Estrogenic activities of diuron metabolites in female Nile tilapia (Oreochromis niloticus).

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Pereira, Thiago Scremin Boscolo; Boscolo, Camila Nomura Pereira; Felício, Andreia Arantes; Batlouni, Sergio Ricardo; Schlenk, Daniel; de Almeida, Eduardo Alves

2016-03-01

Some endocrine disrupting chemicals (EDCs) can alter the estrogenic activities of the organism by directly interacting with estrogen receptors (ER) or indirectly through the hypothalamus-pituitary-gonadal axis. Recent studies in male Nile tilapia (Oreochromis niloticus) indicated that diuron may have anti-androgenic activity augmented by biotransformation. In this study, the effects of diuron and three of its metabolites were evaluated in female tilapia. Sexually mature female fish were exposed for 25 days to diuron, as well as to its metabolites 3,4-dichloroaniline (DCA), 3,4-dichlorophenylurea (DCPU) and 3,4-dichlorophenyl-N-methylurea (DCPMU), at concentrations of 100 ng/L. Diuron metabolites caused increases in E2 plasma levels, gonadosomatic indices and in the percentage of final vitellogenic oocytes. Moreover, diuron and its metabolites caused a decrease in germinative cells. Significant differences in plasma concentrations of the estrogen precursor and gonadal regulator17α-hydroxyprogesterone (17α-OHP) were not observed. These results show that diuron metabolites had estrogenic effects potentially mediated through enhanced estradiol biosynthesis and accelerated the ovarian development of O. niloticus females. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regional differences in the prostate of the neonatally estrogenized mouse

International Nuclear Information System (INIS)

Pylkkaenen, L.S.; Santti, R.; Newbold, R.; McLachlan, J.A.

1991-01-01

Neonatal estrogenization of the mouse with diethylstilbestrol resulted in time-of-exposure and dose-dependent inhibition of the growth of the prostatic lobes observed at the age of 2 mon. The critical time was the days 1-6 of postnatal life. In neonatally estrogenized (neoDES) mice, responses to 5 alpha-dihydrotestosterone in terms of nuclear 3H-thymidine labelling were altered concomitantly with the inhibition of growth and were in accordance with changes in the relative volumes of epithelium, glandular lumina, and interacinar stroma. Secondary estrogen treatment of neoDES mice with 17 beta-estradiol did not increase 3H-thymidine labelling in the prostate of control or neoDES mice. However, it induced squamous epithelial metaplasia in periurethral collecting ducts and proximal parts of coagulating glands of neoDES animals. In control mice only slight epithelial hyperplasia could be observed after similar treatment. Estrogen receptors, located immunocytochemically in nuclei of stromal cell, corresponded with the sites of increased estrogen sensitivity, observed as metaplastic transformation. When the neoDES animals aged, epithelial hyperplasia and dysplasia could be observed at distinct prostatic sites, ie, the periurethral collecting ducts and the coagulating glands and periurethral glands, and stromal inflammation become more extensive. Almost identical location of the epithelial changes and the altered estrogen response is suggestive of causal relationship

Estrogen responsiveness of the TFIID subunit TAF4B in the normal mouse ovary and in ovarian tumors.

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Wardell, Jennifer R; Hodgkinson, Kendra M; Binder, April K; Seymour, Kimberly A; Korach, Kenneth S; Vanderhyden, Barbara C; Freiman, Richard N

2013-11-01

Estrogen signaling in the ovary is a fundamental component of normal ovarian function, and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Herein, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, are increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol and that this response occurs within hours after stimulation. Furthermore, this increase occurs via nuclear estrogen receptors both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase in Taf4b mRNA in estrogen-supplemented mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation.

Estrogenic mediation of serotonergic and neurotrophic systems: implications for female mood disorders.

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Borrow, Amanda P; Cameron, Nicole M

2014-10-03

Clinical research has demonstrated a significant sex difference in the occurrence of depressive disorders. Beginning at pubertal onset, women report a higher incidence of depression than men. Women are also vulnerable to the development of depressive disorders such as premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression. These disorders are associated with reproductive stages involving changes in gonadal hormone levels. Specifically, female depression and female affective behaviors are influenced by estradiol levels. This review argues two major mechanisms by which estrogens influence depression and depressive-like behavior: through interactions with neurotrophic factors and through an influence on the serotonergic system. In particular, estradiol increases brain derived neurotrophic factor (BDNF) levels within the brain, and alters serotonergic expression in a receptor subtype-specific manner. We will take a regional approach, examining these effects of estrogens in the major brain areas implicated in depression. Finally, we will discuss the gaps in our current knowledge of the effects of estrogens on female depression, and the potential utility for estrogen receptor modulators in treatment for this disorder. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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Murakami, Gen

2016-01-01

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

Beneficial effects of estrogen in a mouse model of cerebrovascular insufficiency.

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Naohito Kitamura

Full Text Available BACKGROUND: The M(5 muscarinic acetylcholine receptor is known to play a crucial role in mediating acetylcholine dependent dilation of cerebral blood vessels. Previously, we reported that male M(5 muscarinic acetylcholine knockout mice (M5R(-/- mice suffer from a constitutive constriction of cerebral arteries, reduced cerebral blood flow, dendritic atrophy, and short-term memory loss, without necrosis and/or inflammation in the brain. METHODOLOGY/PRINCIPAL FINDINGS: We employed the Magnetic Resonance Angiography to study the area of the basilar artery in male and female M5R(-/- mice. Here we show that female M5R(-/- mice did not show the reduction in vascular area observed in male M5R(-/- mice. However, ovariectomized female M5R(-/- mice displayed phenotypic changes similar to male M5R(-/- mice, strongly suggesting that estrogen plays a key role in the observed gender differences. We found that 17beta-estradiol (E2 induced nitric oxide release and ERK activation in a conditional immortalized mouse brain cerebrovascular endothelial cell line. Agonists of ERalpha, ERbeta, and GPR30 promoted ERK activation in this cell line. Moreover, in vivo magnetic resonance imaging studies showed that the cross section of the basilar artery was restored to normal in male M5R(-/- mice treated with E2. Treatment with E2 also improved the performance of male M5R(-/- mice in a cognitive test and reduced the atrophy of neural dendrites in the cerebral cortex and hippocampus. M5R(-/- mice also showed astrocyte swelling in cortex and hippocampus using the three-dimensional reconstruction of electron microscope images. This phenotype was reversed by E2 treatment, similar to the observed deficits in dendrite morphology and the number of synapses. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that M5R(-/- mice represent an excellent novel model system to study the beneficial effects of estrogen on cerebrovascular function and cognition. E2 may offer new therapeutic

Estrogen Responsiveness of the TFIID Subunit TAF4B in the Normal Mouse Ovary and in Ovarian Tumors1

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Wardell, Jennifer R.; Hodgkinson, Kendra M.; Binder, April K.; Seymour, Kimberly A.; Korach, Kenneth S.; Vanderhyden, Barbara C.; Freiman, Richard N.

2013-01-01

ABSTRACT Estrogen signaling in the ovary is a fundamental component of normal ovarian function, and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Herein, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, are increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol and that this response occurs within hours after stimulation. Furthermore, this increase occurs via nuclear estrogen receptors both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase in Taf4b mRNA in estrogen-supplemented mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation. PMID:24068106

Estrogen receptor-a in the medial amygdala prevents stress-induced elevations in blood pressure in females

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Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in femal...

Vertebrate estrogen regulates the development of female characteristics in silkworm, Bombyx mori.

Science.gov (United States)

Shen, Guanwang; Lin, Ying; Yang, Congwen; Xing, Runmiao; Zhang, Haiyan; Chen, Enxiang; Han, Chaoshan; Liu, Hongling; Zhang, Weiwei; Xia, Qingyou

2015-01-01

The vertebrate estrogens include 17-β-estradiol (E2), which has an analog in silkworm ovaries. In this study, the Bombyx mori vitellogenin gene (BmVg) was used as a biomarker to analyze the function of the E2 in silkworm. In most oviparous animals, Vg has female-specific expression. However, BmVg expression was also detected in B. mori males. Stage specific fluctuation of BmVg expression was similar in males and females, but expression levels in males were lower than in females. E2 treatment by injection or feeding of male larvae in the final instar stage induced and stimulated male BmVg transcription and protein synthesis. When silkworm ovary primordia were transplanted into males, BmVg was induced in male fat bodies. Transplanted ovaries primordia were also able to develop into ovaries and produce mature eggs. When females were treated with E2 promoted BmVg/BmVn protein accumulation in hemolymph, ovaries and eggs. However, BmVg transcription was decreased in female fat bodies. An E2 analog was identified in the hemolymph of day 3 wandering silkworms using high-performance liquid chromatography. Estradiol titers from fifth late-instar larvae to pupal stage were determined by enzyme-linked immunosorbent assay. The results suggested that silkworms synthesized a vertebrate E2 analog. This study found that E2 promoted the synthesis of BmVg, a female typical protein in silkworms. Copyright © 2014 Elsevier Inc. All rights reserved.

Estrogen and the female heart.

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Knowlton, A A; Korzick, D H

2014-05-25

Estrogen has a plethora of effects in the cardiovascular system. Studies of estrogen and the heart span human clinical trials and basic cell and molecular investigations. Greater understanding of cell and molecular responses to estrogens can provide further insights into the findings of clinical studies. Differences in expression and cellular/intracellular distribution of the two main receptors, estrogen receptor (ER) α and β, are thought to account for the specificity and differences in responses to estrogen. Much remains to be learned in this area, but cellular distribution within the cardiovascular system is becoming clearer. Identification of GPER as a third ER has introduced further complexity to the system. 17β-estradiol (E2), the most potent human estrogen, clearly has protective properties activating a signaling cascade leading to cellular protection and also influencing expression of the protective heat shock proteins (HSP). E2 protects the heart from ischemic injury in basic studies, but the picture is more involved in the whole organism and clinical studies. Here the complexity of E2's widespread effects comes into play and makes interpretation of findings more challenging. Estrogen loss occurs primarily with aging, but few studies have used aged models despite clear evidence of differences between the response to estrogen deficiency in adult and aged animals. Thus more work is needed focusing on the effects of aging vs. estrogen loss on the cardiovascular system. Published by Elsevier Ireland Ltd.

Immune-Specific Expression and Estrogenic Regulation of the Four Estrogen Receptor Isoforms in Female Rainbow Trout (Oncorhynchus mykiss

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Ayako Casanova-Nakayama

2018-03-01

Full Text Available Genomic actions of estrogens in vertebrates are exerted via two intracellular estrogen receptor (ER subtypes, ERα and ERβ, which show cell- and tissue-specific expression profiles. Mammalian immune cells express ERs and are responsive to estrogens. More recently, evidence became available that ERs are also present in the immune organs and cells of teleost fish, suggesting that the immunomodulatory function of estrogens has been conserved throughout vertebrate evolution. For a better understanding of the sensitivity and the responsiveness of the fish immune system to estrogens, more insight is needed on the abundance of ERs in the fish immune system, the cellular ratios of the ER subtypes, and their autoregulation by estrogens. Consequently, the aims of the present study were (i to determine the absolute mRNA copy numbers of the four ER isoforms in the immune organs and cells of rainbow trout, Oncorhynchus mykiss, and to compare them to the hepatic ER numbers; (ii to analyse the ER mRNA isoform ratios in the immune system; and, (iii finally, to examine the alterations of immune ER mRNA expression levels in sexually immature trout exposed to 17β-estradiol (E2, as well as the alterations of immune ER mRNA expression levels in sexually mature trout during the reproductive cycle. All four ER isoforms were present in immune organs—head kidney, spleen-and immune cells from head kidney and blood of rainbow trout, but their mRNA levels were substantially lower than in the liver. The ER isoform ratios were tissue- and cell-specific, both within the immune system, but also between the immune system and the liver. Short-term administration of E2 to juvenile female trout altered the ER mRNA levels in the liver, but the ERs of the immune organs and cells were not responsive. Changes of ER gene transcript numbers in immune organs and cells occurred during the reproductive cycle of mature female trout, but the changes in the immune ER profiles differed

Estrogen receptor-alpha-immunoreactive neurons in the periaqueductal gray of the adult ovariectomized female cat

NARCIS (Netherlands)

VanderHorst, Veronique G.J.M.; Meijer, Ellie; Schasfoort, Fabienne C.; Leeuwen, Fred van; Holstege, Gert

1998-01-01

Anatomical and physiological studies in rodent and cat have shown that distinct parts of the midbrain periaqueductal gray (FAG) are important for the estrogen dependent, female reproductive behavior. The present study gives a detailed overview of the estrogen receptor-alpha-immunoreactive (ER-IR)

Absence of ERRalpha in female mice confers resistance to bone loss induced by age or estrogen-deficiency.

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Catherine Teyssier

Full Text Available BACKGROUND: ERRalpha is an orphan member of the nuclear hormone receptor superfamily, which acts as a transcription factor and is involved in various metabolic processes. ERRalpha is also highly expressed in ossification zones during mouse development as well as in human bones and cell lines. Previous data have shown that this receptor up-modulates the expression of osteopontin, which acts as an inhibitor of bone mineralization and whose absence results in resistance to ovariectomy-induced bone loss. Altogether this suggests that ERRalpha may negatively regulate bone mass and could impact on bone fragility that occurs in the absence of estrogens. METHODS/PRINCIPAL FINDINGS: In this report, we have determined the in vivo effect of ERRalpha on bone, using knock-out mice. Relative to wild type animals, female ERRalphaKO bones do not age and are resistant to bone loss induced by estrogen-withdrawal. Strikingly male ERRalphaKO mice are indistinguishable from their wild type counterparts, both at the unchallenged or gonadectomized state. Using primary cell cultures originating from ERRalphaKO bone marrow, we also show that ERRalpha acts as an inhibitor of osteoblast differentiation. CONCLUSION/SIGNIFICANCE: Down-regulating ERRalpha could thus be beneficial against osteoporosis.

[Role played by the adrenal cortex on the luteotrophic action of estrogens during the rat estrus cycle].

Science.gov (United States)

Hassani, M

1978-01-01

Estrogen-induced changes in peripheral blood progesterone concentration have been studied in dexamethasone (DEX) and metopyrone (MET) treated 4-day cyclic female rats. Estradiol benzoate (EB) was injected at 10--11 h on diestrus I and peripheral blood was collected at 16--17 h on diestrus II for progesterone radioimmunoassay. The EB induced-increase in blood progesterone concentration was more pronounced, compared to non-injected females in intact DEX-treated females and in adrenalectomized females treated or not with DEX than in their intact counterparts. The adrenal cortex was then supposed to inhibit the luteotrophic action of EB. When injected for 10--12 days, MET caused an increase in blood progesterone concentration compared to uninjected control animals. No cumulative effects of EB and MET were observed. These results are discussed in the light of knowledge, on the feed-back mechanisms which are involved in the action of estrogen on the pituitary-ovarian-adrenocortical system.

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

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

2011-02-01

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

Specific activity isolation and determination of radioactive Estrogenic Substances in White Clover

International Nuclear Information System (INIS)

Pupiales T, G.; Mejia M, G.

1986-01-01

Due to high number of leguminous that exhibit estrogenic activity, subterranean clover between others, which causes infertility in sheep that eat it. It has been considered that white clover (Trifolium repens, variety Ladino, is an specie of low estrogenic activity, however at Bogota City (Colombia) it has high estrogenic activity and may cause reduction in the dairy cattle fertility. Research done in the IAN (today Ingeominas) over this clover variety, showed that the radioactivity substances presents in the white clover have high activity for stradiol, affecting organs from mouse females; Isoflavonoids from vegetables have an anabolism and utero tropic action; estrogenic activity of clover leaves, was exponentially proportional to the amount of ultraviolet radioactivity, falling upon plants during leaves development stage

Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis.

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Elliot, S J; Berho, M; Korach, K; Doublier, S; Lupia, E; Striker, G E; Karl, M

2007-08-01

Young female mice on a C57Bl/6J (B6) background are considered glomerulosclerosis (GS)-resistant but aging B6 mice develop mild GS. Estrogen deficiency accelerates while estrogen replacement retards GS in young sclerosis-prone oligosyndactyly mutant mice on an ROP background. To explore the effects of sex hormones on glomerular structure and function in the context of gender and genetic background, we studied mice in which the estrogen-receptor (ER) genes alpha- or -beta were deleted (alpha- or betaER knockout (KO)) and crossed into the B6 background. We also studied ovariectomized (Ovx) B6 mice given testosterone. Male and female betaERKO and male alphaERKO mice had no glomerular dysfunction at 9 months of age; however, alphaERKO female mice displayed albuminuria and GS. Ovx prevented glomerular dysfunction in alphaERKO female mice by eliminating endogenous testosterone production while exogenous testosterone induced GS in Ovx B6 mice. Androgen receptor (AR) expression and function was found in microdissected glomeruli and cultured mesangial cells. Testosterone compared to placebo increased both AR expression and TGF-beta1 mRNA levels in glomeruli isolated from female B6 mice. Estrogen deficiency had no deleterious effects on the glomeruli in B6 mice. Our study shows that genetic traits strongly influence the GS-promoting effects of estrogen deficiency while testosterone induces GS in a gender-specific manner.

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

International Nuclear Information System (INIS)

El-Mas, Mahmoud M.; Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

2012-01-01

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

Estrogen receptor beta-selective agonists stimulate calcium oscillations in human and mouse embryonic stem cell-derived neurons.

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Lili Zhang

2010-07-01

Full Text Available Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERalpha and ERbeta on calcium oscillations in neurons derived from human (hES and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERbeta, but not ERalpha. The non-selective ER agonist 17beta-estradiol (E(2 rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERalpha agonist 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyltrisphenol (PPT. In contrast, the selective ERbeta agonists, 2,3-bis(4-Hydroxyphenyl-propionitrile (DPN, MF101, and 2-(3-fluoro-4-hydroxyphenyl-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041 stimulated calcium oscillations similar to E(2. The ERbeta agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERbeta activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERbeta signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds.

In vivo effect of sex steroids on uptake of 3H-leucine by female mouse brain

International Nuclear Information System (INIS)

Seiki, Kanji; Haruki, Yasuo; Imanishi, Yoshio

1978-01-01

In vivo effects of the sex steroids estrogen and progesterone on 3 H-leucine uptake by the brain of mature ovariectomized mice were examined. Animals were divided into three groups: group 1, consisting of control animals treated with sesame oil, group 2, animals treated with estrogen, and group 3, animals first treated with estrogen and then with progesterone. Each group was given a single i.p. injection of 3 H-leucine 2 hr after the last hormonal treatment, and sacrificed 2 hr later. Intensity of the uptake of radiolabeled leucine was measured by counting the number of reduced silver grains over cells in various brain regions using an autoradiographic technique. Group 1 showed a relatively high uptake in the supraoptic nucleus, paraventricular nucleus (PV) and ventromedial nucleus (VM) when compared with that in the remaining hypothalamic nuclei examined. Group 2 showed a significant enhancement of the uptake in all hypothalamic regions except the preoptic periventricular nucleus (PPV) when compared with that in group 1. Group 3 showed enhancement of the uptake in all hypothalamic nuclei when compared with that in group 1. However, only the PV, PPV, VM and periventricular arcuate nucleus revealed a significantly higher uptake than the respective nuclei in group 2. The remaining nuclei showed no change in uptake. Uptake by cells in the ependymal cells and cerebral cortex remained unchanged after hormonal treatment. The present results suggest that in female mice estrogen and estrogen plus progesterone stimulate protein synthesis in most of the hypothalamic nuclei and that the progesterone effect on protein synthesis is greatly influenced by estrogen-priming. (auth.)

Influence of estrogen replacement and aging on the expression of nerve growth factor in the urethra of female rats.

Science.gov (United States)

Zucchi, Eliana V M; Jármy-Di Bella, Zsuzsanna I K; Castro, Rodrigo A; Takano, Claudia C; Simões, Manuel J; Girão, Manoel J B C; Sartori, Marair G F

2012-06-01

To evaluate the expression of nerve growth factor (NGF) in the urethra of adult female rats in different hormonal status using immunohistochemical assay. Forty-eight rats (Rattus norvegicus albinus, Rodentia, Mammalia) from the CEDEME-UNIFESP laboratory animal facility were used in the study. Rats were divided into four groups: group A, 12 non-neutered rats; group B, 12 oophorectomized rats; group C, 12 castrated rats treated with 17β-estradiol for 30 days; and group D, 12 aging rats. Animals were killed by lethal injection and their urethra was removed. NGF expression was evaluated by means of immunohistochemistry using mouse monoclonal primary IgG antibody anti-NGF diluted 1:600, and read under 400× magnification. Digital analysis of the images was done by Imagelab software. The intensity of the dark brown color was used as a measure of NGF cytoplasmatic expression, and was used to quantify the percentage of epithelial and muscular layer cells showing this neurotrophin. After oophorectomy, rats showed a significant increase in NGF expression in the periurethral muscular layer. Compared with oophorectomized rats, NGF expression increased in the epithelial layer and diminished in the periurethral smooth muscle following estrogen administration. In 18-month-old rats, NGF expression was diminished in both epithelial and muscular layers. Hormonal status led to significant differences in NGF protein expression in urethral epithelium and periurethral smooth muscle. Copyright © 2012 Wiley Periodicals, Inc.

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

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

2012-02-01

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

Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

International Nuclear Information System (INIS)

Iwase, Yumiko; Fukata, Hideki; Mori, Chisato

2006-01-01

Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17β-estradiol (E 2 , a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 μM DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 μM E 2 and 25 μM GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at μM level between DES and E 2 on GJIC inhibition was observed, but not between GEN and E 2 . DES and E 2 showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 μM was completely counteracted by ICI 182,780 (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E 2 (10 pM and 20 μM) and GEN (25 μM) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E 2 and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development

Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice.

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Clipperton-Allen, Amy E; Lee, Anna W; Reyes, Anny; Devidze, Nino; Phan, Anna; Pfaff, Donald W; Choleris, Elena

2012-02-28

Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

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Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

2015-03-01

Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. © 2014 International Society for Neurochemistry.

Estrogen effects on angiotensin receptors are modulated by pituitary in female rats

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Douglas, J.G.

1987-01-01

The present studies were designed to test the hypothesis that changes in angiotensin II (ANG II) receptors might modulate the layered target tissue responsiveness accompanying estradiol administration. Estradiol was infused continuously in oophorectomized female rats. Aldosterone was also infused in control and experimental animals to avoid estrogen-induced changes in renin and ANG II. ANG II binding constants were determined in radioreceptor assays. Estradiol increased binding site concentration in adrenal glomerulosa by 76% and decreased binding sites of uterine myometrium and glomeruli by 45 and 24%, respectively. There was an accompanying increase in the affinity of ANG II binding to adrenal glomerulosa and uterine myometrium. Because estrogen is a potent stimulus of prolactin release from the pituitary of rodents, studies were also designed to test the hypothesis that prolactin may mediate some or all of the estrogen-induced effects observed. Hypophysectomy abolished estradiol stimulation of prolactin release and most ANG II receptor changes. Prolactin administration to pituitary intact rats was associated with a 50% increase in receptor density of adrenal glomerulosa simulating estradiol administration. However, the changes in glomeruli and uterine myometrium were opposite in that both tissues also increased receptor density, suggesting that prolactin was not the sole mediator of the estrogen-induced receptor changes. In conclusion, regulation of ANG II receptors in a number of diverse target tissues by estradiol is complex with contributions from estrogens and pituitary factors, which include but do not exclusively involve prolactin

Tamoxifen and ICI 182,780 activate hypothalamic G protein-coupled estrogen receptor 1 to rapidly facilitate lordosis in female rats.

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Long, Nathan; Long, Bertha; Mana, Asma; Le, Dream; Nguyen, Lam; Chokr, Sima; Sinchak, Kevin

2017-03-01

In the female rat, sexual receptivity (lordosis) can be facilitated by sequential activation of estrogen receptor (ER) α and G protein-coupled estrogen receptor 1 (GPER) by estradiol. In the estradiol benzoate (EB) primed ovariectomized (OVX) rat, EB initially binds to ERα in the plasma membrane that complexes with and transactivates metabotropic glutamate receptor 1a to activate β-endorphin neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). This activates MPN μ-opioid receptors (MOP), inhibiting lordosis. Infusion of non-esterified 17β-estradiol into the ARH rapidly reduces MPN MOP activation and facilitates lordosis via GPER. Tamoxifen (TAM) and ICI 182,780 (ICI) are selective estrogen receptor modulators that activate GPER. Therefore, we tested the hypothesis that TAM and ICI rapidly facilitate lordosis via activation of GPER in the ARH. Our first experiment demonstrated that injection of TAM intraperitoneal, or ICI into the lateral ventricle, deactivated MPN MOP and facilitated lordosis in EB-primed rats. We then tested whether TAM and ICI were acting rapidly through a GPER dependent pathway in the ARH. In EB-primed rats, ARH infusion of either TAM or ICI facilitated lordosis and reduced MPN MOP activation within 30min compared to controls. These effects were blocked by pretreatment with the GPER antagonist, G15. Our findings demonstrate that TAM and ICI deactivate MPN MOP and facilitate lordosis in a GPER dependent manner. Thus, TAM and ICI may activate GPER in the CNS to produce estrogenic actions in neural circuits that modulate physiology and behavior. Published by Elsevier Inc.

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

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Kim, Jaekyoon; Tuscher, Jennifer J.; Fortress, Ashley M.

2015-01-01

Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17β-estradiol (E2), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs. PMID:26286657

Flow-injection chemiluminescent determination of estrogen benzoate using the tris(1,10-phenanthroline) ruthenium(II)-permanganate system.

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Ma, Yan; Cao, Wei; Qiao, Shuang; Liu, Wenwen; Yang, Jinghe

2011-01-01

Chemiluminescence (CL) detection for the determination of estrogen benzoate, using the reaction of tris(1,10-phenanthroline)ruthenium(II)-Na(2)SO(3)-permanganate, is described. This method is based on the CL reaction of estrogen benzoate (EB) with acidic potassium permanganate and tris(1,10-phenanthroline)ruthenium(II). The CL intensity is greatly enhanced when Na(2)SO(3) is added. After optimization of the different experimental parameters, a calibration graph for estrogen benzoate is linear in the range 0.05-10 µg/mL. The 3 s limit of detection is 0.024 µg/mL and the relative standard deviation was 1.3% for 1.0 µg/mL estrogen benzoate (n = 11). This proposed method was successfully applied to commercial injection samples and emulsion cosmetics. The mechanism of CL reaction was also studied. Copyright © 2011 John Wiley & Sons, Ltd.

Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats

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Mahó Sándor

2011-07-01

Full Text Available Abstract Background Estrogens exert anti-inflammatory and neuroprotective effects in the brain mainly via estrogen receptors α (ERα and β (ERβ. These receptors are members of the nuclear receptor superfamily of ligand-dependent transcription factors. This study was aimed at the elucidation of the effects of ERα and ERβ agonists on the expression of neuroinflammatory genes in the frontal cortex of aging female rats. Methods To identify estrogen-responsive immunity/inflammation genes, we treated middle-aged, ovariectomized rats with 17β-estradiol (E2, ERα agonist 16α-lactone-estradiol (16α-LE2 and ERβ agonist diarylpropionitrile (DPN, or vehicle by Alzet minipump delivery for 29 days. Then we compared the transcriptomes of the frontal cortex of estrogen-deprived versus ER agonist-treated animals using Affymetrix Rat230 2.0 expression arrays and TaqMan-based quantitative real-time PCR. Microarray and PCR data were evaluated by using Bioconductor packages and the RealTime StatMiner software, respectively. Results Microarray analysis revealed the transcriptional regulation of 21 immunity/inflammation genes by 16α-LE2. The subsequent comparative real-time PCR study analyzed the isotype specific effects of ER agonists on neuroinflammatory genes of primarily glial origin. E2 regulated the expression of sixteen genes, including down-regulation of complement C3 and C4b, Ccl2, Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b, Cd11b, Tlr4 and Tlr9, and up-regulation of defensin Np4 and RatNP-3b, IgG-2a, Il6 and ER gene Esr1. Similar to E2, both 16α-LE2 and DPN evoked up-regulation of defensins, IgG-2a and Il6, and down-regulation of C3 and its receptor Cd11b, Ccl2, RT1-Aw2 and Fcgr2b. Conclusions These findings provide evidence that E2, 16α-LE2 and DPN modulate the expression of neuroinflammatory genes in the frontal cortex of middle-aged female rats via both ERα and ERβ. We propose that ERβ is a promising target to suppress

An Estrogen-Responsive Module in the Ventromedial Hypothalamus Selectively Drives Sex-Specific Activity in Females

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Stephanie M. Correa

2015-01-01

Full Text Available Estrogen-receptor alpha (ERα neurons in the ventrolateral region of the ventromedial hypothalamus (VMHVL control an array of sex-specific responses to maximize reproductive success. In females, these VMHVL neurons are believed to coordinate metabolism and reproduction. However, it remains unknown whether specific neuronal populations control distinct components of this physiological repertoire. Here, we identify a subset of ERα VMHVL neurons that promotes hormone-dependent female locomotion. Activating Nkx2-1-expressing VMHVL neurons via pharmacogenetics elicits a female-specific burst of spontaneous movement, which requires ERα and Tac1 signaling. Disrupting the development of Nkx2-1+ VMHVL neurons results in female-specific obesity, inactivity, and loss of VMHVL neurons coexpressing ERα and Tac1. Unexpectedly, two responses controlled by ERα+ neurons, fertility and brown adipose tissue thermogenesis, are unaffected. We conclude that a dedicated subset of VMHVL neurons marked by ERα, NKX2-1, and Tac1 regulates estrogen-dependent fluctuations in physical activity and constitutes one of several neuroendocrine modules that drive sex-specific responses.

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

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

2017-11-01

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

Role of Estrogen on Prevention of Morphine Addiction in Ovarectomized Female Rats

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A Rafati

2008-04-01

Full Text Available ABSTRACT: Introduction & Objective: Evidence indicates that the biological response and the causes of drug abuse may be different between women and men. These sex differences in drug abuse may be due to socio-cultural factors or biological (hormonal differences. Estrogen is one of the hormones which involves in dopamine release in striatum and nucleus accumbency and also is one of the most important neurotransmitters in central nervous system which has critical role in morphine addiction. So, in this study we survey the role of estrogen on dependency and tendency to morphine in rat as a factor of sex differences in addiction. Materials & Methods: This experimental study was carried out in Yazd University of Medical Sciences. Behavioral changes like morphine craving was evaluated by self-administration as a criterion for tendency and for assessment of dependency. we evaluated withdrawal syndrome sings (e.g. jumping, wet dog shaking, etc in control group (ovarectomized female rats receiving morphine sulfate solution and test group (ovarectomized female rats, pretreated with estradiol benzoate before receiving daily morphine sulfate solution. Data obtained were analyzed by SPSS software, using T-test analysis Results: Results showed that although pretreatment with estradiol in test group might lead to a significant decline in withdrawal syndrome sings in comparison with control group, differences in morphine craving as a criterion for tendency was not significant between the two groups. Conclusion: According to our findings, it seems that estrogen, through central mechanisms and its effect on brain dopaminergic system, reduces the physical dependency to morphine.

Estrogen hormone level of prepubertal female rat treated with Calliandra calothyrsus ethanolic leaf extract

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Setyawati, I.; Wiratmini, N. I.; Narayani, I.

2018-03-01

This research examined the phytoestrogen potential of Calliandra calothyrsus leaf extract in prepubertal female rat (Rattus norvegicus). Sixty weaned female rats (21 days old) were divided into five groups i.e. control (K), negative control which was given 0.5% Na CMC suspension (KN) and treatment groups which were given with C. calothyrsus ethanolic leaf extract doses 25 mg/kg bw (P1), 50 mg/kg bw (P2) and 75 mg/kg bw (P3). The treatment suspension was administered 0.5 mL/rat/day by gavage for 28 days, started at the age of 21st days old. The rats were sacrificed and the blood samples were collected from 4 rats / group at the age of 28th, 42nd and 56th days old, each. The concentration of estrogen hormone levels were measured from blood serum by ELISA kit and were read at 450 nm wavelength with an ELISA Spectrophotometer. Data was analyzed statistically by General Linear Model with 95% of confidence. The result showed that rat’s body weight decreased significantly with the higher doses and the longer the treatment of C. calothyrsus leaf extract due to the anti-nutritive activity of calliandra tannins. The estrogen hormone level was significantly increased at the highest dose. The highest estrogen levels were found in the group of female rats which were given the exctract of 75 mg/kg bw until the age of 42nd days. This results showed that there was a phytoestrogen potential in the C. calothyrsus leaf extract.

Estrogen-dependent efficacy of limb ischemic preconditioning in female rats.

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Pócs, Levente; Janovszky, Ágnes; Garab, Dénes; Terhes, Gabriella; Ocsovszki, Imre; Kaszaki, József; Boros, Mihály; Piffkó, József; Szabó, Andrea

2018-01-01

Our aim was to examine the effects of ischemic preconditioning (IPC) on the local periosteal and systemic inflammatory consequences of hindlimb ischemia-reperfusion (IR) in Sprague-Dawley rats with chronic estrogen deficiency (13 weeks after ovariectomy, OVX) in the presence and absence of chronic 17beta-estradiol supplementation (E2, 20 µg kg -1 , 5 days/week for 5 weeks); sham-operated (non-OVX) animals served as controls. As assessed by intravital fluorescence microscopy, rolling and the firm adhesion of polymorphonuclear neutrophil leukocytes (PMNs) gave similar results in the Sham + IR and OVX + IR groups in the tibial periosteal microcirculation during the 3-h reperfusion period after a 60-min tourniquet ischemia. Postischemic increases in periosteal PMN adhesion and PMN-derived adhesion molecule CD11b expressions, however, were significantly reduced by IPC (two cycles of 10'/10') in Sham animals, but not in OVX animals; neither plasma free radical levels (as measured by chemiluminescence), nor TNF-alpha release was affected by IPC. E2 supplementation in OVX animals restored the IPC-related microcirculatory integrity and PMN-derived CD11b levels, and TNF-alpha and free radical levels were reduced by IPC only with E2. An enhanced estrogen receptor beta expression could also be demonstrated after E2 in the periosteum. Overall, the beneficial periosteal microcirculatory effects of limb IPC are lost in chronic estrogen deficiency, but they can be restored by E2 supplementation. This suggests that the presence of endogenous estrogen is a necessary facilitating factor of the anti-inflammatory protection provided by limb IPC in females. The IPC-independent effects of E2 on inflammatory reactions should also be taken into account in this model. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:97-105, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

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Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

2010-01-01

Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

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Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

2016-10-01

Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Estrogen and voluntary exercise interact to attenuate stress-induced corticosterone release but not anxiety-like behaviors in female rats.

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Jones, Alexis B; Gupton, Rebecca; Curtis, Kathleen S

2016-09-15

The beneficial effects of physical exercise to reduce anxiety and depression and to alleviate stress are increasingly supported in research studies. The role of ovarian hormones in interactions between exercise and anxiety/stress has important implications for women's health, given that women are at increased risk of developing anxiety-related disorders, particularly during and after the menopausal transition. In these experiments, we tested the hypothesis that estrogen enhances the positive impact of exercise on stress responses by investigating the combined effects of exercise and estrogen on anxiety-like behaviors and stress hormone levels in female rats after an acute stressor. Ovariectomized female rats with or without estrogen were given access to running wheels for one or three days of voluntary running immediately after or two days prior to being subjected to restraint stress. We found that voluntary running was not effective at reducing anxiety-like behaviors, whether or not rats were subjected to restraint stress. In contrast, stress-induced elevations of stress hormone levels were attenuated by exercise experience in estrogen-treated rats, but were increased in rats without estrogen. These results suggest that voluntary exercise may be more effective at reducing stress hormone levels if estrogen is present. Additionally, exercise experience, or the distance run, may be important in reducing stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Systematic assessment of microneedle injection into the mouse cornea.

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Matthaei, Mario; Meng, Huan; Bhutto, Imran; Xu, Qingguo; Boelke, Edwin; Hanes, Justin; Jun, Albert S

2012-06-20

Corneal intrastromal injection is an important mode of gene-vector application to subepithelial layers. In a mouse model, this procedure is substantially complicated by the reduced corneal dimensions. Furthermore, it may be difficult to estimate the corneal area reached by the volume of a single injection. This study aimed to investigate intrastromal injections into the mouse cornea using different microneedles and to quantify the effect of injecting varying volumes. A reproducible injection technique is described. Forty eyes of 20 129 Sv/J mice were tested. India ink was intrastromally injected using 30° beveled 33 G needles, tri-surface 25° beveled 35 G needles, or hand-pulled and 25° beveled glass needles. Each eye received a single injection of a volume of 1 or 2 μL. Corneoscleral buttons were fixed and flat mounted for computer-assisted quantification of the affected corneal area. Histological assessment was performed to investigate the intrastromal location of the injected dye. A mean corneal area of 5.0 ± 1.4 mm(2) (mean ± SD) and 7.7 ± 1.4 mm(2) was covered by intrastromal injections of 1 and 2 μL, respectively. The mean percentage of total corneal area reached ranged from 39% to 53% for 1 μL injections, and from 65% to 81% for 2 μL injections. Injections using the 33 G needles tended to provide the highest distribution area. Perforation rates were 8% for 30° beveled 33 G needles and 44% for tri-surface beveled 35 G needles. No perforation was observed with glass needle; however, intrastromal breakage of needle tips was noted in 25% of these cases. Intracorneal injection using a 30° beveled 33 G needle was safe and effective. The use of tri-surface beveled 35 G needles substantially increased the number of corneal perforations. Glass needles may break inside the corneal stroma. Injections of 1 μL and 2 μL resulted in an overall mean of 49% and 73% respectively of total corneal area involved.

Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

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Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

2009-02-11

Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

Role of estrogen in lung cancer based on the estrogen receptor-epithelial mesenchymal transduction signaling pathways

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Zhao XZ

2015-10-01

Full Text Available Xiao-zhen Zhao,1,* Yu Liu,1,* Li-juan Zhou,1,* Zhong-qi Wang,1 Zhong-hua Wu,2 Xiao-yuan Yang31Department of Tumor, Longhua Hospital, 2Center of Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA*These authors contributed equally to this workBackground/aim: Estrogen is reported to promote the occurrence and development of several human cancers. Increasing evidence shows that most human lung tumors exert estrogen receptor expression. In the present study, we investigated the underlying mechanism of estrogen effect in lung cancer through estrogen receptor-epithelial–mesechymal-transition signaling pathways for the first time.Materials and methods: A total of 36 inbred C57BL/6 mice (18 male and 18 female were injected subcutaneously with human lung adenocarcinoma cell line, Lewis. After the lung tumor model was established, mice with lung adenocarcinoma were randomly divided into three groups for each sex (n=6, such as vehicle group, estrogen group, and estrogen plus tamoxifen group. The six groups of mice were sacrificed after 21 days of drug treatment. Tumor tissue was stripped and weighed, and tumor inhibition rate was calculated based on average tumor weight. Protein and messenger RNA (mRNA expressions of estrogen receptor α (ERα, estrogen receptor β (ERβ, phosphatidylinositol 3'-kinase (PI3K, AKT, E-cadherin, and vimentin were detected in both tumor tissue and lung tissue by using immunohistochemistry and real-time reverse transcription-polymerase chain reaction.Results: 1 For male mice: in the estrogen group, estrogen treatment significantly increased ERα protein and mRNA expressions in tumor tissue and protein expression of PI3K, AKT, and vimentin in both tumor tissue and lung tissue compared with the vehicle-treated group. Besides, m

Estrogen receptor-α mediates the detrimental effects of neonatal diethylstilbestrol (DES) exposure in the murine reproductive tract

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Couse, John F.; Korach, Kenneth S.

2004-01-01

It is generally believed that estrogen receptor-dependent and -independent pathways are involved in mediating the developmental effects of the synthetic estrogen, diethylstilbestrol (DES). However, the precise role and extent to which each pathway contributes to the resulting pathologies remains unknown. We have employed the estrogen receptor knockout (ERKO) mice, which lack either estrogen receptor-α (αERKO or estrogen receptor-β (βERKO), to gain insight into the contribution of each ER-dependent pathway in mediating the effects of neonatal DES exposure in the female and male reproductive tract tissues of the mouse. Estrogen receptor-α female mice exhibited complete resistance to the chronic effects of neonatal DES exposure that were obvious in exposed wild-type animals, including atrophy and epithelial squamous metaplasia in the uterus; proliferative lesions of the oviduct; and persistent cornification of the vaginal epithelium. DES-mediated reduction in uterine Hoxa10, Hoxa11 and Wnt7a expression that occurs wild-type females during the time of exposure was also absent in αERKO females. In the male, αERKO mice exhibited complete resistance to the chronic effects of neonatal DES exposure on the prostate, including decreased androgen receptor levels, epithelial hyperplasia, and increased basal cell proliferation. Although ERβ is highly expressed in the prostate epithelium, DES-exposed βERKO males exhibited all of the effects of neonatal DES exposure that were observed in similarly exposed wild-type males. Therefore, the lack of DES-effects on gene expression and tissue differentiation in the αERKO uterus and prostate provides unequivocal evidence of an obligatory role for ERα in mediating the detrimental actions of neonatal DES exposure in the murine reproductive tract

Combination of Estrogen and Immunosuppressive Agents to Establish a Mouse Model of Candidiasis with Concurrent Oral and Vaginal Mucosal Infection.

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Wang, Le; Wang, Chong; Mei, Huan; Shen, Yongnian; Lv, Guixia; Zeng, Rong; Zhan, Ping; Li, Dongmei; Liu, Weida

2016-02-01

Mouse model is an appropriate tool for pathogenic determination and study of host defenses during the fungal infection. Here, we established a mouse model of candidiasis with concurrent oral and vaginal mucosal infection. Two C. albicans strains sourced from clinical candidemia (SC5314) and mucosal infection (ATCC62342) were tested in ICR mice. The different combinational panels covering estrogen and immunosuppressive agents, cortisone, prednisolone and cyclophosphamide were used for concurrent oral and vaginal candidiasis establishment. Prednisolone in combination with estrogen proved an optimal mode for concurrent mucosal infection establishment. The model maintained for 1 week with fungal burden reached at least 10(5) cfu/g of tissue. This mouse model was evaluated by in vivo pharmacodynamics of fluconazole and host mucosal immunity of IL-17 and IL-23. Mice infected by SC5314 were cured by fluconazole. An increase in IL-23 in both oral and vaginal homogenates was observed after infection, while IL-17 only had a prominent elevation in oral tissue. This model could properly mimic complicated clinical conditions and provides a valuable means for antifungal assay in vivo and may also provide a useful method for the evaluation of host-fungal interactions.

Effects of x irradiation on estrogen-induced synthetic processes of the avian liver

International Nuclear Information System (INIS)

Holshouser, S.J.; Schjeide, O.A.; Briles, W.E.

1975-01-01

Effects of x irradiation on protein and lipid synthesis were studied, using estrogen-induced yolk protein syntheses by the avian liver as a test model. Female chickens, receiving a single sublethal whole-body exposure of 600 R of x irradiation at 5 wk of age, laid fewer and smaller eggs upon reaching maturity as compared to nonirradiated controls. However, chemical contents and ultracentrifuge patterns of yolk proteins were not found to be qualitatively different. Accordingly, the synthesis of no one major yolk protein appeared to be selectively inhibited by exposure of the bird to irradiation. Injection of Estrogenic Substances into hens over a period of 3 days resulted in a much greater enlargement of livers in control estrogenized birds than in irradiated estrogenized birds. Differences were also ascertained to exist between control and irradiated birds in terms of total liver RNA. This would seem to indicate a greater potential for synthesis of serum yolk protein precursors in nonirradiated estrogenized hens. (U.S.)

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice

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Anchan, Divya; Clark, Sara; Pollard, Kevin; Vasudevan, Nandini

2014-01-01

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17beta estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improv...

Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

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Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

2009-01-01

Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

Systematic assessment of microneedle injection into the mouse cornea

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Matthaei Mario

2012-06-01

Full Text Available Abstract Background Corneal intrastromal injection is an important mode of gene-vector application to subepithelial layers. In a mouse model, this procedure is substantially complicated by the reduced corneal dimensions. Furthermore, it may be difficult to estimate the corneal area reached by the volume of a single injection. This study aimed to investigate intrastromal injections into the mouse cornea using different microneedles and to quantify the effect of injecting varying volumes. A reproducible injection technique is described. Methods Forty eyes of 20 129 Sv/J mice were tested. India ink was intrastromally injected using 30° beveled 33 G needles, tri-surface 25° beveled 35 G needles, or hand-pulled and 25° beveled glass needles. Each eye received a single injection of a volume of 1 or 2 μL. Corneoscleral buttons were fixed and flat mounted for computer-assisted quantification of the affected corneal area. Histological assessment was performed to investigate the intrastromal location of the injected dye. Results A mean corneal area of 5.0 ±1.4 mm2 (mean ± SD and 7.7 ±1.4 mm2 was covered by intrastromal injections of 1 and 2 μL, respectively. The mean percentage of total corneal area reached ranged from 39% to 53% for 1 μL injections, and from 65% to 81% for 2 μL injections. Injections using the 33 G needles tended to provide the highest distribution area. Perforation rates were 8% for 30° beveled 33 G needles and 44% for tri-surface beveled 35 G needles. No perforation was observed with glass needle; however, intrastromal breakage of needle tips was noted in 25% of these cases. Conclusions Intracorneal injection using a 30° beveled 33 G needle was safe and effective. The use of tri-surface beveled 35 G needles substantially increased the number of corneal perforations. Glass needles may break inside the corneal stroma. Injections of 1 μL and 2 μL resulted in an overall mean of 49% and 73% respectively

How to make a sexy snake: estrogen activation of female sex pheromone in male red-sided garter snakes.

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Parker, M Rockwell; Mason, Robert T

2012-03-01

Vertebrates indicate their genetic sex to conspecifics using secondary sexual signals, and signal expression is often activated by sex hormones. Among vertebrate signaling modalities, the least is known about how hormones influence chemical signaling. Our study species, the red-sided garter snake (Thamnophis sirtalis parietalis), is a model vertebrate for studying hormonal control of chemical signals because males completely rely on the female sex pheromone to identify potential mates among thousands of individuals. How sex hormones can influence the expression of this crucial sexual signal is largely unknown. We created two groups of experimental males for the first experiment: Sham (blank implants) and E2 (17β-estradiol implants). E2 males were vigorously courted by wild males in outdoor bioassays, and in a Y-maze E2 pheromone trails were chosen by wild males over those of small females and were indistinguishable from large female trails. Biochemically, the E2 pheromone blend was similar to that of large females, and it differed significantly from Shams. For the second experiment, we implanted males with 17β-estradiol in 2007 but removed the implants the following year (2008; Removal). That same year, we implanted a new group of males with estrogen implants (Implant). Removal males were courted by wild males in 2008 (implant intact) but not in 2009 (removed). Total pheromone quantity and quality increased following estrogen treatment, and estrogen removal re-established male-typical pheromone blends. Thus, we have shown that estrogen activates the production of female pheromone in adult red-sided garter snakes. This is the first known study to quantify both behavioral and biochemical responses in chemical signaling following sex steroid treatment of reptiles in the activation/organization context. We propose that the homogametic sex (ZZ, male) may possess the same targets for activation of sexual signal production, and the absence of the activator (17�

Male-like sexual behavior of female mouse lacking fucose mutarotase

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Lim Dae-sik

2010-07-01

Full Text Available Abstract Background Mutarotases are recently characterized family of enzymes that are involved in the anomeric conversions of monosaccharides. The mammalian fucose mutarotase (FucM was reported in cultured cells to facilitate fucose utilization and incorporation into protein by glycosylation. However, the role of this enzyme in animal has not been elucidated. Results We generated a mutant mouse specifically lacking the fucose mutarotase (FucM gene. The FucM knockout mice displayed an abnormal sexual receptivity with a drastic reduction in lordosis score, although the animals were fertile due to a rare and forced intromission by a typical male. We examined the anteroventral periventricular nucleus (AVPv of the preoptic region in brain and found that the mutant females showed a reduction in tyrosine hydoxylase positive neurons compared to that of a normal female. Furthermore, the mutant females exhibited a masculine behavior, such as mounting to a normal female partner as well as showing a preference to female urine. We found a reduction of fucosylated serum alpha-fetoprotein (AFP in a mutant embryo relative to that of a wild-type embryo. Conclusions The observation that FucM-/- female mouse exhibits a phenotypic similarity to a wild-type male in terms of its sexual behavior appears to be due to the neurodevelopmental changes in preoptic area of mutant brain resembling a wild-type male. Since the previous studies indicate that AFP plays a role in titrating estradiol that are required to consolidate sexual preference of female mice, we speculate that the reduced level of AFP in FucM-/- mouse, presumably resulting from the reduced fucosylation, is responsible for the male-like sexual behavior observed in the FucM knock-out mouse.

Distribution of [35S] taurine in mouse retina after intravitreal and intravascular injection

International Nuclear Information System (INIS)

Pourcho, R.G.

1977-01-01

The distribution of [ 35 S] taurine in mouse retinae was studied by autoradiographic techniques after either intravitreal or intravascular injection. The route of injection did not affect the final localization. The major sites of label accumulation were the outer nuclear layer, the inner nuclear layer, and Mueller cell processes adjacent to the vitreal surface. The distribution was consistent with the interpretation that taurine was localized within two cellular compartments of mouse retina, photoreceptor cells and Mueller cells. (author)

Estrogen and progesterone receptor assay using I-125 estradiol and H-3 promegestone as ligands: Results in female mammary carcinoma

International Nuclear Information System (INIS)

Glaubitt, D.; Hienz, H.A.; Bettges, G.; Carmanns, B.; Lichtenberg, T.; Akademisches Lehrkrankenhaus, Krefeld

1984-01-01

The determination of estrogen and progesterone receptors in the cytosol of carcinoma of the female breast has predictive value as to the success treatment of the patient. An improved estrogen and progesterone receptor assay using 1-125 labelled estradiol and a H-3 tagged synthetic gestagen (H-3 promegestone) as ligands proved to be highly praticable, especially time-saving. (orig.)

Dopamine activates masculine sexual behavior independent of the estrogen receptor alpha.

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Wersinger, S R; Rissman, E F

2000-06-01

Estrogen receptor alpha (ERalpha) is believed to be a critical part of the regulatory processes involved in normal reproduction and sexual behavior. However, in this study we show the ERalpha is not required for display of masculine sexual behavior. Male and female, ERalpha knock-out (ERalphaKO) and wild-type mice were gonadectomized and implanted with testosterone. Sexual behavior and social preferences were tested after injection of the dopamine agonist, apomorphine (APO), or vehicle. All wild-type mice showed normal masculine behavior, including mounts and pelvic thrusts in females, and ejaculation in males. In agreement with past reports, ERalphaKO mice, given vehicle, failed to show mating behavior. Yet, ERalphaKO males given APO showed masculine copulatory behavior and chemoinvestigatory behavior directed at females. ERalphaKO females, treated with APO, mounted and thrusted when tested with receptive females. HPLC revealed that wild-type and ERalphaKO mice had equivalent catecholamine content in brain regions associated with masculine sexual behavior. These data show that the ERalpha is not essential during development or adulthood for the expression of masculine sexual behavior in mice. Moreover, dopamine can activate sexual behavior via a mechanism that either acts on an ER other than ERalpha or via an estrogen-independent pathway.

A self-reconfiguring metamorphic nanoinjector for injection into mouse zygotes

International Nuclear Information System (INIS)

Aten, Quentin T.; Jensen, Brian D.; Howell, Larry L.; Burnett, Sandra H.

2014-01-01

This paper presents a surface-micromachined microelectromechanical system nanoinjector designed to inject DNA into mouse zygotes which are ≈90 μm in diameter. The proposed injection method requires that an electrically charged, DNA coated lance be inserted into the mouse zygote. The nanoinjector's principal design requirements are (1) it must penetrate the lance into the mouse zygote without tearing the cell membranes and (2) maintain electrical connectivity between the lance and a stationary bond pad. These requirements are satisfied through a two-phase, self-reconfiguring metamorphic mechanism. In the first motion subphase a change-point six-bar mechanism elevates the lance to ≈45 μm above the substrate. In the second motion subphase, a compliant folded-beam suspension allows the lance to translate in-plane at a constant height as it penetrates the cell membranes. The viability of embryos following nanoinjection is presented as a metric for quantifying how well the nanoinjector mechanism fulfills its design requirements of penetrating the zygote without causing membrane damage. Viability studies of nearly 3000 nanoinjections resulted in 71.9% of nanoinjected zygotes progressing to the two-cell stage compared to 79.6% of untreated embryos

Role of progesterone and estrogen in the preparation of the uterus and induction of implantation in the mouse

Energy Technology Data Exchange (ETDEWEB)

Huet-Hudson, Y.M.

1989-01-01

The implantation of the embryo into the uterine wall and subsequent decidualization of the uterine endometrium requires ovarian progesterone and estrogen. Prerequisites for implantation include (1) the preparation of the uterus for embryo implantation and (2) increase stromal capillary permeability at the site of embryo attachment. During the first three days of pregnancy, epithelial cells undergo proliferation, death and differentiation, in response to preovaluatory estrogen. These events occur in stromal cells in response to progesterone on days 4 and 5. The mechanism by which the steroid hormones modulate their functions and how estrogen initiates implantation in a progesterone-primed (P{sub 4}) uterus in not clearly understood. The author shows that 24h of P{sub 4}-priming is adequate for induction of implantation in the mouse. In addition, following this initial exposure of the uterus to P{sub 4} a long lasting effect is induced i.e. 24h of priming is no longer required for the induction of implantation. The uterine cell proliferation and differentiation that occurs in response to steroid hormones could be through their modulation of the expression of proto-oncogenes and growth factors. Results show that the proto-oncogene, c-myc and the growth factor, EGF are expressed in a cell-type specific manner in the uterus and are regulated by P{sub 4} and estrogen in a spatial and temporal manner during early pregnancy. It is apparent that c-myc protein in epithelia is primarily regulated by estrogen, while in the stroma by P{sub 4}. {sup 3}H-thymidine incorporation in specific uterine cell-types correlated with expression of the c-myc protein. On the other hand, EGF is always localized to the epithelia and is primarily regulated by estrogen.

Male risk taking, female odors, and the role of estrogen receptors.

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Kavaliers, Martin; Clipperton-Allen, Amy; Cragg, Cheryl L; Gustafsson, Jan-Åke; Korach, Kenneth S; Muglia, Louis; Choleris, Elena

2012-12-05

Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted 'knock-out' ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered. Copyright © 2012 Elsevier Inc. All rights reserved.

Urethral dysfunction in female mice with estrogen receptor β deficiency.

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Yung-Hsiang Chen

Full Text Available Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI. Wild-type (ERβ(+/+ and knockout (ERβ(-/- female mice were generated (aged 6-8 weeks, n = 6 and urethral function and protein expression were measured. Leak point pressures (LPP and maximum urethral closure pressure (MUCP were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography-mass spectrometry (LC-MS/MS analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ERβ(+/+ group, the LPP and MUCP values of the ERβ(-/- group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ(-/- female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ERβ(-/- mice. This study is the first study to estimate protein expression changes in urethras from ERβ(-/- female mice. These changes could be related to the molecular mechanism of ERβ in SUI.

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-09-15

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

A-C Estrogens as Potent and Selective Estrogen Receptor-Beta Agonists (SERBAs) to Enhance Memory Consolidation under Low-Estrogen Conditions.

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Hanson, Alicia M; Perera, K L Iresha Sampathi; Kim, Jaekyoon; Pandey, Rajesh K; Sweeney, Noreena; Lu, Xingyun; Imhoff, Andrea; Mackinnon, Alexander Craig; Wargolet, Adam J; Van Hart, Rochelle M; Frick, Karyn M; Donaldson, William A; Sem, Daniel S

2018-06-04

Estrogen receptor-beta (ERβ) is a drug target for memory consolidation in postmenopausal women. Herein is reported a series of potent and selective ERβ agonists (SERBAs) with in vivo efficacy that are A-C estrogens, lacking the B and D estrogen rings. The most potent and selective A-C estrogen is selective for activating ER relative to seven other nuclear hormone receptors, with a surprising 750-fold selectivity for the β over α isoform and with EC 50 s of 20-30 nM in cell-based and direct binding assays. Comparison of potency in different assays suggests that the ER isoform selectivity is related to the compound's ability to drive the productive conformational change needed to activate transcription. The compound also shows in vivo efficacy after microinfusion into the dorsal hippocampus and after intraperitoneal injection (0.5 mg/kg) or oral gavage (0.5 mg/kg). This simple yet novel A-C estrogen is selective, brain penetrant, and facilitates memory consolidation.

Estrogen-mediated hemangioma-derived stem cells through estrogen receptor-α for infantile hemangioma

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Zhang L

2017-07-01

Full Text Available Ling Zhang,1 Hai Wei Wu,1 Weien Yuan,2 Jia Wei Zheng1 1Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Background: Infantile hemangiomas (IHs are the most common benign vascular tumor of infancy. They occur more frequently in female infants. The cause of hemangioma is currently unknown; however, current studies suggested the importance of estrogen (E2 signaling in hemangioma proliferation. Methods: Hemangioma-derived stem cells (HemSCs were cultured with estrogen for 48–72 h; the cell viability and proliferation were evaluated with the messenger RNA (mRNA and protein expression levels of fibroblast growth factor 2 (FGF2, vascular endothelial growth factor-A (VEGF-A and estrogen receptor-α (ER-α, by application of several in vitro assays, such as methyl thiazolyl tetrazolium (MTT, reverse transcriptase–polymerase chain reaction (RT-PCR, real-time PCR, enzyme-linked immunosorbent assay (ELISA and Western blotting. Also, the cell population’s response to external estrogen was investigated by in vivo experiments. HemSCs and human umbilical vein endothelial cells (HUVECs were mixed and injected subcutaneously into 20 flank of BALB/c-nu mice, which were randomly divided into 5 groups based on different E2 treatment doses (0, 0.01, 0.1 and 1 mg, respectively, 0.1 mg dimethyl sulfoxide (DMSO as control. Each group of mice were treated intramuscularly every week, then 2 and 4 weeks later, the subcutaneous implants were harvested and evaluated the tumor tissues with microvessel density (MVD assay and immunohistochemistry. Results: The study demonstrated that application of E2 increased the expression of FGF2, VEGF-A, and ER-α in HemSCs with the optimal concentration from 10−9 to 10−5 M. Two

Female presence and estrous state influence mouse ultrasonic courtship vocalizations.

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Jessica L Hanson

Full Text Available The laboratory mouse is an emerging model for context-dependent vocal signaling and reception. Mouse ultrasonic vocalizations are robustly produced in social contexts. In adults, male vocalization during courtship has become a model of interest for signal-receiver interactions. These vocalizations can be grouped into syllable types that are consistently produced by different subspecies and strains of mice. Vocalizations are unique to individuals, vary across development, and depend on social housing conditions. The behavioral significance of different syllable types, including the contexts in which different vocalizations are made and the responses listeners have to different types of vocalizations, is not well understood. We examined the effect of female presence and estrous state on male vocalizations by exploring the use of syllable types and the parameters of syllables during courtship. We also explored correlations between vocalizations and other behaviors. These experimental manipulations produced four main findings: 1 vocalizations varied among males, 2 the production of USVs and an increase in the use of a specific syllable type were temporally related to mounting behavior, 3 the frequency (kHz, bandwidth, and duration of syllables produced by males were influenced by the estrous phase of female partners, and 4 syllable types changed when females were removed. These findings show that mouse ultrasonic courtship vocalizations are sensitive to changes in female phase and presence, further demonstrating the context-sensitivity of these calls.

Levels of estrogen, carcinoembryonic antigen and cancer antigen of breast in Sudanese female with breast cancer

International Nuclear Information System (INIS)

Abdelhadi, H. A.; Sirelkhatim, D. A.; Eltayeb, E. A.; Ahmed, W. A.; Elhussein, B.

2006-12-01

This study was conducted during the period from february 2004 to july 2004; with the objective of measuring the levels of estrogen (E2), carcinoembryonic antigen (CEA) and cancer antigen of breast (CA-15.3) so as to facilitate the early diagnosis of breast cancer and to determine the involvement of these parameters as risk factors for breast cancer. Ninety blood samples were collected from Sudanese females, divided into two groups; control group and patients groups. The patients group was sixty Sudanese females visiting the Radio Isotope Center, Khartoum (RICK) and they were confirmed as breast cancer patients by histopathology. The levels of the above mentioned parameters were determined by using radioimmunoassay technique. The results showed that , no significant (P=0.05) difference between the levels of the estrogen in patients compared to the control, on the other hand, there was non-significant (p<0.05) elevation in CEA levels in the patients with breast cancer compared to the control. The levels of CA 15.3 was significantly (p<0.0001) higher in the breast cancer patients compared to the control.(Author)

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

International Nuclear Information System (INIS)

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

1988-01-01

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

JMJD3 Is Crucial for the Female AVPV RIP-Cre Neuron-Controlled Kisspeptin-Estrogen Feedback Loop and Reproductive Function.

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Song, Anying; Jiang, Shujun; Wang, Qinghua; Zou, Jianghuan; Lin, Zhaoyu; Gao, Xiang

2017-06-01

The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. Although most studies have focused on the hierarchy from the brain to the gonad, many questions remain unresolved concerning the feedback from the gonad to the central nervous system, especially regarding the potential epigenetic modifications in hypothalamic neurons. In the present report, we generated genetically modified mice lacking histone H3 lysine 27 (H3K27) demethylase Jumonji domain-containing 3 (JMJD3) in hypothalamic rat-insulin-promoter-expressing neurons (RIP-Cre neurons). The female mutant mice displayed late-onset obesity owing to reduced locomotor activity and decreased energy expenditure. JMJD3 deficiency in RIP-Cre neurons also results in delayed pubertal onset, an irregular estrous cycle, impaired fertility, and accelerated ovarian failure in female mice owing to the dysregulation of the hypothalamic-ovarian axis. We found that JMJD3 directly regulates Kiss1 gene expression by binding to the Kiss1 promoter and triggering H3K27me3 demethylation in the anteroventral periventricular (AVPV) nucleus. Further study confirmed that the aberrations arose from impaired kisspeptin signaling in the hypothalamic AVPV nucleus and subsequent estrogen deficiency. Estrogen replacement therapy can reverse obesity in mutant mice. Moreover, we demonstrated that Jmjd3 is an estrogen target gene in the hypothalamus. These results provide direct genetic and molecular evidence that JMJD3 is a key mediator for the kisspeptin-estrogen feedback loop. Copyright © 2017 Endocrine Society.

Contribution of Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells to Chimeras through Injection and Coculture of Embryos

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Guo, Jitong; Wu, Baojiang; Li, Shuyu; Bao, Siqin; Zhao, Lixia; Hu, Shuxiang; Sun, Wei; Su, Jie; Dai, Yanfeng; Li, Xihe

2014-01-01

Blastocyst injection and morula aggregation are commonly used to evaluate stem cell pluripotency based on chimeric contribution of the stem cells. To assess the protocols for generating chimeras from stem cells, 8-cell mouse embryos were either injected or cocultured with mouse embryonic stem cells and induced pluripotent stem cells, respectively. Although a significantly higher chimera rate resulted from blastocyst injection, the highest germline contribution resulted from injection of 8-cel...

Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model

Directory of Open Access Journals (Sweden)

Park Seung S

2012-12-01

Full Text Available Abstract Background Advancing female age remains a difficult problem in infertility treatment. Ovarian angiogenesis plays an important role in follicular development and the activation of ovarian angiogenesis has been emerged as a new strategy for the improvement of age-related decline of oocyte quality. BMP-6 affect gonadotropin signals in granulosa cells and it promotes normal fertility by enabling appropriate response to LH and normal oocyte quality. BMP-6 has a potential role in regulation of angiogenesis and regulates the expression of inhibitor of DNA-binding proteins (Ids. Ids involved in the control and timing of follicle selection and granulosa cells differentiation. Especially, Id-1 is well-characterized target of BMP-6 signaling. Therefore, this study investigated whether co-administration of BMP-6 during superovulation process improves ovarian response, oocyte quality and expression of Id-1 and vascular endothelial growth factor (VEGF in the ovary of aged female using a mouse model. Methods Aged C57BL/6 female mice (26–31 weeks old were superovulated by injection with 0.1 mL of 5 IU equine chorionic gonadotropin (eCG containing recombinant mouse BMP-6 at various doses (0, 0.01, 0.1, 1, and 10 ng, followed by injection with 5 IU human chorionic gonadotropin (hCG 48 h later. Then, the mice were immediately paired with an individual male. The aged control group was superovulated without BMP-6. Young mice of 6–9 weeks old were superovulated without BMP-6 as a positive control for superovulation and in vitro culture of embryos. Eighteen hours after hCG injection, zygotes were retrieved and cultured for 4 days. Both ovaries of each mouse were provided in the examination of ovarian expression of Id-1 and VEGF by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry. Results Administration of 0.1 ng BMP-6 significantly increased the number and blastocyst formation rate of oocytes ovulated and ovarian

Estrogen receptor-independent catechol estrogen binding activity: protein binding studies in wild-type, Estrogen receptor-alpha KO, and aromatase KO mice tissues.

Science.gov (United States)

Philips, Brian J; Ansell, Pete J; Newton, Leslie G; Harada, Nobuhiro; Honda, Shin-Ichiro; Ganjam, Venkataseshu K; Rottinghaus, George E; Welshons, Wade V; Lubahn, Dennis B

2004-06-01

Primary evidence for novel estrogen signaling pathways is based upon well-documented estrogenic responses not inhibited by estrogen receptor antagonists. In addition to 17beta-E2, the catechol estrogen 4-hydroxyestradiol (4OHE2) has been shown to elicit biological responses independent of classical estrogen receptors in estrogen receptor-alpha knockout (ERalphaKO) mice. Consequently, our research was designed to biochemically characterize the protein(s) that could be mediating the biological effects of catechol estrogens using enzymatically synthesized, radiolabeled 4-hydroxyestrone (4OHE1) and 4OHE2. Scatchard analyses identified a single class of high-affinity (K(d) approximately 1.6 nM), saturable cytosolic binding sites in several ERalphaKO estrogen-responsive tissues. Specific catechol estrogen binding was competitively inhibited by unlabeled catechol estrogens, but not by 17beta-E2 or the estrogen receptor antagonist ICI 182,780. Tissue distribution studies indicated significant binding differences both within and among various tissues in wild-type, ERalphaKO, and aromatase knockout female mice. Ligand metabolism experiments revealed extensive metabolism of labeled catechol estrogen, suggesting that catechol estrogen metabolites were responsible for the specific binding. Collectively, our data provide compelling evidence for the interaction of catechol estrogen metabolites with a novel binding protein that exhibits high affinity, specificity, and selective tissue distribution. The extensive biochemical characterization of this binding protein indicates that this protein may be a receptor, and thus may mediate ERalpha/beta-independent effects of catechol estrogens and their metabolites.

Sex Steroid Hormones Matter for Learning and Memory: Estrogenic Regulation of Hippocampal Function Inmale and Female Rodents

Science.gov (United States)

Frick, Karyn M.; Kim, Jaekyoon; Tuscher, Jennifer J.; Fortress, Ashley M.

2015-01-01

Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17ß-estradiol (E[subscript 2]), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes…

Wnt16 Is Associated with Age-Related Bone Loss and Estrogen Withdrawal in Murine Bone.

Directory of Open Access Journals (Sweden)

Henry Todd

Full Text Available Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, bone strength and ultimately fracture risk. Wnt16 acts on osteoblasts and osteoclasts and, in cortical bone, is predominantly derived from osteoblasts. This led us to hypothesize that low bone mass would be associated with low levels of Wnt16 expression and that Wnt16 expression would be increased by anabolic factors, including mechanical loading. We therefore investigated Wnt16 expression in the context of ageing, mechanical loading and unloading, estrogen deficiency and replacement, and estrogen receptor α (ERα depletion. Quantitative real time PCR showed that Wnt16 mRNA expression was lower in cortical bone and marrow of aged compared to young female mice. Neither increased nor decreased (by disuse mechanical loading altered Wnt16 expression in young female mice, although Wnt16 expression was decreased following ovariectomy. Both 17β-estradiol and the Selective Estrogen Receptor Modulator Tamoxifen increased Wnt16 expression relative to ovariectomy. Wnt16 and ERβ expression were increased in female ERα-/- mice when compared to Wild Type. We also addressed potential effects of gender on Wnt16 expression and while the expression was lower in the cortical bone of aged males as in females, it was higher in male bone marrow of aged mice compared to young. In the kidney, which we used as a non-bone reference tissue, Wnt16 expression was unaffected by age in either males or females. In summary, age, and its associated bone loss, is associated with low levels of Wnt16 expression whereas bone loss associated with disuse has no effect on Wnt16 expression. In the artificially loaded mouse tibia we observed no loading-related up-regulation of Wnt16 expression but provide evidence that its expression is influenced by estrogen receptor signaling. These findings suggest that while Wnt16 is not an

Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

Science.gov (United States)

Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

2017-10-15

Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

Estrogenic and anti-androgenic activities of 4-nitrophenol in diesel exhaust particles

International Nuclear Information System (INIS)

Li Chunmei; Taneda, Shinji; Suzuki, Akira K.; Furuta, Chie; Watanabe, Gen; Taya, Kazuyoshi

2006-01-01

A 4-nitrophenol (PNP) isolated from diesel exhaust particles (DEP) has been identified as a vasodilator. PNP is also a known degradation product of the insecticide parathion. We used uterotrophic and Hershberger assays to study the estrogenic and anti-androgenic activities of PNP in-vivo. In ovariectomized immature female rats injected subcutaneously with 1, 10, or 100 mg/kg PNP daily for 7 days, significant (P < 0.05) increases in uterine weight were seen in only those receiving 10 or 100 mg/kg PNP. Furthermore, in castrated immature male rats implanted with a silastic tube (length, 5 mm) containing crystalline testosterone and injected subcutaneously with 0.01, 0.1, or 1 mg/kg PNP daily for 5 days, those receiving the doses of 0.1 mg/kg showed significant (P < 0.05) weight decreases in seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscles, and glans penis. Plasma FSH and LH levels did not change in female rats but were significantly (P < 0.05) increased in male rats treated with 0.1 mg/kg PNP. These results clearly demonstrated that PNP has estrogenic and anti-androgenic activities in-vivo. Our results therefore suggest that diesel exhaust emissions and the degradation of parathion can lead to accumulation of PNP in air, water, and soil and thus could have serious deleterious effects on wildlife and human health

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-09-15

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

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin administration and high-fat diet on the body weight and hepatic estrogen metabolism in female C3H/HeN mice

International Nuclear Information System (INIS)

Zhu Baoting; Gallo, Michael A.; Burger, Conney W.; Meeker, Robert J.; Cai, May Xiaoxin; Xu Shiyao; Conney, Allan H.

2008-01-01

We studied the effect of administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by i.p. injection once every 2 weeks in combination with a high-fat (HF) diet for 8 or 16 weeks on the body and organ weight changes as well as on the hepatic enzyme activity for estrogen metabolism in C3H/HeN female mice. Administration of TCDD at 100 μg/kg b.w. once every 2 weeks for 8 weeks increased the body weight by 46% in the HF diet-fed animals, but not in the regular diet-fed animals. This is the first observation suggesting that TCDD at a high dose (100 μg/kg b.w.), but not at lower doses (1 or 10 μg/kg b.w.), may have a strong obesity-inducing effect in C3H/HeN mice fed an HF diet. While TCDD increased liver weight and decreased thymus weight in animals, these effects were enhanced by feeding animals an HF diet. Metabolism studies showed that TCDD administration for 8 or 16 weeks increased the liver microsomal activity for the 2- and 4-hydroxylation of 17β-estradiol in animals fed a control diet, but surprisingly not in animals fed an HF diet. Treatment with TCDD dose-dependently increased the hepatic activity for the O-methylation of catechol estrogens in both control and HF diet-fed animals, and it also decreased the levels of liver microsomal sulfatase activity for hydrolysis of estrone-3-sulfate. TCDD did not significantly affect the hepatic enzyme activity for the glucuronidation or esterification of endogenous estrogens. It is suggested that enhanced metabolic inactivation of endogenous estrogens by hepatic estrogen-metabolizing enzymes in TCDD-treated, control diet-fed animals contributes importantly to the reduced incidence of estrogen-associated tumors in animals treated with TCDD

A Bone Metastasis Nude Mouse Model Created by Ultrasound Guided Intracardiac Injection of Breast Cancer Cells: the Micro-CT, MRI and Bioluminescence Imaging Analysis

Energy Technology Data Exchange (ETDEWEB)

Park, Young Jin; Song, Eun Hye; Kim, Seol Hwa; Song, Ho Taek; Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Sang Hyun [Korean Minjok Leadership Academy, Heongsung (Korea, Republic of)

2011-01-15

The purpose of this study was to develop a nude mouse model of bone metastasis by performing intracardiac injection of breast cancer cells under ultrasonography guidance and we wanted to evaluate the development and the distribution of metastasis in vivo using micro-CT, MRI and bioluminescence imaging. Animal experiments were performed in 6-week-old female nude mice. The animals underwent left ventricular injection of 2x105 MDA-MB-231Bo-Luc cells. After injection of the tumor cells, serial bioluminescence imaging was performed for 7 weeks. The findings of micro-CT, MRI and the histology were correlated with the 'hot' lesions seen on the bioluminescence imaging. Metastasis was found in 62.3% of the animals. Two weeks after intracardiac injection, metastasis to the brain, spine and femur was detected with bioluminescence imaging with an increasing intensity by week 7. Micro-CT scan confirmed multiple osteolytic lesions at the femur, spine and skull. MRI and the histology were able to show metastasis in the brain and extraskeletal metastasis around the femur. The intracardiac injection of cancer cells under ultrasonography guidance is a safe and highly reproducible method to produce bone metastasis in nude mice. This bone metastasis nude mouse model will be useful to study the mechanism of bone metastasis and to validate new therapeutics

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

Science.gov (United States)

Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

2016-05-10

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

Electroporation of Postimplantation Mouse Embryos In Utero.

Science.gov (United States)

Huang, Cheng-Chiu; Carcagno, Abel

2018-02-01

Gene transfer by electroporation is possible in mouse fetuses within the uterus. As described in this protocol, the pregnant female is anesthetized, the abdominal cavity is opened, and the uterus with the fetuses is exteriorized. A solution of plasmid DNA is injected through the uterine wall directly into the fetus, typically into a cavity like the brain ventricle, guided by fiber optic illumination. Electrodes are positioned on the uterus around the region of the fetus that was injected, and electrical pulses are delivered. The uterus is returned to the abdominal cavity, the body wall is sutured closed, and the female is allowed to recover. The manipulated fetuses can then be collected and analyzed at various times after the electroporation. This method allows experimental access to later-stage developing mouse embryos. © 2018 Cold Spring Harbor Laboratory Press.

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

DEFF Research Database (Denmark)

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

2000-01-01

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

KBERG: KnowledgeBase for Estrogen Responsive Genes

DEFF Research Database (Denmark)

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

2007-01-01

Estrogen has a profound impact on human physiology affecting transcription of numerous genes. To decipher functional characteristics of estrogen responsive genes, we developed KnowledgeBase for Estrogen Responsive Genes (KBERG). Genes in KBERG were derived from Estrogen Responsive Gene Database...... (ERGDB) and were analyzed from multiple aspects. We explored the possible transcription regulation mechanism by capturing highly conserved promoter motifs across orthologous genes, using promoter regions that cover the range of [-1200, +500] relative to the transcription start sites. The motif detection...... is based on ab initio discovery of common cis-elements from the orthologous gene cluster from human, mouse and rat, thus reflecting a degree of promoter sequence preservation during evolution. The identified motifs are linked to transcription factor binding sites based on the TRANSFAC database. In addition...

PGC-1{beta} regulates mouse carnitine-acylcarnitine translocase through estrogen-related receptor {alpha}

Energy Technology Data Exchange (ETDEWEB)

Gacias, Mar; Perez-Marti, Albert; Pujol-Vidal, Magdalena; Marrero, Pedro F. [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain); Haro, Diego, E-mail: dharo@ub.edu [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain); Relat, Joana [Department of Biochemistry and Molecular Biology, School of Pharmacy and the Institute of Biomedicine of the University of Barcelona (IBUB) (Spain)

2012-07-13

Highlights: Black-Right-Pointing-Pointer The Cact gene is induced in mouse skeletal muscle after 24 h of fasting. Black-Right-Pointing-Pointer The Cact gene contains a functional consensus sequence for ERR. Black-Right-Pointing-Pointer This sequence binds ERR{alpha} both in vivo and in vitro. Black-Right-Pointing-Pointer This ERRE is required for the activation of Cact expression by the PGC-1/ERR axis. Black-Right-Pointing-Pointer Our results add Cact as a genuine gene target of these transcriptional regulators. -- Abstract: Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficiency causes a variety of pathological conditions, such as hypoketotic hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and it can be fatal in newborns and infants. Here we report that expression of the Cact gene is induced in mouse skeletal muscle after 24 h of fasting. To gain insight into the control of Cact gene expression, we examine the transcriptional regulation of the mouse Cact gene. We show that the 5 Prime -flanking region of this gene is transcriptionally active and contains a consensus sequence for the estrogen-related receptor (ERR), a member of the nuclear receptor family of transcription factors. This sequence binds ERR{alpha}in vivo and in vitro and is required for the activation of Cact expression by the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1/ERR axis. We also demonstrate that XTC790, the inverse agonist of ERR{alpha}, specifically blocks Cact activation by PGC-1{beta} in C2C12 cells.

PGC-1β regulates mouse carnitine–acylcarnitine translocase through estrogen-related receptor α

International Nuclear Information System (INIS)

Gacias, Mar; Pérez-Martí, Albert; Pujol-Vidal, Magdalena; Marrero, Pedro F.; Haro, Diego; Relat, Joana

2012-01-01

Highlights: ► The Cact gene is induced in mouse skeletal muscle after 24 h of fasting. ► The Cact gene contains a functional consensus sequence for ERR. ► This sequence binds ERRα both in vivo and in vitro. ► This ERRE is required for the activation of Cact expression by the PGC-1/ERR axis. ► Our results add Cact as a genuine gene target of these transcriptional regulators. -- Abstract: Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficiency causes a variety of pathological conditions, such as hypoketotic hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and it can be fatal in newborns and infants. Here we report that expression of the Cact gene is induced in mouse skeletal muscle after 24 h of fasting. To gain insight into the control of Cact gene expression, we examine the transcriptional regulation of the mouse Cact gene. We show that the 5′-flanking region of this gene is transcriptionally active and contains a consensus sequence for the estrogen-related receptor (ERR), a member of the nuclear receptor family of transcription factors. This sequence binds ERRαin vivo and in vitro and is required for the activation of Cact expression by the peroxisome proliferator-activated receptor gamma coactivator (PGC)-1/ERR axis. We also demonstrate that XTC790, the inverse agonist of ERRα, specifically blocks Cact activation by PGC-1β in C2C12 cells.

Endothelial Estrogen Receptor-α Does Not Protect Against Vascular Stiffness Induced by Western Diet in Female Mice.

Science.gov (United States)

Manrique, Camila; Lastra, Guido; Ramirez-Perez, Francisco I; Haertling, Dominic; DeMarco, Vincent G; Aroor, Annayya R; Jia, Guanghong; Chen, Dongqing; Barron, Brady J; Garro, Mona; Padilla, Jaume; Martinez-Lemus, Luis A; Sowers, James R

2016-04-01

Consumption of a diet high in fat and refined carbohydrates (Western diet [WD]) is associated with obesity and insulin resistance, both major risk factors for cardiovascular disease (CVD). In women, obesity and insulin resistance abrogate the protection against CVD likely afforded by estrogen signaling through estrogen receptor (ER)α. Indeed, WD in females results in increased vascular stiffness, which is independently associated with CVD. We tested the hypothesis that loss of ERα signaling in the endothelium exacerbates WD-induced vascular stiffening in female mice. We used a novel model of endothelial cell (EC)-specific ERα knockout (EC-ERαKO), obtained after sequential crossing of the ERα double floxed mice and VE-Cadherin Cre-recombinase mice. Ten-week-old females, EC-ERαKO and aged-matched genopairs were fed either a regular chow diet (control diet) or WD for 8 weeks. Vascular stiffness was measured in vivo by pulse wave velocity and ex vivo in aortic explants by atomic force microscopy. In addition, vascular reactivity was assessed in isolated aortic rings. Initial characterization of the model fed a control diet did not reveal changes in whole-body insulin sensitivity, aortic vasoreactivity, or vascular stiffness in the EC-ERαKO mice. Interestingly, ablation of ERα in ECs reduced WD-induced vascular stiffness and improved endothelial-dependent dilation. In the setting of a WD, endothelial ERα signaling contributes to vascular stiffening in females. The precise mechanisms underlying the detrimental effects of endothelial ERα in the setting of a WD remain to be elucidated.

Fecundity, 17ß-estradiol concentrations and expression of vitellogenin and estrogen receptor genes throughout the ovarian cycle in female Eastern mosquitofish from three lakes in Florida

DEFF Research Database (Denmark)

Kristensen, T.; Edwards, T. M.; Kohno, S.

2007-01-01

Previous studies of Eastern mosquitofish in contaminated Lake Apopka, Florida, have documented reduced sperm count and sexual behaviour in males but increased fecundity and liver weight in females, compared to nearby reference lakes. Liver weight can be an indicator of vitellogenin (Vtg) synthesis...... in fish, such as the mosquitofish. It was therefore hypothesized that estrogenic organochlorine pesticides, present at elevated concentrations in animals from Lake Apopka, could cause the reproductive disorders in males, as well as increase female fecundity. We initiated a test of this hypothesis...... by examining the relationship between 17β-estradiol (E2) tissue concentrations, hepatic estrogen receptor α (ERα) and Vtg A, B and C gene expression and fecundity in sexually mature female Eastern mosquitofish from Lake Apopka and two reference lakes, Lake Woodruff and Lake Orange. We observed that female...

The Role and Use of Estrogens Following Trauma.

Science.gov (United States)

Weniger, Maximilian; Angele, Martin K; Chaudry, Irshad H

2016-09-01

Several lines of evidence indicate that female sex is a protective factor in trauma and hemorrhage. In both clinical and experimental studies, proestrus females have been shown to have better chances of survival and reduced rates of posttraumatic sepsis. Estrogen receptors are expressed in a variety of tissues and exert genomic, as well as nongenomic effects. By improving cardiac, pulmonary, hepatic, and immune function, estrogens have been shown to prolong survival in animal models of hemorrhagic shock. Despite encouraging results from experimental studies, retrospective clinical studies have not clearly pointed to advantages of estrogens following trauma-hemorrhage, which may be due to insufficient study design. Therefore, this review aims to give an overview on the current evidence and emphasizes on the importance of further clinical investigation on estrogens following trauma.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on estrogenic responses

Energy Technology Data Exchange (ETDEWEB)

Romkes, M.

1988-01-01

The competitive receptor binding affinities of thirteen 2-substituted-3,7,8-trichlorodibenzo-p-dioxins to hepatic cytosol from rat, mouse, guinea pig and hamster were determined using ({sup 3}H)-2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) as the radio-ligand. Significant species-dependent structural differences in the Ah receptor ligand binding site were observed and support the heterologous nature of the receptor protein. The interactions of 2,3,7,8-TCDD and estrogenic responses in the female rat and human breast cancer cells were also investigated. Cotreatment of 25-day-old female Long Evans rats with 20 or 80 ug/kg of 2,3,7,8-TCDD resulted in a dose-dependent decrease in both uterine and hepatic estrogen receptor (ER) levels. Moreover, these levels are decreased for at least ten days and appear to be related to the tissue persistence of 2,3,7,8-TCDD. In contrast, estradiol elevated uterine and hepatic ER levels and increased uterine wet weights. Cotreatment of the rats with 2,3,7,8-TCDD and estradiol resulted in hepatic and uterine ER levels which were comparable to those observed in the control rats; in addition, 2,3,7,8-TCDD also antagonized the effects of estradiol-induced uterine wet weights.

Prevalence and Correlates of Female Condom Use and Interest Among Injection Drug-Using Female Sex Workers in Two Mexico–US Border Cities

OpenAIRE

Stockman, Jamila K.; Morris, Meghan D.; Martinez, Gustavo; Lozada, Remedios; Patterson, Thomas L.; Ulibarri, Monica D.; Vera, Alicia; Strathdee, Steffanie A.

2012-01-01

Little is known about female condom use among female sex workers who inject drugs (FSW-IDUs) in Northern Mexico, where HIV/STI prevalence is high. We examined the prevalence and correlates of female condom use and interest in female condom use among FSW-IDUs aged ≥18 years in Tijuana and Ciudad Juárez, Mexico enrolled in a behavioral intervention designed to reduce high-risk sexual and injection behaviors. Of 621 FSW-IDUs, 8 % reported ever using female condoms, and 67.2 % expressed interest ...

Rapid Estrogen Receptor-Mediated Mechanisms Determine the Sexually Dimorphic Sensitivity of Ventricular Myocytes to 17β-Estradiol and the Environmental Endocrine Disruptor Bisphenol A

Science.gov (United States)

Belcher, Scott M.; Chen, Yamei; Yan, Sujuan

2012-01-01

Previously we showed that 17β-estradiol (E2) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca2+ handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E2 or BPA on Ca2+ handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E2 on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10−12 m, and the most efficacious concentrations for each were at 10−9 m. Sensitivity to E2 and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E2 suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ERβ knockout mouse model showed that ERα and ERβ have opposing actions in myocytes and that the balance between ERβ and ERα signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E2 and BPA is dominated by the stimulatory ERβ-mediated signaling, and the absence of BPA and E2 responsiveness in males is due to a counterbalancing-suppressive action of ERα. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ERα and ERβ signaling. PMID:22166976

Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17 α-methylestradiol in normal and tumor-bearing rats

International Nuclear Information System (INIS)

Feenstra, A.; Vaalburg, W.; Nolten, G.M.J.; Reiffers, S.; Talma, A.G.; Wiegman, T.; van der Molen, H.D.; Woldring, M.G.

1983-01-01

Tritiated 17α-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17α-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (K/sub d/ = 1.96 x 10 -10 M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 h after injection. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23 to 30% of the uptake in the uterus. Tritiated 17α-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that a 17 α-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical

Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females.

Science.gov (United States)

Tonn Eisinger, Katherine R; Gross, Kellie S; Head, Brian P; Mermelstein, Paul G

2018-03-10

Estrogen receptors α and β (ERα and ERβ) have a unique relationship with metabotropic glutamate receptors (mGluRs) in the female rodent brain such that estradiol is able to recruit intracellular G-protein signaling cascades to influence neuronal physiology, structure, and ultimately behavior. While this association between ERs and mGluRs exists in many cell types and brain regions, its effects are perhaps most striking in the nucleus accumbens (NAc). This review will discuss the original characterization of ER/mGluR signaling and how estradiol activity in the NAc confers increased sensitivity to drugs of abuse in females through this mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice

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Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice spe...

Experimental transmission of M. leprae in the testis of mice, born from 131I-injected females

International Nuclear Information System (INIS)

Sushida, Kiyo

1974-01-01

Six strains of M. leprae taken from lepromatous leprosy patients were inoculated into the testes of '' 131 I-F 1 '' mice, which were divided into two groups. The first group was born of females which had been subcutaneously injected with 131 I-100 μc during pregnancy; the second group was born of females which had been injected before pregnancy. The '' 131 I-F 1 '' mice which were born of females injected with 131 I-100 μc, during pregnancy were then inoculated with leprous bacilli described above, showed the presence of the so-called ''globi'' in the testes. When samples of leprous bacilli (LL28, LL32, LL33) taken from patients who had not been receiving anti-leprous drug treatments were injected into the 131 I-F 1 mice, globi were also found. When leprous bacilli from leproma removed from patients under treatment were injected into mice born from females which had been injected with 131 I-100 μc either during or before their pregnancy, no globi were found. Even though bacilli (LL32, LL33, LL34) from untreated patients were injected into mice born of females who were injected with 131 I-100 μc before pregnancy, no globi were found. (auth.)

Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall.

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Ripperda, Christopher M; Maldonado, Pedro Antonio; Acevedo, Jesus F; Keller, Patrick W; Akgul, Yucel; Shelton, John M; Word, Ruth Ann

2017-07-01

Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium. Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury.

Age-Associated Changes in Estrogen Receptor Ratios Correlate with Increased Female Susceptibility to Coxsackievirus B3-Induced Myocarditis

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Andreas Koenig

2017-11-01

Full Text Available Sexual bias is a hallmark in various diseases. This review evaluates sexual dimorphism in clinical and experimental coxsackievirus B3 (CVB3 myocarditis, and how sex bias in the experimental disease changes with increased age. Coxsackieviruses are major causes of viral myocarditis, an inflammation of the heart muscle, which is more frequent and severe in men than women. Young male mice infected with CVB3 develop heart-specific autoimmunity and severe myocarditis. Females infected during estrus (high estradiol develop T-regulatory cells and when infected during diestrus (low estradiol develop autoimmunity similar to males. During estrus, protection depends on estrogen receptor alpha (ERα, which promotes type I interferon, activation of natural killer/natural killer T cells and suppressor cell responses. Estrogen receptor beta has opposing effects to ERα and supports pro-inflammatory immunity. However, the sexual dimorphism of the disease is significantly ameliorated in aged animals when old females become as susceptible as males. This correlates to a selective loss of the ERα that is required for immunosuppression. Therefore, sex-associated hormones control susceptibility in the virus-mediated disease, but their impact can alter with the age and physiological stage of the individual.

Dual cloud point extraction coupled with hydrodynamic-electrokinetic two-step injection followed by micellar electrokinetic chromatography for simultaneous determination of trace phenolic estrogens in water samples.

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Wen, Yingying; Li, Jinhua; Liu, Junshen; Lu, Wenhui; Ma, Jiping; Chen, Lingxin

2013-07-01

A dual cloud point extraction (dCPE) off-line enrichment procedure coupled with a hydrodynamic-electrokinetic two-step injection online enrichment technique was successfully developed for simultaneous preconcentration of trace phenolic estrogens (hexestrol, dienestrol, and diethylstilbestrol) in water samples followed by micellar electrokinetic chromatography (MEKC) analysis. Several parameters affecting the extraction and online injection conditions were optimized. Under optimal dCPE-two-step injection-MEKC conditions, detection limits of 7.9-8.9 ng/mL and good linearity in the range from 0.05 to 5 μg/mL with correlation coefficients R(2) ≥ 0.9990 were achieved. Satisfactory recoveries ranging from 83 to 108% were obtained with lake and tap water spiked at 0.1 and 0.5 μg/mL, respectively, with relative standard deviations (n = 6) of 1.3-3.1%. This method was demonstrated to be convenient, rapid, cost-effective, and environmentally benign, and could be used as an alternative to existing methods for analyzing trace residues of phenolic estrogens in water samples.

Distribution and excretion of /sup 115m/cadmium and its transfer to egg and bone in laying female and estrogenized male Japanese quail

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Nishimura, M; Sakuta, M; Okamoto, K; Urakawa, N

1974-01-01

The distribution of /sup 115m/cadmium and its transfer to the egg were investigated in laying Japanese quail. Furthermore, the influence of estrogens on the tissue uptake of /sup 115m/cadmium was analyzed in adult male quail. Whole-body sections of a laying quail were prepared. Autoradiograms were made in birds killed 1, 24, 48, 96, 192 and 384 hours after a single injection of /sup 115m/cadmium chloride. During the first 48 hours following the injection, high concentrations of /sup 115m/cadmium were detected in the liver, kidneys, pancreas, proventriculus, uterus and small intestine. In eggs laid, /sup 115m/cadmium was detected only in the yolk. Its amount in the yolk was the highest in the second egg and decreased afterwards in the increasing order of oviposition sequence. The amount of the second egg was 0.21 percent of the given. In the male quail after estrogenization, the concentration of /sup 115m/cadmium increased in the femur and decreased in the liver, whole blood, and blood corpuscle, but was not affected at all in the kidney or blood plasma. These effects were dependent on the dose of estradiol benzoate. The cumulative contents of /sup 115m/cadmium in feces and urine for 192 hours were 28.42 +/- 0.73 (mean +/- standard error) percent of the dose given in laying quail, 25.83 +/- 0.91 percent in untreated males, and 27.81 +/- 0.63 percent in estrogenized males. It appeared that the increased uptake of cadmium in the femur by the estrogenization was roughly parallel with the formation of intramedullary bone. 22 references, 8 figures.

Ovarian function's role during cancer cachexia progression in the female mouse.

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Hetzler, Kimbell L; Hardee, Justin P; LaVoie, Holly A; Murphy, E Angela; Carson, James A

2017-05-01

Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The Apc Min/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female Apc Min/+ mouse. Our study of ovarian reproductive function in female Apc Min/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female Apc Min/+ mice. Copyright © 2017 the American Physiological Society.

Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

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Lyes eDerouiche

2015-12-01

Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

Bulk derivatization and direct injection of human cerebrospinal fluid for trace-level quantification of endogenous estrogens using trap-and-elute liquid chromatography with tandem mass spectrometry.

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Fan, Hui; Papouskova, Barbora; Lemr, Karel; Wigginton, Jane G; Schug, Kevin A

2014-08-01

Although there are existing methods for determining estrogen in human bodily fluids including blood plasma and serum, very little information is available regarding estrogen levels in human cerebrospinal fluid (CSF), which is critical to assess in studies of neuroprotective functions and diffusion of neuroprotective estrogens across the blood-brain barrier. To address this problem, a liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of four endogenous estrogens (estrone, 17α-estradiol, 17β-estradiol, and estriol) in human CSF was developed. An aliquot (300 μL) of human CSF was bulk derivatized using dansyl chloride in the sample and 10 μL was directly injected onto a restricted-access media trap column for protein removal. No off-line sample extraction or cleanup was needed. The limits of detection of estrone, 17α-estradiol, 17β-estradiol, and estriol were 17, 28, 13, and 30 pg/mL, respectively, which is in the parts-per-trillion regime. The method was then applied to human CSF collected from ischemic trauma patients. Endogenous estrogens were detected and quantified, demonstrating the effectiveness of this method. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

hebp3, a novel member of the heme-binding protein gene family, is expressed in the medaka meninges with higher abundance in females due to a direct stimulating action of ovarian estrogens.

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Nakasone, Kiyoshi; Nagahama, Yoshitaka; Okubo, Kataaki

2013-02-01

The brains of teleost fish exhibit remarkable sexual plasticity throughout their life span. To dissect the molecular basis for the development and reversal of sex differences in the teleost brain, we screened for genes differentially expressed between sexes in the brain of medaka (Oryzias latipes). One of the genes identified in the screen as being preferentially expressed in females was found to be a new member of the heme-binding protein gene family that includes hebp1 and hebp2 and was designated here as hebp3. The medaka hebp3 is expressed in the meninges with higher abundance in females, whereas there is no expression within the brain parenchyma. This female-biased expression of hebp3 is not attributable to the direct action of sex chromosome genes but results from the transient and reversible action of estrogens derived from the ovary. Moreover, estrogens directly activate the transcription of hebp3 via a palindromic estrogen-responsive element in the hebp3 promoter. Taken together, our findings demonstrate that hebp3 is a novel transcriptional target of estrogens, with female-biased expression in the meninges. The definite but reversible sexual dimorphism of the meningeal hebp3 expression may contribute to the development and reversal of sex differences in the teleost brain.

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

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Fiorindo, R. P.; Negulesco, J. A.

1980-01-01

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Ovarian function’s role during cancer cachexia progression in the female mouse

Science.gov (United States)

Hetzler, Kimbell L.; Hardee, Justin P.; LaVoie, Holly A.; Murphy, E. Angela

2017-01-01

Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The ApcMin/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female ApcMin/+ mouse. Our study of ovarian reproductive function in female ApcMin/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female ApcMin/+ mice. PMID:28292759

Novel estrogen receptor-related Transcripts in Marisa cornuarietis; a freshwater snail with reported sensitivity to estrogenic chemicals.

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Bannister, Richard; Beresford, Nicola; May, Denise; Routledge, Edwin J; Jobling, Susan; Rand-Weaver, Mariann

2007-04-01

We have isolated novel molluskan steroid receptor transcripts orthologous to vertebrate estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) from the freshwater snail Marisa cornuarietis. Radiolabeled ligand binding analyses showed that neither recombinant receptor protein specifically bound 17beta-estradiol over the range applied (0.3-9.6 nM). These novel receptor transcripts have thus been designated mcER-like and mcERR respectively. Quantitative PCR revealed mcER-like to be expressed ubiquitously throughout a range of male and female structures studied, including neural and reproductive tissues. Highest absolute levels were seen in the male penis-sheath complex. The mcERR mRNA was also expressed ubiquitously throughout all male and female tissues analyzed here, with very low absolute transcript numbers in female accessory sex structures compared to other tissues.

Multiple estrogen receptor subtypes influence ingestive behavior in female rodents.

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Santollo, Jessica; Daniels, Derek

2015-12-01

Postmenopausal women are at an increased risk of obesity and cardiovascular-related diseases. This is attributable, at least in part, to loss of the ovarian hormone estradiol, which inhibits food and fluid intake in humans and laboratory animal models. Although the hypophagic and anti-dipsogenic effects of estradiol have been well documented for decades, the precise mechanisms underlying these effects are not fully understood. An obvious step toward addressing this open question is identifying which estrogen receptor subtypes are involved and what intracellular processes are involved. This question, however, is complicated not only by the variety of estrogen receptor subtypes that exist, but also because many subtypes have multiple locations of action (i.e. in the nucleus or in the plasma membrane). This review will highlight our current understanding of the roles that specific estrogen receptor subtypes play in mediating estradiol's anorexigenic and anti-dipsogenic effects along with highlighting the many open questions that remain. This review will also describe recent work being performed by our laboratory aimed at answering these open questions. Copyright © 2015 Elsevier Inc. All rights reserved.

Estradiol target neurons in the hypothalamic arcuate nucleus and lateral ventromedial nucleus of young adult, reproductively senescent, and monosodium glutamate-lesioned female golden hamsters

International Nuclear Information System (INIS)

Blaha, G.C.; Lamperti, A.A.

1983-01-01

Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After 3 H-estradiol ( 3 H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of 3 H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females with ARC lesions had very few 3 H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although 3 H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell

Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

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Rajesh Kumar

Full Text Available Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄, an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂ levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP-9 as well as modulating transforming growth factor (TGF-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

Estrogen and early-onset Alzheimer's disease

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5 years) and place of

SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

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Tao Shen

2014-01-01

Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma.

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Lauren E Woodard

2010-06-01

Full Text Available Hydrodynamic injection is an effective method for DNA delivery in mouse liver and is being translated to larger animals for possible clinical use. Similarly, phiC31 integrase has proven effective in mediating long-term gene therapy in mice when delivered by hydrodynamic injection and is being considered for clinical gene therapy applications. However, chromosomal aberrations have been associated with phiC31 integrase expression in tissue culture, leading to questions about safety.To study whether hydrodynamic delivery alone, or in conjunction with delivery of phiC31 integrase for long-term transgene expression, could facilitate tumor formation, we used a transgenic mouse model in which sustained induction of the human C-MYC oncogene in the liver was followed by hydrodynamic injection. Without injection, mice had a median tumor latency of 154 days. With hydrodynamic injection of saline alone, the median tumor latency was significantly reduced, to 105 days. The median tumor latency was similar, 106 days, when a luciferase donor plasmid and backbone plasmid without integrase were administered. In contrast, when active or inactive phiC31 integrase and donor plasmid were supplied to the mouse liver, the median tumor latency was 153 days, similar to mice receiving no injection.Our data suggest that phiC31 integrase does not facilitate tumor formation in this C-MYC transgenic mouse model. However, in groups lacking phiC31 integrase, hydrodynamic injection appeared to contribute to C-MYC-induced hepatocellular carcinoma in adult mice. Although it remains to be seen to what extent these findings may be extrapolated to catheter-mediated hydrodynamic delivery in larger species, they suggest that caution should be used during translation of hydrodynamic injection to clinical applications.

Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

International Nuclear Information System (INIS)

Mai, Leemin; Pan, Jenntser

1990-01-01

The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 μg/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 μg/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 μg/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective

p53 Loss Synergizes with Estrogen and Papillomaviral Oncogenes to Induce Cervical and Breast Cancers

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Shai, Anny; Pitot, Henry C.; Lambert, Paul F.

2010-01-01

Whereas the tumor suppressor p53 gene is frequently mutated in most human cancers, this is not the case in human papillomavirus (HPV)-associated cancers, presumably because the viral E6 oncoprotein inactivates the p53 protein. The ability of E6 to transform cells in tissue culture and induce cancers in mice correlates in part with its ability to inactivate p53. In this study, we compared the expression of the HPV16 E6 oncogene to the conditional genetic disruption of p53 in the context of a mouse model for cervical cancer in which estrogen is a critical cofactor. Nearly all of the K14Crep53f/f mice treated with estrogen developed cervical cancer, a stark contrast to its complete absence in like-treated K14E6WTp53f/f mice, indicating that HPV16 E6 must only partially inactivate p53. p53-independent activities of E6 also contributed to carcinogenesis, but in the female reproductive tract, these activities were manifested only in the presence of the HPV16 E7 oncogene. Interestingly, treatment of K14Crep53f/f mice with estrogen also resulted in mammary tumors after only a short latency, many of which were positive for estrogen receptor α. The majority of these mammary tumors were of mixed cell types, suggestive of their originating from a multipotent progenitor. Furthermore, a subset of mammary tumors arising in the estrogen-treated, p53-deficient mammary glands exhibited evidence of an epithelial to mesenchymal transition. These data show the importance of the synergy between estrogen and p53 insufficiency in determining basic properties of carcinogenesis in hormone-responsive tissues, such as the breast and the reproductive tract. PMID:18413729

Estrogen signaling in the proliferative endometrium: implications in endometriosis

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Rita de Cássia Pereira da Costa e Silva

2016-02-01

Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents

International Nuclear Information System (INIS)

Mercado-Feliciano, Minerva; Cora, Michelle C.; Witt, Kristine L.; Granville, Courtney A.; Hejtmancik, Milton R.; Fomby, Laurene; Knostman, Katherine A.; Ryan, Michael J.; Newbold, Retha; Smith, Cynthia; Foster, Paul M.; Vallant, Molly K.; Stout, Matthew D.

2012-01-01

Black cohosh rhizome (Actaea racemosa) is used as a remedy for pain and gynecological ailments; modern preparations are commonly sold as ethanolic extracts available as dietary supplements. Black cohosh was nominated to the National Toxicology Program (NTP) for toxicity testing due to its widespread use and lack of safety data. Several commercially available black cohosh extracts (BCE) were characterized by the NTP, and one with chemical composition closest to formulations available to consumers was used for all studies. Female B6C3F1/N mice and Wistar Han rats were given 0, 15 (rats only), 62.5 (mice only), 125, 250, 500, or 1000 mg/kg/day BCE by gavage for 90 days starting at weaning. BCE induced dose-dependent hematological changes consistent with a non-regenerative macrocytic anemia and increased frequencies of peripheral micronucleated red blood cells (RBC) in both species. Effects were more severe in mice, which had decreased RBC counts in all treatment groups and increased micronucleated RBC at doses above 125 mg/kg. Dose-dependent thymus and liver toxicity was observed in rats but not mice. No biologically significant effects were observed in other organs. Puberty was delayed 2.9 days at the highest treatment dose in rats; a similar magnitude delay in mice occurred in the 125 and 250 mg/kg groups but not at the higher doses. An additional uterotrophic assay conducted in mice exposed for 3 days to 0.001, 0.01, 0.1, 1, 10, 100 and 500 mg/kg found no estrogenic or anti-estrogenic activity. These are the first studies to observe adverse effects of BCE in rodents. -- Highlights: ► Mice and rats were dosed with black cohosh extract for 90 days starting at weaning. ► Hematological changes were consistent with a non-regenerative macrocytic anemia. ► Peripheral micronucleated red blood cell frequencies increased. ► Puberty was delayed 2.9 days in rats. ► No estrogenic/anti-estrogenic activity was seen in the uterotrophic assay.

An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents

Energy Technology Data Exchange (ETDEWEB)

Mercado-Feliciano, Minerva; Cora, Michelle C.; Witt, Kristine L. [National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, Research Triangle Park, NC (United States); Granville, Courtney A.; Hejtmancik, Milton R.; Fomby, Laurene; Knostman, Katherine A.; Ryan, Michael J. [Battelle Memorial Institute, Columbus, OH (United States); Newbold, Retha; Smith, Cynthia; Foster, Paul M.; Vallant, Molly K. [National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, Research Triangle Park, NC (United States); Stout, Matthew D., E-mail: StoutM@niehs.nih.gov [National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, Research Triangle Park, NC (United States)

2012-09-01

Black cohosh rhizome (Actaea racemosa) is used as a remedy for pain and gynecological ailments; modern preparations are commonly sold as ethanolic extracts available as dietary supplements. Black cohosh was nominated to the National Toxicology Program (NTP) for toxicity testing due to its widespread use and lack of safety data. Several commercially available black cohosh extracts (BCE) were characterized by the NTP, and one with chemical composition closest to formulations available to consumers was used for all studies. Female B6C3F1/N mice and Wistar Han rats were given 0, 15 (rats only), 62.5 (mice only), 125, 250, 500, or 1000 mg/kg/day BCE by gavage for 90 days starting at weaning. BCE induced dose-dependent hematological changes consistent with a non-regenerative macrocytic anemia and increased frequencies of peripheral micronucleated red blood cells (RBC) in both species. Effects were more severe in mice, which had decreased RBC counts in all treatment groups and increased micronucleated RBC at doses above 125 mg/kg. Dose-dependent thymus and liver toxicity was observed in rats but not mice. No biologically significant effects were observed in other organs. Puberty was delayed 2.9 days at the highest treatment dose in rats; a similar magnitude delay in mice occurred in the 125 and 250 mg/kg groups but not at the higher doses. An additional uterotrophic assay conducted in mice exposed for 3 days to 0.001, 0.01, 0.1, 1, 10, 100 and 500 mg/kg found no estrogenic or anti-estrogenic activity. These are the first studies to observe adverse effects of BCE in rodents. -- Highlights: ► Mice and rats were dosed with black cohosh extract for 90 days starting at weaning. ► Hematological changes were consistent with a non-regenerative macrocytic anemia. ► Peripheral micronucleated red blood cell frequencies increased. ► Puberty was delayed 2.9 days in rats. ► No estrogenic/anti-estrogenic activity was seen in the uterotrophic assay.

Genistein Stimulates Jejunum Chloride Secretion via an Akt-Mediated Pathway in Intact Female Mice

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Lana Leung

2015-02-01

Full Text Available Background/Aims: We have previously shown that daily subcutaneous injections with the naturally occurring phytoestrogen genistein (600 mg genistein/kg body weight/day, 600G results in a significantly increased basal intestinal chloride, Cl-, secretion (Isc, a measure of transepithelial secretion in intact C57BL/6J female mice after 1-week of treatment, compared to controls (DMSO vehicle injected. Removal of endogenous estrogen via ovariectomy (OVX had no effect on the 600G-mediated increase in basal Isc. Methods: Given the estrogen-like characteristics of genistein, we compared the effects of daily estradiol (E2 injections (10 mg E2/kg body weight/day, 10E2 on basal Isc in intact and OVX mice. In intact mice, 10E2 was without effect on basal Isc, however, in OVX mice, 10E2 significantly increased basal Isc (mimicked 600G. The goal of the current study was to characterize the intracellular signaling pathways responsible for mediating 600G- or 10E2-stimulated increases in basal Isc in intact female or OVX mice. Results: We measured total protein expression in isolated segments of jejunum using western blot from the following six groups of mice; intact or OVX with; 600G, 10E2 or control. The proteins of interest were: Akt, p-Akt, p-PDK1, p-PTEN, p-c-Raf, p-GSK-3β, rap-1 and ERK1/2. All blots were normalized to GAPDH levels (n = 6-18/group. Conclusion: These data suggest that the presence of the endogenous sex steroid, estrogen, modifies the intracellular signaling pathway required to mediate Cl- secretion when the intestine is exposed to exogenous 600G or E2. These studies may have relevance for designing pharmacological tools for women with intestinal chloride secretory dysfunctions.

Environmental estrogen(s) induced swimming behavioural alterations in adult zebrafish (Danio rerio).

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Goundadkar, Basavaraj B; Katti, Pancharatna

2017-09-01

The present study is an attempt to investigate the effects of long-term (75days) exposure to environmental estrogens (EE) on the swimming behaviour of zebrafish (Danio rerio). Adult zebrafish were exposed semi-statically to media containing commonly detected estrogenic water contaminants (EE2, DES and BPA) at a concentration (5ng/L) much lower than environmentally recorded levels. Time spent in swimming, surface preference, patterns and path of swimming were recorded (6mins) for each fish using two video cameras on day 15, 30 60 and 75. Video clips were analysed using a software program. Results indicate that chronic exposure to EE leads to increased body weight and size of females, reduced (Pswimming time, delay in latency, increased (P<0.05) immobility, erratic movements and freezing episodes. We conclude that estrogenic contamination of natural aquatic systems induces alterations in locomotor behaviour and associated physiological disturbances in inhabitant fish fauna. Copyright © 2017 Elsevier B.V. All rights reserved.

Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion.

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Qin, Sisi; Ingle, James N; Liu, Mohan; Yu, Jia; Wickerham, D Lawrence; Kubo, Michiaki; Weinshilboum, Richard M; Wang, Liewei

2017-08-18

We previously performed a case-control genome-wide association study in women treated with selective estrogen receptor modulators (SERMs) for breast cancer prevention and identified single nucleotide polymorphisms (SNPs) in ZNF423 as potential biomarkers for response to SERM therapy. The ZNF423rs9940645 SNP, which is approximately 200 bp away from the estrogen response elements, resulted in the SNP, estrogen, and SERM-dependent regulation of ZNF423 expression and, "downstream", that of BRCA1. Electrophoretic mobility shift assay-mass spectrometry was performed to identify proteins binding to the ZNF423 SNP and coordinating with estrogen receptor alpha (ERα). Clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing was applied to generate ZR75-1 breast cancer cells with different ZNF423 SNP genotypes. Both cultured cells and mouse xenograft models with different ZNF423 SNP genotypes were used to study the cellular responses to SERMs and poly(ADP-ribose) polymerase (PARP) inhibitors. We identified calmodulin-like protein 3 (CALML3) as a key sensor of this SNP and a coregulator of ERα, which contributes to differential gene transcription regulation in an estrogen and SERM-dependent fashion. Furthermore, using CRISPR/Cas9-engineered ZR75-1 breast cancer cells with different ZNF423 SNP genotypes, striking differences in cellular responses to SERMs and PARP inhibitors, alone or in combination, were observed not only in cells but also in a mouse xenograft model. Our results have demonstrated the mechanism by which the ZNF423 rs9940645 SNP might regulate gene expression and drug response as well as its potential role in achieving more highly individualized breast cancer therapy.

Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD

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Nilfer Sahin

2018-05-01

Full Text Available Estrogen has a crucial role in the regulation of reproductive and neuroendocrine function and exerts its effects through two classes of receptors, nuclear and membrane estrogen receptors (mERs. G protein-coupled estrogen receptor 1 (GPER is a member of mERs, and despite limited research on the levels of GPER in patients with psychiatric diseases, a role of GPER in such conditions has been suggested. Here we evaluated serum estrogen and GPER levels in children with attention deficit hyperactivity disorder (ADHD in relation to their age- and gender-matched healthy controls. A total of 82 children were included in the study, 47 drug- naïve patients with ADHD (age: 6–12 years; male/female: 34/13 and 35 healthy controls (age: 6–12 years; male/female: 19/16. The subgroups according to ADHD types were inattentive, hyperactive/impulsive, and combined. Serum estrogen was measured using an immunoassay system, while serum GPER was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. Estrogen levels in children with ADHD were similar as in control group, while GPER levels were significantly lower in ADHD group compared to controls (p < 0.05. Logistic regression analysis showed a significant association between GPER levels and ADHD (p < 0.05, and no association between estrogen levels and ADHD (p > 0.05. No significant differences were found in GPER and estrogen levels between ADHD subgroups (p > 0.05. To the best of our knowledge, this study is the first to investigate estrogen and GPER levels in ADHD. Our preliminary findings suggest a relationship between serum GPER levels and ADHD, and this should be further investigated.

Effects of triclosan on hormones and reproductive axis in female Yellow River carp (Cyprinus carpio): Potential mechanisms underlying estrogen effect.

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Wang, Fan; Guo, Xiangmeng; Chen, Wanguang; Sun, Yaowen; Fan, Chaojie

2017-12-01

Triclosan (TCS), a member of the class of compounds called pharmaceutical and personal care products (PPCPs), is a broad antibacterial and antifungal agent found in a lot of consumer products. However, TCS hormone effect mechanism in teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were exposed to 1/20, 1/10 and 1/5 LC 50 TCS (96h LC 50 of TCS to carp) under semi-static conditions for 42days. Vitellogenin (Vtg), 17β-estradiol (E 2 ), testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, we also examined the mRNA expressions of aromatase, GtHs-β, GnRH, and Er by quantitative real-time PCR (qRT-PCR). The results indicated that 1/5 LC 50 TCS induced Vtg in hepatopancreas of female carps by interference with the hypothalamic-pituitary-gonadal (HPG) axis at multiple potential loci through three mechanisms: (a) TCS exposure enhanced the mRNA expression of hypothalamus and gonadal aromatase which converts androgens into estrogens, subsequently increasing serum concentrations of E 2 to induce Vtg in hepatopancreas; (b) TCS treatment increased GnRH and GtH-β mRNA expression and secretion, causing the disturbance of reproductive endocrine and the increase of E 2 to induce Vtg in hepatopancreas; (c) TCS exposure enhanced synthesis and secretion of Er, then it bound to Er to active Vtg synthesis. These mechanisms showed that TCS may induce Vtg production in female Yellow River carp by Er-mediated and non-Er-mediated pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac autonomic modulation by estrogen in female mice undergoing ambulatory monitoring and in vivo electrophysiologic testing.

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Saba, Samir; Shusterman, Vladimir; Usiene, Irmute; London, Barry

2004-04-01

Estrogen is an important modulator of cardiovascular risk, but its mechanism of action is not fully understood. We investigated the effect of ovariectomy and its timing on the cardiac electrophysiology in mice. Thirty female mice (age 18.8 +/- 3.1 weeks) underwent in vivo electrophysiologic testing before and after autonomic blockade. Fifteen mice were ovariectomized prepuberty (PRE) and ten postpuberty (POST), 2 weeks prior to electrophysiologic testing. Five age-matched sham-operated female mice (Control) served as controls. A subset of 13 mice (5 PRE, 3 POST, and 5 Controls) underwent 24-hour ambulatory monitoring. With ambulatory monitoring, the average (668 +/- 28 vs 769 +/- 52 b/min, P = 0.008) and minimum (485 +/- 47 vs 587 +/- 53 b/min, P = 0.02) heart rates were significantly slower in the ovariectomized mice (PRE and POST groups) compared to the Control group. At baseline electrophysiologic testing, there were no significant differences among the ovariectomized and intact mice in any of the measured parameters. With autonomic blockade, the Control group had a significantly larger change (delta) in the atrioventricular (AV) nodal Wenckebach (AVW) periodicity (deltaAVW = 11.3 +/- 2.9 vs 2.1 +/- 7.3 ms, P = 0.05) and functional refractory period (deltaFRP = 11.3 +/- 2.1 vs 1.25 +/- 6.8 ms, P = 0.02) compared to the ovariectomized mice. These results were not altered by the time of ovariectomy (PRE vs POST groups). Our results suggest that estrogen modulates the autonomic inputs into the murine sinus and AV nodes. These findings, if replicated in humans, might underlie the observed clustering of certain arrhythmias around menstruation and explain the higher incidence of arrhythmias in men and postmenopausal women.

Effects of Vitex agnus-castus fruit on sex hormones and antioxidant indices in a d-galactose-induced aging female mouse model.

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Ahangarpour, Akram; Najimi, Seyedeh Asma; Farbood, Yaghoob

2016-11-01

Aging is associated with the loss of endocrine function. In this study, Vitex agnus-castus (Vitex), which has antioxidant effects and high levels of phytoestrogen, was investigated with regard to the hypothalamic-pituitary-gonadal axis and antioxidant indices in natural aging and in a d-galactose induced aging model in female mice. The mice were subcutaneously injected with d-galactose (500 mg/kg/d for 45 days). Extract of Vitex (600 mg/kg/bid for 7 days by gavage) was used to treat d-galactose-induced aging and natural aging in mice. Seventy-two female NMRI mice (48 3-month-old normal mice and 24 18-24-month-old mice), weighing 30-35 g were randomly divided into six groups: control, Vitex, d-galactose, Vitex + d-galactose, Aging, and Vitex + Aging. The antioxidant indices and sex hormone levels were subsequently measured by enzyme-linked immunosorbent assay kits. Body weight and the levels of malondialdehyde (MDA), follicle-stimulating hormone, and luteinizing hormone levels were significantly increased in the d-galactose aging and natural aging groups, whereas catalase and superoxide dismutase (SOD) activity and estrogen level were significantly decreased in these same groups. d-Galactose can also disrupt the estrous cycle and damage the uterus and ovarian tissues. Vitex could effectively attenuate these alterations. Vitex improved some aging events in the reproductive system of female mice. Therefore, because of its apparent antiaging effects, Vitex can be suitable for some aging problems such as oxidative stress, female sex hormone deficiency, and an atrophic endometrium. Copyright © 2016. Published by Elsevier Taiwan LLC.

Immunoprecipitation assay of alpha-fetoprotein synthesis by cultured mouse hepatoma cells treated with estrogens and glucocorticoids.

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Rosebrock, J A; Parker, C L; Kute, T E

1981-01-01

This investigation was to study the biosynthesis of 3H-labeled alpha-fetoprotein (AFP) by cultured mouse hepatoma (HEPA-2) cells. Both the function and regulation of this oncodevelopmental gene are unknown. However, evidence indicates that mechanisms controlling the expression of AFP involve aspects of both normal embryonic development and neoplastic transformation. the secretion of AFP was analyzed during different phases of the growth cycle to provide information on AFP production using standard culture conditions. The highest rate of secretion occurred during the stationary phase, followed by the late logarithmic and early logarithmic phases of growth, respectively. The production of AFP was then determined following the addition of glucocorticoids and estrogens in an attempt to understand hormonal factors that may be involved. Studies utilizing estradiol-17 beta indicated that the secretion of AFP did not appear to be sensitive to this steroid even though sucrose density gradient analysis of HEPA-2 cytosol, for estrogenic receptors, revealed competitive binding moieties on the 8S and 4S regions of the gradient. In contrast, the secretion of the total complement of proteins, including AFP, was significantly stimulated by the glucocorticoids, dexamethasone and corticosterone. Analysis of HEPA-2 cytosol for glucocorticoid receptors revealed binding components in the 7S and 3-4S regions of the gradient. The 3H-dexamethasone binding appeared to be stereospecific since nonlabeled dexamethasone, but not nonlabeled estradiol-17 beta, effectively displaced the bound radioactivity. The glucocorticoid-binding component in HEPA-2 therefore displayed characteristics reported for glucocorticoid receptors in normal liver and other hepatomas.

Factors associated with pathways toward concurrent sex work and injection drug use among female sex workers who inject drugs in northern Mexico.

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Morris, Meghan D; Lemus, Hector; Wagner, Karla D; Martinez, Gustavo; Lozada, Remedios; Gómez, Rangel María Gudelia; Strathdee, Steffanie A

2013-01-01

To identify factors associated with time to initiation of (i) sex work prior to injecting drugs initiation; (ii) injection drug use prior to sex work initiation; and (iii) concurrent sex work and injection drug use (i.e. initiated at the same age) among female sex workers who currently inject drugs (FSW-IDU). Parametric survival analysis of baseline data for time to initiation event. Tijuana and Ciudad Juarez situated on the Mexico-US border. A total of 557 FSW-IDUs aged ≥18 years. Interview-administered surveys assessing context of sex work and injection drug use initiation. Nearly half (n = 258) initiated sex work prior to beginning to inject, a third (n = 163) initiated injection first and a quarter (n = 136) initiated both sex work and injection drug use concurrently. Low education and living in Ciudad Juarez accelerated time to sex work initiation. Being from a southern Mexican state and initiating drug use with inhalants delayed the time to first injection drug use. Having an intimate partner encourage entry into sex work and first injecting drugs to deal with depression accelerated time to initiating sex work and injection concurrently. Early physical abuse accelerated time to initiating sex work and injection, and substantially accelerated time to initiation of both behaviors concurrently. Among female sex workers who currently inject drugs in two Mexican-US border cities, nearly half appear to initiate sex work prior to beginning to inject, nearly one-third initiate injection drug use before beginning sex work and one-quarter initiate both behaviors concurrently. Predictors of these three trajectories differ, and this provides possible modifiable targets for prevention. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

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

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Flores, Roberto; Shi, Jianxin; Fuhrman, Barbara; Xu, Xia; Veenstra, Timothy D; Gail, Mitchell H; Gajer, Pawel; Ravel, Jacques; Goedert, James J

2012-12-21

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

Pathophysiological Role of Transient Receptor Potential Ankyrin 1 in a Mouse Long-Lasting Cystitis Model Induced by an Intravesical Injection of Hydrogen Peroxide

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Shohei Oyama

2017-11-01

Full Text Available Chronic inflammatory bladder disorders, such as interstitial cystitis/bladder pain syndrome, are associated with poor quality of life. The exact pathological processes remain unclear, but accumulating evidence suggests that reactive oxidative species (ROS are involved in urinary bladder disorders. Transient receptor potential ankyrin 1 (TRPA1, the most sensitive TRP channel to ROS, was shown to be responsible for urinary bladder abnormalities and hyperalgesia in an acute cystitis model. However, the roles of TRPA1 in chronic inflammatory bladder are not fully understood. We previously established a novel mouse cystitis model induced by intravesical injection of hydrogen peroxide (H2O2, resulting in long-lasting frequent urination, bladder inflammation, pain-related behavior, and histopathological changes. In the present study, we investigated the pathophysiological role of TRPA1 in the H2O2-induced long-lasting cystitis mouse model. Under anesthesia, 1.5% H2O2 solution was introduced transurethrally into the bladder of female wild-type (WT and TRPA1-knockout mice and maintained for 30 min. This increased the number of voids in WT mice at 1 and 7 days after injection, but reduced the number in TRPA1-knockout mice at 1 day but not 7 days after injection. Spontaneous locomotor activities (increase in freezing time and decrease in distance moved were reduced at 3 h after injection in WT mice, whereas the spontaneous visceral pain-related behaviors were attenuated in TRPA1-knockout mice. Furthermore, upregulation of c-fos mRNA in the spinal cord at 1 day after injection was observed in WT but not TRPA1-knockout mice. However, there was no difference in histopathological changes in the urinary bladder, such as edematous thickening in the submucosa, between WT and TRPA1-knockout mice at 1 or 7 days after injection. Finally, Trpa1 mRNA levels in the L5-S1 dorsal root ganglion were not altered, but levels in the urinary bladder were drastically increased

Estrogen Signaling Contributes to Sex Differences in Macrophage Polarization during Asthma.

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Keselman, Aleksander; Fang, Xi; White, Preston B; Heller, Nicola M

2017-09-01

Allergic asthma is a chronic Th2 inflammation in the lungs that constricts the airways and presents as coughing and wheezing. Asthma mostly affects boys in childhood and women in adulthood, suggesting that shifts in sex hormones alter the course of the disease. Alveolar macrophages have emerged as major mediators of allergic lung inflammation in animal models as well as humans. Whether sex differences exist in macrophage polarization and the molecular mechanism(s) that drive differential responses are not well understood. We found that IL-4-stimulated bone marrow-derived and alveolar macrophages from female mice exhibited greater expression of M2 genes in vitro and after allergen challenge in vivo. Alveolar macrophages from female mice exhibited greater expression of the IL-4Rα and estrogen receptor (ER) α compared with macrophages from male mice following allergen challenge. An ERα-specific agonist enhanced IL-4-induced M2 gene expression in macrophages from both sexes, but more so in macrophages from female mice. Furthermore, IL-4-stimulated macrophages from female mice exhibited more transcriptionally active histone modifications at M2 gene promoters than did macrophages from male mice. We found that supplementation of estrogen into ovariectomized female mice enhanced M2 polarization in vivo upon challenge with allergen and that macrophage-specific deletion of ERα impaired this M2 polarization. The effects of estrogen are long-lasting; bone marrow-derived macrophages from ovariectomized mice implanted with estrogen exhibited enhanced IL-4-induced M2 gene expression compared with macrophages from placebo-implanted littermates. Taken together, our findings suggest that estrogen enhances IL-4-induced M2 gene expression and thereby contributes to sex differences observed in asthma. Copyright © 2017 by The American Association of Immunologists, Inc.

Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries.

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Zhang, Hua; Zheng, Wenjing; Shen, Yan; Adhikari, Deepak; Ueno, Hiroo; Liu, Kui

2012-07-31

It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent Rosa26(rbw/+);Ddx4-Cre germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.

The role of estrogen in bone growth and formation: changes at puberty

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Divya Singh

2010-12-01

Full Text Available Divya Singh1, Sabyasachi Sanyal2, Naibedya Chattopadhyay11Division of Endocrinology, 2Division of Drug Target Discovery and Development, Central Drug Research Institute (Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, IndiaAbstract: A high peak bone mass (PBM at skeletal maturity is a good predictor for lower rate of fracture risks in later life. Growth during puberty contributes significantly to PBM achievement in women and men. The growth hormone (GH/insulin-like growth factor 1 (IGF-1 axis has a critical role in pubertal bone growth. There is an increase in GH and IGF-1 levels during puberty; thus, it is assumed that sex steroids contribute to higher GH/IGF-1 action during growth. Recent studies indicate that estrogen increases GH secretion in boys and girls, and the major effect of testosterone on GH secretion is via aromatization to estrogen. Estrogen is pivotal for epiphyseal fusion in young men and women. From studies of individuals with a mutated aromatase gene and a case study of male patient with defective estrogen receptor-alpha (ER-α, it is clear that estrogen is indispensable for normal pubertal growth and growth plate fusion. ER-α and estrogen receptor-beta (ER-β have been localized in growth plate and bone. ER knockout studies have shown that ER-α-/- female mice have reduced linear appendicular growth, while ER-β-/- mice have increased appendicular growth. No such effect is seen in ER-β-/- males; however, repressed growth is seen in ER-α-/- males, resulting in shorter long bones. Thus, ER-β represses longitudinal bone growth in female mice, while it has no function in the regulation of longitudinal bone growth in male mice. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.Keywords: peak bone mass, puberty, estrogen, growth plate

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice.

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Anchan, Divya; Clark, Sara; Pollard, Kevin; Vasudevan, Nandini

2014-01-01

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17β estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improve spatial memory, suggesting that GPR30 plays a role in hippocampal-dependent cognition. In this study, we investigated the effect of a similar chronic administration of G-1 on behaviors that denote anxiety in adult ovariectomized female mice, using the elevated plus maze (EPM) and the open field test as well as the activation of the ERK pathway in the hippocampus. Although estradiol benzoate had no effect on behaviors in the EPM or the open field, G-1 had an anxiolytic effect solely in the open field that was independent of ERK signaling in either the ventral or dorsal hippocampus. Such an anxiolytic effect may underlie the ability of G-1 to increase spatial memory, by acting on the hippocampus.

Ovarian steroids regulate tachykinin and tachykinin receptor gene expression in the mouse uterus

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Patak Eva

2009-07-01

Full Text Available Abstract Background In the mouse uterus, pregnancy is accompanied by changes in tachykinin and tachykinin receptor gene expression and in the uterotonic effects of endogenous tachykinins. In this study we have investigated whether changes in tachykinin expression and responses are a result of changes in ovarian steroid levels. Methods We quantified the mRNAs of tachykinins and tachykinin receptors in uteri from ovariectomized mice and studied their regulation in response to estrogen and progesterone using real-time quantitative RT-PCR. Early (3 h and late (24 h responses to estrogen were evaluated and the participation of the estrogen receptors (ER, ERalpha and ERbeta, was analyzed by treating mice with propylpyrazole triol, a selective ERalpha agonist, or diarylpropionitrile, a selective agonist of ERbeta. Results All genes encoding tachykinins (Tac1, Tac2 and Tac4 and tachykinin receptors (Tacr1, Tacr2 and Tacr3 were expressed in uteri from ovariectomized mice. Estrogen increased Tac1 and Tacr1 mRNA after 3 h and decreased Tac1 and Tac4 expression after 24 h. Tac2 and Tacr3 mRNA levels were decreased by estrogen at both 3 and 24 h. Most effects of estrogen were also observed in animals treated with propylpyrazole triol. Progesterone treatment increased the levels of Tac2. Conclusion These results show that the expression of tachykinins and their receptors in the mouse uterus is tightly and differentially regulated by ovarian steroids. Estrogen effects are mainly mediated by ERalpha supporting an essential role for this estrogen receptor in the regulation of the tachykinergic system in the mouse uterus.

21 CFR 862.1275 - Estrogens (total, nonpregnancy) test system.

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2010-04-01

..., estradiol, and estriol) in plasma, serum, and urine of males and nonpregnant females. Measurement of... infertility, amenorrhea (absence of menses) differentiation of primary and secondary ovarian malfunction, estrogen secreting testicular and ovarian tumors, and precocious puberty in females. (b) Classification...

Elevated expression of H19 and Igf2 in the female mouse eye.

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Björn Reinius

Full Text Available The catalogue of genes expressed at different levels in the two sexes is growing, and the mechanisms underlying sex differences in regulation of the mammalian transcriptomes are being explored. Here we report that the expression of the imprinted non-protein-coding maternally expressed gene H19 was female-biased specifically in the female mouse eye (1.9-fold, p = 3.0E-6 while not being sex-biased in other somatic tissues. The female-to-male expression fold-change of H19 fell in the range expected from an effect of biallelic versus monoallelic expression. Recently, the possibility of sex-specific parent-of-origin allelic expression has been debated. This led us to hypothesize that H19 might express biallelically in the female mouse eye, thus escape its silencing imprint on the paternal allele specifically in this tissue. We therefore performed a sex-specific imprinting assay of H19 in female and male eye derived from a cross between Mus musculus and Mus spretus. However, this analysis demonstrated that H19 was exclusively expressed from the maternal gene copy, disproving the escape hypothesis. Instead, this supports that the female-biased expression of H19 is the result of upregulation of the single maternal. Furthermore, if H19 would have been expressed from both gene copies in the female eye, an associated downregulation of Insulin-like growth factor 2 (Igf2 was expected, since H19 and Igf2 compete for a common enhancer element located in the H19/Igf2 imprinted domain. On the contrary we found that also Igf2 was significantly upregulated in its expression in the female eye (1.2-fold, p = 6.1E-3, in further agreement with the conclusion that H19 is monoallelically elevated in females. The female-biased expression of H19 and Igf2 specifically in the eye may contribute to our understanding of sex differences in normal as well as abnormal eye physiology and processes.

Increasing women's sexual desire: The comparative effectiveness of estrogens and androgens.

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Cappelletti, Maurand; Wallen, Kim

2016-02-01

Both estradiol and testosterone have been implicated as the steroid critical for modulating women's sexual desire. By contrast, in all other female mammals only estradiol has been shown to be critical for female sexual motivation and behavior. Pharmaceutical companies have invested heavily in the development of androgen therapies for female sexual desire disorders, but today there are still no FDA approved androgen therapies for women. Nonetheless, testosterone is currently, and frequently, prescribed off-label for the treatment of low sexual desire in women, and the idea of testosterone as a possible cure-all for female sexual dysfunction remains popular. This paper places the ongoing debate concerning the hormonal modulation of women's sexual desire within a historical context, and reviews controlled trials of estrogen and/or androgen therapies for low sexual desire in postmenopausal women. These studies demonstrate that estrogen-only therapies that produce periovulatory levels of circulating estradiol increase sexual desire in postmenopausal women. Testosterone at supraphysiological, but not at physiological, levels enhances the effectiveness of low-dose estrogen therapies at increasing women's sexual desire; however, the mechanism by which supraphysiological testosterone increases women's sexual desire in combination with an estrogen remains unknown. Because effective therapies require supraphysiological amounts of testosterone, it remains unclear whether endogenous testosterone contributes to the modulation of women's sexual desire. The likelihood that an androgen-only clinical treatment will meaningfully increase women's sexual desire is minimal, and the focus of pharmaceutical companies on the development of androgen therapies for the treatment of female sexual desire disorders is likely misplaced. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis.

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Wang, Hao; Sun, Xuming; Chou, Jeff; Lin, Marina; Ferrario, Carlos M; Zapata-Sudo, Gisele; Groban, Leanne

2017-08-01

Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER. Copyright © 2016 Elsevier B.V. All rights reserved.

Female partners of opioid-injecting men in the Republic of Georgia: an initial characterization

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Lund Ingunn O

2012-11-01

Full Text Available Abstract Background HIV and Hepatitis C virus (HCV infections are strongly related to injection drug use in the Republic of Georgia. Little information is available about HIV and HCV status, sexual risk, support for their partner, and risk for physical violence among the female partners of opioid-injecting men in the Republic of Georgia, many of whom may not be using drugs, yet may be at high risk of being infected with HIV and HCV from their drug-using partners. Methods In order to better understand the risks for females whose partners are injecting drugs, the present study conducted an initial investigation of the non-substance-using female partners of 40 opioid-injecting men who were participating in a clinical trial examining the feasibility and efficacy of a 22-week comprehensive intervention that paired behavioral treatment with naltrexone. The 40 female partners were assessed at their male partners’ study intake. Results The female sample was 32.3 years old (SD=6.7, 37 (93% were married, with 15.5 years of education. A majority reported at least partial employment the majority of the time during the past 3 years, with only one woman reported being unemployed most of the time during the past 3 years. They self-reported they were 3% HIV-positive and 8% HCV-positive. Their HIV sex risk scores indicated a relatively low risk. However, only 4 (10% women reported using a condom most of the time while having sex and 15 (38% report not having had sex during the last 30 days. Experiences of interpersonal violence were common, with 42% reporting physical abuse by their partner during the last year and 48% reporting feeling unsafe in their current relationship. Conclusions The alarmingly high rate of failure to use barrier protection methods, together with the high percentage who did not know their HIV and HCV status, suggest that it may be beneficial to include non-substance-using female partners in prevention programs along with their partners

The effect of 17β-estradiol on cutaneous wound healing in protein-malnourished ovariectomized female mouse model.

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

2014-01-01

Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.

The effect of 17β-estradiol on cutaneous wound healing in protein-malnourished ovariectomized female mouse model.

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Kanae Mukai

Full Text Available Cutaneous wound healing is delayed by protein malnutrition (PM. On the other hand, estrogen promotes cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.

Urinary estrogen metabolites and self-reported infertility in women infected with Schistosoma haematobium.

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Júlio Santos

Full Text Available BACKGROUND: Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its association with the presence of schistosome-derived catechol-estrogens. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was undertaken of female residents of a region in Bengo province, Angola, endemic for schistosomiasis haematobia. Ninety-three women and girls, aged from two (parents interviewed to 94 years were interviewed on present and previous urinary, urogenital and gynecological symptoms and complaints. Urine was collected from the participants for egg-based parasitological assessment of schistosome infection, and for liquid chromatography diode array detection electron spray ionization mass spectrometry (LC/UV-DAD/ESI-MSn to investigate estrogen metabolites in the urine. Novel estrogen-like metabolites, potentially of schistosome origin, were detected in the urine of participants who were positive for eggs of S. haematobium, but not detected in urines negative for S. haematobium eggs. The catechol-estrogens/ DNA adducts were significantly associated with schistosomiasis (OR 3.35; 95% CI 2.32-4.84; P≤0.001. In addition, presence of these metabolites was positively associated with infertility (OR 4.33; 95% CI 1.13-16.70; P≤0.05. CONCLUSIONS/SIGNIFICANCE: Estrogen metabolites occur widely in diverse

Estrogens and progression of diabetic kidney damage.

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Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

2011-01-01

It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

TNF-{alpha} mediates the stimulation of sclerostin expression in an estrogen-deficient condition

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Kim, Beom-Jun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Bae, Sung Jin [Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Sun-Young; Lee, Young-Sun; Baek, Ji-Eun; Park, Sook-Young [Asan Institute for Life Sciences, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Seung Hun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Koh, Jung-Min, E-mail: jmkoh@amc.seoul.kr [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Kim, Ghi Su [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of)

2012-07-20

Highlights: Black-Right-Pointing-Pointer Estrogen deprivation stimulates the bony sclerostin levels with reversal by estrogen. Black-Right-Pointing-Pointer TNF-{alpha} increases the activity and expression of MEF2 in UMR-106 cells. Black-Right-Pointing-Pointer TNF-{alpha} blocker prevents the stimulation of bony sclerostin expression by ovariectomy. Black-Right-Pointing-Pointer No difference in bony sclerostin expression between sham-operated and ovariectomized nude mice. -- Abstract: Although recent clinical studies have suggested a possible role for sclerostin, a secreted Wnt antagonist, in the pathogenesis of postmenopausal osteoporosis, the detailed mechanisms how estrogen deficiency regulates sclerostin expression have not been well-elucidated. Bilateral ovariectomy or a sham operation in female C57BL/6 mice and BALB/c nude mice was performed when they were seven weeks of age. The C57BL/6 mice were intraperitoneally injected with phosphate-buffered serum (PBS), 5 {mu}g/kg {beta}-estradiol five times per week for three weeks, or 10 mg/kg TNF-{alpha} blocker three times per week for three weeks. Bony sclerostin expression was assessed by immunohistochemistry staining in their femurs. The activity and expression of myocyte enhancer factors 2 (MEF2), which is essential for the transcriptional activation of sclerostin, in rat UMR-106 osteosarcoma cells were determined by luciferase reporter assay and western blot analysis, respectively. Bony sclerostin expression was stimulated by estrogen deficiency and it was reversed by estradiol supplementation. When the UMR-106 cells were treated with well-known, estrogen-regulated cytokines, only TNF-{alpha}, but not IL-1 and IL-6, increased the MEF2 activity. Consistently, TNF-{alpha} also increased the nuclear MEF2 expression. Furthermore, the TNF-{alpha} blocker prevented the stimulation of bony sclerostin expression by ovariectomy. We also found that there was no difference in sclerostin expression between ovariectomized

TNF-α mediates the stimulation of sclerostin expression in an estrogen-deficient condition

International Nuclear Information System (INIS)

Kim, Beom-Jun; Bae, Sung Jin; Lee, Sun-Young; Lee, Young-Sun; Baek, Ji-Eun; Park, Sook-Young; Lee, Seung Hun; Koh, Jung-Min; Kim, Ghi Su

2012-01-01

Highlights: ► Estrogen deprivation stimulates the bony sclerostin levels with reversal by estrogen. ► TNF-α increases the activity and expression of MEF2 in UMR-106 cells. ► TNF-α blocker prevents the stimulation of bony sclerostin expression by ovariectomy. ► No difference in bony sclerostin expression between sham-operated and ovariectomized nude mice. -- Abstract: Although recent clinical studies have suggested a possible role for sclerostin, a secreted Wnt antagonist, in the pathogenesis of postmenopausal osteoporosis, the detailed mechanisms how estrogen deficiency regulates sclerostin expression have not been well-elucidated. Bilateral ovariectomy or a sham operation in female C57BL/6 mice and BALB/c nude mice was performed when they were seven weeks of age. The C57BL/6 mice were intraperitoneally injected with phosphate-buffered serum (PBS), 5 μg/kg β-estradiol five times per week for three weeks, or 10 mg/kg TNF-α blocker three times per week for three weeks. Bony sclerostin expression was assessed by immunohistochemistry staining in their femurs. The activity and expression of myocyte enhancer factors 2 (MEF2), which is essential for the transcriptional activation of sclerostin, in rat UMR-106 osteosarcoma cells were determined by luciferase reporter assay and western blot analysis, respectively. Bony sclerostin expression was stimulated by estrogen deficiency and it was reversed by estradiol supplementation. When the UMR-106 cells were treated with well-known, estrogen-regulated cytokines, only TNF-α, but not IL-1 and IL-6, increased the MEF2 activity. Consistently, TNF-α also increased the nuclear MEF2 expression. Furthermore, the TNF-α blocker prevented the stimulation of bony sclerostin expression by ovariectomy. We also found that there was no difference in sclerostin expression between ovariectomized nude mice and sham-operated nude mice. In conclusion, these results suggest that TNF-α originating from T cells may be at least in part

Loss of miR-10a activates Lpo and collaborates with activated Wnt signaling in inducing intestinal Neoplasia in female mice

DEFF Research Database (Denmark)

Stadthagen Gomez, Gustavo; Tehler, Disa Elisabet; Høyland-Kroghsbo, Nina Molin

2013-01-01

, in the Apc(min) mouse model of intestinal neoplasia, female miR-10a deficient mice develop significantly more adenomas than miR-10(+/+) and male controls. We further found that Lpo is extensively upregulated in the intestinal epithelium of mice deprived of miR-10a. Using in vitro assays, we demonstrate...... that the primary miR-10a target KLF4 can upregulate transcription of Lpo, whereas siRNA knockdown of KLF4 reduces LPO levels in HCT-116 cells. Furthermore, Klf4 is upregulated in the intestines of miR-10a knockout mice. Lpo has previously been shown to have the capacity to oxidize estrogens into potent...... depurinating mutagens, creating an instable genomic environment that can cause initiation of cancer. Therefore, we postulate that Lpo upregulation in the intestinal epithelium of miR-10a deficient mice together with the predominant abundance of estrogens in female animals mainly accounts for the sex...

Innate immunity is sufficient for the clearance of Chlamydia trachomatis from the female mouse genital tract.

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Sturdevant, Gail L; Caldwell, Harlan D

2014-10-01

Chlamydia muridarum and Chlamydia trachomatis, mouse and human strains, respectively, have been used to study immunity in a murine model of female genital tract infection. Despite evidence that unique genes of these otherwise genomically similar strains could play a role in innate immune evasion in their respective mouse and human hosts, there have been no animal model findings to directly support this conclusion. Here, we infected C57BL/6 and adaptive immune-deficient Rag1(-/-) female mice with these strains and evaluated their ability to spontaneously resolve genital infection. Predictably, C57BL/6 mice spontaneously cleared infection caused by both chlamydial strains. In contrast, Rag1(-/-) mice which lack mature T and B cell immunity but maintain functional innate immune effectors were incapable of resolving C. muridarum infection but spontaneously cleared C. trachomatis infection. This distinct dichotomy in adaptive and innate immune-mediated clearance between mouse and human strains has important cautionary implications for the study of natural immunity and vaccine development in the mouse model. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.

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Marisa R Buchakjian

Full Text Available Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection. Luciferase expression measured by real-time bioluminescence imaging increases over time, with an initial robust increase following viral injection, followed by a steady rise over the next several weeks as primary tumors develop and grow. Intramuscular injections were more commonly associated with evidence of systemic viral distribution than subcutaneous injections. All mice developed soft tissue sarcomas at the primary injection site, with histological examination identifying 93% of tumors as invasive pleomorphic sarcomas based on microscopic morphology and immunohistochemical expression of sarcoma markers. A lymphocytic infiltrate was present in 64% of the sarcomas in this immunocompetent model and 71% of tumors expressed PD-L1. This is the first report of a viral-Cre mediated Trp53/Pten mouse model of undifferentiated pleomorphic sarcoma. The bioluminescence imaging feature, along with high penetrance of the model and its immunological characteristics, makes it suited for pre-clinical studies of soft tissue sarcoma.

Estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury

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Vida Naderi

2015-02-01

Full Text Available Objective(s:Estrogen (E2 has neuroprotective effects on blood-brain-barrier (BBB after traumatic brain injury (TBI. In order to investigate the roles of estrogen receptors (ERs in these effects, ER-α antagonist (MPP and, ER-β antagonist (PHTPP, or non-selective estrogen receptors antagonist (ICI 182780 were administered. Materials and Methods: Ovariectomized rats were divided into 10 groups, as follows: Sham, TBI, E2, oil, MPP+E2, PHTPP+E2, MPP+PHTPP+E2, ICI+E2, MPP, and DMSO. E2 (33.3 µg/Kg or oil were administered 30 min after TBI. 1 dose (150 µg/Kg of each of MPP, PHTPP, and (4 mg/kg ICI182780 was injected two times, 24 hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content and brain edema (brain water content evaluated 5 hr and 24 hr after the TBI were evaluated, respectively. Results: The results showed that E2 reduced brain edema after TBI compared to vehicle (P

Why do females use botulinum toxin injections?

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Carter Singh

2015-01-01

Full Text Available Background: Botulinum toxin (BT use for enhancing the facial features has become a commonly accepted form of aesthetic intervention. This study conducted a self-report survey of female BT users in order to explore the motivating factors in its use (cost-benefit analysis. Settings and Design: This is a cross-sectional exploratory pilot study. Materials and Methods: Self-report questionnaires were administered to 41 consecutive clients attending an independent medical practice for BT injections for cosmetic purposes. All the participants were females and represented a range of age groups from the 20s to above 60s. Items in the nonstandardized questionnaire elicited questions relating to the reasons for and against BT use. Statistical Analysis Used: Descriptive analysis was used rather than inferential statistics, and involved ranking the responses according to the most likely reasons for using BT and disadvantages of its use. Results: In general, the primary motivating factor for BT use was to improve self-esteem, and the greatest disadvantage involved financial costs associated with the procedure. Conclusions: The main findings of this study suggest that females who use BT for aesthetic purposes are motivated by personal psychological gains (intrapersonal attributes rather than social gains (interpersonal factors. In other words, they do not believe that having BT will equate to being treated any better by other people but would rather provide them with confidence and satisfaction regarding their self-image.

The role of estrogen in cutaneous ageing and repair.

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Wilkinson, Holly N; Hardman, Matthew J

2017-09-01

Combined advances in modern medical practice and increased human longevity are driving an ever-expanding elderly population. Females are particularly at risk of age-associated pathology, spending more of their lives in a post-menopausal state. Menopause, denoted by a rapid decline in serum sex steroid levels, accelerates biological ageing across the body's tissues. Post-menopause physiological changes are particularly noticeable in the skin, which loses structural architecture and becomes prone to damage. The sex steroid most widely discussed as an intrinsic contributor to skin ageing and pathological healing is 17β-estradiol (or estrogen), although many others are involved. Estrogen deficiency is detrimental to many wound-healing processes, notably inflammation and re-granulation, while exogenous estrogen treatment widely reverses these effects. Over recent decades, many of the molecular and cellular correlates to estrogen's beneficial effect on normal skin homeostasis and wound healing have been reported. However, disparities still exist, particularly in the context of mechanistic studies investigating estrogen receptor signalling and its potential cellular effects. New molecular techniques, coupled with increased understanding of estrogen in skin biology, will provide further opportunities to develop estrogen receptor-targeted therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

The selective estrogen receptor alpha agonist Org 37663 induces estrogenic effects but lacks antirheumatic activity: a phase IIa trial investigating efficacy and safety of Org 37663 in postmenopausal female rheumatoid arthritis patients receiving stable background methotrexate or sulfasalazine.

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van Vollenhoven, Ronald F; Houbiers, Jos G A; Buttgereit, Frank; In 't Hout, Joanna; Boers, Maarten; Leij, Susanne; Kvien, Tore K; Dijkmans, Ben A C; Szczepański, Leszek; Szombati, Istvan; Sierakowski, Stanislaw; Miltenburg, André M M

2010-02-01

Multiple lines of evidence suggest that sex hormones may play a role in the pathogenesis or clinical expression of rheumatoid arthritis (RA). Studies on the effects of exogenous estrogens in RA patients have yielded contradictory results. We undertook this study to determine the effects of the selective estrogen receptor alpha (ERalpha) agonist Org 37663 in patients with RA, in terms of both its estrogenic effects and its ability to ameliorate disease activity. A 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-finding, proof-of-concept trial was initiated to obtain data on the efficacy and safety of Org 37663 in postmenopausal female patients with RA who were receiving background treatment with either methotrexate or sulfasalazine. Patients were randomized to receive placebo or Org 37663 at doses of 4 mg/day, 15 mg/day, or 50 mg/week. The primary efficacy variable was the Disease Activity Score in 28 joints (DAS28). Org 37663 induced a clear biologic, estrogenic response in several organ systems, including a dose-related increase in levels of sex hormone binding globulin. However, the DAS28 decreased similarly for all treatment groups including placebo, indicating lack of clinical efficacy of Org 37663 in this trial. The observed lack of clinical benefit in RA patients treated with an ERalpha agonist, in association with a clear biologic response to the study drug, provides evidence that a biologically relevant ERalpha-mediated estrogenic effect is not associated with a clinically relevant effect on RA symptoms and signs.

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

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Estrogens act in the ventromedial hypothalamic nucleus (VMH) to regulate body weight homeostasis. However, the molecular mechanisms underlying these estrogenic effects are unknown. We show that activation of estrogen receptor-a (ERa) stimulates neural firing of VMH neurons expressing ERa, and these ...

Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury

NARCIS (Netherlands)

de Vries, Heleen A. H.; Ponds, Fraukje A. M.; Nieuwenhuijs, Vincent B.; Morphett, Arthur; Padbury, Robert T. A.; Barritt, Greg J.

2013-01-01

Introduction. Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question.

Impact of estrogen receptor α gene and oxytocin receptor gene polymorphisms on female sexuality

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Anastasia K Armeni

2017-02-01

Full Text Available Over the past decades, research attention has increasingly been paid to the neurobiological component of sexual behavior. The aim of the present study was to investigate the correlation of estrogen receptor α (ERA gene polymorphism (rs2234693-PvuII (T→C substitution and oxytocin receptor gene polymorphism (rs53576 (G→A substitution with sexuality parameters of young, healthy women. One hundred thirty-three Greek heterosexual women, students in higher education institutions, 20–25 years of age, sexually active, with normal menstrual cycles (28–35 days, were recruited in the study. Exclusion criteria were chronic and/or major psychiatric diseases, use of oral contraceptive pills (OCs, polycystic ovary syndrome (PCOS, thyroid diseases as well as drugs that are implicated in hypothalamus–pituitary–gonadal axis. T allele (wildtype of rs2234693 (PvuII polymorphism of ERA gene was correlated with increased levels of arousal and lubrication, whereas A allele (polymorphic of rs53576 (OXTR polymorphism was correlated with increased arousal levels. The simultaneous presence of both T allele of rs2234693 (PvuII and A allele of rs53576 (OXTR polymorphisms (T + A group was correlated with increased arousal, orgasm levels as well as female sexual function index full score. To our knowledge, this is the first study to investigate the interaction between ERA and OXTR with regard to sexual function in women. Female sexuality is a complex behavioral trait that encompasses both biological and psychological components. It seems that variability in female sexual response stems from genetic variability that characterizes endocrine, neurotransmitter and central nervous system influences.

Steroid metabolism in the mouse placenta

International Nuclear Information System (INIS)

Okker-Reitsma, G.H.

1976-01-01

The purpose of the study described in this thesis was to investigate the capacity for steroid synthesis of the mouse placenta - especially the production of progesterone, androgens and estrogens - and to determine, if possible, the relation of steroid synthesis to special cell types. In an introductory chapter the androgen production in the mouse placenta is surveyed by means of a histochemical and bioindicator study of different stages of development of the placenta. The metabolism of [ 3 H]-dehydroepiandrosterone and [ 3 H]-progesterone by mouse placental tissue in vitro is studied. The metabolism of [ 3 H]-progesterone by the mouse fetal adrenal in vitro is also studied

Estrogen, Estrogen Receptor and Lung Cancer

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Li-Han Hsu

2017-08-01

Full Text Available Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR, and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

Estrogens and Androgens in Skeletal Physiology and Pathophysiology.

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Almeida, Maria; Laurent, Michaël R; Dubois, Vanessa; Claessens, Frank; O'Brien, Charles A; Bouillon, Roger; Vanderschueren, Dirk; Manolagas, Stavros C

2017-01-01

Estrogens and androgens influence the growth and maintenance of the mammalian skeleton and are responsible for its sexual dimorphism. Estrogen deficiency at menopause or loss of both estrogens and androgens in elderly men contribute to the development of osteoporosis, one of the most common and impactful metabolic diseases of old age. In the last 20 years, basic and clinical research advances, genetic insights from humans and rodents, and newer imaging technologies have changed considerably the landscape of our understanding of bone biology as well as the relationship between sex steroids and the physiology and pathophysiology of bone metabolism. Together with the appreciation of the side effects of estrogen-related therapies on breast cancer and cardiovascular diseases, these advances have also drastically altered the treatment of osteoporosis. In this article, we provide a comprehensive review of the molecular and cellular mechanisms of action of estrogens and androgens on bone, their influences on skeletal homeostasis during growth and adulthood, the pathogenetic mechanisms of the adverse effects of their deficiency on the female and male skeleton, as well as the role of natural and synthetic estrogenic or androgenic compounds in the pharmacotherapy of osteoporosis. We highlight latest advances on the crosstalk between hormonal and mechanical signals, the relevance of the antioxidant properties of estrogens and androgens, the difference of their cellular targets in different bone envelopes, the role of estrogen deficiency in male osteoporosis, and the contribution of estrogen or androgen deficiency to the monomorphic effects of aging on skeletal involution. Copyright © 2017 the American Physiological Society.

Estrogen influences dolichyl phosphate distribution among glycolipid pools in mouse uteri

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Carson, D.D.; Tang, J.; Hu, G.

1987-03-24

To determine the role that dolichyl phosphate availability plays in this induction, the authors studied the effects of estrogen priming on the content of dolichyl phosphate and the distribution of dolichyl phosphate among various glycolipids in uteri. Dolichol-linked saccharides were metabolically labeled to equilibrium with either (/sup 3/H)glucosamine or (/sup 3/H)mannose and extracted from primary explants of uterine tissue. The amount of dolichol-linked saccharide was calculated from the specific radioactivity determined for the corresponding sugar nucleotides extracted from the tissues. The major dolichol-linked saccharides identified were mannosylphosphoryldolichol (MPD), oligosaccharylpyrophosphorydolichol (OSL), and N,N'-diacetylchitobiosylpyrophosphoryldolichol (CBL). Estrogen increased the levels of MPD and OSL 4-fold; however, CBL levels did not change. After 3 days of treatment, the levels of these glycolipids were very similar to those in uteri from pregnant mice. The specific activity of GPD synthase was similar under all conditions studied. These studies provide the first determination of the levels of dolichol-linked saccharides in tissues and how these levels change during hormonal induction of glycoprotein assembly. Coupled with earlier studies, the present work demonstrates that among a number of key points of N-linked oligosaccharide assembly and transfer only synthesis of MPD increases coordinately with the increase observed in lipid- and protein-linked oligosaccharide assembly that occurs in vivo in response to estrogen. They suggest that control of MPD levels is an important regulatory aspect of N-linked glycoprotein assembly in this system.

Expressions of Uroplakins in the Mouse Urinary Bladder with Cyclophosphamide-Induced Cystitis

OpenAIRE

Choi, Seong Hoo; Byun, Youngmin; Lee, Gilho

2009-01-01

Even though uroplakins (UPs) are believed to serve a strong protective barrier against toxic materials, cyclophosphamide (CP) causes extensive cystitis. We investigated the expression of UPs in the urothelium in CP induced mouse cystitis. A total of 27 ICR female mice received a single intraperitoneal injection of 200 mg CP/kg. Nine CP-treated mice and 6 controls were sequentially killed at 12, 24, and 72 hr post injection. Extensive cystitis and an increased vesical weight were seen. These a...

Estrogens and the risk of complex regional pain syndrome (CRPS).

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de Mos, M; Huygen, F J P M; Stricker, B H Ch; Dieleman, J P; Sturkenboom, M C J M

2009-01-01

Since complex regional pain syndrome (CRPS) shows a clear female predominance, we investigated the association between the cumulative as well as current exposure to estrogens, and CRPS. A population-based case-control study was conducted in the Integrated Primary Care Information (IPCI) project in the Netherlands. Cases were identified from electronic records (1996-2005) and included if they were confirmed during a visit (using International Association for the Study of Pain Criteria), or had been diagnosed by a specialist. Controls were matched to cases on gender, age, calendar time, and injury. Measures of cumulative endogenous estrogen exposure were obtained by questionnaire and included age of menarche and menopause, menstrual life, and cumulative months of pregnancy and breast-feeding. Current estrogen exposure at CRPS onset was retrieved from the electronic medical records and determined by current pregnancy or by the use of oral contraceptive (OC) drugs or hormonal replacement therapy (HRT). Hundred and forty-three female cases (1493 controls) were included in analyses on drug use and pregnancies, while cumulative endogenous estrogen exposure was studied in 53 cases (58 controls) for whom questionnaire data were available. There was no association between CRPS and either cumulative endogenous estrogen exposure, OC, or HRT use. CRPS onset was increased during the first 6 months after pregnancy (OR: 5.6, 95%CI: 1.0-32.4), although based on small numbers. We did not find an association between CRPS onset and cumulative endogenous estrogen exposure or current OC or HRT use, but more powered studies are needed to exclude potential minor associations.

Estradiol upregulates calcineurin expression via overexpression of estrogen receptor alpha gene in systemic lupus erythematosus

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Hui-Li Lin

2011-04-01

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease primarily affecting women (9:1 compared with men. To investigate the influence of female sex hormone estrogen on the development of female-biased lupus, we compared the expression of estrogen receptor alpha (ERα gene and protein levels as well as expression of T-cell activation gene calcineurin in response to estrogen in peripheral blood lymphocytes (PBLs from SLE patients and normal controls. PBLs were isolated from 20 female SLE patients and 6 normal female controls. The amount of ERα protein in PBL was measured by flow cytometry. The expression of ERα and calcineurin messenger RNA was measured by semi-quantitative reverse transcription-polymerase chain reaction. Calcineurin phosphatase activity was measured by calcineurin assay kit. The expression of ERα messenger RNA and ERα protein was significantly increased (p=0.001 and p=0.023, respectively in PBL from SLE patients compared with that from normal controls. In addition, the basal calcineurin in PBL from SLE patients was significantly higher (p=0.000 than that from normal controls, and estrogen-induced expression of calcineurin was increased (p=0.007 in PBL from SLE patients compared with that from normal controls, a 3.15-fold increase. This increase was inhibited by the ERα antagonism ICI 182,780. The effects of ER antagonism were also found in calcineurin activity. These data suggest that overexpression of ERα gene and enhanced activation of calcineurin in response to estrogen in PBL may contribute to the pathogenesis of female dominant in SLE.

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

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Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

2017-10-01

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency

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Andrea Z. Tuckett

2017-05-01

Full Text Available Abstract Background Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice is feasible and facilitates the generation of functional T cells conferring protective immunity. Methods Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase+, CD45.1+ and injected intravenously or intrathymically into both male and female, young or aged NOD-scid IL2rγnull recipients. The in vivo fate of injected cells was analyzed by bioluminescence imaging and flow cytometry of thymus- and spleen-derived T cell populations. In addition to T cell reconstitution, we evaluated mice for evidence of immune dysregulation based on diabetes development and graft-versus-host disease. T cell immunity following intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγnull mice was assessed in a B cell lymphoma model. Results Despite the small size of the thymic remnant in NOD-scid IL2rγnull mice, we were able to accomplish precise intrathymic delivery of hematopoietic stem and progenitor cells by ultrasound-guided injection. Thymic reconstitution following intrathymic injection of healthy allogeneic hematopoietic cells was most effective in young male recipients, indicating that even in the setting of severe immunodeficiency, sex and age are important variables for thymic function. Allogeneic T cells generated in intrathymically injected NOD-scid IL2rγnull mice displayed anti-lymphoma activity in vivo, but we found no evidence for severe auto/alloreactivity in T cell-producing NOD-scid IL2rγnull mice, suggesting that immune dysregulation is not a major concern

Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy

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Sarzi, Emmanuelle; Seveno, Marie; Angebault, Claire

2016-01-01

levels of steroid precursor pregnenolone in females, causing an early-onset vision loss, abolished by ovariectomy. In addition, steroid production in retina is also increased which, in conjunction with high circulating levels, impairs estrogen receptor expression and mitochondrial respiratory complex IV...... tested the hypothesis of deregulated steroid production in retina due to a disease-causing OPA1 mutation and its contribution to the visual phenotypic variations. Using the mouse model carrying the human recurrent OPA1 mutation, we disclosed that Opa1 haploinsufficiency leads to very high circulating...

Shenfu injection attenuates neurotoxicity of bupivacaine in cultured mouse spinal cord neurons

Institute of Scientific and Technical Information of China (English)

XIONG Li-ze; WANG Qiang; LIU Mu-yun; PENG Ye; LI Qing-bo; LU Zhi-hong; LEI Chong

2007-01-01

Background Our previous in vivo study in the rat demonstrates that Shenfu injection, a clinically used extract preparation from Chinese herbs, attenuates neural and cardiac toxicity induced by intravenous infusion of bupivacaine, a local anesthetic. This study was designed to investigate whether bupivacaine could induce a toxic effect in primary cultured mouse spinal cord neuron and if so, whether the Shenfu injection had a similar neuroprotective effect in the cell model. Methods The spinal cords from 11- to 14-day-old fetal mice were minced and incubated. Cytarabine was added into the medium to inhibit the proliferation of non-neuronal cells. The immunocytochemical staining of β-tubulin was used to determine the identity of cultured cells. The cultured neurons were randomly assigned into three sets treated with various doses of bupivacaine, Shenfu and bupivacaine+Shenfu, for 48 hours respectively. Cell viability in each group was analyzed by methyl thiazoleterazolium (MTT) assay. Results The viability of the cultured neurons treated with bupivacaine at concentrations of 0.01%, 0.02%, 0.04% and 0.08% was decreased in a dose-dependent manner. Although the Shenfu injection at concentrations ranging from 1/50 to 1/12.5 (V/V) had no significant influence on the viability of cultured neurons (P＜0.05 vs control), the injection significantly increased the cellular viability of cultured neurons pretreated with 0.03% bupivacaine (P＜0.05). Conclusion Although Shenfu injection itself has no effect on spinal neurons, it was able to reduce the bupivacaine induced neurotoxicity in vitro.

Polycystic Ovary Induction in Mouse by Testosterone Enanthate

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Zahra Kalhori

2014-03-01

Full Text Available Background &Objective: Polycystic ovary is the most common cause of infertility in Women. Animal models are required for understanding the pathogenesis of polycystic ovary. The objective of this study then was to develop an animal model for inducing the polycystic ovaries using testosterone enanthate.Materials & Methods: In this study, for inducing the polycystic ovary phenotype, female rats about12-14 days-old were injected daily with testosterone enanthate for 2 and 4 weeks (experiment groups: 1 and 2, while the control groups (1 and 2 were injected only with vehicle.The ovaries from both groups were fixed and then were used for histological studies.Results: Testosterone enanthate treatment causes the histological changes in mouse ovary and significantly increased the percentage of preantral and cystic follicles and decreased the percentage of antral follicles in the experiment group, comparing with the control group (P<0.05.Conclusion: It concluded that testosterone enanthate can induces polycystic ovary in mouse.

Surviving in two worlds: social and structural violence of Thai female injecting drug users.

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Haritavorn, Niphattra

2014-01-01

Thai females injecting drugs are ensnared in a web of problems arising from forms of prejudice that magnify their vulnerability. They are vulnerable, at risk, and exposed to a high degree of social suffering. This paper aims to elucidate how social production and structural violence combine to shape the lives of these women. Using a qualitative methodology, two focus groups with 5 key informants and in-depth interviews involving a total of 35 women injecting drugs were conducted in Bangkok. The findings reveal that the structural environment that directly impacts upon these women's lives becomes the reason for their suffering. The structural environment puts these women at risk of violence in numerous social settings in which these women engage as well as generating tension at a subjective level (i.e. the habitus) of these women. Thai female injecting drug users are trapped in a difficult tension between the demands for being Thai women seeking to exist in the masculine world of drug use but at the same time meeting Thai society's expectations of womanhood. Unequal gender relations are manifest in the everyday violence that women face in the drug community, culminating in the essential nature of women being questioned, undermined and threatened. Living in the drug community, women are subjected to violence and harassment, and gendered brutality by intimate partners. In conclusion, the social suffering that Thai female injecting drug users find themselves confronting is confined to dilemmas cause by tensions between drug use and the overriding gender habitus. Copyright © 2013 Elsevier B.V. All rights reserved.

Female sexual arousal in amphibians.

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Wilczynski, Walter; Lynch, Kathleen S

2011-05-01

Rather than being a static, species specific trait, reproductive behavior in female amphibians is variable within an individual during the breeding season when females are capable of reproductive activity. Changes in receptivity coincide with changes in circulating estrogen. Estrogen is highest at the point when females are ready to choose a male and lay eggs. At this time female receptivity (her probability of responding to a male vocal signal) is highest and her selectivity among conspecific calls (measured by her probability of responding to a degraded or otherwise usually unattractive male signal) is lowest. These changes occur even though females retain the ability to discriminate different acoustic characteristics of various conspecific calls. After releasing her eggs, female amphibians quickly become less receptive and more choosy in terms of their responses to male sexual advertisement signals. Male vocal signals stimulate both behavior and estrogen changes in amphibian females making mating more probable. The changes in female reproductive behavior are the same as those generally accepted as indicative of a change in female sexual arousal leading to copulation. They are situationally triggered, gated by interactions with males, and decline with the consummation of sexual reproduction with a chosen male. The changes can be triggered by either internal physiological state or by the presence of stimuli presented by males, and the same stimuli change both behavior and physiological (endocrine) state in such a way as to make acceptance of a male more likely. Thus amphibian females demonstrate many of the same general characteristics of changing female sexual state that in mammals indicate sexual arousal. Copyright © 2010 Elsevier Inc. All rights reserved.

Gender, Estrogen, and Obliterative Lesions in the Lung

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Hamza Assaggaf

2017-01-01

Full Text Available Gender has been shown to impact the prevalence of several lung diseases such as cancer, asthma, chronic obstructive pulmonary disease, and pulmonary arterial hypertension (PAH. Controversy over the protective effects of estrogen on the cardiopulmonary system should be of no surprise as clinical trials of hormone replacement therapy have failed to show benefits observed in experimental models. Potential confounders to explain these inconsistent estrogenic effects include the dose, cellular context, and systemic versus local tissue levels of estrogen. Idiopathic PAH is disproportionately found to be up to 4 times more common in females than in males; however, estrogen levels cannot explain why males develop PAH sooner and have poorer survival. Since the sex steroid hormone 17β-estradiol is a mitogen, obliterative processes in the lung such as cell proliferation and migration may impact the growth of pulmonary tissue or vascular cells. We have reviewed evidence for biological differences of sex-specific lung obliterative lesions and highlighted cell context-specific effects of estrogen in the formation of vessel lumen-obliterating lesions. Based on this information, we provide a biological-based mechanism to explain the sex difference in PAH severity as well as propose a mechanism for the formation of obliterative vascular lesions by estrogens.

Effects of estrogen on very low-density lipoprotein triglyceride metabolism in fed and fasted chicks

International Nuclear Information System (INIS)

Park, J.R.

1988-01-01

A single injection of estrogen into growing chicks resulted in a marked elevation in plasma triglyceride (TG) followed by phospholipid (PL) and cholesterol (CH) in both fed and fasted chicks. Estrogen caused a development of massive fatty liver in fed chicks. Hepatic malic enzyme and glucose-6-phosphate dehydrogenase activities also increased significantly in fed chicks and, to a small extent, in fasted chicks. Very low density lipoproteins (VLDL) were barely detectable in the fasted control plasma. However, the VLDL concentration increased markedly upon estrogen injection, becoming the most prevalent lipoprotein in the plasma. The administration of estrogen resulted in an increase in oleic acid and a decrease in linoleic acid content except in the cholesteryl ester of VLDL and LDL. VLDL of estrogenized birds had β-mobility on agarose gel electrophoresis, and they eluted in two peaks on agarose gel filtration chromatography. Both peaks on gel filtration exhibited the same β-mobility on agarose gel electrophoresis. Nevertheless, the apoprotein composition of these two peaks were substantially different from each other; apo B was not present in the first peak VLDL. VLDL-TG kinetic studies conducted in vivo, using 14 C-TG-VLDL prepared endogenously from control and estrogenized chicks revealed that VLDL-TG produced from the former had a higher fractional catabolic rate (FCR) than VLDL-TG from the latter

The ERa-PI3K cascade in proopiomelanocortin progenitor neurons regulates feeding and glucose balance in female mice

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Estrogens act upon estrogen receptor (ER)a to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ERa sp...

HIV risk, health, and social characteristics of sexual minority female injection drug users in Baltimore

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German, Danielle; Latkin, Carl A.

2015-01-01

Female injection drug users {IDU} who report sex with women are at increased risk for HIV and social instability, but it is important to assess whether these disparities also exist according to sexual minority identity rather than behaviorally defined categories. Within a sample of current IDU in Baltimore, about 17% of female study participants (n=307) identified as gay/lesbian/bisexual. In controlled models, sexual minorities were three times as likely to report sex exchange behavior and four times as likely to report a recent STI. Injection risk did not differ significantly, but sexual minority women reported higher prevalence of socio-economic instability, negative health indicators, and fewer network financial, material, and health support resources. There is a need to identify and address socio-economic marginalization, social support, and health issues among female IDUs who identify as lesbian or bisexual. PMID:25504312

Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters

NARCIS (Netherlands)

Bui, H.N.; Schagen, S.E.; Klink, D.T.; Delemarre-van de Waal, H.A.; Blankenstein, M.A.; Heijboer, A.C.

2013-01-01

Introduction: In our hospital, female-To-male (FtM) transgender adolescents from the age of 16 are treated with two- or four-weekly intra-muscular injections of testosterone-esters. Some patients treated with four-weekly injections have complaints of fatigue and experience mood swings towards the

The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: A randomized placebo-controlled study.

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Tawfik, Abeer Attia; Osman, Mai Abdel Raouf

2018-02-01

Hair is an essential part of a woman's appearance and attractiveness. This is reflected in the predominantly psychological morbidity that can be associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss. To evaluate the efficacy and safety of autologous platelet-rich plasma in the treatment of female pattern hair loss. Thirty female patients with female pattern hair loss were randomly assigned to receive autologous PRP injection into a selected area, and another area was injected with normal saline as a placebo. Sessions were performed weekly for a maximum total of four sessions. Patients were followed up 6 months after the end of last session. The outcome was assessed both subjectively and objectively. There was a statistical significant difference between PRP and placebo areas (Phair density and hair thickness as measured by a folliscope. The hair pull test became negative in PRP-injected areas in 25 patients (83%) with average number of three hairs. Global pictures showed a significant improvement in hair volume and quality together with a high overall patient satisfaction in PRP-injected sites, and these results were maintained during the 6-month follow- up. Platelet-rich plasma injections can be regarded as an alternative for the treatment of female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio. © 2017 Wiley Periodicals, Inc.

The relationship between ovarian steroids and uterine estrogen receptors during late pregnancy

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Cathey, T.M.; Chung, Kyung W. (Univ. of Oklahoma, Oklahoma City (USA))

1991-01-01

Although a direct interdependence exists between the ovarian steroids, estrogen and progesterone, the exact role of these two hormones during pregnancy, especially late pregnancy, is not completely understood. Investigations have been conducted to determine whether the circulating levels of progesterone and estrogen or changes in the ratio of progesterone/estrogen in relation to the concentration of uterine estrogen receptors are associated with triggering parturition. Ninety-day old female rats were sacrificed at gestation days 14, 16, 18, 20 and two days post-partum. The plasma levels of estradiol and progesterone were measured by solid-phase radioimmunoassay. Uterine cytosol was subjected to a charcoal binding assay to determine the concentration of estrogen receptors. Our findings demonstrate that there is a significant drop in both plasma progesterone and estradiol during late pregnancy. Also indicated is a significant increase in uterine estrogen receptors throughout late pregnancy. Finally, during this period there is a direct correlation between the shift in the progesterone/estrogen ratio and the increase in the concentration of uterine estrogen receptors in late pregnancy.

The relationship between ovarian steroids and uterine estrogen receptors during late pregnancy

International Nuclear Information System (INIS)

Cathey, T.M.; Chung, Kyung W.

1991-01-01

Although a direct interdependence exists between the ovarian steroids, estrogen and progesterone, the exact role of these two hormones during pregnancy, especially late pregnancy, is not completely understood. Investigations have been conducted to determine whether the circulating levels of progesterone and estrogen or changes in the ratio of progesterone/estrogen in relation to the concentration of uterine estrogen receptors are associated with triggering parturition. Ninety-day old female rats were sacrificed at gestation days 14, 16, 18, 20 and two days post-partum. The plasma levels of estradiol and progesterone were measured by solid-phase radioimmunoassay. Uterine cytosol was subjected to a charcoal binding assay to determine the concentration of estrogen receptors. Our findings demonstrate that there is a significant drop in both plasma progesterone and estradiol during late pregnancy. Also indicated is a significant increase in uterine estrogen receptors throughout late pregnancy. Finally, during this period there is a direct correlation between the shift in the progesterone/estrogen ratio and the increase in the concentration of uterine estrogen receptors in late pregnancy

Intraocular Injection of ES Cell-Derived Neural Progenitors Improve Visual Function in Retinal Ganglion Cell-Depleted Mouse Models

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Mundackal S. Divya

2017-09-01

Full Text Available Retinal ganglion cell (RGC transplantation is a promising strategy to restore visual function resulting from irreversible RGC degeneration occurring in glaucoma or inherited optic neuropathies. We previously demonstrated FGF2 induced differentiation of mouse embryonic stem cells (ESC to RGC lineage, capable of retinal ganglion cell layer (GCL integration upon transplantation. Here, we evaluated possible improvement of visual function by transplantation of ES cell derived neural progenitors in RGC depleted glaucoma mice models. ESC derived neural progenitors (ES-NP were transplanted into N-Methyl-D-Aspartate (NMDA injected, RGC-ablated mouse models and a pre-clinical glaucoma mouse model (DBA/2J having sustained higher intra ocular pressure (IOP. Visual acuity and functional integration was evaluated by behavioral experiments and immunohistochemistry, respectively. GFP-expressing ES-NPs transplanted in NMDA-injected RGC-depleted mice differentiated into RGC lineage and possibly integrating into GCL. An improvement in visual acuity was observed after 2 months of transplantation, when compared to the pre-transplantation values. Expression of c-Fos in the transplanted cells, upon light induction, further suggests functional integration into the host retinal circuitry. However, the transplanted cells did not send axonal projections into optic nerve. Transplantation experiments in DBA/2J mouse showed no significant improvement in visual functions, possibly due to both host and transplanted retinal cell death which could be due to an inherent high IOP. We showed that, ES NPs transplanted into the retina of RGC-ablated mouse models could survive, differentiate to RGC lineage, and possibly integrate into GCL to improve visual function. However, for the survival of transplanted cells in glaucoma, strategies to control the IOP are warranted.

Identification of choriogenin cis-regulatory elements and production of estrogen-inducible, liver-specific transgenic Medaka.

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Ueno, Tetsuro; Yasumasu, Shigeki; Hayashi, Shinji; Iuchi, Ichiro

2004-07-01

Choriogenins (chg-H, chg-L) are precursor proteins of egg envelope of medaka and synthesized in the spawning female liver in response to estrogen. We linked a gene construct chg-L1.5 kb/GFP (a 1.5 kb 5'-upstream region of the chg-L gene fused with a green fluorescence protein (GFP) gene) to another construct emgb/RFP (a cis-regulatory region of embryonic globin gene fused with an RFP gene), injected the double fusion gene construct into 1- or 2-cell-stage embryos, and selected embryos expressing the RFP in erythroid cells. From the embryos, we established two lines of chg-L1.5 kb/GFP-emgb/RFP-transgenic medaka. The 3-month-old spawning females and estradiol-17beta (E2)-exposed males displayed the liver-specific GFP expression. The E2-dependent GFP expression was detected in the differentiating liver of the stage 37-38 embryos. In addition, RT-PCR and whole-mount in situ hybridization showed that the E2-dependent chg expression was found in the liver of the stage 34 embryos of wild medaka, suggesting that such E2-dependency is achieved shortly after differentiation of the liver. Analysis using serial deletion mutants fused with GFP showed that the region -426 to -284 of the chg-L gene or the region -364 to -265 of the chg-H gene had the ability to promote the E2-dependent liver-specific GFP expression of its downstream gene. Further analyses suggested that an estrogen response element (ERE) at -309, an ERE half-site at -330 and a binding site for C/EBP at -363 of the chg-L gene played important roles in its downstream chg-L gene expression. In addition, this transgenic medaka may be useful as one of the test animals for detecting environmental estrogenic steroids.

Ovariectomy and subsequent treatment with estrogen receptor agonists tune the innate immune system of the hippocampus in middle-aged female rats.

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Miklós Sárvári

Full Text Available The innate immune system including microglia has a major contribution to maintenance of the physiological functions of the hippocampus by permanent monitoring of the neural milieu and elimination of tissue-damaging threats. The hippocampus is vulnerable to age-related changes ranging from gene expression to network connectivity. The risk of hippocampal deterioration increases with the decline of gonadal hormone supply. To explore the impact of hormone milieu on the function of the innate immune system in middle-aged female rats, we compared mRNA expression in the hippocampus after gonadal hormone withdrawal, with or without subsequent estrogen replacement using estradiol and isotype-selective estrogen receptor (ER agonists. Targeted profiling assessed the status of the innate immune system (macrophage-associated receptors, complement, inhibitory neuronal ligands, local estradiol synthesis (P450 aromatase and estrogen reception (ER. Results established upregulation of macrophage-associated (Cd45, Iba1, Cd68, Cd11b, Cd18, Fcgr1a, Fcgr2b and complement (C3, factor B, properdin genes in response to ovariectomy. Ovariectomy upregulated Cd22 and downregulated semaphorin3A (Sema3a expression, indicating altered neuronal regulation of microglia. Ovariectomy also led to downregulation of aromatase and upregulation of ERα gene. Of note, analogous changes were observed in the hippocampus of postmenopausal women. In ovariectomized rats, estradiol replacement attenuated Iba1, Cd11b, Fcgr1a, C3, increased mannose receptor Mrc1, Cd163 and reversed Sema3a expression. In contrast, reduced expression of aromatase was not reversed by estradiol. While the effects of ERα agonist closely resembled those of estradiol, ERβ agonist was also capable of attenuating the expression of several macrophage-associated and complement genes. These data together indicate that the innate immune system of the aging hippocampus is highly responsive to the gonadal hormone milieu

Estrogen Levels in the three Trimesters

African Journals Online (AJOL)

estrogen levels in first, second and third trimesters of pregnant albino rats. MATERIALS AND METHODS. TEST SUBJECTS. 20 female albino rats and 6 male albino rats, with initial weight of 165-180g were purchase from the animal house of Department of Animal and. Environmental Biology , University of Benin,. Benin city ...

Estrogen and progesterone stimulate Schwann cell proliferation in a sex- and age-dependent manner

DEFF Research Database (Denmark)

Svenningsen, Åsa Fex; Kanje, M

1999-01-01

The effects of estrogen and progesterone on Schwann cell proliferation were studied in cultured segments of the rat sciatic nerve from adult male, female, and newborn rats, by measurement of [3H thymidine incorporation or bromo-deoxy-uridine- (BrdU)-labelling and immunocytochemistry. Estrogen (10...

Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice.

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Buckley, Jill; Willingham, Emily; Agras, Koray; Baskin, Laurence S

2006-02-21

Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors alpha and beta, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females), we measured the lengths of the casts and performed ANOVA analysis on these data. Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias) and masculinizing females (longer urethras). Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen alpha and beta, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor alpha mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor alpha and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl estradiol. The results suggest that

Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice

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Baskin Laurence S

2006-02-01

Full Text Available Abstract Background Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. Methods We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors α and β, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females, we measured the lengths of the casts and performed ANOVA analysis on these data. Results Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias and masculinizing females (longer urethras. Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen α and β, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor α mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor α and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl

Estrogen use and early onset Alzheimer's disease: a population-based study

NARCIS (Netherlands)

A.J.C. Slooter (Arjen); J.B. Bronzova (Juliana); J.C.M. Witteman (Jacqueline); C.M. van Duijn (Cornelia); C. van Broeckhoven (Christine); A. Hofman (Albert)

1999-01-01

textabstractEstrogen use may be protective for Alzheimer's disease with late onset. However, the effects on early onset Alzheimer's disease are unclear. This issue was studied in a population based setting. For each female patient, a female control was matched on age (within 5

Brain uptake of pipecolic acid, amino acids, amines following intracarotid injection in the mouse

International Nuclear Information System (INIS)

Nishio, H.; Giacobini, E.

1981-01-01

The uptake of pipecolic acid by the mouse brain was compared to that of several amino acids and amines, following an injection of a double-labeled mixture into the carotid artery. In general, BUI (brain uptake index) values were lower in the mouse than those previously reported in the rat. The only exception was proline. Lysine, a precursor of pipecolic acid biosynthesis in brain, showed a higher BUI than pipecolic acid. The BUI of D,L-[3H]pipecolic acid was found to be 3.39 (at 0.114 mM). This was saturable between a concentration of 0.114 and 3.44 mM. Kinetic analysis suggests the presence of two kinds of transport systems. Substances structurally related to pipecolic acid, such as nipecotic acid, isonipecotic acid, L-proline, and piperidine show a significant inhibitory effect. Amont the amino acids tested, only GABA showed an inhibitory effect. Data are reported which, when considered with other findings present evidence that pipecolic acid is (1) synthesized both in vitro and in vivo in the mouse brain, (2) actively transported in vivo into the brain, and (3) taken up in vitro by synaptosomal preparations

MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer.

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Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Conzen, Suzanne D; Karczmar, Gregory S

2017-07-01

High resolution 3D MRI was used to study contrast agent distribution and leakage in normal mouse mammary glands and glands containing in situ cancer after intra-ductal injection. Five female FVB/N mice (~19weeks old) with no detectable mammary cancer and eight C3(1) SV40 Tag virgin female mice (~15weeks old) with extensive in situ cancer were studied. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple and approximately 15μL of a Gadodiamide was injected slowly over 1min into the nipple and throughout the duct on one side of the inguinal gland. Following injection, the mouse was placed in a 9.4T MRI scanner, and a series of high resolution 3D T1-weighted images was acquired with a temporal resolution of 9.1min to follow contrast agent leakage from the ducts. The first image was acquired at about 12min after injection. Ductal enhancement regions detected in images acquired between 12 and 21min after contrast agent injection was five times smaller in SV40 mouse mammary ducts (pcontrast agent from the SV40 ducts. The contrast agent washout rate measured between 12min and 90min after injection was ~20% faster (p<0.004) in SV40 mammary ducts than in FVB/N mammary ducts. These results may be due to higher permeability of the SV40 ducts, likely due to the presence of in situ cancers. Therefore, increased permeability of ducts may indicate early stage breast cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Substance p regulates puberty onset and fertility in the female mouse.

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Simavli, Serap; Thompson, Iain R; Maguire, Caroline A; Gill, John C; Carroll, Rona S; Wolfe, Andrew; Kaiser, Ursula B; Navarro, Víctor M

2015-06-01

Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1(-/-) mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice.

The estrogen-related receptors (ERRs): potential targets against bone loss.

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Zhang, Ling; Wong, Jiemin; Vanacker, Jean-Marc

2016-10-01

Bone loss and the resulting skeletal fragility is induced by several pathological or natural conditions, the most prominent of which being aging as well as the decreased levels of circulating estrogens in post-menopause females. To date, most treatments against bone loss aim at preventing excess bone resorption. We here summarize data indicating that the estrogen-related receptors (ERRs) α and γ prevent bone formation. Inhibiting these receptors may thus constitute an anabolic approach by increasing bone formation.

Estrogen inhibits lysyl oxidase and decreases mechanical function in engineered ligaments.

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Lee, Cassandra A; Lee-Barthel, Ann; Marquino, Louise; Sandoval, Natalie; Marcotte, George R; Baar, Keith

2015-05-15

Women are more likely to suffer an anterior cruciate ligament (ACL) rupture than men, and the incidence of ACL rupture in women rises with increasing estrogen levels. We used an engineered ligament model to determine how an acute rise in estrogen decreases the mechanical properties of ligaments. Using fibroblasts isolated from human ACLs from male or female donors, we engineered ligaments and determined that ligaments made from female ACL cells had more collagen and were equal in strength to those made from male ACL cells. We then treated engineered ligaments for 14 days with low (5 pg/ml), medium (50 pg/ml), or high (500 pg/ml) estrogen, corresponding to the range of in vivo serum estrogen concentrations and found that collagen within the grafts increased without a commensurate increase in mechanical strength. Mimicking the menstrual cycle, with 12 days of low estrogen followed by 2 days of physiologically high estrogen, resulted in a decrease in engineered ligament mechanical function with no change in the amount of collagen in the graft. The decrease in mechanical stiffness corresponded with a 61.7 and 76.9% decrease in the activity of collagen cross-linker lysyl oxidase with 24 and 48 h of high estrogen, respectively. Similarly, grafts treated with the lysyl oxidase inhibitor β-aminoproprionitrile (BAPN) for 24 h showed a significant decrease in ligament mechanical strength [control (CON) = 1.58 ± 0.06 N; BAPN = 1.06 ± 0.13 N] and stiffness (CON = 7.7 ± 0.46 MPa; BAPN = 6.1 ± 0.71 MPa) without changing overall collagen levels (CON = 396 ± 11.5 μg; BAPN = 382 ± 11.6 μg). Together, these data suggest that the rise in estrogen during the follicular phase decreases lysyl oxidase activity in our engineered ligament model and if this occurs in vivo may decrease the stiffness of ligaments and contribute to the elevated rate of ACL rupture in women. Copyright © 2015 the American Physiological Society.

Targeted basic research to highlight the role of estrogen and estrogen receptors in the cardiovascular system.

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Dworatzek, Elke; Mahmoodzadeh, Shokoufeh

2017-05-01

Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but major evidence points to the contribution of sex steroid hormone, 17β-estradiol (E2), and its receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). In this review, we summarize past and present studies that implicate E2 and ER as important determinants of sexual dimorphism in the physiology and pathophysiology of the heart. In particular, we give an overview of studies aimed to reveal the role of E2 and ER in the physiology of the observed sex differences in CVD using ER knock-out mice. Finally, we discuss recent findings from novel transgenic mouse models, which have provided new information on the sexual dimorphic roles of ER specifically in cardiomyocytes under pathological conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

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Butler, Michael J; Hildebrandt, Ryan P; Eckel, Lisa A

2018-05-25

Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect. Copyright © 2017. Published by Elsevier Inc.

Upregulation of estrogen receptor expression in the uterus of ovariectomized B6C3F1 mice and Ishikawa cells treated with bromoethane

International Nuclear Information System (INIS)

Aoyama, Hiroaki; Couse, John F.; Hewitt, Sylvia C.; Haseman, Joseph K.; He, Hong; Zheng, Xiaolin; Majstoravich, Sonja; Korach, Kenneth S.; Dixon, D.

2005-01-01

In a 2-year NTP bioassay, Bromoethane (BE) was found to induce endometrial neoplasms in the uterus of B6C3F1 mice [; ]. In women, hormonal influences, such as 'unopposed' estrogenic stimulus, have been implicated as important etiologic factors in uterine cancer. BE, however, does not affect the serum concentrations of sex hormones in female B6C3F1 mice [] and the mechanism of BE-induced uterine carcinogenesis still remains unclear. In the present study, we examined the estrogenic effects of BE on the uterus of ovariectomized B6C3F1 mice and on Ishikawa cells. Groups of 6 mice were given daily s.c. injections of 0, 100, 500 or 1000 mg BE/kg for 3 consecutive days. Mice treated with 17β-estradiol served as positive controls. Mice were necropsied 24 h after the final injection, and uteri were weighed and examined histologically and immunohistochemically along with the vagina. Changes observed in the estrogen-treated mice included increased uterine weights, edema and inflammation of the endometrium, increased epithelial layers of the uterine and vaginal lumens and keratinization of the vaginal epithelium. In the BE-treated mice, no such changes occurred; however, immunohistochemical staining of the uterus revealed a significant increase in immunoexpression of the estrogen receptor alpha (ERα) in the two higher dose groups. Analysis of mRNA also showed slightly increased uterine ERα expression in these groups. Upregulated expression of ERα was confirmed in BE-treated Ishikawa cells, in which Western blotting analyses identified an intense signal at approximately 66 kDa, which is consistent with ERα. These data suggest that upregulated expression of ERα may be important in the induction of endometrial neoplasms in BE-treated mice

Postmenopausal Estrogen Therapy and Risk of Gallstone Disease

DEFF Research Database (Denmark)

Simonsen, Maja Hellfritzsch; Erichsen, Rune; Frøslev, Trine

2013-01-01

BACKGROUND: Female gender and increasing age are key risk factors for gallstone disease; therefore, postmenopausal women are at high risk. Estrogen increases cholesterol saturation of bile and may further increase gallstone risk, but population-based evidence is sparse. OBJECTIVE: Our objective......, and parity. RESULTS: We identified 16,386 cases with gallstone disease and 163,860 controls. A total of 1,425 cases (8.7 %) and 8,930 controls (5.4 %) were current estrogen users, yielding an adjusted OR for gallstone disease of 1.74 (95 % CI 1.64-1.85) compared with non-users. The corresponding adjusted...

Autoradiographic determination of catechol estrogen binding sites in brain, pituitary and uterus

International Nuclear Information System (INIS)

Parvizi, N.; Sar, M.; Duncan, G.E.; Stumpf, W.E.

1985-01-01

The anatomical pattern of nuclear binding of 2-OH[6,9- 3 H]estradiol ([ 3 H]2-OHE 2 ) in brain, pituitary and uterus have been studied autoradiographically. Autoradiograms of forebrain, pituitary and uterus show nuclear concentrations of radioactivity in certain cells. This nuclear concentration is abolished when unlabelled 2-OHE 2 or E 2 was injected prior to the injection of [ 3 H]2-OHE 2 . In the brain nuclear labelling is observed in the septal-preoptic region, in the anterior hypothalamic area, and in the central hypothalamic area. Some estrogen-sensitive nuclear groups, such as lateral septum and hippocampus, do not show accumulation of radioactivity. In the uterus, luminal and glandular epithelium, stromal cell and muscle cells are labelled. A comparison of the quantitative nuclear uptake of radioactivity and of the different time intervals after the injection of different doses shows similar uptake of nuclear radioactivity. This is comparable to data obtained after [6,7- 3 H]estradiol ([ 3 H]E 2 ) injection. The results provide clear evidence for nuclear binding of catechol estrogens of the same magnitude as [ 3 H]E 2 after in vivo treatment. (Auth.).0

Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex.

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Shiroishi, T; Hanzawa, N; Sagai, T; Ishiura, M; Gojobori, T; Steinmetz, M; Moriwaki, K

1990-01-01

The wm7 haplotype of the major histocompatibility complex (MHC), derived from the Japanese wild mouse Mus musculus molossinus, enhances recombination specific to female meiosis in the K/A beta interval of the MHC. We have mapped crossover points of fifteen independent recombinants from genetic crosses of the wm7 and laboratory haplotypes. Most of them were confined to a short segment of approximately 1 kilobase (kb) of DNA between the A beta 3 and A beta 2 genes, indicating the presence of a female-specific recombinational hotspot. Its location overlaps with a sex-independent hotspot previously identified in the Mus musculus castaneus CAS3 haplotype. We have cloned and sequenced DNA fragments surrounding the hotspot from the wm7 haplotype and the corresponding regions from the hotspot-negative B10.A and C57BL/10 strains. There is no significant difference between the sequences of these three strains, or between these and the published sequences of the CAS3 and C57BL/6 strains. However, a comparison of this A beta 3/A beta 2 hotspot with a previously characterized hotspot in the E beta gene revealed that they have a very similar molecular organization. Each hotspot consists of two elements, the consensus sequence of the mouse middle repetitive MT family and the tetrameric repeated sequences, which are separated by 1 kb of DNA.

The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis.

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Romero, Iris L; Lee, WooSeok; Mitra, Anirban K; Gordon, Ilyssa O; Zhao, Yan; Leonhardt, Payton; Penicka, Carla V; Mui, Keeley L; Krausz, Thomas N; Greene, Geoffrey L; Lengyel, Ernst

2012-01-01

To test if estrogen promotes carcinogenesis in vitro and in a genetic mouse model of ovarian cancer and whether its effects can be inhibited by a novel selective estrogen receptor modulator (SERM), bazedoxifene. Bazedoxifene was synthesized and it was confirmed that the drug abrogated the uterine stimulatory effect of 17β-estradiol in mice. To determine if hormones alter tumorigenesis in vivo LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with vehicle control, 17β-estradiol or bazedoxifene. Hormone receptor status of a cell line established from LSL-K-ras(G12D/+)Pten(loxP/loxP) mouse ovarian tumors was characterized using Western blotting and immunohistochemistry. The cell line was treated with hormones and invasion assays were performed using Boyden chambers and proliferation was assessed using MTT assays. In vitro 17β-estradiol increased both the invasion and proliferation of ovarian cancer cells and bazedoxifene reversed these effects. However, in the genetic mouse model neither treatment with 17β-estradiol nor bazedoxifene changed mean tumor burden when compared to treatment with placebo. The mice in all treatment groups had similar tumor incidence, metastatic nodules and ascites. While 17β-estradiol increases the invasion and proliferation of ovarian cancer cells, these effects do not translate into increased tumor burden in a genetic mouse model of endometrioid ovarian cancer. Likewise, while the SERM reversed the detrimental effects of estrogen in vitro, there was no change in tumor burden in mice treated with bazedoxifene. These findings demonstrate the complex interplay between hormones and ovarian carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse

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Lu Lu

2010-11-01

Full Text Available Abstract Background Sexual dimorphism in brain gene expression has been recognized in several animal species. However, the relevant regulatory mechanisms remain poorly understood. To investigate whether sex-biased gene expression in mammalian brain is globally regulated or locally regulated in diverse brain structures, and to study the genomic organisation of brain-expressed sex-biased genes, we performed a large scale gene expression analysis of distinct brain regions in adult male and female mice. Results This study revealed spatial specificity in sex-biased transcription in the mouse brain, and identified 173 sex-biased genes in the striatum; 19 in the neocortex; 12 in the hippocampus and 31 in the eye. Genes located on sex chromosomes were consistently over-represented in all brain regions. Analysis on a subset of genes with sex-bias in more than one tissue revealed Y-encoded male-biased transcripts and X-encoded female-biased transcripts known to escape X-inactivation. In addition, we identified novel coding and non-coding X-linked genes with female-biased expression in multiple tissues. Interestingly, the chromosomal positions of all of the female-biased non-coding genes are in close proximity to protein-coding genes that escape X-inactivation. This defines X-chromosome domains each of which contains a coding and a non-coding female-biased gene. Lack of repressive chromatin marks in non-coding transcribed loci supports the possibility that they escape X-inactivation. Moreover, RNA-DNA combined FISH experiments confirmed the biallelic expression of one such novel domain. Conclusion This study demonstrated that the amount of genes with sex-biased expression varies between individual brain regions in mouse. The sex-biased genes identified are localized on many chromosomes. At the same time, sexually dimorphic gene expression that is common to several parts of the brain is mostly restricted to the sex chromosomes. Moreover, the study uncovered

Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

International Nuclear Information System (INIS)

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

2006-01-01

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

Endocrine disruption of sexual selection by an estrogenic herbicide in the mealworm beetle (Tenebrio molitor).

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McCallum, Malcolm L; Matlock, Makensey; Treas, Justin; Safi, Barroq; Sanson, Wendy; McCallum, Jamie L

2013-12-01

The role that endocrine disruption could play in sexual selection remains relatively untested, and although estrogens occur in insects, little information exists about their biological role in insect reproduction. Atrazine is a commonly applied herbicide that mimics estrogen in vertebrates. Tenebrio molitor were raised from egg to adult under a gradation of environmentally relevant atrazine exposures and a non-treated control. Atrazine was delivered in the drinking water ad libitum. Female T. molitor were provided with a choice between unrelated males raised under three levels of atrazine exposures. Female preference for males demonstrated a non-monotonic inverted U-shaped response to atrazine exposure. There was no significant difference between the control and the high exposure to atrazine. Excluding the control, female preference increased as exposure concentration increased. These results have important repercussions for nonlethal effects of endocrine disruption on populations, their capacity to interfere with sexual selection, and the role of estrogen in pheromone communication among insects.

Rapid and acute effects of estrogen on time perception in male and female rats

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Kristen ePleil

2011-10-01

Full Text Available Sex differences in the rapid and acute effects of estrodiol on time perception were investigated in adult male and female Sprague-Dawley rats. Because estrodiol has been shown to increase striatal dopamine release, it may be able to modify time perception and timed performance by increasing the speed of an internal clock in a manner similar to indirect dopamine agonists such as amphetamine and cocaine. Two groups of females (neonatally estradiol-treated/adult ovariectomized and neonatally oil-treated/adult ovariectomized and 2 groups of males (neonatally castrated and adult castrated were trained in a 2 s vs. 8 s duration bisection procedure and tested using intermediate signal durations. After obtaining oil-injected baseline psychometric functions over several days, rats were administered 5μg of estradiol for 4 days and behaviorally evaluated 30 min following each injection. This oil-estradiol administration cycle was subsequently repeated 3 times following the re-establishment of baseline training. Results revealed significant sex differences in the initial baseline functions that were not modifiable by organizational hormones, with males’ duration bisection functions shifted horizontally to the left of females’. Upon the first administration of estradiol, females, but not males, showed a significant, transient leftward shift in their bisection functions, indicative of an increase in clock speed. After extensive retraining in the duration bisection procedure, rats that were exposed to gonadal hormones during the first week of life showed a significant rightward shift in their bisection functions on the fourth day of estradiol administration during each cycle, suggesting a decrease in clock speed. Taken together, our results support the view that there are multiple mechanisms of estrogens’ action in the striatum that modulate dopaminergic activity and are differentially organized by gonadal steroids during early brain development.

ESTROGEN RECEPTOR-alpha IMMUNOREACTIVE NEURONS IN THE BRAINSTEM AND SPINAL CORD OF THE FEMALE RHESUS MONKEY : SPECIES-SPECIFIC CHARACTERISTICS

NARCIS (Netherlands)

Vanderhorst, V. G. J. M.; Terasawa, E.; Ralston, H. J.

2009-01-01

The distribution pattern of estrogen receptors in the rodent CNS has been reported extensively, but mapping of estrogen receptors in primates is incomplete. In this study we describe the distribution of estrogen receptor alpha immunoreactive (ER-alpha 1R) neurons in the brainstem and spinal cord of

Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

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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

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

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Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

2001-05-15

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females. Copyright 2001 Academic Press.

The role of transdermal estrogen sprays and estradiol topical emulsion in the management of menopause-associated vasomotor symptoms

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Amy M Egras

2010-05-01

Full Text Available Amy M Egras, Elena M UmlandJefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Vasomotor symptoms (VMS are among the most bothersome complaints of postmenopausal women. To date, the most widely studied and effective treatment for VMS is hormone replacement therapy, consisting of estrogen (in women without a uterus or estrogen plus progestin (in women with a uterus. Traditionally, oral estrogens have been used for treatment. However, over the years, additional estrogen formulations have been developed including transdermal patches; vaginal rings, creams, and tablets; and injectable preparations. Two newer formulations are transdermal estrogen spray and estradiol topical emulsion. This review evaluates the current literature assessing the use of these two newer formulations for the treatment of VMS associated with menopause.Keywords: menopause, vasomotor symptoms, transdermal estrogen spray, estradiol topical emulsion

Tepung Tempe Kaya Isoflavon Meningkatkan Kadar Kalsium, Posfor dan Estrogen Plasma Tikus Betina Normal

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I Nyoman Suarsana

2012-11-01

Full Text Available This research aimed to study the effect of isoflavon-riched tempe flour on calcium (Ca, phosphate(P, and estrogen levels in plasma et normal female rats during their growth period. A level oftwenty-five 2 months old female Sprague Dawley rats with an avarage body weight of 200 g wasrandomly divided into into 5 groups: one with control group (KO: without treatment and fourtreatment groups (K1, K2, K3, K4 : animals were given tempe flour with isoflavon at 1; 2; 4; and 6 mg/200 g/bw, respectively. The treatment was conducted for two months, following this blood plasmawas collected to analyse the level of calcium, phosphor, and estrogen, respectively. The resultshowed that although the plasma level of Ca, P, and estrogen was higher in the treatment groupcompare to the control group, this was not significantly different (P>0,05. The highest plasmalevel of Ca, P, and estrogen was seen in anmal receiving tempe flour with 4 mg/ 200 g bw/dayisoflavon.

Effect of vitamin E on preovulatory stage irradiated female mouse expressed as chromosomal abnormalities in generated embryos

International Nuclear Information System (INIS)

Salimi, M.; Mozdarani, H.

2006-01-01

The present study has been carried out to investigate the effects of preovulatory stage gamma-irradiation of female mice in the absence or presence of vitamin E on numerical chromosome abnormalities in 8-cell embryos after mating with non- irradiated males. Materials and Methods: The 8-11 weeks adult female NMRl mice were whole body irradiated at preovulatory stage (post PMSG injection and about 12-18 hours before Injecting HCG) with 4 Gy gamma-rays generated from a cobalt-60 source alone or in combination with 200 IU/kg vitamin E, intraperitoneally administered one hour prior to irradiation. Soon after HCG injection super ovulated irradiated females were mated with non-irradiated males. About 68-h post coitus (p.c), 8-cell embryos were flushed from the oviducts of pregnant mice and were fixed on slides using standard methods in order to screen for metaphase spreads and numerical chromosome abnormalities. Results: In control embryos, 8% of metaphase plates were aneuploidy whereas in preovulatory stage irradiated female mice, about 50% of metaphase plates of embryos showed numerical chromosome aberrations (P nd meiotic division. Reduction of the frequency of chromosome aberrations in the presence of vitamin E is probably due to antioxidant effects of this vitamin, and scavenging free radicals induced by gamma-rays in mice oocytes' environment

Bisphenol A exposure in utero disrupts early oogenesis in the mouse.

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Martha Susiarjo

2007-01-01

Full Text Available Estrogen plays an essential role in the growth and maturation of the mammalian oocyte, and recent studies suggest that it also influences follicle formation in the neonatal ovary. In the course of studies designed to assess the effect of the estrogenic chemical bisphenol A (BPA on mammalian oogenesis, we uncovered an estrogenic effect at an even earlier stage of oocyte development--at the onset of meiosis in the fetal ovary. Pregnant mice were treated with low, environmentally relevant doses of BPA during mid-gestation to assess the effect of BPA on the developing ovary. Oocytes from exposed female fetuses displayed gross aberrations in meiotic prophase, including synaptic defects and increased levels of recombination. In the mature female, these aberrations were translated into an increase in aneuploid eggs and embryos. Surprisingly, we observed the same constellation of meiotic defects in fetal ovaries of mice homozygous for a targeted disruption of ERbeta, one of the two known estrogen receptors. This, coupled with the finding that BPA exposure elicited no additional effects in ERbeta null females, suggests that BPA exerts its effect on the early oocyte by interfering with the actions of ERbeta. Together, our results show that BPA can influence early meiotic events and, importantly, indicate that the oocyte itself may be directly responsive to estrogen during early oogenesis. This raises concern that brief exposures during fetal development to substances that mimic or antagonize the effects of estrogen may adversely influence oocyte development in the exposed female fetus.

Effect of an estrogen-deficient state and alendronate therapy on bone loss resulting from experimental periapical lesions in rats.

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Xiong, Haofei; Peng, Bin; Wei, Lili; Zhang, Xiaolei; Wang, Li

2007-11-01

The aim of the research was to evaluate the impact of an estrogen-deficient state and alendronate (ALD) therapy on bone loss resulting from experimental periapical lesions in rats. Periapical lesions were induced on ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After sample preparation, histologic and radiographic examination for periapical bone loss area and an enzyme histochemical test for tartrate-resistant acid phosphatase (TRAP) were performed. The results showed that OVX significantly increased bone loss resulting from periradicular lesions. After daily subcutaneous injection of ALD, the bone loss area and the number of TRAP-positive cells (osteoclasts) were reduced. These findings suggested that alendronate may protect against increased bone loss from experimental periapical lesions in estrogen-deficient rats. Given recent recognition of adverse effects of bisphosphonates, including an increased risk for osteonecrosis, the findings from this study should not be interpreted as a new indication for ALD treatment. However, they may offer insight into understanding and predicting outcomes in female postmenopausal patients already on ALD therapy for medical indications.

Expression of extracellular matrix components is disrupted in the immature and adult estrogen receptor β-null mouse ovary.

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Alexandra Zalewski

Full Text Available Within the ovary, Estrogen Receptor β (ERβ is localized to the granulosa cells of growing follicles. 17β-estradiol (E2 acting via ERβ augments the actions of follicle stimulating hormone in granulosa cells, leading to granulosa cell differentiation and formation of a preovulatory follicle. Adult ERβ-null females are subfertile and possess ovaries with reduced numbers of growing follicles and corpora lutea. Because the majority of E2 production by granulosa cells occurs once puberty is reached, a role for ERβ in the ovary prior to puberty has not been well examined. We now provide evidence that lack of ERβ disrupts gene expression as early as post-natal day (PND 13, and in particular, we identify a number of genes of the extracellular matrix (ECM that are significantly higher in ERβ-null follicles than in wildtype (WT follicles. Considerable changes occur to the ECM occur during normal folliculogenesis to allow for the dramatic growth, cellular differentiation, and reorganization of the follicle from the primary to preovulatory stage. Using quantitative PCR and immunofluorescence, we now show that several ECM genes are aberrantly overexpressed in ERβ-null follicles. We find that Collagen11a1, a protein highly expressed in cartilage, is significantly higher in ERβ-null follicles than WT follicles as early as PND 13, and this heightened expression continues through PND 23-29 into adulthood. Similarly, Nidogen 2, a highly conserved basement membrane glycoprotein, is elevated in ERβ-null follicles at PND 13 into adulthood, and is elevated specifically in the ERβ-null focimatrix, a basal lamina-like matrix located between granulosa cells. Focimatrix laminin and Collagen IV expression were also higher in ERβ-null ovaries than in WT ovaries at various ages. Our findings suggest two novel observations: a that ERβ regulates granulosa cell gene expression ovary prior to puberty, and b that ERβ regulates expression of ECM components in the

Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

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Sullivan, Elinor L; Shearin, Jean; Koegler, Frank H; Cameron, Judy L

2012-04-01

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

Effects of Estrogen in Gender-dependent Fetal Programming of Adult Cardiovascular Dysfunction.

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Chen, Zewen; Wang, Lei; Ke, Jun; Xiao, DaLiao

2018-03-01

Epidemiological studies and experimental studies have demonstrated that intrauterine adverse environment increases the risk of cardiovascular disease (CVD) in adulthood. However, whether an individual develops a cardiovascular dysfunctional phenotype may depend on genetic background, age, and sex. In this review, we summarize some of the recent experimental animal studies in the developmental programming of adult CVD with an emphasis on sex differences and the potential role of estrogen in mediating sexual dimorphism. Few epidemiological studies report the effect of sex on the developmental programming of CVD. However, numerous experimental animal studies have shown a sex difference in fetal programming of adult cardiovascular dysfunction. Most of the animal studies indicate that male offspring develop cardiovascular dysfunction and CVD in adulthood, whereas adult females appear to be protected. Estrogen is one of the key factors that contributes to the sex difference of adult CVD. Estrogen/its receptor (ER) may interact with the RAS system by changes of DNA methylation patterns at the target gene promoter, serve as an antioxidant to counteract the prenatal insults-induced heightened ROS, and function as an eNOS activator to increase vasodilation, resulting in the protection of female offspring from the development of hypertension and other CVDs. These studies suggest that estrogen/ER may contribute to sex differences in cardiovascular response to an adverse intrauterine environment and play a significant role in modulating the cardiovascular response in adulthood. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

'Women at risk': the health and social vulnerabilities of the regular female partners of men who inject drugs in Delhi, India.

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Sharma, Vartika; Sarna, Avina; Luchters, Stanley; Sebastian, Mary; Degomme, Olivier; Saraswati, Lopamudra Ray; Madan, Ira; Thior, Ibou; Tun, Waimar

2015-01-01

Needle and syringe sharing is common among people who inject drugs and so is unprotected sex, which consequently puts their sex partners at risk of sexually transmitted infections (STIs) including HIV and other blood-borne infections, like hepatitis. We undertook a nested study with the regular female partners of men who inject drugs participating in a longitudinal HIV incidence study in Delhi, India. In-depth interviews were conducted with female partners of 32 men. The interviews aimed to gather focused and contextual knowledge of determinants of safe sex and reproductive health needs of these women. Information obtained through interviews was triangulated and linked to the baseline behavioural data of their partner (index men who injected drugs). The study findings illustrate that women in monogamous relationships have a low perception of STI- and HIV-related risk. Additionally, lack of awareness about hepatitis B and C is a cause of concern. Findings also suggest impact of male drug use on the fertility of the female partner. It is critical to empower regular female partners to build their self-risk assessment skills and self-efficacy to negotiate condom use. Future work must explore the role of drug abuse among men who inject drugs in predicting fertility and reproductive morbidity among their female partners.

Estrogenic Activities of Fatty Acids and a Sterol Isolated from Royal Jelly

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Isohama, Yoichiro; Maruyama, Hiroe; Yamada, Yayoi; Narita, Yukio; Ohta, Shozo; Araki, Yoko; Miyata, Takeshi; Mishima, Satoshi

2008-01-01

We have previously reported that royal jelly (RJ) from honeybees (Apis mellifera) has weak estrogenic activity mediated by interaction with estrogen receptors that leads to changes in gene expression and cell proliferation. In this study, we isolated four compounds from RJ that exhibit estrogenic activity as evaluated by a ligand-binding assay for the estrogen receptor (ER) β. These compounds were identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid, trans-2-decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding of 17β-estradiol to ERβ, although more weakly than diethylstilbestrol or phytoestrogens. However, these compounds had little or no effect on the binding of 17β-estradiol to ERα. Expression assays suggested that these compounds activated ER, as evidenced by enhanced transcription of a reporter gene containing an estrogen-responsive element. Treatment of MCF-7 cells with these compounds enhanced their proliferation, but concomitant treatment with tamoxifen blocked this effect. Exposure of immature rats to these compounds by subcutaneous injection induced mild hypertrophy of the luminal epithelium of the uterus, but was not associated with an increase in uterine weight. These findings provide evidence that these compounds contribute to the estrogenic effect of RJ. PMID:18830443

Estrogenic Activities of Fatty Acids and a Sterol Isolated from Royal Jelly

Directory of Open Access Journals (Sweden)

Kazu-Michi Suzuki

2008-01-01

Full Text Available We have previously reported that royal jelly (RJ from honeybees (Apis mellifera has weak estrogenic activity mediated by interaction with estrogen receptors that leads to changes in gene expression and cell proliferation. In this study, we isolated four compounds from RJ that exhibit estrogenic activity as evaluated by a ligand-binding assay for the estrogen receptor (ER β. These compounds were identified as 10-hydroxy-trans-2-decenoic acid, 10-hydroxydecanoic acid, trans-2-decenoic acid and 24-methylenecholesterol. All these compounds inhibited binding of 17β-estradiol to ERβ, although more weakly than diethylstilbestrol or phytoestrogens. However, these compounds had little or no effect on the binding of 17β-estradiol to ERα. Expression assays suggested that these compounds activated ER, as evidenced by enhanced transcription of a reporter gene containing an estrogen-responsive element. Treatment of MCF-7 cells with these compounds enhanced their proliferation, but concomitant treatment with tamoxifen blocked this effect. Exposure of immature rats to these compounds by subcutaneous injection induced mild hypertrophy of the luminal epithelium of the uterus, but was not associated with an increase in uterine weight. These findings provide evidence that these compounds contribute to the estrogenic effect of RJ.

Control of the Mammary Cell Cycle Clock by Estrogen and Progesterone

National Research Council Canada - National Science Library

Weinberg, Robert

1999-01-01

Both the growth and the development of the mammary gland are controlled by the female hormones estrogen and progesterone, and by interactions between the epithelial and stromal compartments of the breast...

Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells.

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Benedek, Gil; Zhang, Jun; Nguyen, Ha; Kent, Gail; Seifert, Hilary A; Davin, Sean; Stauffer, Patrick; Vandenbark, Arthur A; Karstens, Lisa; Asquith, Mark; Offner, Halina

2017-09-15

Sex hormones promote immunoregulatory effects on multiple sclerosis. In the current study we evaluated the composition of the gut microbiota and the mucosal-associated regulatory cells in estrogen or sham treated female mice before and after autoimmune encephalomyelitis (EAE) induction. Treatment with pregnancy levels of estrogen induces changes in the composition and diversity of gut microbiota. Additionally, estrogen prevents EAE-associated changes in the gut microbiota and might promote the enrichment of bacteria that are associated with immune regulation. Our results point to a possible cross-talk between the sex hormones and the gut microbiota, which could promote neuroprotection. Copyright © 2017 Elsevier B.V. All rights reserved.

The ERα-PI3K Cascade in Proopiomelanocortin Progenitor Neurons Regulates Feeding and Glucose Balance in Female Mice.

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Zhu, Liangru; Xu, Pingwen; Cao, Xuehong; Yang, Yongjie; Hinton, Antentor Othrell; Xia, Yan; Saito, Kenji; Yan, Xiaofeng; Zou, Fang; Ding, Hongfang; Wang, Chunmei; Yan, Chunling; Saha, Pradip; Khan, Sohaib A; Zhao, Jean; Fukuda, Makoto; Tong, Qingchun; Clegg, Deborah J; Chan, Lawrence; Xu, Yong

2015-12-01

Estrogens act upon estrogen receptor (ER)α to inhibit feeding and improve glucose homeostasis in female animals. However, the intracellular signals that mediate these estrogenic actions remain unknown. Here, we report that anorexigenic effects of estrogens are blunted in female mice that lack ERα specifically in proopiomelanocortin (POMC) progenitor neurons. These mutant mice also develop insulin resistance and are insensitive to the glucose-regulatory effects of estrogens. Moreover, we showed that propyl pyrazole triol (an ERα agonist) stimulates the phosphatidyl inositol 3-kinase (PI3K) pathway specifically in POMC progenitor neurons, and that blockade of PI3K attenuates propyl pyrazole triol-induced activation of POMC neurons. Finally, we show that effects of estrogens to inhibit food intake and to improve insulin sensitivity are significantly attenuated in female mice with PI3K genetically inhibited in POMC progenitor neurons. Together, our results indicate that an ERα-PI3K cascade in POMC progenitor neurons mediates estrogenic actions to suppress food intake and improve insulin sensitivity.

Estrogen receptor-alpha-immunoreactive neurons in the mesencephalon, pons and medulla oblongata of the female golden hamster

NARCIS (Netherlands)

Boers, J; Gerrits, PO; Holstege, G

1999-01-01

Recent studies have revealed brainstem-spinal pathways involved in the generation of receptive behavior in hamster and cat, and the enormous influence of estrogen on these pathways. The present study gives an overview of the location of estrogen receptor-alpha-immunoreactive neurons (ER-alpha-IR) in

Estrogenic suppression of binge-like eating elicited by cyclic food restriction and frustrative-nonreward stress in female rats

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Di Bonaventura, Maria Vittoria Micioni; Lutz, Thomas A.; Romano, Adele; Pucci, Mariangela; Geary, Nori; Asarian, Lori; Cifani, Carlo

2017-01-01

Objective Because binge eating and emotional eating vary through the menstrual cycle in human females, we investigated cyclic changes in binge-like eating in female rats and their control by estrogens. Method Binge-like eating was elicited by three cycles of 4 days of food restriction and 4 days of free feeding followed by a single frustrative nonreward-stress episode (15 min visual and olfactory exposure to a familiar palatable food) immediately before presentation of the palatable food. Results Intact rats showed binge-like eating during the diestrous and proestrous phases of the ovarian cycle, but not during the estrous (peri-ovulatory) phase. Ovariectomized (OVX) rats not treated with estradiol (E2) displayed binge-like eating, whereas E2-treated OVX rats did not. The procedure did not increase signs of anxiety in an open-field test. OVX rats not treated with E2 that were subjected to food restriction and sacrificed immediately after frustrative nonreward had increased numbers of cells expressing phosphorylated extracellular signal-regulated kinases (ERK) in the central nucleus of the amygdala (CeA), paraventricular nucleus of hypothalamus (PVN), and dorsal and ventral bed nucleus of the stria terminalis (BNST) compared with non-restricted or E2-treated rats. Discussion These data suggest that this female rat model is appropriate for mechanistic studies of some aspects of menstrual-cycle effects on emotional and binge eating in human females, that anxiety is not a sufficient cause of binge-like eating, and that the PVN, CeA and BNST may contribute to information processing underlying binge-like eating. PMID:28230907

Control of the Mammary Cell Cycle Clock by Estrogen and Progesterone

National Research Council Canada - National Science Library

Weinberg, Robert

2001-01-01

Both the growth and the development of the mammary gland are controlled by the female hormones estrogen, prolactin and progesterone, and by interactions between the epithelial and stromal compartments of the breast...

Memory enhancement by Tamoxifen on amyloidosis mouse model.

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Pandey, Deepika; Banerjee, Sugato; Basu, Mahua; Mishra, Nibha

2016-03-01

Tamoxifen (TMX) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer. Earlier studies show its neuroprotection via regulating apoptosis, microglial functions, and synaptic plasticity. TMX also showed memory enhancement in ovariectomized mice, and protection from amyloid induced damage in hippocampal cell line. These reports encouraged us to explore the role of TMX in relevance to Alzheimer's disease (AD). We report here, the effect of TMX treatment a) on memory, and b) levels of neurotransmitters (acetylcholine (ACh) and dopamine (DA)) in breeding-retired-female mice injected with beta amyloid1-42 (Aβ1-42). Mice were treated with TMX (10mg/kg, i.p.) for 15 days. In Morris water maze test, the TMX treated mice escape latency decreased during training trials. They also spent longer time in the platform quadrant on probe trial, compared to controls. In Passive avoidance test, TMX treated mice avoided stepping on the shock chamber. This suggests that TMX protects memory from Aβ induced toxicity. In frontal cortex, ACh was moderately increased, with TMX treatment. In striatum, dopamine was significantly increased, 3,4-dihydroxyphenylacetic acid (DOPAC) level and DOPAC/DA ratio was decreased post TMX treatment. Therefore, TMX enhances spatial and contextual memory by reducing dopamine metabolism and increasing ACh level in Aβ1-42 injected-breeding-retired-female mice. Copyright © 2015. Published by Elsevier Inc.

Low dose bisphenol S or ethinyl estradiol exposures during the perinatal period alter female mouse mammary gland development.

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Kolla, SriDurgaDevi; Morcos, Mary; Martin, Brian; Vandenberg, Laura N

2018-03-08

Throughout life, mammary tissue is strongly influenced by hormones. Scientists have hypothesized that synthetic chemicals with hormonal activities could disrupt mammary gland development and contribute to breast diseases and dysfunction. Bisphenol S (BPS) is an estrogenic compound used in many consumer products. In this study, CD-1 mice were exposed to BPS (2 or 200 μg/kg/day) during pregnancy and lactation. Mice exposed to 0.01 or 1 μg/kg/day ethinyl estradiol (EE2), a pharmaceutical estrogen, were also evaluated. Mammary glands from female offspring were collected prior to the onset of puberty, during puberty, and in early adulthood. Growth parameters, histopathology, cell proliferation and expression of hormone receptors were quantified. Our evaluations revealed age- and dose-specific effects of BPS that were different from the effects of EE2, and distinct from the effects of BPA that have been reported previously. These assessments suggest that individual xenoestrogens may have unique effects on this sensitive tissue. Copyright © 2018 Elsevier Inc. All rights reserved.

A new mouse model for renal lesions produced by intravenous injection of diphtheria toxin A-chain expression plasmid

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Nakamura Shingo

2004-04-01

Full Text Available Abstract Background Various animal models of renal failure have been produced and used to investigate mechanisms underlying renal disease and develop therapeutic drugs. Most methods available to produce such models appear to involve subtotal nephrectomy or intravenous administration of antibodies raised against basement membrane of glomeruli. In this study, we developed a novel method to produce mouse models of renal failure by intravenous injection of a plasmid carrying a toxic gene such as diphtheria toxin A-chain (DT-A gene. DT-A is known to kill cells by inhibiting protein synthesis. Methods An expression plasmid carrying the cytomegalovirus enhancer/chicken β-actin promoter linked to a DT-A gene was mixed with lipid (FuGENE™6 and the resulting complexes were intravenously injected into adult male B6C3F1 mice every day for up to 6 days. After final injection, the kidneys of these mice were sampled on day 4 and weeks 3 and 5. Results H-E staining of the kidney specimens sampled on day 4 revealed remarkable alterations in glomerular compartments, as exemplified by mesangial cell proliferation and formation of extensive deposits in glomerular basement membrane. At weeks 3 and 5, gradual recovery of these tissues was observed. These mice exhibited proteinuria and disease resembling sub-acute glomerulonephritis. Conclusions Repeated intravenous injections of DT-A expression plasmid DNA/lipid complex caused temporary abnormalities mainly in glomeruli of mouse kidney. The disease in these mice resembles sub-acute glomerulonephritis. These DT-A gene-incorporated mice will be useful as animal models in the fields of nephrology and regenerative medicine.

HIV risk, health, and social characteristics of sexual minority female injection drug users in Baltimore

OpenAIRE

German, Danielle; Latkin, Carl A.

2015-01-01

Female injection drug users {IDU} who report sex with women are at increased risk for HIV and social instability, but it is important to assess whether these disparities also exist according to sexual minority identity rather than behaviorally defined categories. Within a sample of current IDU in Baltimore, about 17% of female study participants (n=307) identified as gay/lesbian/bisexual. In controlled models, sexual minorities were three times as likely to report sex exchange behavior and fo...

Estrogen Repression of MicroRNAs Is Associated with High Guanine Content in the Terminal Loop Sequences of Their Precursors

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Amit Cohen

2017-08-01

Full Text Available Widespread microRNA (miRNA repression is a phenomenon observed in mammals after exposure to cigarette smoke and in many types of cancer. A comprehensive reduction in miRNA expression after treatment with the hormone estrogen has also previously been described. Here, we reveal a conserved association of miRNA downregulation after estrogen exposure in zebrafish, mouse, and human breast cancer cell line, with a high guanine content in the terminal loop sequences of their precursors, and offer a possible link between estrogen-related miRNA-adducts formation and carcinogenesis. We also show common gene expression patterns shared by breast cancer tumors and estrogen-treated zebrafish, suggesting that this organism can be used as a powerful model system for the study of human breast cancer.

Immunocytochemical localization of estrogen receptors in the normal male and female canine urinary tract and prostate

International Nuclear Information System (INIS)

Schulze, H.; Barrack, E.R.

1987-01-01

We have used the monoclonal estrogen receptor (ER) antibody H222Sp gamma to localize ER by immunocytochemistry in frozen sections of the normal canine urinary tract of both sexes and of the normal prostate of the male. Striking regional heterogeneity of ER location was observed. In the urinary tract, specific ER staining was confined to nuclei of the transitional epithelium (mucosa) and subjacent stroma (submucosa) of the prostatic urethra in the male dog and of the proximal urethra in the female dog. In both sexes there was a gradient of ER staining intensity along these urethral segments. In the male, ER staining intensity was highest in the region of the verumontanum. The pattern and intensity of staining were similar in the male prostatic urethra and female proximal urethra, indicating a similar concentration of ER in these tissues, which have the same embryological origin. No specific staining was found in the kidney, ureter, bladder, or distal urethra of either sex. In the normal prostate, specific immunocytochemical ER staining was confined to nuclei of the prostatic stroma and prostatic ductal epithelium. Specific staining intensity appeared to be higher in the periurethral region of the prostate than in the periphery. No specific staining was found in the acinar epithelium of the prostate. Based on overall staining intensity there appeared to be a higher concentration of ER in the urethra than in the prostate. Scatchard analysis of [ 3 H]estradiol binding confirmed a similar ER content in the urethra of male and female dogs and a higher ER content in the prostatic urethra than in the prostate itself (P less than 0.001)

Estrogen-induced transcription factor EGR1 regulates c-Kit transcription in the mouse uterus to maintain uterine receptivity for embryo implantation.

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Park, Mira; Kim, Hye-Ryun; Kim, Yeon Sun; Yang, Seung Chel; Yoon, Jung Ah; Lyu, Sang Woo; Lim, Hyunjung Jade; Hong, Seok-Ho; Song, Haengseok

2018-07-15

Early growth response 1 (Egr1) is a key transcription factor that mediates the action of estrogen (E 2 ) to establish uterine receptivity for embryo implantation. However, few direct target genes of EGR1 have been identified in the uterus. Here, we demonstrated that E 2 induced EGR1-regulated transcription of c-Kit, which plays a crucial role in cell fate decisions. Spatiotemporal expression of c-Kit followed that of EGR1 in uteri of ovariectomized mice at various time points after E 2 treatment. E 2 activated ERK1/2 and p38 to induce EGR1, which then activated c-Kit expression in the uterus. EGR1 transfection produced rapid and transient induction of c-KIT in a time- and dose-dependent manner. Furthermore, luciferase assays to measure c-Kit promoter activity confirmed that a functional EGR1 binding site(s) (EBS) was located within -1 kb of the c-Kit promoter. Site-directed mutagenesis and chromatin immunoprecipitation-PCR for three putative EBS within -1 kb demonstrated that the EBS at -818/-805 was critical for EGR1-dependent c-Kit transcription. c-Kit expression was significantly increased in the uterus on day 4 and administration of Masitinib, a c-Kit inhibitor, effectively interfered with embryo implantation. Collectively, our results showed that estrogen induces transcription factor EGR1 to regulate c-Kit transcription for uterine receptivity for embryo implantation in the mouse uterus. Copyright © 2017 Elsevier B.V. All rights reserved.

A study of possible associations between single nucleotide polymorphisms in the estrogen receptor 2 gene and female sexual desire.

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Gunst, Annika; Jern, Patrick; Westberg, Lars; Johansson, Ada; Salo, Benny; Burri, Andrea; Spector, Tim; Eriksson, Elias; Sandnabba, N Kenneth; Santtila, Pekka

2015-03-01

Female sexual desire and arousal problems have been shown to have a heritable component of moderate size. Previous molecular genetic studies on sexual desire have mainly focused on genes associated with neurotransmitters such as dopamine and serotonin. Nevertheless, there is reason to believe that hormones with more specific functions concerning sexuality could have an impact on sexual desire and arousal. The aim of the present study was to investigate the possible effects of 17 single nucleotide polymorphisms (SNPs) located in estrogen receptor genes on female sexual desire and subjective and genital arousal (lubrication). Based on previous research, we hypothesized that ESR1 and ESR2 are relevant genes that contribute to female sexual desire and arousal. The desire, arousal, and lubrication subdomains of the Female Sexual Function Index self-report questionnaire were used. The present study involved 2,448 female twins and their sisters aged 18-49 who had submitted saliva samples for genotyping. The participants were a subset from a large-scale, population-based sample. We found nominally significant main effects on sexual desire for three ESR2 -linked SNPs when controlled for anxiety, suggesting that individuals homozygous for the G allele of the rs1271572 SNP, and the A allele of the rs4986938 and rs928554 SNPs had lower levels of sexual desire. The rs4986938 SNP also had a nominally significant effect on lubrication. No effects for any of the SNPs on subjective arousal could be detected. The number of nominally significant results for SNPs in the ESR2 gene before correcting for multiple testing suggests that further studies on the possible influence of this gene on interindividual variation in female sexual functioning are warranted. In contrast, no support for an involvement of ESR1 was obtained. Our results should be interpreted with caution until replicated in independent, large samples. © 2014 International Society for Sexual Medicine.

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice[S

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Palmisano, Brian T.; Le, Thao D.; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M.

2016-01-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. PMID:27354419

Reversal of androgen inhibition of estrogen-activated sexual behavior by cholinergic agents.

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Dohanich, G P; Cada, D A

1989-12-01

Androgens have been found to inhibit lordosis activated by estrogen treatment of ovariectomized female rats. In the present experiments, dihydrotestosterone propionate (200 micrograms for 3 days) inhibited the incidence of lordosis in ovariectomized females treated with estradiol benzoate (1 microgram for 3 days). This inhibition of lordosis was reversed 15 min after bilateral intraventricular infusion of physostigmine (10 micrograms/cannula), an acetylcholinesterase inhibitor, or carbachol (0.5 microgram/cannula), a cholinergic receptor agonist. This reversal of inhibition appears to be mediated by cholinergic muscarinic receptors since pretreatment with scopolamine (4 mg/kg, ip), a muscarinic receptor blocker, prevented the reversal of androgen inhibition by physostigmine. These results indicate that androgens may inhibit estrogen-activated lordosis through interference with central cholinergic muscarinic mechanisms.

Ept7 influences estrogen action in the pituitary gland and body weight of rats.

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Kurz, Scott G; Dennison, Kirsten L; Samanas, Nyssa Becker; Hickman, Maureen Peters; Eckert, Quincy A; Walker, Tiffany L; Cupp, Andrea S; Shull, James D

2014-06-01

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

Chlropyrifos-methyl shows anti-androgenic activity without estrogenic activity in rats

International Nuclear Information System (INIS)

Kang, Hwan Goo; Jeong, Sang Hee; Cho, Joon Hyoung; Kim, Dong Gyu; Park, Jong Myung; Cho, Myung Haing

2004-01-01

Chlorpyrifos-methyl (CPM), an organophosphate insecticide, widely used for grain storage and agriculture, has been suspected as endocrine disrupter by a few in vitro studies. This study was performed to investigate the (anti-) estrogenicity and (anti-) androgenicity of CPM in vivo using immature rat uterotrophic assay and rat Hershberger assay. CPM with or without 17β-estradiol were administered to 20 days old female rats to investigate its (anti-) estrogenic activity. Uterine and vaginal weight, uterine epithelial cell height were not affected by the treatment of CPM (2, 10, 50, 250 mg/kg). CPM 250 mg/kg potentiated relative vagina weight in 17β-estradiol treated immature female rats without any changing of uterine weight. Relative liver weight was increased with decrease of body weight by CPM 250 mg/kg treatment. Uterine cell proliferation tested with bromodeoxyuridine labeling index was not observed in CPM treated rats. CPM with or without testosterone propionate were administered to castrated rat of 51 days old for 10 days to investigate the (anti-)androgenic activity,. The weight of relative and absolute androgen-dependent accessory sex organs; seminal vesicle with coagulating glands (SV/CG), ventral prostate gland (VP), glans penis (GP), levator ani plus bulbocarvernosus muscle (LABC) and Cowper's gland (CG,) were unchanged by the treatment of CPM alone. While CPM induced the increase of relative adrenal gland weight, CPM 50 mg/kg decreased the weights of CV/CG, VP, CG and LABC without change of GP without changing of GP when it was treated with TP. In conclusion, CPM dose not show estrogenic and anti-estrogenic activity in immature female rats, but it represents anti-androgenic activity by inhibition of the TP-stimulated increase of the weight of accessory sex organs

Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats

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Wang Fang

2012-05-01

Full Text Available Abstract Background The polycystic ovary syndrome (PCOS affects approximately 6-10% of women of reproductive age and is characterized by chronic anovulation and hyperandrogenism. However, a comprehensive understanding of the mechanisms that dictate androgen overproduction is lacking, which may account for inconsistencies between measures of androgen excess and clinical presentation in individual cases. Methods A rat model of PCOS was established by injecting dehydroepiandrosterone sulfoconjugate (DHEAS into pregnant females. Rats were administered with DHEAS (60 mg/kg/d subcutaneously (s.c. for all 20 days of pregnancy (Group A, or for the first 10 days (Group B, or from day 11 to day 20 (Group C. Controls were administered with injection oil (0.2 ml/day s.c. throughout pregnancy (Group D. The litter rate, abortion rate, and offspring survival rate in each group were recorded. Serum androgen and estrogen were measured and the morphological features of the ovaries were examined by light and electron microscopy in the offspring of each group. Results We found that rats injected with DHEAS throughout pregnancy (group A lost fertility. Rats injected with DHEAS during early pregnancy (group B exhibited more serious aberrations in fertility than both Group C, in which rats were injected with DHEAS during late pregnancy (P  Conclusions Our results indicate that androgen excess during pregnancy can decrease rat fertility. Excess androgen at the early stage of pregnancy causes high reproductive toxicity, leading to abnormality of ovarian morphology and functions in female offspring.

Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice.

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Palmisano, Brian T; Le, Thao D; Zhu, Lin; Lee, Yoon Kwang; Stafford, John M

2016-08-01

Elevated plasma TGs increase risk of cardiovascular disease in women. Estrogen treatment raises plasma TGs in women, but molecular mechanisms remain poorly understood. Here we explore the role of cholesteryl ester transfer protein (CETP) in the regulation of TG metabolism in female mice, which naturally lack CETP. In transgenic CETP females, acute estrogen treatment raised plasma TGs 50%, increased TG production, and increased expression of genes involved in VLDL synthesis, but not in nontransgenic littermate females. In CETP females, estrogen enhanced expression of small heterodimer partner (SHP), a nuclear receptor regulating VLDL production. Deletion of liver SHP prevented increases in TG production and expression of genes involved in VLDL synthesis in CETP mice with estrogen treatment. We also examined whether CETP expression had effects on TG metabolism independent of estrogen treatment. CETP increased liver β-oxidation and reduced liver TG content by 60%. Liver estrogen receptor α (ERα) was required for CETP expression to enhance β-oxidation and reduce liver TG content. Thus, CETP alters at least two networks governing TG metabolism, one involving SHP to increase VLDL-TG production in response to estrogen, and another involving ERα to enhance β-oxidation and lower liver TG content. These findings demonstrate a novel role for CETP in estrogen-mediated increases in TG production and a broader role for CETP in TG metabolism. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Role of female sex hormones, estradiol and progesterone, in mast cell behaviour

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Oliver eZierau

2012-06-01

Full Text Available Female sex hormones have long been suspected to have an effect on mast cell (MC behaviour. This assumption is based on the expression of hormone receptors in MCs as well as on the fact that many MC-related pathophysiological alterations have a different prevalence in females than in males. Further, serum IgE levels are much higher in allergic female mice compared to male mice. Ovariectomized rats developed less airway inflammation compared to sham controls. Following estrogen replacement ovariectomized rats re-established airway inflammation levels’ found in intact females. In humans, a much higher asthma prevalence was found in women at reproductive age as compared to men. Serum levels of estradiol and progesterone have been directly correlated with the clinical and functional features of asthma. Around 30 to 40% of women who have asthma experienced worsening of their symptoms during the perimenstrual phase, the so-called perimenstrual asthma. Postmenopausal women receiving hormone replacement therapy have an increased risk of new onset of asthma. Beside, estrus cycle dependent changes on female sex hormones are related to changes on MC number in mouse uterine tissue and estradiol and progesterone were shown to induce uterine MC maturation and degranulation. We will discuss here the currently available information concerning the role of these female sex hormones on MC behavior.

Estrogen Signaling in Lung Cancer: An Opportunity for Novel Therapy

International Nuclear Information System (INIS)

Baik, Christina S.; Eaton, Keith D.

2012-01-01

Lung cancer is the leading cause of cancer death in U.S. and represents a major public health burden. Epidemiologic data have suggested that lung cancer in women may possess different biological characteristics compared to men, as evidenced by a higher proportion of never-smokers among women with lung cancer. Emerging data indicate that female hormones such as estrogen and progesterone play a significant role in lung carcinogenesis. It has been reported that estrogen and progesterone receptors are expressed in lung cancer cell lines as well as in patient-derived tumors. Hormone related risk factors such as hormone replacement therapy have been implicated in lung carcinogenesis and several preclinical studies show activity of anti-estrogen therapy in lung cancer. In this review, we summarize the emerging evidence for the role of reproductive hormones in lung cancer and implications for lung cancer therapy

Estrogen-Related Receptors and the control of bone cell fate.

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Carnesecchi, Julie; Vanacker, Jean-Marc

2016-09-05

Bone loss is naturally occurring in aging males and females and exacerbated in the latter after menopause, altogether leading to cumulative skeleton fragility and increased fracture risk. Two types of therapeutic strategies can be envisioned to counteract age- or menopause-associated bone loss, aiming at either reducing bone resorption exerted by osteoclasts or, alternatively, promoting bone formation by osteoblasts. We here summarize data suggesting that inhibition of the Estrogen-Related Receptors α and/or γ could promote bone formation and compensate for bone loss induced by ageing or estrogen-deficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

Energy Technology Data Exchange (ETDEWEB)

Tsuchida, Tatsuro [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: tsucchy@fmsrsa.fukui-med.ac.jp; Okazawa, Hidehiko [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Yoshida, Yoshio [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Itoh, Harumi [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)

2007-02-15

Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16{alpha}-[{sup 18}F]fluoro-17{beta}-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03{+-}1.05 vs. 3.97{+-}1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration.

In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

International Nuclear Information System (INIS)

Tsuchida, Tatsuro; Okazawa, Hidehiko; Mori, Tetsuya; Kobayashi, Masato; Yoshida, Yoshio; Fujibayashi, Yasuhisa; Itoh, Harumi

2007-01-01

Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16α-[ 18 F]fluoro-17β-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03±1.05 vs. 3.97±1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration

Effects of estrogen and gender on cataractogenesis induced by high-LET radiation

International Nuclear Information System (INIS)

Henderson, M.A.; Rusek, A.; Valluri, S.; Garrett, J.; Lopez, J.; Caperell-Grant, A.; Mendonca, M.; Bigsby, R.; Dynlacht, J.

2010-01-01

Planning for long-duration manned lunar and interplanetary missions requires an understanding of radiation-induced cataractogenesis. Previously, it was demonstrated that low-linear energy transfer (LET) irradiation with 10 Gy of 60 Co γ rays resulted in an increased incidence of cataracts in male rats compared to female rats. This gender difference was not due to differences in estrogen, since male rats treated with the major secreted estrogen 17-β-estradiol (E2) showed an identical increase compared to untreated males. We now compare the incidence and rate of progression of cataracts induced by high-LET radiation in male and female Sprague-Dawley rats. Rats received a single dose of 1 Gy of 600 MeV 56 Fe ions. Lens opacification was measured at 2-4 week intervals with a slit lamp. The incidence and rate of progression of radiation-induced cataracts was significantly increased in the animals in which estrogen was available from endogenous or exogenous sources. Male rats with E2 capsules implanted had significantly higher rates of progression compared to male rats with empty capsules implanted (P = 0.025) but not compared to the intact female rats. These results contrast with data obtained after low-LET irradiation and suggest the possibility that the different types of damage caused by high- and low-LET radiation may be influenced differentially by steroid sex hormones.

Prolactin-sensitive neurons express estrogen receptor-α and depend on sex hormones for normal responsiveness to prolactin.

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Furigo, Isadora C; Kim, Ki Woo; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; de Alencar, Amanda; Pedroso, João A B; Metzger, Martin; Donato, Jose

2014-05-30

Estrogens and prolactin share important target tissues, including the gonads, brain, liver, kidneys and some types of cancer cells. Herein, we sought anatomical and functional evidence of possible crosstalk between prolactin and estrogens in the mouse brain. First, we determined the distribution of prolactin-responsive neurons that express the estrogen receptor α (ERα). A large number of prolactin-induced pSTAT5-immunoreactive neurons expressing ERα mRNA were observed in several brain areas, including the anteroventral periventricular nucleus, medial preoptic nucleus, arcuate nucleus of the hypothalamus, ventrolateral subdivision of the ventromedial nucleus of the hypothalamus (VMH), medial nucleus of the amygdala and nucleus of the solitary tract. However, although the medial preoptic area, periventricular nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus, retrochiasmatic area, dorsomedial subdivision of the VMH, lateral hypothalamic area, dorsomedial nucleus of the hypothalamus and ventral premammillary nucleus contained significant numbers of prolactin-responsive neurons, these areas showed very few pSTAT5-immunoreactive cells expressing ERα mRNA. Second, we evaluated prolactin sensitivity in ovariectomized mice and observed that sex hormones are required for a normal responsiveness to prolactin as ovariectomized mice showed a lower number of prolactin-induced pSTAT5 immunoreactive neurons in all analyzed brain nuclei compared to gonad-intact females. In addition, we performed hypothalamic gene expression analyses to determine possible post-ovariectomy changes in components of prolactin signaling. We observed no significant changes in the mRNA expression of prolactin receptor, STAT5a or STAT5b. In summary, sex hormones exert a permissive role in maintaining the brain's prolactin sensitivity, most likely through post-transcriptional mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

[Effects of Liangxue Jiedu Decoction in treating psoriasis in a mouse psoriasis model].

Science.gov (United States)

Gu, Min-Jie; Gao, Shang-Pu; Li, Yong-Mei

2009-06-01

To study the effects of Liangxue Jiedu Decoction, a compound traditional Chinese herbal medicine with the function of blood-cooling and detoxicating, in treating psoriasis in mice and to explore its mechanism. (1) Sixty mice were randomly divided into Liangxue Jiedu Decoction group, compound Indigo Naturalis capsule group, acitretin capsule group and normal saline group. Another 10 mice were selected as blank control. After 2-week administration, mice were sacrificed to obtain samples. After hematoxylin and eosin (HE) staining, tail scales with granular layers were calculated by an optical microscope. (2) Except for ten mice in blank group, sixty female mice were injected intraperitoneally with diethylstilbestrol once daily. After 3-day injection, mice were randomly divided into four groups and treated as above description. After 2-week treatment, all mice were injected intraperitoneally with colchicine (2 mg/kg), and sacrificed 6 h after the injection. The mitotic rate in virginal epithelium was calculated after HE staining. Compared with normal saline, Liangxue Jiedu Decoction could significantly inhibit the mitosis of mouse vaginal epithelium (P mouse tail-scale epidermis (P < 0.01). The mechanism of Liangxue Jiedu Decoction in treating psoriasis may be related to promoting granular cell growth and inhibiting proliferation of epidermic cells.

Estrogenic Effect of 70% Ethanol Turmeric (Curcuma domestica Val. Extract on Ovariectomized Female Mice (Mus musculus L.

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A.N. Dewi

2007-11-01

Full Text Available The influence of extract turmeric (Curcuma domestica Val. on endometrium thickness, vaginal epithelium, mammary gland, and protein of estrogen receptor of ovariectomized mice was examined. Twenty five ovariectomized mice which were divided into five groups, were treated by ethynilestradiol (8,4 x 10-3 g, aquades (10 ml, and turmeric extract at doses 230 mg/kg b.w.; 310 mg/kg b.w.; and 390 mg/kg b.w. for eight days. At the end of experiments the mice were killed, then the uterus, vagina, and mammae were removed and the wet weight of uterus was recorded. Uterus, vagina, and mammae were examined histologically. Estrogen receptor protein from uterus were analized by using SDS-PAGE. One way anava test showed that turmeric extract at doses 310 mg/kg b.w. and 390 mg/kg b.w give estrogenic effect on vaginal ephitelium, endometrium thickness, and diametre of mammary glands. SDS-PAGE analysis showed there were differences in protein concentration between control and treatment groups which were seen in the thickness of the bands. Estrogen receptor band could be detected in sampel of treatment groups at molecular weight 45 kDa.

Gene repressive mechanisms in the mouse brain involved in memory formation.

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Yu, Nam-Kyung; Kaang, Bong-Kiun

2016-04-01

Gene regulation in the brain is essential for long-term plasticity and memory formation. Despite this established notion, the quantitative translational map in the brain during memory formation has not been reported. To systematically probe the changes in protein synthesis during memory formation, our recent study exploited ribosome profiling using the mouse hippocampal tissues at multiple time points after a learning event. Analysis of the resulting database revealed novel types of gene regulation after learning. First, the translation of a group of genes was rapidly suppressed without change in mRNA levels. At later time points, the expression of another group of genes was downregulated through reduction in mRNA levels. This reduction was predicted to be downstream of inhibition of ESR1 (Estrogen Receptor 1) signaling. Overexpressing Nrsn1, one of the genes whose translation was suppressed, or activating ESR1 by injecting an agonist interfered with memory formation, suggesting the functional importance of these findings. Moreover, the translation of genes encoding the translational machineries was found to be suppressed, among other genes in the mouse hippocampus. Together, this unbiased approach has revealed previously unidentified characteristics of gene regulation in the brain and highlighted the importance of repressive controls. [BMB Reports 2016; 49(4): 199-200].

Why estrogens matter for behavior and brain health.

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Galea, Liisa A M; Frick, Karyn M; Hampson, Elizabeth; Sohrabji, Farida; Choleris, Elena

2017-05-01

The National Institutes of Health (NIH) has required the inclusion of women in clinical studies since 1993, which has enhanced our understanding of how biological sex affects certain medical conditions and allowed the development of sex-specific treatment protocols. However, NIH's policy did not previously apply to basic research, and the NIH recently introduced a new policy requiring all new grant applications to explicitly address sex as a biological variable. The policy itself is grounded in the results of numerous investigations in animals and humans illustrating the existence of sex differences in the brain and behavior, and the importance of sex hormones, particularly estrogens, in regulating physiology and behavior. Here, we review findings from our laboratories, and others, demonstrating how estrogens influence brain and behavior in adult females. Research from subjects throughout the adult lifespan on topics ranging from social behavior, learning and memory, to disease risk will be discussed to frame an understanding of why estrogens matter to behavioral neuroscience. Copyright © 2016 Elsevier Ltd. All rights reserved.

The dose of HBV genome contained plasmid has a great impact on HBV persistence in hydrodynamic injection mouse model.

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Li, Lei; Li, Sheng; Zhou, Yun; Yang, Lu; Zhou, Di; Yang, Yan; Lu, Mengji; Yang, Dongliang; Song, Jingjiao

2017-10-25

Hydrodynamic injection (HI) of hepatitis B virus (HBV) mouse model is an useful tool for HBV related research in vivo. However, only 40% of C57/BL6 mice injected with 10 μg HBV genome contained plasmid (pAAV-HBV1.2), serum HBsAg more than 6 months and none of the BALB/c mice injected with 10 μg pAAV-HBV1.2 plasmid DNA, serum HBsAg positive more than 4 weeks in the previous study. In this study, C57/BL6 and BALB/c mice were hydrodynamic injected with different doses of pAAV-HBV1.2 plasmid DNA. HBV related serum markers were detected by ELISA. ALT levels in the serum were measured using full automated biochemistry analyzer. HBcAg positive cells in the liver were detected by immunohistochemical staining. The mRNA levels of IRF3, ISGs including ISG15, OAS, PKR and immune factors including IFNγ, TNFα, TGFβ, IL-6, IL-10, PDL1 in liver of the mice were quantified by qRT-PCR. The results showed that the mice injected with 100 μg high-concentration or 1 μg low-concentration of pAAV-HBV1.2 plasmid DNA did not excert dominant influence on HBV persistence. In contrast, injection of 5 μg intermediate-dose of pAAV-HBV1.2 plasmid DNA led to significant prolonged HBsAg expression and HBV persistence in both C57/BL6 (80% of the mice with HBsAg positive more than 6 months) and BALB/c (60% of the mice with HBsAg positive more than 3 months) mice. IFNγ was significant up-regulated in liver of the mice injected with 1 μg or 100 μg pAAV-HBV1.2 plasmid DNA. TNFα was up-regulated significantly in liver of the mice injected with 100 μg pAAV-HBV1.2 plasmid DNA. Moreover, PDL1 was significant up-regulated in liver of the mice injected with 5 μg pAAV-HBV1.2 plasmid DNA. In this paper we demonstrated that, in the HBV HI mouse model, the concentration of injected pAAV-HBV1.2 plasmid DNA contributes to the diverse kinetics of HBsAg and HBeAg in the serum as well as HBcAg expression level in the liver, which then determined the HBV persisternce, while the antiviral

Estrogen and progesterone receptor status in breast cancer in Kuwait female population

International Nuclear Information System (INIS)

Paszko, Z.; Padzik, H.; Nasralla, M.Y.; Bouzubar, N.; Omar, Y.T.; Jazzaf, H.; Temmin, L.

1993-01-01

The levels cytosol estrogen (ERc) and progesterone (PRc) receptors were determined in 315 primary breast cancers of female Arab patients aged 23-80 years. Most of breast cancers (78%) occurred in women aged 21-50 years, and only 22% were in women aged 51-80 years. Breast cancers containing ERc and PRc concentrations in the range 5-50 fmol/mg of cytosol protein (mg c.p.) were found with with similar frequency in women aged under or over 50 years (53% of ERc and 43% for PRc, respectively). On the other hand, breast cancer with ERc values of >50 and >100 fmol/mg c.p. were twice as frequent in in women aged over 50 years as in women aged under 50 years. The frequency of breast cancers with PRc level of over 50 fmol/mg c.p. in women aged over 50 years was only half that in those aged under 50 years. In breast cancers of Kuwait Arab women the higher values of ERc (>100 fmol/mg c.p.) and PRc (>50 fmol/mg c.p.) were less frequent than in other populations reported in literature. The low frequency of breast cancer on postmenopausal Kuwait women is associated with low proportions of tumors with higher ERc and PRc contents. In contrast to this, data from literature indicate that in the the North Western European and American populations the postmenopausal incidence rise of breast cancers is associated with increased proportions of tumors with higher ERc and PRc levels. (author)

Membrane estrogen receptors - is it an alternative way of estrogen action?

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Soltysik, K; Czekaj, P

2013-04-01

The functions of estrogens are relatively well known, however the molecular mechanism of their action is not clear. The classical pathway of estrogen action is dependent on ERα and ERβ which act as transcription factors. The effects of this pathway occur within hours or days. In addition, so-called, non-classical mechanism of steroid action dependent on membrane estrogen receptors (mER) was described. In this mechanism the effects of estrogen action are observed in a much shorter time. Here we review the structure and cellular localization of mER, molecular basis of non-classical mER action, physiological role of mER as well as implications of mER action for cancer biology. Finally, some concerns about the new estrogen receptor - GPER and candidates for estrogen receptors - ER-X and ERx, are briefly discussed. It seems that mER is a complex containing signal proteins (signalosome), as IGF receptor, EGF receptor, Ras protein, adaptor protein Shc, non-receptor kinase c-Src and PI-3K, what rationalizes production of second messengers. Some features of membrane receptors are almost identical if compared to nuclear receptors. Probably, membrane and nuclear estrogen receptors are not separate units, but rather the components of a complex mechanism in which they both cooperate with each other. We conclude that the image of the estrogen receptor as a simple transcription factor is a far-reaching simplification. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors.

Effects of perinatal daidzein exposure on subsequent behavior and central estrogen receptor α expression in the adult male mouse.

Science.gov (United States)

Yu, Chengjun; Tai, Fadao; Zeng, Shuangyan; Zhang, Xia

2013-06-03

Daidzein is one of the most important isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The potential role of daidzein in the prevention of some chronic diseases has drawn public attention and increased its consumption in human, including in pregnant women and adolescent. It is unclear whether perinatal exposure to daidzein through maternal diets affects subsequent behavior and central estrogen receptor α (ERα) expression in male adults. Following developmental exposure to daidzein through maternal diets during perinatal period, subsequent anxiety-like behavior, social behavior, spatial learning and memory of male mice at adulthood were assessed using a series of tests. The levels of central ER α expression were also examined using immunocytochemistry. Compared with the controls, adult male mice exposed to daidzein during the perinatal period showed significantly less exploration, higher levels of anxiety and aggression. They also displayed more social investigation for females and a tendency to improve spatial learning and memory. The mice with this early daidzein treatment demonstrated significantly higher levels of ERα expression in several brain regions such as the bed nucleus of the stria terminalis, medial preoptic, arcuate hypothalamic nucleus and central amygdaloid mucleus, but decreased it in the lateral septum. Our results indicated that perinatal exposure to daidzein enhanced masculinization on male behaviors which is assocciated with alterations in ERα expression levels led by perinatal daidzein exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

Estrogen supplementation failed to attenuate biochemical indices of neutrophil infiltration or damage in rat skeletal muscles following ischemia.

Science.gov (United States)

Tiidus, Peter M; Deller, Mirada; Bombardier, Eric; Gül, Mustafa; Liu, X Linda

2005-01-01

This study examined the effects of estrogen supplementation on markers of neutrophil infiltration and damage in skeletal muscle of rats following ischemia. Male and female gonad-intact rats, with or without 14 days of estrogen supplementation were subjected to two hours of hind-limb ischemia and sacrificed at 24, 48 or 72 hours post-ischemia. Control animals were sacrificed without ischemia. Plantaris and red and white gastrocneimus muscles were removed and assayed for myeloperoxidase (MPO), a marker of neutrophil infiltration, and glucose-6-phosphate dehydrogenase (G6PD) and beta-glucuronidase (betaGLU), as markers of muscle damage. Significant elevations of MPO, G6PD and betaGLU activities were observed at various time points post-ischemia. No systematic differences between genders were noted in any of the measures. Estrogen supplementation in both male and female animals failed to significantly attenuate post-ischemia increases in MPO, G6PD and betaGLU activities in any of the muscles studied and in some cases accentuated activities of some of these measures. Unlike previous findings following exercise in skeletal muscle, this study failed to demonstrate estrogen-induced attenuation of indices of neutrophil infiltration or damage in skeletal muscles of rats up to 72 hours following ischemia. This demonstrates that estrogen may not consistently attenuate neutrophil infiltration and that a number of variables including damage modality, tissue or estrogen level may influence this.

Estrogen supplementation failed to attenuate biochemical indices of neutrophil infiltration or damage in rat skeletal muscles following ischemia

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PETER M TIIDUS

2005-01-01

Full Text Available This study examined the effects of estrogen supplementation on markers of neutrophil infiltration and damage in skeletal muscle of rats following ischemia. Male and female gonad-intact rats, with or without 14 days of estrogen supplementation were subjected to two hours of hind-limb ischemia and sacrificed at 24, 48 or 72 hours post-ischemia. Control animals were sacrificed without ischemia. Plantaris and red and white gastrocneimus muscles were removed and assayed for myeloperoxidase (MPO, a marker of neutrophil infiltration, and glucose-6-phosphate dehydrogenase (G6PD and ß-glucuronidase (GLU, as markers of muscle damage. Significant elevations of MPO, G6PD and GLU activities were observed at various time points post-ischemia. No systematic differences between genders were noted in any of the measures. Estrogen supplementation in both male and female animals failed to significantly attenuate post-ischemia increases in MPO, G6PD and GLU activities in any of the muscles studied and in some cases accentuated activities of some of these measures. Unlike previous findings following exercise in skeletal muscle, this study failed to demonstrate estrogen-induced attenuation of indices of neutrophil infiltration or damage in skeletal muscles of rats up to 72 hours following ischemia. This demonstrates that estrogen may not consistently attenuate neutrophil infiltration and that a number of variables including damage modality, tissue or estrogen level may influence this.

Endocrine disrupting chemicals (EDCs) and female cancer: Informing the patients

OpenAIRE

Racho?, Dominik

2016-01-01

Breast and uterine cancer are the most frequent female gender related neoplasms whose growth is mostly estrogen dependent. Therefore, any EDC exhibiting estrogenic effects may increase the risk of these two malignancies. This review focuses on the potential role of EDCs with estrogenic potential on the risk of breast and uterine neoplasms but also points to the possible role of the exposure to EDCs in the pathogenesis of ovarian and cervical cancer. It also underlines the necessity of informi...

[Bone metabolism and cardiovascular function update. Estrogen and its therapeutic potential for bone and vascular health].

Science.gov (United States)

Ohta, Hiroaki

2014-07-01

Despite its long-standing role as a "guardian angel" for the female body, estrogen has recently been dethroned from its status as an "elixir" and its use has been restricted due to its oncogenic potential as well as its coagulation system-associated risk. However, it is recognized that estrogen not only works against bone resorption but also improves vascular function. In this regard, it is suggested that estrogen may have a role in improving deteriorated bone quality through its antioxidant action, while this same effect with the SERMs, which may be accounted for by the presence of estrogen, remains yet to be established. Not only evidence needs to be accumulated to support the vascular effects of the SERMs, but their pleiotropic, rather than extra-skeletal, effects, as likely mediated by the estrogen receptors distributed throughout the body, remain to be elucidated.

A parameter for detecting estrogenic exposure in the copepod Acartia tonsa

DEFF Research Database (Denmark)

Andersen, Henrik Rasmus; Halling-Sørensen, Bent; Kusk, Kresten Ole

1999-01-01

Literature on the basic endocrinology of crustaceans, such as crab, lobster and shrimp, suggest that estrogens, e.g., 17 beta-estradiol, are stimulating hormones in female sexual maturation and egg production in crustaceans. The copepod Acartia tonsa, has continuous egg production. A profile...

Estrogen receptor-a in medial amygdala neurons regulates body weight

Science.gov (United States)

Estrogen receptor–a (ERa) activity in the brain prevents obesity in both males and females. However, the ERa-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded–1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels ...

Association study of the estrogen receptor I gene (ESR1) in anorexia nervosa and eating disorders: No replication found

NARCIS (Netherlands)

Slof-Op 't Landt, M.C.T.; van Furth, E.F.; Meulenbelt, I.; Bartels, M.; Slagboom, P.E.; Boomsma, D.I.

2014-01-01

Objective The female preponderance and onset around puberty in the majority of eating disorders (EDs) suggest that sex hormones, like estrogens, may be involved in the onset of these disorders. An eight-SNP haplotype at the estrogen receptor I (ESR1) gene was found to be associated with anorexia

Estrogenic control of behavioral sex change in the bluehead wrasse, Thalassoma bifasciatum.

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Marsh-Hunkin, K Erica; Heinz, Heather M; Hawkins, M Beth; Godwin, John

2013-12-01

Estrogens activate male-typical sexual behavior in several mammalian and avian models. Estrogen signaling also appears critical in the control of sex change in some fishes, in which it is instead decreases in estradiol levels that may permit development of male-typical behaviors. The bluehead wrasse is a protogynous hermaphrodite that exhibits rapid increases in aggressive and male-typical courtship behavior as females undergo sex change. Removal of the ovaries does not prevent these changes. In two field experiments involving gonadally-intact and gonadectomized females, estradiol (E2) implants prevented behavioral sex change in large females who were made the largest members of their social groups through removals of more dominant fish. In contrast, cholesterol-implanted control females showed full behavioral sex change, along with a higher frequency both of aggressive interactions and of male-typical courtship displays than occurred in E2-implanted animals. To assess potential neural correlates of these behavioral effects of E2, we evaluated abundances of aromatase mRNA using in situ hybridization. Aromatase mRNA was more abundant in the POA of E2-implanted females than in cholesterol-implanted controls in gonadally-intact females. The lack of behavioral sex change coupled with increased levels of aromatase mRNA are consistent with an inhibitory role for E2, likely of neural origin, in regulating socially controlled sex change.

Evaluation of Follicular Synchronization Caused by Estrogen Administration and Its Reproductive Outcome

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Wu, Bi; Shi, Yan; Gong, Xia; Yu, Lin; Chen, Qiuju; Wang, Jian; Sun, Zhaogui

2015-01-01

To evaluate multiple follicular development synchronization after estrogen stimulation in prepubertal mice, follicular responsiveness to gonadotropin superovulation, the prospective reproductive potential and ovarian polycystic ovary syndrome (PCOS)-like symptoms at adulthood, prepubertal mice were intraperitoneally injected with estrogen to establish an animal model with solvent as control. When synchronized tertiary follicles in ovaries, in vitro oocyte maturation and fertilization rates, blastocyst formation rate, developmental potential into offspring by embryo transfer, adult fertility and PCOS-like symptoms, and involved molecular mechanisms were focused, it was found that estrogen stimulation (10μg/gBW) leads to follicular development synchronization at the early tertiary stage in prepubertal mice; reproduction from oocytes to offspring could be realized by means of the artificial reproductive technology though the model mice lost their natural fertility when they were reared to adulthood; and typical symptoms of PCOS, except changes in inflammatory pathways, were not remained up to adulthood. So in conclusion, estrogen can lead to synchronization in follicular development in prepubertal mice, but does not affect reproductive outcome of oocytes, and no typical symptoms of PCOS remained at adulthood despite changes related to inflammation. PMID:26010950

Evaluation of follicular synchronization caused by estrogen administration and its reproductive outcome.

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Bi Wu

Full Text Available To evaluate multiple follicular development synchronization after estrogen stimulation in prepubertal mice, follicular responsiveness to gonadotropin superovulation, the prospective reproductive potential and ovarian polycystic ovary syndrome (PCOS-like symptoms at adulthood, prepubertal mice were intraperitoneally injected with estrogen to establish an animal model with solvent as control. When synchronized tertiary follicles in ovaries, in vitro oocyte maturation and fertilization rates, blastocyst formation rate, developmental potential into offspring by embryo transfer, adult fertility and PCOS-like symptoms, and involved molecular mechanisms were focused, it was found that estrogen stimulation (10 μg/gBW leads to follicular development synchronization at the early tertiary stage in prepubertal mice; reproduction from oocytes to offspring could be realized by means of the artificial reproductive technology though the model mice lost their natural fertility when they were reared to adulthood; and typical symptoms of PCOS, except changes in inflammatory pathways, were not remained up to adulthood. So in conclusion, estrogen can lead to synchronization in follicular development in prepubertal mice, but does not affect reproductive outcome of oocytes, and no typical symptoms of PCOS remained at adulthood despite changes related to inflammation.

Genomic priming of the antisecretory response to estrogen in rat distal colon throughout the estrous cycle.

LENUS (Irish Health Repository)

O'Mahony, Fiona

2009-11-01

The secretion of Cl(-) across distal colonic crypt cells provides the driving force for the movement of fluid into the luminal space. 17beta-Estradiol (E2) produces a rapid and sustained reduction in secretion in females, which is dependent on the novel protein kinase C delta (PKC delta) isozyme and PKA isoform I targeting of KCNQ1 channels. This sexual dimorphism in the E2 response is associated with a higher expression level of PKC delta in female compared with the male tissue. The present study revealed the antisecretory response is regulated throughout the female reproductive (estrous) cycle and is primed by genomic regulation of the kinases. E2 (1-10 nm) decreased cAMP-dependent secretion in colonic epithelia during the estrus, metestrus, and diestrus stages. A weak inhibition of secretion was demonstrated in the proestrus stage. The expression levels of PKC delta and PKA fluctuated throughout the estrous cycle and correlated with the potency of the antisecretory effect of E2. The expression of PKC delta and PKA were up-regulated by estrogen at a transcriptional level via a PKC delta-MAPK-cAMP response element-binding protein-regulated pathway indicating a genomic priming of the antisecretory response. PK Cdelta was activated by the membrane-impermeant E2-BSA, and this response was inhibited by the estrogen receptor antagonist ICI 182,780. The 66-kDa estrogen receptor-alpha isoform was present at the plasma membrane of female colonic crypt cells with a lower abundance found in male colonic crypts. The study demonstrates estrogen regulation of intestinal secretion both at a rapid and transcriptional level, demonstrating an interdependent relationship between both nongenomic and genomic hormone responses.

Disturbance of Mammary UDP-Glucuronosyltransferase Represses Estrogen Metabolism and Exacerbates Experimental Breast Cancer.

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Zhou, Xueyan; Zheng, Ziqiang; Xu, Chang; Wang, Juan; Min, Mengjun; Zhao, Yun; Wang, Xi; Gong, Yinhan; Yin, Jiale; Guo, Meng; Guo, Dong; Zheng, Junnian; Zhang, Bei; Yin, Xiaoxing

2017-08-01

The progression of breast cancer is closely related to the levels of estrogens within the body. UDP-glucuronosyltransferase (UGT) is an important class of phase II metabolizing enzymes, playing a pivotal role in detoxifying steroid hormone. In the present study, we aim at uncovering the potential dysregulation pattern of UGT and its role in estrogen metabolism and in the pathogenesis of breast cancer. Female Sprague-Dawley rats were treated with 100 mg/kg dimethylbenz(a)anthracene (DMBA) to induce breast cancer. Our results showed that the expression and activity of UGT in mammary tissues were downregulated significantly in DMBA rats. Consistent with this, levels of estradiol, 4-hydroxylated estradiol, and 2-hydroxylated estradiol were increased in both mammary tissues and serum, supporting a notable accumulation of toxic estrogen species in the target tissue of breast cancer. In addition, we also observed the decreased cell migration, cell proliferation, and DNA damage in UGT-transfected MCF-7 cells, suggesting a protective role of UGT against estrogen-induced mammary carcinogenesis. Taken together, these results indicated that accumulation of estrogens induced by UGT deficiency is a critical factor to induce the development of breast cancer. UGT contributes to estrogen elimination, and its glucuronidation capacity influences the estrogen signaling pathway and the pathogenesis of breast cancer. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Natural and molecular history of prolactinoma: insights from a Prlr-/- mouse model.

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Bernard, Valérie; Villa, Chiara; Auguste, Aurélie; Lamothe, Sophie; Guillou, Anne; Martin, Agnès; Caburet, Sandrine; Young, Jacques; Veitia, Reiner A; Binart, Nadine

2018-01-19

Lactotroph adenoma, also called prolactinoma, is the most common pituitary tumor but little is known about its pathogenesis. Mouse models of prolactinoma can be useful to better understand molecular mechanisms involved in abnormal lactotroph cell proliferation and secretion. We have previously developed a prolactin receptor deficient ( Prlr -/- ) mouse, which develops prolactinoma. The present study aims to explore the natural history of prolactinoma formation in Prlr -/- mice, using hormonal, radiological, histological and molecular analyses to uncover mechanisms involved in lactotroph adenoma development. Prlr -/- females develop large secreting prolactinomas from 12 months of age, with a penetrance of 100%, mimicking human aggressive densely granulated macroprolactinoma, which is a highly secreting subtype. Mean blood PRL measurements reach 14 902 ng/mL at 24 months in Prlr -/- females while PRL levels were below 15 ng/mL in control mice ( p model in ACI rats, we pinpointed 218 concordantly differentially expressed (DE) genes involved in cell cycle, mitosis, cell adhesion molecules, dopaminergic synapse and estrogen signaling. Pathway/gene-set enrichment analyses suggest that the transcriptomic dysregulation in both models of prolactinoma might be mediated by a limited set of transcription factors (i.e., STAT5, STAT3, AhR, ESR1, BRD4, CEBPD, YAP, FOXO1) and kinases (i.e., JAK2, AKT1, BRAF, BMPR1A, CDK8, HUNK, ALK, FGFR1, ILK). Our experimental results and their bioinformatic analysis provide insights into early genomic changes in murine models of the most frequent human pituitary tumor.

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

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Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

2016-07-01

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. Copyright © 2016 Elsevier Inc. All rights reserved.

Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts

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Jan D. Raguse

2017-01-01

Full Text Available Background. Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Methods. Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ERα in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Results. Expression of ERα was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1 were found. Conclusion. The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

Possible Estrogen Dependency in the Pathogenesis of Branchial Cleft Cysts.

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Raguse, Jan D; Anagnostopoulos, Ioannis; Doll, Christian; Heiland, Max; Jöhrens, Korinna

2017-01-01

Even though branchial cleft cysts are currently accepted as a congenital anomaly, there is often a long delay until clinical presentation; branchial cleft cysts classically appear in the second to fourth decade of life. Our observation of their occurrence in three pregnant women encouraged us to contemplate a possible hormonal influence. Immunohistological analysis was performed for the evaluation of the estrogen receptor alpha (ER α ) in paraffin-embedded tissue specimens of 16 patients with a diagnosis of branchial cleft cyst, with three of them being pregnant. Expression of ER α was detected within epithelial cells only in branchial cleft cysts in pregnant females; moreover, higher growth fractions (Ki-67/Mib1) were found. The fact that the estrogen receptor was expressed only in pregnant women, in contrast to 13 investigated cases, may suggest that the high level of estrogen in pregnancy is a possible explanation for the spontaneous growth of branchial cleft cysts.

Estrogen, stress and the brain: progress toward unraveling gender discrepancies in major depressive disorder.

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Shansky, Rebecca M

2009-07-01

Women are twice as likely as men to develop major depressive disorder (MDD) and, while the neurobiological factors underlying this discrepancy are yet to be identified, estrogen almost certainly plays a role. MDD can be precipitated or exacerbated by exposure to stress and there is substantial evidence to suggest that estrogen can interact with stress systems to produce unique stress effects in females. This review integrates current research in animal models regarding estrogen-stress interactions in three areas of the brain known to be relevant to MDD: the hippocampus, the amygdala and the prefrontal cortex. The results from these studies are discussed in the context of MDD, and their implications for future treatment of MDD in women are explored.

Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors

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2013-01-01

Opioids are widely used as the pain reliever and also notorious for being addictive drugs. Sex differences in the opioid analgesia and addiction have been reported and investigated in human subjects and animal models. Yet, the molecular mechanism underlying the differences between males and females is still unclear. Here, we reviewed the literature describing the sex differences in analgesic responses and addiction liabilities to clinically relevant opioids. The reported interactions among opioids, estrogens, opioid receptors, and estrogen receptors are also evaluated. We postulate that the sex differences partly originated from the crosstalk among the estrogen and opioid receptors when stimulated by the exogenous opioids, possibly through common secondary messengers and the downstream gene transcriptional regulators. PMID:24010861

In vitro biomonitoring of contamination by estrogenic compounds in coastal environments: comments on the use of M. galloprovincialis.

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David, Arthur; Fenet, Hélène; Escande, Aurélie; Munaron, Dominique; Rosain, David; Maillot-Maréchal, Emmanuelle; Aït-Aïssa, Selim; Casellas, Claude; Gomez, Elena

2012-02-01

The use of mussel extracts in in vitro bioassays which express the estrogen receptor could provide valuable information on the bioavailability of endocrine disruptors in coastal environments. The aim of this study was to assess the temporal variability of the estrogenic responses in bioassays in Mytilus galloprovincialis. A 6-month in situ experiment was conducted in order to follow the estrogenic activity on MELN cell line during the reproduction stages of mussels. Estradiol equivalents (EEQ) determined in mussels using the MELN cell lines ranged from 0.79 to 3.72 ng/g dry weight (d.w.) in males, from 0.42 to 2.33 ng/g d.w. in females and from 3.41 to 4.2 d.w. in undifferentiated bivalves. We observed an increase in EEQ values during the spawning stage for males, not for female. The maximal EEQ values were observed at the indifferent stage. We discuss these results in regards to the actual knowledge on mussels' reproductive cycle and to the possible impact of xeno-estrogens. Variations of E2 levels in mussels must be taken into account for further studies on xeno-estrogens monitoring using hER reporter cell-lines bioassays. Copyright © 2010 Wiley Periodicals, Inc.

Role of β1 integrins and bacterial adhesins for Yop injection into leukocytes in Yersinia enterocolitica systemic mouse infection.

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Deuschle, Eva; Keller, Birgit; Siegfried, Alexandra; Manncke, Birgit; Spaeth, Tanja; Köberle, Martin; Drechsler-Hake, Doreen; Reber, Julia; Böttcher, Ralph T; Autenrieth, Stella E; Autenrieth, Ingo B; Bohn, Erwin; Schütz, Monika

2016-02-01

Injection of Yersinia outer proteins (Yops) into host cells by a type III secretion system is an important immune evasion mechanism of Yersinia enterocolitica (Ye). In this process Ye invasin (Inv) binds directly while Yersinia adhesin A (YadA) binds indirectly via extracellular matrix (ECM) proteins to β1 integrins on host cells. Although leukocytes turned out to be an important target of Yop injection by Ye, it was unclear which Ye adhesins and which leukocyte receptors are required for Yop injection. To explain this, we investigated the role of YadA, Inv and β1 integrins for Yop injection into leukocytes and their impact on the course of systemic Ye infection in mice. Ex vivo infection experiments revealed that adhesion of Ye via Inv or YadA is sufficient to promote Yop injection into leukocytes as revealed by a β-lactamase reporter assay. Serum factors inhibit YadA- but not Inv-mediated Yop injection into B and T cells, shifting YadA-mediated Yop injection in the direction of neutrophils and other myeloid cells. Systemic Ye mouse infection experiments demonstrated that YadA is essential for Ye virulence and Yop injection into leukocytes, while Inv is dispensable for virulence and plays only a transient and minor role for Yop injection in the early phase of infection. Ye infection of mice with β1 integrin-depleted leukocytes demonstrated that β1 integrins are dispensable for YadA-mediated Yop injection into leukocytes, but contribute to Inv-mediated Yop injection. Despite reduced Yop injection into leukocytes, β1 integrin-deficient mice exhibited an increased susceptibility for Ye infection, suggesting an important role of β1 integrins in immune defense against Ye. This study demonstrates that Yop injection into leukocytes by Ye is largely mediated by YadA exploiting, as yet unknown, leukocyte receptors. Copyright © 2015. Published by Elsevier GmbH.

Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

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Ammy M. Santiago

2016-10-01

Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

The site of action of intrahypothalamic estrogen implants in feminine sexual behavior: an autoradiographic analysis

International Nuclear Information System (INIS)

Davis, P.G.; Krieger, M.S.; Barfield, R.J.; McEwen, B.S.; Pfaff, D.W.

1982-01-01

Estrogenic stimulation of the ventromedial hypothalamus is sufficient to prime progesterone-facilitated estrous behavior in ovariectomized rats. To determine precisely the site(s) of estrogenic stimulation and the locus of its priming action on estrous behavior, we used steroid autoradiographic methods to assess the diffusion of [ 3 H]estradiol ([ 3 H]E 2 ) from behaviorally effective implants diluted 1:300 with cholesterol. Ovariectomized rats received [ 3 H]E 2 -cholesterol implants aimed at the ventromedial hypothalamic nucleus (VMN). Females were tested twice for feminine sexual behavior after stereotaxic surgery. They received progesterone on the day of behavioral testing. Animals were killed on the day after the second behavior test, cannulae were removed, and the brains were frozen rapidly and processed for autoradiography. Five of eight females with bilateral implants aimed at the VMN exhibited female sexual behavior in at least one of the two tests. Of these, four also showed proceptive behavior. Histological examination of brain sections indicated that behaviorally effective implants were located in, or adjacent to, the central portions of VMN. Implants from nonreceptive animals were located at the extreme anterior or posterior aspects of the VMN. The data collected are consistent with the view that estrogen acts within a sharply defined region of the VMN to prime estrons behavior

Gender differences in sexual and injection risk behavior among active young injection drug users in San Francisco (the UFO Study).

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Evans, Jennifer L; Hahn, Judith A; Page-Shafer, Kimberly; Lum, Paula J; Stein, Ellen S; Davidson, Peter J; Moss, Andrew R

2003-03-01

Female injection drug users (IDUs) represent a large proportion of persons infected with HIV in the United States, and women who inject drugs have a high incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Therefore, it is important to understand the role of gender in injection risk behavior and the transmission of blood-borne virus. In 2000-2002, 844 young (<30 years old) IDUs were surveyed in San Francisco. We compared self-reported risk behavior between 584 males and 260 female participants from cross-sectional baseline data. We used logistic regression to determine whether demographic, structural, and relationship variables explained increased needle borrowing, drug preparation equipment sharing, and being injected by another IDU among females compared to males. Females were significantly younger than males and were more likely to engage in needle borrowing, ancillary equipment sharing, and being injected by someone else. Females were more likely than males to report recent sexual intercourse and to have IDU sex partners. Females and males were not different with respect to education, race/ethnicity, or housing status. In logistic regression models for borrowing a used needle and sharing drug preparation equipment, increased risk in females was explained by having an injection partner who was also a sexual partner. Injecting risk was greater in the young female compared to male IDUs despite equivalent frequency of injecting. Overlapping sexual and injection partnerships were a key factor in explaining increased injection risk in females. Females were more likely to be injected by another IDU even after adjusting for years injecting, being in a relationship with another IDU, and other potential confounders. Interventions to reduce sexual and injection practices that put women at risk of contracting hepatitis and HIV are needed.

Comparing effects of metformin and ginger rhizome extract on the pituitary - gonad function in adult female rats with polycystic ovary syndrome

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Mahbobeh Foroozandeh

2017-06-01

Full Text Available Background & aim: Polycystic Ovary Syndrome (PCOS is one of the most common causes of infertility in women. Due to the prevalence of PCOS in worldwide, this study aimed to compare the effect of metformin with ginger on pituitary-gonad function in PCOS adult female rats was performed. Methods: In this experimental study, 72 adult female rats divided to control, sham PCOS and 7 experimental groups PCOS receiving metformin at 500mg/kg, the ginger at doses 100, 200 & 300mg/kg and ginger at doses 100, 200 & 300mg /kg with metformin at 500 mg/kg were used. All injections by gavage and for 28 days were conducted. After phlebotomizing the animals, to measure hormones FSH, LH and estrogen, progesterone and testosterone, their ovaries removed and after preparing tissue sections, follicles were counted. Data obtained by 18-SPSS software and ANOVA and Duncan were analyzed, then the significant difference of data at P> 0.05was considered. Results: The results showed that letrozole by creating PCOS causes to increase atretic follicles, testosterone, estrogen and reduce other follicles and FSH at P<0.01, and metformin and Ginger alone and together cause to reduce atretic follicles, testosterone, estrogen and increase other follicles and FSH at P<0.01. Conclusion: The results showed that metformin and Ginger alone or together cause to improve PCOS, and these improvements in both groups receiving simultaneous ginger with metformin can be seen more.

Injecting drug use: Gendered risk.

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Zahnow, Renee; Winstock, Adam R; Maier, Larissa J; Levy, Jay; Ferris, Jason

2018-06-01

Research demonstrates gender related differences in drug-use practices and risk behaviours. Females' structural vulnerability stemming from traditional gender roles and gender-power relations may enhance their propensity to experience injecting related risk. In this paper we explore gender differences in injection practices at the initiation event, during the first year of injecting and in the most recent 12-month period, to inform more effective harm reduction strategies. Data used in this study were drawn from the Global Drug Survey 2015. The study employs chi-square and logistic regression to assess gender differences in injection behaviours in a sample of current injectors residing in six global regions: North-West Europe; Southern Eastern Europe; North America. South America and Oceania. Females were more likely than males to report being injected by an intimate partner at initiation (OR = 4.4, 95%CI: 2.2-8.8), during the first year of injecting (OR = 4.8, 95% CI: 2.4-9.3) and in the most recent 12-month period (OR = 2.5, 95%CI: 1.0-6.2). Females reported greater difficulties accessing sterile equipment (X 2 (2,N = 453) = 8.2, p = 0.02) and were more likely to share injecting equipment than males (X 2 (1,N = 463) = 3.9, p = 0.05). Our findings highlight females' continued dependence on their intimate partner to administer the injection into the first year of their injecting career. Females remained more likely than males to rely on intimate partners for injection during the most recent 12-month period. Females report greater difficulties in sourcing sterile equipment and are more likely to share injecting equipment. We suggest that these findings reflect the broader social structure in which females are disempowered through traditional gender roles and the lack of gender appropriate harm reduction services. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

2006-03-15

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

Study on the effect of aromatase inhibitors and antiestrogens on the sex differentiation of broiler chicks

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E.A Valizadeh

2011-02-01

Full Text Available During the development of chick embryo, the genotype of the zygote determines the nature of the gonads, which thereafter creates the male or female phenotype. Differentiation of gonads during the period called “critical period for sexual differentiation “is accompanied with beginning of secretion of sexual hormones. Every change in the rate of steroidal hormones concentration during this critical period, affects on the structure of gonads. Therefore, injection of aromatase inhibitors (which blocks the synthesis of estrogen from testostron in 5th day of incubation into the eggs, causes the production of males with female genotype. These sex reversal females have bilateral testes with complete spermatogenesis, having normal physical appearance and behavior. In this study, 14-α-hydroxy 3,6,17, androstan-trion inhibitor (1mg/egg was injected into the eggs. Furthermore, the effect of three anti-estrogens (which blocks the estrogen receptor Tamoxifen, and Clomiphen Citrate and GAR79 were studied. Injection of aromatase inhibitors into the eggs during incubation period caused statistically significant (p

Transient reversal of olfactory preference following castration in male rats: Implication for estrogen receptor involvement.

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Xiao, Kai; Chiba, Atsuhiko; Sakuma, Yasuo; Kondo, Yasuhiko

2015-12-01

We examined the effects of the sex steroid milieu on sexual odor preference of sexually-experienced male rats using an alternate choice paradigm after endocrine manipulations. Gonadally intact (GI) males showed a male typical preference, i.e. spent longer time sniffing estrous females than males or ovariectomized females. At 1-2 weeks after orchidectomy (ORx), the males exhibited a transient preference for sexually vigorous males, a female typical preference pattern, followed by a total loss of preference after 4 weeks. Subcutaneous implantation of a Silastic capsule containing formestane (4-OHA), an aromatase inhibitor, had no effect on the preference of gonadally intact rats, but successfully prevented the emergence of the female typical preference after ORx. Capsules containing testosterone (T), dihydrotestosterone (DHT), or estradiol benzoate (EB), but not those with cholesterol (CH), restored masculine typical preference in ORx males at 2 weeks after the placement. The feminine preference for males was observed at 2-3 weeks after removal of T or EB capsules, but not by the removal of DHT and CH capsules. The results suggest that either exogenous androgen or estrogen maintains the masculine typical odor preference. Estrogen itself or produced through aromatization of circulating T, induces a transient feminine typical preference at a certain decreased titer during its disappearance from the circulation. Estrogen at different titers might determine appearance of masculine or feminine typical olfactory preference in adult ORx rats. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation.

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Kundu, Payel; Neese, Steven L; Bandara, Suren; Monaikul, Supida; Helferich, William G; Doerge, Daniel R; Khan, Ikhlas A; Schantz, Susan L

Age-related declines in cognitive function can impair working memory, reduce speed of processing, and alter attentional resources. In particular, menopausal women may show an acceleration in the rate of cognitive decline as well as an increased vulnerability to brain diseases as estrogens may play a neuroprotective and neurotrophic role in the brain. To treat menopausal symptoms, many women turn to botanical estrogens that are promoted as a safe and natural alternative to traditional hormone replacement therapy. However, the majority of these compounds have not been systematically evaluated for efficacy and safety. The current study investigated the efficacy of the commercially available botanical estrogenic compound isoliquiritigenin (ISL) to alter performance on an operant working memory task, delayed spatial alternation (DSA). ISL is a compound found in licorice root that has been shown to have a wide range of effects on different biological systems, including estrogenic properties. This botanical is currently being used in over the counter dietary supplements. Middle-aged (12-month old) Long-Evans female rats were ovariectomized and orally dosed with either 0 mg, 6 mg, 12 mg or 24 mg of ISL 60 min before testing on the DSA task. The DSA task required the rat to alternate its responses between two retractable levers in order to earn food rewards. Random delays of 0, 3, 6, 9 or 18 s were imposed between opportunities to press. ISL treatment failed to alter DSA performance. Previous work from our research group has found that estrogenic compounds, including 17β-estradiol and the botanical estrogen genistein impair performance on the DSA task. The goal of our botanical estrogens research is to find compounds that offer some of the beneficial effects of estrogen supplementation, without the harmful effects. This work suggests that ISL may not carry the cognitive risks associated with most other estrogenic compounds tested to date. Copyright © 2018

Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid, a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast Cells, and Rat Uterine Tissues.

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Thongon, Natthakan; Boonmuen, Nittaya; Suksen, Kanoknetr; Wichit, Patsorn; Chairoungdua, Arthit; Tuchinda, Patoomratana; Suksamrarn, Apichart; Winuthayanon, Wipawee; Piyachaturawat, Pawinee

2017-05-03

Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound elicited different transcriptional activities of estrogen agonist at low concentrations (0.1-1 μM) and antagonist at high concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes, whereas it attenuated the uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell differentiation and the related bone markers, indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in postmenopausal women.

Hormesis and Female Sex Hormones

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Elvar Theodorsson

2011-05-01

Full Text Available Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.

Does gestrinone antagonize the effects of estrogen on endometrial implants upon the peritoneum of rats?

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Vera Lúcia Rodrigues Lobo

2008-01-01

Full Text Available OBJECTIVE: To evaluate the effects of estrogen treatment in combination with gestrinone on an experimental rat model of endometriosis. METHODS: Uterine transplants were attached to the peritoneum of female Wistar rats via a surgical autotransplantation technique. The implanted area was measured during the proestrus phase and after hormonal treatment. We performed morphometric analysis and examined the macroscopic and morphometric alterations of endometrial implants after hormonal treatment in ovariectomized rats. RESULTS: The high dose of estrogen caused macroscopic increases in the endometrial implant group compared with other groups, which were similar to increases in the proestrus phase. The low dose showed morphometric development of implants, such as an increase in number of endometrial glands, leukocyte infiltration and mitosis. Gestrinone antagonized both doses of estrogen. CONCLUSION: Our findings suggest that gestrinone antagonizes estrogen's effects on rat peritoneal endometrial implants.

Estrogens in breast cancer

International Nuclear Information System (INIS)

Terzieff, V.; Vázquez, A.

2004-01-01

The prolonged exposure to estrogen increases the risk of cancer breast, the precise role of estrogen in the carcinogenesis process is unclear. They are capable of inducing cell proliferation through different channels receptor Estrogen (ER) known, for example through MAPkinasa sensitivity the promoter of proliferation effect depends on the level of RE, or type to â, integrity (mutations may alter its function) and ligand. The different types of estrogens and related compounds have different profile of affinity for RE and effect end. The modulatory role of progestogens proliferation is very complex, and the interaction between the effector pathways of progestin’s, estrogens, EGF and IGF family - maybe others - determines the final effect .. Estrogens are mutagenic per se weak, but is now known for its hepatic metabolism occur highly reactive species such as quinones, and catechol, powerful mutagens in vitro. Direct or indirect genotoxicity probably explains Part of the effects of estrogen on tumor cells. The use of hormone replacement (HTR) increases the risk of CM, as proportional to the time of use. The combination with progestin seems to be increased risk (R R 2). It is unclear the role of phyto estrogens in the prevention the CM. In the male breast is known that the proliferative response to parenchymal different hormonal maneuvers is different. The effect is minimal castration are and maximum with the combination of estrogen and progesterone. It is unclear, however, the risk of the population exposed to hormone therapy for cancer prostate or otherwise

Induction of vitellogenin synthesis by estrogen in avian liver: relationship between level of vitellogenin mRNA and vitellogenin synthesis.

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Mullinix, K P; Wetekam, W; Deeley, R G; Gordon, J I; Meyers, M; Kent, K A; Goldberger, R F

1976-01-01

We have investigated the estrogen-mediated induction of vitellogenin synthesis in rooster liver. We compared the concentrations of vitellogenin messenger RNA (mRNA) in the liver with the concentrations of vitellogenin in the sera of roosters that had recieved various treatments with estrogen. We found no vitellogenin mRNA in the livers of the unstimulated roosters. An initial injection of estrogen was attended by de novo synthesis of vitellogenin mRNA in the liver and accumulation of vitellogenin in the serum. When vitellogenin was no longer present in the serum or liver (the "post-estrogen-serum-negative" state), the liver was found to contain appreciable amounts of vitellogenin mRNA. This mRNA was of the same size as that found in the liver of the rooster actively synthesizing vitellogenin in response to estrogen. Whereas vitellogenin mRNA was in large polysomes in the livers of the roosters actively synthesizing vitellogenin, the vitellogenin mRNA in the liver of the post-estrogen-serum-negative rooster was not associated with polysomes. The possible relevance of these findings to the fact that the rooster responds differently to a primary stimulation with estrogen than to subsequent stimulations is discussed. PMID:1064017

The role of selective estrogen receptor modulators in the treatment of schizophrenia.

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Bratek, Agnieszka; Krysta, Krzysztof; Drzyzga, Karolina; Barańska, Justyna; Kucia, Krzysztof

2016-09-01

Gender differences in schizophrenia have been recognized for a long time and it has been widely accepted that sex steroid hormones, especially estradiol, are strongly attributed to this fact. Two hypotheses regarding estradiol action in psychoses gained special research attention - the estrogen protection hypothesis and hypoestrogenism hypothesis. A growing number of studies have shown benefits in augmenting antipsychotic treatment with estrogens or selective estrogen receptor modulators (SERM). This review is focused on the role of selective estrogen receptor modulators in the treatment of schizophrenic patients. In order to achieve this result PubMed was searched using the following terms: schizophrenia, raloxifene, humans. We reviewed only randomized, placebo-controlled studies. Raloxifene, a selective estrogen receptor modulator was identified as useful to improve negative, positive, and general psychopathological symptoms, and also cognitive functions. All reviewed studies indicated improvement in at least one studied domain. Augmentation with raloxifene was found to be a beneficial treatment strategy for chronic schizophrenia both in female and male patients, however potential side effects (a small increase in the risk of venous thromboembolism and endometrial cancer) should be carefully considered. SERMs could be an effective augmentation strategy in the treatment of both men women with schizophrenia, although further research efforts are needed to study potential long-term side effects.

Differential expression of largemouth bass (Micropterus salmoides) estrogen receptor isotypes alpha, beta, and gamma by estradiol.

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Sabo-Attwood, Tara; Kroll, Kevin J; Denslow, Nancy D

2004-04-15

The expression levels of three estrogen receptor (ER) isotypes alpha, beta, and gamma were quantified in female largemouth bass (Micropterus salmoides) (LMB) liver, ovary, brain, and pituitary tissues. ER alpha and beta expression predominated in the liver, while ERs beta and gamma predominated in the other tissues. Temporally in females, ER alpha was highly up-regulated, ER gamma was slightly up-regulated, and ER beta levels remained unchanged in the liver when plasma 17-beta estradiol (E2) and vitellogenin (Vtg) levels were elevated in the spring. In ovarian tissue from these same fish, all three ERs were maximally expressed in the fall, during early oocyte development and prior to peak plasma E2 levels. When males were injected with E2, ER alpha was highly inducible, ER gamma was moderately up-regulated, and ER beta levels were not affected. None of the ER isotypes were induced by E2 in gonadal tissues. These results combined suggest that the ERs themselves are not regulated in the same manner by E2, and furthermore, do not contribute equally to the transcriptional regulation of genes involved in fish reproduction such as Vtg.

The distribution of estrogen receptor in various organs of rabbit

International Nuclear Information System (INIS)

Son, H.Y.; In, J.W.; Min, B.S.

1978-01-01

For clinical application of radioreceptor assay, we studied preliminarily the distribution of estrogen receptor in various organs of rabbit by a dextran-charcoal method using 6,7- 3 H-es-tradiol. The results were expressed as binding index, which is the ratio of specific estradiol receptor binding radioactivity to total radioactivity. The materials consist of 5 female rabbits and 3 male rabbits. For female rabbits the binding index was highest in the uterine tissue. This binding index of the uterine tissue was 9.4 times that of the liver, 21.9 times that of the kidney, 24.6 times that of the brain, 28.1 times that of the lung and 65.7 times that of the muscle. For male rabbits the binding index was highest in the liver and decreased in the order of the kidney, the testis, the lung, the brain and the muscle. It is suggested that the estrogen receptor is not confined to any specific target organ but is widely distributed in the various organs, to a different degree. (author)

The Distribution of Estrogen Receptor in Various Organs of Rabbit

International Nuclear Information System (INIS)

Son, Ho Young; In, Jae Whan; Min, Byong Sok

1978-01-01

For clinical application of radioreceptor assay, we studied preliminarily the distribution of estrogen receptor in various organs of rabbit by a dextran-charcoal method using 6, 7- 3 H-estradiol. The results were expressed as binding index, which is the ratio of specific estradiol receptor binding radioactivity to total radioactivity. The materials consist of 5 female rabbits and 3 male rabbits. The results were as follows: 1) Female rabbits. The binding index was highest in the uterine tissue. This binding index of the uterine tissue was 9.4 times that of the liver, 21.9 times that of the kidney, 24.6 times that of the brain, 28.1 times that of the lung and 65.7 times that of the muscle. 2) Male rabbits. The binding index was highest in the liver and decreased in the order of the kidney, the testis, the lung, the brain and the muscle. It is suggested that the estrogen receptor is not confined to any specific target organ but is widely distributed in the various organs, to a different degree.

Impact of Estrogens and Estrogen Receptor Alpha (ESR1) in Brain Lipid Metabolism.

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Morselli, Eugenia; de Souza Santos, Roberta; Gao, Su; Ávalos, Yenniffer; Criollo, Alfredo; Palmer, Biff F; Clegg, Deborah J

2018-03-06

Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen-nanodiamond hydrogel

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Hong, Christine; Song, Dayoung; Lee, Dong-Keun; Lin, Lawrence; Pan, Hsin Chuan; Lee, Deborah; Deng, Peng; Liu, Zhenqing; Hadaya, Danny; Lee, Hye-Lim; Mohammad, Abdulaziz; Zhang, Xinli; Lee, Min; Wang, Cun-Yu; Ho, Dean

2017-08-01

Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17β-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2’s clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induce Apoptosis

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2008-09-01

idoxifene has not been developed further because of concerns about uterine prolapse (299]. This side effect is not seen with tamoxifen 5.6.4 Droloxifene...various species (rat, mouse, mon- key, and dog ). Themajor route of excretion of radioactivitywas in the feces. The rat and dog were used to show that...identified in the dog [40]. This phenolic metabolite without the dimethylaminoethyl side chain is a full estrogen [47,49]. The dimethylaminoethoxy side

Non-genomic estrogen regulation of ion transport and airway surface liquid dynamics in cystic fibrosis bronchial epithelium.

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Vinciane Saint-Criq

Full Text Available 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.

Estrogens can disrupt amphibian mating behavior.

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Frauke Hoffmann

Full Text Available The main component of classical contraceptives, 17α-ethinylestradiol (EE2, has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L, alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline.

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

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Khalil, Raouf A

2013-12-15

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

Immunofluorescent detection in the ovary of host antibodies against a secretory ferritin injected into female Haemaphysalis longicornis ticks.

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Galay, Remil Linggatong; Matsuo, Tomohide; Hernandez, Emmanuel Pacia; Talactac, Melbourne Rio; Kusakisako, Kodai; Umemiya-Shirafuji, Rika; Mochizuki, Masami; Fujisaki, Kozo; Tanaka, Tetsuya

2018-04-01

Due to the continuous threat of ticks and tick-borne diseases to human and animal health worldwide, and the drawbacks of chemical acaricide application, many researchers are exploring vaccination as an alternative tick control method. Earlier studies have shown that host antibodies can circulate in the ticks, but it has not been confirmed whether these antibodies can be passed on to the eggs. We previously reported that ticks infesting rabbits immunized with a recombinant secretory ferritin of Haemaphysalis longicornis (HlFER2) had reduced egg production and hatching. Here we attempted to detect the presence of antibodies against HlFER2 in the ovary and eggs of female ticks through immunofluorescent visualization. Purified anti-HlFER2 antibodies or rabbit IgG for control was directly injected to engorged female H. longicornis. Ovaries and eggs after oviposition were collected and prepared for an indirect immunofluorescent antibody test. Positive fluorescence was detected in ovaries one day post-injection of anti-HlFER2 antibodies. Through silencing of Hlfer2 gene, we also determined whether the injected antibodies can specifically bind to native HlFER2. Immunofluorescence was observed in the oocytes of dsLuciferase control ticks injected with anti-HlFER2 antibodies, but not in the oocytes of Hlfer2-silenced ticks also injected with anti-HlFER2 antibodies. Our current findings suggest that host antibodies can be passed on to the oocytes, which is significant in formulating a vaccine that can disrupt tick reproduction. Copyright © 2017 Elsevier B.V. All rights reserved.

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

OpenAIRE

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

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 w...

Reduction in sperm count and increase in abnormal sperm in the mouse following x-irradiation or injection of 22Na

International Nuclear Information System (INIS)

Harrison, A.; Moore, P.C.

1980-01-01

The accumulated reduction in sperm count and increase in the number of aberrant sperm in the mouse were used to compare acute X-irradiation with protracted radiation from an injection of 22 Na. The effects per unit of absorbed dose of acute and protracted radiation were similar on sperm count, but in respect of numbers of abnormal sperm the 22 Na induced a significantly greater maximum than X-rays. (author)

Progesterone--specific binding sites in the kidney of the female baboon

International Nuclear Information System (INIS)

Weaker, F.J.; Herbert, D.C.; Sheridan, P.J.

1984-01-01

The uptake and retention of a radiolabeled synthetic progestin, ORG 2058, was studied in the urinary tract of the female baboon. Four estrogen-primed baboons were injected intravenously with 2.5 micrograms./kg. body weight of 3H-ORG 2058. One animal, which served as a control, received an additional injection of 2.5 mg./kg. body weight of unlabeled progesterone. One hour after the injections, the animals were killed and the kidneys, ureters and urinary bladder were removed and processed for autoradiography. Localization of progestin was observed in the nuclei of the convoluted and straight segments of the distal tubule, the ascending thick limb of the loop of Henle and both cortical and medullary collecting tubules. Connective tissue cells were also labeled in the medulla and cortex of the kidney. An absence of silver grains was noted in the renal corpuscle, all segments of the proximal tubule and the thin loop of Henle. Concentration of the tritiated steroid was not observed in either the ureter or bladder or in any portions of the urinary tract of the control animal. This study suggests that progesterone has a direct effect via a progesterone specific receptor on the various target cells that sequestered the 3H-ORG 2058

Cumulus-specific genes are transcriptionally silent following somatic cell nuclear transfer in a mouse model*

OpenAIRE

Tong, Guo-qing; Heng, Boon-chin; Ng, Soon-chye

2007-01-01

This study investigated whether four cumulus-specific genes: follicular stimulating hormone receptor (FSHr), hyaluronan synthase 2 (Has2), prostaglandin synthase 2 (Ptgs2) and steroidogenic acute regulator protein (Star), were correctly reprogrammed to be transcriptionally silent following somatic cell nuclear transfer (SCNT) in a murine model. Cumulus cells of C57×CBA F1 female mouse were injected into enucleated oocytes, followed by activation in 10 µmol/L strontium chloride for 5 h and sub...

Marijuana, the Endocannabinoid System and the Female Reproductive System.

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Brents, Lisa K

2016-06-01

Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.

The site of action of intrahypothalamic estrogen implants in feminine sexual behavior: an autoradiographic analysis

Energy Technology Data Exchange (ETDEWEB)

Davis, P.G.; Krieger, M.S.; Barfield, R.J.; McEwen, B.S.; Pfaff, D.W.

1982-11-01

Estrogenic stimulation of the ventromedial hypothalamus is sufficient to prime progesterone-facilitated estrous behavior in ovariectomized rats. To determine precisely the site(s) of estrogenic stimulation and the locus of its priming action on estrous behavior, we used steroid autoradiographic methods to assess the diffusion of (/sup 3/H)estradiol ((/sup 3/H)E/sub 2/) from behaviorally effective implants diluted 1:300 with cholesterol. Ovariectomized rats received (/sup 3/H)E/sub 2/-cholesterol implants aimed at the ventromedial hypothalamic nucleus (VMN). Females were tested twice for feminine sexual behavior after stereotaxic surgery. They received progesterone on the day of behavioral testing. Animals were killed on the day after the second behavior test, cannulae were removed, and the brains were frozen rapidly and processed for autoradiography. Five of eight females with bilateral implants aimed at the VMN exhibited female sexual behavior in at least one of the two tests. Of these, four also showed proceptive behavior. Histological examination of brain sections indicated that behaviorally effective implants were located in, or adjacent to, the central portions of VMN. Implants from nonreceptive animals were located at the extreme anterior or posterior aspects of the VMN. The data collected are consistent with the view that estrogen acts within a sharply defined region of the VMN to prime estrons behavior.

THE ROLE OF ESTROGEN IN WOMEN WITH ANDROGENETIC ALOPECIA

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Putu Diah Pratiwi

2013-07-01

Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Hair loss may accured in both male and female population. Hair loss usually accured in Telogenic phase, meanwhile in Anagenic phase hair loss due to chemotherapy or radiation. Female pattern hair loss (FPHL is regarded as hair fall type which is accured in women in common and known as female androgenetic alopecia. Almost 40%, 50 years old female shown hair fall sign, which is developed progressive fibrosing alopecia of central scalp, especially in frontal and parietal area. There are two common treatment for Female pattern Hair Loss are Minoxidil for topical use, and Fenesteride by oral. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs, in turn increase anagenic phase and represed telogenic phase. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Does signaling of estrogen-related receptors affect structure and function of bank vole Leydig cells?

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Pawlicki, P; Milon, A; Zarzycka, M; Galas, J; Tworzydlo, W; Kaminska, A; Pardyak, L; Lesniak, K; Pacwa, A; Bilinska, B; Gorowska-Wojtowicz, E; Kotula-Balak, M

2017-06-01

To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day). Markedly more, XCT 790 (P endogenous estrogen level in treated males. Notably, immunolocalization of ERRs and above proteins, exclusively in Leydig cells, indicated their involvement in Leydig cell function control based on interactions with endogenous estrogen level and/or estrogen signaling via ERRs. Treatment with XCT 790 or DY131 significantly decreased (P endogenous estrogen status in the testis. Further understanding of mechanism(s) by which individual types of ERRs can control Leydig cell function is relevant for predicting and preventing steroidogenic and spermatogenic disorders.

Role of estrogen and levodopa in 1-methyl-4-pheny-l-1, 2, 3, 6-tetrahydropyridine (mptp)-induced cognitive deficit in Parkinsonian ovariectomized mice model: A comparative study.

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Yadav, Satyndra Kumar; Pandey, Shivani; Singh, Babita

2017-11-01

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen. The behavioral recovery in both LD and estrogen treated mice were investigated using the rotarod, foot printing, narrow beam walking test and hanging tests. Non-motor behavioral recovery in both LD and estrogen treated were investigated using the Y-maze and Morris water maze. Furthermore, we performed the biochemical test i.e. catalase, lipid and nitrite in prefrontal cortex as well as nigrostriatal region of mouse brain. We also performed the acetylcholine esterase activity in prefrontal cortex and nigrostriatal region of mice brain. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by immunostaining of tyrosine hydroxylase (TH). Estrogen treatment restored all the deficits induced by MPTP more effectively than levodopa. Estrogen treatment recovered the number of TH-positive cells in both the SN region. Treatment with Estrogen significantly increased the levels of catalase, decreased the level of lipid and nitite in both region SN as well as prefrontal cortex region. Notably, the effect of estrogen was greater than that elicited by levodopa. Acetylcholine esterase activity was significantly increased in MPTP and it was found to be decreased by the treatment of estrogen as well as levodopa, although decrease in the activity was highly significant in estrogen treated group. Our result suggested that estrogen treatment significantly

Estrogenic properties of spices of the traditional Cameroonian dish "Nkui" in ovariectomized Wistar rats.

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Tchoupang, Edwige Nana; Ateba, Sylvin Benjamin; Zingue, Stéphane; Zehl, Martin; Krenn, Liselotte; Njamen, Dieudonné

2016-06-01

Besides the basic role to flavor and color foods, several health benefits have been attributed to spices. The traditional Cameroonian food "Nkui" is prepared using several spices (Afrostyrax lepidophyllus Mildbr., Capsicum frutescens Linn., Fagara leprieurii Guill. et Perr., Fagara tessmannii Engl., Mondia whitei Hook. F. Skell., Pentadiplandra brazzeana Baill., Solanum gilo Raddi., Tetrapleura tetraptera Taub. and Xylopia parviflora A. Rich. Benthane) that are believed to have a positive impact on the female reproductive physiology. Aiming to determine the potential effect of this food on the female reproductive tract, we evaluated the estrogenic properties of aqueous and ethanol extracts of Nkui using a 3-day uterotrophic assay in ovariectomized (OVX) rats. OVX female Wistar rats were randomly separated in several groups of five animals each and submitted to a 3-day uterotrophic assay (per os). At the end of treatment, animals were sacrificed and uterus, vagina and mammary gland collected and fixed in 10 % formalin for histological analysis. These extracts increased the uterine wet weight, the uterine and vaginal epithelial heights, and the lumen and diameter of alveoli in the mammary glands. They also altered the estradiol-induced increase of uterine wet weight. The dichloromethane and methanol fractions of the ethanol extract exhibited estrogenic properties as well by increasing uterine and vaginal endpoints. These results suggest that the spices of "Nkui" contain estrogenic phytoconstituents and this traditional food may be considered as functional.

Fecal estrogen, progestagen and glucocorticoid metabolites during the estrous cycle and pregnancy in the giant anteater (Myrmecophaga tridactyla): evidence for delayed implantation.

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Knott, Katrina K; Roberts, Beth M; Maly, Morgan A; Vance, Carrie K; Debeachaump, Jennifer; Majors, Jackie; Riger, Peter; Decaluwe, Heather; Kouba, Andrew J

2013-08-27

Declining numbers of wild giant anteaters highlight the importance of sustainable captive populations. Unfortunately, captive reproductive management is limited by the lack of external physical indicators of female reproductive status and the aggressive behavior of males. We examined the endocrinology of the estrous cycle and pregnancy, and whether delayed implantation is a gestational strategy for giant anteaters as described for other xenarthrans. Feces were collected from seven captive females 3-5 times weekly and mating was recorded. Concentrations of estrogen (estrone-glucuronide, E1, and estradiol-17β, E2), progestagen (20-oxo-progestagens, P4), and glucocorticoid (GC) metabolites were examined in fecal extracts by enzyme immunoassay. Estrous cycles for nulliparous females (6 cycles, n = 2) compared to the multiparous female (6 cycles, n = 1) were shorter (47.3 +/- 4.3 days versus 62.5 +/- 2.6 days) with relatively lower luteal phase concentrations of P4 (49.4 +/- 2.9 ng/g versus 136.8 +/- 1.8 ng/g). The four remaining females had unclear ovarian activity: two females exhibited apparent luteal activity but unclear fluctuations in estrogens, while the other two females had parallel fecal P4 and estrogens concentrations. Pregnancy ranged 171-183 days with females returning to estrus post-partum as early as 60 days (n = 3, 1.8-4 years of age at mating). Delayed implantation was indicated by a biphasic elevation in fecal P4 metabolites: the initial 4-fold increase occurred for 81-105 days and was followed by a 26-fold secondary rise in P4 metabolites lasting 66-94 days prior to parturition. Fecal GC was correlated with fecal estrogens and greatest during estrus, late pregnancy, and six days prior to parturition (estrous cycle GC, 14.4-62.8 ng/g; pregnancy GC, 13.6-232.7 ng/g). Estrous cycles of giant anteaters occurred year-round, but were shorter and more intermittent in younger nulliparous animals compared to a multiparous female. A pronounced

Visualizing estrogen receptor-a-expressing neurons using a new ERa-ZsGreen reporter mouse line

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A variety of biological functions of estrogens, including regulation of energy metabolism, are mediated by neurons expressingestrogen receptor-a (ERa) in the brain. However, complex intracellular processes in these ERa-expressing neurons are difficult to unravel, due to the lack of strategy to visua...

Estrogens and aging skin

OpenAIRE

Thornton, M. Julie

2013-01-01

Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity...

Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.

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Maximov, Philipp Y; Abderrahman, Balkees; Fanning, Sean W; Sengupta, Surojeet; Fan, Ping; Curpan, Ramona F; Quintana Rincon, Daniela Maria; Greenland, Jeffery A; Rajan, Shyamala S; Greene, Geoffrey L; Jordan, V Craig

2018-05-08

Estrogen therapy was used to treat advanced breast cancer in postmenopausal women for decades until the introduction of tamoxifen. Resistance to long-term estrogen deprivation (LTED) with tamoxifen and aromatase inhibitors used as a treatment for breast cancer inevitably occurs, but unexpectedly low dose estrogen can cause regression of breast cancer and increase disease free survival in some patients. This therapeutic effect is attributed to estrogen-induced apoptosis in LTED breast cancer. Here we describe modulation of the estrogen receptor liganded with antiestrogens (endoxifen, 4-hydroxytamoxifen) and an estrogenic triphenylethylene (TPE) EthoxyTPE (EtOXTPE) on estrogen-induced apoptosis in LTED breast cancer cells. Our results show that the angular TPE estrogen (EtOXTPE) is able to induce the ER-mediated apoptosis only at a later time compared to planar estradiol in these cells. Using RT-PCR, ChIP, Western blotting, molecular modelling and X-ray crystallography techniques we report novel conformations of the ER complex with an angular estrogen EtOXTPE and endoxifen. We propose that alteration of the conformation of the ER complexes, with changes in coactivator binding, governs estrogen-induced apoptosis through the PERK sensor system to trigger an Unfolded Protein Response (UPR). The American Society for Pharmacology and Experimental Therapeutics.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-11-01

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

Effects of Estrogen Fluctuation during the Menstrual Cycle on the Response to Stretch-Shortening Exercise in Females

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Saulė Sipavičienė

2013-01-01

Full Text Available The aim of this study was to investigate whether variation in estrogen levels during the menstrual cycle influences susceptibility to exercise-induced muscle damage after stretch-shortening cycle exercise. Physically active women (n=18; age = 20.2 ± 1.7 yr participated in this research. The subjects performed one session of 100 maximal drop jumps on day 1 or 2 of the follicular phase and another identical session on day 1 or 2 of the ovulatory phase; the order of the sessions was randomized. Quadriceps femoris muscle peak torque evoked by electrical stimulation and maximal voluntary contraction, muscle pain, and CK activity were measured before and at various times up to 72 h after exercise. It was found that the high estrogen level during the ovulatory phase might be related to an earlier return to baseline muscle strength after strenuous stretch-shortening cycle exercise in that phase compared with the follicular phase. The estrogen effect appears to be highly specific to the damaged site because the differences in most EIMD markers (CK, soreness, and low-frequency fatigue between the two menstrual cycle phases were small.

Estrogen-related receptor gamma and hearing function: evidence of a role in humans and mice.

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Nolan, Lisa S; Maier, Hannes; Hermans-Borgmeyer, Irm; Girotto, Giorgia; Ecob, Russell; Pirastu, Nicola; Cadge, Barbara A; Hübner, Christian; Gasparini, Paolo; Strachan, David P; Davis, Adrian; Dawson, Sally J

2013-08-01

Since estrogen is thought to protect pre-menopausal women from age-related hearing loss, we investigated whether variation in estrogen-signalling genes is linked to hearing status in the 1958 British Birth Cohort. This analysis implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult hearing function and was investigated further in a total of 6134 individuals in 3 independent cohorts: (i) the 1958 British Birth Cohort; (ii) a London ARHL case-control cohort; and (iii) a cohort from isolated populations of Italy and Silk Road countries. Evidence of an association between the minor allele of single nucleotide polymorphism (SNP) rs2818964 and hearing status was found in females, but not in males in 2 of these cohorts: p = 0.0058 (London ARHL) and p = 0.0065 (Carlantino, Italy). Furthermore, assessment of hearing in Esrrg knock-out mice revealed a mild 25-dB hearing loss at 5 weeks of age. At 12 weeks, average hearing thresholds in female mice((-/-)) were 15 dB worse than in males((-/-)). Together these data indicate ESRRG plays a role in maintenance of hearing in both humans and mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Distinct functions and regulation of epithelial progesterone receptor in the mouse cervix, vagina, and uterus.

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Mehta, Fabiola F; Son, Jieun; Hewitt, Sylvia C; Jang, Eunjung; Lydon, John P; Korach, Kenneth S; Chung, Sang-Hyuk

2016-04-05

While the function of progesterone receptor (PR) has been studied in the mouse vagina and uterus, its regulation and function in the cervix has not been described. We selectively deleted epithelial PR in the female reproductive tracts using the Cre/LoxP recombination system. We found that epithelial PR was required for induction of apoptosis and suppression of cell proliferation by progesterone (P4) in the cervical and vaginal epithelium. We also found that epithelial PR was dispensable for P4 to suppress apoptosis and proliferation in the uterine epithelium. PR is encoded by the Pgr gene, which is regulated by estrogen receptor α (ERα) in the female reproductive tracts. Using knock-in mouse models expressing ERα mutants, we determined that the DNA-binding domain (DBD) and AF2 domain of ERα were required for upregulation of Pgr in the cervix and vagina as well as the uterine stroma. The ERα AF1 domain was required for upregulation of Pgr in the vaginal stroma and epithelium and cervical epithelium, but not in the uterine and cervical stroma. ERα DBD, AF1, and AF2 were required for suppression of Pgr in the uterine epithelium, which was mediated by stromal ERα. Epithelial ERα was responsible for upregulation of epithelial Pgr in the cervix and vagina. Our results indicate that regulation and functions of epithelial PR are different in the cervix, vagina, and uterus.

Post-proliferative immature radial glial cells female-specifically express aromatase in the medaka optic tectum.

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Akio Takeuchi

Full Text Available Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in the brain of all vertebrates. Much evidence has accumulated that aromatase is highly and exclusively expressed in proliferating mature radial glial cells in the brain of teleost fish even in adulthood, unlike in other vertebrates. However, the physiological significance of this expression remains unknown. We recently found that aromatase is female-specifically expressed in the optic tectum of adult medaka fish. In the present study, we demonstrated that, contrary to the accepted view of the teleost brain, female-specific aromatase-expressing cells in the medaka optic tectum represent a transient subset of post-proliferative immature radial glial cells in the neural stem cell lineage. This finding led us to hypothesize that female-specific aromatase expression and consequent estrogen production causes some sex difference in the life cycle of tectal cells. As expected, the female tectum exhibited higher expression of genes indicative of cell proliferation and radial glial maturation and lower expression of an anti-apoptotic gene than did the male tectum, suggesting a female-biased acceleration of the cell life cycle. Complicating the interpretation of this result, however, is the additional observation that estrogen administration masculinized the expression of these genes in the optic tectum, while simultaneously stimulating aromatase expression. Taken together, these results provide evidence that a unique subpopulation of neural stem cells female-specifically express aromatase in the optic tectum and suggest that this aromatase expression and resultant estrogen synthesis have an impact on the life cycle of tectal cells, whether stimulatory or inhibitory.

Variable Suppression of Serum Thyroxine in Female Mice of Different Inbred Strains by Triiodothyronine Administered in Drinking Water

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Hamidi, Sepehr; Aliesky, Holly; Chen, Chun-Rong; Rapoport, Basil

2010-01-01

Background Recombinant-inbred mouse strains differ in their susceptibility to Graves'-like hyperthyroidism induced by immunization with adenovirus expressing the human thyrotropin (TSH) receptor. Because one genetic component contributing to this susceptibility is altered thyroid sensitivity to TSH receptor agonist stimulation, we wished to quantify thyroid responsiveness to TSH. For such studies, it is necessary to suppress endogenous TSH by administering L-3,5,3′-triiodothyronine (L-T3), with the subsequent decrease in serum thyroxine (T4) reflecting endogenous TSH suppression. Our two objectives were to assess in different inbred strains of mice (i) the extent of serum T4 suppression after L-T3 administration and (ii) the magnitude of serum T4 increase induced by TSH. Methods Mice were tail-bled to establish baseline-serum T4 before L-T3 administration. We initially employed a protocol of L-T3-supplemented drinking water for 7 days. In subsequent experiments, we injected L-T3 intraperitoneally (i.p.) daily for 3 days. Mice were then injected i.p. with bovine TSH (10 mU) and euthanized 5 hours later. Serum T4 was assayed before L-T3 administration, and before and after TSH injection. In some experiments, serum T3 and estradiol were measured in pooled sera. Results Oral L-T3 (3 or 5 μg/mL) suppressed serum T4 levels by 26%–64% in female BALB/c mice but >95% in males. T4 suppression in female B6 mice ranged from 0% to 90%. In C3H mice, L-T3 at 3 μg/mL was ineffective but 5 μg/mL achieved >80% serum T4 reduction. Unlike inbred mice, in outbred CF1 mice the same protocol was more effective: 83% in females and 100% suppression in males. The degree of T4 suppression was unrelated to baseline T4, T3, or estradiol, but was related to mouse weight and postmortem T3, with greater suppression in larger mice (outbred CF1 animals and inbred males). Among females with serum T4 suppression >80%, the increase in serum T4 after TSH injection was greater for BALB

Mitochondria: Target organelles for estrogen action

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Małgorzata Chmielewska

2017-06-01

Full Text Available Estrogens belong to a group of sex hormones, which have been shown to act in multidirectional way. Estrogenic effects are mediated by two types of intracellular receptors: estrogen receptor 1 (ESR1 and estrogen receptor 2 (ESR2. There are two basic mechanisms of estrogen action: 1 classical-genomic, in which the ligand-receptor complex acts as a transcriptional factor and 2 a nongenomic one, which is still not fully understood, but has been seen to lead to distinct biological effects, depending on tissue and ligand type. It is postulated that nongenomic effects may be associated with membrane signaling and the presence of classical nuclear receptors within the cell membrane. Estrogens act in a multidirectional way also within cell organelles. It is assumed that there is a mechanism which manages the migration of ESR into the mitochondrial membrane, wherein the exogenous estrogen affect the morphology of mitochondria. Estrogen, through its receptor, can directly modulate mitochondrial gene expression. Moreover, by regulating the level of reactive oxygen species, estrogens affect the biology of mitochondria. The considerations presented in this paper indicate the pleiotropic effects of estrogens, which represent a multidirectional pathway of signal transduction.

Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.

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Masahito Kawazu

2011-03-01

Full Text Available Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER positivity. In addition, 17-beta-estradiol (E2 induces JMJD2B expression in an ERα dependent manner. JMJD2B interacts with ERα and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERα target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. As a consequence, knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells. Furthermore, Jmjd2b-deletion in mammary epithelial cells exhibits delayed mammary gland development in female mice. Taken together, these findings suggest an essential role for JMJD2B in the estrogen signaling, and identify JMJD2B as a potential therapeutic target in breast cancer.

Association between asthma and female sex hormones.

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Baldaçara, Raquel Prudente de Carvalho; Silva, Ivaldo

2017-01-01

The relationship between sex hormones and asthma has been evaluated in several studies. The aim of this review article was to investigate the association between asthma and female sex hormones, under different conditions (premenstrual asthma, use of oral contraceptives, menopause, hormone replacement therapy and pregnancy). Narrative review of the medical literature, Universidade Federal do Tocantins (UFT) and Universidade Federal de São Paulo (Unifesp). We searched the CAPES journal portal, a Brazilian platform that provides access to articles in the MEDLINE, PubMed, SciELO, and LILACS databases. The following keywords were used based on Medical Subject Headings: asthma, sex hormones, women and use of oral contraceptives. The associations between sex hormones and asthma remain obscure. In adults, asthma is more common in women than in men. In addition, mortality due to asthma is significantly higher among females. The immune system is influenced by sex hormones: either because progesterone stimulates progesterone-induced blocking factor and Th2 cytokines or because contraceptives derived from progesterone and estrogen stimulate the transcription factor GATA-3. The associations between asthma and female sex hormones remain obscure. We speculate that estrogen fluctuations are responsible for asthma exacerbations that occur in women. Because of the anti-inflammatory action of estrogen, it decreases TNF-α production, interferon-γ expression and NK cell activity. We suggest that further studies that highlight the underlying physiopathological mechanisms contributing towards these interactions should be conducted.

Sex differences in selecting between food and cocaine reinforcement are mediated by estrogen.

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Kerstetter, Kerry A; Ballis, Maya A; Duffin-Lutgen, Stevie; Carr, Amanda E; Behrens, Alexandra M; Kippin, Tod E

2012-11-01

Cocaine-dependent women, relative to their male counterparts, report shorter cocaine-free periods and report transiting faster from first use to entering treatment for addiction. Similarly, preclinical studies indicate that female rats, particularly those in the estrus phase of their reproductive cycle, show increased operant responding for cocaine under a wide variety of schedules. Making maladaptive choices is a component of drug dependence, and concurrent reinforcement schedules that examine cocaine choice offers an animal model of the conditions of human drug use; therefore, the examination of sex differences in decision-making may be critical to understanding why women display a more severe profile of cocaine addiction than men. Accordingly, we assessed sex and estrous cycle differences in choice between food (45 mg grain pellets) and intravenous cocaine (0.4 or 1.0 mg/kg per infusion) reinforcement in male, female (freely cycling), and ovariectomized (OVX) females treated with either estrogen benzoate (EB; 5 μg per day) or vehicle. At both cocaine doses, intact female rats choose cocaine over food significantly more than male rats. However, the estrous cycle did not impact the level of cocaine choice in intact females. Nevertheless, OVX females treated with vehicle exhibited a substantially lower cocaine choice compared with those receiving daily EB or to intact females. These results demonstrate that intact females have a greater preference for cocaine over food compared with males. Furthermore, this higher preference is estrogen-dependent, but does not vary across the female reproductive cycle, suggesting that ovarian hormones regulate cocaine choice. The present findings indicate that there is a biological predisposition for females to forgo food reinforcement to obtain cocaine reinforcement, which may substantially contribute to women experiencing a more severe profile of cocaine addiction than men.

Conditional expression of constitutively active estrogen receptor α in chondrocytes impairs longitudinal bone growth in mice

International Nuclear Information System (INIS)

Ikeda, Kazuhiro; Tsukui, Tohru; Imazawa, Yukiko; Horie-Inoue, Kuniko; Inoue, Satoshi

2012-01-01

Highlights: ► Conditional transgenic mice expressing constitutively active estrogen receptor α (caERα) in chondrocytes were developed. ► Expression of caERα in chondrocytes impaired longitudinal bone growth in mice. ► caERα affects chondrocyte proliferation and differentiation. ► This mouse model is useful for understanding the physiological role of ERαin vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caERα ColII , expressing constitutively active mutant estrogen receptor (ER) α in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caERα ColII mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caERα ColII mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caERα ColII mice. These results suggest that ERα is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

Estrogen-mediated inactivation of FOXO3a by the G protein-coupled estrogen receptor GPER

International Nuclear Information System (INIS)

Zekas, Erin; Prossnitz, Eric R.

2015-01-01

Estrogen (17β-estradiol) promotes the survival and proliferation of breast cancer cells and its receptors represent important therapeutic targets. The cellular actions of estrogen are mediated by the nuclear estrogen receptors ERα and ERβ as well as the 7-transmembrane spanning G protein-coupled estrogen receptor (GPER). We previously reported that estrogen activates the phosphoinositide 3-kinase (PI3Kinase) pathway via GPER, resulting in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) production within the nucleus of breast cancer cells; however, the mechanisms and consequences of this activity remained unclear. MCF7 breast cancer cells were transfected with GFP-fused Forkhead box O3 (FOXO3) as a reporter to assess localization in response to estrogen stimulation. Inhibitors of PI3Kinases and EGFR were employed to determine the mechanisms of estrogen-mediated FOXO3a inactivation. Receptor knockdown with siRNA and the selective GPER agonist G-1 elucidated the estrogen receptor(s) responsible for estrogen-mediated FOXO3a inactivation. The effects of selective estrogen receptor modulators and downregulators (SERMs and SERDs) on FOXO3a in MCF7 cells were also determined. Cell survival (inhibition of apoptosis) was assessed by caspase activation. In the estrogen-responsive breast cancer cell line MCF7, FOXO3a inactivation occurs on a rapid time scale as a result of GPER, but not ERα, stimulation by estrogen, established by the GPER-selective agonist G-1 and knockdown of GPER and ERα. GPER-mediated inactivation of FOXO3a is effected by the p110α catalytic subunit of PI3Kinase as a result of transactivation of the EGFR. The SERMs tamoxifen and raloxifene, as well as the SERD ICI182,780, were active in mediating FOXO3a inactivation in a GPER-dependent manner. Additionally, estrogen-and G-1-mediated stimulation of MCF7 cells results in a decrease in caspase activation under proapoptotic conditions. Our results suggest that non-genomic signaling by GPER contributes

Developmental programming: Impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus

International Nuclear Information System (INIS)

Mahoney, Megan M.; Padmanabhan, Vasantha

2010-01-01

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5 mg/kg/day) from day 30 to 90 of gestation (term 147 d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F 2α , just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female.

Developmental programming: impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus.

Science.gov (United States)

Mahoney, Megan M; Padmanabhan, Vasantha

2010-09-01

Bisphenol-A (BPA) and methoxychlor (MXC), two endocrine-disrupting chemicals (EDCs) with estrogenic and antiandrogenic effects, disrupt the reproductive system. BPA has profound effects on luteinizing hormone (LH) surge amplitude, and MXC has profound effects on on LH surge timing in sheep. The neural mechanisms involved in the differential disruption of the LH surge by these two EDCs remain to be elucidated. We tested the hypothesis that the differential effects of BPA and MXC on LH surge system involved changes in hypothalamic gonadotropin-releasing hormone (GnRH) and estrogen receptors (ESR), ESR1 and ESR2, mRNA expression. Pregnant sheep were given daily injections of cottonseed oil (controls), MXC, or BPA (5mg/kg/day) from day 30 to 90 of gestation (term 147d). Offspring from these animals were euthanized as adults, during the late follicular phase following synchronization of estrus with prostaglandin F(2alpha), just before the expected onset of preovulatory LH surge and changes in mRNA expression of hypothalamic GnRH, ESR1, and ESR2 quantified following in situ hybridization. GnRH mRNA expression was significantly lower in both groups of EDC-treated females compared to controls. ESR1 expression was increased in prenatal BPA- but not MXC-treated females in medial preoptic area relative to controls. In contrast, ESR2 expression was reduced in the medial preoptic area of both EDC-treated groups. Differences in expression of ESR1/ESR2 receptors may contribute to the differential effects of BPA and MXC on the LH surge system. These findings provide support that prenatal exposure to EDCs alters the neural developmental trajectory leading to long-term reproductive consequences in the adult female. 2010 Elsevier Inc. All rights reserved.

Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.

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Znamensky, Vladimir; Akama, Keith T; McEwen, Bruce S; Milner, Teresa A

2003-03-15

In addition to genomic pathways, estrogens may regulate gene expression by activating specific signal transduction pathways, such as that involving phosphatidylinositol 3-kinase (PI3-K) and the subsequent phosphorylation of Akt (protein kinase B). The Akt pathway regulates various cellular events, including the initiation of protein synthesis. Our previous studies showed that synaptogenesis in hippocampal CA1 pyramidal cell dendritic spines is highest when brain estrogen levels are highest. To address the role of Akt in this process, the subcellular distribution of phosphorylated Akt immunoreactivity (pAkt-I) in the hippocampus of female rats across the estrous cycle and male rats was analyzed by light microscopy (LM) and electron microscopy (EM). By LM, the density of pAkt-I in stratum radiatum of CA1 was significantly higher in proestrus rats (or in estrogen-supplemented ovariectomized females) compared with diestrus, estrus, or male rats. By EM, pAkt-I was found throughout the shafts and in select spines of stratum radiatum dendrites. Quantitative ultrastructural analysis identifying pAkt-I with immunogold particles revealed that proestrus rats compared with diestrus, estrus, and male rats contained significantly higher pAkt-I associated with (1) dendritic spines (both cytoplasm and plasmalemma), (2) spine apparati located within 0.1 microm of dendritic spine bases, (3) endoplasmic reticula and polyribosomes in the cytoplasm of dendritic shafts, and (4) the plasmalemma of dendritic shafts. These findings suggest that estrogens may regulate spine formation in CA1 pyramidal neurons via Akt-mediated signaling events.

Estrogen receptors in human thyroid gland. An immunohistochemical study

International Nuclear Information System (INIS)

Arain, Shaukat A.; Shah, Munawar H.; Jamal, Qamar; Meo, Sultan A.

2003-01-01

The objective of this study is to determine the estrogen receptors (ER) status (present in the nucleous of cell) in the thyroid gland tissues. For this purpose 50 previously diagnosed cases of various thyroid lesions were selected from the Surgical Pathology Records of Pathology Department, Basic Medical Sciences Institute,Jinnah Postgraduate. Medical Center,Karachi,Pakistan between March and August 2000.The staining was performed on formalin fixed paraffin embeded tissues using monoclonal anti-ER anti-body (clone1D5).Out of 50 cases,8 were noduler goiter,9 cases of adenoma 19 papillary carcinoma, 10 follicular and 4 cases were of medullary carcinoma. Surrounding normal tissue was available in 25 (50%) cases, 4 non-neoplastic and 21 neoplastic lesions.Out of 50 cases ,10(20%) and 40(80%) were females, the youngest patient was a 15-year-old female and the eldest patient was a 56-years-old male. Despite the availability of normal thyroid tissue and a wide range of lesions, none of our cases showed the positive staining. In contrary to many earlier reports by immunohistochemical method using monoclonal antibody (clone1D5) on formalin- fixed praffin-embedded thyroid tissues, the ER is not detectable. The effect of Estrogen on thyroid gland may be indirect one. (author)

Expression of Estrogen Receptor Alpha in Malignant Melanoma

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Parvin Rajabi

2017-01-01

Full Text Available Background: Features of malignant melanoma (MM vary in the different geographic regions of the world. This may be attributable to environmental, ethnic, and genetic factors. The aim of this study was to determine the expression of estrogen receptor alpha (ER-α in MM in Isfahan, Iran. Materials and Methods: This study was planned as a descriptive, analytical, cross-sectional investigation. During this study, paraffin-embedded tissue blocks of patients with a histopathologic diagnosis of MM was studied for ER-α using immunohistochemistry (IHC. Results: In this study, 38 patients (female/male; 20/18 with a definite diagnosis of malignant cutaneous melanoma and mean age of 52.4 ± 11.2 years were investigated. Using envision IHC staining, there were not any cases with ER-α expression. Conclusion: In confirmation to the most previous studies, expression of ER-α was negative in MM. It is recommended to investigate the expression of estrogen receptor beta and other markers in MM.

Alpha-Fetoprotein: From a Diagnostic Biomarker to a Key Role in Female Fertility

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Christelle De Mees

2006-01-01

Full Text Available Alpha-fetoprotein (AFP is a well-known diagnostic biomarker used in medicine to detect fetal developmental anomalies such as neural tube defects or Down's syndrome, or to follow up the development of tumors such as hepatocellular carcinomas. However, and despite the fact that the protein was discovered almost half a century ago, little was known about its physiological function. The study of Afp knock-out mice uncovered a surprising function of AFP: it is essential for female fertility and for expression of normal female behaviors, and this action is mediated through its estrogen binding capacity. AFP sequestrates estrogens and by so doing protects the female developing brain from deleterious (defeminizing/ masculinizing effects of these hormones

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals.

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Bannister, Richard; Beresford, Nicola; Granger, David W; Pounds, Nadine A; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J

2013-09-15

Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p>0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10(-6)M for Gen and >10(-5)M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and

Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta.

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Fujimoto, Nariaki; Honda, Hiroaki; Kitamura, Shigeyuki

2004-01-01

There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.

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

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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.

Tamoxifen-independent recombination in the RIP-CreER mouse.

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Yanmei Liu

Full Text Available BACKGROUND: The inducible Cre-lox system is a valuable tool to study gene function in a spatial and time restricted fashion in mouse models. This strategy relies on the limited background activity of the modified Cre recombinase (CreER in the absence of its inducer, the competitive estrogen receptor ligand, tamoxifen. The RIP-CreER mouse (Tg (Ins2-cre/Esr1 1Dam is among the few available β-cell specific CreER mouse lines and thus it has been often used to manipulate gene expression in the insulin-producing cells of the endocrine pancreas. PRINCIPAL FINDINGS: Here, we report the detection of tamoxifen-independent Cre activity as early as 2 months of age in RIP-CreER mice crossed with three distinct reporter strains. SIGNIFICANCE: Evidence of Cre-mediated recombination of floxed alleles even in the absence of tamoxifen administration should warrant cautious use of this mouse for the study of pancreatic β-cells.

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

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Pinto, Caroline [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056 (United States); Grimaldi, Marina; Boulahtouf, Abdelhay [Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier (France); Pakdel, Farzad [Institut de Recherche sur la Santé, Environnement et Travail (IRSET), INSERM U1085, Université de Rennes 1, Rennes (France); Brion, François; Aït-Aïssa, Sélim [Unité Écotoxicologie In Vitro et In Vivo, INERIS, Parc ALATA, 60550 Verneuil-en-Halatte (France); Cavaillès, Vincent [Institut de Recherche en Cancérologie de Montpellier, Institut National de la Santé de la Recherche Médicale U896, Institut Régional de Cancérologie de Montpellier, Université Montpellier 1, 34298 Montpellier (France); Bourguet, William [U1054, Centre de Biochimie Structurale, CNRS UMR5048, Université Montpellier 1 et 2, 34290 Montpellier (France); Gustafsson, Jan-Ake [Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5056 (United States); Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Huddinge (Sweden); and others

2014-10-01

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

Sensitivity and Specificity of Bioassay of Estrogenicity on Mammary Gland and Uterus of Female Mice

Czech Academy of Sciences Publication Activity Database

Škarda, Josef

2002-01-01

Roč. 51, - (2002), s. 407-412 ISSN 0862-8408 R&D Projects: GA ČR GA523/99/0843; GA AV ČR KSK5020115 Institutional research plan: CEZ:AV0Z5045916 Keywords : Bioassay * Estrogenicity * Mammary gland Subject RIV: ED - Physiology Impact factor: 0.984, year: 2002

Twenty years of the G protein-coupled estrogen receptor GPER: Historical and personal perspectives.

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Barton, Matthias; Filardo, Edward J; Lolait, Stephen J; Thomas, Peter; Maggiolini, Marcello; Prossnitz, Eric R

2018-02-01

Estrogens play a critical role in many aspects of physiology, particularly female reproductive function, but also in pathophysiology, and are associated with protection from numerous diseases in premenopausal women. Steroids and the effects of estrogen have been known for ∼90 years, with the first evidence for a receptor for estrogen presented ∼50 years ago. The original ancestral steroid receptor, extending back into evolution more than 500 million years, was likely an estrogen receptor, whereas G protein-coupled receptors (GPCRs) trace their origins back into history more than one billion years. The classical estrogen receptors (ERα and ERβ) are ligand-activated transcription factors that confer estrogen sensitivity upon many genes. It was soon apparent that these, or novel receptors may also be responsible for the "rapid"/"non-genomic" membrane-associated effects of estrogen. The identification of an orphan GPCR (GPR30, published in 1996) opened a new field of research with the description in 2000 that GPR30 expression is required for rapid estrogen signaling. In 2005-2006, the field was greatly stimulated by two studies that described the binding of estrogen to GPR30-expressing cell membranes, followed by the identification of a GPR30-selective agonist (that lacked binding and activity towards ERα and ERβ). Renamed GPER (G protein-coupled estrogen receptor) by IUPHAR in 2007, the total number of articles in PubMed related to this receptor recently surpassed 1000. In this article, the authors present personal perspectives on how they became involved in the discovery and/or advancement of GPER research. These areas include non-genomic effects on vascular tone, receptor cloning, molecular and cellular biology, signal transduction mechanisms and pharmacology of GPER, highlighting the roles of GPER and GPER-selective compounds in diseases such as obesity, diabetes, and cancer and the obligatory role of GPER in propagating cardiovascular aging, arterial

Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.

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Johnson, Michael D; Kenney, Nicholas; Stoica, Adriana; Hilakivi-Clarke, Leena; Singh, Baljit; Chepko, Gloria; Clarke, Robert; Sholler, Peter F; Lirio, Apolonio A; Foss, Colby; Reiter, Ronald; Trock, Bruce; Paik, Soonmyoung; Martin, Mary Beth

2003-08-01

It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor. The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.

Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.

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Brown, Susan B; Hankinson, Susan E

2015-07-01

Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Copyright © 2015

Estrogen therapy offsets thermal impairment of vitellogenesis, but not zonagenesis, in maiden spawning female Atlantic salmon (Salmo salar

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Kelli Anderson

2017-11-01

Full Text Available In female Atlantic salmon (Salmo salar, exposure to warm summer temperatures causes a reduction in plasma 17β-estradiol (E2, which impairs downstream vitellogenesis and zonagenesis, and reduces egg fertility and embryo survival. The aim of the present study was to determine whether E2-treatment could offset thermal impairment of endocrine function and maintain egg quality in maiden (first-time-spawning S. salar reared at 22 °C. Treatment with E2 at 22 °C stimulated vitellogenin (vtg gene expression and subsequent protein synthesis which promoted oocyte growth and increased egg size relative to untreated fish at 14 and 22 °C. However, E2-treatment at 22 °C was not associated with an increase in egg fertility and embryo survival relative to untreated fish at 22 °C, despite the positive effects of E2-treatment on vitellogenesis and oocyte growth. As there was no evidence to suggest that the estrogen receptor alpha expression was suppressed by high temperature, this could be due to the lack of stimulation on zonagenesis by E2-treatment observed at high temperature during oocyte development. Our results demonstrate that treatment with E2 is not able to maintain zonagenesis or egg quality in maiden S. salar at high temperature, even when vtg gene expression, protein synthesis and subsequent oocyte growth is promoted. This implies that the mechanisms regulating zonagenesis, but not vitellogenesis are impaired at elevated temperature in female S. salar broodstock, and highlights the remarkable complexity of thermally induced endocrine disruption in fish.

Reductions in HIV/STI Incidence and Sharing of Injection Equipment among Female Sex Workers Who Inject Drugs: Results from a Randomized Controlled Trial

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Strathdee, Steffanie A.; Abramovitz, Daniela; Lozada, Remedios; Martinez, Gustavo; Rangel, Maria Gudelia; Vera, Alicia; Staines, Hugo; Magis-Rodriguez, Carlos; Patterson, Thomas L.

2013-01-01

Background We evaluated brief combination interventions to simultaneously reduce sexual and injection risks among female sex workers who inject drugs (FSW-IDUs) in Tijuana and Ciudad Juarez, Mexico during 2008–2010, when harm reduction coverage was expanding rapidly in Tijuana, but less so in Juarez. Methods FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month participated in a randomized factorial trial comparing four brief, single-session conditions combining either an interactive or didactic version of a sexual risk intervention to promote safer sex in the context of drug use, and an injection risk intervention to reduce sharing of needles/injection paraphernalia. Women underwent quarterly interviews and testing for HIV, syphilis, gonorrhea, Chlamydia and Trichomonas, blinding interviewers and assessors to assignment. Poisson regression with robust variance estimation and repeated measures ordinal logistic regression examined effects on combined HIV/STI incidence and receptive needle sharing frequency. Findings Of 584 initially HIV-negative FSW-IDUs, retention was ≥90%. After 12 months, HIV/STI incidence decreased >50% in the interactive vs. didactic sex intervention (Tijuana:AdjRR:0.38,95% CI:0.16–0.89; Juarez: AdjRR:0.44,95% CI:0.19–0.99). In Juarez, women receiving interactive vs. didactic injection risk interventions decreased receptive needle-sharing by 85% vs. 71%, respectively (p = 0.04); in Tijuana, receptive needle sharing declined by 95%, but was similar in active versus didactic groups. Tijuana women reported significant increases in access to syringes and condoms, but Juarez women did not. Interpretation After 12 months in both cities, the interactive sexual risk intervention significantly reduced HIV/STI incidence. Expanding free access to sterile syringes coupled with brief, didactic education on safer injection was necessary and sufficient for achieving robust, sustained

Response of mouse foetus to radiation from Na sup(99m)TcO4

International Nuclear Information System (INIS)

Lathrop, K.A.; Gloria, I.V.; Harper, P.V.

1976-01-01

Technetium has assumed ecological importance as a source of law-level radiation, with the use of sup(99m)Tc in nuclear medicine and production of sup(99m)Tc in power generation reactions. Technetium introduced as pertechnetate into the bloodstream of pregnant females is transported across the placental barrier to the foetus, where a portion appears to be incorporated into biomolecules. When combined as biomolecules, radionuclides that decay by electron capture or isomeric transition show a lethality greater than that predicted in cell cultures and radiation therapy. The decay of sup(99m)Tc by isomeric transition, together with the above considerations, places a high priority on the investigation of its radiation effects due to clinical doses of up to 25 mCi. Female mice were given daily intravenous injections of 0, 5, 50 and 500 μCi of sup(99m)Tc as pertechnetate in isotonic saline throughout gestation, gestation and lactation, or lactation. At two months of age, the progeny were mated with randomly selected litter mates to produce a second generation; the process was repeated for production of the third generation. Only the first generation was irradiated. An injection of 5 μCi/mouse and 10 mCi/human both approximately equal 0.2 μCi/g of body weight; however, the mouse foetus receives an estimated radiation dose of 0.05 rad, and the human 1 rad. Throughout the gestation period, a mouse at the 5 μCi level receives about 100 μCi of sup(99m)Tc, resulting in approximately 1 rad to the foetus. Significant reduction of body weight was noted in all experimental groups. The greatest effects were seen in the progeny of mothers treated during gestation only. These preliminary results reinforce the existing concern about use of sup(99m)Tc-pertechnetate in pregnant or potentially pregnant subjects

Multimodality optical coherence tomography and fluorescence confocal scanning laser ophthalmoscopy for image-guided feedback of intraocular injections in mouse models

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Benavides, Oscar R.; Terrones, Benjamin D.; Leeburg, Kelsey C.; Mehanathan, Sankarathi B.; Levine, Edward M.; Tao, Yuankai K.

2018-02-01

Rodent models are robust tools for understanding human retinal disease and function because of their similarities with human physiology and anatomy and availability of genetic mutants. Optical coherence tomography (OCT) has been well-established for ophthalmic imaging in rodents and enables depth-resolved visualization of structures and image-based surrogate biomarkers of disease. Similarly, fluorescence confocal scanning laser ophthalmoscopy (cSLO) has demonstrated utility for imaging endogenous and exogenous fluorescence and scattering contrast in the mouse retina. Complementary volumetric scattering and en face fluorescence contrast from OCT and cSLO, respectively, enables cellular-resolution longitudinal imaging of changes in ophthalmic structure and function. We present a non-contact multimodal OCT+cSLO small animal imaging system with extended working distance to the pupil, which enables imaging during and after intraocular injection. While injections are routinely performed in mice to develop novel models of ophthalmic diseases and screen novel therapeutics, the location and volume delivered is not precisely controlled and difficult to reproduce. Animals were imaged using a custom-built OCT engine and scan-head combined with a modified commercial cSLO scan-head. Post-injection imaging showed structural changes associated with retinal puncture, including the injection track, a retinal elevation, and detachment of the posterior hyaloid. When combined with imagesegmentation, we believe OCT can be used to precisely identify injection locations and quantify injection volumes. Fluorescence cSLO can provide complementary contrast for either fluorescently labeled compounds or transgenic cells for improved specificity. Our non-contact OCT+cSLO system is uniquely-suited for concurrent imaging with intraocular injections, which may be used for real-time image-guided injections.

GONAD REMATURATION ON Pangasionodon hypophthalmus FEMALE THROUGH INJECTION OF PREGNANT MARE SERUM GONADOTROPIN AND HUMAN CHORIONIC GONADOTROPIN

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Evi Tahapari

2014-06-01

Full Text Available The success of spawning is influenced by internal and external factors. One of the factors that affect the var iabi li ty of Pangasianodon hypophthalmus female reproductive is the change of seasons that cause disrupted continuity of the seed availability, especially in the dry season. In the present study, combination of PMSG (pregnant mare serum gonadotropin + HCG (hormone chorionic gonadotropin hormone injections was done to induce gonad development. The treatments in this study were without hormone injections as control (A, injection of PMSG 10 IU/kg + HCG 10 IU/kg (B, and injection of PMSG 20 IU/kg HCG + 10 IU/kg (C. Injections were conducted at intervals of two weeks as many as six times. The results showed that gonad maturation generally occurs 2-4 weeks after estradiol-17 peak. PMSG + HCG hormone injections gave a significant effect on increasing the quantity and quality of eggs production. The fecundity in the A, B, C treatments, were 233,700±220,676; 300,305±24,581 and 488,433±142,228; respectively. Number of larvae produced from the A, B, C treatments, were 156,979±170,838; 229,997±18,081 and 362,713±101,850; respectively. Combination of PMSG 20 IU/kg + HCG 10 IU/kg hormone injection gave the best result on fecundity and the number of larvae production.

Yersinia enterocolitica targets cells of the innate and adaptive immune system by injection of Yops in a mouse infection model.

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Martin Köberle

2009-08-01

Full Text Available Yersinia enterocolitica (Ye evades the immune system of the host by injection of Yersinia outer proteins (Yops via a type three secretion system into host cells. In this study, a reporter system comprising a YopE-beta-lactamase hybrid protein and a fluorescent staining sensitive to beta-lactamase cleavage was used to track Yop injection in cell culture and in an experimental Ye mouse infection model. Experiments with GD25, GD25-beta1A, and HeLa cells demonstrated that beta1-integrins and RhoGTPases play a role for Yop injection. As demonstrated by infection of splenocyte suspensions in vitro, injection of Yops appears to occur randomly into all types of leukocytes. In contrast, upon infection of mice, Yop injection was detected in 13% of F4/80(+, 11% of CD11c(+, 7% of CD49b(+, 5% of Gr1(+ cells, 2.3% of CD19(+, and 2.6% of CD3(+ cells. Taking the different abundance of these cell types in the spleen into account, the highest total number of Yop-injected cells represents B cells, particularly CD19(+CD21(+CD23(+ follicular B cells, followed by neutrophils, dendritic cells, and macrophages, suggesting a distinct cellular tropism of Ye. Yop-injected B cells displayed a significantly increased expression of CD69 compared to non-Yop-injected B cells, indicating activation of these cells by Ye. Infection of IFN-gammaR (receptor- and TNFRp55-deficient mice resulted in increased numbers of Yop-injected spleen cells for yet unknown reasons. The YopE-beta-lactamase hybrid protein reporter system provides new insights into the modulation of host cell and immune responses by Ye Yops.

The Expression of Leptin, Estrogen Receptors, and Vitellogenin mRNAs in Migrating Female Chum Salmon, : The Effects of Hypo-osmotic Environmental Changes

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Young Jae Choi

2014-04-01

Full Text Available Leptin plays an important role in energy homeostasis and reproductive function in fish, especially in reproduction. Migrating fish, such as salmonoids, are affected by external environmental factors, and salinity changes are a particularly important influence on spawning migrations. The aim of this study was to test whether changes in salinity affect the expression of leptin, estrogen receptors (ERs, and vitellogenin (VTG in chum salmon (Oncorhynchus keta. The expression and activity of leptin, the expression of ERs and VTG, and the levels of estradiol-17β and cortisol increased after the fish were transferred to FW, demonstrating that changes in salinity stimulate the HPG axis in migrating female chum salmon. These findings reveal details about the role of elevated leptin levels and sex steroid hormones in stimulating sexual maturation and reproduction in response to salinity changes in chum salmon.

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

Science.gov (United States)

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

Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1.

Science.gov (United States)

Du, C; Xu, Y; Yang, K; Chen, S; Wang, X; Wang, S; Wang, C; Shen, M; Chen, F; Chen, M; Zeng, D; Li, F; Wang, T; Wang, F; Zhao, J; Ai, G; Cheng, T; Su, Y; Wang, J

2017-04-01

Estrogen is reported to be involved in thrombopoiesis and the disruption of its signaling may cause myeloproliferative disease, yet the underlying mechanisms remain largely unknown. GATA-binding factor 1 (GATA1) is a key regulator of megakaryocyte (MK) differentiation and its deficiency will lead to megakaryoblastic leukemia. Here we show that estrogen can dose-dependently promote MK polyploidization and maturation via activation of estrogen receptor beta (ERβ), accompanied by a significant upregulation of GATA1. Chromatin immunoprecipitation and a dual luciferase assay demonstrate that ERβ can directly bind the promoter region of GATA1 and activate its transcription. Steroid receptor coactivator 3 (SRC3) is involved in ERβ-mediated GATA1 transcription. The deficiency of ERβ or SRC3, similar to the inhibition of GATA1, leads to the impediment of estrogen-induced MK polyploidization and platelet production. Further investigations reveal that signal transducer and activator of transcription 1 signaling pathway downstream of GATA1 has a crucial role in estrogen-induced MK polyploidization, and ERβ-mediated GATA1 upregulation subsequently enhances nuclear factor erythroid-derived 2 expression, thereby promoting proplatelet formation and platelet release. Our study provides a deep insight into the molecular mechanisms of estrogen signaling in regulating thrombopoiesis and the pathogenesis of ER deficiency-related leukemia.

Estrogens and Cognition: Friends or Foes?

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Korol, Donna L.; Pisani, Samantha L.

2015-01-01

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

Testosterone and estrogen impact social evaluations and vicarious emotions: A double-blind placebo-controlled study.

Science.gov (United States)

Olsson, Andreas; Kopsida, Eleni; Sorjonen, Kimmo; Savic, Ivanka

2016-06-01

The abilities to "read" other peoples' intentions and emotions, and to learn from their experiences, are critical to survival. Previous studies have highlighted the role of sex hormones, notably testosterone and estrogen, in these processes. Yet it is unclear how these hormones affect social cognition and emotion using acute hormonal administration. In the present double-blind placebo-controlled study, we administered an acute exogenous dose of testosterone or estrogen to healthy female and male volunteers, respectively, with the aim of investigating the effects of these steroids on social-cognitive and emotional processes. Following hormonal and placebo treatment, participants made (a) facial dominance judgments, (b) mental state inferences (Reading the Mind in the Eyes Test), and (c) learned aversive associations through watching others' emotional responses (observational fear learning [OFL]). Our results showed that testosterone administration to females enhanced ratings of facial dominance but diminished their accuracy in inferring mental states. In men, estrogen administration resulted in an increase in emotional (vicarious) reactivity when watching a distressed other during the OFL task. Taken together, these results suggest that sex hormones affect social-cognitive and emotional functions at several levels, linking our results to neuropsychiatric disorders in which these functions are impaired. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The role of estrogen G-protein coupled receptor 30 (GPR30) and sexual experience in sexual incentive motivation in male rats.

Science.gov (United States)

Hawley, W R; Battista, C; Divack, S R; Morales Núñez, N B

2017-08-01

Male rats exhibit reductions in sexual motivation following systemic administration of drugs that inhibit the conversion of testosterone to estrogen, which indicates that estrogen signaling plays a role in male rat sexual motivation. Given that estrogen G-protein coupled receptor 30 (GPR30) is expressed in brain areas that are important for male sexual behaviors and endocrine function, the primary aim of the current study was to examine the role that GPR30 plays in sexual motivation in both sexually naïve and sexually experienced male rats. Following the final treatment with either a GPR30 antagonist (G-15) or vehicle control, male rats were placed into the center chamber of a larger three-chambered testing arena that was designed to assess sexual incentive motivation. A sexually receptive stimulus female rat and a stimulus male rat were individually confined to one of the two smaller chambers that were each separated by a perforated partition from the larger end chambers, which test rats had access to. Relative to vehicle treated rats, male rats treated with G-15 exhibited a reduction in the percentage of time spent in the vicinity of a sexually receptive female rat. Although G-15 reduced sexual incentive motivation independent of sexual experience, only sexually-naïve rats treated with G-15 did not exhibit a preference for the sexually receptive stimulus female rat. Collectively, these results indicate that interference with estrogen signaling at GPR30 reduces sexual motivation and that the lack of preference for a sexually receptive female rat over a male rat following G-15 treatment is abrogated by previous sexual experience. Copyright © 2017 Elsevier Inc. All rights reserved.

Unique effects of energy versus estrogen deficiency on multiple components of bone strength in exercising women.

Science.gov (United States)

Southmayd, E A; Mallinson, R J; Williams, N I; Mallinson, D J; De Souza, M J

2017-04-01

Many female athletes are energy and/or estrogen deficient, but the independent effects on bone health have not been isolated. Energy deficiency was detrimental at the tibia while estrogen deficiency was detrimental at the radius. Nutrition must be considered alongside menstrual recovery when addressing compromised bone health in female athletes. The purpose of this study was to describe volumetric bone mineral density (vBMD), bone geometry, and estimated bone strength in exercising women (n = 60) grouped according to energy status (energy replete (EnR: n = 30) vs. energy deficient (EnD: n = 30)) and estrogen status (estrogen replete (E 2 R: n = 33) vs. estrogen deficient (E 2 D: n = 27)), resulting in four distinct groups: EnR + E 2 R (n = 17), EnR + E 2 D (n = 13), EnD + E 2 R (n = 16), EnD + E 2 D (n = 14). Energy status was determined using the ratio of measured to predicted resting energy expenditure (mREE/pREE). Estrogen status was based on self-reported menstrual status confirmed by daily evaluation of urinary estrone-1-glucoronide (E1G), pregnanediol glucuronide (PdG), and luteinizing hormone (LH). Eumenorrheic women were considered E 2 R, amenorrheic women were E 2 D, and oligomenorrheic women were categorized based on history of menses in the past year. Bone was assessed using peripheral quantitative computed tomography (pQCT). EnD women exhibited lower total vBMD, trabecular vBMD, cortical area, and BSI at the distal tibia and lower total vBMD, smaller cortical area and cortical thickness, and larger endosteal circumference at the proximal tibia compared to EnR women (p < 0.042). E 2 D women had lower total and cortical vBMD, larger total and trabecular area, and lower BSI at the distal radius and lower cortical vBMD at the proximal radius compared to E 2 R women (p < 0.023). Energy and estrogen interacted to affect total and trabecular area at the distal tibia (p < 0.021). Efforts to correct energy deficiency, which in turn may

Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

Energy Technology Data Exchange (ETDEWEB)

Do, Ji Yeon; Choi, Young Keun [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kook, Hyun [Department of Pharmacology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, Brain Science & Engineering Institute, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Lee, In-Kyu [Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Aging and Metabolism, Kyungpook National University School of Medicine, Daegu (Korea, Republic of); Park, Dong Ho, E-mail: sarasate2222@gmail.com [Department of Ophthalmology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

2015-05-01

Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O{sub 2}). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice.

Retinal hypoxia induces vascular endothelial growth factor through induction of estrogen-related receptor γ

International Nuclear Information System (INIS)

Do, Ji Yeon; Choi, Young Keun; Kook, Hyun; Suk, Kyoungho; Lee, In-Kyu; Park, Dong Ho

2015-01-01

Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues. This study evaluated the role of ERRγ in the ischemic retina and the anti-VEGF potential of GSK5182, a selective inverse agonist of ERRγ. In an oxygen-induced retinopathy (OIR) mouse model, immunohistochemistry showed significantly increased ERRγ expression in the ganglion cell layer at postnatal day (P) 17. In a ganglion cell line (RGC-5), mRNA and protein levels of ERRγ were increased by desferrioxamine treatment and hypoxic conditions (1% O 2 ). Transient transfection of RGC-5 cells revealed that ERRγ regulated Vegfa expression and this was inhibited by GSK5182. Intravitreal injection of GSK5182 into the OIR model at P14 inhibited retinal Vegfa mRNA expression at P17. GSK5182 suppresses hypoxia-induced VEGF expression via ERRγ; therefore, ERRγ could be a treatment target for ischemic retinopathies. - Highlights: • OIR mice exhibited increased ERRγ expression in the ganglion cell layer. • Hypoxia-induced ERRγ expression was observed in retinal ganglion cells. • ERRγ overexpression increased VEGFA expression in retinal ganglion cells. • An ERRγ inverse agonist suppressed VEGFA expression in retinal ganglion cells. • Intravitreal injection of an ERRγ inverse agonist suppressed VEGFA in OIR mice

Estrogen-related receptor α is essential for maintaining mitochondrial integrity in cisplatin-induced acute kidney injury.

Science.gov (United States)

Tsushida, Keigo; Tanabe, Katsuyuki; Masuda, Kana; Tanimura, Satoshi; Miyake, Hiromasa; Arata, Yuka; Sugiyama, Hitoshi; Wada, Jun

2018-04-15

Acute kidney injury (AKI) has been associated with not only higher in-hospital mortality but also the subsequent development of chronic kidney disease (CKD). Recent evidence has suggested the involvement of mitochondrial dysfunction and impaired dynamics in the pathogenesis of AKI. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that acts as a transcription factor to regulate the transcription of genes required for mitochondrial biogenesis and oxidative phosphorylation. In the present study, we examined the effects of ERRα deficiency on the progression of AKI induced by cisplatin. Male C57BL/6 J wild-type and ERRα -/- mice received a single intraperitoneal injection of 20 mg/kg cisplatin. Seventy-two hours after the injection, kidney function and morphology were evaluated. ERRα expression was observed in renal tubules, and cisplatin inhibited its translocation into nuclei. ERRα deficiency exacerbated cisplatin-induced renal dysfunction and tubular injury, as well as oxidative stress and apoptosis. ERRα -/- mice kidneys revealed lower mitochondrial DNA content and swollen mitochondria with reduced cristae. In addition, these mice had lower expression of the mitochondrial fusion protein mitofusin-2. The cisplatin-induced decrease in mitochondrial DNA and altered mitochondrial structure were more severe in ERRα -/- mice. In cultured mouse proximal tubular epithelial cells, the ERRα inverse agonist XCT-790 significantly inhibited mitofusin-2 expression and induced mitochondrial fragmentation. Taken together, our findings suggest the involvement of ERRα in the progression of cisplatin-induced AKI probably through impaired mitochondrial dynamics. Copyright © 2018 Elsevier Inc. All rights reserved.

In vivo behavior of 111In-DTPA in rat and mouse after intra-ventricular administration

International Nuclear Information System (INIS)

Matsushima, Hiroaki; Kato, Makoto; Sugimura, Yukiharu; Hazue, Masaaki

1977-01-01

In vivo behavior of 111 In-DTPA in rat and mouse after intra-ventricular administration was studied. Thus, 50μCi and 35μCi of 111 In-DTPA was injected intraventricularly to rat and mouse respectively. At specific time intervals, the animals were sacrificed, then distribution in organs was determined by radioactivity counting and autoradiographic method. Urinary and fecal excretion were separately collected and excretion rates were estimated. Metabolites in urine of rat were examined with chromatography. A part of 111 In-DTPA injected intra-ventricularly to the animals migrated to subarachnoid space, then radioactivity in cerebrospinal fluid effused into blood with about 1 hr initial half-life. Blood clearance was also rapid, about 1 hr after administration the blood level reached maximum and then decreased showing an initial half-life of about 1 hr. The predominant excretion route in rat was urinary and about 90% and 5% of administered dose were excreted within 48 hr through urine and feces respectively. Judging from the Rf-value of radioactivity peak on chromatograms, 111 In-DTPA seems to be excreted without suffering any metabolic change. Concerning to the behavior of 111 In-DTPA in male and female rat, no difference was observed, and the distribution pattern of 111 In-DTPA in mouse was similar to that of rat. (auth.)

XY females do better than the XX in the African pygmy mouse, Mus minutoides.

Science.gov (United States)

Saunders, Paul A; Perez, Julie; Rahmoun, Massilva; Ronce, Ophélie; Crochet, Pierre-André; Veyrunes, Frédéric

2014-07-01

All therian mammals have a similar XY/XX sex-determination system except for a dozen species. The African pygmy mouse, Mus minutoides, harbors an unconventional system in which all males are XY, and there are three types of females: the usual XX but also XX* and X*Y ones (the asterisk designates a sex-reversal mutation on the X chromosome). The long-term evolution of such a system is a paradox, because X*Y females are expected to face high reproductive costs (e.g., meiotic disruption and loss of unviable YY embryos), which should prevent invasion and maintenance of a sex-reversal mutation. Hence, mechanisms for compensating for the costs could have evolved in M. minutoides. Data gathered from our laboratory colony revealed that X*Y females do compensate and even show enhanced reproductive performance in comparison to the XX and XX*; they produce significantly more offspring due to (i) a higher probability of breeding, (ii) an earlier first litter, and (iii) a larger litter size, linked to (iv) a greater ovulation rate. These findings confirm that rare conditions are needed for an atypical sex-determination mechanism to evolve in mammals, and provide valuable insight into understanding modifications of systems with highly heteromorphic sex chromosomes. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Biochemical changes in mouse lung after subcutaneous injection of the sulfur mustard 2-chloroethyl 4-chlorobutyl sulfide.

Science.gov (United States)

Elsayed, Nabil M; Omaye, Stanley T

2004-07-01

Sulfur mustard (HD) is a vesicant-type chemical warfare agent (CWA) introduced in World War I which continues to be produced, stockpiled, and occasionally deployed by some countries, and could be used potentially by terrorists. Exposure to HD can cause erythema, blisters, corneal opacity, and airway damage. We have reported previously that subcutaneous (SC) injection of immunodeficient athymic nude mice with the half mustard butyl 2-chloroethyl sulfide (BCS) causes systemic biochemical changes in several organs distal to the exposure site. In the present study, we examined the response of non-immunodeficient Swiss Webster mice to the mustard, 2-chloroethyl 4-chlorobutyl sulfide (CECBS). In a pilot study, we found that a single SC injection of 20-25 microl/mouse causes death within 24h. Consequently, we used 5 microl/mouse (approx. 0.017 mg/kg body weight) of neat CECBS or an equal volume of saline as control. We examined the lungs after 1, 24, and 48 h for biochemical changes including total and oxidized glutathione, protein, DNA, and lipid peroxidation contents in tissue homogenate, and superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, and glutathione S-transferases activities in the cytosol. After 1h and/or 24h, we found statistically significant changes that were resolved by 48 h. These changes mimicked those of HD and BCS and were generally consistent with free radical-mediated oxidative stress. The implications of these observations are two-fold. First, dermal exposure to low-dose mustard gas could elicit systemic changes impacting distal organs such as the lungs. It also suggests that antioxidants could potentially modulate the response and reduce the damage. Second, although the use of known CWAs such as HD is prohibited, analogs that are not recognized as agents are as toxic and could be dangerous if acquired and used by potential terrorists.

Estrogen therapy may counterbalance eutrophic remodeling of coronary arteries and increase bradykinin relaxation in a rat model of menopausal hypertension.

Science.gov (United States)

Matrai, Mate; Hetthéssy, Judit R; Nadasy, Gyorgy L; Szekacs, Bela; Mericli, Metin; Acs, Nandor; Monos, Emil; Arbib, Nissim; Varbiro, Szabolcs

2016-07-01

Hypertension causes adverse remodeling and vasomotor alterations in coronaries. Hormones such as estrogen may help counterbalance some of these effects. The aim of this study was to analyze the effects of ovariectomy and estrogen therapy in a rat model of menopausal hypertension induced by angiotensin II (AII). We investigated diameter, tone, and mechanics of intramural coronaries taken from ovariectomized female rats (n = 11) that received chronic AII treatment to induce hypertension, and compared the results with those found in female rats that were also given estrogen therapy (n = 11). The "hypertensive control" group (n = 11) underwent an abdominal sham operation, and received AII. After 4 weeks of AII treatment, side branches of left anterior descendent coronary (approximately 200 μm in diameter) were isolated, cannulated with plastic microcannulas at both ends, and studied in vitro in a vessel chamber. The inner and outer diameter of the arteries were measured by microangiometry, and spontenuous tone, wall thickness, wall cross-sectional area, tangential stress, incremental distensibility, circumferential incremental elastic modulus, thromboxane agonist-induced tone, and bradykinin-induced dilation were calculated. In hypertension, intramural small coronaries show inward eutrophic remodeling after ovariectomy comparing with hypertensive controls. Estrogen therapy had an opposite effect on vessel diameter. Hormone therapy led to an increase in spontaneous tone, allowing for greater dilatative capacity. Estrogen may therefore be considered to counterbalance some of the adverse changes seen in the wall of intramural coronaries in the early stages of chronic hypertension.

In Vivo Anti-estrogenic Effects of Menadione on Hepatic Estrogen-responsive Gene Expression in Male Medaka (Oryzias latipes)

OpenAIRE

Yamaguchi, Akemi; Kohra, Shinya; Ishibashi, Hiroshi; Arizono, Koji; Tominaga, Nobuaki

2008-01-01

Menadione, a synthetic vitamin K3, exhibits anti-estrogenic activity on in vitro assay. However, the in vivo anti-estrogenic effects of menadione have not been determined, while correlations between biological effects and structural changes are unclear. Thus, we investigated the in vivo anti-estrogenic activity of menadione under fluorescent light and dark conditions. Suppression of the hepatic estrogen response genes vitellogenin1 (VTG1), VTG2 and estrogen receptor-α (ER-α) was used as an in...

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Endometrial cancer, types, prognosis, female hormones and antihormones

DEFF Research Database (Denmark)

Ulrich, L S G

2011-01-01

. Prognosis is also dependent on tumor differentiation and stage, and treatment should be adjusted accordingly. In this paper, the different types of endometrial cancer, staging, prognosis, diagnosis, prevention, treatment and their relationship to estrogen and other female hormones are reviewed....

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

Science.gov (United States)

Velasco-Murillo, V

2001-01-01

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

Estrogen receptor α induces prosurvival autophagy in papillary thyroid cancer via stimulating reactive oxygen species and extracellular signal regulated kinases.

Science.gov (United States)

Fan, Dahua; Liu, Shirley Y W; van Hasselt, C Andrew; Vlantis, Alexander C; Ng, Enders K W; Zhang, Haitao; Dong, Yujuan; Ng, Siu Kwan; Chu, Ryan; Chan, Amy B W; Du, Jing; Wei, Wei; Liu, Xiaoling; Liu, Zhimin; Xing, Mingzhao; Chen, George G

2015-04-01

The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown. This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC. The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed. ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor cell survival and promoted apoptosis, confirming the positive role of autophagy in the growth of PTC. ERα contributes to the growth of PTC by enhancing an important prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.

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

Science.gov (United States)

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

2017-05-01

With increased life expectancy, women will spend over three decades of life postmenopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics. In this brief review, we provide a detailed overview of the literature, from basic science findings to human clinical trial evidence, supporting a protective role of estrogens and their receptors, specifically ERα, in maintenance of cardiometabolic health. In so doing, we provide a concise mechanistic discussion of some of the major tissue-specific roles of estrogens signaling through ERα. Taken together, evidence suggests that targeted, perhaps receptor-specific, hormonal therapies can and should be used to optimize the health of women as they transition through menopause, while reducing the undesired complications that have limited the efficacy and use of traditional hormone replacement interventions. Copyright © 2017 Endocrine Society.

The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-Brain Barrier Permeability

NARCIS (Netherlands)

Cipolla, Marilyn J.; Godfrey, Julie A.; Wiegman, Marchien J.

2009-01-01

Objective: We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability. Materials and Methods: Female ovariectomized Sprague-Dawley rats were replaced with estradiol (E-2) and estriol (E-3) (OVX + E;

No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals☆☆☆

Science.gov (United States)

Bannister, Richard; Beresford, Nicola; Granger, David W.; Pounds, Nadine A.; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J.

2013-01-01

Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of

Conjugated equine estrogen enhances rats' cognitive, anxiety, and social behavior

OpenAIRE

Walf, Alicia A.; Frye, Cheryl A.

2008-01-01

The ovarian hormone, 17β-estradiol (E2), has numerous targets in the body and brain, and can influence cognitive, affective, and social behavior. However, functional effects of commonly prescribed E2-based hormone therapies are less known. The effects of conjugated equine estrogen (CEE) on middle-aged female rats for cognitive (object recognition), anxiety (open field, plus maze), and social (social interaction, lordosis) behavior were compared-with vehicle. Our hypothesis that CEE would enha...

Labeled estrogens as mammary tumor probes

International Nuclear Information System (INIS)

Feenstra, A.

1981-01-01

In this thesis estrogens labeled with a gamma or positron emitting nuclide, called estrogen-receptor binding radiopharmaceuticals are investigated as mammary tumour probes. The requirements for estrogen-receptor binding radiopharmaceuticals are formulated and the literature on estrogens labeled for this purpose is reviewed. The potential of mercury-197/197m and of carbon-11 as label for estrogen-receptor binding radiopharmaceuticals is investigated. The synthesis of 197 Hg-labeled 4-mercury-estradiol and 2-mercury-estradiol and their properties in vitro and in vivo are described. It appears that though basically carbon-11 labeled compounds are very promising as mammary tumour probes, their achievable specific activity has to be increased. (Auth.)

Yeast Estrogen Screen Assay as a Tool for Detecting Estrogenic Activity in Water Bodies

Directory of Open Access Journals (Sweden)

Mirjana Bistan

2012-01-01

Full Text Available The presence of endocrine-disrupting compounds in wastewater, surface water, groundwater and even drinking water has become a major concern worldwide, since they negatively affect wildlife and humans. Therefore, these substances should be effectively removed from effluents before they are discharged into surface water to prevent pollution of groundwater, which can be a source of drinking water. Furthermore, an efficient control of endocrine-disrupting compounds in wastewater based on biological and analytical techniques is required. In this study, a yeast estrogen screen (YES bioassay has been introduced and optimized with the aim to assess potential estrogenic activity of waters. First, assay duration, concentration of added substrate to the assay medium and wavelength used to measure the absorbance of the substrate were estimated. Several compounds, such as 17-β-estradiol, 17-α-ethinylestradiol, bisphenol A, nonylphenol, genisteine, hydrocortisone, dieldrin, atrazine, methoxychlor, testosterone and progesterone were used to verify its specificity and sensitivity. The optimized YES assay was sensitive and responded specifically to the selected estrogenic and nonestrogenic compounds in aqueous samples. Potential estrogenicity of influent and effluent samples of two wastewater treatment plants was assessed after the samples had been concentrated by solid-phase extraction (SPE procedure using Oasis® HLB cartridges and methanol as eluting solvent. Up to 90 % of relative estrogenic activity was detected in concentrated samples of influents to wastewater treatment plants and estrogenic activity was still present in the concentrated effluent samples. We found that the introduced YES assay is a suitable screening tool for monitoring the potential estrogenicity of effluents that are discharged into surface water.

Nongenomic Actions of 17-β Estradiol Restore Respiratory Neuroplasticity in Young Ovariectomized Female Rats

Science.gov (United States)

Dougherty, Brendan J.; Kopp, Elizabeth S.

2017-01-01

Gonadal steroids modulate CNS plasticity, including phrenic long-term facilitation (pLTF), a form of spinal respiratory neuroplasticity resulting in increased phrenic nerve motor output following exposure to acute intermittent hypoxia (aIH; three 5 min episodes, 10.5% O2). Despite the importance of respiratory system neuroplasticity, and its dependence on estrogen in males, little is known about pLTF expression or mechanisms of estrogen signaling in females. Here, we tested the hypotheses that (1) pLTF expression in young, gonadally intact female rats would be expressed during estrous cycle stages in which 17β-estradiol (E2) is naturally high (e.g., proestrus vs estrus), (2) pLTF would be absent in ovariectomized (OVX) rats and in physiological conditions in which serum progesterone, but not E2, is elevated (e.g., lactating rats, 3–10 d postpartum), and (3) acute E2 administration would be sufficient to restore pLTF in OVX rats. Recordings of phrenic nerve activity in female Sprague Dawley rats (3–4 months) revealed a direct correlation between serum E2 levels and pLTF expression in cycling female rats. pLTF was abolished with OVX, but was re-established by acute E2 replacement (3 h, intraperitoneal). To identify underlying E2 signaling mechanisms, we intrathecally applied BSA-conjugated E2 over the spinal phrenic motor nucleus and found that pLTF expression was restored within 15 min, suggesting nongenomic E2 effects at membrane estrogen receptors. These data are the first to investigate the role of ovarian E2 in young cycling females, and to identify a role for nongenomic estrogen signaling in any form of respiratory system neuroplasticity. SIGNIFICANCE STATEMENT Exposure to acute intermittent hypoxia induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity that improves breathing in models of spinal cord injury. Although pathways leading to pLTF are well studied in males and estradiol (E2) is known to be required, it has

Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A

International Nuclear Information System (INIS)

Sanders, J. Michael; Coulter, Sherry J.; Knudsen, Gabriel A.; Dunnick, June K.; Kissling, Grace E.; Birnbaum, Linda S.

2016-01-01

Chronic oral treatment of tetrabromobisphenol A (TBBPA) to female Wistar Han rats resulted in increased incidence of cell proliferation at 250 mg/kg and tumor formation in the uterus at higher doses. The present study was designed to test the hypothesis that disruption of estrogen homeostasis was a major mode-of-action for the observed effects. Biological changes were assessed in serum, liver, and the proximal (nearest the cervix) and distal (nearest the ovaries) sections of the uterine horn of Wistar Han rats 24 h following administration of the last of five daily oral doses of 250 mg/kg. Expression of genes associated with receptors, biosynthesis, and metabolism of estrogen was altered in the liver and uterus. TBBPA treatment also resulted in changes in expression of genes associated with cell division and growth. Changes were also observed in the concentration of thyroxine in serum and in expression of genes in the liver and uterus associated with thyroid hormone receptors. Differential expression of some genes was tissue-dependent or specific to tissue location in the uterus. The biological responses observed in the present study support the hypothesis that perturbation of estrogen homeostasis is a major mode-of-action for TBBPA-mediated cell proliferation and tumorigenesis previously observed in the uterus of TBBPA-treated Wistar Han rats. - Highlights: • Perturbation of estrogen homeostasis in TBBPA-treated female rats was investigated. • Gene expression changes were observed in the liver and uterus of these rats. • Genes associated with estrogen biosynthesis and metabolism were affected. • Genes associated with thyroid homeostasis and cell division/growth were affected. • A mechanism of uterine toxicity via endocrine disruption was indicated.

Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A

Energy Technology Data Exchange (ETDEWEB)

Sanders, J. Michael, E-mail: sander10@mail.nih.gov [Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Coulter, Sherry J.; Knudsen, Gabriel A. [Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Dunnick, June K.; Kissling, Grace E. [National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Birnbaum, Linda S. [Laboratory of Toxicology and Toxicokinetics, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

2016-05-01

Chronic oral treatment of tetrabromobisphenol A (TBBPA) to female Wistar Han rats resulted in increased incidence of cell proliferation at 250 mg/kg and tumor formation in the uterus at higher doses. The present study was designed to test the hypothesis that disruption of estrogen homeostasis was a major mode-of-action for the observed effects. Biological changes were assessed in serum, liver, and the proximal (nearest the cervix) and distal (nearest the ovaries) sections of the uterine horn of Wistar Han rats 24 h following administration of the last of five daily oral doses of 250 mg/kg. Expression of genes associated with receptors, biosynthesis, and metabolism of estrogen was altered in the liver and uterus. TBBPA treatment also resulted in changes in expression of genes associated with cell division and growth. Changes were also observed in the concentration of thyroxine in serum and in expression of genes in the liver and uterus associated with thyroid hormone receptors. Differential expression of some genes was tissue-dependent or specific to tissue location in the uterus. The biological responses observed in the present study support the hypothesis that perturbation of estrogen homeostasis is a major mode-of-action for TBBPA-mediated cell proliferation and tumorigenesis previously observed in the uterus of TBBPA-treated Wistar Han rats. - Highlights: • Perturbation of estrogen homeostasis in TBBPA-treated female rats was investigated. • Gene expression changes were observed in the liver and uterus of these rats. • Genes associated with estrogen biosynthesis and metabolism were affected. • Genes associated with thyroid homeostasis and cell division/growth were affected. • A mechanism of uterine toxicity via endocrine disruption was indicated.

Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status

NARCIS (Netherlands)

Kruijver, Frank P. M.; Balesar, Rawien; Espila, Ana M.; Unmehopa, Unga A.; Swaab, Dick F.

2002-01-01

The present study reports the first systematic rostrocaudal distribution of estrogen receptor-a immunoreactivity (ERalpha-ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was

Differential expression patterns and clinical significance of estrogen receptor-α and β in papillary thyroid carcinoma

International Nuclear Information System (INIS)

Huang, Yanhong; Dong, Wenwu; Li, Jing; Zhang, Hao; Shan, Zhongyan; Teng, Weiping

2014-01-01

The incidence of papillary thyroid cancer (PTC) is markedly higher in women than men during the reproductive years. In vitro studies have suggested that estrogen may play an important role in the development and progression of PTC through estrogen receptors (ERs). This study aimed to investigate the expression patterns of the two main ER subtypes, α and β1 (wild-type ERβ), in PTC tissue and their clinical significance. Immunohistochemical staining of thyroid tissue sections was performed to detect ER expression in female patients with PTC (n = 89) and nodular thyroid goiter (NTG; n = 30) using the Elivision™ plus two-step system. The relationships between ER subtype expression and clinicopathological/biological factors were further analyzed. The positive percentage and expression levels of ERα were significantly higher in female PTC patients of reproductive age (18–45 years old; n = 50) than age-matched female NTG patients (n = 30), while ERβ1 exhibited the opposite pattern. There was no difference in ERα or ERβ1 expression between female PTC patients of reproductive age and those of advanced reproductive age (>45 years old; n = 39). In the female PTC patients of reproductive age, ERα expression level was positively correlated with that of Ki-67, while ERβ1 was negatively correlated with mutant P53. Furthermore, more patients with exclusively nuclear ERα expression had extrathyroidal extension (ETE) as compared with those with extranuclear ERα localization. VEGF expression was significantly decreased in female PTC patients of reproductive age with only nuclear ERβ1 expression when compared with those with extranuclear ERβ1 localization. In PTC patients of advanced reproductive age, neither ERα nor ERβ1 expression showed any correlation with that of Ki-67, mutant P53, VEGF, tumor size, TNM stage, ETE, or lymph node metastases. The differential expression patterns of the two ER subtypes between PTC and NTG indicate that ERα may be a useful

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model.

Science.gov (United States)

Sang, Xiuxiu; Wang, Ruilin; Han, Yanzhong; Zhang, Cong'en; Shen, Honghui; Yang, Zhirui; Xiong, Yin; Liu, Huimin; Liu, Shijing; Li, Ruisheng; Yang, Ruichuang; Wang, Jiabo; Wang, Xuejun; Bai, Zhaofang; Xiao, Xiaohe

2017-05-01

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) in vitro , limited research has been done with this drug in vivo . In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon- γ (IFN- γ ) in a dose-dependent manner in CD4 + T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

Select estrogens within the complex formulation of conjugated equine estrogens (Premarin® are protective against neurodegenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease

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Brinton Roberta

2006-03-01

Full Text Available Abstract Background Results of the Women's Health Initiative Memory Study (WHIMS raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE, used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER. Results Cultured basal forebrain neurons were exposed to either β-amyloid25–35 or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17β-estradiol and Δ8,9-dehydroestrone were effective in protecting neurons against β-amyloid25–35-induced intracellular ATP decline

Molecular analysis of human endometrium: Short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling

NARCIS (Netherlands)

P. Hanifi-Moghaddam (Payman); B. Boers-Sijmons (Bianca); A.H.A. Klaassens (Anet); F.H. van Wijk (Heidy); M.A. den Bakker (Michael); M.C. Ott; G.L. Shipley; H.A.M. Verheul (Herman); H.J. Kloosterboer (Helenius); C.W. Burger (Curt); L.J. Blok (Leen)

2007-01-01

textabstractTibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current

Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model.

Science.gov (United States)

de Moura, Nelci Antunes; Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; Barbisan, Luís Fernando

2010-02-01

The potential promoting effect of Diuron was investigated in a mouse model of mammary and urinary bladder carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Four-week old female Swiss mice were allocated to five groups: Groups G1-G3 received DMBA (5 x 1.5 mg/mouse) and BBN (8 x 7.5 mg/mouse) and G4 and G5 groups received only vehicles during the first 6 weeks. At week 7, G1 and G5 groups received basal diet and G2, G3 and G4 groups were fed a diet containing Diuron at 1,250, 2,500 and 2,500 ppm, respectively, during 13 weeks. At week 20, the animals were euthanized and the gross tumors were registered. Mammary glands and urinary bladder were processed for histopathological analysis. Samples from non-tumor areas were evaluated for cell proliferation by 5-bromodeoxyuridine labeling index (BrdU-LI%) and apoptosis. Dietary treatment with Diuron at 1,250 and 2,500 ppm significantly increased BrdU-LI% (P Diuron 2,500 ppm (G3). In contrast, in the mammary gland, Diuron feeding for 13 weeks did not significantly alter cell proliferation and apoptosis indexes or the incidence of hyperplastic lesions or neoplasms in the DMBA/BBN-initiated groups. These findings suggest that Diuron is a promoting agent to the urinary bladder but not to the mammary gland in female Swiss mice submitted to a medium-term two-stage carcinogenesis bioassay.

Using vaginal cytology to assess the estrogenic activity of phytoestrogen-rich herb.

Science.gov (United States)

Malaivijitnond, Suchinda; Chansri, Kullakanya; Kijkuokul, Pisamai; Urasopon, Nontakorn; Cherdshewasart, Wichai

2006-10-11

To assess the estrogenic activities of synthetic estrogen, synthetic phytoestrogen, Pueraria lobata and three distinct cultivars of Pueraria mirifica, a phytoestrogen-rich herb, a vaginal cytology assay in ovariectomized rats were used. Rats were ovariectomized and treated with DW, estradiol valerate (1 mg/kg BW), genistein (0.25-2.5 mg/kg BW), Pueraria lobata and Pueraria mirifica (10-1,000 mg/kg BW) for 14 days. The vaginal cytology was checked daily and the uteri were dissected and weighed at the end of treatment or post-treatment periods. The treatments of DW, genistein and Pueraria lobata did not influence the vaginal epithelium, but the injection of estradiol valerate induced a vaginal cornification from day-3 of treatment to day-14 of post-treatment period. The occurrence of vaginal cornification after treatment and the recovery after the cessation was dependent on dosages and cultivars of Pueraria mirifica. The increments of uterus weight in all rats agreed with the cornification of vaginal epithelium. Although both uterotropic and vaginal cytology assays can be used to assess the estrogenic activity of phytoestrogen-rich herb, however, using vaginal cytology assay has two advantages: (1) we do not need to kill the animals and (2) we can follow up the recovery after the cessation of treatment.

Analysis of estrogenic activity in environmental waters in Rio de Janeiro state (Brazil) using the yeast estrogen screen.

Science.gov (United States)

Dias, Amanda Cristina Vieira; Gomes, Frederico Wegenast; Bila, Daniele Maia; Sant'Anna, Geraldo Lippel; Dezotti, Marcia

2015-10-01

The estrogenicity of waters collected from an important hydrological system in Brazil (Paraiba do Sul and Guandu Rivers) was assessed using the yeast estrogen screen (YES) assay. Sampling was performed in rivers and at the outlets of conventional water treatment plants (WTP). The removal of estrogenic activity by ozonation and chlorination after conventional water treatment (clarification and sand filtration) was investigated employing samples of the Guandu River spiked with estrogens and bisphenol A (BPA). The results revealed a preoccupying incidence of estrogenic activity at levels higher than 1ngL(-1) along some points of the rivers. Another matter of concern was the number of samples from WTPs presenting estrogenicity surpassing 1ngL(-1). The oxidation techniques (ozonation and chlorination) were effective for the removal of estrogenic activity and the combination of both techniques led to good results using less amounts of oxidants. Copyright © 2015 Elsevier Inc. All rights reserved.

Radioautography of the central nervous system and pituitary after 3H steroid hormones injection into different mammals

International Nuclear Information System (INIS)

Warembourg, M.

1977-01-01

The central nervous system and pituitary of various mammals were examined by radioautography after injection of different tritiated steroid hormones. After injection of 3 H estradiol into ovariectomized mice, radioautograms revealed a significant labelling in cells of the amygdala, the bed nucleus of the stria terminalis, the nucleus preopticus medialis, the nuclei arcuatus and ventro-medialis. After injection of 3 H testosterone into castrated rats, the central nervous system and the anterior pituitary contained labelled cells. In the hypothalamus, the distribution pattern of androgen-neurons appears to be similar from the estrogen-neuron areas. After injection of 3 H progesterone into castrated estrogen-primed guinea-pigs, labelled neurons have been in the regions of nucleus arcuatus and nucleus preopticus suprachiasmaticus. After injection of 3 H corticosterone into adrenalectomized male rats, radioactivity was found to be selectively concentrated in neurons of septum, hippocampal complex indusium griseum, amygdala and in certain areas of the cortex. Most of the silver grains were localized in the nuclei of labelled cells. On the other hand, after injection of 3 H dexamethasone radioactivity concentration was high in the medial basal hypothalamus, in the anterior pituitary and in the pineal gland. Differences appear to exist in the topographic distribution of dexamethasone and corticosterone-concentrating cells [fr

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

Science.gov (United States)

Korol, Donna L; Pisani, Samantha L

2015-08-01

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

Effects of the aromatase inhibitor Letrozole on serum immunoglobulin and lysozyme levels in immunized rainbow trout (Oncorhynchus mykiss Walbaum females

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Paria Akbary

2013-12-01

Full Text Available Letrozole is a synthetic aromatase inhibitor and interfere in the committed step in the synthesis of endogenous estrogens from androgens. Also estrogens regulate the immune system in teleost. Changes of 17- β- esrtradiol (E2, serum immunoglobulin and lysozyme levels were measured using a method based on the ability of lysozyme to lyse the bacterium Micrococcus lysodeikticus, enzyme-linked immunosorbent assay (ELISA and ELISA respectively. Twelve broodstocks were injected weekly with 2.5 mg kg-1 letrozole (an endocrine disrupter component two months before spawning season and vaccinated intraperitoneally (i.p with a bacterin (inactivated L. garviae one month before spawning. Twelve broodstocks for vaccination and twelve female rainbow trout as control group were also immiunised (i.p with the bacterin and injected (i.p with PBS, respectively. In the group received 2.5 mg AI kg-1 per week, serum E2 levels were significantly lower than that of other groups. Total immunoglobulin level and lysozyme activity were significantly higher in the parents received 2.5 mg kg-1 per week and were immunized with 10-9 cells ml-1 Lactococcus garvieae  compared to the group which immunized with L. garvieae and the control (non- immunized. The present study, suggests that aromatase inhibitors such as letrozole may be a potential tool to regulate the synthesis of E2, is involved in the hormone- immune system interaction in rainbow trout.

Effect of Intracytoplasmic Sperm Injection (ICSI on Mouse Embryos Preimplantational Development

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Claudia Cârstea

2012-05-01

Full Text Available It is known that the in vitro culture (IVC of preimplantation embryos is associated with changes in gene expression. It is however, not known if the method of fertilization affects the global pattern of gene expression. We compared the development of mouse blastocysts produced by intracytoplasmic sperm injection (ICSI versus blastocysts fertilized in vivo and cultured in vitro from the zygote stage (IVC. At the end of cultivation (96 hrs for blastocyst stage embryos, expanded blastocysts of each group were randomly selected, and ICM and total cells number were differentially stained. The total cell number of blastocysts was estimated by counting the total number of nuclei using DAPI staining. Cell number for inner cell mass (ICM was estimated by counting the OCT4 (POU5FL positive cells. Digitally recombined, composite images were analyzed using the Zeiss Axion Vision software and Zeiss Apotome. All 5–10 optical sections were divided using a standard grid over each layer to count all. Comparing the total cells and the ICM cells number, it appears that each method of fertilization has a unique pattern development. The developmental rate and the total cell number of the blastocyst were significantly lower in ICSI versus in vivo fertilized embryos which affect the embryonic developmental rate and the total cell number of blastocysts.

Experimental studies on the radio-sensitizing effect of hydrogen peroxide injected in the transplanted mouse tumor. Usefulness of hyaluronic acid supplementation

International Nuclear Information System (INIS)

Akima, Ryo; Tokuhiro, Shiho; Tsuzuki, Kazuhiro; Ue, Hironobu; Ogawa, Yasuhiro

2009-01-01

Therapeutic efficacy of linac is said to be reduced to 1/3 in advanced tumors which mostly consist of hypoxic cells resistant to radiation (Rd). Local administration of hydrogen peroxide (HP) increases oxygen partial pressure at the site because tissue oxygenation occurs by HP degradation by peroxidase and catalase, and thereby radio-sensitization of those Rd-resistant cells can be expected. Authors have shown the anti-tumor efficacy of HP+Rd in vitro, in vivo, and in clinic with their regimen of KORTUC (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas). In the third study above (clinical trial), they supplemented hyaluronate (ha) in the HP solution, and the present experiment was performed to see whether ha had any effect in the efficacy of KORTUC regimen. SCCVII tumor cells were subcutaneously transplanted in the femur of female C3H/HE mouse (7 wks old, about 20 g b. wt.) and 10 days later, 0.25 mL of phosphate buffered saline (PBS, control), 0.5% HP in PBS (HP gr), or 0.83% ha in the HP (ha gr) was injected in the tumor of about 1 cm diameter. After shielding the mouse with 4.5 mm thick Cu plate except for the tumor-bearing leg, the exposed tumor was locally irradiated (IRR) by 6 MeV electron beam with 30 Gy in the linac (EXL-20TP, Mitsubishi Electric) using the bolus for uniform dose distribution. Survivals at 60 days following irradiation were found to be 0, 0, 25.0, 87.5, 100 and 100% in the control, HP gr, ha gr, control/IRR, HP/IRR gr and ha/IRR gr, respectively. Tumor growth at 31 days was found to be suppressed in more significant order of ha/IRR gr, HP/IRR gr, control/IRR than non-IRR groups. The results suggested that ha could be useful in the anti-tumor efficacy of HP possibly due to ha viscous property for uniform distribution of HP in the tumor. (K.T.)

Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors

Energy Technology Data Exchange (ETDEWEB)

Madureira, Tânia Vieira, E-mail: tvmadureira@icbas.up.pt [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal); Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal); Urbatzka, Ralph [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Castro, L. Filipe C. [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Faculty of Sciences (FCUP), U.Porto—University of Porto, Department of Biology, Rua do Campo Alegre, P 4169-007 Porto (Portugal); Rocha, Eduardo [Interdisciplinary Centre of Marine and Environmental Research (CIIMAR/CIMAR), U.Porto—University of Porto, Rua dos Bragas 289, P 4050-123 Porto (Portugal); Institute of Biomedical Sciences Abel Salazar, U.Porto (ICBAS)—University of Porto, Laboratory of Histology and Embryology, Department of Microscopy, Rua Jorge Viterbo Ferreira 228, P 4050-313 Porto (Portugal)

2015-12-15

Highlights: • Evidence of crosstalk between estrogens and peroxisomal pathways in brown trout. • VtgA and ERα mRNA levels increased after 1, 10 and 50 μM of ethinylestradiol (EE2). • ERβ-1, catalase and urate oxidase mRNA levels decreased after estrogenic stimuli. • Estrogenic effects in VtgA, ERα and Uox mRNA levels were reverted by ICI 182,780. • Immunofluorescence/electron microscopy shows smaller peroxisomes after 50 μM of EE2. - Abstract: Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96 h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol—EE2) at 1, 10 and 50 μM; (2) an ER antagonist (ICI 182,780) at 10 and 50 μM; and (3) mixtures of both (Mix I—10 μM EE2 and 50 μM ICI; Mix II—1 μM EE2 and 10 μM ICI and Mix III—1 μM EE2 and 50 μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A—VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase—Uox, 17β-hydroxysteroid dehydrogenase 4—17β-HSD4, peroxin 11α—Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50 μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα m

Estrogenic and anti-estrogenic influences in cultured brown trout hepatocytes: Focus on the expression of some estrogen and peroxisomal related genes and linked phenotypic anchors

International Nuclear Information System (INIS)

Madureira, Tânia Vieira; Malhão, Fernanda; Pinheiro, Ivone; Lopes, Célia; Ferreira, Nádia; Urbatzka, Ralph; Castro, L. Filipe C.; Rocha, Eduardo

2015-01-01

Highlights: • Evidence of crosstalk between estrogens and peroxisomal pathways in brown trout. • VtgA and ERα mRNA levels increased after 1, 10 and 50 μM of ethinylestradiol (EE2). • ERβ-1, catalase and urate oxidase mRNA levels decreased after estrogenic stimuli. • Estrogenic effects in VtgA, ERα and Uox mRNA levels were reverted by ICI 182,780. • Immunofluorescence/electron microscopy shows smaller peroxisomes after 50 μM of EE2. - Abstract: Estrogens, estrogenic mimics and anti-estrogenic compounds are known to target estrogen receptors (ER) that can modulate other nuclear receptor signaling pathways, such as those controlled by the peroxisome proliferator-activated receptor (PPAR), and alter organelle (inc. peroxisome) morphodynamics. By using primary isolated brown trout (Salmo trutta f. fario) hepatocytes after 72 and 96 h of exposure we evaluated some effects in selected molecular targets and in peroxisomal morphological features caused by: (1) an ER agonist (ethinylestradiol—EE2) at 1, 10 and 50 μM; (2) an ER antagonist (ICI 182,780) at 10 and 50 μM; and (3) mixtures of both (Mix I—10 μM EE2 and 50 μM ICI; Mix II—1 μM EE2 and 10 μM ICI and Mix III—1 μM EE2 and 50 μM ICI). The mRNA levels of the estrogenic targets (ERα, ERβ-1 and vitellogenin A—VtgA) and the peroxisome structure/function related genes (catalase, urate oxidase—Uox, 17β-hydroxysteroid dehydrogenase 4—17β-HSD4, peroxin 11α—Pex11α and PPARα) were analyzed by real-time polymerase chain reaction (RT-PCR). Stereology combined with catalase immunofluorescence revealed a significant reduction in peroxisome volume densities at 50 μM of EE2 exposure. Concomitantly, at the same concentration, electron microscopy showed smaller peroxisome profiles, exacerbated proliferation of rough endoplasmic reticulum, and a generalized cytoplasmic vacuolization of hepatocytes. Catalase and Uox mRNA levels decreased in all estrogenic stimuli conditions. VtgA and ERα m

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

Science.gov (United States)

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

2015-12-29

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

Estrogen

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... menopause ('change of life', the end of monthly menstrual periods). Some brands of estrogen are also used ... you.Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

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Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Tsukui, Tohru [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Imazawa, Yukiko; Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi, E-mail: INOUE-GER@h.u-tokyo.ac.jp [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

2012-09-07

Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

Effects of Garlic (Allium sativum L. Hydroalcoholic Extract on Estrogen, Progesterone and Testosterone Levels in Rats Exposed to Cell Phone Radiation

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Behnaz Hajiuon

2014-12-01

Full Text Available Background: The aim of this study was to investigate the probable effects of radiation and consumption of garlic on estrogen, progesterone and testosterone levels. Materials and Methods: In this experimental study, 5 male and 5 female groups of rat were used: control, sham (under exposed, experimental 1 (receiving garlic extract, and experimental 2 and 3 (receiving both extract and microwaves. After a one month, rats were weighed and serum levels of hormones were measured. Results: In male the mean body weight in the sham showed a significant decrease, whereas, an increase was seen in the experimental 3 compared with sham. Also, mean plasma testosterone levels in experimental 2 and 3 were reduced. Estrogen showed this decrease in all groups. Also in all groups progesterone showed increase. In female the mean body weights in different groups showed no significant changes, whereas a significant increase was seen in serum level of progesterone in experimental 2 and 3. Conclusion: Although, microwaves can cause weight lost, presence of allicin and vitamins A and B in garlic can compensate some of this weight lost. Microwaves and garlic extract have fewer effects on female reproductive system, reflected only in the serum progesterone concentration. Also they reflected in the number of Leydig cells and serum testosterone and estrogen concentration. The differences observed in the responses of male and female to cell phone radiation might be attributed to the position of gonads in the body and sensitivity of testis to heat.

Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo.

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Lijiang Zhang

Full Text Available Pure anti-estrogen fulvestrant has been shown to be a promising ER antagonist for locally advanced and metastatic breast cancer. Unfortunately, a significant proportion of patients developed resistance to this type of endocrine therapy but the molecular mechanisms governing cellular responsiveness to this agent remain poorly understood. Here, we've reported that knockdown of estrogen receptor coactivator MED1 sensitized fulvestrant resistance breast cancer cells to fulvestrant treatment. We found that MED1 knockdown further promoted cell cycle arrest induced by fulvestrant. Using an orthotopic xenograft mouse model, we found that knockdown of MED1 significantly reduced tumor growth in mice. Importantly, knockdown of MED1 further potentiated tumor growth inhibition by fulvestrant. Mechanistic studies indicated that combination of fulvestrant treatment and MED1 knockdown is able to cooperatively inhibit the expression of ER target genes. Chromatin immunoprecipitation experiments further supported a role for MED1 in regulating the recruitment of RNA polymerase II and transcriptional corepressor HDAC1 on endogenous ER target gene promoter in the presence of fulvestrant. These results demonstrate a role for MED1 in mediating resistance to the pure anti-estrogen fulvestrant both in vitro and in vivo.

Levels of estrogen, carcinoembryonic antigen and cancer antigen of breast in breast cancer patients

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Abdelhadi, H. A.

2005-09-01

This study was conducted during the period from february 2004 to July 2004; with the objective of measuring the levels of estrogen (E2), carcinoembryonic antigen (CEA) and cancer antigen of breast (CA-15.3) so as to facilitate the early diagnosis of breast cancer and determine the involvement of these parameters as risk factors for breast cancer. Ninety blood samples were collected from Sudanese females, divided into two groups; control group and patient groups. The patients group was sixty Sudanese females visiting the Radio Isotope Center, Khartoum (RICK) and they were confirmed as breast cancer patient by histopathology. The levels of the above mentioned parameters were determined by using radioimmunoassay technique. The results showed that, no significant (p=0.05) difference between the levels of the estrogen in patients compared to the control, on the other hand there was non significant (p>0.05) elevation in CEA levels in the patients with breast cancer compared to the control. The level of CA15.3 was significantly (p<0.0001) higher in the breast cancer patients compared to the control.(Author)

Male/female differences in neuroprotection and neuromodulation of brain dopamine.

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Mélanie eBourque

2011-09-01

Full Text Available The existence of a sex difference in Parkinson’s disease is observed in several variables, including susceptibility of the disease, age at onset and symptoms. These differences between men and women represent a significant characteristic of Parkinson’s disease which suggests that estrogens may exert beneficial effects against the development and the progression of the disease. This paper reviews the neuroprotective and neuromodulator effect of 17β-estradiol and progesterone as compared to androgens in the nigrostriatal dopaminergic system of both female and male rodents. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mice model of Parkinson’s disease and methamphetamine toxicity faithfully reproduce the sex differences of Parkinson’s disease in that endogenous estrogen levels appear to influence the vulnerability to toxins targeting the nigrostriatal dopaminergic system. Exogenous 17β-estradiol and/or progesterone treatments show neuroprotective properties against nigrostriatal dopaminergic toxins while androgens fail to induce beneficial effect. Sex steroids treatments show males and females difference in their neuroprotective action against methamphetamine toxicity. Nigrostriatal dopaminergic structure and function, as well as the distribution of estrogen receptors, show sex difference and may influence the susceptibility to the toxins and the response to sex steroids. Genomic and non-genomic actions of 17β-estradiol converge to promote survival factors and the presence of both estrogen receptors α and β are critical to 17β-estradiol neuroprotective action against MPTP toxicity.

Transgenic mouse models of hormonal mammary carcinogenesis: advantages and limitations.

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Kirma, Nameer B; Tekmal, Rajeshwar R

2012-09-01

Mouse models of breast cancer, especially transgenic and knockout mice, have been established as valuable tools in shedding light on factors involved in preneoplastic changes, tumor development and malignant progression. The majority of mouse transgenic models develop estrogen receptor (ER) negative tumors. This is seen as a drawback because the majority of human breast cancers present an ER positive phenotype. On the other hand, several transgenic mouse models have been developed that produce ER positive mammary tumors. These include mice over-expressing aromatase, ERα, PELP-1 and AIB-1. In this review, we will discuss the value of these models as physiologically relevant in vivo systems to understand breast cancer as well as some of the pitfalls involving these models. In all, we argue that the use of transgenic models has improved our understanding of the molecular aspects and biology of breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill].

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López Moratalla, Natalia; Errasti Alcalá, Tania; Santiago, Esteban

2011-01-01

In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures.

"Doctor, are you trying to kill me?": ambivalence about the patient package insert for estrogen.

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Watkins, Elizabeth Siegel

2002-01-01

In 1976, the U.S. Food and Drug Administration proposed new requirements for patient labeling for estrogens prescribed for menopausal and postmenopausal women. This paper explores the variety of responses to this proposal from women and their husbands, feminist and consumer activists, physicians, pharmacists, and pharmaceutical manufacturers, as represented in letters written to the FDA. The drug industry and the medical profession opposed patient labeling on the grounds of cost and a resentment of governmental intrusion. Feminists and consumer advocates were in favor of the idea, but the response from current estrogen users was mixed: most women wished to be better informed, but many expressed concern that estrogen would be removed from the market. This ambivalence suggests unresolved tensions regarding conceptions of female aging, the medical management of menopause and aging, informed consent in medicine, and governmental regulation of medical practice. The debate thus represents an important moment in the history of women's health care.

Localization of Estrogen Receptors α and β in the Articular Surface of the Rat Femur

International Nuclear Information System (INIS)

Oshima, Yasushi; Matsuda, Ken-ichi; Yoshida, Atsuhiko; Watanabe, Nobuyoshi; Kawata, Mitsuhiro; Kubo, Toshikazu

2007-01-01

It has been suggested that the degradation of the articular cartilage and osteoarthritis (OA) are associated with gender and the estrogen hormone. Although many investigators have reported the presence of the estrogen receptors (ERs) α and β in the articular cartilage, the localization of these receptors and the difference in their in vivo expression have not yet been clearly demonstrated. We performed immunofluorescence staining of ERα and ERβ to elucidate the localization of the ERs and to note the effects of gender and the aging process on these receptors. The results revealed that ERα and ERβ were expressed in the articular cartilage and subchondral bone layers of adult rats of both sexes. We also observed the high expression of these receptors in immature rats. In contrast, their expression levels decreased in an ovariectomised model, as a simulation of postmenopause, and in aged female rats. Therefore, this study suggests the direct effects of estrogen and ER expression on articular surface metabolism

Differential effects of migration and deportation on HIV infection among male and female injection drug users in Tijuana, Mexico.

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Strathdee, Steffanie A; Lozada, Remedios; Ojeda, Victoria D; Pollini, Robin A; Brouwer, Kimberly C; Vera, Alicia; Cornelius, Wayne; Nguyen, Lucie; Magis-Rodriguez, Carlos; Patterson, Thomas L

2008-07-30

HIV prevalence is rising, especially among high risk females in Tijuana, Baja California, a Mexico-US border city situated on major migration and drug trafficking routes. We compared factors associated with HIV infection among male and female injection drug users (IDUs) in Tijuana in an effort to inform HIV prevention and treatment programs. IDUs aged > or = 18 years were recruited using respondent-driven sampling and underwent testing for HIV, syphilis and structured interviews. Logistic regression identified correlates of HIV infection, stratified by gender. Among 1056 IDUs, most were Mexican-born but 67% were born outside Tijuana. Reasons for moving to Tijuana included deportation from the US (56% for males, 29% for females), and looking for work/better life (34% for females, 15% for males). HIV prevalence was higher in females versus males (10.2% vs. 3.5%, p = 0.001). Among females (N = 158), factors independently associated with higher HIV prevalence included younger age, lifetime syphilis infection and living in Tijuana for longer durations. Among males (N = 898), factors independently associated with higher HIV prevalence were syphilis titers consistent with active infection, being arrested for having 'track-marks', having larger numbers of recent injection partners and living in Tijuana for shorter durations. An interaction between gender and number of years lived in Tijuana regressed on HIV infection was significant (p = 0.03). Upon further analysis, deportation from the U.S. explained the association between shorter duration lived in Tijuana and HIV infection among males; odds of HIV infection were four-fold higher among male injectors deported from the US, compared to other males, adjusting for all other significant correlates (p = 0.002). Geographic mobility has a profound influence on Tijuana's evolving HIV epidemic, and its impact is significantly modified by gender. Future studies are needed to elucidate the context of mobility and HIV acquisition in

Estrogen receptor β and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats.

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Kudwa, Andrea E; McGivern, Robert F; Handa, Robert J

2014-04-22

The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressors and is controlled by neurons residing in the paraventricular nucleus of the hypothalamus (PVN). Although gonadal steroid hormones can influence HPA reactivity to stressors, the exact mechanism of action is not fully understood. It is known, however, that estrogen receptor β (ERβ) inhibits HPA reactivity and decreases anxiety-like behavior in rodents. Since ERβ is co-expressed with oxytocin (OT) in neurons of the PVN, an ERβ-selective agonist was utilized to test the whether ERβ decreases stress-induced HPA reactivity and anxiety-like behaviors via an OTergic pathway. Adult gonadectomized male and female rats were administered diarylpropionitrile, or vehicle, peripherally for 5days. When tested for anxiety-like behavior on the elevated plus maze (EPM), diarylpropionitrile-treated males and females significantly increased time on the open arm of the EPM compared to vehicle controls indicating that ERβ reduces anxiety-like behaviors. One week after behavioral evaluation, rats were subjected to a 20minute restraint stress. Treatment with diarylpropionitrile reduced CORT and ACTH responses in both males and females. Subsequently, another group of animals was implanted with cannulae directed at the lateral ventricle. One week later, rats underwent the same protocol as above but with the additional treatment of intracerebroventricular infusion with an OT antagonist (des Gly-NH2 d(CH2)5 [Tyr(Me)(2), Thr(4)] OVT) or VEH, 20min prior to behavioral evaluation. OT antagonist treatment blocked the effects of diarylpropionitrile on the display of anxiety-like behaviors and plasma CORT levels. These data indicate that ERβ and OT interact to modulate the HPA reactivity and the display of anxiety-like behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

Tumorigenic Effects of Tamoxifen on the Female Genital Tract

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Kaei Nasu M.D., Ph.D.

2008-01-01

Full Text Available Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It acts as both an estrogen antagonist in breast tissue and an estrogen agonist in the female lower genital tract. Tamoxifen causes severe gynecologic side effects, such as endometrial cancer. This review focuses on the effects of prolonged tamoxifen treatment on the human female genital tract and considers its tumorigenicity in the gynecologic organs through clinical data analysis. Tamoxifen is associated with an increased incidence of benign endometrial lesions such as polyps and hyperplasia and a two- to four-fold increased risk of endometrial cancer in postmenopausal patients. Moreover, the incidence of functional ovarian cysts is significantly high in premenopausal tamoxifen users. To prevent tamoxifen from having severe side effects in gynecologic organs, frequent gynecological examination should be performed for both premenopausal and postmenopausal patients with breast cancer who are treated with this drug.

Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones.

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Anker, Justin J; Carroll, Marilyn E

2011-01-01

Human and animal research indicates the presence of sex differences in drug abuse. These data suggest that females, compared to males, are more vulnerable to key phases of the addiction process that mark transitions in drug use such as initiation, drug bingeing, and relapse. Recent data indicate that the female gonadal hormone estrogen may facilitate drug abuse in women. For example, phases of the menstrual cycle when estrogen levels are high are associated with enhanced positive subjective measures following cocaine and amphetamine administration in women. Furthermore, in animal research, the administration of estrogen increases drug taking and facilitates the acquisition, escalation, and reinstatement of cocaine-seeking behavior. Neurobiological data suggest that estrogen may facilitate drug taking by interacting with reward- and stress-related systems. This chapter discusses sex differences in and hormonal effects on drug-seeking behaviors in animal models of drug abuse. The neurobiological basis of these differences and effects are also discussed.

Interactions between the cytomegalovirus promoter and the estrogen response element: implications for design of estrogen-responsive reporter plasmids.

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Derecka, K; Wang, C K; Flint, A P F

2006-07-01

We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)ERE) was not estrogen responsive. Inhibition of ERE function was not due to an effect in trans or due to lack of estrogen receptor. It was not due to an interaction between the cmv promoter and the SeAP gene. cmv promoter function was dependent on NF-kappaB, and mutagenesis in the NF-kappaB sites reduced basal reporter expression without imparting responsiveness to estrogen. A mutation in the TATA box also failed to impart estrogen responsiveness. Modeling of DNA accessibility indicated the ERE was inserted at a site accessible to transcription factors. We conclude that the cmv promoter inhibits ERE function in cis when the two sequences are located in the same construct, and that this effect does not involve an interaction between cmv and reporter gene, NF-kappaB sites or the TATA box, or DNA inaccessibility.

The Estrogen Receptor-β Expression in De Quervain’s Disease

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Po-Chuan Shen

2015-11-01

Full Text Available Stenosing tenosynovitis of the first dorsal compartment of the wrist (a.k.a. de Quervain’s disease is common but how estrogen is involved is still unknown. We previously reported that inflammation was involved in the pathogenesis of this ailment. In the present study, we extended our investigation of estrogen receptor (ER-β expression to determine whether estrogen is involved in the pathogenesis of de Quervain’s. Intraoperative retinaculum samples were collected from 16 patients with the ailment. Specimens were histologically graded by collagen structure and immunohistochemically evaluated by quantifying the expression of ER-β, interleukin (IL-1β and IL-6 (inflammatory cytokines, cyclooxygenase (COX-2 (an inflammatory enzyme, and vascular endothelial growth factor (VEGF, and Von Willebrand’s factor (vWF. De Quervain’s occurs primarily in women. The female:male ratio in our study was 7:1. We found that ER-β expression in the retinaculum was positively correlated with disease grade and patient age. Additionally, disease severity was associated with inflammatory factors—IL-1β and IL-6, COX-2, and VEGF and vWF in tenosynovial tissue. The greater the levels of ER-β expression, tissue inflammation, and angiogenesis are, the more severe de Quervain’s disease is. ER-β might be a useful target for novel de Quervain’s disease therapy.

Estrogen inhibits RANKL-stimulated osteoclastic differentiation of human monocytes through estrogen and RANKL-regulated interaction of estrogen receptor-α with BCAR1 and Traf6

International Nuclear Information System (INIS)

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

2009-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Robinson, Lisa J., E-mail: robinsonlj@msx.upmc.edu [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Yaroslavskiy, Beatrice B.; Griswold, Reed D.; Zadorozny, Eva V.; Guo, Lida; Tourkova, Irina L. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Blair, Harry C. [Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Veteran' s Affairs Medical Center, Pittsburgh, PA 15243 (United States)

2009-04-15

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

Interactions Between the Cytomegalovirus Promoter and the Estrogen Response Element: Implications for Design of Estrogen-Responsive Reporter Plasmids

OpenAIRE

Derecka, K.; Wang, C.K.; Flint, A.P.F.

2006-01-01

We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)...

New once-a-month injectable contraceptives, with particular reference to Cyclofem/Cyclo-Provera.

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Hall, P E

1998-08-01

Once-a-month injectable contraceptives containing a progestogen and an estrogen have been developed that disrupt vaginal bleeding patterns less than the widely used progestogen-only preparations. Pharmacokinetic studies were undertaken of dosages and ratios of the progestogens and the respective estrogens. In Phase III clinical trials, annual pregnancy rates were below 0.4% for Mesigyna (norethisterone enanthate/estradiol valerate, Schering AG, Berlin, Germany) and below 0.2% for Cyclofem (MPA/E2C) (medroxyprogesterone acetate/estradiol cypionate, Aplicaciones Farmaceuticas, SA, Mexico and PT Tunggal, Indonesia). More than two-thirds of women had predictable, regular cycles, and discontinuation due to bleeding-related problems occurred less than half as often as with progestogen-only injectables. With MPA/E2C, return to fertility is similar to that observed with other hormonal or intrauterine methods, and both products have little effect on lipids or hemostasis. Introductory trials of MPA/E2C in 12000 women with 100000 woman-months of experience confirmed the high efficacy of the product in routine use. The use of MPA/E2C in a non-reusable injection device, Uniject (Becton Dickinson, Franklin Lakes, NJ) is discussed. Once-a-month hormonal contraceptives have been shown to provide a safe contraceptive option for all women and an alternative for women who wish to use injectable formulations that cause less disruption in vaginal bleeding and minimal side effects.

Bisphenol A induces oxidative stress and DNA damage in hepatic tissue of female rat offspring

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Jehane I. Eid

2015-08-01

Full Text Available Bisphenol A (BPA is an endocrine disrupting compound widely spread in our living environment. It is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to the limited information concerning the effect of BPA on the liver, the present study was designed to assess hepatic tissue injury induced by early life exposure to BPA in female rat offspring. Rat dams (n = 9 were gavaged with 0.5 and 50 mg of BPA/kg b.w./day throughout lactation until weaning. The sham group received olive oil for the same duration while the control group did not receive any injection. The liver tissue was collected from female pups at different pubertal periods (PND50, 90 and 110 to evaluate oxidative stress biomarkers, extent of DNA damage and histopathological changes. Our results indicated that early life exposure to BPA significantly increased oxidative/nitrosative stress, decreased antioxidant enzyme activities, induced DNA damage and chronic severe inflammation in the hepatic tissue in a time dependent manner. These data suggested that BPA causes long-term adverse effects on the liver, which leads to deleterious effects in the liver of female rat offspring.

A recombinant estrogen receptor fragment-based homogeneous fluorescent assay for rapid detection of estrogens.