We show in ovariectomized rats receiving estradiol or control treatment that (1) RYGB-induced body weight loss and (2) the satiating efficacy of endogenous glucagon-like peptide-1 and cholecystokinin satiation were significantly increased in estradiol-treated rats. These data are relevant to the care of obese women, in particular perimenopausal women, undergoing bariatric surgery. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Estradiol Valerate and Remifemin ameliorate ovariectomy-induced decrease in a serotonin dorsal raphe-preoptic hypothalamus pathway in rats.

PubMed

Wang, Wenjuan; Cui, Guangxia; Jin, Biao; Wang, Ke; Chen, Xing; Sun, Yu; Qin, Lihua; Bai, Wenpei

2016-11-01

Perimenopausal syndromes begin as ovarian function ceases and the most common symptoms are hot flushes. Data indicate that the projections of serotonin to hypothalamus may be involved in the mechanism of hot flushes. Therefore, the aim of this study is to investigate the potential role of the serotonin dorsal raphe-preoptic hypothalamus pathway for hot flushes in an animal model of menopause. We determined the changes in serotonin expression in the dorsal raphe (DR) and preoptic anterior hypothalamus (POAH) in ovariectomized rats. We also explored the therapeutical effects of estradiol valerate and Remifemin in this model. Eighty female Sprague-Dawley rats were randomly assigned to sham-operated (SHAM) group, ovariectomy (OVX) group with vehicle, ovariectomy with estradiol valerate treatment (OVX+E) group and ovariectomy with Remifemin (OVX+ICR) group. Serotonin expression was evaluated in the DR and POAH using immunofluorescence and quantified in the DR using an enzyme-linked immunosorbent assay (ELISA). Apoptosis was analyzed in the DR by TUNEL assay. The number of serotonin immunoreactive neurons and the level of serotonin expression in the DR decreased significantly following OVX compared to the SHAM group. No TUNEL-positive cells were detected in the DR in any group. In addition, following OVX, the number of serotonin-positive fibers decreased significantly in the ventromedial preoptic nucleus (VMPO), especially in the ventrolateral preoptic nucleus (VLPO). Treatment with either estradiol or Remifemin for 4 weeks countered the OVX-induced decreases in serotonin levels in both the DR and the hypothalamus, with levels in the treated rats similar to those in the SHAM group. A fluorescently labeled retrograde tracer was injected into the VLPO at the 4-week time point. A significantly lower percentage of serotonin with CTB double-labeled neurons in CTB-labeled neurons was demonstrated after ovariectomy, and both estradiol and Remifemin countered this OVX-induced decrease. We conclude that serotonin pathway is changed after ovariectomy, including the serotonin synthesis in DR and serotonin fibers in PO/AH, both E and Remifemin have an equivalent therapeutic effect on it. Copyright © 2016 Elsevier GmbH. All rights reserved.

Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers.

PubMed

Mueck, A O; Seeger, H; Petersen, G; Schulte-Wintrop, E; Wallwiener, D

2001-12-01

In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.

Isoflurane preconditioning protects neurons from male and female mice against oxygen and glucose deprivation and is modulated by estradiol only in neurons from female mice.

PubMed

Johnsen, D; Murphy, S J

2011-12-29

The volatile anesthetic, isoflurane, can protect the brain if administered before an insult such as an ischemic stroke. However, this protective "preconditioning" response to isoflurane is specific to males, with females showing an increase in brain damage following isoflurane preconditioning and subsequent focal cerebral ischemia. Innate cell sex is emerging as an important player in neuronal cell death, but its role in the sexually dimorphic response to isoflurane preconditioning has not been investigated. We used an in vitro model of isoflurane preconditioning and ischemia (oxygen and glucose deprivation, OGD) to test the hypotheses that innate cell sex dictates the response to isoflurane preconditioning and that 17β-estradiol attenuates any protective effect from isoflurane preconditioning in neurons via nuclear estrogen receptors. Sex-segregated neuron cultures derived from postnatal day 0-1 mice were exposed to either 0% or 3% isoflurane preconditioning for 1 h. In separate experiments, 17β-estradiol and the non-selective estrogen receptor antagonist ICI 182,780 were added 24 h before preconditioning and then removed at the end of the preconditioning period. Twenty-three hours after preconditioning, all cultures underwent 2 h of OGD. Twenty-four hours following OGD, cell viability was quantified using calcein-AM fluorescence. We observed that isoflurane preconditioning increased cell survival following subsequent OGD regardless of innate cell sex, but that the presence of 17β-estradiol before and during isoflurane preconditioning attenuated this protection only in female neurons independent of nuclear estrogen receptors. We also found that independent of preconditioning treatment, female neurons were less sensitive to OGD compared with male neurons and that transient treatment with 17β-estradiol protected both male and female neurons from subsequent OGD. More studies are needed to determine how cell type, cell sex, and sex steroids like 17β-estradiol may impact on anesthetic preconditioning and subsequent ischemic outcomes in the brain. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Confirmation of the progesterone receptor as an efficient marker of treatment with 17β-estradiol in veal calves.

PubMed

Pezzolato, Marzia; Botta, Mario; Baioni, Elisa; Richelmi, Guia Benedetta; Pitardi, Danilo; Varello, Katia; Caramelli, Maria; Bozzetta, Elena

2016-01-01

Under current European Union legislation the use of anabolic steroids in food-producing livestock is banned because of their long-term adverse effects on human health. We examined the expression profile of the immunohistochemical marker progesterone receptor in veal calves' sex accessory glands following experimental administration of anabolic compounds. The aim was to confirm the accuracy of the immunohistochemical approach in the detection of the over-expression of the progesterone receptor induced by the administration of sexual steroids at low levels (17β-estradiol and nandrolone alone or in combination). A total of 217 male veal calves were randomly divided into four groups: group A (104 calves) treated with 17β-estradiol (5 mg/head; 4 weekly injections); group B (20 calves) treated with nandrolone (50 mg/head; 4 weekly injections); group C (20 calves) treated with the association of the two steroids (5 mg estradiol + 50 mg nandrolone; 4 weekly injections); and group K (73 calves) kept as a control. All the sexual accessory glands were collected at the slaughterhouse (15 days after the last administration) and subjected to immunohistochemical staining with anti-progesterone receptor antibody. All the calves treated with 17β-estradiol alone or in association with nandrolone (groups A and C) showed strong positivity, while nandrolone-treated calves and controls (groups B and K) gave negative results to the immunohistochemical investigation. The statistical analysis showed that the progesterone receptor is a significant predictor of 17β-estradiol treatment alone or in association with nandrolone (p < 0.001): the immunohistochemical study resulted in 100% sensitivity (CI = 95%: 97.1-100%) and specificity (CI = 95%: 95.1-100%) for prostate and 99% sensitivity (CI = 95%: 95.6-100%) and 100% specificity (CI = 95%: 95.1-100%) for bulbo-urethral glands. The data confirm that this innovative biological approach offers a reliable tool to enhance the efficacy of the histological test to detect illegal treatments with estrogens alone or in association with androgens.

Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.

PubMed

Banciu, Adela; Banciu, Daniel Dumitru; Mustaciosu, Cosmin Catalin; Radu, Mihai; Cretoiu, Dragos; Xiao, Junjie; Cretoiu, Sanda Maria; Suciu, Nicolae; Radu, Beatrice Mihaela

2018-05-09

Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine myometrium and their gene expression regulation by beta-estradiol in pregnant conditions. Further exploration of the calcium signaling in TCs and its modulation by estrogen hormones will contribute to the understanding of labor and pregnancy mechanisms and to the development of effective strategies to reduce the risk of premature birth.

Testosterone Represses Estrogen Signaling by Upregulating miR-22: A Mechanism for Imbalanced Steroid Hormone Production in Preeclampsia.

PubMed

Shao, Xuan; Liu, Yanlei; Liu, Ming; Wang, Yongqing; Yan, Liying; Wang, Hao; Ma, Liyang; Li, Yu-Xia; Zhao, Yangyu; Wang, Yan-Ling

2017-04-01

Preeclampsia, a multisystem syndrome occurring during mid- to late gestation in humans, is a leading cause of maternal and perinatal morbidity and mortality. Patients usually present with high circulating testosterone and reduced estradiol production, but the mechanisms remain unclear. Revealing the mechanism that modulating the imbalance of testosterone and estradiol in preeclampsia is of great value in understanding the cause of the disease. The placenta is the predominant source of steroid hormone production during gestation, and we observed markedly increased 17β-HSD3 (17β-hydroxysteroid dehydrogenase 3) levels and downregulated aromatase expression, the key enzymes responsible for synthesis of testosterone and estradiol, respectively, in preeclamptic placentas compared with controls. Furthermore, we found a significant upregulation of microRNA (miR)-22 in preeclamptic placentas. In a trophoblast cell line, JEG-3 cells, testosterone repressed the expression of aromatase and estrogen receptor α and the production of estradiol while promoting miR-22 expression. miR-22 directly targeted and inhibited estrogen receptor α expression while indirectly decreasing aromatase expression and estradiol production by interfering with estrogen receptor α signaling. Furthermore, inhibition of miR-22 expression significantly reversed the inhibitory effect of testosterone on de novo estradiol synthesis in human trophoblastic cells. The findings reveal a mechanism underlying the balanced production of androgen and estrogen modulated by miR-22 in the human placenta and provide new insights into the pathogenesis of preeclampsia from the aspect of endocrine regulation. © 2017 American Heart Association, Inc.

Fate of glucuronide conjugated estradiol in the environment

USDA-ARS?s Scientific Manuscript database

The fate and transport of conjugated reproductive hormones, which are polar compared to parent hormones, are little understood. Laboratory bench-scale soil (Hamar; Sandy, mixed, frigid typic Endoaquolls) sorption studies were conducted using [14C] 17ß-estradiol-3-glucuronide for a range of concentra...

17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Seulki, E-mail: sl10f@naver.com; Lee, Minjong, E-mail: minjonglee2@naver.com; Kim, Jong Bin, E-mail: kkimjp@hanmail.net

17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCCmore » cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.« less

Naproxen or Estradiol for Bleeding and Spotting with the Levonorgestrel Intrauterine System: A Randomized Controlled Trial

PubMed Central

MADDEN, Tessa; PROEHL, Sarah; ALLSWORTH, Jenifer E.; SECURA, Gina M.; PEIPERT, Jeffrey F.

2011-01-01

Objective To evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women initiating the levonorgestrel-releasing intrauterine system (LNG-IUS). Study Design We conducted a randomized controlled trial of naproxen, estradiol, or placebo administered over the first 12 weeks of LNG-IUS use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. Results There were 129 women randomized to naproxen (n=42), estradiol (n=44), or placebo (n=43). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared to placebo, 42.9% versus 16.3% (p=0.03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (RRadj 0.90, 95%CI 0.84–0.97) compared to placebo. More frequent bleeding and spotting was observed in the estradiol group (RRadj 1.25, 95%CI 1.17–1.34). Conclusions Administration of naproxen resulted in a reduction in bleeding and spotting days compared to placebo. (150 words) PMID:22055339

Effect of neonatal ovariectomy and estradiol treatment on corticosterone release in response to stress in the adult female rat.

PubMed

McCormick, Cheryl M

2011-01-01

Although organizational effects of sex hormones in early life on hypothalamic-pituitary-adrenal function have been reported for males, the findings are mixed for females, likely the result of not controlling for adult gonadal status. In experiment 1, females were ovariectomized (OVX) either on postnatal day 1 or as adults and given estradiol benzoate (EB) and progesterone implants or not as adults. Corticosterone release in response to restraint stress was responsive to hormonal replacement irrespective of timing of OVX: without replacement, both OVX groups had lower corticosterone concentrations after restraint stress than did OVX groups with replacement and gonadally intact females. Thus, neonatal OVX did not alter the activational effects of sex hormones in adulthood. In a second experiment, females administered a dose of EB on postnatal day 1 had a more rapid decline of corticosterone concentrations after restraint as adults compared to oil-treated females, irrespective of whether they were OVX as neonates or as adults (all groups were given estradiol replacement as adults). Thus, evidently there are organizational effects of the sex hormonal milieu of the neonatal female, although this is a modest effect compared to previous reports in males.

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

EPA Science Inventory

We propose that gene expression changes in accessible tissues such as blood often reflect those in inaccessible tissues, thus offering a convenient biomonitoring method to provide insight into the effects of environmental toxicants on such tissues. In this pilot study, gene expre...

TISSUE DISTRIBUTION AND HISTOLOGY OF FITC AND FITC-17B-ESTRADIOL IN CUNNER (TAUTOGOLABRUS ADSPERSUS) AFTER SUBCUTANEOUS IMPLANTATION IN A CONTROL RELEASE MATRIX

EPA Science Inventory

Peritoneal injection is a major route for chemical introduction into fish for toxicological studies. This procedure, however, causes rapid exposure to toxicants. Long-term studies to determine effects of estrogenic chemicals on fish reproduction require a methodology that allows ...

Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats.

PubMed

Lin, Chao-Wei; Chen, Bi; Huang, Ke-Lun; Dai, Yu-Sen; Teng, Hong-Lin

2016-04-01

17β-estradiol (E2) has been shown to have neuroprotective effects in different central nervous system diseases. The mechanisms underlying estrogen neuroprotection in spinal cord injury (SCI) remain unclear. Previous studies have shown that autophagy plays a crucial role in the course of nerve injury. In this study, we showed that E2 treatment improved the restoration of locomotor function and decreased the loss of motor neurons in SCI rats. Real-time PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3II and beclin-1 expression. Immunohistochemical study further confirmed that the immunoreactivity of LC3 in the motor neurons was down-regulated when treated with E2. In vitro studies demonstrated similar results that E2 pretreatment decreased the autophagic activity induced by rapamycin (autophagy sensitizer) and increased viability in a PC12 cell model. These results indicated that the neuroprotective effects of E2 in SCI are partly related to the suppression of excessive autophagy.

Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review.

PubMed

Lete, Iñaki; Chabbert-Buffet, Nathalie; Jamin, Christian; Lello, Stefano; Lobo, Paloma; Nappi, Rossella E; Pintiaux, Axelle

2015-01-01

Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.

Steroid sulfatase inhibition success and limitation in breast cancer clinical assays: an underlying mechanism.

PubMed

Sang, Xiaoye; Han, Hui; Poirier, Donald; Lin, Sheng Xiang

2018-05-24

Steroid sulfatase is detectable in most hormone-dependent breast cancers. STX64, an STS inhibitor, induced tumor reduction in animal assay. Despite success in phase І clinical trial, the results of phase II trial were not that significant. Breast Cancer epithelial cells (MCF-7 and T47D) were treated with two STS inhibitors (STX64 and EM1913). Cell proliferation, cell cycle, and the concentrations of estradiol and 5α-dihydrotestosterone were measured to determine the endocrinological mechanism of sulfatase inhibition. Comparisons were made with inhibitions of reductive 17β-hydroxysteroid dehydrogenases (17β-HSDs). Proliferation studies showed that DNA synthesis in cancer cells was modestly decreased (approximately 20%), accompanied by an up to 6.5% in cells in the G0/G1 phase and cyclin D1 expression reduction. The concentrations of estradiol and 5α-dihydrotestosterone were decreased by 26% and 3% respectively. However, supplementation of 5α-dihydrotestosterone produced a significant increase (approximately 35.6%) in the anti-proliferative effect of sulfatase inhibition. This study has clarified sex-hormone control by sulfatase in BC, suggesting that the different roles of estradiol and 5α-dihydrotestosterone can lead to a reduction in the effect of sulfatase inhibition when compared with 17β-HSD7 inhibition. This suggests that combined treatment of sulfatase inhibitors with 17β-HSD inhibitors such as the type7 inhibitor could hold promise for hormone-dependent breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in the concentrations of four maternal steroids during embryonic development in the threespined stickleback (Gasterosteus aculeatus).

PubMed

Paitz, Ryan Thomas; Mommer, Brett Christian; Suhr, Elissa; Bell, Alison Marie

2015-08-01

Embryonic exposure to steroids often leads to long-term phenotypic effects. It has been hypothesized that mothers may be able to create a steroid environment that adjusts the phenotypes of offspring to current environmental conditions. Complicating this hypothesis is the potential for developing embryos to modulate their early endocrine environment. This study utilized the threespined stickleback (Gasterosteus aculeatus) to characterize the early endocrine environment within eggs by measuring four steroids (progesterone, testosterone, estradiol, and cortisol) of maternal origin. We then examined how the concentrations of these four steroids changed over the first 12 days post fertilization (dpf). Progesterone, testosterone, estradiol, and cortisol of maternal origin could be detected within unfertilized eggs and levels of all four steroids declined in the first 3 days following fertilization. While levels of progesterone, testosterone, and estradiol remained low after the initial decline, levels of cortisol rose again by 8 dpf. These results demonstrate that G. aculeatus embryos begin development in the presence of a number of maternal steroids but levels begin to change quickly following fertilization. This suggests that embryonic processes change the early endocrine environment and hence influence the ability of maternal steroids to affect development. With these findings, G. aculeatus becomes an intriguing system in which to study how selection may act on both maternal and embryonic processes to shape the evolutionary consequence of steroid-mediated maternal effects. © 2015 Wiley Periodicals, Inc.

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

21 CFR 556.240 - Estradiol and related esters.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD Specific Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol... increments above the concentrations of estradiol naturally present in untreated animals: (a) In uncooked...

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...

Decrease in water-soluble 17beta-Estradiol and testosterone in composted poultry manure with time.

PubMed

Hakk, Heldur; Millner, Patricia; Larsen, Gerald

2005-01-01

Little attention has been paid to the environmental fate of the hormones 17beta-estradiol and testosterone excreted in animal waste. Land application of manure has a considerable potential to affect the environment with these endocrine disrupting compounds (EDCs). Composting is known to decompose organic matter to a stable, humus-like material. The goal of the present study was to quantitatively assess levels of water-soluble 17beta-estradiol and testosterone in composting chicken manure with time. Chicken layer manure was mixed with hay, straw, decomposed leaves, and starter compost, adjusted to approximately 60% moisture, and placed into a windrow. A clay-amended windrow was also prepared. Windrows were turned weekly, and temperature, oxygen, and CO(2) in the composting mass were monitored for either 133 or 139 d. Commercial enzyme immunoassay kits were used to quantitate the levels of 17beta-estradiol and testosterone in aqueous sample extracts. Water-soluble quantities of both hormones diminished during composting. The decrease in 17beta-estradiol followed first-order kinetics, with a rate constant k = -0.010/d. Testosterone levels declined at a slightly higher rate than 17beta-estradiol (i.e., k = -0.015/d). Both hormones could still be measured in aqueous extracts of compost sampled at the conclusion of composting. The decline in water-soluble 17beta-estradiol and testosterone in extracts of clay-amended compost was not statistically different from normal compost. These data suggest that composting may be an environmentally friendly technology suitable for reducing, but not eliminating, the concentrations of these endocrine disrupting hormones at concentrated animal operation facilities.

Do mollusks use vertebrate sex steroids as reproductive hormones? II. Critical review of the evidence that steroids have biological effects.

PubMed

Scott, Alexander P

2013-02-01

In assessing the evidence as to whether vertebrate sex steroids (e.g. testosterone, estradiol, progesterone) have hormonal actions in mollusks, ca. 85% of research papers report at least one biological effect; and 18 out of 21 review papers (published between 1970 and 2012) express a positive view. However, just under half of the research studies can be rejected on the grounds that they did not actually test steroids, but compounds or mixtures that were only presumed to behave as steroids (or modulators of steroids) on the basis of their effects in vertebrates (e.g. Bisphenol-A, nonylphenol and sewage treatment effluents). Of the remaining 55 papers, some can be criticized for having no statistical analysis; some for using only a single dose of steroid; others for having irregular dose-response curves; 40 out of the 55 for not replicating the treatments; and 50 out of 55 for having no within-study repetition. Furthermore, most studies had very low effect sizes in comparison to fish-based bioassays for steroids (i.e. they had a very weak 'signal-to-noise' ratio). When these facts are combined with the fact that none of the studies were conducted with rigorous randomization or 'blinding' procedures (implying the possibility of 'operator bias') one must conclude that there is no indisputable bioassay evidence that vertebrate sex steroids have endocrinological or reproductive roles in mollusks. The only observation that has been independently validated is the ability of estradiol to trigger rapid (1-5 min) lysosomal membrane breakdown in hemocytes of Mytilus spp. This is a typical 'inflammatory' response, however, and is not proof that estradiol is a hormone - especially when taken in conjunction with the evidence (discussed in a previous review) that mollusks have neither the enzymes necessary to synthesize vertebrate steroids nor nuclear receptors with which to respond to them. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Repressive effect of the phytoestrogen genistein on estradiol-induced uterine leiomyoma cell proliferation.

PubMed

Miyake, Asako; Takeda, Takashi; Isobe, Aki; Wakabayashi, Atsuko; Nishimoto, Fumihito; Morishige, Ken-Ichirou; Sakata, Masahiro; Kimura, Tadashi

2009-06-01

Uterine leiomyomas are the most common gynecological benign tumor and greatly affect reproductive health and well-being. They are the predominant indication for hysterectomy in premenopausal women. Current epidemiological study reported that soy products intake is inversely associated with diseases leading to hysterectomy. Genistein is a soy-derived phytoestrogen and its inhibitory effect on leiomyoma cell proliferation is reported. In this study, we investigated the siginificant inhibitory effect of genistein on estradiol (E(2))-induced leiomyoma cells proliferation. The Eker rat-derived uterine leiomyoma cell line ELT-3 cells were used. Cell proliferation was assessed by counting the number of cells. The expression of estrogen receptors and peroxisome proliferator-activated receptor-gamma (PPARgamma) was evaluated by Western blot analysis. PPARgamma was expressed in ELT-3 cells and genistein acted as PPARgamma ligand. This inhibitory effect of genistein was attenuated by the treatment of cells with PPARgamma antagonist bisphenol A diglycidyl ether (BADGE) or GW9662. These experimental findings in vitro show that the repressive effect of genistein on E(2)-induced ELT-3 cell proliferation is through the activation of PPARgamma. Genistein may be useful as an alternative therapy for leiomyoma.

Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study

PubMed Central

Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet

2017-01-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. PMID:28324068

Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study.

PubMed

Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet; Flaws, Jodi A

2017-06-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. Copyright © 2017 Endocrine Society.

Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

PubMed Central

Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

2011-01-01

Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

PubMed

Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

2011-03-10

The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

INTERACTION OF ESTRADIOL AND 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN AN OVULATION MODEL: EVIDENCE FOR SYSTEMIC POTENTIATION AND LOCAL OVARIAN EFFECTS. (R826132)

EPA Science Inventory

Immature rats were treated with estradiol cypionate, (ECP, 0, 0.1, 1, or 2 mg/kg s.c.) followed 24 h later by TCDD (0 or 10 g/kg orally). Follicular development was induced with eC...

Sufficient progesterone-priming prior to estradiol stimulation is required for optimal induction of the cervical prostaglandin system in pregnant sheep at 0.7 gestations.

PubMed

Wu, Wen Xuan; Coksaygan, Turhan; Chakrabarty, Kaushik; Collins, Valta; Rose, James C; Nathanielsz, Peter W

2005-08-01

The purposes of this study were to determine the separate and interactive functions of progesterone and estradiol in regulating the cervical prostaglandin (PG) system in pregnant sheep at 0.7 gestations. At 106-108 days of gestational age (dGA), ewes were treated with vehicle for 14 days (n = 5) or vehicle for 12 days followed by estradiol 5 mg twice a day, intramuscularly for 2 days (n = 5) or progesterone 100 mg, twice a day, intramuscularly for 14 days (n = 5) or progesterone 100 mg twice a day, intramuscularly for 10 days and then 2 days vehicle followed by estradiol 5 mg twice a day intramuscularly for 2 days (n = 5). At 121-123 dGA, cervical tissues were obtained under halothane anesthesia. Cervical RNA and protein were extracted and analyzed for prostaglandin-endoperoxide synthase 2 (COX2), two PGE(2) receptors, PTGER2 and PTGER4, and estrogen receptor alpha (ESR1) by Northern and Western blot analysis. Immunocytochemistry and in situ hybridization were applied to localize cellular distribution of COX2, PTGER2, and PTGER4 in the cervix. Data were analyzed by ANOVA. COX2 and PTGER4 mRNAs and proteins were increased (P < 0.05) in ewes treated with combined estradiol and progesterone but not in ewes treated with estradiol or progesterone alone compared with controls. ESR1 mRNA was increased in ewes treated with progesterone and estradiol plus progesterone. In contrast, PTGER2 mRNA and protein remained the same after all treatments. COX2 mRNA and protein were localized only in cervical glandular epithelial cells, whereas PTGER2 and PTGER4 were localized in both cervical glandular epithelial and smooth muscle cells. In conclusion, these data suggest that additional progesterone priming at 0.7 gestations synergizes with estradiol to induce cervical COX2, PTGER4, and ESR1 and support our hypothesis that stimulation of the cervical PG system by estradiol is optimized by sufficient progesterone priming in the pregnant sheep cervix.

Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol (Alesse). North american Levonorgestrel Study Group (NALSG).

PubMed

Archer, D F; Maheux, R; DelConte, A; O'Brien, F B

1999-11-01

The efficacy and safety of a low-dose 21-day combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol were evaluated in an open-label, multicenter trial. A total of 1708 subjects with regular menstrual cycles (27,011 cycles) were evaluated. The oral contraceptive was administered once a day for 21 days, followed by 7 days of placebo for a complete cycle. During 26,554 cycles evaluated for efficacy, 18 pregnancies occurred (Pearl index of 0.88); 6 of these events were attributable to subject noncompliance. After 30 cycles of exposure the cumulative rate of withdrawal as a result of accidental pregnancy was 1.9%. Breakthrough bleeding (with or without spotting) occurred in 12.9% of the cycles and spotting alone occurred in 10.1% of the cycles. The 2 most common adverse events cited as reasons for discontinuation were headache (2% of subjects) and metrorrhagia (2%). One serious event led to withdrawal of a subject. Overall, the results of this study demonstrate that the monophasic regimen of 100 microg levonorgestrel and 20 microg ethinyl estradiol offers effective contraception, acceptable cycle control, and a good tolerability profile.

Estrogen Replacement Regulates Vaginal Innervations in Ovariectomized Adult Virgin Rats: A Histological Study.

PubMed

Li, Ting; Ma, Yuanyuan; Zhang, Hong; Yan, Ping; Huo, Lili; Hu, Yongyan; Chen, Xi; Li, Ting; Zhang, Miao; Liu, Zhaohui

2017-01-01

Background . Our previous Gräfenberg spot findings confirmed that the distal-third areas of the anterior vaginal wall bore a significantly greater number of nerves and sexual hormone may have certain degree of influence on these significant differences. However, the role of estrogen in vaginal innervations remains controversial. Methods . To investigate whether hormonal-neural interactions occur in the vagina, sixty rats were randomly divided into six groups: Sham-operated, ovariectomy, and 4 treatment groups. After 2 weeks of treatment, vaginal biopsies were prepared with hematoxylin and eosin and PGP9.5 using immunohistochemistry. Results . The density of small nerve fibers was significantly higher in the distal-half areas of intact vaginal walls than the proximal-half areas ( P = 0.001). In contrast, the overall PGP 9.5-ir fiber innervation density was significantly decreased in the OVX rats subjected to surgical menopause. Sustained estrogen administration for 2 weeks resulted in nerve fiber proliferation, with values reaching normal levels in the low-dose estradiol valerate group. Conclusion . Our findings indicate that systemic hormonal therapy with low-dose estradiol valerate is effective and safe for treating deficient vaginal innervation caused by low level of estrogen activity in menopausal women and may aid studies to identify an optimal estradiol dose to provide relief from vaginal discomfort.

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,…

77 FR 31722 - New Animal Drugs; Change of Sponsor; Estradiol; Estradiol Benzoate and Testosterone Propionate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Change of Sponsor; Estradiol; Estradiol Benzoate.... ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect a change of sponsor for 17 new animal drug applications (NADAs) and abbreviated new...

[Influence of estradiol on tryptophan hydroxylase and 5-hydroxytryptamine content in raphe nuclei of rats under forced swimming stress].

PubMed

Yang, Fu-zhong; Wu, Yan; Zhang, Wei-guo; Cai, Yi-yun; Shi, Shen-xun

2010-07-20

To investigate the effect of estradiol (E2) on tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) content in raphe nuclei of rats under forced swimming stress and explore the role of estrogen and stress in disease mechanism of depression in women. At Week 3 post-ovariectomy, 35 ovariectomized (OVX) female SD rats were randomly divided into 5 groups (n = 7): non-stress group, control group, estradiol (E2) group and fluoxetine (FLX) group and E2 plus FLX group. Animals were administered with different drugs for 2 weeks. At Day 14, animals except those in the non-stress group were subjected to the 15 min forced swimming test (FST). At 2 hours post-FST, all animals including those in the non-stress group were perfused with 4% paraformaldehyde and brains removed for TPH and 5-HT immunofluorescence staining. We compared the content of TPH and 5-HT by observing and calculating the integrated optical density (IOD) of immunofluorescent-positive signals in raphe nuclei. (1) The IOD value of TPH- and 5-HT-positive region in raphe nuclei of rats in the control group was significantly lower than that of the non-stress group (P < 0.01); (2) the IOD value of TPH- and 5-HT-positive region in raphe nuclei of rats in the E2, FLX and E2 plus FLX groups was significantly higher than that in the control group (P < 0.05). Forced swimming stress can decrease the TPH and 5-HT content in raphe nuclei. Such changes can be prevented by a pre-administration of estradiol. Similar results are observed with antidepressant fluoxetine. These effects may underlie the role of estradiol and stress in the disease mechanism of depression in women.

Estrone sulfate source of estrone and estradiol formation in isolated human hair roots: identification of a pathway linked to hair growth phase and subject to site-, gender-, and age-related modulations.

PubMed

Wehner, Gabriele; Schweikert, Hans-Udo

2014-04-01

The present study investigated the metabolism of estrone sulfate into bioactive estrogens in the human hair root, including the effects of hair growth phase, anatomical site, gender, and age. Healthy male (n = 18) and female (n = 20) subjects were investigated. Growing (anagen) and resting (telogen) hair roots were collected from selected scalp and body sites. Estrone sulfate metabolism in the hair root yielded substantial levels of estrone and estradiol. Estrogen synthesis exceeded that associated with aromatization of androgens in a previous study. In subjects <50 years old, estrogen synthesis in scalp hair was lower in men than in women. Comparable levels of estrogen formation were observed in 1) male and female axillary and pubic hair and 2) male beard hair. These levels were higher than the estrogen levels detected in the in scalp hair of men <50 years old. With increasing age, estrogen synthesis increased in men and decreased in women. In telogen hair from all body sites, the capacity to form estrone from estrone sulfate remained unaffected, whereas the ability to form estradiol decreased by 62% and 86% in men and women, respectively. Estrogen formation from estrone sulfate in sexually dimorphic hair is linked to the hair growth phase and is subject to gender- and age-related modulations. The magnitude of the in situ estrogen synthesis from estrone sulfate and the selective arrest of estradiol synthesis at the end of the hair cycle suggest that this pathway plays a crucial role in the regulation of human hair growth.

Effect of diets containing soy protein isolate on bone formation are mediated through non-classical estrogenic signaling in pre-pubertal rats

USDA-ARS?s Scientific Manuscript database

Most soy foods contain isoflavones which under certain conditions may have estrogen-like actions. We have studied the effects of soy protein isolate (SPI) on bone quality and compared these effects to 17 ß-estradiol (E2). Weanling male and female rats were either fed a SPI-containing diet, or admini...

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex.

PubMed

Herrera, Jose L; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M; Alonso, Rafael; Wandosell, Francisco G

2018-01-01

Different dietary ratios of n -6/ n -3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n -6/ n -3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n -3 and n -6 LC-PUFAs.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex

PubMed Central

Herrera, Jose L.; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G.; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M.; Alonso, Rafael; Wandosell, Francisco G.

2018-01-01

Different dietary ratios of n−6/n−3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n−6/n−3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n−3 and n−6 LC-PUFAs. PMID:29740285

Origin of estradiol fatty acid esters in human ovarian follicular fluid.

PubMed

Pahuja, S L; Kim, A H; Lee, G; Hochberg, R B

1995-03-01

The estradiol fatty acid esters are the most potent of the naturally occurring steroidal estrogens. These esters are present predominantly in fat, where they are sequestered until they are hydrolyzed by esterases. Thus they act as a preformed reservoir of estradiol. We have previously shown that ovarian follicular fluid from patients undergoing gonadotropin stimulation contains very high amounts of estradiol fatty acid esters (approximately 10(-7) M). The source of these esters is unknown. They can be formed by esterification of estradiol in the follicular fluid by lecithin:cholesterol acyltransferase (LCAT), or in the ovary by an acyl coenzyme A:acyltransferase. In order to determine which of these enzymatic processes is the source of the estradiol esters in the follicular fluid, we incubated [3H]estradiol with follicular fluid and cells isolated from human ovarian follicular fluid and characterized the fatty acid composition of the [3H]estradiol esters biosynthesized in each. In addition, we characterized the endogenous estradiol fatty acid esters in the follicular fluid and compared them to the biosynthetic esters. The fatty acid composition of the endogenous esters was different than those synthesized by the cellular acyl coenzyme A:acyltransferase, and the same as the esters synthesized by LCAT, demonstrating that the esters are produced in situ in the follicular fluid. Although the role of these estradiol esters in the ovary is not known, given their remarkable estrogenic potency it is highly probable that they have an important physiological role.

Organizational effects of diethylstilbestrol on brain vasotocin and sexual behavior in male quail.

PubMed

Viglietti-Panzica, Carla; Montoncello, Barbara; Mura, Elena; Pessatti, Marzia; Panzica, GianCarlo

2005-04-15

In Japanese quail, we previously described a sexual dimorphism of the parvocellular vasotocin system of the limbic region that, as the reproductive behavior, is steroid-sensitive and is organized during embryonic life by the exposure to estradiol. We verified in this study whether diethylstilbestrol, a chemical xenoestrogen, has analogous organizational effects on the vasotocin system of limbic regions and on copulatory behavior of male Japanese quail. We injected in the yolk sac of 3 day-old quail embryos diethylstilbestrol or estradiol benzoate (a treatment which suppresses male copulatory behavior in adulthood and reduces vasotocin innervation), or sesame oil (control). No further hormonal manipulations were performed after hatching. Sexual behavior was recorded in males at the age of 6 weeks. Estradiol- and diethylstilbestrol-treated males exhibited a total suppression of copulatory behavior. After behavioral tests, all males were sacrificed and brain sections processed for vasotocin immunocytochemistry. Significant decrease in the density of vasotocin immunoreactivity was detected in the medial preoptic nucleus, in the bed nucleus of stria terminalis, and in the lateral septum of diethylstilbestrol-treated males. The magnocellular vasotocin neurons were, in contrast, not affected. In conclusion, the present data demonstrate that embryonic treatment with diethylstilbestrol induces a full sex reversal of behavioral phenotype as well as a significant decrease of vasotocin expression in the preoptic-limbic region in male Japanese quail. Therefore, the parvocellular vasotocin system could represent an optimal model to investigate the effects of pollutants on neural circuits controlling reproductive functions.

A Comparison of Pathology Found in Three Marine Fish Treated with Endocrine Disrupting Compounds

EPA Science Inventory

Endocrine-disrupting chemicals (EDCs), such as the estrogen estradiol (E2) have been reported to affect fish reproduction. This study histopathologically compared and evaluated the effect of EDCs in three species of treated fish. Juvenile male summer flounder (Paralichthys dentat...

Transcriptomics and ecological risk assessment: Case studies with fish exposed to bisphenol A and diethylstilbesterol

EPA Science Inventory

Bisphenol A (BPA) and diethylstilbesterol (DES) are endocrine active chemicals whose actions as estrogen receptor agonists are well characterized. Bisphenol A, while comparatively weak as an estrogen relative to 17â-estradiol (E2) or 17á-ethynyl estradiol (EE2), is a...

Sorption of bisphenol A, 17a-ethinyl estradiol and phenanthrene on thermally and hydrothermally produced biochars

USDA-ARS?s Scientific Manuscript database

In this study, organic contaminant removal potential of biochars made from various agricultural residuals was investigated through sorption experiments. The model pollutants include endocrine disrupting chemicals (EDCs) such as common estrogenic compounds, bisphenol A (BPA) and 17a-ethinyl estradiol...

Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty.

PubMed

Freire, Analía Verónica; Gryngarten, Mirta Graciela; Ballerini, María Gabriela; Arcari, Andrea Josefina; Escobar, María Eugenia; Bergadá, Ignacio; Ropelato, María Gabriela

2016-01-01

Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment. © 2015 S. Karger AG, Basel.

Progesterone is essential for maintenance and growth of uterine leiomyoma.

PubMed

Ishikawa, Hiroshi; Ishi, Kazutomo; Serna, Vanida Ann; Kakazu, Rafael; Bulun, Serdar E; Kurita, Takeshi

2010-06-01

Uterine leiomyomata (ULs) represent the most common tumor in women and can cause abnormal uterine bleeding, large pelvic masses, and recurrent pregnancy loss. Although the dependency of UL growth on ovarian steroids is well established, the relative contributions of 17beta-estradiol and progesterone are yet to be clarified. Conventionally, estradiol has been considered the primary stimulus for UL growth, and studies with cell culture and animal models support this concept. In contrast, no research model has clearly demonstrated a requirement of progesterone in UL growth despite accumulating clinical evidence for the essential role of progesterone in this tumor. To elucidate the functions of ovarian steroids in UL, we established a xenograft model reflecting characteristics of these tumors by grafting human UL tissue beneath the renal capsule of immunodeficient mice. Leiomyoma xenografts increased in size in response to estradiol plus progesterone through cell proliferation and volume increase in cellular and extracellular components. The xenograft growth induced by estradiol plus progesterone was blocked by the antiprogestin RU486. Furthermore, the volume of established UL xenografts decreased significantly after progesterone withdrawal. Surprisingly, treatment with estradiol alone neither increased nor maintained the tumor size. Although not mitogenic by itself, estradiol induced expression of progesterone receptor and supported progesterone action on leiomyoma xenografts. Taken together, our findings define that volume maintenance and growth of human UL are progesterone dependent.

Effect of steroid treatment of endometrial cells on blastocyst development during co-culture.

PubMed

Goff, A K; Smith, L C

1998-04-01

The objective of this study was to determine if treatment of endometrial cells with progesterone or progesterone plus estradiol would improve the development of bovine embryos to the blastocyst stage during co-culture. After IVF, bovine embryos were cultured with oviduct epithelial cells for 3 d. In Experiment 1 the embryos were cultured with a) oviduct epithelial cells; b) endometrial epithelial cells (EEC); c) EEC with 10 ng/ml progesterone (EEC + P); or d) EEC with 10 ng/ml progesterone and 10 pg/ml estradiol (EEC + PE) for 6 d. In Experiment 2 the embryos were cultured with a) oviduct epithelial cells; b) endometrial stromal cells (ESC); c) ESC with 10 ng/ml progesterone (ESC + P); or d) ESC with 10 ng/ml progesterone and 10 pg/ml estradiol (ESC + PE) for 6 d. Results from Experiment 1 showed that endometrial epithelial cells supported development to the blastocyst stage as effectively as the oviduct cells; however, the size of the blastocysts was smaller for the endometrial cells. There was no effect of steroid hormone treatment on development to the blastocyst stage or on the size of the blastocysts. Results from Experiment 2 showed that stromal cells supported development to the blastocyst stage as effectively as oviduct cells. The hatching rate was lower when the embryos were co-cultured with stromal cells than oviduct epithelial cells; but there was no effect of steroid treatment. These data show that untreated endometrial epithelial cells are as effective as oviduct cells in maintaining embryo development to the blastocyst stage. However, embryo development was not improved by steroid treatment of the cells.

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

PubMed Central

CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

2010-01-01

The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E2 in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E2-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels. PMID:22993572

Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

PubMed

Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

2010-05-01

The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

Protective Actions of 17β-Estradiol and Progesterone on Oxidative Neuronal Injury Induced by Organometallic Compounds

PubMed Central

Ishihara, Yasuhiro; Takemoto, Takuya; Yamazaki, Takeshi

2015-01-01

Steroid hormones synthesized in and secreted from peripheral endocrine glands pass through the blood-brain barrier and play a role in the central nervous system. In addition, the brain possesses an inherent endocrine system and synthesizes steroid hormones known as neurosteroids. Increasing evidence shows that neuroactive steroids protect the central nervous system from various harmful stimuli. Reports show that the neuroprotective actions of steroid hormones attenuate oxidative stress. In this review, we summarize the antioxidative effects of neuroactive steroids, especially 17β-estradiol and progesterone, on neuronal injury in the central nervous system under various pathological conditions, and then describe our recent findings concerning the neuroprotective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds, tributyltin, and methylmercury. PMID:25815107

Clinical and metabolic effects of medroxyprogesterone acetate and ethinyl estradiol plus drospirenone in women with polycystic ovary syndrome.

PubMed

Ozdemir, Suna; Görkemli, Hüseyin; Gezginç, Kazim; Ozdemir, Mustafa; Kiyici, Aysel

2008-10-01

To investigate the effects of treatment with medroxyprogesterone acetate (MPA), 10 days per month for 6 months, on lipid and carbohydrate metabolism in women with polycystic ovary syndrome (PCOS). Sixty-three women with PCOS were randomized to receive MPA or ethinyl estradiol plus drospirenone. There were no changes in lipid or carbohydrate metabolism in the MPA group, but serum levels of luteinizing hormone (P<0.001) and total testosterone (P<0.003) significantly decreased, as did the free androgen index (P<0.02) and acne (P<0.03) and seborrhea (P<0.04) scores. In the ethinyl estradiol plus drospirenone group lipid and hormone values significantly increased whereas acne, seborrhea, hair loss, and Ferriman-Gallwey scores decreased. There was no statistically significant change in the total cholesterol to high-density cholesterol ratio in either group. Treatment of PCOS patients with MPA provided good menstrual cycle control, beneficial changes in hormonal values associated with hyperandrogenism, and no significant changes in lipid or carbohydrate metabolism.

Feeding an enhanced diet to Holstein heifers during the preweaning period alters steroid receptor expression and increases cellular proliferation.

PubMed

Geiger, A J; Parsons, C L M; Akers, R M

2017-10-01

Preweaning diet and estradiol treatment alters mammary development. Our objectives were to study the effects of diet and estradiol on proliferation of mammary epithelial cells and expression of estrogen receptor α (ESR1) and progesterone receptors (PGR) in these cells. Thirty-six Holstein heifer calves were raised on (1) a control milk replacer fed at 0.44 kg of powder/head per day, dry matter (DM) basis (restricted, R; 20.9% crude protein, 19.8% fat, DM basis), or (2) an enhanced milk replacer fed at 1.08 kg of powder/head per day, DM basis (Enhanced, EH; 28.9% crude protein, 26.2% fat, DM basis). Milk replacer was fed for 8 wk. At weaning, a subset (n = 6/diet) of calves were euthanized and had tissue harvested. Remaining calves received estradiol implants (E 2 ) or placebo and were euthanized at wk 10 to harvest tissue. Treatments were (1) R, (2) R + E 2 (R-E2), (3) EH, and (4) EH + E 2 (EH-E2). One day before euthanasia calves were given bromo-2'-deoxyuridine (BrdU; 5 mg/kg of body weight). At euthanization, mammary parenchyma was removed and fixed. Tissue sections from zone 1 (cisternal), 2 (medial), and 3 (distal) within the mammary gland were stained with hematoxylin and eosin and antibodies to measure expression of ESR1, PGR, and incorporation of BrdU. At wk 8, R-fed calves had more PGR-expressing cells in distal parenchyma; however, PGR expression intensity was greater in EH-fed calves. The proportion of cells expressing ESR1 was not affected by diet, but expression intensity (receptors per positive cell) was greater in EH-fed calves across all zones (62-81%). Overall, the percent BrdU-positive epithelial cells was 2 and 0.5 fold greater for EH-fed calves in zone 2 and 3. The proportion of labeled cells was greater in terminal ductal units than in subtending ducts, and treatment effects were more evident in terminal ductal units. At wk 10, calves treated with estradiol had 3.9-fold greater PGR expression intensity. The intensity and percent of cells expressing ESR1 was lowest in estradiol-treated calves. Overall, estradiol-treated calves had the greatest number of proliferating epithelial cells. Moreover, in zone 3, EH-E2 calves had a higher percentage of proliferating cells than in all other treatments. Results indicate both diet and estradiol administration alter proliferation rates of the mammary epithelium and that changes in expression of ESR1 and PGR are involved in enhanced mammary development. The data support our hypothesis that enhanced preweaning feeding increases the mammary tissue responsiveness to mammogenic stimulation. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Androgen-estrogen synergy in rat levator ani muscle Glucose-6-phosphate dehydrogenase

NASA Technical Reports Server (NTRS)

Max, S. R.

1984-01-01

The effects of castration and hormone administration on the activity of glucose-6-phosphate dehydrogenase in the rat levator ani muscle were studied. Castration caused a decrease in enzyme activity and in wet weight of the levator ani muscle. Chronic administration of testosterone propionate increased glucose-6-phosphate dehydrogenase activity in the levator ani muscle of castrated rats; the magnitude of the recovery of enzyme activity was related to the length of time of exposure to testosterone propionate after castration as well as to the length of time the animals were castrated. The longer the period of castration before exposure to testosterone propionate, the greater the effect. This result may be related to previously reported castration-mediated increases in androgen receptor binding in muscle. Dihydrotestosterone was less effective than testosterone propionate in enhancing glucose-6-phosphate dehydrogenase activity in the levator ani muscle from castrated rats; estradiol-17-beta alone was ineffective. Combined treatment with estradiol-17-beta and dihydrotestosterone, however, was as effective as testosterone alone. Thus, androgens and estrogens may exert synergistic effects on levator ani muscle.

Placental peptides metabolism and maternal factors as predictors of risk of gestational diabetes in pregnant women. A case-control study

PubMed Central

Fondjo, Linda Ahenkorah; Gmagna, Peter; Ghartey, Frank Naku; Awe, Martin Akilla

2017-01-01

Background Gestational diabetes is a risk factor for perinatal complications; include shoulder dystocia, birth injuries such as bone fractures and nerve palsies. It is associated with later development of type 2 diabetes, the risk of macrosomia and other long-term health effects of infants born to diabetic mothers. The study assesses placental peptides and maternal factors as potential predictors of gestational diabetes among pregnant women. Material and methods A total of 200 pregnant women were recruited for the study, 150 pregnant women without pre gestational diabetes including 50 women with low risk factors of diabetes as controls and 50 other pregnant women with pregestational diabetes as control. Fasting blood glucose and the lipid profile were determined by enzymatic methods using Envoy® 500 reagents (Vital Diagnostics, USA). Glycated haemoglobin was assessed using the Cation Exchange resin method. Leptin and the Human Placenta Lactogen were assayed using the Sandwich-ELISA technique. Beta chorionic gonadotrophin, insulin, progesterone and estradiol were determined using chemilumiscence imunoassay technique on MAGLUMI 600 analyzer. Anthropometry, including BMI and blood pressure were also measured. Results Fasting plasma glucose (FBG), insulin, insulin resistance, glycated haemoglobin and Human Placenta Lactogen(HPL)were significantly (p<0.0001) increased in the pregestational diabetic women whereas progesterone and estradiol were significantly decreased. In the second trimester however, there was no significant difference (p>0.05) in estradiol, insulin, insulin resistance and HPL between the pregnant women who developed gestational diabetes and those who did not. Leptin, progesterone and FBG were significantly increased in those who developed GDM. The risk of developing gestational diabetes increased with overweight (OR = 1.76, P = 0.370) and family history of diabetes (OR = 2.18, P = 0.282). Conclusion Leptin, progesterone, estradiol estimated in this study were increased in the gestational diabetes mellitus women and fairly predicted gestational diabetes in the non-diabetics pregnant women. Obesity, aging and family history of diabetes were strongly predictive of gestational diabetes. PMID:28732072

Placental peptides metabolism and maternal factors as predictors of risk of gestational diabetes in pregnant women. A case-control study.

PubMed

Ngala, Robert Amadu; Fondjo, Linda Ahenkorah; Gmagna, Peter; Ghartey, Frank Naku; Awe, Martin Akilla

2017-01-01

Gestational diabetes is a risk factor for perinatal complications; include shoulder dystocia, birth injuries such as bone fractures and nerve palsies. It is associated with later development of type 2 diabetes, the risk of macrosomia and other long-term health effects of infants born to diabetic mothers. The study assesses placental peptides and maternal factors as potential predictors of gestational diabetes among pregnant women. A total of 200 pregnant women were recruited for the study, 150 pregnant women without pre gestational diabetes including 50 women with low risk factors of diabetes as controls and 50 other pregnant women with pregestational diabetes as control. Fasting blood glucose and the lipid profile were determined by enzymatic methods using Envoy® 500 reagents (Vital Diagnostics, USA). Glycated haemoglobin was assessed using the Cation Exchange resin method. Leptin and the Human Placenta Lactogen were assayed using the Sandwich-ELISA technique. Beta chorionic gonadotrophin, insulin, progesterone and estradiol were determined using chemilumiscence imunoassay technique on MAGLUMI 600 analyzer. Anthropometry, including BMI and blood pressure were also measured. Fasting plasma glucose (FBG), insulin, insulin resistance, glycated haemoglobin and Human Placenta Lactogen(HPL)were significantly (p<0.0001) increased in the pregestational diabetic women whereas progesterone and estradiol were significantly decreased. In the second trimester however, there was no significant difference (p>0.05) in estradiol, insulin, insulin resistance and HPL between the pregnant women who developed gestational diabetes and those who did not. Leptin, progesterone and FBG were significantly increased in those who developed GDM. The risk of developing gestational diabetes increased with overweight (OR = 1.76, P = 0.370) and family history of diabetes (OR = 2.18, P = 0.282). Leptin, progesterone, estradiol estimated in this study were increased in the gestational diabetes mellitus women and fairly predicted gestational diabetes in the non-diabetics pregnant women. Obesity, aging and family history of diabetes were strongly predictive of gestational diabetes.

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

USDA-ARS?s Scientific Manuscript database

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) ...