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...

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.

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.

Effects of repeated 9 and 30-day exposure to extremely low-frequency electromagnetic fields on social recognition behavior and estrogen receptors expression in olfactory bulb of Wistar female rats.

PubMed

Bernal-Mondragón, C; Arriaga-Avila, V; Martínez-Abundis, E; Barrera-Mera, B; Mercado-Gómez, O; Guevara-Guzmán, R

2017-02-01

We investigated the short- and long-term effects of extremely low-frequency electromagnetic fields (EMF) on social recognition behavior and expression of α- and β-estrogen receptors (ER). Rats were exposed to 60-Hz electromagnetic fields for 9 or 30 days and tested for social recognition behavior. Immunohistochemistry and western blot assays were performed to evaluate α- and β-ER expression in the olfactory bulb of intact, ovariectomized (OVX), and ovariectomized+estradiol (E2) replacement (OVX+E2). Ovariectomization showed impairment of social recognition after 9 days of EMF exposure and a complete recovery after E2 replacement and so did those after 30 days. Short EMF exposure increased expression of β-ER in intact, but not in the others. Longer exposure produced a decrease in intact but an increase in OVX and OVX+E2. Our findings suggest a significant role for β-estrogen receptors and a lack of effect for α-estrogen receptors on a social recognition task. EMF: extremely low frequency electromagnetic fields; ERs: estrogen receptors; OB: olfactory bulb; OVX: ovariectomized; OVX + E 2 : ovariectomized + estradiol replacement; IEI: interexposure interval; β-ER: beta estrogen receptor; E 2 : replacement of estradiol; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; WB: Western blot; PBS: phosphate-buffer saline; PB: phosphate-buffer.

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

PubMed

Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

2014-01-01

Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.

PubMed

Musicki, Biljana; Liu, Tongyun; Strong, Travis D; Lagoda, Gwen A; Bivalacqua, Trinity J; Burnett, Arthur L

2010-05-01

Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17beta (15 microg). Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction.

Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat Vagina

PubMed Central

Musicki, Biljana; Liu, Tongyun; Strong, Travis D.; Lagoda, Gwen A.; Bivalacqua, Trinity J.; Burnett, Arthur L.

2010-01-01

Introduction Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17β (15 μg). Main Outcome Measures Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. Conclusions These results define novel estrogen signaling mechanisms in the vagina which involve eNOS phosphorylation and eNOS-caveolin-1 interaction. PMID:20233295

The epidemiology of serum sex hormones in postmenopausal women

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

Cauley, J.A.; Kuller, L.H.; LeDonne, D.

1989-06-01

Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sexmore » hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.« less

Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies.

PubMed

Wise, P M; Dubal, D B; Wilson, M E; Rau, S W; Böttner, M; Rosewell, K L

2001-11-01

We have shown that 17beta-estradiol exerts profound protective effects against stroke-like ischemic injury in female rats. These effects are evident using physiological levels of estradiol replacement in ovariectomized rats and require hormone treatment prior to the time of injury. The protective actions of estradiol appear to be most prominent in the cerebral cortex, where cell death is not apparent until at least 4 h after the initiation of ischemic injury and where cell death is thought to be apoptotic in nature. Middle-aged rats remain equally responsive to the protective actions of estradiol. The maintenance of responsiveness of the cerebral cortex to the neuroprotective actions of estradiol was unexpected since responsiveness of the hypothalamus to estradiol decreases dramatically by the time animals are middle-aged. We believe that the protective actions of estradiol require the estrogen receptor-alpha, since estradiol does not protect in estrogen receptor-alpha knockout mice. We have also implemented a method of culturing cerebral cortical explants to assess the protective effects of estradiol in vitro. This model exhibits remarkable parallelisms with our in vivo model of brain injury. We have found that 17beta-estradiol decreases the extent of cell death and that this protective effect requires hormone pretreatment. Finally, 17alpha-estradiol, which does not interact effectively with the estrogen receptor, does not protect; and addition of ICI 182,780, an estrogen receptor antagonist, blocks the protective actions of estradiol. We have begun to explore the molecular and cellular mechanisms of estradiol-mediated protection. In summary, our findings demonstrate that estradiol exerts powerful protective effects both in vivo and in vitro and suggest that these actions are mediated by estrogen receptors.

Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study.

PubMed

de Fraga, Rogerio; Palma, Paulo; Dambros, Miriam; Riccetto, Cassio L Z; Mandarim-de-Lacerda, Carlos; Miyaoka, Ricardo

2009-05-01

The authors quantified the nerve fibers in the bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old). Group 1: remained intact; Group 2: underwent bilateral ovariectomy, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 3: sham-operated, and after 30 days was started on subcutaneous sesame oil replacement (0.2 ml per day) for 90 days; Group 4: bilateral ovariectomy, and after 30 days was started on subcutaneous injection of 17β-estradiol (10 μg/kg body weight) for 90 days. S-100 was used to stain nerves myelinized fibers on paraffin rat bladder sections. The G-50 grid system was used to quantitatively analyze the fibers. Long-term estrogen deprivation caused significant changes in bladder innervations, which can be characterized by a decreased number of nerve fibers by 65% (p < 0.001).

Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception.

PubMed

Tønnes Pedersen, Anette; Cleemann, Line; Main, Katharina M; Juul, Anders

2018-01-01

Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Thus, girls with delayed puberty should be evaluated for an underlying pathology before any treatment, including oral contraception, is initiated. Estrogen replacement is important and natural 17β-estradiol, preferably transdermally, is the preferred choice, whereas the oral route can be used as an alternative depending on patient preference and compliance. Sexual activity is often delayed in the hypogonadal adolescent girl. In the adolescent hypogonadal girl, hormone replacement therapy (HRT) most likely has been initiated at the time she becomes sexually active. If a risk of unwanted pregnancy cannot be ruled out, there is a need to consider contraception. This consideration does not contradict the principles of HRT but can be included as a part of the substitution, e.g. oral contraceptives containing 17β-estradiol or a progestogen intrauterine device combined with continuous 17β-estradiol (transdermal or oral). © 2018 S. Karger AG, Basel.

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.

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.

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.

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.

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 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.

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.

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.

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

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

Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats

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

Phrakonkham, Pascal; Chevalier, Joelle; Desmetz, Catherine

2007-10-15

The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological and molecular analyses on reproductivemore » organs. The impact on the oxidative metabolism of estradiol and on associated cytochrome P450 (CYP) activities was evaluated in liver microsomes. The relative wet weights of both the uterus and the vagina were increased in the equol group, but no significant changes in proliferating cell nuclear antigen or hormone receptor mRNA expression were noticed. In contrast, genistein and daidzein did not induce uterotrophy but caused an overexpression of estrogen receptor {alpha} mRNA which could correspond to a long-lasting effect of physiological concentrations of estrogens. The hepatic metabolism of estradiol was influenced by daidzein which increased the synthesis of putative mutagenic derivatives. At the same time, genistein favored estrogen 2-hydroxylation, and equol decreased 4-hydroxyestrogen production. Surprisingly, no significant alteration in hepatic CYP activities was detected. Taken together, these results demonstrate that isoflavonoid-based bone-sparing treatments are able to cause side effects on other estrogen-sensitive target organs when given in the long-term.« less

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.

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.

Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

PubMed Central

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

2015-01-01

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

Consistent high clinical pregnancy rates and low ovarian hyperstimulation syndrome rates in high-risk patients after GnRH agonist triggering and modified luteal support: a retrospective multicentre study.

PubMed

Iliodromiti, Stamatina; Blockeel, Christophe; Tremellen, Kelton P; Fleming, Richard; Tournaye, Herman; Humaidan, Peter; Nelson, Scott M

2013-09-01

Are clinical pregnancy rates satisfactory and the incidence of OHSS low after GnRH agonist trigger and modified intensive luteal support in patients with a high risk of ovarian hyperstimulation syndrome (OHSS)? GnRH agonist trigger combined with 1500 IU hCG at the time of oocyte retrieval and subsequent estradiol and progesterone replacement in OHSS high-risk patients can facilitate fresh embryo transfer with high clinical pregnancy rates and a low risk of severe OHSS. Conventional luteal support packages are inadequate to facilitate a fresh transfer after a GnRH agonist trigger. A low dose of hCG (1500 IU) after oocyte aspiration can be used to replace the actions of early luteal LH to sustain implantation and the function of the early corpus luteum, although the level of risk of severe OHSS with this strategy is unclear. This international multicentre retrospective case study, including 275 women at high risk of OHSS, was undertaken during the period January 2011-December 2012. Women were identified as at high risk of OHSS, based on IVF response, ovarian reserve characteristics and previous history of having had treatment, in three clinical IVF centres in UK, Belgium and Australia. All three centres used a GnRH agonist trigger followed by one bolus of 1500 IU hCG 1h after oocyte retrieval. Moreover, the luteal phase was supported with daily vaginal progesterone and twice daily estradiol valerate. A total of 275 autologous cycles with fresh transfer were undertaken in a cohort of high-risk women as defined by baseline characteristics [median (interquartile range)]: age 31.6 (29-35) years, antral follicle count median 25 (18-34) and anti-Müllerian hormone median 49.1 pmol/l (35.2-69.3). At the end of stimulation, the peak estradiol median of 12 000 pmol/l (9400-15 914) and the mean oocyte yield of 17.8 ± 8.4 confirmed a high response. The overall clinical pregnancy rate was 41.8% per cycle started, with only two cases of severe OHSS reported (0.72%). No significant differences in clinical pregnancy rates between centres were identified. This is a retrospective study and future randomized controlled trials will be able to compare whether these outcomes can be improved upon by either segmentation of the stimulation cycle and embryo transfer or alternative aggressive luteal support strategies. In women who are undergoing ovarian stimulation and who develop an excessive ovarian response, the use of a GnRH agonist trigger combined with modified luteal support can provide the opportunity to proceed to fresh embryo transfer with adequate clinical pregnancy rates. However, this procedure will not completely eliminate the risk of OHSS and for women with an extreme ovarian response or with significant comorbidity, where the possibility of severe OHSS is unacceptable, we recommend GnRH agonist trigger followed by a freeze-all policy to completely avoid OHSS.

The Role of Androgens and Estrogens on Healthy Aging and Longevity

PubMed Central

Dillon, E. Lichar; Urban, Randall J.; Sheffield-Moore, Melinda

2012-01-01

Aging is associated with a loss of sex hormone in both men (andropause) and women (menopause). In men, reductions in testosterone can trigger declines in muscle mass, bone mass, and in physical function. In women, the impact of the loss of sex hormones, such as estradiol, on bone is well elucidated, but evidence is limited on whether the loss of estradiol negatively affects muscle mass and physical function. However, deficiencies in multiple anabolic hormones have been shown to predict health status and longevity in older persons. Thus, consideration should be given as to whether targeted hormone replacement therapies may prove effective at treating clinical conditions, such as age-related sarcopenia, cancer cachexia, and/or acute or chronic illnesses. If initiated carefully in the appropriate clinical population, hormone replacement therapies in men and women may prevent and reverse muscle and bone loss and functional declines and perhaps promote healthy aging and longevity. PMID:22451474

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.

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.

[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.

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.

Physiologic Estrogen Replacement Increases Bone Density in Adolescent Girls with Anorexia Nervosa

PubMed Central

Misra, Madhusmita; Katzman, Debra; Miller, Karen K.; Mendes, Nara; Snelgrove, Deirdre; Russell, Melissa; Goldstein, Mark; Ebrahimi, Seda; Clauss, Laura; Weigel, Thomas; Mickley, Diane; Schoenfeld, David; Herzog, David B.; Klibanski, Anne

2011-01-01

Background Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low bone mineral density (BMD) in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiological estrogen doses that mimic puberty on BMD has not been examined. Subjects and Methods We enrolled 110 girls with AN and 40 normal-weight controls (C) 12–18y of similar maturity. Subjects were studied for 18 months. Mature AN [bone age (BA) ≥15 y; n=96] were randomized to transdermal 100mcg 17β-estradiol (with cyclic progesterone) or placebo for 18m. Immature AN (BA <15y; n=14) were randomized to incremental low dose oral ethinyl-estradiol (3.75mcg daily from 0–6m, 7.5mcg from 6–12m, 11.25mcg from 12–18m) to mimic pubertal estrogen increases, or placebo for the 18m duration. Results All BMD measures assessed by dual energy x-ray absorptiometry (DXA) were lower in AN than C. At baseline, AN randomized to estrogen (AN E+) did not differ from those randomized to placebo (AN E−) for age, maturity, height, BMI, amenorrhea duration and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with AN E− group, even after controlling for baseline age and weight. Conclusion Physiological estradiol replacement increases spine and hip BMD in girls with AN. PMID:21698665

The Phytoestrogen Genistein Produces Similar Effects as 17β-Estradiol on Anxiety-Like Behavior in Rats at 12 Weeks after Ovariectomy

PubMed Central

Rivadeneyra-Domínguez, Eduardo; Herrera-Huerta, Emma Virginia; Santos-Torres, Andrea

2017-01-01

The phytoestrogen genistein produces anxiolytic-like effects in ovariectomized rats, which highlights its potential therapeutic effect in ameliorating anxiety in surgical menopausal women. However, no studies have directly compared the effects of identical doses of genistein and 17β-estradiol, the main estrogen used in hormone replacement therapy in menopausal women. The present study evaluated the anxiolytic-like effects of identical doses of genistein and 17β-estradiol (0.045, 0.09, and 0.18 mg/kg/7 days, s.c.) in a surgical menopause model in rats in the elevated plus maze and locomotor activity tests at 12 weeks after ovariectomy. Additionally, the participation of estrogen receptor-β in the anxiolytic-like effect of genistein and 17β-estradiol was explored by previous administration of the 5 mg/kg tamoxifen antagonist. Genistein and 17β-estradiol (0.09 and 0.18 mg/kg) similarly reduced anxiety-like behavior in the elevated plus maze and also increased the time spent grooming and rearing, without affecting crossing in locomotor activity test. These effects were blocked by tamoxifen. Present results indicate that the phytoestrogen genistein has a similar behavioral profile as 17β-estradiol in rats at 12 weeks after ovariectomy through action at the estrogen receptor-β. Thus genistein has potential for reducing anxiety-like behavior associated with low concentrations of ovarian hormones, which normally occurs during natural and surgical menopause. PMID:29226152

Interrelationship Between Alcohol Intake and Endogenous Sex-Steroid Hormones on Diabetes Risk in Postmenopausal Women.

PubMed

Rohwer, Rachelle D; Liu, Simin; You, Nai-Chieh; Buring, Julie E; Manson, JoAnn E; Song, Yiqing

2015-01-01

We examined whether circulating concentrations of sex hormones, including estradiol, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS), were associated with alcohol intake or mediated the alcohol-type 2 diabetes (T2D) association. Among women not using hormone replacement therapy and free of baseline cardiovascular disease, cancer, and diabetes in the Women's Health Study, 359 incident cases of T2D and 359 matched controls were chosen during 10 years of follow-up. Frequent alcohol intake (≥1 drink/day) was positively and significantly associated with higher plasma estradiol concentrations in an age-adjusted model (β = 0.14, 95% confidence interval [CI], 0.03, 0.26), compared to rarely/never alcohol intake. After adjusting for additional known covariates, this alcohol-estradiol association remained significant (β = 0.19, 95% CI, 0.07, 0.30). Testosterone (β = 0.13, 95% CI, -0.05, 0.31), SHBG (β = 0.07, 95% CI, -0.07, 0.20), and DHEAS (β = 0.14, 95% CI, -0.04, 0.31) showed positive associations without statistical significance. Estradiol alone or in combination with SHBG appeared to influence the observed protective association between frequent alcohol consumption and T2D risk, with a 12%-21% reduction in odds ratio in the multivariate-adjusted models. Our cross-sectional analysis showed positive associations between alcohol intake and endogenous estradiol concentrations. Our prospective data suggested that baseline concentrations of estradiol, with or without SHBG, might influence the alcohol-T2D association in postmenopausal women.

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

Improved delivery through biological membranes. XXXL: Solubilization and stabilization of an estradiol chemical delivery system by modified beta-cyclodextrins.

PubMed

Brewster, M E; Estes, K S; Loftsson, T; Perchalski, R; Derendorf, H; Mullersman, G; Bodor, N

1988-11-01

A dihydropyridine in equilibrium pyridinium salt chemical delivery system (CDS) for estradiol (E2CDS) was complexed with various modified beta-cyclodextrins including hydroxyethyl-beta-cyclodextrin (HECD), hydroxypropyl-beta-cyclodextrin (HPCD), and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMCD). Complex formation with all of these cyclodextrins resulted in dramatic increases in the water solubility of E2CDS. Studies on the complex of E2CDS and HPCD (E2CDS-CD) indicated that the encapsulated estrogen was approximately four times more stable than the unmanipulated CDS, producing an estimated half-life of degradation of 4 years compared with 1.2 years for the uncomplexed drug at room temperature. The complexation of E2CDS and HPCD also stabilized the dihydronicotinate in solutions containing potassium ferricyanide. This formulation was shown to be equivalent to E2CDS in dimethyl sulfoxide in delivering the oxidized, estradiol precursor (E2Q+) to the brain, and also produced similar biological responses; these included decreased luteinizing hormone (LH) secretion and a decrease in the rate of weight gain in castrated female rats.

A comparative multicenter study of two transdermal estradiol replacement therapies in the treatment of postmenopausal symptoms.

PubMed

Van Leusden, H A; Albertyn, G; Verlaine, C; Van Ruymbeke, J

1993-01-01

Comparison of the effects of treatment of two transdermal therapeutic systems for estrogen replacement therapy with regard to efficacy, tolerability, and acceptance. Open randomized. Multicenter. A study population of 104 postmenopausal women was randomized on a 1:1 basis to treatment with one of two estradiol patches, System (Cilag) and Estraderm (Ciba-Geigy). Systolic and diastolic BP, hot flushes, night sweating, fatigue, insomnia, depression, nervousness, headache, vaginal discomfort (efficacy variables); bleeding, dermatological symptoms, comfort and adhesiveness of patch, and other possible causes of discontinuation (tolerability); general evaluation by patient (acceptance). Considering all efficacy variables, 53% of Systen and 46% of Estraderm patients found the therapy satisfactory. Tolerability was somewhat higher in the Systen group. Adhesiveness of the patch was significantly better for Systen. Overall, 79% of Systen patients and 62% of Estraderm patients evaluated treatment as "good" or "very good." The majority of patients in both groups found the patch very comfortable or only slightly obtrusive.

[Analysis of prescriptions associated to hormone replacement therapy in Midi-Pyrénées region].

PubMed

Gass-Jégu, Florence; Damase-Michel, Christine; Hurault-Delarue, Caroline; Bourrel, Robert; Montastruc, Jean-Louis

2012-01-01

The aim of the present study was 1- to describe hormone replacement therapy (HRT) prescription in Midi-Pyrénées region (South West France) and 2- to compare the prescriptions of associated drugs to those of women who took HRT with prescriptions to women who did not take HRT. From 2004 to 2008, HRT prescription decreased for women aged 50 to 59 years in Midi-Pyrénées: 13.95% to 10.33% estradiol/progestin association consumers. During the first 6 months of 2008, 20,161 women took the association estradiol/progestin. Transdermal/percutaneous forms of estradiol (71.21%) and natural progesterone were mainly prescribed. The number of different dispensed drugs was significantly higher in the HRT group: 5.18 versus 2.82 in the control group (p < 0.0001). All classes were concerned except antineoplastic drugs and immunomodulators, drugs for diabetes and raloxifene which were more prescribed to controls. In the period of the study, 7,035 patients took estrogen alone (25.87% of HRT consumers). The same phenomena were observed in this group. Women exposed to HRT in Midi-Pyrénées, great consumers of drugs, represent a population who require particular medical supervision, because of the risks of HRT and pathologies and/or numerous associated drugs. © 2012 Société Française de Pharmacologie et de Thérapeutique.

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.

Hormone therapy alters the composition of the vaginal microflora in ovariectomized rats.

PubMed

Bezirtzoglou, E; Voidarou, Ch; Papadaki, A; Tsiotsias, A; Kotsovolou, O; Konstandi, M

2008-05-01

The aim of the present study was to evaluate the alterations that may take place in the bacterial genital tract flora in the absence of ovarian hormones. The role of hormone replacement therapy was also assessed. For this purpose, various bacteria were identified from the vaginal flora of ovariectomized and sham operated female rats, following the Bergey's manual criteria. The data of this study showed that substantial differences exist in the vaginal bacterial microflora between ovariectomized and normal cyclic rats. Ovariectomy was associated with a lower total bacterial load that may be due mainly to the absence of Lactobacillus. Anaerobic bacteria were also absent. Streptococcus and Enterococcus were also not favored in an environment lacking the ovarian hormones. In contrast, C. perfringens, Bacteroides, S. epidermidis, and S. aureus were detected in high numbers in ovariectomized rats. In terms of the impact of hormone replacement therapy on vaginal flora, only estradiol (EE2) restored Lactobacillus levels in ovariectomized rats, whereas all hormonal schemes used brought Streptococcus, Clostridium lec (-), and C. perfringens, the spore and vegetative forms, close to those detected in normal cyclic female rats. In conclusion, ovarian hormones appeared to be regulatory factors that favor the presence of a broad variety of bacteria, which are members of the normal genital tract flora. On the other hand, ovariectomy modifies the vaginal microbial profile, and hormone replacement therapy based mainly on schemes containing EE2 could alleviate this disturbance.

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...

ACTH and Cortisol Response to Dex/CRH Testing in Women with and without Premenstrual Dysphoria during GnRH Agonist-Induced Hypogonadism and Ovarian Steroid Replacement

PubMed Central

Lee, Ellen E.; Nieman, Lynnette K.; Martinez, Pedro E.; Harsh, Veronica L.; Rubinow, David R.

2012-01-01

Context: During conditions of ovarian suppression, women with premenstrual dysphoria (PMD) experience abnormal behavioral responses to physiological levels of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation frequently accompanies depression, and ovarian steroids regulate HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We hypothesized that women with PMD would show abnormalities of HPA axis function analogous to those reported in depressive illness, and that ovarian steroids would differentially regulate HPA axis function in women with PMD compared with asymptomatic controls (AC). Objective: Our objective was to characterize the HPA axis response to physiological levels of estradiol and progesterone in women with PMD and AC. Design and Setting: We conducted an open-label trial of the GnRH agonist depot Lupron with ovarian steroid replacement administered in a double-blind crossover design in an outpatient clinic. Participants: Forty-three women (18 with prospectively confirmed PMD and 25 AC) participated. Interventions: Women received Lupron for 6 months. After 3 months of hypogonadism, women received 5 wk each of estradiol (100-μg patch daily) or progesterone (suppositories 200 mg twice daily). During each condition, combined dexamethasone-suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were performed. Main Outcome Measures: Plasma cortisol and ACTH levels were evaluated. Results: HPA axis function was similar in PMD compared with AC. In all, progesterone significantly increased the secretion of cortisol compared with estradiol [area under the curve (t74 = 3.1; P < 0.01)] and urinary free cortisol (t74 = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under the curve (t74 = 2.4; P < 0.05)]. Conclusions: HPA axis regulation is normal in PMD, suggesting that the pathophysiology of PMD differs from major depression. As observed previously, progesterone but not estradiol up-regulates HPA axis function in women. PMID:22466349

Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results.

PubMed

Ruszala, Anna; Wojcik, Malgorzata; Zygmunt-Gorska, Agata; Janus, Dominika; Wojtys, Joanna; Starzyk, Jerzy B

2017-08-01

The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). In 14 TS (mean age 13.8), LE (17β-estradiol, 62.5 μg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17β-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17β-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 μIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.

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.

Physical activity and sex hormone levels in estradiol- and placebo-treated postmenopausal women.

PubMed

Choudhury, Farzana; Bernstein, Leslie; Hodis, Howard N; Stanczyk, Frank Z; Mack, Wendy J

2011-10-01

Postmenopausal changes in the hormonal milieu in women with or without hormone therapy are hypothesized to be the pathway for a number of menopause-associated modifications in physiology and disease risk. Physical activity may modify these changes in women's hormone profiles. The crucial yet complex relationship between physical activity and physiologic and pharmacologic sex hormone levels in postmenopausal women has not been investigated sufficiently. Using structured recall, physical activity was assessed longitudinally during a period of 2 years in 194 postmenopausal women (90 randomized to 1 mg 17β-estradiol treatment daily and 104 randomized to placebo) in the Estrogen in the Prevention of Atherosclerosis Trial. The levels of physical activity were correlated with the serum sex hormone and the serum hormone-binding globulin levels in each treatment group. Among the placebo-treated women, total energy expenditure was positively associated with sex hormone-binding globulin (SHBG; P < 0.001) and inversely associated with testosterones (total, bioavailable, or free) and androstenedione (P < 0.001 for all), as well as with estradiol (P = 0.02). In estradiol-treated women, estradiol levels were inversely associated with total energy expenditure (P = 0.002) and weekly hours spent in moderate or more vigorous physical activity (P = 0.001). Physical activity is associated with lower serum levels of estradiol in both hormone therapy-treated and untreated women. In placebo-treated women only, physical activity is associated with reduced androgen levels and elevated SHBG levels.

Selective estrogen receptor modulator effects of epimedium extracts on breast cancer and uterine growth in nude mice.

PubMed

Indran, Inthrani Raja; Zhang, Shi-Jun; Zhang, Zhi Wei; Sun, Feng; Gong, Yinhan; Wang, Xiaochong; Li, Jun; Erdelmeier, Clemens A J; Koch, Egon; Yong, Eu Leong

2014-01-01

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model. To that end, athymic and ovariectomized female nude mice were subcutaneously injected into the mammary fat pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free feeds, alone or in combination with ethinyl estradiol or different doses of the estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike ethinyl estradiol, it did not promote the growth of breast cancer xenograft volume and weight, with the highest dose showing a significant reduction in growth and ERα protein content. Moreover, the extract increased uterine weight at the lowest dose, while higher doses had no effects. Put together, our data shows for the first time that despite the estrogenic activity of E. brevicornum, its action is largely tissue specific and dose-dependent. Our data on E. brevicornum presents in vivo evidence for its selective estrogen receptor modulator effect and warrants exploration of its use as an alternative to hormone replacement therapy in menopausal women. Georg Thieme Verlag KG Stuttgart · New York.

Impact of physiologic estrogen replacement on anxiety symptoms, body shape perception, and eating attitudes in adolescent girls with anorexia nervosa: data from a randomized controlled trial.

PubMed

Misra, Madhusmita; Katzman, Debra K; Estella, Nara Mendes; Eddy, Kamryn T; Weigel, Thomas; Goldstein, Mark A; Miller, Karen K; Klibanski, Anne

2013-08-01

Anorexia nervosa is characterized by low weight, aberrant eating attitudes, body image distortion, and hypogonadism. Anxiety is a common comorbid condition. Estrogen replacement reduces anxiety in animal models, and reported variations in food intake across the menstrual cycle may be related to gonadal steroid levels. The impact of estrogen replacement on anxiety, eating attitudes, and body image has not been reported in anorexia nervosa. We hypothesized that physiologic estrogen replacement would ameliorate anxiety and improve eating attitudes without affecting body image in anorexia nervosa. Girls 13-18 years old with anorexia nervosa (DSM-IV) were randomized to transdermal estradiol (100 μg twice weekly) with cyclic progesterone or placebo patches and pills for 18-months, between 2002 and 2010. The State-Trait Anxiety Inventory for Children (STAIC), the Eating Disorders Inventory-2 (EDI-2), and the Body Shape Questionnaire (BSQ-34) were administered. 72 girls completed these measures at baseline (n=38 [girls receiving estrogen] and n=34 [girls receiving placebo]) and 37 at 18 months (n=20 [girls receiving estrogen] and n=17 [girls receiving placebo]). The primary outcome measure was the change in these scores over 18 months. Estrogen replacement caused a decrease in STAIC-trait scores (-3.05 [1.22] vs. 2.07 [1.73], P=.02), without impacting STAIC-state scores (-1.11 [2.17] vs. 0.20 [1.42], P=.64). There was no effect of estrogen replacement on EDI-2 or BSQ-34 scores. Body mass index (BMI) changes did not differ between groups, and effects of estrogen replacement on STAIC-trait scores persisted after controlling for BMI changes (P=.03). Increases in serum estradiol were significantly associated with decreases in STAIC-trait scores (Spearman ρ = -0.45, P=.03). Estrogen replacement improved trait anxiety (the tendency to experience anxiety) but did not impact eating attitudes or body shape perception. ClinicalTrials.gov identifier: NCT00088153. © Copyright 2013 Physicians Postgraduate Press, Inc.

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.

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.

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.

Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients.

PubMed

Lasarte, Sandra; Samaniego, Rafael; Salinas-Muñoz, Laura; Guia-Gonzalez, Mauriel A; Weiss, Linnea A; Mercader, Enrique; Ceballos-García, Elena; Navarro-González, Teresa; Moreno-Ochoa, Laura; Perez-Millan, Federico; Pion, Marjorie; Sanchez-Mateos, Paloma; Hidalgo, Andres; Muñoz-Fernandez, Maria A; Relloso, Miguel

2016-02-01

Estradiol-based contraceptives and hormonal replacement therapy predispose women to Candida albicans infections. Moreover, during the ovulatory phase (high estradiol), neutrophil numbers decrease in the vaginal lumen and increase during the luteal phase (high progesterone). Vaginal secretions contain chemokines that drive neutrophil migration into the lumen. However, their expression during the ovarian cycle or in response to hormonal treatments are controversial and their role in vaginal defense remains unknown.To investigate the transepithelial migration of neutrophils, we used adoptive transfer of Cxcr2(-/-) neutrophils and chemokine immunofluorescence quantitative analysis in response to C. albicans vaginal infection in the presence of hormones.Our data show that the Cxcl1/Cxcr2 axis drives neutrophil transepithelial migration into the vagina. Progesterone promotes the Cxcl1 gradient to favor neutrophil migration. Estradiol disrupts the Cxcl1 gradient and favors neutrophil arrest in the vaginal stroma; as a result, the vagina becomes more vulnerable to pathogens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Effects of ovariectomy and estrogen replacement therapy on laryngeal tissue: a histopathological experimental animal study.

PubMed

Tatlipinar, Arzu; Günes, Pembegül; Ozbeyli, Dilek; Cimen, Burak; Gökçeer, Tanju

2011-12-01

To determine the histopathological effect of estrogen deficiency and hormone replacement treatment on laryngeal tissue in ovariectomized rats. Animal study. The study was conducted at the animal experiment laboratory of Marmara University School of Medicine, Istanbul, Turkey. Six-month-old female Wistar albino rats were divided into the following 3 groups (n = 8 per group): sham-operated control, ovariectomized, and ovariectomized with estrogen replacement. Rats in the ovariectomized with estrogen replacement group received 17 β-estradiol valerate (200 µg/kg, subcutaneously) once a week. Animals were killed after 8 weeks of intervention. Significant changes were observed in the ovariectomized group when edema in lamina propria, inflammation in squamous, respiratory epithelia and lamina propria, pseudostratification, and cilia loss were assessed. Except cilia loss, there were no significant differences in the assessments between the sham-operated control and ovariectomized with estrogen replacement groups. On the basis of histopathological evaluations, it was shown that estrogen replacement helped to improve laryngeal changes due to experimentally induced menopause.

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

Aptamer/Au nanoparticles/cobalt sulfide nanosheets biosensor for 17β-estradiol detection using a guanine-rich complementary DNA sequence for signal amplification.

PubMed

Huang, Ke-Jing; Liu, Yu-Jie; Zhang, Ji-Zong; Cao, Jun-Tao; Liu, Yan-Ming

2015-05-15

We have developed a sensitive sensing platform for 17β-estradiol by combining the aptamer probe and hybridization reaction. In this assay, 2-dimensional cobalt sulfide nanosheet (CoS) was synthesized by a simple hydrothermal method with L-cysteine as sulfur donor. An electrochemical aptamer biosensor was constructed by assembling a thiol group tagged 17β-estradiol aptamer on CoS and gold nanoparticles (AuNPs) modified electrode. Methylene blue was applied as a tracer and a guanine-rich complementary DNA sequence was designed to bind with the unbound 17β-estradiol aptamer for signal amplification. The binding of guanine-rich DNA to the aptamer was inhibited when the aptamer captured 17β-estradiol. Using guanine-rich DNA in the assay greatly amplified the redox signal of methylene blue bound to the detection probe. The CoS/AuNPs film formed on the biosensor surface appeared to be a good conductor for accelerating the electron transfer. The method demonstrated a high sensitivity of detection with the dynamic concentration range spanning from 1.0×10(-9) to 1.0×10(-12) M and a detection limit of 7.0×10(-13) M. Besides, the fabricated biosensor exhibited good selectivity toward 17β-estradiol even when interferents were presented at 100-fold concentrations. Our attempt will extend the application of the CoS nanosheet and this signal amplification assay to biosensing areas. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective Effects of 17β-Estradiol on Hippocampal Myelinated Fibers in Ovariectomized Middle-aged Rats.

PubMed

Xiao, Qian; Luo, Yanmin; Lv, Fulin; He, Qi; Wu, Hong; Chao, Fenglei; Qiu, Xuan; Zhang, Lei; Gao, Yuan; Huang, Chunxia; Wang, Sanrong; Zhou, Chunni; Zhang, Yi; Jiang, Lin; Tang, Yong

2018-06-14

Estrogen replacement therapy (ERT) improves hippocampus-dependent cognition. This study investigated the impact of estrogen on hippocampal volume, CA1 subfield volume and myelinated fibers in the CA1 subfield of middle-aged ovariectomized rats. Ten-month-old bilaterally ovariectomized (OVX) female rats were randomly divided into OVX + E2 and OVX + Veh groups. After four weeks of subcutaneous injection with 17β-estradiol or a placebo, the OVX + E2 rats exhibited significantly short mean escape latency in a spatial learning task than that in the OVX + Veh rats. Using stereological methods, we did not observe significant differences in the volumes of the hippocampus and CA1 subfields between the two groups. However, using stereological methods and electron microscopy techniques, the total length of myelinated fibers and the total volumes of myelinated fibers, myelin sheaths and myelinated axons in the CA1 subfields of OVX + E2 rats were significantly 38.1%, 34.2%, 36.1% and 32.5%, respectively, higher than those in the OVX + Veh rats. After the parameters were calculated according to different diameter ranges, the estrogen replacement-induced remodeling of myelinated fibers in CA1 was mainly manifested in the myelinated fibers with a diameter of <1.0 μm. Therefore, four weeks of continuous E2 replacement improved the spatial learning capabilities of middle-aged ovariectomized rats. The E2 replacement-induced protection of spatial learning abilities might be associated with the beneficial effects of estrogen on myelinated fibers, particularly those with the diameters less than 1.0 μm, in the hippocampal CA1 region of middle-aged ovariectomized rats. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Sex hormone concentrations and the risk of breast cancer recurrence in postmenopausal women without hot flashes.

PubMed

Emond, Jennifer A; Patterson, Ruth E; Natarajan, Loki; Laughlin, Gail A; Gold, Ellen B; Pierce, John P

2011-05-01

We examined if the reduced risk of breast cancer events seen among women without baseline hot flash symptoms in the Women's Healthy Eating and Living (WHEL) dietary intervention trial was related to changes in sex hormone concentrations. Baseline and year one concentrations of total and bioavailable estradiol, and testosterone and sex hormone-binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Cox proportional hazard models tested interaction terms between study arm and baseline hormone concentrations adjusted for study site, antiestrogen use, positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use. Sex hormone concentrations did not differ by study arm at baseline nor at year one. Twenty-two (9.8%) events occurred in the intervention arm versus 42 (18.9%) in the comparison arm (P = 0.009). Baseline bioavailable testosterone was significantly, positively associated with additional events (HR 1.69, 95% CI: 1.00-2.84; P = 0.049). There were significant interactions between the intervention and total (P = 0.015), and bioavailable (P = 0.050) testosterone: the intervention was more protective among participants with higher baseline total (HR 0.3, 95% CI: 0.2-0.7) or bioavailable (HR 0.4, 95% CI: 0.2-0.7) testosterone than for participants with lower baseline total (HR 0.8, 95% CI: 0.4-1.5) or bioavailable (HR 0.8, 95% CI: 0.4-1.5) testosterone. No significant effects were seen for estradiol or SHBG. The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone. Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence. ©2011 AACR.

Daidzein–Estrogen Interaction in the Rat Uterus and Its Effect on Human Breast Cancer Cell Growth

PubMed Central

Gaete, Leonardo; Bustamante, Rodrigo; Villena, Joan; Lemus, Igor; Gidekel, Manuel; Cabrera, Gustavo; Astorga, Paola

2012-01-01

Abstract Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17β (E2; subcutaneous, 0.33 mg/kg body weight). In addition, we investigated the effects of daidzein (1 μg/mL) or E2 on the growth of human breast cancer cells in culture. Results indicate that daidzein stimulates growth of breast cancer cells and potentiates estrogen-induced cell proliferation in the uterus. We suggest caution for the use of daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new phytoestrogens that selectively inhibit cell proliferation in the uterus and breast. PMID:23216111

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

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.

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

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

PubMed

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

2015-07-22

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

[Effect of estradiol on the prolactin content in the adenohypophysis of sexually mature and immature rats].

PubMed

Arse, Kh A

1979-01-01

Gel electrophoresis was used in a comparative study of prolactin content in the hypophysis of rats of different age and sex, and at various stages of the estral cycle. The hormone level in the pubertal rats was twice or thrice greater than in the immature ones; it was by 16% less at the diestrus than at the estrus stage. There was no change in the hypophysis prolactin content in male rats at puberty. Ovariectomy was accompained by a sharp reduction of prolactin in the hypophysis. Replacing estradiol therapy increased the amount of prolactin in the hypophysis, without bringing it, however, to the level characteristic of intact rats. Estrogens are responsible for the maintenance of prolactin level, but apparently other factors influencing its content in the hypophysis also exist.

A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency

PubMed Central

Hubayter, Ziad R; Popat, Vaishali; Vanderhoof, Vien H; Ndubizu, Obioma; Johnson, Diane; Mao, Edie; Calis, Karim A; Troendle, James F.; Nelson, Lawrence M.

2010-01-01

Objective To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency Design Case-control with nested prospective cohort Setting Clinical Research Center, National Institutes of Health Patients Women with primary ovarian insufficiency without estrogen replacement for two weeks (N=97) and regularly menstruating control women (N=42) Interventions Single injection of 300 IU hrFSH Main outcome measures Change in serum estradiol at 24 hours Results Antral follicles ≥ 3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter ≥ 8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels as compared to patients without such follicles. In controls estradiol levels increased significantly after FSH administration but in patients this was not the case despite the presence of an antral follicle ≥ 8 mm. Conclusion Most women with 46,XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles ≥ 8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated. PMID:19939372

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.

Age-dependent Effects of 17β-estradiol on the Dynamics of Estrogen Receptor β (ERβ) Protein–Protein Interactions in the Ventral Hippocampus*

PubMed Central

Mott, Natasha N.; Pinceti, Elena; Rao, Yathindar S.; Przybycien-Szymanska, Magdalena M.; Prins, Sarah A.; Shults, Cody L.; Yang, Xinli; Glucksman, Marc J.; Roberts, James L.; Pak, Toni R.

2014-01-01

Recent clinical evidence suggests that the neuroprotective and beneficial effects of hormone therapy may be limited by factors related to age and reproductive status. The patient's age and length of time without circulating ovarian hormones are likely to be key factors in the specific neurological outcomes of hormone therapy. However, the mechanisms underlying age-related changes in hormone efficacy have not been determined. We hypothesized that there are intrinsic changes in estrogen receptor β (ERβ) function that determine its ability to mediate the actions of 17β-estradiol (E2) in brain regions such as the ventral hippocampus. In this study, we identified and quantified a subset of ERβ protein interactions in the ventral hippocampus that were significantly altered by E2 replacement in young and aged animals, using two-dimensional differential gel electrophoresis coupled with liquid chromatography–electrospray ionization–tandem mass spectrometry. This study demonstrates quantitative changes in ERβ protein–protein interactions with E2 replacement that are dependent upon age in the ventral hippocampus and how these changes could alter processes such as transcriptional regulation. Thus, our data provide evidence that changes in ERβ protein interactions are a potential mechanism for age-related changes in E2 responsiveness in the brain after menopause. PMID:24390426

Reproductive Hormones Modify Reception of Species-Typical Communication Signals in a Female Anuran

PubMed Central

Lynch, Kathleen S.; Wilczynski, Walter

2008-01-01

In many vertebrates, the production and reception of species-typical courtship signals occurs when gonadotropin and gonadal hormone levels are elevated. These hormones may modify sensory processing in the signal receiver in a way that enhances behavioral responses to the signal. We examined this possibility in female túngara frogs (Physalaemus pustulosus) by treating them with either gonadotropin (which elevated estradiol) or saline and exposing them to either mate choruses or silence. Expression of an activity-dependent gene, egr-1, was quantified within two sub-nuclei of the auditory midbrain to investigate whether gonadotropin plus chorus exposure induced greater egr-1 induction than either of these stimuli alone. The laminar nucleus (LN), a sub-nucleus of the torus semicircularis that contains steroid receptors, exhibited elevated egr-1 induction in response to chorus exposure and gonadotropin treatment. Further analysis revealed that neither chorus exposure nor gonadotropin treatment alone elevated egr-1 expression in comparison to baseline levels whereas gonadotropin + chorus exposure did. This suggests that mate signals and hormones together produce an additive effect so that together they induce more egr-1 expression than either alone. Our previously published studies of female túngara frogs reveal that (1) gonadotropin-induced estradiol elevations also increase behavioral responses to male signals, and (2) reception of male signals elevates estradiol levels in the female. Here, we report data that reveal a novel mechanism by which males exploit female sensory processing to increase behavioral responses to their courtship signals. PMID:18032889

AC-186, a Selective Nonsteroidal Estrogen Receptor β Agonist, Shows Gender Specific Neuroprotection in a Parkinson’s Disease Rat Model

PubMed Central

2013-01-01

Drugs that selectively activate estrogen receptor β (ERβ) are potentially safer than the nonselective estrogens currently used in hormonal replacement treatments that activate both ERβ and ERα. The selective ERβ agonist AC-186 was evaluated in a rat model of Parkinson’s disease induced through bilateral 6-hydroxydopamine lesions of the substantia nigra. In this model, AC-186 prevented motor, cognitive, and sensorimotor gating deficits and mitigated the loss of dopamine neurons in the substantia nigra, in males, but not in females. Furthermore, in male rats, 17β-estradiol, which activates ERβ and ERα with equal potency, did not show the same neuroprotective benefits as AC-186. Hence, in addition to a beneficial safety profile for use in both males and females, a selective ERβ agonist has a differentiated pharmacological profile compared to 17β-estradiol in males. PMID:23898966

Estrogen Replacement Improves Verbal Memory and Executive Control in Oligomenorrheic/Amenorrheic Athletes in a Randomized Controlled Trial.

PubMed

Baskaran, Charumathi; Cunningham, Brooke; Plessow, Franziska; Singhal, Vibha; Woolley, Ryan; Ackerman, Kathryn E; Slattery, Meghan; Lee, Hang; Lawson, Elizabeth A; Eddy, Kamryn; Misra, Madhusmita

2017-05-01

Both estrogen and exercise may have cognition enhancing benefits; however, young oligomenorrheic/amenorrheic athletes (OA) with estrogen deficiency have not been evaluated for cognitive deficits. Our objective was to determine whether 6 months of estrogen replacement will impact cognitive domains in OA. We hypothesized that estrogen replacement would improve verbal memory and executive control in OA. We performed cognitive assessments at baseline and after 6 months in 48 OA (14-25 years) randomized to estrogen (EST+) (oral 30 µg ethinyl estradiol [n = 16] or transdermal 100 µg 17-β-estradiol patch [n = 13]) or no estrogen (EST-) (n = 19) in an ongoing clinical trial. Neurocognitive testing included California Verbal Learning Test-Second Edition (CVLT-II) (for verbal memory) and Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS-CWIT) (executive control). On average, subjects (mean ± SEM age: 19.9 ± 3.1 years, body mass index: 20.6 ± 2.3 kg/m²) participated in 10.3 ± 5.9 hours per week of weight-bearing activities of their lower limbs. The EST+ group performed better for CVLT-II verbal memory scores for immediate recall over 6 months of therapy compared to EST- (P < .05) even after controlling for baseline scores and age. Changes in D-KEFS-CWIT scores over 6 months did not differ between the groups. However, the EST+ group had greater improvements in inhibition-switching completion time over 6 months compared with the EST- group after controlling for baseline scores and age (P = .01). OA show improvements in verbal memory and executive control following 6 months of estrogen replacement. These findings in athletes, who are in their prime of neurocognitive development, underscore the need for future studies exploring cognition in OA. ClinicalTrials.gov identifier: NCT00946192. © Copyright 2017 Physicians Postgraduate Press, Inc.

Role of estrogen and progesterone in the modulation of CNG-A1 and Na/K+-ATPase expression in the renal cortex.

PubMed

Gracelli, Jones B; Souza-Menezes, Jackson; Barbosa, Carolina M L; Ornellas, Felipe S; Takiya, Christina M; Alves, Leandro M; Wengert, Mira; Feltran, Georgia da Silva; Caruso-Neves, Celso; Moyses, Margareth R; Prota, Luiz F M; Morales, Marcelo M

2012-01-01

The steroid hormones, estrogen and progesterone, are involved mainly in the control of female reproductive functions. Among other effects, estrogen and progesterone can modulate Na(+) reabsorption along the nephron altering the body's hydroelectrolyte balance. In this work, we analyzed the expression of cyclic nucleotide-gated channel A1 (CNG-A1) and α1 Na(+)/K(+)-ATPase subunit in the renal cortex and medulla of female ovariectomized rats and female ovariectomized rats subjected to 10 days of 17β-estradiol benzoate (2.0 µg/kg body weight) and progesterone (1.7 mg/kg body weight) replacement. Na(+)/K(+) ATPase activity was also measured. Immunofluorescence localization of CNG-A1 in the cortex and medulla was performed in control animals. We observed that CNG-A1 is localized at the basolateral membrane of proximal and distal tubules. Female ovariectomized rats showed low expression of CNG-A1 and low expression and activity of Na(+)/K(+) ATPase in the renal cortex. When female ovariectomized rats were subjected to 17β-estradiol benzoate replacement, normalization of CNG-A1 expression and Na(+)/K(+) ATPase expression and activity was observed. The replacement of progesterone was not able to recover CNG-A1 expression and Na(+)/K(+) ATPase expression at the control level. Only the activity of Na(+)/K(+) ATPase was able to be recovered at control levels in animals subjected to progesterone replacement. No changes in expression and activity were observed in the renal medulla. The expression of CNG-A1 is higher in cortex compared to medulla. In this work, we observed that estrogen and progesterone act in renal tissues modulating CNG-A1 and Na(+)/K(+) ATPase and these effects could be important in Na(+) and water balance. Copyright © 2012 S. Karger AG, Basel.

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.

Effects of short-term hormonal replacement on learning and on basal forebrain ChAT and TrkA content in ovariectomized rats.

PubMed

Espinosa-Raya, Judith; Plata-Cruz, Noemí; Neri-Gómez, Teresa; Camacho-Arroyo, Ignacio; Picazo, Ofir

2011-02-23

It has been proposed that sex steroid hormones improve performance in some cognitive tasks by regulating the basal forebrain cholinergic function. However, the molecular basis of such influence still remains unknown. Current study analyzed the performance of ovariectomized rats in an autoshaping learning task after a short-term treatment with 17β-estradiol (E2: 4 and 40μg/kg) and/or progesterone (P4: 4mg/kg). These results were correlated with basal forebrain choline acetyltransferase (ChAT) and TrkA protein content. The high dose of E2 enhanced both acquisition in the autoshaping task and the content of ChAT and TrkA. P4 treatment increased ChAT and TrkA content without affecting performance of rats in the autoshaping learning task. Interestingly, the continuous and simultaneous administration of E2 plus P4 did not significantly modify behavioral and biochemical evaluated parameters. These results address the influence of both E2 and P4 on cholinergic and TrkA activity and suggest that the effects of ovarian hormones on cognitive performance involve basal forebrain cholinergic neurons. Copyright © 2010 Elsevier B.V. All rights reserved.

The influence of postnatal nutrition on reproductive tract and endometrial gland development in dairy calves.

PubMed

Wilson, Meghan L; McCoski, Sarah R; Geiger, Adam J; Akers, R Michael; Johnson, Sally E; Ealy, Alan D

2017-04-01

Uterine gland development occurs after birth in cattle and other mammals. The timeline of gland development has been described in various species, but little is known about how postnatal diet influences uterine gland development. This is especially concerning in dairy heifers, where a variety of milk replacer and whole milk nutrition options exist. Little work also exists in cattle to describe how early exposure to steroids influences reproductive tract and uterine gland development. The objective of this work was to determine the effects of early postnatal plane of nutrition and estrogen supplementation on uterine gland development in calves. In both studies, Holstein heifer calves were assigned to restricted milk replacer (R-MR) or enhanced milk replacer (EH-MR) diets. In study 1, calves (R-MR, n = 6; EH-MR, n = 5) were euthanized at 8 wk. In study 2, calves were weaned at 8 wk and administered estradiol (R-MR, n = 6; EH-MR, n = 6) or placebo (R-MR, n = 6; EH-MR, n = 5) for an additional 14 d before euthanasia. Average daily gain and final body weight was greater in both studies in heifers fed the enhanced diet. At 8 wk, EH-MR calves had a greater number of glands and a smaller average gland size, but total gland area was not different from the R-MR group. At 10 wk, uterine gland number and size were not affected by diet or estrogen. Expression profiles of several paracrine mediators of gland development were examined. Increases in transcript abundance for IGF1 and IGFBP3 and a decrease in abundance of WNT7A were detected in calves fed the enhanced diet at 8 wk of age. Plane of nutrition did not affect transcript profiles at 10 wk of age, but estradiol supplementation decreased MET and WNT7A transcript abundance. To conclude, heifer calves on a restricted diet exhibited a uterine morphology and transcript profile suggestive of delayed uterine gland development. These changes appear to be corrected by wk 10 of life. Also, this work provides evidence supporting the contention that early estradiol exposure has detrimental effects on uterine gene expression. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

PubMed

Tirabassi, G; delli Muti, N; Gioia, A; Biagioli, A; Lenzi, A; Balercia, G

2014-04-01

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

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.

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.

Effect of Penetration Enhancers on the Percuaneous Delivery of Hormone Replacement Actives.

PubMed

Trimble, John O; Light, Bob

2017-01-01

Transdermal compositions for hormone replacement are comprised of exogenous hormones that are biochemically similar to those produced endogenously by the ovaries or elsewhere in the body. In this work, estradiol, estriol, and testosterone were loaded in transdermal vehicles, prepared using one of three selected penetration enhancer mixtures: Vehicle 1 (olive oil and oleic acid), Vehicle 2 (isopropyl palmitate and lecithin), and Vehicle 3 (isopropyl myristate and lecithin). The influence of penetration enhancers on transdermal delivery was evaluated using Franz-type diffusion cells and Normal Human 3D Model of Epidermal Tissue. Results showed that drug delivery is affected by the penetration enhancer used in the transdermal composition. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.

PubMed

Davis, D L; Telang, N T; Osborne, M P; Bradlow, H L

1997-04-01

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.

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.

Replacement of Mushroom Cage Gastrostomy Tube Using a Modified Technique to Allow Percutaneous Replacement with an Endoscopic Tube in Patients with Amyotrophic Lateral Sclerosis

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

Ammar, Thoraya; Rio, Alan; Ampong, Mary Ann

2010-06-15

Radiologic inserted gastrostomy (RIG) is the preferred method in our institution for enteral feeding in amyotrophic lateral sclerosis (ALS). Skin-level primary-placed mushroom cage gastrostomy tubes become tight with weight gain. We describe a minimally invasive radiologic technique for replacing mushroom gastrostomy tubes with endoscopic mushroom cage tubes in ALS. All patients with ALS who underwent replacement of a RIG tube were included. Patients were selected for a modified replacement when the tube length of the primary placed RIG tube was insufficient to allow like-for-like replacement. Replacement was performed under local anesthetic and fluoroscopic guidance according to a preset technique, withmore » modification of an endoscopic mushroom cage gastrostomy tube to allow percutaneous placement. Assessment of the success, safety, and durability of the modified technique was undertaken. Over a 60-month period, 104 primary placement mushroom cage tubes in ALS were performed. A total of 20 (19.2%) of 104 patients had a replacement tube positioned, 10 (9.6%) of 104 with the modified technique (male n = 4, female n = 6, mean age 65.5 years, range 48-85 years). All tubes were successfully replaced using this modified technique, with two minor complications (superficial wound infection and minor hemorrhage). The mean length of time of tube durability was 158.5 days (range 6-471 days), with all but one patient dying with a functional tube in place. We have devised a modification to allow percutaneous replacement of mushroom cage gastrostomy feeding tubes with minimal compromise to ALS patients. This technique allows tube replacement under local anesthetic, without the need for sedation, an important consideration in ALS.« less

Cytological and cytochemical analysis of the effects of hormones on postradiation changes in testicular sex and incretory cells. [. gamma. rays; x rays; mice

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

Kondratenko, V.G.; Ganzenko, L.F.; Stakanov, V.A.

1979-06-01

Cytochemical and cytological analysis demonstrated that administration of testosterone propionate or estradiol propionate alters nuclear nucleoproteins of Leydig and Sertoli cells, as well as spermatogeneic elements. It was shown that the hormones modify the testicular reactions to radiation and, by influencing regulation of spermatogenesis, exert a protective action.

Nest box exploration may stimulate breeding physiology and alter mRNA expression in the medial preoptic area of female European starlings.

PubMed

Spool, Jeremy A; Jay, Melannie D; Riters, Lauren V

2018-04-25

Environmental resources are proposed to fine-tune the timing of breeding, yet how they may do so remains unclear. In female European starlings ( Sturnus vulgaris ), nest cavities are limited resources that are necessary for breeding. Females that explore nest cavities, compared to those that do not, readily perform sexually-motivated behaviors. We assigned female starlings to aviaries with 1) no nest boxes, 2) nest boxes, or 3) nest boxes, plants, flowing water, insects and berries to test the hypothesis that environmental resources alter neural systems to stimulate mating behavior. Compared to other females, females that were housed with and explored nest boxes had higher estradiol, higher preproenkephalin (PENK) mRNA, and lower levels of D1 and D2 dopamine receptor mRNA in the medial preoptic area (mPOA), a region in which opioids and dopamine modify female sexual behaviors and sexual motivation. Additionally, in the mPOA, PENK and tyrosine hydroxylase mRNA positively predicted, whereas estrogen receptor beta mRNA negatively predicted nest box exploration. In the ventromedial hypothalamus, a region in which estradiol acts to stimulate sexual behavior, estrogen receptor alpha mRNA was highest in females that had access to but did not explore nest cavities. It is likely that seasonal increases in estradiol modify mRNA in the mPOA to facilitate nest cavity exploration. It is also possible that nest cavity exploration further alters gene expression in the mPOA, functioning to coordinate mating with resource availability. Thus nest cavity exploration may be a form of self-stimulation that alters neural systems to fine-tune sexual behavior. © 2018. Published by The Company of Biologists Ltd.

Functional characterization of estrogen receptor subtypes, ER{alpha} and ER{beta}, mediating vitellogenin production in the liver of rainbow trout

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

Leanos-Castaneda, Olga; Kraak, Glen van der

2007-10-15

The estrogen-dependent process of vitellogenesis is a key function on oviparous fish reproduction and it has been widely used as an indicator of xenoestrogen exposure. The two estrogen receptor (ER) subtypes, ER{alpha} and ER{beta}, are often co-expressed in the liver of fish. The relative contribution of each ER subtype to modulate vitellogenin production by hepatocytes was studied using selected compounds known to preferentially interact with specific ER subtypes: propyl-pyrazole-triol (PPT) an ER{alpha} selective agonist, methyl-piperidino-pyrazole (MPP) an ER{alpha} selective antagonist, and diarylpropionitrile (DPN) an ER{beta} selective agonist. First, the relative binding affinity of the test compounds to estradiol for rainbowmore » trout hepatic nuclear ER was determined using a competitive ligand binding assay. All the test ligands achieved complete displacement of specific [{sup 3}H]-estradiol binding from the nuclear ER extract. This indicates that the test ligands have the potential to modify the ER function in the rainbow trout liver. Secondly, the ability of the test compounds to induce or inhibit vitellogenin production by primary cultures of rainbow trout hepatocytes was studied. Estradiol and DPN were the only compounds that induced a dose-dependent increase on vitellogenin synthesis. The lack of vitellogenin induction by PPT indicates that ER{alpha} could not have a role on this reproductive process whereas the ability of DPN to induce vitellogenin production supports the participation of ER{beta}. In addition, this hypothesis is reinforced by the results obtained from MPP plus estradiol. On one hand, the absence of suppressive activity of MPP in the estradiol-induced vitellogenin production does not support the participation of ER{alpha}. On the other hand, once blocked ER{alpha} with MPP, the only manifestation of agonist activity of estradiol would be achieved via ER{beta}. In conclusion, the present results indicate that vitellogenin production is mainly mediated through ER{beta}, implying, furthermore that compounds which only exhibit ER{alpha} selectivity are not detected by vitellogenin bioassay.« less

The effects of progesterone selection on psychological symptoms in hormone replacement therapy.

PubMed

Caglayan, Emel Kiyak; Kara, Mustafa; Etiz, Sema; Kumru, Pinar; Aka, Nurettin; Kose, Gultekin

2014-01-01

The aim of this study is to evaluate the effects of hormone replacement therapy using dienogest and medroxyprogesterone acetate on psychological symptoms in perimenopausal and postmenopausal women. A total of 73 patients who sought treatment at the menopause units of the authors' gynecology and obstetrics clinics between of November 2003 and October 2004 complaining of vasomotor symptoms were included in the study prospectively. The cases were divided into two groups: Group I (37 patients) was given 2 mg estradiol valerate and 2 mg dienogest, and Group II (36 patients) was given 2 mg estradiol valerate and 10 mg medroxyprogesterone acetate. The groups' results in months 0 and 6 were compared through the evaluation of vasomotor and psychological symptom levels. No significant difference was found between the groups when the initial levels of vasomotor and psychological symptom subtypes were compared (p = 0.16). It was observed that all the psychological symptoms decreased in the 6th month in the group using dienogest in comparison with the initial situation, and that psychological symptoms increased in the group using medroxyprogesterone acetate in the evaluation performed in the 6th month compared with the initial levels. It was also found out that there was a statistically significant difference between the two groups when compared in terms of these symptoms (p < 0.0001). While the use of dienogest normalizes the general psychological situation and sleep, it was observed that the use of medroxyprogesterone acetate (MPA) worsens the general psychological situation.

Effects of tibolone on sulfatase pathway of estrogens metabolism and on growth of MCF-7 human breast tumors implanted in ovariectomized nude mice.

PubMed

Desreux, Joëlle; Kloosterboer, Helenius; Noël, Agnès; Frankenne, Francis; Lemaire, Madeleine; Putman, Monique; Foidart, Jean-Michel

2007-01-01

The benefits of estrogen plus progestin in healthy post-menopausal women remain uncertain. Tibolone, with its in vitro documented inhibitory effects on estrogens metabolism and its selective action on breast, may be an alternative that could favorably influence the health benefit of hormone replacement therapy. We studied the effect of tibolone on the tumor growth of MCF-7 cells implanted in 40 ovariectomized nude mice, receiving subcutaneous pellets of 17beta-estradiol, estrone, estrone-sulfate or vehicle, and daily gavages of tibolone or placebo. Tibolone, although used at high dose, did not stimulate nor inhibit the estrogen-induced tumors, nor the tumors in estrogen-deprived mice. Measurements of plasma levels of estrogens indicated that tibolone potently stimulated sulfotransferase activity, but intra-tumor levels of estrogens were not significantly modified by tibolone. This in vivo study performed with high dose of orally administered tibolone that allowed its hepatic conversion into active metabolites has shown no significant effect on breast tumors growth. Tibolone increased the circulating sulfated estrogens by its activity on the hepatic sulfation but not the intra-tumor levels of estrogens (free or sulfated). However, further studies of dose-response curve and molecular markers are needed to exclude definitely a stimulatory effect of tibolone on tumor growth.

Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis

PubMed Central

Deshpande, Dipti; Kethireddy, Sravani; Janero, David R.; Amiji, Mansoor M.

2016-01-01

Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE)-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs) with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/-) mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease. PMID:26840601

Associations of lead and cadmium with sex hormones in adult males

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

Kresovich, Jacob K., E-mail: jkreso2@uic.edu; Argos, Maria; Turyk, Mary E.

Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999–2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood leadmore » was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. - Highlights: • We used a nationally representative dataset (NHANES) and employed sample weighting. • We examined associations between lead and cadmium with sex-hormone levels. • Blood lead level was positively associated with serum testosterone and SHBG levels. • Blood cadmium level was positively associated with SHBG levels, modified by lead. • Diabetes, smoking and cadmium modified lead and testosterone association.« less

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

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.

Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor α in Hippocampus of Ovariectomized Rats.

PubMed

Allahtavakoli, Mohammad; Honari, Najmeh; Pourabolli, Iran; Kazemi Arababadi, Mohammad; Ghafarian, Hossein; Roohbakhsh, Ali; Esmaeili Nadimi, Ali; Shamsizadeh, Ali

2015-07-01

Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. 24 female Wistar rats weighing 180-220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERα and prevented the decrease in uterine weight of ovariectomized rats. Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERα gene expression in the hippocampal formation.

Vitex Agnus Castus Extract Improves Learning and Memory and Increases the Transcription of Estrogen Receptor α in Hippocampus of Ovariectomized Rats

PubMed Central

Allahtavakoli, Mohammad; Honari, Najmeh; Pourabolli, Iran; Kazemi Arababadi, Mohammad; Ghafarian, Hossein; Roohbakhsh, Ali; Esmaeili Nadimi, Ali; Shamsizadeh, Ali

2015-01-01

Introduction: Lower level of estrogen hormone is considered as an important factor for loss of learning and memory in postmenopausal women. Although estrogen replacement therapy is used for compensation, but long-term usage of estrogen is associated with a higher risk of hormone-dependent cancers. Phytoestrogens, due to fewer side effects, have been proposed to prevent menopause-related cognitive decline. Methods: 24 female Wistar rats weighing 180–220 g were used in this study. The animals were ovariectomized and randomly divided into four groups including, control and two groups which received 8 and 80 mg/kg Vitex agnus castus (VAC) ethanolic extract orally. The last groups were treated with 40 μg/kg of estradiol valerat. Step-through passive avoidance (STPA) test was used for the evaluation of learning and memory. The hippocampal estrogen receptor α (ERα) expression was measured using Real-Time PCR. Results: The results demonstrated that VAC extract or estradiol had better performance on step-through passive avoidance test than control group (all P<0.05). Moreover, administration of either estradiol or VAC extract increased the hippocampal mRNA level of ERα and prevented the decrease in uterine weight of ovariectomized rats. Discussion: Based on our data, VAC extract improves learning and memory in ovariectomized rats. The positive effect of VAC extract on learning and memory is possibly associated with an increase in ERα gene expression in the hippocampal formation. PMID:26904176

Aromatase expression is linked to estrogenic sensitivity of periurethral muscles in female rabbits.

PubMed

de los Ángeles Carrasco-Ruiz, María; García-Villamar, Verónica; López-García, Kenia; Sánchez-García, Octavio; Pacheco, Pablo; Cuevas, Estela; Martínez-Gómez, Margarita; Castelán, Francisco

2015-06-01

Beyond its role in the conversion of androgens to estrogens, the expression of aromatase could influence on the estrogenic signalling in targeted tissues. Considering the well-defined biochemical and physiological differences between the pubococcygeus (Pcm) and bulbospongiosus (Bsm) muscles in female rabbits, it is presently hypothesized that the aromatase expression is differentially linked to the estrogen sensitivity of each muscle. To this end, serum estradiol levels and the aromatase expression, presence of ERα and ERβ and morphometry were evaluated in the Pcm and Bsm of female rabbits allocated in control, ovariectomized (OVX) and OVX treated with estradiol benzoate (OVX + EB) groups. Aromatase expression was high in the Pcm. Independently to serum estradiol, ovariectomy increased aromatase expression in the Pcm while decreased it in the Bsm. The EB treatment avoided the effect of ovariectomy only in the Pcm. The number of immunoreactive nuclei anti-ERα and anti-ERβ was high in the Pcm of OVX and OVX + EB rabbits, while those in the Bsm remained unchanged. The number of peripheral nuclei per fibre and the cross-sectional area-to-myonucleus ratio were modified only in the Pcm. Our findings support aromatase expression in the Pcm, and Bsm of rabbits is differentially linked to estrogenic sensitivity of each muscle. Copyright © 2015 John Wiley & Sons, Ltd.

The effects of polychlorinated biphenyls (Aroclor 1242) on thyroxine, estradiol, molt, and plumage characteristics in the American kestrel (Falco sparverius)

USGS Publications Warehouse

Quinn, M.J.; French, J.B.; McNabb, F.M.A.; Ottinger, M.A.

2002-01-01

The purpose of this experiment was to determine the effects of Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), on plumage characteristics and molt in the American kestrel, Falco sparverills. Several characteristics of plumage. including color and molt schedule, are modulated by hormonal signals and hence may be modified by endocrine-active contaminants. If so, the functions of plumage (e.g. communication for mating or territorial defense) may be compromised by exposure to such compounds. Captive American kestrels were fed Aroclor 1242 at 0. 6.0. and 60.0 ppm (n = 6 males and 6 females per treatment) mixed in their normal diet. Concentrations of plasma estradiol and thyroxine were measured weekly from the beginning of treatment. Measured plumage characteristics included width of the black subterminal band on the tail, color (a composite index of hue and saturation), reflectance from 230 to 800 min. pattern of feather loss and regrowth on the tail and wing. and timing of onset and duration of molt. Aroclor 1242 depressed plasma thyroxine. Plasma estradiol levels remained low due to the phase of the breeding cycle. Treatments did not disrupt the measured plumage characteristics. This may be due to timing or dose of exposure or to genetic factors.

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.

Seventeenth breeding-bird census. 34. Diked wet meadow

USGS Publications Warehouse

Quinn, M.J.; Ottinger, M.A.; French, J.B.

2000-01-01

Several characteristics of plumage, including color and molt schedule, are influenced by hormonal signals, and hence may be modified by endocrine active contaminants. If so, the functions of plumage (e.g. communication for mating or territorial defense), may be compromised by exposure to such compounds. Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental toxins that can disrupt endocrine function in laboratory animals. Captive American kestrels (Falco sparverius) were fed PCBs (Aroclor 1242) at 6 and 60 ppm, thyroxine at 10 ppm, estradiol at 1.4 ppm, and a thyroid hormone blocker (propylthiouracil: PTU) at 2000 ppm, mixed in their normal diet. Plumage characteristics measured included: the width of the black subterminal band on the tail, brightness (a composite index of hue and saturation), reflectance from 230 - 800 nm (measured on a reflectance spectrophotometer), the pattern of feather loss and regrowth on the tail and wing, and the timing of onset and the duration of molt. PCB-treated birds did not differ from controls, but birds treated with thyroxine were significantly different from those dosed with estradiol or PTU in the width of subterminal tail bands, reflectance, and duration of molt. Thus, although hormone treatments did modify some of the plumage characteristics we measured, PCB treatments at these exposure levels did not.

Electrochemical sensor based on molecularly imprinted membranes at platinum nanoparticles-modified electrode for determination of 17β-estradiol.

PubMed

Yuan, Lihua; Zhang, Jun; Zhou, Ping; Chen, Jiaxing; Wang, Ruoyu; Wen, Tingting; Li, Yun; Zhou, Xuemin; Jiang, Huijun

2011-11-15

In this paper, an electrochemical sensor for 17β-estradiol (E2) based on the molecular imprinting polymer (MIP) membranes had been constructed. 6-mercaptonicotinic acid (MNA) and E2 were first assembled on the surface of platinum nanoparticles-modified glassy carbon electrode (PtNPs/GCE) by the formation of Pt-S bonds and hydrogen-bonding interactions, and subsequently the polymer membranes were formed by electropolymerization. Finally, a novel molecularly imprinted sensor (MIS) was obtained after removal of E2. Experimental parameters such as deposition time, scan cycles, pH value and accumulation condition were optimized. Under optimal conditions, the MIS exhibited a large adsorption capacity and high selectivity. A good linearity was obtained in the range of 3.0×10(-8)-5.0×10(-5)molL(-1) (r=0.996) with an estimated detection limit of 1.6×10(-8)molL(-1). MIS had been successfully used to analyze E2 in water samples without complex pretreatment. Meanwhile, the average recoveries were higher than 93.9% with RSD<3.7%. All results above reveal that MIS is an effective electrochemical technique to determine E2 real-time in complicated matrix. Copyright © 2011 Elsevier B.V. All rights reserved.

Associations of lead and cadmium with sex hormones in adult males.

PubMed

Kresovich, Jacob K; Argos, Maria; Turyk, Mary E

2015-10-01

Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999-2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood lead was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

PubMed Central

Yasrebi, Ali; Hsieh, Anna; Mamounis, Kyle J.; Krumm, Elizabeth A.; Yang, Jennifer A.; Magby, Jason; Hu, Pu; Roepke, Troy A.

2015-01-01

Ghrelin’s receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. PMID:26577678

Endocrine basis of the reproductive pattern of the Gentoo penguin (Pygoscelis papua): winter breeding and extended laying period in northern populations.

PubMed

Mauget, R; Garcia, V; Jouventin, P

1995-05-01

Changes in plasma LH, prolactin, testosterone, estradiol, and progesterone were investigated throughout moult and reproduction in free-living male and female Gentoo penguins (Pygoscelis papua) at Crozet Island (46 degrees S, 51 degrees E), where this species is able to relay after a reproductive failure. In both sexes, LH, prolactin, and steroid hormones, remained at basal levels during the moult. LH level was highest at the time of arrival at the colony for breeding and, although it decreased after courtship, it did not drop at basal value by incubation and first chick brooding period. Prolactin peaked for both chick brooding periods; replacement clutch was associated with an increased secretion of LH, whereas high prolactin levels were maintained. Testosterone, in male, and estradiol, in female, peaked during courtship I and chick brooding II; progesterone, in female, peaked during courtship I and II. These hormonal patterns are consistent with those observed in passerine species which are also able to relay after a reproductive failure. Winter breeding observed at Crozet Island might reflect the extreme adaptive capacity of Gentoo penguin species.

Estradiol in saliva for monitoring follicular stimulation in an in vitro fertilization program

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

Belkien, L.D.; Bordt, J.; Moeller, P.

1985-09-01

A rapid and sensitive radioimmunoassay (RIA) was developed to compare serum and saliva estradiol (E/sub 2/) levels in patients undergoing ovulation induction in an in vitro fertilization and embryo transfer (IVF-ET) program. Serum and saliva E/sub 2/ were compared in 23 patients. The sensitivity of the saliva RIA standard curve was 11 fmol/tube (equal to 3.2 pg/tube). There was a highly significant correlation between serum and saliva E/sub 2/ throughout the stimulated cycles. The ratio of serum to saliva E/sub 2/ was constant throughout the stimulated cycles. The E/sub 2/ concentration per follicle was 1548 pmol/l in serum and 23more » pmol/l in saliva. Mean E/sub 2/ levels in saliva (+/- SD) were 74 +/- 21 pmol/l at midcycle and 46 +/- 12 pmol/l at midluteal phase. The findings indicate that measurement of saliva E/sub 2/ provides a reliable, noninvasive method and may replace serum measurements for monitoring stimulated cycles in an IVF-ET program.« less

Premenopausal women with early breast cancer treated with estradiol suppression have severely deteriorated bone microstructure.

PubMed

Ramchand, Sabashini K; Seeman, Ego; Wang, Xiao-Fang; Ghasem-Zadeh, Ali; Francis, Prudence A; Ponnusamy, Evangeline J; Bardin, Michele S; Bui, Minh; Zebaze, Roger; Zajac, Jeffrey D; Grossmann, Mathis

2017-10-01

In premenopausal women with early estrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition reduce estradiol production precipitously. The resulting unbalanced and rapid bone remodelling replaces older bone with less bone that is less fully mineralized. We hypothesized that these changes result in severe microstructural deterioration and reduced matrix mineralization density. Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 27 premenopausal women, mean age 43.3years (range 30.4 to 53.7) with early breast cancer made estradiol deficient for 17months (range 6-120) using ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal and 35 postmenopausal controls, mean age 62.6years (range 60.2 to 65.5). Cortical and trabecular microstructure were quantified using Strax software. Compared with premenopausal controls, the women with breast cancer had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher but cortical thickness was not reduced. Compared with postmenopausal controls 20years older, cases had comparable or lower trabecular bone volume and comparable cortical porosity and thickness. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar. The severe cortical porosity and trabecular deterioration associated with estradiol depletion and the longevity of premenopausal women with early breast cancer treated with endocrine therapy provide a compelling rationale to investigate the efficacy of antiresorptive therapy initiated at the time of breast cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of acute and subchronic AT1 receptor blockade on cardiovascular, hydromineral and neuroendocrine responses in female rats.

PubMed

Araujo, Iracema Gomes; Elias, Lucila Leico Kagohara; Antunes-Rodrigues, José; Reis, Luís Carlos; Mecawi, Andre Souza

2013-10-02

Female Wistar rats were ovariectomized (OVX) and separated into two groups that received either estradiol cypionate (EC, 40 μg/kg, sc; OVX-EC) or vehicle (corn oil, sc; OVX-oil) for 14 consecutive days. On the 7th day of treatment, a subset of animals from both the OVX-oil and OVX-EC groups was subjected to subchronic losartan (AT1 receptor antagonist) treatment (0.1g/L in drinking water; ~15 mg/kg/day) for 7 days. Other group of OVX-oil and OVX-EC rats was submitted to an acute losartan injection (100mg/kg, ip) on the 14th day of hormone replacement. In both protocols, the following parameters were measured: I) mean arterial pressure (MAP) and heart rate (HR); II) water and 0.3M saline intake; III) angiotensin II (ANG II), atrial natriuretic peptide (ANP), vasopressin (AVP) and oxytocin (OT) plasma concentrations; and IV) urinary and plasma sodium concentrations. Acute AT1 blockade induced a significant reduction in the MAP in the OVX rats, resulting in increased HR and water intake, which were attenuated by estradiol therapy. Acute AT1 blockade also increased ANG II and OT and reduced ANP plasma concentrations, with no changes in AVP secretion. In addition, acute hypotension was accompanied by a decrease in natriuresis, which was unaltered by estradiol. Subchronic AT1 blockade induced a significant decrease in MAP without changing HR in both groups. Additionally, subchronic losartan treatment induced sodium appetite in OVX rats. Prolonged AT1 blockade increased ANG II and AVP and reduced ANP plasma concentrations. Moreover, it increased natriuresis but did not alter plasma OT concentrations. Finally, estradiol treatment attenuated the increase in salt intake and plasma ANG II concentrations induced by subchronic AT1 blockade. In conclusion, our results suggest differential adaptive responses to the acute or subchronic losartan treatment in OVX and OVX-EC rats. © 2013.

Corps of Engineers Final New and Modified Replacement Nationwide Permits 2000

EPA Pesticide Factsheets

Final new and modified replacement Nationwide Permits require that the Corps be notified of activities impacting more than one-tenth of an acre. The NWPs also provide additional protections to critical resource waters, 100-yr floodplains, and streams.

State of the art systematic review of bone disease in anorexia nervosa.

PubMed

Misra, Madhusmita; Golden, Neville H; Katzman, Debra K

2016-03-01

Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Search terms included "anorexia nervosa" AND "bone density" for the period 1995-2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. © 2015 Wiley Periodicals, Inc.

Cutaneous estradiol permeation, penetration and metabolism in pig and man.

PubMed

Mahmoud, A; Haberland, A; Dürrfeld, M; Heydeck, D; Wagner, S; Schafer-Korting, M

2005-01-01

Drug development in dermatotherapy and also development of transdermal therapeutic systems (TTS) demand high-predictive in vitro models to estimate drug levels in skin and systemic uptake. Here we compare three ready-to-use models, reconstructed human epidermis, split porcine skin and the perfused porcine forelimb. 17beta-Estradiol (E(2)), which is highly metabolized by skin cells, serves as model drug since E(2) application is of high relevance in hormone replacement therapy while topical E(2) may promote wound healing. E(2) TTS, gel and an ethanolic solution were investigated for cutaneous penetration, permeation and metabolism. E(2) TTS enabled an E(2) uptake of 42.9% of the applied dose accompanied by a high percentage of E(2) metabolism (30% of the penetrated dose) in the perfused porcine forelimb. In Franz cell experiments with reconstructed human epidermis and split porcine skin, the gel allowed an E(2) uptake of 41.7 and 22.9% of the applied dose accompanied by a high E(2) metabolism (42.6 and 28.6% of the penetrated dose). Due to toxic effects of the vehicle, this was not true with an ethanolic solution, then E(2) permeation and metabolism were clearly diminished. Most importantly, the in vitro models proved to be predictive with respect to the E(2)/estrone ratio in female plasma under transdermal hormone replacement therapy. In vitro tests should reduce the need for both animal and human studies for cutaneous uptake and metabolism in the future. Copyright 2005 S. Karger AG, Basel.

An increase in estradiol facilitates the onset of paternal behavior in the dwarf hamster (Phodopus campbelli).

PubMed

Romero-Morales, Luis; Martínez-Torres, Martín; Cárdenas, Mario; Álvarez, Carmen; Carmona, Agustín; Cedillo, Benita; Loya-Zurita, Eduardo; Luis, Juana

2018-03-01

In the dwarf hamster (Phodopus campbelli), activational effects of testosterone (T) and estradiol (E 2 ) in the regulation of paternal behavior have been repeatedly rejected because peripheral concentrations of E 2 do not change across the reproductive cycle of males. Further, castration no affected paternal behavior despite that both T and E 2 concentrations decreased significantly. However, the role of these hormones has not been evaluated in models of castration and hormonal replacement in virgin males. Here, we analysed the effects of E 2 and T in paternal behavior in virgin male dwarf hamster (Phodopus campbelli). Thirty paternal (PAT) males were bilaterally castrated; of them, 10 were implanted with T, 10 with E 2 and 10 males received no treatment. Other 10 PAT males underwent sham-castration. Seventeen aggressive (AGG) males were also bilaterally castrated; of these, 10 AGG received E 2 replacement, 7 were not treated. Other 7 AGG males were submitted to sham-castration. Following treatments, paternal behavior tests were conducted again. T and E 2 levels in plasma were quantified by radioimmunoassay (RIA). The results showed that the treatments did not affect the paternal behavior of males that were initially paternal. Neither castration nor sham-castration surgery affected the behavior of AGG males. However, when these males were treated with E 2 and the concentrations of this hormone increase significantly they became paternal. Our data suggest that an increase in E 2 levels shifted infanticidal behavior to paternal behavior in dwarf hamster. Copyright © 2018 Elsevier Inc. All rights reserved.

State of the Art Systematic Review of Bone Disease in Anorexia Nervosa

PubMed Central

Misra, Madhusmita; Golden, Neville H.; Katzman, Debra K.

2016-01-01

Objective Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Method Search terms included “anorexia nervosa” AND “bone density” for the period 1995–2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. Results AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. Discussion To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. PMID:26311400

Physiologically assessed hot flashes and endothelial function among midlife women.

PubMed

Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; von Känel, Roland; Landsittel, Doug P; Matthews, Karen A

2017-08-01

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P < 0.05) indicated that among the younger tertile of women in the sample (age 40-53 years), the presence of hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study.

PubMed

Schliep, Karen C; Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Zhang, Cuilin; Ye, Aijun; Stanford, Joseph B; Hammoud, Ahmad O; Porucznik, Christina A; Wactawski-Wende, Jean

2012-02-01

Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = -0.15; 95% CI: -0.26, -0.05) and positively associated among Asian women (β = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively. Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race.

Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study123

PubMed Central

Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Zhang, Cuilin; Ye, Aijun; Stanford, Joseph B; Hammoud, Ahmad O; Porucznik, Christina A; Wactawski-Wende, Jean

2012-01-01

Background: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. Objective: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Design: Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Results: Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = −0.15; 95% CI: −0.26, −0.05) and positively associated among Asian women (β = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively. Conclusions: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race. PMID:22237060

TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mice.

PubMed

Vallcaneras, Sandra; Ghersa, Federica; Bastón, Juan; Delsouc, María Belén; Meresman, Gabriela; Casais, Marilina

2017-09-01

Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55-/- (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at -80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites. © 2017 Society for Endocrinology.

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.

46 CFR 54.10-3 - Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103). 54.10-3 Section 54.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-3 Marine inspectors (replaces UG-90 and UG-91, and...

46 CFR 54.10-3 - Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103). 54.10-3 Section 54.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-3 Marine inspectors (replaces UG-90 and UG-91, and...

46 CFR 54.10-3 - Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103). 54.10-3 Section 54.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-3 Marine inspectors (replaces UG-90 and UG-91, and...

46 CFR 54.10-3 - Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103). 54.10-3 Section 54.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-3 Marine inspectors (replaces UG-90 and UG-91, and...

46 CFR 54.10-3 - Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Marine inspectors (replaces UG-90 and UG-91, and modifies UG-92 through UG-103). 54.10-3 Section 54.10-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-3 Marine inspectors (replaces UG-90 and UG-91, and...

Nonlinear wave choked inlets

NASA Technical Reports Server (NTRS)

1979-01-01

The quasi-one dimensional flow program was modified in two ways. The Runge-Kutta subroutine was replaced with a subroutine which used a modified divided difference form of the Adams Pece method and the matrix inversion routine was replaced with a pseudo inverse routine. Calculations were run using both the original and modified programs. Comparison of the calculations showed that the original Runge-Kutta routine could not detect singularity near the throat and was integrating across it. The modified version was able to detect the singularity and therefore gave more valid calculations.

Influence of sex hormone levels on gingival enlargement in adolescent patients undergoing fixed orthodontic therapy: A pilot study

PubMed Central

Hosadurga, Rajesh; Nabeel Althaf, M. S.; Hegde, Shashikanth; Rajesh, Kashyap S.; Arun Kumar, M. S.

2016-01-01

Background: Sex hormones may be a modifying factor in the periodontal disease pathogenesis. Aim: The association between gingival enlargement and sex hormone levels in adolescent patients undergoing fixed orthodontic therapy needs to be determined. Settings and Design: This study was conducted in the Department of Periodontology in association with the Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangaluru. Materials and Methods: A pilot study was conducted on 21 adolescent patients between the age group of 13–19 years, who had undergone fixed orthodontic therapy for at least 3 months. Apicocoronally, the gingival enlargement was assessed by the index described by Miller and Damm. Miranda and Brunet index was used to assess gingival overgrowth in the buccal–lingual direction in the interdental papilla. Furthermore, the patients were assigned to two groups - Group 1-GE and Group 2-non-GE. Sex hormones assessed were estradiol and progesterone in females and testosterone in males in both groups. Results: 57.1% of the study population had enlargement of the gingiva. The mean plaque score was 0.59 and 0.56, respectively, in both groups. A statistically significant relationship was found between estradiol and testosterone levels with gingival enlargement. However, a significant relationship was not obtained for progesterone levels with the gingival enlargement. Conclusion: Direct correlation between estradiol, testosterone, and gingival enlargement was seen. PMID:27994419

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.

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.

C-nor-9,11-secoestranes as modified estrogens and fertility regulation.

PubMed

Lal, K; Sharma, I; Agarwal, A K; Agnihotri, A; Ray, S

1988-06-01

The synthesis of C-nor-9,11-secoestradiol (4) has been achieved from 17 beta-acetoxy-11-chloro-3-methoxy-C-nor-9,11-secoestra-1,3,5(10)-tr ien-9-one (1) through a sequence of reactions without affecting the stereochemistry of estradiol-17 beta. Removal of the 9-keto function of 1 by hydrogenolysis and its subsequent treatment with Na/NH3 gives C-nor-9,11-secoestradiol 3-(methyl ether) (3), which has been demethylated under alkaline conditions to furnish C-nor-9,11-secoestradiol (4). Pyridinium chlorochromate oxidation of 3 gives the corresponding 17-ketone 6. Jones' oxidation of 4 to the ketone 5 and reaction of 5 and 6 with lithium acetylide gives corresponding 17 alpha-ethynyl derivatives 7 and 8. Relative binding affinity to estradiol-17 beta receptors and uterotropic, antiuterotrophic, and antiimplantation activities of compounds 3-8 have been studied. The effect of conformational flexibility on ligand-receptor interaction of these compounds is discussed.

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…

Discordant Genotypic Sex and Phenotype Variations in Two Spanish Siblings with 17α-Hydroxylase/17,20-Lyase Deficiency Carrying the Most Prevalent Mutated CYP17A1 Alleles of Brazilian Patients.

PubMed

Fernández-Cancio, Mónica; García-García, Emilio; González-Cejudo, Carmen; Martínez-Maestre, María-Angeles; Mangas-Cruz, Miguel-Angel; Guerra-Junior, Gil; Pandi de Mello, Maricilda; Arnhold, Ivo J P; Nishi, Mirian Y; Bilharinho Mendonça, Berenice; García-Arumí, Elena; Audí, Laura; Tizzano, Eduardo; Carrascosa, Antonio

2017-01-01

17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia caused by mutations in CYP17A1. Two phenotypic female sisters, aged 17 and 15 years and with 46,XY and 46,XX karyotypes, respectively, presented with primary amenorrhea and absent secondary sexual characteristics. The elder sib also presented with high blood pressure. Both patients had elevated levels of ACTH, gonadotropins, progesterone, corticosterone, and deoxycorticosterone, and reduced levels of estradiol, testosterone, androstenedione, 17-OH-P, DHEA-S, cortisol, aldosterone, and renin activity. The CYP17A1 gene was sequenced, and polymorphic haplotypes were further analyzed in the Spanish family and in Brazilian patients. The 2 sisters were compound heterozygous for p.Arg362Cys and p.Trp406Arg mutations, previously described as the most prevalent mutations in Brazilian families of Spanish (p.Trp406Arg) or Portuguese (p.Arg362Cys) origin. Analysis of polymorphisms in CYP17A1 suggested that the paternal allele with p.Arg362Cys may share a common origin with the Brazilian carriers, while the maternal allele with p.Trp406Arg did not. Hydrocortisone and sex hormone replacement therapy was initiated in both patients. In conclusion, one CYP17A1 mutation (p.Arg362Cys) may share a common ancestry in Brazilian and our present Spanish patients, while p.Trp406Arg may have arisen separately. The elder patient (46,XY) developed a more severe phenotype and a poorer response to estradiol replacement therapy. © 2017 S. Karger AG, Basel.

The Integrated Hypothalamic Tachykinin-Kisspeptin System as a Central Coordinator for Reproduction

PubMed Central

Bosch, Martha A.; León, Silvia; Simavli, Serap; True, Cadence; Pinilla, Leonor; Carroll, Rona S.; Seminara, Stephanie B.; Tena-Sempere, Manuel; Rønnekleiv, Oline K.; Kaiser, Ursula B.

2015-01-01

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r−/− mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreased LH release in ovariectomized-sham replaced females, as documented for NK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons and GnRH neurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons. PMID:25422875

The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction.

PubMed

Navarro, Víctor M; Bosch, Martha A; León, Silvia; Simavli, Serap; True, Cadence; Pinilla, Leonor; Carroll, Rona S; Seminara, Stephanie B; Tena-Sempere, Manuel; Rønnekleiv, Oline K; Kaiser, Ursula B

2015-02-01

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r(-/-) mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreased LH release in ovariectomized-sham replaced females, as documented for NK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons and GnRH neurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.

17β Estradiol increases resilience and improves hippocampal synaptic function in helpless ovariectomized rats

PubMed Central

Bredemann, Teruko M.; McMahon, Lori L.

2014-01-01

Summary Memory impairment is the most commonly reported cognitive symptom associated with major depressive disorder. Decreased hippocampal volume and neurogenesis in depression link hippocampal dysfunction with deficits in memory. Stress decreases hippocampal dendritic spine density and long-term potentiation (LTP) at glutamate synapses, a cellular correlate of learning and memory. However, elevated plasma levels of 17β estradiol (E2) during proestrus increase hippocampal structure and function, directly opposing the negative consequences of stress. In women, significant fluctuations in ovarian hormones likely increase vulnerability of hippocampal circuits to stress, potentially contributing to the greater incidence of depression compared to men. Using the learned helplessness model of depression and ovariectomized female rats, we investigated whether acquisition of helplessness and hippocampal synaptic dysfunction is differentially impacted by the presence or absence of plasma E2. We find that inescapable shock induces a greater incidence of helplessness in vehicle- versus E2-treated OVX rats. In the vehicle-treated group, LTP was absent at CA3-CA1 synapses in slices only from helpless rats, and CA1 spine density was decreased compared to resilient rats. In contrast, significant LTP was observed in slices from E2-treated helpless rats; importantly, spine density was not different between E2-treated helpless and resilient rats, dissociating spine density from the LTP magnitude. We also find that E2 replacement can reverse previously established helpless behavior. Thus, our results show that E2 replacement in OVX rats increases resilience and improves hippocampal plasticity, suggesting that E2 therapy may increase resilience to stress and preserve hippocampal function in women experiencing large fluctuations in plasma estrogen levels. PMID:24636504

Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis

PubMed Central

Basha, Maureen E.; Chang, Shaohua; Burrows, Lara J.; Lassmann, Jenny; Wein, Alan J.; Moreland, Robert S.; Chacko, Samuel K.

2013-01-01

Introduction Vaginal atrophy is a consequence of menopause however little is known concerning the effect of a decrease in systemic estrogen on vaginal smooth muscle structure and function. As the incidence of pelvic floor disorders increases with age, it is important to determine if estrogen regulates the molecular composition and contractility of the vaginal muscularis. Aim The goal of this study was to determine the effect of estrogen on molecular and functional characteristics of the vaginal muscularis utilizing a rodent model of surgical menopause. Methods 3–4 month old Sprague Dawley rats underwent sham laparotomy (Sham, n=18) or ovariectomy (Ovx, n=39). Two weeks following surgery, animals received a subcutaneous osmotic pump containing vehicle (Sham, Ovx) or 17- β estradiol (Ovx). Animals were euthanized one week later and the proximal vagina was collected for analysis of contractile protein expression and in vitro studies of contractility. Measurements were analyzed using a one-way ANOVA followed by Tukey's post hoc analysis (α= 0.05). Main Outcome Measures Protein and mRNA transcript expression levels of contractile proteins, in vitro measurements of vaginal contractility Results Ovariectomy decreased the expression of carboxyl-terminal myosin heavy chain isoform SM1 and h-caldesmon and reduced the amplitude of contraction of the vaginal muscularis in response to KCl. Estradiol replacement reversed these changes. No differences were detected in the % vaginal muscularis, mRNA transcript expression of amino terminal MHC isoforms, l-caldesmon expression and maximal velocity of shortening. Conclusion Systemic estrogen replacement restores functional and molecular characteristics of the vaginal muscularis of ovariectomized rats. Our results indicate that menopause is associated with changes in the vaginal muscularis, which may contribute to the increased incidence of pelvic floor disorders with age. PMID:23438289

[Local infiltration analgesia in total joint replacement].

PubMed

de Jonge, Tamás; Görgényi, Szabolcs; Szabó, Gabriella; Torkos, Miklós Bulcsú

2017-03-01

Total hip and knee replacment surgeries are characterized by severe postoperative pain. Local infiltration analgesia is proved to be very effective. However this method has not been widely used in Hungary. To evaluate the efficacy of the local infiltration analgesia with modified components in patients underwent total hip or knee replacement surgery. Data of 99 consecutive patients underwent primary total hip or knee replacement surgery were evaluated prospectively. In all the 99 surgeries modified local infiltration analgesia was applied. Postoperative pain reported on a visual analog scale was recorded as well as the need for further analgetics during the first 18 hours after surgery. The cost of the analgetic drugs was calculated. The control group comprised 97 consecutive patients underwent total hip or knee replacement, where local infiltration analgesia was not applied. Statistical analysis was done. Patients received local infiltration analgesia reported significantly less pain (p<0.001). The need for postoperatively given analgetics was almost 50% less, and the cost of all postoperative analgetics was 47% less than in the control group. In total hip and knee replacement surgeries the modified local infiltration analgesia decreases postoperative pain effectively and contribute to the early mobilization of the patients. Orv. Hetil., 2017, 158(9), 352-357.

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).” ...

17β-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor β in the aging female rat brain.

PubMed

Shults, Cody L; Dingwall, Caitlin B; Kim, Chun K; Pinceti, Elena; Rao, Yathindar S; Pak, Toni R

2018-01-01

Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens. Estrogen receptors (ERs) are subject to alternative splicing, the spliced variants increase following menopause, and they fail to efficiently activate estrogen-dependent signaling pathways. However, the factors that regulate the alternative splicing of ERs remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17β-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERβ. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol.

PubMed

Yasrebi, Ali; Hsieh, Anna; Mamounis, Kyle J; Krumm, Elizabeth A; Yang, Jennifer A; Magby, Jason; Hu, Pu; Roepke, Troy A

2016-02-15

Ghrelin's receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile of Luteolin-7-O-glucoside Isolated from Trifolium alexandrinum L. in Ovariectomized Rats.

PubMed

Ammar, N M; El-Hawary, S S; Mohamed, D A; El-Halawany, A M; El-Anssary, A A; El-Kassem, L T Abou; Hussein, R A; Jaleel, G A Abdel; El-Dosoky, A H

2016-05-01

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis.

PubMed

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-06-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

PubMed Central

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-01-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

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

PubMed

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

2015-02-01

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

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...

Tetragonia tetragonioides (Pall.) Kuntze protects estrogen-deficient rats against disturbances of energy and glucose metabolism and decreases proinflammatory cytokines.

PubMed

Ryuk, Jin Ah; Ko, Byoung-Seob; Lee, Hye Won; Kim, Da Sol; Kang, Suna; Lee, Yong Hyen; Park, Sunmin

2017-03-01

Tetragonia tetragonioides (Pall.) Kuntze (TTK) and JakYakGamCho-Tang (JGT) have been used for improving women's health and treating inflammatory diseases. We determined that the long-term consumption of these herbal extracts alleviates the progression of postmenopausal symptoms in high-fat-diet fed ovariectomized (OVX) rats, and further explored the mechanisms involved. Five groups of OVX rats were fed high fat diets that were supplemented with either 2% dextrin (control), 2% TTK (70% ethanol extract), 2% JGT (water extract), 1% JGT + 1% TTK (JGTT), or 30 µg/kg body weight/day of 17β-estradiol (positive control). After eight weeks of dietary intervention, the herbal treatments did not change the serum concentrations of 17β-estradiol or uterine weight in control rats, but they were higher in the positive-control group. TTK rats exhibited higher daily energy expenditure, particularly fat oxidation, without modifying the energy intake than the controls. TTK lowered the fat mass but lean body mass of the abdomen and leg were increased. JGT decreased periuterine fat mass and lean body mass more than the control but the decrease was not as much as TTK. TTK resulted in substantially lower serum concentrations of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1, than the control and JGT had lesser effect than TTK. Insulin resistance, determined by homeostasis model assessment estimate for assessing insulin resistance (HOMA-IR) and insulin tolerance test, was reduced in the decreasing order of control, JGT, JGTT, and TTK and the HOMA-IR of TTK was similar to the positive control. TTK, but not JGT, enhanced glucose tolerance compared with the control, although the serum insulin levels in TTK were lower compared to the control. Interestingly, the β-cell masses were much greater in the TTK and JGTT groups than in the control, and they were comparable to the positive control. The increases in β-cell masses in TTK and JGTT groups were associated with enhanced β-cell proliferation and suppressed apoptosis, which was related to the decreased TNF-α and interleukin-1β expressions. In conclusion, JGTT did not improve menopausal symptoms better than TTK itself. TTK itself prevented the OVX-induced impairments in energy, lipid, and glucose metabolism, similar to the positive control, without changing serum 17β-estradiol levels and potentiating insulin signaling and decreasing proinflammatory cytokines. TTK may be a useful intervention to alleviate some menopausal symptoms similar to selective estrogen receptor modulators and should be investigated with further human study. Impact statement Menopause decreases the quality of life in middle-aged women and herbal remedies are sometimes used as alternatives for hormone replacement therapy, which may have detrimental side effects. Although several herbal extracts have been studied, no remedies improve all the menopausal symptoms. In this study, the 70% ethanol extract of Tetragonia tetragonioides (Pall.) Kuntze (TTK) reduced the symptoms of hot flushes and improved energy, glucose, and lipid metabolism in estrogen-deficient animals without increasing serum 17β-estradiol levels. This extract acts like a selective estrogen receptor modulator and it may be a useful intervention for alleviating menopausal symptoms. This is the first study to show that the 70% ethanol extract of TTK has the potential to treat menopause-associated symptoms and metabolic disturbances. It may be a useful intervention for alleviating the symptoms of menopause in women if its efficacy can be confirmed in human studies.

Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone.

PubMed

Dias, Jenny Pena; Veldhuis, Johannes D; Carlson, Olga; Shardell, Michelle; Chia, Chee W; Melvin, Denise; Egan, Josephine M; Basaria, Shehzad

2017-04-01

Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone. Thirty-seven men, ≥65years with total testosterone <350ng/dL were randomized to 5g transdermal testosterone gel (TT), 1mg oral aromatase inhibitor (AI) or placebo daily for 12months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6months. At 3months, mean GH and in IGF-1 were similar between the three groups. At 6months, IGF-1 significantly increased by Δ 15.3±10.3ng/ml in the TT-group compared to placebo (P=0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P=0.04; AI-group, P=0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P=0.0018) compared to placebo while it remained unchanged in the AI-group (P=0.059). In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Can we induce spermatogenesis in the domestic cat using an in vitro tissue culture approach?

PubMed Central

Amaral, Sandra; Tavares, Renata S.; Schlatt, Stefan; Ramalho-Santos, João

2018-01-01

The reduced number of animals in most wild felid populations implies a loss of genetic diversity. The death of juveniles, prior to the production of mature sperm, represents a loss of potential genetic contribution to future populations. Since 2011 mouse testicular organ culture has introduced an alternative mechanism to produce sperm in vitro from immature tissue. However, extension of this technology to other species has remained limited. We have used the domestic cat (Felis catus) as a model for wild felids to investigate spermatogenesis initiation and regulation, with the mouse serving as a control species. Testicular tissue fragments were cultured in control medium or medium supplemented with knockout serum replacement (KSR), AlbuMax, beta-estradiol or AlbuMax plus beta-estradiol. Contrary to expectations, and unlike results obtained in mouse controls, no germ cell differentiation could be detected. The only germ cells observed after six weeks of culture were spermatogonia regardless of the initial stage of tubule development in the donor tissue. Moreover, the number of spermatogonia decreased with time in culture in all media tested, especially in the medium supplemented with KSR, while AlbuMax had a slight protective effect. The combination of AlbuMax and beta-estradiol led to an increase in the area occupied by seminiferous tubules, and thus to an increase in total number of spermatogonial cells. Considering all the media combinations tested the stimulus for felid germ cell differentiation in this type of system seems to be different from the mouse. Studies using other triggers of differentiation and tissue survival factors should be performed to pursue this technology for the genetic diversity preservation in wild felids. PMID:29414992

Cognitive function variations in postmenopausal women treated with continuous, combined HRT or tibolone. A comparison.

PubMed

Pan, Hsien-An; Wang, Shan-Tair; Pai, Ming-Chyi; Chen, Chih-Hung; Wu, Meng-Hsing; Huang, Ko-En

2003-05-01

To compare cognitive function in postmenopausal women receiving continuous hormone replacement therapy and those receiving tibolone. This was a 6-month, prospective, single-blind, single center, randomized study. A total of 50 healthy, postmenopausal women were enrolled. In the end, 40 women completed the 6-month follow-up. One group (23 subjects) received conjugated equine estrogens (CEE), 0.625 mg/d, and medroxyprogesterone acetate (MPA), 5 mg/d. The other group (17 subjects) received tibolone, 2.5 mg/d. Their serum estradiol levels and Cognitive Abilities Screening Instrument (CASI) and Mini-Mental State Examination (MMSE) scores were obtained before starting and after 3 and 6 months of treatment. There was a significant increase in the serum estradiol level in the CEE + MPA group, especially after 3 months of treatment, but there was no increase in the estradiol level in the tibolone group. The CASI and MMSE scores of the CEE + MPA group and the tibolone group after 3 and 6 months of treatment showed no significant difference between the two groups apart from the MMSE at the 3-month follow-up. We saw an increasing trend in CASI and MMSE scores after treatment in both groups; however, the increases were not statistically significant. The rate of increase of both CASI and MMSE scores in the CEE + MPA group was greater than in the tibolone group, though the difference was not significant. This preliminary study demonstrated that both CEE + MPA and tibolone can preserve cognitive function and may be able to prevent cognitive decline in postmenopausal women during short-term treatment. Our results also show that continuous, combined CEE + MPA seems to be marginally more effective than tibolone in improving cognitive processes; however, long-term study is needed to follow-up such effect.

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

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.

Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

PubMed Central

2011-01-01

Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2. PMID:21952234

Correlation of the penetration enhancement with the influence of an alcohol/tocopheryl polyethylene glycol succinate (TPGS) cosolvent system on the molecular structure of the stratum corneum of nude mouse skin as examined by microscopic FTIR/DSC

NASA Astrophysics Data System (ADS)

Liou, Yi-Bo; Ho, Hsiu-O.; Chen, Shin-Yi; Sheu, Ming-Thau

2009-10-01

Tocopheryl polyethylene glycol succinate (TPGS) is a water-soluble derivative of natural source of vitamin E, which possesses a dual nature of lipophilicity and hydrophilicity, similar to a surface-active agent. The penetration enhancement of estradiol by an ethanol and TPGS cosolvent system (EtOH/TPGS) has been confirmed. In this study, the correlation of the penetration enhancement with the influence of the EtOH/TPGS cosolvent system on biophysical changes of the stratum corneum (SC) as examined by Fourier transformation infrared spectrometry differential scanning calorimetry (FTIR/DSC) was investigated. Thermotropic changes in the asymmetrical and symmetrical C-H stretching of hydrocarbon chains of lipids, and amide I and II bands that characterize the protein structure of the SC treated with different concentrations of the EtOH/TPGS cosolvent were examined in this investigation. Results demonstrated that a strong correlation of the influence on biophysical changes of the SC treated with the EtOH/TPGS cosolvent system with the penetration enhancement of estradiol by the corresponding cosolvent system was not evident. It was concluded that the incorporation of TPGS in the cosolvent system seemed only to have insignificantly modified the structural features of the SC. It was not obvious that the penetrant had encountered these modifications resulting in an improvement in the penetration of estradiol by TPGS.

Neuroendocrine modulation and repercussions of female reproductive aging.

PubMed

Wise, Phyllis M; Smith, Matthew J; Dubal, Dena B; Wilson, Melinda E; Rau, Shane W; Cashion, Adrienne B; Böttner, Martina; Rosewell, Katherine L

2002-01-01

The menopause marks the end of a woman's reproductive life. During the postmenopausal period, plasma estrogen concentrations decrease dramatically and remain low for the rest of her life, unless she chooses to take hormone replacement therapy. During the past 20 years, we have learned that changes in the central nervous system are associated with and may influence the timing of the menopause in women. Recently, it has become clear that estrogens act on more than just the hypothalamus, pituitary, ovary, and other reproductive organs. In fact, they play roles in a wide variety of nonreproductive functions. With the increasing life span of humans from approximately 50 to 80 years and the relatively fixed age of the menopause, a larger number of women will spend over one third of their lives in the postmenopausal state. It is not surprising that interest has increased in factors that govern the timing of the menopause and the repercussions of the lack of estrogen on multiple aspects of women's health. We have used animal models to better understand the complex interactions between the ovary and the brain that lead to the menopause and the repercussions of the hypoestrogenic state. Our results show that when rats reach middle age, the patterns and synchrony of multiple neurochemical events that are critical to the preovulatory gonadotropin-releasing hormone (GnRH) surge undergo subtle changes. The precision of rhythmic pattern of neurotransmitter dynamics depends on the presence of estradiol. Responsiveness to this hormone decreases in middle-aged rats. The lack of precision in the coordination in the output of neural signals leads to a delay and attenuation of the luteinizing hormone surge, which lead to irregular estrous cyclicity and, ultimately, to the cessation of reproductive cycles. We also have examined the impact of the lack of estrogen on the vulnerability of the brain to injury. Our work establishes that the absence of estradiol increases the extent of cell death after stroke-like injury and that treatment with low physiological levels of estradiol are profoundly neuroprotective. We have begun to explore the cellular and molecular mechanisms that underlie this novel nonreproductive action of estrogens. In summary, our studies show that age-related changes in the ability of estradiol to coordinate the neuroendocrine events that lead to regular preovulatory GnRH surges contribute to the onset of irregular estrous cycles and eventually to acyclicity. Furthermore, we have shown that the lack of estradiol increases the vulnerability of the brain to injury and neurodegeneration.

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

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.

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

In vitro bioactivity of 17alpha-estradiol.

PubMed

Sievernich, André; Wildt, Ludwig; Lichtenberg-Fraté, Hella

2004-12-01

A miniaturised short-term in vitro assay based on the activation of the human estrogen receptor alpha and genetically modified yeast (Saccharomyces cerevisiae) cells was performed to explore the capacity of this system to monitor the bioactivity of estrogenic compounds, particularly 17alpha- and 17beta-estradiol. Together with the human estrogen receptor (hER)-alpha plasmid, the reporter plasmid containing a yeast-optimised version of the green fluorescent protein (yEGFP) linked to three repeats of the cis-acting estrogen hormone-responsive element (ERE) were expressed in a strain being deleted in the pleiotropic drug resistance transporters Pdr5, Snq2 and Yor1, known to facilitate efflux of organic compounds including steroids and chemotherapeutics. Agonists that bind to hER in vitro trigger estrogen receptor-mediated transcriptional activation of the GFP reporter gene monitored by fluorescence emission at 535 nm. The sensitivity of the assay was tested with various 17alpha- and 17beta-estradiol concentrations, yielding a detection limit of 5 pg/ml (0.018 nM) for the agonist 17beta-E2 in solvent and in human charcoal-stripped serum using a S. cerevisiae pdr5, snq2 and yor1 mutant strain. For 17alpha-estradiol only, at approximately 1500 pg/ml a similar fluorescence response compared to 100 pg/ml 17beta-E2 was observed implicating a much weaker potency of this stereoisomer. The specificity of the system was tested by expression of a truncated hER lacking the ligand-binding domain E and by administration of the androgen, 4-androsten 3,17 dione. Both controls did not yield an increase in fluorescence emission. This fluorescence emission assay enables detection of estrogenic biological activity induced by direct agonists, such as 17beta-E2 at concentrations similar to those found in human sera or by estrogen-like chemicals.

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.

Composite aortic root replacement using the classic or modified Cabrol coronary artery implantation technique.

PubMed

Garlicki, Miroslaw; Roguski, K; Puchniewicz, M; Ehrlich, Marek P

2006-08-01

We report in this study our results with composite aortic root replacement (CVR) using the classic or modified Cabrol coronary implantation technique. From October 2001 to March 2005, 25 patients underwent aortic root replacement. In all cases, the indication for surgery was a degenerative aneurysm with a diameter of more than 6 cm. Seven patients had undergone a previous aortic operation on the ascending aorta. Mean age was 53+/-13 years and 22 patients were male. Mean Euroscore was 5.2+/-2.4. Aortic insufficiency was present in all patients. Two patients had Marfan syndrome. The 30-day mortality was 0%. Two patients required profound hypothermic circulatory arrest. Mean aortic cross-clamp time was 91+/-24 minutes and the mean circulatory arrest time was 24+/-15 minutes. No patients developed a pseudoaneurysm after the operation. We conclude that composite aortic root replacement with the classic or modified Cabrol technique results in a low operative mortality. However, it should be only used when a "button" technique is not feasible.

Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.

PubMed

Klipping, Christine; Duijkers, Ingrid; Parke, Susanne; Mellinger, Uwe; Serrani, Marco; Junge, Wolfgang

2011-01-01

A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance. The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel. Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2 mg/dienogest 2 mg, 17 days estradiol valerate 2 mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three. Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel. The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.

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.

Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome.

PubMed

Maliqueo, Manuel; Benrick, Anna; Marcondes, Rodrigo Rodrigues; Johansson, Julia; Sun, Miao; Stener-Victorin, Elisabet

2017-01-01

What is the central question of this study? The effectiveness of low-frequency electroacupuncture in the treatment of metabolic disorders associated with polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder characterized by an imbalance in sex steroid production, is controversial. What is the main finding and its importance? In a rat model of PCOS induced by the inhibition of P450 aromatase, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol but did not improve the insulin resistance or the adipose tissue dysfunction, suggesting that a balance of sex steroids is needed to restore the metabolic function in this rat model of PCOS. Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may ameliorate its metabolic disturbances, probably by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or β-adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (200 μg day -1 ) or placebo pellets were implanted in prepubertal Wistar rats. Six weeks thereafter, rats were treated for 5-6 weeks with the following: low-frequency electroacupuncture (5 days per week); a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg kg -1 , 5 days per week); or 17β-estradiol (2.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue-specific glucose uptake, lipid profile, adipocyte size, serum concentrations of adiponectin and insulin, and gene expression in inguinal fat were measured. All treatments increased circulating levels of low-density lipoprotein-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusion, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol without affecting insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation, probably mediated by the action of estradiol or the β-adrenergic pathway. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

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.

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.

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.

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...

Excess fat in the abdomen but not general obesity is associated with poorer metabolic and cardiovascular health in premenopausal and postmenopausal Asian women.

PubMed

Goh, Victor Hng Hang; Hart, William George

2018-01-01

To examine the associations of various metabolites and hormones and hormone replacement therapy (HRT) with obesity. This is a cross-sectional study of 1326 Singaporean women. A DXA-derived percent body fat (PBF) of ≥35% and percent abdominal fat (PAbdF) of >21.8% were used, respectively, to define women with general (GOb) and abdominal (AbdOb) obesity. Higher levels of insulin and glucose, lower levels of HDL, higher levels of TC/HDL and HOMA values, and different levels of some hormones were noted only in the women with abdominal, and not general obesity. The incidence of general and abdominal obesity was higher in postmenopausal women with or without HRT, except that those who were on conjugated estradiol-only HRT had no increase in the incidence of general obesity compared with premenopausal women. Abdominal obesity is associated with insulin resistance and with higher risks of metabolic syndrome and cardiovascular diseases, whereas general obesity is not. Abdominal obesity may predispose to a higher risk of diabetes. The onset of the menopause tends to increase the incidence of general and abdominal obesity, except that postmenopausal women on conjugated estradiol HRT appear to be relatively protected from general obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Low plasma PDGF-BB levels are associated with estradiol in postmenopausal osteoporosis: PDGF-BB mediated by estradiol in women.

PubMed

Tang, Lanhua; Xia, Zhuying; Luo, Zhongwei; Long, Haitao; Zhu, Yong; Zhao, Shushan

2017-08-01

Objective This study aimed to investigate the association between low plasma Platelet-derived growth factor-BB (PDGF-BB) levels and oestradiol in Postmenopausal osteoporosis (PMOP). Methods This prospective study measured plasma PDGF-BB and oestradiol levels in outpatients who were admitted to our hospital. Participants were screened and then allocated to three groups: normal young women, postmenopausal control, and PMOP. Additionally, Sprague-Dawley rats underwent either sham surgery or bilateral ovariectomy (OVX), and were divided into the following groups: sham, OVX, OVX + oestradiol, and OVX + PDGF-BB. Plasma oestradiol and PDGF-BB levels were measured using commercially available ELISA kits. Results A total of 121 participants, including 69 normal young women, 28 patients with primary PMOP, and 24 age-matched postmenopausal women were enrolled. Plasma oestradiol and PDGF-BB levels were lower in postmenopausal women, especially in PMOP ( P < 0.01). Pearson correlations analysis showed that PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age ( P < 0.01). The OVX rat model showed that oestradiol replacement increased plasma PDGF-BB levels, while PDGF-BB systematic treatment had no effect on plasma oestradiol levels. Conclusions Plasma PDGF-BB levels are maintained by oestrogen in normal young women and play a major role in PMOP.

Chemically modified cellulose paper as a thin film microextraction phase.

PubMed

Saraji, Mohammad; Farajmand, Bahman

2013-11-01

In this paper, chemically modified cellulose paper was introduced as a novel extracting phase for thin film microextraction (TFME). Different reagents (Octadecyltrichlorosilane, diphenyldichlorosilane, cyclohexyl isocyanate and phenyl isocyanate) were used to modify the cellulose papers. The modified papers were evaluated as a sorbent for the extraction of some synthetic and natural estrogenic hormones (17α-ethynylestradiol, estriol and estradiol) from aqueous samples. Liquid chromatography-fluorescence detection was used for the quantification of the extracted compounds. The cellulose paper modified with phenyl isocyanate showed the best affinity to the target compounds. TEME parameters such as desorption condition, shaking rate, sample ionic strength and extraction time were investigated and optimized. Limit of detections were between 0.05 and 0.23μgL(-1) and relative standard deviations were less than 11.1% under the optimized condition. The calibration curves were obtained in the range of 0.2-100μgL(-1) with a good linearity (r(2)>0.9935). Wastewater, human urine, pool and river water samples were studied as real samples for the evaluation of the method. Relative recoveries were found to be between 75% and 101%. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of female and male sex steroids on body composition in the rabbit model.

PubMed

Alexandersen, P; Hassager, C; Christiansen, C

2001-09-01

To study the influence on body composition of estrogen replacement therapy (ERT) in female rabbits and of replacement therapy with testosterone (TRT) in male rabbits using dual-energy X-ray absorptiometry (DEXA). Cholesterol-fed female and male rabbits receiving a weight-restricted diet (100 g/day) were used. Total lean tissue mass (LTM), total body fat tissue mass (FTM) and total tissue mass (TTM) were determined by DEXA at baseline, after which the animals were gonadectomized and treated with sex steroids. Soft body composition was then determined again after 30-31 weeks of treatment. Relative to controls, ERT with estradiol (E2) doses of 2 and 4 mg/day significantly increased LTM (p < 0.001), whereas E2 0.5 and 1 mg/day had a neutral effect on LTM. The change in fat mass, however, was not statistically significant between groups. In male rabbits, compared with castrated control rabbits, LTM decreased in testosterone-treated animals (by 7-12%; p < 0.001) but FTM decreased relatively more (by 66-79%; p < 0.0001). In both genders, body weight correlated with TTM as determined by DEXA (r = 0.89-0.91, p < 0.0001). In this in vivo model of growing rabbits, estrogen replacement significantly increased LTM in female animals, whereas testosterone replacement significantly decreased FTM in males, suggesting that soft body composition of both genders is significantly affected by replacement with sex steroids. Until comparable human data are available, it is speculated that similar changes in soft body composition may occur in humans treated with sex steroids.

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,…

Comparative Biological Effects and Potency of 17a- and 17ß-Estradiol In Fathead Minnows

USDA-ARS?s Scientific Manuscript database

17ß-estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17a-estradiol, a diastereoisomer of 17ß-estradiol, exists in the li...

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...

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.

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.

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.

Association between self-report adherence measures and oestrogen suppression among breast cancer survivors on aromatase inhibitors.

PubMed

Brier, Moriah J; Chambless, Dianne; Gross, Robert; Su, H Irene; DeMichele, Angela; Mao, Jun J

2015-09-01

Poor adherence to oral adjuvant hormonal therapy for breast cancer is a common problem, but little is known about the relationship between self-report adherence measures and hormonal suppression. We evaluated the relationship of three self-report measures of medication adherence and oestrogen among patients on aromatase inhibitors (AIs). We recruited 235 women with breast cancer who were prescribed AI therapy. Participants self-reported AI adherence by completing the following: (1) a single item asking whether they took an AI in the last month, (2) a modified Morisky Medication Adherence Scale-8 (MMAS-8) and (3) the Visual Analog Scale (VAS). Serum estrone and estradiol were analysed using organic solvent extraction and Celite column partition chromatography, followed by radioimmunoassay. Ten percent of participants reported they had not taken an AI in the last month and among this group, median estrone (33.2 pg/ml [interquartile range (IQR)=22.3]) and estradiol levels (7.2 pg/mL [IQR=3.3]) were significantly higher than those in participants who reported AI use (median estrone=11.5 pg/mL [IQR=4.9]; median estradiol=3.4 pg/mL [IQR=2.1]; p<0.001). This relationship held when controlling for race and AI drug type. A single-item monthly-recall adherence measure for AIs was associated with oestrogen serum levels. This suggests that patient-reported monthly adherence may be a useful measure to identify early non-adherence behaviour and guide interventions to improve patient adherence to hormonal treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

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) ...

The Benefit of Modified Rehabilitation and Minimally Invasive Techniques in Total Hip Replacement

PubMed Central

Lilikakis, Anastasios K; Gillespie, Beryl; Villar, Richard N

2008-01-01

INTRODUCTION We wished to assess if an intensive rehabilitation regimen alone, or one combined with modified anaesthetic and surgical techniques, can change the speed of rehabilitation or the length of hospital stay after total hip replacement. PATIENTS AND METHODS We compared 44 patients who had followed a traditional care pathway, with 38 patients who had rehabilitated under a new rehabilitation protocol, with 40 patients who had also received modified, minimally invasive techniques. The speed of rehabilitation was measured in terms of three specific milestones accomplished on the day after surgery. RESULTS We found a statistically significant improvement in the day after surgery each activity was possible. The length of hospital stay was reduced from 6.5 days to 5.4 days to 4.1 days, a difference which was also statistically significant. CONCLUSIONS The data support the view that a new rehabilitation protocol alone can reduce the length of hospital stay and hasten rehabilitation. The combination of modified anaesthetic and minimally invasive surgical techniques with the new rehabilitation regimen can further improve short-term outcome after total hip replacement. PMID:18634739

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.

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.

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

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.

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.

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.

Properties of concrete modified with waste Low Density Polyethylene and saw dust ash

NASA Astrophysics Data System (ADS)

Srimanikandan, P.; Sreenath, S.

2017-07-01

The increase in industrialization creates need for disposal of large quantity of by-products. To overcome the difficulty of disposal, these by-products can be used as a replacement for raw material. In this concern, non-conventional industrial wastes such as plastic bags, PET bottles, pulverized waste Low Density Polyethylene (LDPE) and biological waste such as saw-dust ash, coconut coir were used as a replacement in concrete. In this project, saw-dust ash and pulverized waste LDPE were introduced as the partial replacement for cement and fine aggregates respectively. 0%, 5%, 10%, 15% and 20% of sand by volume was replaced with LDPE and 0%, 1%, 3%, 5% and 10% of cement by volume was replaced with saw dust ash. Standard cube, cylinder and prism specimens were cast to assess the compressive strength, split tensile strength and flexural strength of modified concrete after 28 days of curing. Optimum percentage of replacement was found by comparing the test results. The mix with 5% of LDPE and 3% of saw dust ash showed a better result among the other mixes.

European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy.

PubMed

Ekman, Bertil; Fitts, David; Marelli, Claudio; Murray, Robert D; Quinkler, Marcus; Zelissen, Pierre M J

2014-05-09

Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387). Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy. Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK and Sweden, with recruitment soon to be initiated in the Netherlands. EU-AIR will provide a unique opportunity not only to collect long-term safety data on a modified-release preparation of glucocorticoid but also to evaluate baseline data on conventional glucocorticoid replacement. Such data should help to improve the treatment of AI.

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.

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.

Estradiol Transdermal Patch

MedlinePlus

Most brands of estradiol transdermal patches are used to treat hot flushes (hot flashes; sudden strong feelings of heat ... different medication that does not contain estrogen. Most brands of estradiol transdermal patches are also sometimes used ...

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.

Detection of 17 β-Estradiol in Environmental Samples and for Health Care Using a Single-Use, Cost-Effective Biosensor Based on Differential Pulse Voltammetry (DPV).

PubMed

Dai, Yifan; Liu, Chung Chiun

2017-03-29

Environmental estrogen pollution and estrogen effects on the female reproductive system are well recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproductive system. 17 β-estradiol is carcinogenic and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects psychological well-being such as depression, fatigue and others. Thus, a simple method of detecting 17 β-estradiol will be important for both environmental estrogen pollution and health care. This study demonstrates a single-use, cost-effective 17 β-estradiol biosensor system which can be used for both environmental and health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe(CN)₆/K₄Fe(CN)₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER-α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied were between 2.25 pg/mL and 2250 pg/mL; Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulated urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone, which has a similar chemical structure and molecular weight as those of 17 β-estradiol, was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

De Novo Synthesized Estradiol Protects against Methylmercury-Induced Neurotoxicity in Cultured Rat Hippocampal Slices

PubMed Central

Ishihara, Yasuhiro; Komatsu, Shota; Munetsuna, Eiji; Onizaki, Masahiro; Ishida, Atsuhiko; Kawato, Suguru; Mukuda, Takao

2013-01-01

Background Estrogen, a class of female sex steroids, is neuroprotective. Estrogen is synthesized in specific areas of the brain. There is a possibility that the de novo synthesized estrogen exerts protective effect in brain, although direct evidence for the neuroprotective function of brain-synthesized estrogen has not been clearly demonstrated. Methylmercury (MeHg) is a neurotoxin that induces neuronal degeneration in the central nervous system. The neurotoxicity of MeHg is region-specific, and the molecular mechanisms for the selective neurotoxicity are not well defined. In this study, the protective effect of de novo synthesized 17β-estradiol on MeHg-induced neurotoxicity in rat hippocampus was examined. Methodology/Principal Findings Neurotoxic effect of MeHg on hippocampal organotypic slice culture was quantified by propidium iodide fluorescence imaging. Twenty-four-hour treatment of the slices with MeHg caused cell death in a dose-dependent manner. The toxicity of MeHg was attenuated by pre-treatment with exogenously added estradiol. The slices de novo synthesized estradiol. The estradiol synthesis was not affected by treatment with 1 µM MeHg. The toxicity of MeHg was enhanced by inhibition of de novo estradiol synthesis, and the enhancement of toxicity was recovered by the addition of exogenous estradiol. The neuroprotective effect of estradiol was inhibited by an estrogen receptor (ER) antagonist, and mimicked by pre-treatment of the slices with agonists for ERα and ERβ, indicating the neuroprotective effect was mediated by ERs. Conclusions/Significance Hippocampus de novo synthesized estradiol protected hippocampal cells from MeHg-induced neurotoxicity via ERα- and ERβ-mediated pathways. The self-protective function of de novo synthesized estradiol might be one of the possible mechanisms for the selective sensitivity of the brain to MeHg toxicity. PMID:23405170

Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

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

Gupta, Rupesh K., E-mail: drrupesh@illinois.ed; Singh, Jeffery M., E-mail: jsingh20@illinois.ed; Leslie, Tracie C., E-mail: tleslie2@illinois.ed

2010-01-15

Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 mug/ml) and MEHP (0.1-10 mug/ml) directly inhibit antral follicular growth andmore » estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.« less

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.

77 FR 18801 - Notice of Application for Non-Capacity Amendment of License and Soliciting Comments, Motions To...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... new high efficiency turbine runners, replacing runner seals, replacing or modifying head covers; (2) conducting non-destructive examination and possible rehabilitation and modification of shafts; (3...

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.

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.

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.

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.

Properties of Cement Mortar Produced from Mixed Waste Materials with Pozzolanic Characteristics.

PubMed

Yen, Chi-Liang; Tseng, Dyi-Hwa; Wu, Yue-Ze

2012-07-01

Waste materials with pozzolanic characteristics, such as sewage sludge ash (SSA), coal combustion fly ash (FA), and granulated blast furnace slag (GBS), were reused as partial cement replacements for making cement mortar in this study. Experimental results revealed that with dual replacement of cement by SSA and GBS and triple replacement by SSA, FA, and GBS at 50% of total cement replacement, the compressive strength (Sc) of the blended cement mortars at 56 days was 93.7% and 92.9% of the control cement mortar, respectively. GBS had the highest strength activity index value and could produce large amounts of CaO to enhance the pozzolanic activity of SSA/FA and form calcium silicate hydrate gels to fill the capillary pores of the cement mortar. Consequently, the Sc development of cement mortar with GBS replacement was better than that without GBS, and the total pore volume of blended cement mortars with GBS/SSA replacement was less than that with FA/SSA replacement. In the cement mortar with modified SSA and GBS at 70% of total cement replacement, the Sc at 56 days was 92.4% of the control mortar. Modifying the content of calcium in SSA also increased its pozzolanic reaction. CaCl(2) accelerated the pozzolanic activity of SSA better than lime did. Moreover, blending cement mortars with GBS/SSA replacement could generate more monosulfoaluminate to fill capillary pores.

Properties of Cement Mortar Produced from Mixed Waste Materials with Pozzolanic Characteristics

PubMed Central

Yen, Chi-Liang; Tseng, Dyi-Hwa; Wu, Yue-Ze

2012-01-01

Abstract Waste materials with pozzolanic characteristics, such as sewage sludge ash (SSA), coal combustion fly ash (FA), and granulated blast furnace slag (GBS), were reused as partial cement replacements for making cement mortar in this study. Experimental results revealed that with dual replacement of cement by SSA and GBS and triple replacement by SSA, FA, and GBS at 50% of total cement replacement, the compressive strength (Sc) of the blended cement mortars at 56 days was 93.7% and 92.9% of the control cement mortar, respectively. GBS had the highest strength activity index value and could produce large amounts of CaO to enhance the pozzolanic activity of SSA/FA and form calcium silicate hydrate gels to fill the capillary pores of the cement mortar. Consequently, the Sc development of cement mortar with GBS replacement was better than that without GBS, and the total pore volume of blended cement mortars with GBS/SSA replacement was less than that with FA/SSA replacement. In the cement mortar with modified SSA and GBS at 70% of total cement replacement, the Sc at 56 days was 92.4% of the control mortar. Modifying the content of calcium in SSA also increased its pozzolanic reaction. CaCl2 accelerated the pozzolanic activity of SSA better than lime did. Moreover, blending cement mortars with GBS/SSA replacement could generate more monosulfoaluminate to fill capillary pores. PMID:22783062

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.

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

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.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.

PubMed

Geber, Selmo; Brandão, Augusto H F; Sampaio, Marcos

2012-06-15

Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student's t-test and Pearson's correlation test. We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

Experimental Investigation of the Mechanical and Durability Properties of Crumb Rubber Concrete.

PubMed

Liu, Hanbing; Wang, Xianqiang; Jiao, Yubo; Sha, Tao

2016-03-07

Recycling waste tire rubber by incorporating it into concrete has become the preferred solution to dispose of waste tires. In this study, the effect of the volume content of crumb rubber and pretreatment methods on the performances of concrete was evaluated. Firstly, the fine aggregate and mixture were partly replaced by crumb rubber to produce crumb rubber concrete. Secondly, the mechanical and durability properties of crumb rubber concrete with different replacement forms and volume contents had been investigated. Finally, the crumb rubber after pretreatment by six modifiers was introduced into the concrete mixture. Corresponding tests were conducted to verify the effectiveness of pretreatment methods as compared to the concrete containing untreated crumb rubber. It was observed that the mechanical strength of crumb rubber concrete was reduced, while durability was improved with the increasing of crumb rubber content. 20% replacement of fine aggregate and 5% replacement of the total mixture exhibited acceptable properties for practical applications. In addition, the results indicated that the modifiers had a positive impact on the mechanical and durability properties of crumb rubber concrete. It avoided the disadvantage of crumb rubber concrete having lower strength and provides a reference for the production of modified crumb rubber concrete.

Experimental Investigation of the Mechanical and Durability Properties of Crumb Rubber Concrete

PubMed Central

Liu, Hanbing; Wang, Xianqiang; Jiao, Yubo; Sha, Tao

2016-01-01

Recycling waste tire rubber by incorporating it into concrete has become the preferred solution to dispose of waste tires. In this study, the effect of the volume content of crumb rubber and pretreatment methods on the performances of concrete was evaluated. Firstly, the fine aggregate and mixture were partly replaced by crumb rubber to produce crumb rubber concrete. Secondly, the mechanical and durability properties of crumb rubber concrete with different replacement forms and volume contents had been investigated. Finally, the crumb rubber after pretreatment by six modifiers was introduced into the concrete mixture. Corresponding tests were conducted to verify the effectiveness of pretreatment methods as compared to the concrete containing untreated crumb rubber. It was observed that the mechanical strength of crumb rubber concrete was reduced, while durability was improved with the increasing of crumb rubber content. 20% replacement of fine aggregate and 5% replacement of the total mixture exhibited acceptable properties for practical applications. In addition, the results indicated that the modifiers had a positive impact on the mechanical and durability properties of crumb rubber concrete. It avoided the disadvantage of crumb rubber concrete having lower strength and provides a reference for the production of modified crumb rubber concrete. PMID:28773298

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.

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.

Regulation of estrogen receptor beta mRNA in the brain: opposite effects of 17beta-estradiol and the phytoestrogen, coumestrol.

PubMed

Patisaul, H B; Whitten, P L; Young, L J

1999-04-06

Estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) are differentially distributed in the brain and likely mediate different estrogen-dependent processes. ERbeta is abundant in the bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus of the hypothalamus and the amygdala of the rat. In the paraventricular nucleus, which is devoid of ERalpha, ERbeta is colocalized with the neuropeptides, oxytocin and vasopressin, suggesting a potential functional role for ERbeta in the regulation of these peptides. We examined the regulation of ERbeta mRNA expression in the rat brain by 17beta-estradiol and the phytoestrogen, coumestrol. 17beta-Estradiol treatment decreased ERbeta mRNA in situ hybridization signal by 44.5% in the paraventricular nucleus of the hypothalamus (PVN), but had no effect in the bed nucleus of the stria terminalis (BnST) or the medial preoptic nucleus (MPA). In contrast, dietary exposure to coumestrol increased ERbeta mRNA signal by 47.5% in the PVN but had no effect in the BnST or the MPA. These data demonstrate that like ERalpha, ERbeta is down regulated by estrogen in a region specific manner in the rat brain. Furthermore, exposure to coumestrol may modulate ERbeta-dependent processes by acting as an anti-estrogen at ERbeta. This data contradicts results from cell transfection assays which suggest an estrogenic activity of coumestrol on ERbeta, indicating that the mode of action may be tissue specific, or that metabolism of dietary coumestrol may alter its effects. Because the highest concentrations of phytoestrogens are found in legumes, vegetables and grains, they are most prevalent in vegetarian and traditional Asian diets. Understanding the neuroendocrine effects of phytoestrogens is particularly important now that they are being marketed as a natural alternative to estrogen replacement therapy and sold in highly concentrated pills and powders. Copyright 1999 Elsevier Science B.V.

Influence of androgen receptor CAG polymorphism on sexual function recovery after testosterone therapy in late-onset hypogonadism.

PubMed

Tirabassi, Giacomo; Corona, Giovanni; Biagioli, Andrea; Buldreghini, Eddi; delli Muti, Nicola; Maggi, Mario; Balercia, Giancarlo

2015-02-01

Androgen receptor (AR) CAG polymorphism has been found to influence sexual function. However, no study has evaluated its potential to condition sexual function recovery after testosterone replacement therapy (TRT) in a large cohort of hypogonadic subjects. To evaluate the role of this polymorphism in sexual function improvement after TRT in late-onset hypogonadism (LOH). Seventy-three men affected by LOH were retrospectively considered. Evaluations were performed before TRT started (time 0) and before the sixth undecanoate testosterone injection. International Index of Erectile Function (IIEF) questionnaire (erectile function [EF], orgasmic function [OF], sexual desire [SD], intercourse satisfaction [IS], overall satisfaction [OS], and total IIEF-15 score); total and free testosterone and estradiol; AR gene CAG repeat number. TRT induced a significant increase in total and free testosterone and estradiol. All IIEF domains significantly improved after TRT. AR CAG repeats negatively and significantly correlated with all the variations (Δ-) of sexual function domains, except for Δ-OS. Conversely, Δ-total testosterone was found to be positively and significantly correlated with sexual function domain variations, except for Δ-IS and Δ-OS. Δ-estradiol did not correlate significantly with any of the variations of sexual function domains. After inclusion in generalized linear models, the number of AR gene CAG triplets was found to be independently and negatively associated with Δ-EF, Δ-SD, Δ-IS, and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated with Δ-EF, Δ-OF, Δ-SD, and Δ-Total IIEF-15 score. However, after including time 0 total testosterone in the model, AR gene CAG triplets remained independently and negatively associated only with Δ-EF and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated only with Δ-EF. Longer length of AR gene CAG repeat tract seems to lower TRT-induced improvement of sexual function in LOH. © 2014 International Society for Sexual Medicine.

Modifying gravity: you cannot always get what you want.

PubMed

Starkman, Glenn D

2011-12-28

The combination of general relativity (GR) and the Standard Model of particle physics disagrees with numerous observations on scales from our Solar System up. In the canonical concordance model of Lambda cold dark matter (ΛCDM) cosmology, many of these contradictions between theory and data are removed or alleviated by the introduction of three completely independent new components of stress energy--the inflaton, dark matter and dark energy. Each of these in its turn is meant to have dominated (or to currently dominate) the dynamics of the Universe. There is, until now, no non-gravitational evidence for any of these dark sectors, nor is there evidence (though there may be motivation) for the required extension of the Standard Model. An alternative is to imagine that it is GR that must be modified to account for some or all of these disagreements. Certain coincidences of scale even suggest that one might expect not to make independent modifications of the theory to replace each of the three dark sectors. Because they must address the most different types of data, attempts to replace dark matter with modified gravity are the most controversial. A phenomenological model (or family of models), modified Newtonian dynamics, has, over the last few years, seen several covariant realizations. We discuss a number of challenges that any model that seeks to replace dark matter with modified gravity must face: the loss of Birkhoff's theorem, and the calculational simplifications it implies; the failure to explain clusters, whether static or interacting, and the consequent need to introduce dark matter of some form, whether hot dark matter neutrinos or dark fields that arise in new sectors of the modified gravity theory; the intrusion of cosmological expansion into the modified force law, which arises precisely because of the coincidence in scale between the centripetal acceleration at which Newtonian gravity fails in galaxies and the cosmic acceleration. We conclude with the observation that, although modified gravity may indeed manage to replace dark matter, it is likely to do so by becoming or at least incorporating a dark matter theory itself.

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.

Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.

PubMed

Twigt, John M; Hammiche, Fatima; Sinclair, Kevin D; Beckers, Nicole G; Visser, Jenny A; Lindemans, Jan; de Jong, Frank H; Laven, Joop S E; Steegers-Theunissen, Régine P

2011-02-01

Folate is a methyl donor. Availability of folate affects DNA methylation profiles and thereby gene expression profiles. We investigated the effects of low-dose folic acid use (0.4 mg/d) on the ovarian response to mild and conventional ovarian stimulation in women. In a randomized trial among subfertile women, 24 and 26 subjects received conventional and mild ovarian stimulation, respectively. Blood samples were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine, anti-Müllerian hormone (AMH), estradiol, and folate. Folic acid use was validated by questionnaire and serum folate levels. Preovulatory follicles were visualized, counted, and diameters recorded using transvaginal ultrasound. The relation between folic acid use and ovarian response was assessed using linear regression analysis. Folic acid use modified the ovarian response to ovarian stimulation treatment. The estradiol response was higher in nonfolic acid users receiving conventional treatment [β(interaction) = 0.52 (0.07-0.97); P = 0.03], and this effect was independent of serum AMH levels and the preovulatory follicle count. In the conventional treatment, the mean follicle number was also greater in nonusers compared with the users group (14.1 vs. 8.9, P = 0.03). Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation, independent of AMH and follicle count. The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development, affecting immature follicles. Deleterious effects of folate deficiency, like DNA hypomethylation and oxidative stress, can help to explain our observations.

Cognitive Impacts of Estrogen Treatment in Androgen-Deprived Males: What Needs to be Resolved.

PubMed

Wibowo, Erik

2017-01-01

Many prostate cancer (PCa) patients are on androgen deprivation therapy (ADT) as part of their cancer treatments but ADT may lead to cognitive impairments. ADT depletes men of both androgen and estrogen. Whether estradiol supplementation can improve cognitive impairments in patients on ADT is understudied. To summarize data on the effects of estradiol treatment on cognitive function of androgen-deprived genetic male populations (PCa patients and male-to-female transsexuals) and castrated male animals. Publications were identified by a literature search on PubMed and Google Scholar. While some studies showed that estradiol improves cognitive function (most notably, spatial ability) for castrated rats, what remains uninvestigated are: 1) whether estradiol can improve cognition after long-term androgen deprivation, 2) how estradiol affects memory retention, and 3) how early vs. delayed estradiol treatment after castration influences cognition. For androgendeprived genetic males, estradiol treatment may improve some cognitive functions (e.g., verbal and visual memory), but the findings are not consistent due to large variability in the study design between studies. Future studies are required to determine the best estradiol treatment protocol to maximize cognitive benefits for androgen-deprived genetic males. Tests that assess comparable cognitive domains in human and rodents are needed. What particularly under-investigated is how the effects of estradiol on cognitive ability intersect with other parameters; sleep, depression and physical fatigue. Such studies have clinical implications to improve the quality of life for both PCa patients on ADT as well as for male-to-female transsexuals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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)

Influence of ferutinin on bone metabolism in ovariectomized rats. II: Role in recovering osteoporosis

PubMed Central

Ferretti, Marzia; Bertoni, Laura; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Carnevale, Gianluca; Benelli, Augusta; Zanoli, Paola; Palumbo, Carla

2010-01-01

The aim of the present investigation, which represents an extension of a previous study, was to investigate the effect of ferutinin in recovering severe osteoporosis due to estrogen deficiency after rat ovariectomy and to compare phytoestrogen effects with those of estrogens commonly used in hormone replacement therapy (HRT) by women with postmenopausal osteoporosis. The animal model used was the Sprague–Dawley ovariectomized rat. Ferutinin was orally administered (2 mg kg−1 per day) for 30 or 60 days starting from 2 months after ovariectomy (i.e. when osteoporosis was clearly evident) and its effects were compared with those of estradiol benzoate (1.5 μg per rat twice a week, subcutaneously injected) vs. vehicle-treated ovariectomized (OVX) and sham-operated (SHAM) rats. Histomorphometric analyses were performed on trabecular bone of lumbar vertebrae (4th and 5th) and distal femoral epiphysis, as well as on cortical bone of femoral diaphysis. Bone histomorphometric analyses showed that ferutinin seems to display the same effects on bone mass recorded with estradiol benzoate, thus suggesting that it could enhance the recovery of bone loss due to severe estrogen deficiency in OVX rats. On this basis, the authors propose listing ferutinin among the substances representing a potential alternative for the treatment of postmenopausal osteoporosis, which occurs as a result of estrogen deficiency. PMID:20492429

Estrogen-dependent effects on behavior, lipid-profile, and glycemic index of ovariectomized rats subjected to chronic restraint stress.

PubMed

da Silva, Caroline Calice; Lazzaretti, Camilla; Fontanive, Tiago; Dartora, Daniela Ravizzoni; Bauereis, Brian; Gamaro, Giovana Duzzo

2014-03-01

Stress has been shown to negatively affect the immune system, alter the body's metabolism, and play a strong role in the development of mood disorders. These effects are mainly driven through the release of hormones from the hypothalamic-pituitary-adrenal axis (HPA). Additionally, women are more likely to be affected by stress due to the estrogen fluctuation associated with their menstrual cycle. This study aims to evaluate the effect of chronic restraint stress, applied for 30 days, and estrogen replacement on behavior, glucose level, and the lipid profile of ovariectomized rats. Our results suggest that stress increases sweet food consumption in OVX females treated with estradiol (E2), but reduces consumption in animals not treated. Furthermore, stress increases locomotor activity and anxiety as assessed by the Open Field test and in the Elevated Plus Maze. Similarly, our results suggest that E2 increases anxiety in female rats under the same behavioral tests. In addition, stress reduces glucose and TC levels. Moreover, stress increase TG levels in the presence of E2 and decrease in its absence, as well as the estradiol increase TG levels in stressed groups and reduced in non-stressed groups. Our data suggest an important interaction between stress and estrogen, showing that hormonal status can induce changes in the animal's response to stress. Copyright © 2014 Elsevier B.V. All rights reserved.

A combinatorial approach to synthetic transcription factor-promoter combinations for yeast strain engineering

DOE PAGES

Dossani, Zain Y.; Reider Apel, Amanda; Szmidt-Middleton, Heather; ...

2017-10-30

Despite the need for inducible promoters in strain development efforts, the majority of engineering in Saccharomyces cerevisiae continues to rely on a few constitutively active or inducible promoters. Building on advances that use the modular nature of both transcription factors and promoter regions, we have built a library of hybrid promoters that are regulated by a synthetic transcription factor. The hybrid promoters consist of native S. cerevisiae promoters, in which the operator regions have been replaced with sequences that are recognized by the bacterial LexA DNA binding protein. Correspondingly, the synthetic transcription factor (TF) consists of the DNA binding domainmore » of the LexA protein, fused with the human estrogen binding domain and the viral activator domain, VP16. The resulting system with a bacterial DNA binding domain avoids the transcription of native S. cerevisiae genes, and the hybrid promoters can be induced using estradiol, a compound with no detectable impact on S. cerevisiae physiology. Using combinations of one, two or three operator sequence repeats and a set of native S. cerevisiae promoters, we obtained a series of hybrid promoters that can be induced to different levels, using the same synthetic TF and a given estradiol. Finally, this set of promoters, in combination with our synthetic TF, has the potential to regulate numerous genes or pathways simultaneously, to multiple desired levels, in a single strain.« less

Musculo-skeletal pain, psychological distress, and hormones during the menopausal transition.

PubMed

Finset, Arnstein; Øverlie, Inger; Holte, Arne

2004-01-01

To investigate the relationship between sex hormones (estradiol, testosterone, androstendione, DHEA-S) and prolactin on one hand and musculo-skeletal pain and psychological distress on the other during the menopausal transition. Fifty-seven regularly menstruating women, who were studied over five consecutive years, who reached menopause before the fifth assessment, and did not use hormone replacement therapy were included in the study. Hormones were sampled and a questionnaire including questions on psychological distress and musculo-skeletal pain were administered at the five points of assessment. Data on last year before menopause (T1), first (T2) and second (T3) year after menopause are reported. DHEA-S, but neither testosterone nor androstendione, was inversely related to distress and pain. Pain contributed to the variance of DHEA-S over the menopausal transition, whereas DHEA-S levels did not predict pain or distress when baseline levels were controlled for. Prolactin was at T1 and T2 positively associated with distress and at T2 positively associated with musculo-skeletal pain. Musculo-skeletal pain pre-menopause was significantly related to estradiol. DHEA-S was negatively associated, and prolactin positively associated with musculo-skeletal pain and psychological distress. Whereas post-menopause DHEA-S levels were influenced by pain scores, no significant effect of pre-menopause hormones on post-menopause pain and distress was found.

A combinatorial approach to synthetic transcription factor‐promoter combinations for yeast strain engineering

PubMed Central

Dossani, Zain Y.; Reider Apel, Amanda; Szmidt‐Middleton, Heather; Hillson, Nathan J.; Deutsch, Samuel; Keasling, Jay D.

2017-01-01

Abstract Despite the need for inducible promoters in strain development efforts, the majority of engineering in Saccharomyces cerevisiae continues to rely on a few constitutively active or inducible promoters. Building on advances that use the modular nature of both transcription factors and promoter regions, we have built a library of hybrid promoters that are regulated by a synthetic transcription factor. The hybrid promoters consist of native S. cerevisiae promoters, in which the operator regions have been replaced with sequences that are recognized by the bacterial LexA DNA binding protein. Correspondingly, the synthetic transcription factor (TF) consists of the DNA binding domain of the LexA protein, fused with the human estrogen binding domain and the viral activator domain, VP16. The resulting system with a bacterial DNA binding domain avoids the transcription of native S. cerevisiae genes, and the hybrid promoters can be induced using estradiol, a compound with no detectable impact on S. cerevisiae physiology. Using combinations of one, two or three operator sequence repeats and a set of native S. cerevisiae promoters, we obtained a series of hybrid promoters that can be induced to different levels, using the same synthetic TF and a given estradiol. This set of promoters, in combination with our synthetic TF, has the potential to regulate numerous genes or pathways simultaneously, to multiple desired levels, in a single strain. PMID:29084380

A combinatorial approach to synthetic transcription factor-promoter combinations for yeast strain engineering

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

Dossani, Zain Y.; Reider Apel, Amanda; Szmidt-Middleton, Heather

Despite the need for inducible promoters in strain development efforts, the majority of engineering in Saccharomyces cerevisiae continues to rely on a few constitutively active or inducible promoters. Building on advances that use the modular nature of both transcription factors and promoter regions, we have built a library of hybrid promoters that are regulated by a synthetic transcription factor. The hybrid promoters consist of native S. cerevisiae promoters, in which the operator regions have been replaced with sequences that are recognized by the bacterial LexA DNA binding protein. Correspondingly, the synthetic transcription factor (TF) consists of the DNA binding domainmore » of the LexA protein, fused with the human estrogen binding domain and the viral activator domain, VP16. The resulting system with a bacterial DNA binding domain avoids the transcription of native S. cerevisiae genes, and the hybrid promoters can be induced using estradiol, a compound with no detectable impact on S. cerevisiae physiology. Using combinations of one, two or three operator sequence repeats and a set of native S. cerevisiae promoters, we obtained a series of hybrid promoters that can be induced to different levels, using the same synthetic TF and a given estradiol. Finally, this set of promoters, in combination with our synthetic TF, has the potential to regulate numerous genes or pathways simultaneously, to multiple desired levels, in a single strain.« less

[Customization of hormonal contraception].

PubMed

DE Leo, Vincenzo; Cianci, Antonio; DI Carlo, Costantino; Cappelli, Valentina; Fruzzetti, Franca

2018-02-01

In the last few years new oral contraceptives have been marketed showing a better safety profile for women. They are the result of important changes made to the old compounds. As far as the estrogenic component, with the aim of decreasing side effects, the dose of ethinyl estradiol has been reduced and synthetic estrogens have been replaced by natural estradiol, further improving the safety profile. Also the progestin component in the last years has been changed in terms of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic progestin, but now there is the possibility of choosing progestins without androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate), very useful in patients with hyperandrogenism. Some of these progestins, like Drospirenone, represented the real held contributing, because of its antimineralcorticoid action, to reduce an important side effect like fluid retention; moreover there is the possibility to choose products with high progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting very effective in women with abnormal uterine bleedings. Also the regimens of administration have been changed, by shortening or eliminating the tablet-free period; in this way the women may avoid premenstrual symptoms. The oral is not the only route of administration, but today there are alternative routes like transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro-intestinal interferences and possible mistakes in pill intake.

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.

Replaceable filters and cones for flared-tubing connectors

NASA Technical Reports Server (NTRS)

Grant, L. E.; Howland, B. T.

1970-01-01

Connector is modified by machining the cone from one end before the fitting is bored to accommodate a metallic-filament type of slip-in filter. Thus, when surface of the cone is damaged, only the cone needs replacement.

Note: Modified anvil design for improved reliability in DT-Cup experiments.

PubMed

Hunt, Simon A; Dobson, David P

2017-12-01

The Deformation T-Cup (DT-Cup) is a modified 6-8 multi-anvil apparatus capable of controlled strain-rate deformation experiments at pressures greater than 18 GPa. Controlled strain-rate deformation was enabled by replacing two of the eight cubic "second-stage" anvils with hexagonal cross section deformation anvils and modifying the "first-stage" wedges. However, with these modifications approximately two-thirds of experiments end with rupture of the hexagonal anvils. By replacing the hexagonal anvils with cubic anvils and, split, deformation wedge extensions, we restore the massive support to the deformation anvils that were inherent in the original multi-anvil design and prevent deformation anvil failure. With the modified parts, the DT-Cup has an experimental success rate that is similar to that of a standard hydrostatic 6-8 multi-anvil apparatus.

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.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

PubMed Central

2012-01-01

Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH. PMID:22703959

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

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

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.

Adiposity and Hot Flashes in Midlife Women: A Modifying Role of Age

PubMed Central

Santoro, Nanette; Matthews, Karen A.

2011-01-01

Background: The nature of the relationship between adiposity and hot flashes has been debated, but it has not been examined using physiological measures of hot flashes. We examined associations between body size/composition and physiologically assessed hot flashes among women with hot flashes. Methods: A subcohort of women in the Study of Women's Health Across the Nation (n = 52; 25 African-American and 27 non-Hispanic Caucasian; ages, 54 to 63 yr) who reported hot flashes, had their uterus and ovaries, and were not taking medications impacting hot flashes were recruited in 2008–2009. Women completed anthropometric measures [bioimpedance analysis of total percentage of body fat, body mass index (BMI), waist circumference], a blood draw (estradiol, SHBG, FSH, dehydroepiandrosterone sulfate), and 4 d of ambulatory sternal skin conductance monitoring with diary (physiological and reported hot flashes, respectively). Associations between anthropometrics and hot flashes were estimated with generalized estimating equations with covariates age, race, and anxiety. Results: Higher BMI (odds ratio, 0.97; 95% confidence interval, 0.94–0.99; P < 0.05) and waist circumference (odds ratio, 0.98; 95% confidence interval, 0.97–0.99; P < 0.01) were associated with fewer physiological hot flashes. Interactions by age (P < 0.05) indicated that inverse associations of body fat, BMI, and waist circumference with hot flashes were most apparent among the oldest women in the sample. Estradiol and SHBG reduced but did not eliminate age-related variations in relations between body size/composition and hot flashes. Conclusion: Higher adiposity was associated with fewer physiological hot flashes among older women with hot flashes. A modifying role of age must be considered in understanding the role of adiposity in hot flashes. PMID:21778220

Adiposity and hot flashes in midlife women: a modifying role of age.

PubMed

Thurston, Rebecca C; Santoro, Nanette; Matthews, Karen A

2011-10-01

The nature of the relationship between adiposity and hot flashes has been debated, but it has not been examined using physiological measures of hot flashes. We examined associations between body size/composition and physiologically assessed hot flashes among women with hot flashes. A subcohort of women in the Study of Women's Health Across the Nation (n = 52; 25 African-American and 27 non-Hispanic Caucasian; ages, 54 to 63 yr) who reported hot flashes, had their uterus and ovaries, and were not taking medications impacting hot flashes were recruited in 2008-2009. Women completed anthropometric measures [bioimpedance analysis of total percentage of body fat, body mass index (BMI), waist circumference], a blood draw (estradiol, SHBG, FSH, dehydroepiandrosterone sulfate), and 4 d of ambulatory sternal skin conductance monitoring with diary (physiological and reported hot flashes, respectively). Associations between anthropometrics and hot flashes were estimated with generalized estimating equations with covariates age, race, and anxiety. Higher BMI (odds ratio, 0.97; 95% confidence interval, 0.94-0.99; P < 0.05) and waist circumference (odds ratio, 0.98; 95% confidence interval, 0.97-0.99; P < 0.01) were associated with fewer physiological hot flashes. Interactions by age (P < 0.05) indicated that inverse associations of body fat, BMI, and waist circumference with hot flashes were most apparent among the oldest women in the sample. Estradiol and SHBG reduced but did not eliminate age-related variations in relations between body size/composition and hot flashes. Higher adiposity was associated with fewer physiological hot flashes among older women with hot flashes. A modifying role of age must be considered in understanding the role of adiposity in hot flashes.

Estradiol effects on behavior and serum oxytocin are modified by social status and polymorphisms in the serotonin transporter gene in female rhesus monkeys.

PubMed

Michopoulos, Vasiliki; Checchi, Marta; Sharpe, Desiree; Wilson, Mark E

2011-04-01

Despite the well-documented relation between estradiol (E2) and behavior, exposure to stressors may modify sensitivity to E2. The effects of E2 on behavior are, in part, likely related to their modulation of the serotonin (5HT) and oxytocin systems. The short allele (s-variant) polymorphism found in the promoter region of the SLC6A4 gene that encodes the 5HT transporter (5HTT) modulates responsivity to stressors. The current study used ovariectomized adult female rhesus monkeys to evaluate how exposure to the psychosocial stressor of social subordination and polymorphisms in the gene encoding 5HTT influence the behavioral effects of E2 and immunoreactive serum oxytocin. Dominant females had higher levels of oxytocin than subordinate animals even though E2 increased immunoreactive serum oxytocin in all females. E2 increased affiliative behaviors in all animals, with even more of these prosocial behaviors directed at dominant females. S-variant females, regardless of social status, were more aggressive toward more subordinate cage mates and these behaviors too were increased by E2. Subordinate s-variant females are most often involved in agonistic behavior, less affiliative behavior, and were less responsive to the anxiolytic action of E2. The results show that the short allele of the 5HTT gene synergizes with psychosocial stress exposure to affect the behavioral efficacy of E2 while confirming the actions of E2 for producing generalized behavioral arousal in females. Whether differences in the central action of 5HT and/or oxytocin are responsible for this effect requires further study. Copyright © 2011 Elsevier Inc. All rights reserved.

Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats.

PubMed

Luine, V N

1985-08-01

Administration of estradiol to gonadectomized female, but not male rats, is associated with increased activity of choline acetyltransferase in the medial aspect of the horizontal diagonal band nucleus, the frontal cortex, and CA1 of the dorsal hippocampus. Four other basal forebrain cholinergic nuclei did not show changes in choline acetyltransferase activity after estradiol. These data have implications for possible benefits of estradiol administration to patients with senile dementia of the Alzheimer's type.

Ovariectomy ameliorates dextromethorphan - induced memory impairment in young female rats

PubMed Central

Jahng, Jeong Won; Cho, Hee Jeong; Kim, Jae Goo; Kim, Nam Youl; Lee, Seoul; Lee, Yil Seob

2006-01-01

We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28–37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17β-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats. PMID:16563229

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha.

PubMed

Mosquera, Laurivette; Colón, Jennifer M; Santiago, José M; Torrado, Aranza I; Meléndez, Margarita; Segarra, Annabell C; Rodríguez-Orengo, José F; Miranda, Jorge D

2014-05-02

17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen׳s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition. Copyright © 2014 Elsevier B.V. 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

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.

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.

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.

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

GPER expressed on microglia mediates the anti-inflammatory effect of estradiol in ischemic stroke.

PubMed

Zhao, Tian-Zhi; Ding, Qian; Hu, Jun; He, Shi-Ming; Shi, Fei; Ma, Lian-Ting

2016-04-01

Stroke could lead to serious morbidity, of which ischemic stroke counts for majority of the cases. Inflammation plays an important role in the pathogenesis of ischemic stroke, thus drugs targeting inflammation could be potentially neuroprotective. Estradiol was shown to be neuroprotective as well as anti-inflammatory in animal models of ischemic stroke with unclear mechanism. We hypothesize that the anti-inflammatory and neuroprotective effect of estradiol is mediated by the estradiol receptor G protein-coupled estrogen receptor 1 (GPER) expressed on microglia. We have generated the rat global cerebral ischemic model and the primary microglia culture to study the neuroprotective and anti-inflammatory effect of estradiol. We have further used pharmacological methods and siRNA knockdown approach to study the underlying mechanism. We found that estradiol reduced the level of proinflammatory cytokines including IL-1β and TNF-α, both in vivo and in vitro. We also found that the specific GPER agonist G1 could reduce the level of IL-1β (P = 0 P = 0.0017, one-way ANOVA and post hoc test) and TNF-α (P < 0.0001) in the primary microglia culture. Moreover, the specific GPER antagonist G15 was able to abolish the anti-inflammatory effect of estradiol. Estradiol failed to reduce the level of IL-1β (P = 0.4973, unpaired Student's t-test) and TNF-α (P = 0.1627) when GPER was knocked down. Our studies have suggested that GPER expressed on microglia mediated the anti-inflammatory effect of estradiol after ischemic stroke. Our studies could potentially help to develop more specific drugs to manage inflammation postischemic stroke.

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

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.

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.

Improved Butanol-Methanol (BUME) Method by Replacing Acetic Acid for Lipid Extraction of Biological Samples.

PubMed

Cruz, Mutya; Wang, Miao; Frisch-Daiello, Jessica; Han, Xianlin

2016-07-01

Extraction of lipids from biological samples is a critical step in lipidomics, especially for shotgun lipidomics where lipid extracts are directly infused into a mass spectrometer. The butanol-methanol (BUME) extraction method was originally developed to extract lipids from plasma samples with 1 % acetic acid. Considering some lipids are sensitive to acidic environments, we modified this protocol by replacing acetic acid with lithium chloride solution and extended the modified extraction to tissue samples. Although no significant reduction of plasmalogen levels in the acidic BUME extracts of rat heart samples was found, the modified method was established to extract various tissue samples, including rat liver, heart, and plasma. Essentially identical profiles of the majority of lipid classes were obtained from the extracts of the modified BUME and traditional Bligh-Dyer methods. However, it was found that neither the original, nor the modified BUME method was suitable for 4-hydroxyalkenal species measurement in biological samples.

Improved Butanol-Methanol (BUME) Method by Replacing Acetic Acid for Lipid Extraction of Biological Samples

PubMed Central

Cruz, Mutya; Wang, Miao; Frisch-Daiello, Jessica; Han, Xianlin

2016-01-01

Extraction of lipids from biological samples is a critical step in lipidomics, especially for shotgun lipidomics where lipid extracts are directly infused into a mass spectrometer. The butanol-methanol (BUME) extraction method was originally developed to extract lipids from plasma samples with 1% acetic acid. Considering some lipids are sensitive to acidic environments, we modified this protocol by replacing acetic acid with lithium chloride solution and extended the modified extraction to tissue samples. Although no significant reduction of plasmalogen levels in the acidic BUME extracts of rat heart samples was found, the modified method was established to extract various tissue samples, including rat liver, heart, and plasma. Essentially identical profiles of the majority of lipid classes were obtained from the extracts of the modified BUME and traditional Bligh-Dyer methods. However, it was found that neither the original, nor the modified BUME method was suitable for 4-hydroxyalkenal species measurement in biological samples. PMID:27245345

Estradiol-promoted accumulation of receptor in nuclei of porcine endometrium cells. Immunogold electron microscopy of resting and estradiol-stimulated cells.

PubMed

Sierralta, W D; Jakob, F; Thole, H; Engel, P; Jungblut, P W

1992-01-01

Endometrium was collected by curettage from castrated pigs, either untreated or exposed to estradiol in vivo by intrauterine injection, and processed for electron microscopy. The resin LR Gold was used for embedding, and sections were floated on droplets of 10 nm diameter gold particles, coated with the immunoglobulin-G1 (IgG1) fraction or its Fab2 fragment of a monospecific polyclonal antiserum raised in goats against the C-terminal half of the estradiol receptor. On average, only one gold particle per microns 2 became attached in the cytoplasmic area of untreated cells, whereas four were found over the nuclear area. These figures rose to 2-3/microns 2 and 15-26/microns 2, respectively, within 10 min after exposure to estradiol. The labeling intensities of nuclei in cell clusters and of coprocessed nuclei released from cells ruptured during curettage were identical in all situations. Nuclear pores were frequently tagged after estradiol treatment. The proportions of tagging densities in nuclei of untreated and estradiol-exposed cells corresponded to those of receptor contents measured in extracts of isolated nuclei by ligand binding. This correlation was not seen for the cytoplasmic compartment of untreated cells, the scarce tagging of which is interpreted by hidden antigenic determinants. Our morphological analyses support the conclusions drawn from biochemical data (Sierralta et al., 1992) of an estradiol-promoted translocation of receptor from the cytoplasm into the nucleus.

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.

Biomineralization in metakaolin modified cement mortar to improve its strength with lowered cement content.

PubMed

Li, Mengmeng; Zhu, Xuejiao; Mukherjee, Abhijit; Huang, Minsheng; Achal, Varenyam

2017-05-05

The role of industrial byproduct as supplementary cementitious material to partially replace cement has greatly contributed to sustainable environment. Metakaolin (MK), one of such byproduct, is widely used to partial replacement of cement; however, during cement replacement at high percentage, it may not be a good choice to improve the strength of concrete. Thus, in the present study, biocement, a product of microbially induced carbonate precipitation is utilized in MK-modified cement mortars to improve its compressive strength. Despite of cement replacement with MK as high as 50%, the presented technology improved compressive strength of mortars by 27%, which was still comparable to those mortars with 100% cement. The results proved that biomineralization could be effectively used in reducing cement content without compromising compressive strength of mortars. Biocementation also reduced the porosity of mortars at all ages. The process was characterized by SEM-EDS to observe bacterially-induced carbonate crystals and FTIR spectroscopy to predict responsible bonding in the formation of calcium carbonate. Further, XRD analysis identified bio/minerals formed in the MK-modified mortars. The study also encourages combining biological role in construction engineering to solve hazardous nature of cement and at same time solve the disposal problem of industrial waste for sustainable environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Foreword: Proceedings From the First Annual Lumbar Total Disc Replacement Summit.

PubMed

Blumenthal, Scott; Buttermann, Glenn; Garcia, Rolando; Gornet, Matthew; Grunch, Betsy; Guyer, Richard; Janssen, Michael; Kimball, Brent; Lewis, Adam; Mesiwala, Ali; Miller, Lynn; Morreale, Joseph; Reed, William; Sandhu, Faheem; Shackleford, Ian; Yue, James; Zigler, Jack; OConnell, Brent; Ferko, Nicole; Hollmann, Sarah

2017-12-15

: This publication focuses on proceedings from the First Annual Lumbar Total Disc Replacement Summit, held October 25, 2016 in Boston, MA. The Summit brought together 17 thought leading surgeons who employed a modified-Delphi method to determine where consensus existed pertaining to the utilization of lumbar total disc replacement as a standard of care for a subpopulation of patients suffering from degenerative disc disease.

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...

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...

Regulation of preovulatory estradiol and its impacts throughout the bovine estrous cycle

USDA-ARS?s Scientific Manuscript database

Preovulatory estradiol has been reported to play a critical role in follicular cell growth, initiation of estrus, oocyte maturation, sperm transport, uterine environment, and embryo survival. Furthermore, cattle with elevated preovulatory estradiol (HighE2) concentrations prior to fixed time AI had...

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...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

21 CFR 522.1940 - Progesterone and estradiol benzoate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Progesterone and estradiol benzoate. 522.1940 Section 522.1940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...: (1) Suckling beef calves—(i) Amount—(A) 100 milligrams (mg) progesterone and 10 mg estradiol benzoate...

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 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

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.

Use of specific radioimmunoassays to determine the renal clearance rates of estrone and 17. beta. -estradiol during the menstrual cycle. [Tritium tracer techniques

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

Wright, K.; Collins, D.C.; Preedy, J.R.K.

Specific RIAs requiring ether extraction only were established for estrone and 17..beta..-estradiol both in plasma and in urine from the nonpregnant female. These assays were used to measure the renal clearance rates of estrone and of 17..beta..-estradiol in eight ambulatory women in the follicular and in the luteal phases of the menstrual cycle. The mean (+-SE) for the renal clearance rate of estrone was 0.71 +- 0.058 ml/min in the follicular phase and 1.26 +- 0.35 ml/min in the luteal phase. The mean (+-SE) renal clearance rate of 17..beta..-estradiol was 0.44 +- 0.055 ml/min in the follicular phase and 0.29more » +- 0.043 ml/min in the luteal phase. There was no significant difference in the renal clearance rates of either estrone or of 17..beta..-estradiol between the follicular and luteal phases of the cycle. The renal clearances of estrone and 17..beta..-estradiol were highly correlated (r = 0.84; P < 0.01). The renal clearance rate of estrone was significantly greater than that of 17..beta..-estradiol in both phases of the cycle (P < 0.01).« less

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.

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.

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.

[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.

The effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ovarian ultrasonographic markers, body fat mass index, leptin, and ghrelin.

PubMed

Cakiroglu, Y; Vural, B; Isgoren, S

2013-07-01

Polycystic ovary syndrome (PCOS) is considered as the most common endocrinopathy among women of reproductive age. Oral contraceptives (OCs) and metformin are one of the main drug groups in the long-term treatment of PCOS. This study was undertaken to investigate the effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ultrasonographic markers, body fat mass (BFM) index, leptin-ghrelin. This was a prospective clinical study conducted at Kocaeli University Department of Obstetrics and Gynecology on 42 PCOS patients. Patients were randomly allocated into two groups [Group I (n = 22): drospirenone-ethinyl estradiol (DEE); Group II (n = 20): drospirenone-ethinyl estradiol + metformin (M)] according to Body Mass Index (BMI) findings. Patients were evaluated in terms of leptin-ghrelin, ultrasound, and body fat distribution before and 6 months after therapy. Main outcome measures were to investigate the effects of drospirenone-ethinyl estradiol and drospirenone-ethinyl estradiol + metformin on ovarian ultrasonographic markers, BFM index, leptin, and ghrelin. In patients with higher BMI, ovarian volume, numbers of follicles, stromal area, and echogenicity have been reported to be larger. In group II, a negative correlation between ghrelin and abdominal fat mass after treatment has been noted, whereas in group I a positive correlation between leptin and abdominal fat mass after treatment has been observed. Addition of metformin could have beneficial effects on abdominal fat mass. Stromal area measurement and assessment of fat mass with Dual X-ray Absorptiometry could be helpful as a quantitative way of measurement.

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

USDA-ARS?s Scientific Manuscript database

Previous reports suggest increased circulating concentrations of estradiol prior to GnRH induced ovulation improved conception rates and pregnancy maintenance in beef cattle, and cultured granulosa cells from animals with high antral follicle numbers produced more estradiol and had increased express...

The effects of preovulatory estradiol on the uterine environment and conceptus survival from fertilization to maternal recognition of pregnancy

USDA-ARS?s Scientific Manuscript database

Preovulatory estradiol is known to impact embryo quality and survival. The objective of this study is to determine the effects of preovulatory estradiol on the uterine environment and conceptus survival through maternal recognition of pregnancy. Beef cows/heifers were synchronized and artificially...

A cyclized peptide derived from alpha fetoprotein inhibits the proliferation of ER-positive canine mammary cancer cells.

PubMed

Torres, Cristian Gabriel; Pino, Ana María; Sierralta, Walter Daniel

2009-06-01

The effects of estradiol (E2) and of an AFP-derived cyclized peptide (cP) on the proliferation of primary cultures of cancer cells isolated from spontaneous canine mammary tumors were studied. The cellular response to E2 and cP was related to the expression of estradiol receptor (isoforms alpha and beta). In ER-positive cells, 2 nM estradiol increased cell proliferation and the phosphorylation of ERK1/2; 2 microg/ml cP inhibited all these effects. Estradiol also increased HER2 immunoreactivity in ER-positive cells, an effect that was reverted to its basal values by cP. Estradiol stimulated in these cells the release of MMP2 and MMP9 and the shedding of HB-EGF, effects that the cP did not affect. ER-negative cells were refractory to estradiol or cP. All canine mammary tumor cells in culture responded to treatments analogously to human mammary cancer cells. Our results support the proposal of cP as a new, potentially effective therapeutic agent for the management of mammary cancer.

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.

"MARK I" MEASUREMENT METHODOLOGY FOR POLLUTION PREVENTION PROGRESS OCCURRING AS A RESULT OF PRODUCT DECISIONS

EPA Science Inventory

A methodology for assessing progress in pollution prevention resulting from product redesign, reformulation or replacement is described. The method compares the pollution generated by the original product with that from the modified or replacement product, taking into account, if...

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.

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.

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.

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.

The effect of chronic estrogen application on bile and gallstone composition in women with cholelithiasis.

PubMed

Sieron, Dominik; Czerny, Boguslaw; Sieron-Stoltny, Karolina; Karasiewicz, Monika; Bogacz, Anna; Seremak-Mrozikiewicz, Agnieszka; Kotrych, Daniel; Boron, Dariusz; Mrozikiewicz, Przemyslaw

2016-03-01

Chronic application of third generation progestagens as contraceptives or hormone replacement therapy (HRT) could influence the serum lipid profile, and consequently the bile and gallstone composition. The aim of this study was to determine components of serum, bile and gallstones in women of reproductive age or postmenopausal women using hormonal third generation for at least two years. We enrolled 101 Caucasian women with cholelithiasis. The study included 45 women of reproductive age and 56 postmenopausal women who were divided into subgroups receiving or not exogenous female hormones. In patients we determined serum levels of 17β-estradiol, triglycerides, HDL and LDL cholesterol as well as composition of gallstones and bile. The postmenopausal women showed a significant reduction in the concentration of bile acids in serum while the application of HRT caused an increase in their contents. Serum total and LDL cholesterol in postmenopausal women was higher than in women without hormonal contraception and postmenopausal patients with HRT. Moreover, women taking the exogenous hormones showed a reduced content of calcium ions in both serum, bile and gallstones. Our observations confirm that the chronic use of oral contraceptives and hormone replacement therapy cause an increase in bile lithogenity.

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

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.

Rcan2 and estradiol independently regulate body weight in female mice

PubMed Central

Ding, Ling-Cui; Gong, Qian-Qian; Li, Shi-Wei; Fu, Xiao-Long; Jin, Ye-Cheng; Zhang, Jian; Gao, Jian-Gang; Sun, Xiao-Yang

2017-01-01

Rcan2 increases food intake and plays an important role in the development of age- and diet- induced obesity in male mice. However, in females, wild-type mice grow almost at a similar rate as Rcan2−/− mice on normal chow diet from 6 weeks of age. Here we showed that the ability of Rcan2 to promote weight gain was attenuated by energy expenditure mediated by 17β-estradiol in female mice. Using ovariectomy-operated models, we found that 17β-estradiol deprivation did not alter food intake, but induced more weight gain in wild-type mice than Rcan2−/− mice. If wild-type mice ingested equally as Rcan2−/− mice, in the same ovarian state they exhibited similar weight changes, but the mice in ovariectomized groups were significantly heavier than the ovarian-intact mice, suggesting that body weight is not only regulated by Rcan2, but also by 17β-estradiol. Furthermore, we demonstrated that Rcan2 and 17β-estradiol independently regulated body weight even on high-fat diets. Therefore, our findings indicate that Rcan2 and 17β-estradiol regulate body weight through different mechanisms. Rcan2 increases food intake, whereas 17β-estradiol promotes energy expenditure. These findings provide novel insights into the sexual dimorphism of body weight regulation. PMID:28624805

Sex, estradiol, and spatial memory in a food-caching corvid.

PubMed

Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit; Schlinger, Barney A

2015-09-01

Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. Copyright © 2015 Elsevier Inc. All rights reserved.

SEX, ESTRADIOL, AND SPATIAL MEMORY IN A FOOD-CACHING CORVID

PubMed Central

Rensel, Michelle A.; Ellis, Jesse M.S.; Harvey, Brigit; Schlinger, Barney A.

2015-01-01

Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. PMID:26232613

A synthetic peptide derived from alpha-fetoprotein inhibits the estradiol-induced proliferation of mammary tumor cells in culture through the modulation of p21.

PubMed

Sierralta, Walter D; Epuñan, María J; Reyes, José M; Valladares, Luis E; Pino, Ana M

2008-01-01

A stable cyclized 9-mer peptide (cP) containing the active site of alpha-alpha fetoprotein (alphaFP) has been shown to be effective for prevention of estrogen-stimulated tumor cell proliferation in culture or of xenographt growth in immunodeficient mice. cP does not block 17beta-estradiol (E2) binding to its receptors, but rather appears to interfere with intracellular processing of the signal that supports growth. To obtain insight on that mechanism we studied the effect of cP on the proliferation of MCF-7 cells in culture. Proliferation in the presence of 2 microM E2 is decreased up to 40% upon addition of 2 microg ml(-1) cP to the medium; the presence of cP did not increase cell death, cP reduced also the proliferation of estrogen-dependent ZR75-1 cells but had no effect on autonomous MDA-MB-231 cells, cP did not modify the number of binding sites for labeled E2 or affected cell death. We detected increased nuclear p21Cip1 immunoreactivity after cP treatment. Our results suggest that cP acts via p21Cip1 to slow the process of MCF-7 cells through the cycle.

Cellular organization of pre-mRNA splicing factors in several tissues. Changes in the uterus by hormone action.

PubMed

George-Téllez, R; Segura-Valdez, M L; González-Santos, L; Jiménez-García, L F

2002-05-01

In the mammalian cell nucleus, splicing factors are distributed in nuclear domains known as speckles or splicing factor compartments (SFCs). In cultured cells, these domains are dynamic and reflect transcriptional and splicing activities. We used immunofluorescence and confocal microscopy to monitor whether splicing factors in differentiated cells display similar features. Speckled patterns are observed in rat hepatocytes, beta-cells, bronchial and intestine epithelia and also in three cell types of the uterus. Moreover, the number, distribution and sizes of the speckles vary among them. In addition, we studied variations in the circular form (shape) of speckles in uterine cells that are transcriptionally modified by a hormone action. During proestrus of the estral cycle, speckles are irregular in shape while in diestrus I they are circular. Experimentally, in castrated rats luminal epithelial cells show a pattern where speckles are dramatically rounded, but they recover their irregular shape rapidly after an injection of estradiol. The same results were observed in muscle and gland epithelial cells of the uterus. We concluded that different speckled patterns are present in various cells types in differentiated tissues and that these patterns change in the uterus depending upon the presence or absence of hormones such as estradiol.

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

PubMed

London, Andrew; Jensen, Jeffrey T

2016-07-01

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Association of circulating concentrations of estradiol during the preovulatory period and expression of steroidogenic enzymes in beef cows

USDA-ARS?s Scientific Manuscript database

Cows with greater circulating concentrations of estradiol during the preovulatory period (HighE2) have increased pregnancy success following a fixed-time AI protocol. Furthermore, these animals have an enhanced ability to produce estradiol as indicated by increased expression of CYP19A1 and LHR wit...

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...

76 FR 40451 - Agency Information Collection (Application for Ordinary Life Insurance) Activity Under OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... (Application for Ordinary Life Insurance) Activity Under OMB Review AGENCY: Veterans Benefits Administration... for Ordinary Life Insurance, Replacement Insurance for Modified Life Reduced at Age 65, National Service Life Insurance, VA Form 29-8485. b. Application for Ordinary Life Insurance, Replacement Insurance...

77 FR 34281 - Airworthiness Directives; Schweizer Aircraft Corporation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

... brackets, inspecting the mounting brackets for wear greater than 0.002-inch deep, and replacing the mounting bracket if the bracket wear exceeds 0.002-inch deep. [cir] Modifying the aft fuselage assembly by... areas, and replacing the spar if the wear exceeds 0.002-inch deep. [cir] Inspecting for rivet...

Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β

PubMed Central

Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

2017-01-01

Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ. PMID:28404976

Estrogen enhances mismatch repair by induction of MLH1 expression via estrogen receptor-β.

PubMed

Lu, Jun-Yu; Jin, Peng; Gao, Wei; Wang, De-Zhi; Sheng, Jian-Qiu

2017-06-13

Epidemiological data demonstrated that hormone replace treatment has protective effect against colorectal cancer (CRC). Our previous studies showed that this effect may be associated with DNA mismatch repair. This study aims to investigate the mechanism of estrogen induction of MLH1, and whether colorectal tumor proliferation can be inhibited through induction of MLH1 by estrogen signal pathway. Human CRC cell lines were used to examine the regulation of MLH1 expression by over-expression and depletion of estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), under the treatment with 17β-estradiol or β-Estradiol 6-(O-carboxy-methyl)oxime:BSA, followed by a real-time Q-PCR and Western blotting analysis. Luciferase reporter and chromatin immunoprecipitation assays were used to identify the estrogen response elements in the proximal promoter of MLH1 gene. Then, the influence of estrogen-induced MLH1 on CRC tumor growth were determined in vitro and in vivo. We found that mismatch repair ability and microsatellite stability of cells were enhanced by estrogen via induction of MLH1 expression, which was mediated by ERβ, through a transcriptional activation process. Furthermore, we identified that ERβ exerted an inhibitory effect on CRC tumor proliferation in vitro and in vivo, combined with 5-FU, through up-regulation of MLH1 expression. Finally, we concluded that estrogen enhances mismatch repair ability and tumor inhibition effect in vitro and in vivo, via induction of MLH1 expression mediated by ERβ.

Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer's Disease.

PubMed

Kwakowsky, Andrea; Milne, Michael R; Waldvogel, Henry J; Faull, Richard L

2016-12-17

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer's disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer's disease.

Effect of Estradiol on Neurotrophin Receptors in Basal Forebrain Cholinergic Neurons: Relevance for Alzheimer’s Disease

PubMed Central

Kwakowsky, Andrea; Milne, Michael R.; Waldvogel, Henry J.; Faull, Richard L.

2016-01-01

The basal forebrain is home to the largest population of cholinergic neurons in the brain. These neurons are involved in a number of cognitive functions including attention, learning and memory. Basal forebrain cholinergic neurons (BFCNs) are particularly vulnerable in a number of neurological diseases with the most notable being Alzheimer’s disease, with evidence for a link between decreasing cholinergic markers and the degree of cognitive impairment. The neurotrophin growth factor system is present on these BFCNs and has been shown to promote survival and differentiation on these neurons. Clinical and animal model studies have demonstrated the neuroprotective effects of 17β-estradiol (E2) on neurodegeneration in BFCNs. It is believed that E2 interacts with neurotrophin signaling on cholinergic neurons to mediate these beneficial effects. Evidence presented in our recent study confirms that altering the levels of circulating E2 levels via ovariectomy and E2 replacement significantly affects the expression of the neurotrophin receptors on BFCN. However, we also showed that E2 differentially regulates neurotrophin receptor expression on BFCNs with effects depending on neurotrophin receptor type and neuroanatomical location. In this review, we aim to survey the current literature to understand the influence of E2 on the neurotrophin system, and the receptors and signaling pathways it mediates on BFCN. In addition, we summarize the physiological and pathophysiological significance of E2 actions on the neurotrophin system in BFCN, especially focusing on changes related to Alzheimer’s disease. PMID:27999310

Glabridin and glycyrrhizic acid show no beneficial effect on the chemical composition and mechanical properties of bones in ovariectomized rats, when administered in moderate dose.

PubMed

Kaczmarczyk-Sedlak, Ilona; Klasik-Ciszewska, Sylwia; Wojnar, Weronika

2016-10-01

One of the major causes of osteoporosis and bone fracture in postmenopausal women is estrogen deficiency. To prevent the fractures, and avoid the side effects of hormone replacement therapy, phytoestrogens including the isoflavonoids are used. In the presented study two constituents occurring in the licorice root-the isoflavane glabridin and triterpenoid saponin glycyrrhizic acid were examined on the skeletal system of ovariectomized rats. The female Wistar rats were divided into five groups: control group, ovariectomized group as well as three ovariectomized groups treated with estradiol (0.2mg/kg), glabridin (5mg/kg) or glycyrrhizic acid (15mg/kg). All substances were administered orally for 4 weeks. The estradiol served as a positive control. The mechanical properties of femoral diaphysis, tibial metaphysis and femoral neck were assessed using bending and compression tests. Moreover the chemical composition of the femur, tibia and L-4 vertebra - content of water, organic substances and minerals - was determined. Ovariectomy induced unfavorable changes in the skeletal system of the rats. Administration of glabridin and glycyrrhizic acid to the ovariectomized rats did not improve analyzed parameters of the bones. Obtained results indicate, that the tested substances revealed no beneficial effect on the mechanical properties and chemical composition of the tested bones, thus they cannot be used as the osteoporosis protective agents. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. 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.

17β-Estradiol enhances sulforaphane cardioprotection against oxidative stress.

PubMed

Angeloni, Cristina; Teti, Gabriella; Barbalace, Maria Cristina; Malaguti, Marco; Falconi, Mirella; Hrelia, Silvana

2017-04-01

The lower incidence of ischemic heart disease in female with respect to male gender suggests the possibility that female sex hormones could have specific effects in cardiovascular protection. 17β-Estradiol is the predominant premenopausal circulating form of estrogen and has a protective role on the cardiovascular system. Recent evidences suggest that gender can influence the response to cardiovascular medications; therefore, we hypothesized that sex hormones could also modulate the cardioprotective effects of nutraceutical compounds, such as the isothiocyanate sulforaphane, present in Brassica vegetables. This study was designed to explore the protective effects of sulforaphane in the presence of 17β-estradiol against H 2 O 2 -induced oxidative stress in primary cultures of rat cardiomyocytes. Interestingly, 17β-estradiol enhanced sulforaphane protective activity against H 2 O 2 -induced cell death with respect to sulforaphane or 17β-estradiol alone as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane ability to counteract oxidative stress, reducing intracellular reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels and increasing the expression of phase II enzymes. Using specific antagonists of estrogen receptor α and β, we observed that these effects are not mediated by estrogen receptors. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the presence of specific inhibitors of these kinases reduced the protective effect of sulforaphane in the presence of 17β-estradiol. Sulforaphane and 17β-estradiol co-treatment counteracted cell morphology alterations induced by H 2 O 2 as evidenced by transmission electron microscopy. Our results demonstrated, for the first time, that estrogens could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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

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.

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

17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

PubMed

Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

2016-12-01

The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive improvement. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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.

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.

Determination of estradiol valerate in pharmaceutical preparations and human serum by flow injection chemiluminescence.

PubMed

Liu, Wenwen; Xie, Liangxiao; Liu, Hongshuang; Xu, Shichao; Hu, Bingcheng; Cao, Wei

2013-01-01

A novel method for the detection of trace estradiol valerate (EV) in pharmaceutical preparations and human serum was developed by inhibition of luminol chemiluminescence (CL) by estradiol valerate on the zinc deuteroporphyrin (ZnDP)-enhanced luminol-K3 Fe(CN)6 chemiluminescence system. Under optimized experimental conditions, CL intensity and concentration of estradiol valerate had a good linear relationship in the ranges of 8.0 × 10(-8) to 1.0 × 10(-5) g/mL. Detection limit (3σ) was estimated to be 3.5 × 10(-8) g/mL. The proposed method was applied successfully for the determination of estradiol valerate in pharmaceutical preparations and human serum and recoveries were 97.0-105.0% and 95.5-106.0%, respectively. The possible mechanism of the CL system is discussed. Copyright © 2012 John Wiley & Sons, Ltd.

Estradiol and cognitive function: Past, present and future

PubMed Central

Luine, Victoria N.

2014-01-01

A historical perspective on estradiol’s enhancement of cognitive function is presented, and research, primarily in animals, but also in humans, is reviewed. Data regarding the mechanisms underlying the enhancements are discussed. Newer studies showing rapid effects of estradiol on consolidation of memory through membrane interactions and activation of inter-cellular signaling pathways are reviewed as well as studies focused on traditional genomic mechanisms. Recent demonstrations of intra-neuronal estradiol synthesis and possible actions as a neurosteroid to promote memory are discussed. This information is applied to the critical issue of the current lack of effective hormonal (or other) treatments for cognitive decline associated with menopause and aging. Finally, the critical period hypothesis for estradiol effects is discussed along with novel strategies for hormone/drug development. Overall, the historical record documents that estradiol positively impacts some aspects of cognitive function, but effective therapeutic interventions using this hormone have yet to be realized. PMID:25205317

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.

Effects of continuous vs. cycling estrogen replacement on the acquisition, retention and expression of place- and response-learning in the open-field tower maze.

PubMed

Lipatova, Olga; Byrd, Dennis; Green, John T; Toufexis, Donna J

2014-10-01

Estrogen has been shown to either enhance or impair learning and memory in female rats. The use of different experimental paradigms or estrogen treatment regimens may contribute to these disparate findings. In order to assess the effect of different estradiol (E2) treatments on several aspects of cognition, we trained ovariectomized female rats with either continuous, cycling, or vehicle E2 replacement, in an open-field tower maze task (OFTM) designed to test reference memory in a low-stress environment. In addition, in order to compare two distinct learning and memory systems, rats were trained to use either a dorsolateral striatum-based response type learning or a hippocampal-based place type learning to solve the maze. Results showed that cyclic, but not continuous, E2 replacement facilitated the acquisition of spatial memory in place-learners. Neither E2 regimen affected acquisition in response-learners. Additionally, when all experimental groups were performing at asymptote, rats were evaluated for performance stability by changing the location of their start position in the OFTM. Both regimens of E2 disrupted the expression of spatial memory in place-learners following the novel start position. However, E2 replacement protected ovariectomized female rats from the disruption of memory expression following a start position change in response-learners. Additionally all experimental groups performed equally well when tested following a 21-day period during which rats were absent from the maze. These results suggest that E2 fluctuation is particularly important in the acquisition of hippocampal-mediated spatial learning, and that hippocampal-based memory may be subject to disruption following environmental change, while striatum-based memory is subject to protection. Copyright © 2014 Elsevier Inc. All rights reserved.

Reversal learning in gonadectomized marmosets with and without hormone replacement: are males more sensitive to punishment?

PubMed

LaClair, Matthew; Lacreuse, Agnès

2016-05-01

This study examined sex differences in executive function in middle-aged gonadectomized marmosets (Callithrix jacchus) with or without hormonal replacement. We tested ten castrated male (mean age 5.5 years) marmosets treated with testosterone cypionate (T, n = 5) or vehicle (n = 5) on Reversal Learning, which contributes to cognitive flexibility, and the Delayed Response task, measuring working memory. Their performance was compared to that of 11 ovariectomized females (mean age = 3.7 years) treated with Silastic capsules filled with 17-β estradiol (E2, n = 6) or empty capsules (n = 5), previously tested on the same tasks (Lacreuse et al. in J Neuroendocrinol 26:296-309, 2014. doi: 10.1111/jne.12147). Behavioral observations were conducted daily. Females exhibited more locomotor behaviors than males. Males and females did not differ in the number of trials taken to reach criterion on the reversals, but males had significantly longer response latencies, regardless of hormone replacement. They also had a greater number of refusals than females. Additionally, both control and T-treated males, but not females, had slower responses on incorrect trials, suggesting that males were making errors due to distraction, lack of motivation or uncertainty. Furthermore, although both males and females had slower responding following an incorrect compared to a correct trial, the sex difference in response latencies was disproportionally large following an incorrect trial. No sex difference was found in the Delayed Response task. Overall, slower response latencies in males than females during Reversal Learning, especially during and following an incorrect trial, may reflect greater sensitivity to punishment (omission of reward) and greater performance monitoring in males, compared to females. Because these differences occurred in gonadectomized animals and regardless of hormone replacement, they may be organized early in life.

Estradiol selectively enhances auditory function in avian forebrain neurons

PubMed Central

Caras, Melissa L.; O’Brien, Matthew; Brenowitz, Eliot A.; Rubel, Edwin W

2012-01-01

Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or non-breeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate-level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate-level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner. PMID:23223283

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 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.

Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement.

PubMed

Marques, Danuzia A; de Carvalho, Débora; da Silva, Glauber S F; Szawka, Raphael E; Anselmo-Franci, Janete A; Bícego, Kênia C; Gargaglioni, Luciane H

2015-07-01

The aim of this study was to examine how estrous cycle, ovariectomy, and hormonal replacement affect the respiratory [ventilation (V̇e), tidal volume, and respiratory frequency], metabolic (V̇o2), and thermoregulatory (body temperature) responses to hypercapnia (7% CO2) in female Wistar rats. The parameters were measured in rats during different phases of the estrous cycle, and also in ovariectomized (OVX) rats supplemented with 17β-estradiol (OVX+E2), with a combination of E2 and progesterone (OVX+E2P), or with corn oil (OVX+O, vehicle). All experiments were conducted on day 8 after ovariectomy. The intact animals did not present alterations during normocapnia or under hypercapnia in V̇e, tidal volume, respiratory frequency, V̇o2, and V̇e/V̇o2 in the different phases of the estrous cycle. However, body temperature was higher in female rats on estrus. Hormonal replacement did not change the ventilatory, thermoregulatory, or metabolic parameters during hypercapnia, compared with the OVX animals. Nevertheless, OVX+E2, OVX+E2P, and OVX+O presented lower hypercapnic ventilatory responses compared with intact females on the day of estrus. Also, rats in estrus showed higher V̇e and V̇e/V̇o2 during hypercapnia than OVX animals. The data suggest that other gonadal factors, besides E2 and P, are possibly involved in these responses. Copyright © 2015 the American Physiological Society.

A Modified Jaeger's Method for Measuring Surface Tension.

ERIC Educational Resources Information Center

Ntibi, J. Effiom-Edem

1991-01-01

A static method of measuring the surface tension of a liquid is presented. Jaeger's method is modified by replacing the pressure source with a variable pressure head. By using this method, stationary air bubbles are obtained thus resulting in controllable external parameters. (Author/KR)

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.

Estradiol levels in women predict skin conductance response but not valence and expectancy ratings in conditioned fear extinction.

PubMed

White, Emily C; Graham, Bronwyn M

2016-10-01

Anxiety disorders are more prevalent in women than men. One contributing factor may be the sex hormone estradiol, which is known to impact the long term recall of conditioned fear extinction, a laboratory procedure that forms the basis of exposure therapy for anxiety disorders. To date, the literature examining estradiol and fear extinction in humans has focused primarily on physiological measures of fear, such as skin conductance response (SCR) and fear potentiated startle. This is surprising, given that models of anxiety identify at least three important components: physiological symptoms, cognitive beliefs, and avoidance behavior. To help address this gap, we exposed women with naturally high (n=20) or low estradiol (n=19), women using hormonal contraceptives (n=16), and a male control group (n=18) to a fear extinction task, and measured SCR, US expectancy and CS valence ratings. During extinction recall, low estradiol was associated with greater recovery of SCR, but was not related to US expectancy or CS evaluation. Importantly, women using hormonal contraceptives showed a dissociation between SCR and cognitive beliefs: they exhibited a greater recovery of SCR during extinction recall, yet reported similar US expectancy and CS valence ratings to the other female groups. This divergence underscores the importance of assessing multiple measures of fear when examining the role of estradiol in human fear extinction, especially when considering the potential of estradiol as an enhancement for psychological treatments for anxiety disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

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.

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.

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

Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats

PubMed Central

Selvamani, Amutha; Sohrabji, Farida

2009-01-01

While human observational studies and animal studies report a neuroprotective role for estrogen therapy in stroke, the multicenter placebo-controlled Women's Health Initiative (WHI) study concluded that hormone therapy increased the risk for stroke in postmenopausal women. The present study therefore tested the hypothesis that estrogen replacement would increase the severity of a stroke-like injury in females when this replacement occurs after a prolonged hypoestrogenic period, such as the menopause or reproductive senescence, but not when given to females that were normally cycling immediately prior to the hormone replacement. Two groups of female rats were used: multiparous females with normal but lengthened estrus cycles (mature adults), and older multiparous females currently in a persistent acyclic state (reproductive senescent). Animals were either used intact, or were bilaterally ovariectomized and immediately replaced with a 17β-estradiol pellet or control pellet. Animals were subject to a forelimb placing test (a test for sensorimotor deficit) and thereafter to middle cerebral artery occlusion (MCAo) by stereotaxic injection of the vasoconstrictive peptide endothelin-1, adjacent to the MCA. One week after stroke, behavioral tests were performed again. Cortical and striatal infarct volume, measured from brain slices, was significantly greater in intact reproductive senescent females as compared to intact mature adults. Furthermore, estrogen treatment to ovariectomized mature adult females significantly reduced the cortical infarct volume. Paradoxically, estrogen treatment to ovariectomized reproductive senescent females significantly increased cortical and striatal infarct volumes as compared to control pellet replaced senescent females. Significant post-stroke behavioral deficit was observed in all groups on the side contralateral to the lesion, while senescent females also exhibited deficits on the ipsilateral side, in the cross-midline forelimb placement test. Using an animal model that approximates the natural ovarian aging process, these findings strongly support the hypothesis that the effectiveness of estrogen therapy in protecting brain health may depend critically on the time of initiation with respect to a female's reproductive status. PMID:18829137

A critical period of progesterone withdrawal precedes menstruation in macaques

PubMed Central

Slayden, Ov D; Brenner, Robert M

2006-01-01

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

Combined modified en bloc corpectomy with replacement of the aorta in curative interdisciplinary treatment of a large osteosarcoma infiltrating the aorta.

PubMed

Pilger, Amrei; Tsilimparis, Nikolaos; Bockhorn, Maximilian; Trepel, Martin; Dreimann, Marc

2016-05-01

We report a case of a large three-level spinal osteosarcoma infiltrating the adjacent aorta. This is the first case in which a combined modified three-level en bloc corpectomy with resection and replacement of the adjacent aorta was successful as a part of interdisciplinary curative treatment. Case report. The surgical procedure was performed as a two-step treatment. A heart lung machine (HLM) was not used, in order to avoid cerebral and spinal ischemia and to decrease the risk of hematogenous tumor metastases. Instead, a bypass from the left subclavian artery the distal descending aorta was used. We modified the en bloc corpectomy procedure, leaving a dorsal segment of the vertebral bodies to enable rapid surgery. The procedure was successful and the en bloc resection of the vertebral body with aortal resection could be achieved. Except for pallhypesthesia in the left dermatomes Th7-Th10, the patient does not have any postoperative neurologic deficits. Combined corpectomy with aortic replacement should be considered as a reasonable option in the curative treatment of osteosarcoma with consideration of the immense surgical risks. The use of an HLM is not necessary, especially considering the inherent risk of hematogenous tumor metastases. Modified corpectomy leaving a dorsal vertebral body segment was considered a reasonable variation since tumor-free margins could still be expected.

The Geochemical Behavior and Transport Characteristics of Xenoestrogens

NASA Astrophysics Data System (ADS)

Wallace, T. C.; Bennett, P. C.

2003-12-01

Xenoestrogens are estrogenic active synthetic chemicals that mimic the actions of female sex hormones. Xenoestrogens can be produced synthetically and naturally, and exposure can occur from a variety of sources- food additives, plastics, pesticides, or pharmaceuticals. These environmental chemicals are also known as endocrine disruptors because exposure to low doses (ng/L) have been linked to adverse effects in the reproductive and developmental stages in aquatic species (i.e. reproductive anomalies, feminization, infertility, alterations in growth during life cycles, and changes in community structures). Determining the exposure risks of these toxicological compounds, however, requires a better understanding of the geochemical behavior and transport of synthetic estrogens it is discharged to. Estrogen and its metabolites are also useful tracers because of their specific medical usage (sources from birth control pills, estrogen replacement therapy, and livestock farming), slow degradation before excretion, and unique physiochemical properties (low volatility, hydrophobicity, and high Kow). Estradiol concentrations analyzed by an enzyme-linked immunoassay (ELISA) show that <2-55 ng/L are discharged to Walnut Creek, a stream that also connects to the Colorado River(TX). The bioavailability of these compounds is affected by sorption processes, where xenoestrogens become associated with solid phases. A series of batch sorption experiments using sediment collected from Walnut Creek downstream of an Austin waste water treatment plant and synthetic estrogen standards (Simga@ Estrone, 17B-Estradiol, and Estriol), examined the distribution of estrogen between solid and aqueous phases. Analysis of the concentrations sorbed to sediment result in Freundlich sorption isotherms using HPLC/UV techniques (High Performance Liquid Chromatography with UV detectors- 220 and 280nm). Sorption occurs rapidly with 98% of 17B-Estradiol sorbed within 30 minutes (Estriol=80%, Estrone=95%), which is compared to photolysis degradation rates under UV and a broader spectrum sun lamp. Ultraviolet/Visible (UV/VIS) spectroscopy of the estrogen standards with dilute fulvic acid may indicate complexing with organic material. The hydrophobic nature of estrogen molecules due to a phenolic group seem to play a large role in the sorption rate. This sorption may alter direct photolysis decay rates, thereby acting as both a `sunscreen' and a carrier by increasing the exposure distance and bioavailability of xenoestrogens in the aquatic environment.

Ovariectomy induces a shift in fuel availability and metabolism in the hippocampus of the female transgenic model of familial Alzheimer's.

PubMed

Ding, Fan; Yao, Jia; Zhao, Liqin; Mao, Zisu; Chen, Shuhua; Brinton, Roberta Diaz

2013-01-01

Previously, we demonstrated that reproductive senescence in female triple transgenic Alzheimer's (3×TgAD) mice was paralleled by a shift towards a ketogenic profile with a concomitant decline in mitochondrial activity in brain, suggesting a potential association between ovarian hormone loss and alteration in the bioenergetic profile of the brain. In the present study, we investigated the impact of ovariectomy and 17β-estradiol replacement on brain energy substrate availability and metabolism in a mouse model of familial Alzheimer's (3×TgAD). Results of these analyses indicated that ovarian hormones deprivation by ovariectomy (OVX) induced a significant decrease in brain glucose uptake indicated by decline in 2-[(18)F]fluoro-2-deoxy-D-glucose uptake measured by microPET-imaging. Mechanistically, OVX induced a significant decline in blood-brain-barrier specific glucose transporter expression, hexokinase expression and activity. The decline in glucose availability was accompanied by a significant rise in glial LDH5 expression and LDH5/LDH1 ratio indicative of lactate generation and utilization. In parallel, a significant rise in ketone body concentration in serum occurred which was coupled to an increase in neuronal MCT2 expression and 3-oxoacid-CoA transferase (SCOT) required for conversion of ketone bodies to acetyl-CoA. In addition, OVX-induced decline in glucose metabolism was paralleled by a significant increase in Aβ oligomer levels. 17β-estradiol preserved brain glucose-driven metabolic capacity and partially prevented the OVX-induced shift in bioenergetic substrate as evidenced by glucose uptake, glucose transporter expression and gene expression associated with aerobic glycolysis. 17β-estradiol also partially prevented the OVX-induced increase in Aβ oligomer levels. Collectively, these data indicate that ovarian hormone loss in a preclinical model of Alzheimer's was paralleled by a shift towards the metabolic pathway required for metabolism of alternative fuels in brain with a concomitant decline in brain glucose transport and metabolism. These findings also indicate that estrogen plays a critical role in sustaining brain bioenergetic capacity through preservation of glucose metabolism.

40 CFR 1042.605 - Dressing engines already certified to other standards for nonroad or heavy-duty highway engines...

Code of Federal Regulations, 2012 CFR

2012-07-01

... and all related components. (ii) Replacing an original turbocharger, except that small-volume engine manufacturers may replace an original turbocharger on a recreational engine with one that matches the performance of the original turbocharger. (iii) Modify or design the marine engine cooling or aftercooling...

40 CFR 1042.605 - Dressing engines already certified to other standards for nonroad or heavy-duty highway engines...

Code of Federal Regulations, 2011 CFR

2011-07-01

... and all related components. (ii) Replacing an original turbocharger, except that small-volume engine manufacturers may replace an original turbocharger on a recreational engine with one that matches the performance of the original turbocharger. (iii) Modify or design the marine engine cooling or aftercooling...

40 CFR 1042.605 - Dressing engines already certified to other standards for nonroad or heavy-duty highway engines...

Code of Federal Regulations, 2013 CFR

2013-07-01

... and all related components. (ii) Replacing an original turbocharger, except that small-volume engine manufacturers may replace an original turbocharger on a recreational engine with one that matches the performance of the original turbocharger. (iii) Modify or design the marine engine cooling or aftercooling...

40 CFR 1042.605 - Dressing engines already certified to other standards for nonroad or heavy-duty highway engines...

Code of Federal Regulations, 2014 CFR

2014-07-01

... and all related components. (ii) Replacing an original turbocharger, except that small-volume engine manufacturers may replace an original turbocharger on a recreational engine with one that matches the performance of the original turbocharger. (iii) Modify or design the marine engine cooling or aftercooling...

Carbohydrate modified phenol-formaldehyde resins

Treesearch

Anthony H. Conner; Linda F. Lorenz

1986-01-01

For adhesive self-sufficiency, the wood industry needs new adhesive systems in which all or part of the petroleum-derived phenolic component is replaced by a renewable material without sacrificing high durability or ease of bonding. We tested the bonding of wood veneers, using phenolic resins in which part of the phenol-formaldehyde was replaced with carbohydrates. Our...

Modified Nance palatal arch appliance for anterior tooth replacement.

PubMed

Sethi, Ntasha; Shanthraj, Srinivas L; Muraleedharan, Manju; Mallikarjuna, Rachappa

2013-06-07

The following case report presents a new and an innovative technique for the postextraction replacement of maxillary central incisors using the natural teeth as pontics. The novel appliance fabricated fully satisfied the demands of the adolescent patient for a fixed prosthetic, while fulfilling the aesthetic and functional requirements presented by the case.

Modified Nance palatal arch appliance for anterior tooth replacement

PubMed Central

Sethi, Ntasha; Shanthraj, Srinivas L; Muraleedharan, Manju; Mallikarjuna, Rachappa

2013-01-01

The following case report presents a new and an innovative technique for the postextraction replacement of maxillary central incisors using the natural teeth as pontics. The novel appliance fabricated fully satisfied the demands of the adolescent patient for a fixed prosthetic, while fulfilling the aesthetic and functional requirements presented by the case. PMID:23749860

76 FR 22298 - Airworthiness Directives; Cessna Aircraft Company (Cessna) Model 172 Airplanes Modified by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-21

... AD requires installing a full authority digital engine control (FADEC) backup battery, replacing the... battery every 12 calendar months. This AD was prompted by an incident where an airplane experienced an in... battery, replacing the supplement pilot's operating handbook and FAA approved airplane flight manual, and...

Functional characterization of steam jet-cooked buckwheat flour as a fat replacer in cake-baking

USDA-ARS?s Scientific Manuscript database

Fancy buckwheat flour was thermo-mechanically modified by steam jet-cooking and the resulting product was evaluated as a fat replacer for the use in cakes with reduced-fat content. Steam jet-cooking caused the integrity of buckwheat flour components to be disrupted, significantly changing the physi...

Quality characteristics of low fat ostrich meat patties formulated with either pork lard or modified corn starch, soya isolate and water.

PubMed

Hoffman, L C; Mellett, F D

2003-10-01

A trained taste panel could not distinguish (P>0.05) between ostrich meat patties containing either 10% pork lard or 10% of a modified starch/protein isolate (fat replacer) mixture. The panel could distinguish between the types of ostrich muscle/meat cuts used with a significant (P<0.05) number preferring ostrich patties made from meat containing a higher collagen content (±3% vs <1%). The chemical analysis of the patties showed that within the meat classes (Class fillet-de-membraned, Class A-very lean off-cuts and Class B-off-cuts containing visual connective tissue and some fat), the patties containing the pork fat had a +6% higher total fat content than those containing the fat replacer. The fatty acid profiles of the various products were in accordance with the meat type and fat or fat replacer used. The mineral profile was as expected for lean ostrich meat that had spices added. It is concluded that fat replacers can be used successfully for the production of low fat ostrich patties without any negative quality attributes being perceived.

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.

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.

Interrelations between random walks on diagrams (graphs) with and without cycles.

PubMed

Hill, T L

1988-05-01

Three topics are discussed. A discrete-state, continuous-time random walk with one or more absorption states can be studied by a presumably new method: some mean properties, including the mean time to absorption, can be found from a modified diagram (graph) in which each absorption state is replaced by a one-way cycle back to the starting state. The second problem is a random walk on a diagram (graph) with cycles. The walk terminates on completion of the first cycle. This walk can be replaced by an equivalent walk on a modified diagram with absorption. This absorption diagram can in turn be replaced by another modified diagram with one-way cycles back to the starting state, just as in the first problem. The third problem, important in biophysics, relates to a long-time continuous walk on a diagram with cycles. This diagram can be transformed (in two steps) to a modified, more-detailed, diagram with one-way cycles only. Thus, the one-way cycle fluxes of the original diagram can be found from the state probabilities of the modified diagram. These probabilities can themselves be obtained by simple matrix inversion (the probabilities are determined by linear algebraic steady-state equations). Thus, a simple method is now available to find one-way cycle fluxes exactly (previously Monte Carlo simulation was required to find these fluxes, with attendant fluctuations, for diagrams of any complexity). An incidental benefit of the above procedure is that it provides a simple proof of the one-way cycle flux relation Jn +/- = IIn +/- sigma n/sigma, where n is any cycle of the original diagram.

Biological and mechanical properties of an experimental glass-ionomer cement modified by partial replacement of CaO with MgO or ZnO.

PubMed

Kim, Dong-Ae; Abo-Mosallam, Hany; Lee, Hye-Young; Lee, Jung-Hwan; Kim, Hae-Won; Lee, Hae-Hyoung

2015-01-01

Some weaknesses of conventional glass ionomer cement (GIC) as dental materials, for instance the lack of bioactive potential and poor mechanical properties, remain unsolved.Objective The purpose of this study was to investigate the effects of the partial replacement of CaO with MgO or ZnO on the mechanical and biological properties of the experimental glass ionomer cements.Material and Methods Calcium fluoro-alumino-silicate glass was prepared for an experimental glass ionomer cement by melt quenching technique. The glass composition was modified by partial replacement (10 mol%) of CaO with MgO or ZnO. Net setting time, compressive and flexural properties, and in vitrorat dental pulp stem cells (rDPSCs) viability were examined for the prepared GICs and compared to a commercial GIC.Results The experimental GICs set more slowly than the commercial product, but their extended setting times are still within the maximum limit (8 min) specified in ISO 9917-1. Compressive strength of the experimental GIC was not increased by the partial substitution of CaO with either MgO or ZnO, but was comparable to the commercial control. For flexural properties, although there was no significance between the base and the modified glass, all prepared GICs marked a statistically higher flexural strength (p<0.05) and comparable modulus to control. The modified cements showed increased cell viability for rDPSCs.Conclusions The experimental GICs modified with MgO or ZnO can be considered bioactive dental materials.

17 beta-estradiol modifies nitric oxide-sensitive guanylyl cyclase expression and down-regulates its activity in rat anterior pituitary gland.

PubMed

Cabilla, Jimena P; Díaz, María del Carmen; Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Lasaga, Mercedes; Duvilanski, Beatriz H

2006-09-01

Previous studies showed that 17 beta-estradiol (17 beta-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17 beta-E2 disrupts the inhibitory effect of NO on prolactin release, decreasing sGC activity and affecting the cGMP pathway in anterior pituitary gland of adult ovariectomized and estrogenized rats. To ascertain the mechanisms by which 17 beta-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17 beta-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17 beta-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing alpha1 and decreasing beta1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6-9 h after 17 beta-E2 administration. 17beta-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17 beta-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17 beta-E2, because they were not observed with the administration of other steroids such as progesterone and 17 alpha-estradiol. This inhibitory action of 17beta-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17 beta-E2 action. 17 beta-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17 beta-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC beta 1 subunit and sGC activity in a specific, ER-dependent manner.

Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice.

PubMed

Iqbal, Ramsha; Jain, Gaurav K; Siraj, Fouzia; Vohora, Divya

2018-07-01

Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABA A receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of status epilepticus and can be pursued further. Copyright © 2018 Elsevier B.V. All rights reserved.

Estrogen levels modify scopolamine-induced amnesia in gonadally intact rats.

PubMed

de Macêdo Medeiros, André; Izídio, Geison Souza; Sousa, Diego Silveira; Macedo, Priscila Tavares; Silva, Anatildes Feitosa; Shiramizu, Victor Kenji Medeiros; Cabral, Alicia; Ribeiro, Alessandra Mussi; Silva, Regina Helena

2014-08-04

Previous studies suggested that estrogen plays a role in cognitive function by modulating the cholinergic transmission. However, most of the studies dealing with this subject have been conducted using ovariectomized rats. In the present study we evaluated the effects of physiological and supra-physiological variation of estrogen levels on scopolamine-induced amnesia in gonadally intact female rats. We used the plus-maze discriminative avoidance task (PMDAT) in order to evaluate anxiety levels and motor activity concomitantly to the memory performance. In experiment 1, female Wistar rats in each estrous cycle phase received scopolamine (1 mg/kg) or saline i.p. 20 min before the training session in the PMDAT. In experiment 2, rats in diestrus received estradiol valerate (1 mg/kg) or sesame oil i.m., and scopolamine (1 mg/kg) or saline i.p., 45 min and 20 min before the training, respectively. In experiment 3, rats in diestrus received scopolamine (1 mg/kg) or saline i.p. 20 min before the training, and estradiol valerate (1 mg/kg) or sesame oil i.m. immediately after the training session. In all experiments, a test session was performed 24 h later. The main results showed that: (1) scopolamine impaired retrieval and induced anxiolytic and hyperlocomotor effects in all experiments; (2) this cholinergic antagonist impaired acquisition only in animals in diestrus; (3) acute administration of estradiol valerate prevented the learning impairment induced by scopolamine and (4) interfered with memory consolidation process. The results suggest that endogenous variations in estrogen levels across the estrous cycle modulate some aspects of memory mediated by the cholinergic system. Indeed, specifically in diestrus, a stage with low estrogen levels, the impairment produced by scopolamine on the acquisition was counteracted by exogenous administration of the hormone, whereas the posttraining treatment potentiated the negative effects of scopolamine during the consolidation phase of memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Urogenital teratogenicity of synthetic and natural estrogens in the rat: diethylstilbestrol and estradiol

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

Henry, E.C.

1984-01-01

Diethylstilbestrol (DES), a synthetic estrogen and a carcinogen, is a potent urogenital teratogen in humans and rodents. The natural estrogen, estradiol (E/sub 2/), induces malformations in rats only at a maternal toxic dose. This difference in potency could result from differences in fetal sensitivity, or in the distribution and/or metabolism of the two compounds. The current studies tested the hypothesis that the teratogenicity of DES is mediated by its estrogenic activity (rather than its metabolic activation). The two estrogens were directly compared by injecting them into day 19 fetuses, bypassing any maternal modifying factors. Both DES (0.1, 1 or 10more » ..mu..g/fetus) and E/sub 2/ (10 or 100 ..mu..g/fetus) caused dose-related incidences of urogenital malformations (diagnosed at 6-7 weeks), but DES was 10- to 100-fold more potent. Between 24 h and 9 days after DES or E/sub 2/ exposure, histologic evidence of estrogenic stimulation was observed, including premature myometrial growth and differentiation, and vaginal epithelial thickening. Thus, DES and E/sub 2/ act directly in the fetus, to produce similar teratogenic effects, without maternal mediation. Following both maternal and fetal administration of /sup 14/C-DES or /sup 3/H-E/sub 2/, the /sup 14/C (from DES) was concentrated in fetal tissues, whereas /sup 3/H (from E/sub 2/) was retained in fetal plasma (protein-bound). Fetal genital tract contained the largest proportion of unchanged E/sub 2/ (74%) or DES (86%). It was concluded that (1) the teratogenicity of DES reflects its estrogenic activity in the fetus; (2) the fetus is sensitive to a brief exposure to estrogens, including LY and (3) the synthetic estrogen is more potent that estradiol because of its greater availability to fetal genital tissues: protein binding and rapid metabolism reduce the teratogenicity of the natural estrogen.« less

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.

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.

First trimester β-hCG and estradiol levels in singleton and twin pregnancies after assisted reproduction.

PubMed

Póvoa, Ana; Xavier, Pedro; Matias, Alexandra; Blicksttein, Isaac

2017-07-28

To compare levels of β-hCG and estradiol collected during the first trimester in singleton and twin pregnancies following assisted reproduction technologies (ART). We prospectively evaluated 50 singleton and 47 dichorionic twin pregnancies that eventually ended in live births. Patients were recruited from a single ART center with standard treatment protocols followed by fresh embryo transfers. Hormone measurements were performed within a narrow gestational age range and analyzed in a single laboratory thus minimizing inter- and intra-assay variability. We measured serum β-hCG at 13 days after embryo transfer as well as samples of β-hCG and estradiol at 8-9 weeks+6 days. No significant differences existed between singletons and twins in respect to demographic and cycle characteristics. β-hCG and estradiol were all significantly higher in twins (P<0.05). The data confirms the higher levels of β-hCG and estradiol in twins, pointing to the potential role of these placental hormones in early support of a twin pregnancy.

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.

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.

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.

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

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.

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.

Evidence of a local negative role for cocaine and amphetamine regulated transcript (CART), inhibins and low molecular weight insulin like growth factor binding proteins in regulation of granulosa cell estradiol production during follicular waves in cattle

PubMed Central

Kobayashi, Yasuhiro; Jimenez-Krassel, Fermin; Ireland, James J; Smith, George W

2006-01-01

The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system. PMID:16611367

ESTROGEN LEVELS DO NOT RISE WITH TESTOSTERONE TREATMENT FOR TRANSGENDER MEN.

PubMed

Chan, Kelly J; Jolly, Divya; Liang, Jennifer J; Weinand, Jamie D; Safer, Joshua D

2018-04-01

Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any. Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up. With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up. These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men. Abbreviation: BMI = body mass index.

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.

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

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.

Estradiol Membrane-Initiated Signaling and Female Reproduction.

PubMed

Micevych, Paul E; Wong, Angela May; Mittelman-Smith, Melinda Anne

2015-07-01

The discoveries of rapid, membrane-initiated steroid actions and central nervous system steroidogenesis have changed our understanding of the neuroendocrinology of reproduction. Classical nuclear actions of estradiol and progesterone steroids affecting transcription are essential. However, with the discoveries of membrane-associated steroid receptors, it is becoming clear that estradiol and progesterone have neurotransmitter-like actions activating intracellular events. Ultimately, membrane-initiated actions can influence transcription. Estradiol membrane-initiated signaling (EMS) modulates female sexual receptivity and estrogen feedback regulating the luteinizing hormone (LH) surge. In the arcuate nucleus, EMS activates a lordosis-regulating circuit that extends to the medial preoptic nucleus and subsequently to the ventromedial nucleus (VMH)--the output from the limbic and hypothalamic regions. Here, we discuss how EMS leads to an active inhibition of lordosis behavior. To stimulate ovulation, EMS facilitates astrocyte synthesis of progesterone (neuroP) in the hypothalamus. Regulation of GnRH release driving the LH surge is dependent on estradiol-sensitive kisspeptin (Kiss1) expression in the rostral periventricular nucleus of the third ventricle (RP3V). NeuroP activation of the LH surge depends on Kiss1, but the specifics of signaling have not been well elucidated. RP3V Kiss1 neurons appear to integrate estradiol and progesterone information which feeds back onto GnRH neurons to stimulate the LH surge. In a second population of Kiss1 neurons, estradiol suppresses the surge but maintains tonic LH release, another critical component of the estrous cycle. Together, evidence suggests that regulation of reproduction involves membrane action of steroids, some of which are synthesized in the brain. © 2015 American Physiological Society.

Estradiol Variability, Stressful Life Events and the Emergence of Depressive Symptomatology during the Menopause Transition

PubMed Central

Gordon, Jennifer L.; Rubinow, David R.; Eisenlohr-Moul, Tory A; Leserman, Jane; Girdler, Susan S.

2015-01-01

Objective To examine the role of estradiol fluctuation in triggering depressive symptoms in the menopause transition and assess the role of recent very stressful life events (VSLEs) as a moderating factor in this relationship. Methods 52 euthymic women in the menopause transition or early postmenopause (age 45–60) who were assigned to the placebo arm of a randomized controlled trial of hormone therapy provided the data for this report. At enrollment, women’s experience of recent VSLEs, depressive symptoms, serum estradiol and progesterone were assessed. At months 1, 8 and 14, depressive symptoms and hormones were re-assessed and participants underwent a stressor battery involving a speech and a mental arithmetic task. Participants rated their feelings of anxiety, fear, anger and rejection. The standard deviation of estradiol provided an index of hormone variability over the entire 14 months. Results Greater estradiol variability across the 14 months predicted greater depressive symptoms at month 14, though only in women reporting a higher number of VSLEs at baseline (39% of women reported ≤1 recent event). Greater estradiol variability also predicted greater feelings of rejection to the laboratory stressor at months 8 and 14. Furthermore, among women reporting higher VSLEs at baseline, feelings of rejection in response to the laboratory stressor at month 8 predicted depressive symptoms at month 14. Conclusion These data suggest estradiol variability may enhance emotional sensitivity to psychosocial stress, particularly sensitivity to social rejection. Combined with VSLEs proximate to the menopause transition, this increased sensitivity may contribute to the development of depressed mood. PMID:26529616

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.

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.

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.

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.

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

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

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.

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.

Sexual Function in Women on Estradiol or Venlafaxine for Hot Flushes: A Randomized Controlled Trial

PubMed Central

Reed, Susan D.; Mitchell, Caroline M.; Joffe, Hadine; Cohen, Lee; Shifren, Jan L.; Newton, Katherine M.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; LaCroix, Andrea Z.; Guthrie, Katherine A.

2014-01-01

Objective To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. Methods In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between oral estradiol 0.5 mg/day or venlafaxine 75 mg/day (both compared with placebo). Measures included composite and 6 domain scores from the Female Sexual Function Index (FSFI) and sexually related personal distress. Results Participants were aged 54.6 (standard deviation [SD] 3.8) years, 59% Caucasian, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline FSFI score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean FSFI change from baseline to week-8 was 1.4 (95% Confidence Interval [CI] -0.4, 3.2) for estradiol, 1.1 (95% CI -0.5, 2.7) for venlafaxine and -0.3 (95% CI -1.6, 1.0) for placebo. Composite FSFI and sexually-related distress change from baseline did not differ between estradiol and placebo (p= 0.38, p=0.30) or venlafaxine and placebo (p=0.79, p=0.48). Among sexually active women, FSFI domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0, 0.6) for estradiol; -0.6 (95% CI -1.2, 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2, 1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction. Conclusions Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8-weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although subtle increase in desire (estradiol), and decreases in orgasm and pain (venlafaxine) may exist. PMID:25004335

Osteoblast and osteoclast behaviors in the turnover of attachment bones during medaka tooth replacement.

PubMed

Mantoku, Akiko; Chatani, Masahiro; Aono, Kazushi; Inohaya, Keiji; Kudo, Akira

2016-01-15

Tooth replacement in polyphyodont is a well-organized system for maintenance of homeostasis of teeth, containing the dynamic structural change in skeletal tissues such as the attachment bone, which is the supporting element of teeth. Histological analyses have revealed the character of tooth replacement, however, the cellular mechanism of how skeletal tissues are modified during tooth replacement is largely unknown. Here, we showed the important role of osteoblasts for controlling osteoclasts to modify the attachment bone during tooth replacement in medaka pharyngeal teeth, coupled with an osterix-DsRed/TRAP-GFP transgenic line to visualize osteoblasts and osteoclasts. In the turnover of the row of attachment bones, these bones were resorbed at the posterior side where most developed functional teeth were located, and generated at the anterior side where teeth were newly erupted, which caused continuous tooth replacement. In the cellular analysis, osteoclasts and osteoblasts were located at attachment bones separately, since mature osteoclasts were localized at the resorbing side and osteoblasts gathered at the generating side. To demonstrate the role of osteoclasts in tooth replacement, we established medaka made deficient in c-fms-a by TALEN. c-fms-a deficient medaka showed hyperplasia of attachment bones along with reduced bone resorption accompanied by a low number of TRAP-positive osteoclasts, indicating an important role of osteoclasts in the turnover of attachment bones. Furthermore, nitroreductase-mediated osteoblast-specific ablation induced disappearance of osteoclasts, indicating that osteoblasts were essential for maintenance of osteoclasts for the proper turnover. Taken together, our results suggested that the medaka attachment bone provides the model to understand the cellular mechanism for tooth replacement, and that osteoblasts act in the coordination of bone morphology by supporting osteoclasts. Copyright © 2015 Elsevier Inc. All rights reserved.

75 FR 78177 - Airworthiness Directives; Cessna Aircraft Company (Cessna) Model 172 Airplanes Modified by...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... battery, replacing the supplement pilot's operating handbook and FAA approved airplane flight manual, and replacing the FADEC backup battery every 12 calendar months. This proposed AD was prompted by an incident... allow the FADEC to shut down or reset if the main battery is depleted and the electrical charging system...

Modified artificial bee colony for the vehicle routing problems with time windows.

PubMed

Alzaqebah, Malek; Abdullah, Salwani; Jawarneh, Sana

2016-01-01

The natural behaviour of the honeybee has attracted the attention of researchers in recent years and several algorithms have been developed that mimic swarm behaviour to solve optimisation problems. This paper introduces an artificial bee colony (ABC) algorithm for the vehicle routing problem with time windows (VRPTW). A Modified ABC algorithm is proposed to improve the solution quality of the original ABC. The high exploration ability of the ABC slows-down its convergence speed, which may due to the mechanism used by scout bees in replacing abandoned (unimproved) solutions with new ones. In the Modified ABC a list of abandoned solutions is used by the scout bees to memorise the abandoned solutions, then the scout bees select a solution from the list based on roulette wheel selection and replace by a new solution with random routs selected from the best solution. The performance of the Modified ABC is evaluated on Solomon benchmark datasets and compared with the original ABC. The computational results demonstrate that the Modified ABC outperforms the original ABC also produce good solutions when compared with the best-known results in the literature. Computational investigations show that the proposed algorithm is a good and promising approach for the VRPTW.

Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?

PubMed

Ma, Qiang; Huang, Hui; Sun, Long; Zhou, Tong; Zhu, Jingyuan; Cheng, Xuemin; Duan, Lijv; Li, Zhiyuan; Cui, Liuxin; Ba, Yue

2017-12-01

The occurrence of endemic fluorosis is derived from high fluoride levels in drinking water and industrial fumes or dust. Reproductive disruption is also a major harm caused by fluoride exposure besides dental and skeletal lesions. However, few studies focus on the mechanism of fluoride exposure on male reproductive function, especially the possible interaction of fluoride exposure and gene polymorphism on male reproductive hormones. Therefore, we conducted a cross-sectional study in rural areas of Henan province in China to explore the interaction between the estrogen receptor alpha (ERα) gene and fluoride exposure on reproductive hormone levels in male farmers living in the endemic fluorosis villages. The results showed that fluoride exposure significantly increased the serum level of estradiol in the hypothalamic-pituitary-testicular (HPT) axis in male farmers. Moreover, the observations indicated that fluoride exposure and genetic markers had an interaction on serum concentration of follicle-stimulating hormone and estradiol, and the interaction among different loci of the ERα gene could impact the serum testosterone level. Findings in the present work suggest that chronic fluoride exposure in drinking water could modulate the levels of reproductive hormones in males living in endemic fluorosis areas, and the interaction between fluoride exposure and ERα polymorphisms might affect the serum levels of hormones in the HPT axis in male farmers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ovarian hormones and binge eating: exploring associations in community samples

PubMed Central

Klump, K. L.; Keel, P. K.; Culbert, K. M.; Edler, C.

2010-01-01

Background Significant associations between changes in ovarian hormones and binge eating are present across the menstrual cycle in women with bulimia nervosa. However, no study has examined these relationships in a non-clinical sample, despite the need for these data for designing risk-factor studies. Method In study 1, we modified several continuous measures of binge eating and identified those that were most sensitive to menstrual-cycle fluctuations in a non-clinical sample of 10 women who completed measures for 35 days. In study 2, we explored associations between ovarian hormones and binge-eating scores in nine women who completed these same measures for 65 days and provided daily saliva samples for assays of estradiol and progesterone concentrations. Results In study 1, the Emotional Eating subscale of the Dutch Eating Behavior Questionnaire exhibited superior reliability and was most sensitive to predicted menstrual-cycle changes in binge eating (i.e. increased scores in the mid-luteal/premenstrual compared with follicular/ovulatory phases). In study 2, this scale showed predicted inverse associations with estradiol and positive associations with progesterone across the menstrual cycle that could not be accounted for by changes in negative affect. Conclusion Associations between ovarian hormones and binge eating are robust and present in clinical and non-clinical samples. Findings support the ability to examine the role of ovarian hormones as risk factors for binge eating in large-scale prospective studies and twin studies. PMID:18307829

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.

Gonadal Hormone Modulation of Mu, Kappa, and Delta Opioid Antinociception in Male and Female Rats

PubMed Central

Stoffel, Erin C.; Ulibarri, Catherine M.; Folk, John E.; Rice, Kenner C.

2005-01-01

Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50°C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. In females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat. Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. PMID:15820914

The preclinical biology of a new potent and selective progestin: trimegestone.

PubMed

Winneker, Richard C; Bitran, Daniel; Zhang, Zhiming

2003-11-01

Trimegestone (TMG) is a 19-norpregnane progestin being developed, in combination with an estrogen, for the treatment of postmenopausal symptoms. TMG binds to the human progesterone receptor with an affinity greater than medroxyprogesterone acetate (MPA), norethindrone (NET), and levonorgestrel (LNG). In contrast, TMG binds with low affinity to the androgen, glucocorticoid and mineralocorticoid receptor and has no measurable affinity for the estrogen receptor. Compared to other progestins, TMG demonstrates an improved separation of its PR affinity from its affinity to other classical steroid hormone receptors. In vivo, TMG has potent progestin activity. For example, TMG produces glandular differentiation of the uterine endometrium in rabbits and is about 30 and 60 times more potent than MPA and NET, respectively. In the rat, TMG maintains pregnancy, induces deciduoma formation, inhibits ovulation and has uterine anti-estrogenic activity. With respect to these endpoints, TMG appears to be more potent and selective on uterine epithelial responses than other classical progestin responses. In vivo, TMG does not have significant androgenic, glucocorticoid, anti-glucocorticoid or mineralocorticoid activity but does have anti-mineralocorticoid activity and modest anti-androgenic effects. This overall profile is qualitatively similar to progesterone. When TMG is administered chronically, it antagonizes the effect of estradiol on the uterus but does not antagonize the beneficial bone sparing activity of estradiol. In rat studies evaluating CNS GABAA receptor modulatory activity, TMG is less active on this likely undesirable endpoint than progesterone and norethindrone acetate, which may translate into fewer mood-related side effects. The results indicate that TMG is a potent and selective progestin with a preclinical profile well suited for hormone replacement therapy.

Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent model with high serum testosterone: Protective effect and emergence of unstable epithelial microenvironment.

PubMed

Gonçalves, Bianca F; de Campos, Silvana G P; Góes, Rejane M; Scarano, Wellerson R; Taboga, Sebastião R; Vilamaior, Patricia S L

2017-06-01

Estrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. We adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. Histopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. Estrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time. © 2017 Wiley Periodicals, Inc.

Analysis of Kalirin-7 Knockout Mice Reveals Different Effects in Female Mice

PubMed Central

Mazzone, Christopher M.; Larese, Taylor P.; Kiraly, Drew D.; Eipper, Betty A.

2012-01-01

Estradiol treatment of ovariectomized rodents is known to affect the morphology of dendritic spines and produce behavioral and cognitive effects. Kalirin-7 (Kal7), a postsynaptic density (PSD)-localized Rho-guanine nucleotide exchange factor, is important for dendritic spine formation and stability. Male Kal7 knockout [Kal7(KO)] mice exhibit a number of abnormal behavioral and biochemical phenotypes. Given that chronic 17β-estradiol (E2) replacement of ovariectomized rats enhanced Kal7 expression in the hippocampus and primary hippocampal cultures, we assessed the behavioral and biochemical effects of chronic E2 treatment of ovariectomized female wild-type and Kal7(KO) mice. Both intact and ovariectomized Kal7(KO) female mice exhibited decreased anxiety-like behavior compared with the corresponding wild type in the elevated zero maze and were unaffected by E2 treatment. Chronic E2 decreased locomotor activity in the open field and enhanced performance in a passive-avoidance fear conditioning task, which were both unaffected by genotype. Kal7(KO) female mice engaged in significantly more object exploration, both familiar and novel, than did wild-type females. E2 enhanced the acute locomotor response to cocaine, with no significant effect of genotype. Similar to Kal7(KO) males, Kal7(KO) females had decreased levels of N-methyl-d-aspartate receptor 2B in hippocampal PSD fractions with no effect of E2 treatment. The differing behavioral effects of Kal7 ablation in female and male mice may offer insight into the molecular underpinnings of these differences. PMID:22989522

Simultaneous measurement of total estradiol and testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry.

PubMed

Zhou, Hui; Wang, Yuesong; Gatcombe, Matthew; Farris, Jacob; Botelho, Julianne C; Caudill, Samuel P; Vesper, Hubert W

2017-10-01

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone-related disorders in patient care and translational research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03-48.5 nM (0.75-1400 ng/dL) and estradiol 11.0-5138 pM (2.99-1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and -0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for 2 years with mean bias -0.7% (95% CI -1.6% to 0.2%) for testosterone and 0.1% (95% CI -2.2% to 2.3%) for estradiol. The method precision over a 2-year period for quality control pools at low, medium, and high concentrations was 2.7-2.9% for testosterone and 3.3-5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies.

Simultaneous measurement of total Estradiol and Testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry

PubMed Central

Zhou, Hui; Wang, Yuesong; Gatcombe, Matthew; Farris, Jacob; Botelho, Julianne C.; Caudill, Samuel P.; Vesper, Hubert W.

2017-01-01

Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone related disorders in patient care and translation research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03–48.5 nM (0.75–1400 ng/dL) and estradiol 11.0–5138 pM (2.99–1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and −0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for two years with mean bias −0.7% (95%CI: −1.6% to 0.2%) for testosterone and 0.1% (95%CI: −2.2% to 2.3%) for estradiol. The method precision over a 2-year period for Quality Control pools at low, medium and high concentrations was 2.7–2.9% for testosterone and 3.3–5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies. PMID:28801832

A hormone pulse induces transient changes in the subcellular distribution and leads to a lysosomal accumulation of the estradiol receptor alpha in target tissues.

PubMed

Qualmann, B; Kessels, M M; Thole, H H; Sierralta, W D

2000-06-01

An intrauterine pulse-stimulation with estradiol induced changes in the subcellular localization of estrogen receptor alpha in porcine endometrium, as detected with F(ab') fragments of various anti-receptor antibodies covalently linked to nanogold. The low-sterically hindered immunoreagents--recognizing different epitopes within the hormone binding domain--allowed for an efficient immunolabeling of estradiol receptor alpha, detecting it both in the cytoplasm and the nucleus of nonstimulated epithelium cells. In the cytoplasm, the receptor often seemed to be associated with actin filaments and the endoplasmatic reticulum. After the stimulation with estradiol, a predominantly nuclear localization and a labeling of nucleoli was observed. Our immunoelectron microscopy study demonstrates a localization of the receptor in cytoplasmic organelles that increased after the hormone pulse. These organelles exhibited the morphological properties of lysosomes and relocated to the perinuclear area. In analogous cytoplasmic organelles, the presence of cathepsin D was detected via indirect immunogold labeling, justifying their classification as lysosomes. Quantitative examinations revealed that not only the number of lysosomes in the proximity of the nucleus but also their immunostaining for estradiol receptor alpha increased significantly after the hormone pulse. Thus, estradiol induces both the rapid shift of receptor into the nucleus, a slower perinuclear accumulation of lysosomes and an increase of lysosomal ERalpha-immunoreactivity. These results suggest a role for lysosomes in the degradation of receptor shuttling out of the nucleus. This could serve as termination of the estradiol receptor alpha-dependent activation of target cells. This hypothesis is strengthened by the fact that the receptor content in uterine tissue declined drastically few hours after the hormone pulse.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases.

PubMed

Obradovic, Milan; Bjelogrlic, Predrag; Rizzo, Manfredi; Katsiki, Niki; Haidara, Mohamed; Stewart, Alan J; Jovanovic, Aleksandra; Isenovic, Esma R

2013-09-01

Obesity is associated with aberrant sodium/potassium-ATPase (Na(+)/K(+)-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na(+)/K(+)-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na(+)/K(+)-ATPase levels. The primary female sex steroid estradiol has long been recognized to be important in a wide variety of physiological processes. Numerous studies, including ours, have shown that estradiol is one of the major factors controlling the activity and expression of Na(+)/K(+)-ATPase in the cardiovascular (CV) system. However, the effects of estradiol on Na(+)/K(+)-ATPase in both normal and pathological conditions, such as obesity, remain unclear. Increasing our understanding of the molecular mechanisms by which estradiol mediates its effects on Na(+)/K(+)-ATPase function may help to develop new strategies for the treatment of CV diseases. Herein, we discuss the latest data from animal and clinical studies that have examined how pathophysiological conditions such as obesity and the action of estradiol regulate Na(+)/K(+)-ATPase activity.

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.

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.

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.

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

Xenogeneic Decellularized Scaffold: A Novel Platform for Ovary Regeneration

PubMed Central

Liu, Wen-Yue; Lin, Shi-Gang; Zhuo, Ru-Yi; Xie, Yuan-Yuan; Pan, Wei

2017-01-01

Women younger than 40 years may face early menopause because of premature ovarian failure (POF). The cause of POF can be idiopathic or iatrogenic, especially the cancer-induced oophorectomy and chemo- or radiation therapy. The current treatments, including hormone replacement therapy (HRT) and cryopreservation techniques, have increased risk of ovarian cancer and may reintroduce malignant cells after autografting. Decellularization technique has been regarded as a novel regenerative medicine strategy for organ replacement, wherein the living cells of an organ are removed, leaving the extracellular matrix (ECM) for cellular seeding. This study aimed to produce a xenogeneic decellularized ovary (D-ovary) scaffold as a platform for ovary regeneration and transplantation. We have developed a novel decellularization protocol for porcine ovary by treatment with physical, chemical, and enzymatic methods. Using hematoxylin and eosin (H&E) staining, DAPI staining, scanning electron microscopy (SEM), and quantitative analysis, this approach proved effective in removing cellular components and preserving ECM. Furthermore, the results of biological safety evaluation demonstrated that the D-ovary tissues were noncytotoxic for rat ovarian cells in vitro and caused only a minimal immunogenic response in vivo. In addition, the D-ovary tissues successfully supported rat granulosa cell penetration ex vivo and showed an improvement in estradiol (E2) hormone secretion. PMID:27981878

Xenogeneic Decellularized Scaffold: A Novel Platform for Ovary Regeneration.

PubMed

Liu, Wen-Yue; Lin, Shi-Gang; Zhuo, Ru-Yi; Xie, Yuan-Yuan; Pan, Wei; Lin, Xian-Feng; Shen, Fei-Xia

2017-02-01

Women younger than 40 years may face early menopause because of premature ovarian failure (POF). The cause of POF can be idiopathic or iatrogenic, especially the cancer-induced oophorectomy and chemo- or radiation therapy. The current treatments, including hormone replacement therapy (HRT) and cryopreservation techniques, have increased risk of ovarian cancer and may reintroduce malignant cells after autografting. Decellularization technique has been regarded as a novel regenerative medicine strategy for organ replacement, wherein the living cells of an organ are removed, leaving the extracellular matrix (ECM) for cellular seeding. This study aimed to produce a xenogeneic decellularized ovary (D-ovary) scaffold as a platform for ovary regeneration and transplantation. We have developed a novel decellularization protocol for porcine ovary by treatment with physical, chemical, and enzymatic methods. Using hematoxylin and eosin (H&E) staining, DAPI staining, scanning electron microscopy (SEM), and quantitative analysis, this approach proved effective in removing cellular components and preserving ECM. Furthermore, the results of biological safety evaluation demonstrated that the D-ovary tissues were noncytotoxic for rat ovarian cells in vitro and caused only a minimal immunogenic response in vivo. In addition, the D-ovary tissues successfully supported rat granulosa cell penetration ex vivo and showed an improvement in estradiol (E2) hormone secretion.

Interferon Inducers against Infectious Diseases

DTIC Science & Technology

1990-07-13

22 7. Induction of IFN in Micoe by IC-(PLL- monosaccharides ............................... *23 8. ICL- CDS04...seeking to replace both PLL and CM by modifying the PLL with engrafted polysaccharides . 2. Background A number of candidates have been developed in this...expanders, or being closely related to such. These include gelatin, anionically-modified gelatin, oarboxymethyl polysaocharides, sulfated polysaccharides

Identification of centrarchid hepcidins and evidence that 17β-estradiol disrupts constitutive expression of hepcidin-1 and inducible expression of hepcidin-2 in largemouth bass (Micropterus salmoides)

USGS Publications Warehouse

Robertson, L.S.; Iwanowicz, L.R.; Marranca, J.M.

2009-01-01

Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site in the amino-terminus that is missing in hepcidin-2, suggesting that hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins are predominately expressed in the liver of largemouth bass, similar to other fish and mammals. Experimental exposure of pond-raised largemouth bass to 17β-estradiol and/or the bacteria Edwardsiella ictaluri led to distinct changes in expression of hep-1 and hep-2. Estradiol reduced the constitutive expression of hep-1 in the liver. Bacterial exposure induced expression of hep-2, suggesting that hepcidin-2 may have an antimicrobial function, and this induction was abolished by estradiol. To our knowledge, this is the first report of the regulation of hepcidin expression by estradiol in either fish or mammals.

Identification of centrarchid hepcidins and evidence that 17beta-estradiol disrupts constitutive expression of hepcidin-1 and inducible expression of hepcidin-2 in largemouth bass (Micropterus salmoides).

PubMed

Robertson, Laura S; Iwanowicz, Luke R; Marranca, Jamie Marie

2009-06-01

Hepcidin is a highly conserved antimicrobial peptide and iron-regulatory hormone. Here, we identify two hepcidin genes (hep-1 and hep-2) in largemouth bass (Micropterus salmoides) and smallmouth bass (Micropterus dolomieu). Hepcidin-1 contains a putative ATCUN metal-binding site in the amino-terminus that is missing in hepcidin-2, suggesting that hepcidin-1 may function as an iron-regulatory hormone. Both hepcidins are predominately expressed in the liver of largemouth bass, similar to other fish and mammals. Experimental exposure of pond-raised largemouth bass to 17beta-estradiol and/or the bacteria Edwardsiella ictaluri led to distinct changes in expression of hep-1 and hep-2. Estradiol reduced the constitutive expression of hep-1 in the liver. Bacterial exposure induced expression of hep-2, suggesting that hepcidin-2 may have an antimicrobial function, and this induction was abolished by estradiol. To our knowledge, this is the first report of the regulation of hepcidin expression by estradiol in either fish or mammals.

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.

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.

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.

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

Modified bases enable high-efficiency oligonucleotide-mediated allelic replacement via mismatch repair evasion

PubMed Central

Wang, Harris H.; Xu, George; Vonner, Ashley J.; Church, George

2011-01-01

Genome engineering using single-stranded oligonucleotides is an efficient method for generating small chromosomal and episomal modifications in a variety of host organisms. The efficiency of this allelic replacement strategy is highly dependent on avoidance of the endogenous mismatch repair (MMR) machinery. However, global MMR inactivation generally results in significant accumulation of undesired background mutations. Here, we present a novel strategy using oligos containing chemically modified bases (2′-Fluoro-Uridine, 5-Methyl-deoxyCytidine, 2,6-Diaminopurine or Iso-deoxyGuanosine) in place of the standard T, C, A or G to avoid mismatch detection and repair, which we tested in Escherichia coli. This strategy increases transient allelic-replacement efficiencies by up to 20-fold, while maintaining a 100-fold lower background mutation level. We further show that the mismatched bases between the full length oligo and the chromosome are often not incorporated at the target site, probably due to nuclease activity at the 5′ and 3′ termini of the oligo. These results further elucidate the mechanism of oligo-mediated allelic replacement (OMAR) and enable improved methodologies for efficient, large-scale engineering of genomes. PMID:21609953

Effects of 17β-estradiol on emissions of greenhouse gases in simulative natural water body.

PubMed

Ruan, Aidong; Zhao, Ying; Liu, Chenxiao; Zong, Fengjiao; Yu, Zhongbo

2015-05-01

Environmental estrogens are widely spread across the world and are increasingly thought of as serious contaminators. The present study looks at the influence of different concentrations of 17β-estradiol on greenhouse gas emissions (CO2 , CH4 , and N2 O) in simulated systems to explore the relationship between environmental estrogen-pollution and greenhouse gas emissions in natural water bodies. The present study finds that 17β-estradiol pollution in simulated systems has significant promoting effects on the emissions of CH4 and CO2 , although no significant effects on N2 O emissions. The present study indicates that 17β-estradiol has different effects on the different elements cycles; the mechanism of microbial ecology is under review. © 2015 SETAC.

Progesterone levels in letrozole associated controlled ovarian stimulation for fertility preservation in breast cancer patients.

PubMed

Goldrat, O; Gervy, C; Englert, Y; Delbaere, A; Demeestere, I

2015-09-01

Are progesterone levels after letrozole-associated controlled ovarian stimulation (COS) for fertility preservation in breast cancer patients, lower than after standard in vitro fertilization (IVF) cycles? During the luteal phase of letrozole-associated COS cycles (triggered with human chorionic gonadotrophin (hCG)) progesterone levels are similarly elevated to those obtained after standard COS without letrozole. Current fertility preservation strategies for breast cancer patients include association of COS with the aromatase inhibitor letrozole to harvest several mature oocytes while maintaining low estradiol levels. Data on progesterone levels are however lacking despite growing evidence of the role of progesterone in breast tumorigenesis. This is a prospective observational study comparing estradiol and progesterone levels of 21 breast cancer patients undergoing letrozole-associated COS with 21 infertile patients undergoing standard COS for IVF and/or intra cytoplasmic sperm injection (ICSI). All patients underwent COS with a GnRH antagonist protocol. In the fertility preservation group, ovulation induction was started in the follicular or luteal phase depending on the chemotherapy schedule and in 10 cases a GnRH antagonist was administered during luteal phase to induce luteolysis. Final oocyte maturation was induced by hCG in all patients. Estradiol and progesterone levels were measured on the day of hCG, at oocyte retrieval, and on days 3 and 8 after oocyte retrieval. Hormone levels in fertility preservation patients were compared with those observed in infertility patients. While estradiol levels were significantly lower in the fertility preservation group compared with the control group (P < 0.001), progesterone levels were similar at all times, including patients receiving a GnRH antagonist during the luteal phase. The studied populations (breast cancer and infertile patients) are different, which may induce selection bias. The small sample size limits the study's statistical power and the possibility to perform multivariate analysis. Recruitment of the study and control patients was completed at the same time; however, enrollment of controls started at a later time. While the use of letrozole in fertility preservation patients has a favorable effect on estrogen levels, no benefit is seen for progesterone levels which are high and comparable with progesterone levels after standard COS in IVF patients. As progesterone has been associated with tumor cell proliferation, caution is mandatory. Modified protocols including GnRH agonist triggering should be investigated. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Generalization of the quasi-geostrophic Eliassen-Palm flux to include eddy forcing of condensation heating

NASA Technical Reports Server (NTRS)

Stone, P. H.; Salustri, G.

1984-01-01

A modified Eulerian form of the Eliassen-Palm flux which includes the effect of eddy forcing on condensation heating is defined. With the two-dimensional vector flux in the meridional plane which is a function of the zonal mean eddy fluxes replaced by the modified flux, both the Eliassen-Palm theorem and a modified but more general form of the nonacceleration theorem for quasi-geostrophic motion still hold. Calculations of the divergence of the modified flux and of the eddy forcing of the moisture field are presented.

Effects at early stage of life of elevated milk replacer feeding on growth rate, plasma IGF-I concentration and intestinal nutrient transporter expression in Holstein bull calves.

PubMed

Orihashi, Takenori; Mashiko, Takanori; Sera, Kenji; Roh, Sang-Gun; Katoh, Kazuo; Obara, Yoshiaki

2012-01-01

In order to evaluate the effects of an elevated amount of modified milk replacer on body weight, daily gain, starter intake, plasma endocrine parameters and expression of nutrient transporters in small intestinal epithelia, Holstein bull calves (n=24) were fed for 60days either with the usual amount of 24% crude protein (CP) and 20% fat milk (CF) replacer (C group), or with a double amount of a modified milk replacer of 28% CP and 16% CF (E group). Body weight from D20 to D60 and daily gain before D40 was greater or tended to be greater for the E group than the C group. Plasma concentrations of insulin-like growth factor-1 (IGF-I) and insulin were greater for the E group than the C group on D28 but not on D56, without changing plasma growth hormone levels. Gene expression for sodium-dependent glucose transporter 1 and fatty acid translocase (CD36) was altered in day- and intestine-dependent manners. From these findings, we conclude that an elevated intake of milk replacer given up to 40days old is sufficient to enhance body weight, which may be associated with increased plasma IGF-I concentrations, in Holstein bulls. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial.

PubMed

Markey, Oonagh; Vasilopoulou, Dafni; Kliem, Kirsty E; Koulman, Albert; Fagan, Colette C; Summerhill, Keith; Wang, Laura Y; Grandison, Alistair S; Humphries, David J; Todd, Susan; Jackson, Kim G; Givens, David I; Lovegrove, Julie A

2017-05-23

Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.

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

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

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.

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib.

PubMed

Girgert, Rainer; Emons, Günter; Gründker, Carsten

2017-02-01

Triple-negative breast cancers (TNBCs) are neither susceptible to endocrine therapy due to a lack of estrogen receptor α expression nor trastuzumab. TNBCs frequently overexpress epidermal growth factor receptor (EGFR) and membrane bound estrogen receptor, GPER. To a certain extent the growth of TNBCs is stimulated by 17β-estradiol via GPER. We analyzed whether inhibition of EGFR by gefitinib reduces the expression of GPER and subsequent signal transduction in TNBC cells. Dependence of proliferation on 17β-estradiol was determined using Alamar Blue assay. Expression of GPR30 and activation of c-src, EGFR and cAMP-responsive element binding (CREB) protein by 17β-estradiol was analyzed by western blotting. Expression of c-fos, cyclin D1 and aromatase was determined using RT-PCR. Gefitinib reduced GPER expression concentration‑ and time‑dependently. In HCC70 cells, GPER expression was reduced to 15±11% (p<0.05) after treatment with 200 nM gefitinib for four days, and in HCC1806 cells GPER expression was reduced to 39±5% (p<0.01) of the control. 17β-estradiol significantly increased the percentage of HCC1806 cells within 7 days to 145±29% of the control (HCC70, 110±8%). This increase in cell growth was completely prevented in both TNBC cell lines after GPR30 expression was downregulated by treatment with 200 nM gefitinib. In HCC1806 cells, activation of c-src was increased by 17β-estradiol to 350±50% (p<0.01), and gefitinib reduced src activation to 110%. Similar results were obtained in the HCC70 cells. Phosphorylation of EGFR increased to 240±40% (p<0.05) in the HCC1806 cells treated with 17β-estradiol (HCC70, 147±25%). Gefitinib completely prevented this activation. Phosphorylation of CREB and induction of c-fos, cyclin D1 and aromatase expression by 17β-estradiol were all prevented by gefitinib. These experiments conclusively show that reduction of GPER expression is a promising therapeutic approach for TNBC.

Estradiol blood test

MedlinePlus

... development Changes of the outer genitals Distribution of body fat Menopause In men, a small amount of estradiol ... syndrome , Turner syndrome Rapid weight loss or low body fat Risks Veins and arteries vary in size from ...

Modified quadrupole mass analyzer RGA-100 for beam plasma research in forevacuum pressure range

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

Zolotukhin, D. B.; Tyunkov, A. V.; Yushkov, Yu. G., E-mail: yuyushkov@gmail.com

2015-12-15

The industrial quadrupole RGA-100 residual gas analyzer was modified for the research of electron beam-generated plasma at forevacuum pressure range. The standard ionizer of the RGA-100 was replaced by three electrode extracting unit. We made the optimization of operation parameters in order to provide the maximum values of measured currents of any ion species. The modified analyzer was successfully tested with beam plasma of argon, nitrogen, oxygen, and hydrocarbons.

Modified Acyl-ACP desaturase

DOEpatents

Cahoon, Edgar B.; Shanklin, John; Lindqvist, Ylva; Schneider, Gunter

1999-03-30

Disclosed is a method for modifying the chain length and double bond positional specificities of a soluble plant fatty acid desaturase. More specifically, the method involves modifying amino acid contact residues in the substrate binding channel of the soluble fatty acid desaturase which contact the fatty acid. Specifically disclosed is the modification of an acyl-ACP desaturase. Amino acid contact residues which lie within the substrate binding channel are identified, and subsequently replaced with different residues to effect the modification of activity.

Modified acyl-ACP desaturase

DOEpatents

Cahoon, Edgar B.; Shanklin, John; Lindgvist, Ylva; Schneider, Gunter

1998-01-06

Disclosed is a methods for modifying the chain length and double bond positional specificities of a soluble plant fatty acid desaturase. More specifically, the method involves modifying amino acid contact residues in the substrate binding channel of the soluble fatty acid desaturase which contact the fatty acid. Specifically disclosed is the modification of an acyl-ACP desaturase. Amino acid contact residues which lie within the substrate binding channel are identified, and subsequently replaced with different residues to effect the modification of activity.

Prosthetic valve sparing aortic root replacement: an improved technique.

PubMed

Leacche, Marzia; Balaguer, Jorge M; Umakanthan, Ramanan; Byrne, John G

2008-10-01

We describe a modified surgical technique to treat patients with a previous history of isolated aortic valve replacement who now require aortic root replacement for an aneurysmal or dissected aorta. This technique consists of replacing the aortic root with a Dacron conduit, leaving intact the previously implanted prosthesis, and re-implanting the coronary arteries in the Dacron graft. Our technique differs from other techniques in that we do not leave behind any aortic tissue remnant and also in that we use a felt strip to obliterate any gap between the old sewing ring and the newly implanted graft. In our opinion, this promotes better hemostasis. We demonstrate that this technique is safe, feasible, and results in acceptable outcomes.

Dead pixel replacement in LWIR microgrid polarimeters.

PubMed

Ratliff, Bradley M; Tyo, J Scott; Boger, James K; Black, Wiley T; Bowers, David L; Fetrow, Matthew P

2007-06-11

LWIR imaging arrays are often affected by nonresponsive pixels, or "dead pixels." These dead pixels can severely degrade the quality of imagery and often have to be replaced before subsequent image processing and display of the imagery data. For LWIR arrays that are integrated with arrays of micropolarizers, the problem of dead pixels is amplified. Conventional dead pixel replacement (DPR) strategies cannot be employed since neighboring pixels are of different polarizations. In this paper we present two DPR schemes. The first is a modified nearest-neighbor replacement method. The second is a method based on redundancy in the polarization measurements.We find that the redundancy-based DPR scheme provides an order-of-magnitude better performance for typical LWIR polarimetric data.

National Athletic Trainers' Association Position Statement: Fluid Replacement for Athletes

PubMed Central

Casa, Douglas J.; Armstrong, Lawrence E.; Hillman, Susan K.; Montain, Scott J.; Reiff, Ralph V.; Rich, Brent S. E.; Roberts, William O.; Stone, Jennifer A.

2000-01-01

Objective: To present recommendations to optimize the fluid-replacement practices of athletes. Background: Dehydration can compromise athletic performance and increase the risk of exertional heat injury. Athletes do not voluntarily drink sufficient water to prevent dehydration during physical activity. Drinking behavior can be modified by education, increasing accessibility, and optimizing palatability. However, excessive overdrinking should be avoided because it can also compromise physical performance and health. We provide practical recommendations regarding fluid replacement for athletes. Recommendations: Educate athletes regarding the risks of dehydration and overhydration on health and physical performance. Work with individual athletes to develop fluid-replacement practices that optimize hydration status before, during, and after competition. Imagesp224-a PMID:16558633

Perturbative Yang-Mills theory without Faddeev-Popov ghost fields

NASA Astrophysics Data System (ADS)

Huffel, Helmuth; Markovic, Danijel

2018-05-01

A modified Faddeev-Popov path integral density for the quantization of Yang-Mills theory in the Feynman gauge is discussed, where contributions of the Faddeev-Popov ghost fields are replaced by multi-point gauge field interactions. An explicit calculation to O (g2) shows the equivalence of the usual Faddeev-Popov scheme and its modified version.

The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

PubMed Central

Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

2010-01-01

In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

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

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

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.

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.

Low HAP Materials

DTIC Science & Technology

2009-09-01

Use maleinized triglycerides to replace UPE • Use novel bio-based reactive diluent to replace styrene Bio-Based Carbon Fibers and Thermosetting Resins...SERDP proposed new start, FY10 • Microbially breakdown lignin into oligomers that can be melt spun and carbonized • Modify renewable...D5045-93 • Designed plant oil-based toughening agents • Uses phase separation to capture MFA reactive diluent • Increases toughness while decreasing

17betaE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFkappaB-dependent pathway.

PubMed

Zhang, Hui; Zhao, Xingbo; Liu, Shu; Li, Jijun; Wen, Zeqing; Li, Mingjiang

2010-04-12

The objective of this study was to explore the mechanism of phosphatase and tensin homolog (PTEN) loss in endometriosis. We found that aberrant PTEN expression and mitogen-activated protein kinases (MAPK)/ERK, phosphoinositide 3-kinase (PI3K)/AKt, and nuclear factor-kappaB (NFkappaB) signaling overactivities coexisted in endometriosis. In vitro, 17beta-estradiol rapidly activated the 3 pathways in endometriotic cells and specific inhibitions on the 3 pathways respectively blocked 17beta-estradiol-induced cell proliferation. 17beta-estradiol suppressed PTEN transcription and expression in endometriotic cells which was abolished by specific NFkappaB inhibition. Total/nuclear PTEN-loss and MAPK/ERK, PI3K/AKt, and NFkappaB signal overactivities coexist in endometriosis. In vitro, 17beta-estradiol can promotes cell proliferation in endometriosis by activating PI3K/AKt pathway via an NFkappaB/PTEN-dependent pathway. For the first time we propose the possibility of the presence of a positive feedback-loop: 17beta-estradiol-->high NFkappaB-->low PTEN-->high PI3K-->high NFkappaB, in endometriosis, which may finally promote the proliferation of ectopic endometrial epithelial cells and in turn contributes to the progression of the disease.

Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

PubMed

Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

2004-06-01

Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial.

PubMed

Madden, Tessa; Proehl, Sarah; Allsworth, Jenifer E; Secura, Gina M; Peipert, Jeffrey F

2012-02-01

The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. Copyright © 2012 Mosby, Inc. 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.

Modified acyl-ACP desaturase

DOEpatents

Cahoon, E.B.; Shanklin, J.; Lindgvist, Y.; Schneider, G.

1998-01-06

Disclosed is a method for modifying the chain length and double bond positional specificities of a soluble plant fatty acid desaturase. More specifically, the method involves modifying amino acid contact residues in the substrate binding channel of the soluble fatty acid desaturase which contact the fatty acid. Specifically disclosed is the modification of an acyl-ACP desaturase. Amino acid contact residues which lie within the substrate binding channel are identified, and subsequently replaced with different residues to effect the modification of activity. 1 fig.

Modified Acyl-ACP desaturase

DOEpatents

Cahoon, E.B.; Shanklin, J.; Lindqvist, Y.; Schneider, G.

1999-03-30

Disclosed is a method for modifying the chain length and double bond positional specificities of a soluble plant fatty acid desaturase. More specifically, the method involves modifying amino acid contact residues in the substrate binding channel of the soluble fatty acid desaturase which contact the fatty acid. Specifically disclosed is the modification of an acyl-ACP desaturase. Amino acid contact residues which lie within the substrate binding channel are identified, and subsequently replaced with different residues to effect the modification of activity. 2 figs.

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.

Orphanin FQ-ORL-1 regulation of reproduction and reproductive behavior in the female.

PubMed

Sinchak, Kevin; Dalhousay, Lauren; Sanathara, Nayna

2015-01-01

Orphanin FQ (OFQ/N) and its receptor, opioid receptor-like receptor-1 (ORL-1), are expressed throughout steroid-responsive limbic and hypothalamic circuits that regulate female ovarian hormone feedback and reproductive behavior circuits. The arcuate nucleus of the hypothalamus (ARH) is a brain region that expresses OFQ/N and ORL-1 important for both sexual behavior and modulating estradiol feedback loops. Within the ARH, the activation of the OFQ/N-ORL-1 system facilitates sexual receptivity (lordosis) through the inhibition of β-endorphin neuronal activity. Estradiol initially activates ARH β-endorphin neurons to inhibit lordosis. Simultaneously, estradiol upregulates coexpression of OFQ/N and progesterone receptors and ORL-1 in ARH β-endorphin neurons. Ovarian hormones regulate pre- and postsynaptic coupling of ORL-1 to its G protein-coupled signaling pathways. When the steroid-primed rat is nonreceptive, estradiol acts pre- and postsynaptically to decrease the ability of the OFQ/N-ORL-1 system to inhibit ARH β-endorphin neurotransmission. Conversely, when sexually receptive, ORL-1 signaling is restored to inhibit β-endorphin neurotransmission. Although steroid signaling that facilitates lordosis converges to deactivate ARH β-endorphin neurons, estradiol-only facilitation of lordosis requires the activation of ORL-1, but estradiol+progesterone does not, indicating that multiple circuits mediate ovarian hormone signaling to deactivate ARH β-endorphin neurons. Research on the role of OFQ/N-ORL-1 in ovarian hormone feedback loops is just beginning. In the rat, OFQ/N may act to terminate gonadotropin-releasing hormone and luteinizing hormone release under positive and negative feedbacks. In the ewe, it appears to directly inhibit gonadotropin-releasing hormone release to mediate progesterone-negative feedback. As a whole, the localization and actions of OFQ/N-ORL-1 system indicate that it may mediate the actions of estradiol and progesterone to synchronize reproductive behavior and ovarian hormone feedback loops. © 2015 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

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.

Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.

PubMed

Ahrendt, Hans-Joachim; Makalová, Dagmar; Parke, Susanne; Mellinger, Uwe; Mansour, Diana

2009-11-01

This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol. This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years. Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG. A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC.

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.

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.

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

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.

[Role of estrogen-sensitive neurons in the arcuate region of the hypothalamus in the mechanism of luteinizing hormone release].

PubMed

Babichev, V N; Ignatkov, V Ia

1978-01-01

Experiments were conducted on rats; estradiol brought to the arcuate region of the hypothalamus by means of microionophoresis led to the increase of the region of the hypothalamus by means of microionophoresis led to the increase of the blood luteinizing hormone (LH) level during the following stages of the estral cycle-diestrus 1, diestrus 2, and the first half day of the proestrus; as to the second half of the proestrus day--estradiol decreased its level. Changes in the LH level in the hypophysis under the influence of the microionophoretic introduction of estradiol into the arcuate region occurred during the second half of the day of diestrus 2 (reduction), and during the estrus (elevation). In the majority of cases a rise of the blood level was combined with the neuron activation in the arcuate region under the influence of estradiol.

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.

Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans

PubMed Central

Salinas-Muñoz, Laura; Campos-Fernández, Raúl; Mercader, Enrique; Olivera-Valle, Irene; Fernández-Pacheco, Carlota; Matilla, Lara; García-Bordas, Julio; Brazil, Jennifer C.; Parkos, Charles A.; Asensio, Fernando; Muñoz-Fernández, Maria A.; Hidalgo, Andrés; Sánchez-Mateos, Paloma; Samaniego, Rafael; Relloso, Miguel

2018-01-01

Estradiol-based therapies predispose women to vaginal infections. Moreover, it has long been known that neutrophils are absent from the vaginal lumen during the ovulatory phase (high estradiol). However, the mechanisms that regulate neutrophil influx to the vagina remain unknown. We investigated the neutrophil transepithelial migration (TEM) into the vaginal lumen. We revealed that estradiol reduces the CD44 and CD47 epithelial expression in the vaginal ectocervix and fornix, which retain neutrophils at the apical epithelium through the estradiol receptor-alpha. In contrast, luteal progesterone increases epithelial expression of CD44 and CD47 to promote neutrophil migration into the vaginal lumen and Candida albicans destruction. Distinctive to vaginal mucosa, neutrophil infiltration is contingent to sex hormones to prevent sperm from neutrophil attack; although it may compromise immunity during ovulation. Thus, sex hormones orchestrate tolerance and immunity in the vaginal lumen by regulating neutrophil TEM. PMID:29881378

A continuous regimen of levonorgestrel/ethinyl estradiol for contraception and elimination of menstruation.

PubMed

Jensen, Jeffrey T

2008-03-01

Clinicians and patients desiring amenorrhea for therapeutic or social reasons will find continuous-use 90 microg levonorgestrel/20 microg ethinyl estradiol to be an attractive oral contraceptive dosing option. Although other formulations of oral contraceptives can be dosed in a continuous manner off-label, the convenience of a 28-day dose pack represents a major advance that will likely increase acceptability of the strategy. The availability of FDA-approved continuous-use 90 microg levonorgestrel/20 microg ethinyl estradiol will help mainstream continuous oral contraception in the same way that Preven and Plan B helped legitimize and mainstream emergency contraception. Patients wishing to use continuous 90 microg levonorgestrel/20 microg ethinyl estradiol must recognize and accept that unscheduled breakthrough bleeding is typical during the first four to six cycles of use. Control of cycle-related symptoms may emerge as an off-label indication for use.

Estrogen Receptor-Alpha (ESR1) Governs the Lower Female Reproductive Tract Vulnerability to Candida albicans.

PubMed

Salinas-Muñoz, Laura; Campos-Fernández, Raúl; Mercader, Enrique; Olivera-Valle, Irene; Fernández-Pacheco, Carlota; Matilla, Lara; García-Bordas, Julio; Brazil, Jennifer C; Parkos, Charles A; Asensio, Fernando; Muñoz-Fernández, Maria A; Hidalgo, Andrés; Sánchez-Mateos, Paloma; Samaniego, Rafael; Relloso, Miguel

2018-01-01

Estradiol-based therapies predispose women to vaginal infections. Moreover, it has long been known that neutrophils are absent from the vaginal lumen during the ovulatory phase (high estradiol). However, the mechanisms that regulate neutrophil influx to the vagina remain unknown. We investigated the neutrophil transepithelial migration (TEM) into the vaginal lumen. We revealed that estradiol reduces the CD44 and CD47 epithelial expression in the vaginal ectocervix and fornix, which retain neutrophils at the apical epithelium through the estradiol receptor-alpha. In contrast, luteal progesterone increases epithelial expression of CD44 and CD47 to promote neutrophil migration into the vaginal lumen and Candida albicans destruction. Distinctive to vaginal mucosa, neutrophil infiltration is contingent to sex hormones to prevent sperm from neutrophil attack; although it may compromise immunity during ovulation. Thus, sex hormones orchestrate tolerance and immunity in the vaginal lumen by regulating neutrophil TEM.

A tristate optical logic system

NASA Astrophysics Data System (ADS)

Basuray, A.; Mukhopadhyay, S.; Kumar Ghosh, Hirak; Datta, A. K.

1991-09-01

A method is described to represent data in a tristate logic system which are subsequently replaced by Modified Trinary Numbers (MTN). This system is advantagegeous in parallel processing as carry and borrow free operations in arithmatic computation is possible. The logical operations are also modified according to the three states available. A possible practical application of the same using polarized light is also suggested.

Measurements of AAFE RADSCAT antenna characteristics

NASA Technical Reports Server (NTRS)

Cross, A. E.; Jones, W. L., Jr.; Jones, A. L.

1977-01-01

Antenna characteristics (active and passive) for a modified AAFE-RADSCAT parabolic dish antenna are documented for a variety of antenna configurations. The modified antenna was a replacement for the original unit which was damaged in January 1975. Pattern measurements made at Langley Research Center and Johnson Space Center are presented, with an analysis of the results. Antenna loss measurements are also presented and summarized.

Rice husk ash (RHA) as a partial cement replacement in modifying peat soil properties

NASA Astrophysics Data System (ADS)

Daud, Nik Norsyahariati Nik; Daud, Mohd Nazrin Mohd; Muhammed, Abubakar Sadiq

2018-02-01

This paper describes the effect of rice husk ash (RHA) and ordinary Portland cement (OPC) as a potential binder for modifying the properties of peat soil. The amounts RHA and OPC added to the peat soil sample, as percentage of the dry soil mass were in the range of 10-15% and 15%, respectively. Observations were made for the changes in the properties of the soil such as maximum dry density (MDD), optimum moisture content (OMC) and shear strength. Scanning Electron Micrograph-Energy Dispersive X-Ray (SEM-EDX) test were also conducted to observe the microstructure of treated and untreated peat soil. The results show that the modified soil of MDD and OMC values are increased due to the increment amount of binder material. Shear strength values of modified peat showing a good result by assuming that it is relative to the formation of major reaction products such as calcium silicate hydrate (C-S-H). The presence of C-S-H formation is indicated by the results produced from microstructural analysis of peat before and after modification process. This depicts the potential usage of RHA as a partial cement replacement in peat soil which is also improving its engineering properties.

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.

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

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.

Increased plasma viscosity in young women with polycystic ovary syndrome using an oral contraceptive containing 35 μg ethinyl estradiol and 2 mg cyproterone acetate.

PubMed

Markantes, George; Saltamavros, Alexandros D; Vervita, Vasiliki; Armeni, Anastasia K; Karela, Anastasia; Adonakis, George; Decavalas, George; Georgopoulos, Neoklis A

2011-12-01

To investigate the influence of 6 months of treatment with an oral contraceptive (OC) containing 35 μ g ethinyl estradiol and 2 mg cyproterone acetate on plasma viscosity (PV) in young women with polycystic ovary syndrome (PCOS). Patients with PCOS were assessed for PV before and after 6 months of treatment with an OC containing 35 μg ethinyl estradiol and 2 mg cyproterone acetate. PV was determined by a viscometer Type 53610/I SCHOTT-Instruments, Mainz at 37°C. Subjects were recruited from the Department of Obstetrics and Gynaecology, Division of Reproductive Endocrinology at the University Hospital of Patras, Greece. The study included 66 young women with PCOS. PV. In PCOS women as a whole, PV at baseline was 1.249 ± 0.049 mm(2)/s (n = 66). After 6 months of treatment with an OC containing 35 μg ethinyl estradiol and 2 mg cyproterone acetate, PV was increased to 1.268 ± 0.065 mm(2)/s (p = 0.038). The difference between PV before and after 6 months of treatment with an OC containing 35 μg ethinyl estradiol and 2 mg cyproterone acetate (Δviscosity) was 0.01864 ± 0.071452 mm(2)/s. ΔViscosity was related to ?fibrinogen (r = 0.270, p = 0.046), to Δhematocrit (r = 0.514, p = 0.09) and to Δtriglycerides (r = 0.292, p = 0.021). Young women with PCOS presented an increased PV under OC treatment with 35 μg ethinyl estradiol and 2 mg cyproterone acetate.

Behaviour and occurrence of estrogens in municipal sewage treatment plants--II. Aerobic batch experiments with activated sludge.

PubMed

Ternes, T A; Kreckel, P; Mueller, J

1999-01-12

Aerobic batch experiments containing a diluted slurry of activated sludge from a real sewage treatment plant (STP) near Frankfurt/Main were undertaken, in order to investigate the persistence of natural estrogens and contraceptives under aerobic conditions. The batch experiments showed that while in contact with activated sludge the natural estrogen 17 beta-estradiol was oxidized to estrone, which was further eliminated in the batch experiments in an approximate linear time dependence. Further degradation products of estrone were not observed. 16 alpha-hydroxyestrone was rapidly eliminated, again without detection of further degradation products. The contraceptive 17 alpha-ethinylestradiol was principally persistent under the selected aerobic conditions, whereas mestranol was rapidly eliminated and small portions of 17 alpha-ethinylestradiol were formed by demethylation. Additionally, two glucuronides of 17 beta-estradiol (17 beta-estradiol-17-glucuronide and 17 beta-estradiol-3-glucuronide) were cleaved in contact with the diluted activated sludge solution and thus 17 beta-estradiol was released. The glucuronidase activity of the activated sludge was further confirmed by the cleavage of 4-methylumbelliferyl-beta-D-glucuronide (MUF-beta-glucuronide) in a solution of a activated sludge slurry and Milli-Q-water (1:100, v/v). The turnover rate obtained was approximately steady state, with a turnover rate of 0.1 mumol/l for the released MUF. Hence, it is very likely that the glucuronic acid moiety of 17 beta-estradiol glucuronides and other estrogen glucuronides become cleaved in a real municipal STP, so that the concentrations of the free estrogens increase.