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Sample records for stimulation shifts estradiol

  1. Genital Sensory Stimulation Shifts Estradiol Intraoviductal Signaling from Nongenomic to Genomic Pathways, Independently from Prolactin Surges

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    C PEÑARROJA-MATUTAN0

    2007-01-01

    Full Text Available Estradiol (E2 accelerates oviductal egg transport through nongenomic pathways involving oviductal protein phosphorylation in non-mated rats, and through genomic pathways in mated rats. Here we investigated the ability of cervico-vaginal stimulation (CVS to switch the mode of action of E2 in the absence of other male-associated components. Pro-estrous rats were subjected to CVS with a glass rod and 12 hours later were injected subcutaneously with E2 and intrabursally with the RNA synthesis inhibitor Actinomycin D or the protein phosphorylation inhibitor H-89. The number of eggs in the oviduct, assessed 24 h later, showed that Actinomycin D, but not H-89 blocked the E2-induced egg transport acceleration. This clearly indicates that CVS alone, without other mating-associated signals, is able to shift E2 signaling from nongenomic to genomic pathways. Since mating and CVS activate a neuroendocrine reflex that causes iterative prolactin (PRL surges, the involvement of PRL pathway in this phenomenon was evaluated. Prolactin receptor mRNA and protein expression in the rat oviduct was demonstrated by RT-PCR and Western blot, but their levels were not different on day 2 of the cycle (C2 or pregnancy (P2. Activated ST AT 5a/b (phosphorylated was detected by Western blot on P2 in the ovary, but not in the oviduct, showing that mating does not stimulate this PRL signalling pathway in the oviduct. Other rats subjected to CVS in the evening of pro-estrus were treated with bromoergocriptine to suppress PRL surges. In these rats, H-89 did not block the E2-induced acceleration of egg transport suggesting that PRL surges are not essential to shift E2 signaling pathways in the oviduct. We conclude that CVS is one of the components of mating that shifts E2 signaling in the oviduct from nongenomic to genomic pathways, and this effect is independent of PRL surges elicited by mating

  2. Estradiol stimulation of inositolphospholipid metabolism in human endometrial fibroblasts

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    Iida, K.; Imai, A.; Tamaya, T.

    1989-01-01

    Stimulated inositolphospholipid turnover has been proposed to constitute a signal-transducing mechanism in many cell types. To determine the inositolphospholipid turnover during stimulation by 17 beta-estradiol, the turnover kinetics of phospholipids was investigated in human endometrial fibroblasts. In cells incubated with [ 32 P] phosphate for 1 h, estradiol rapidly and persisitently (for at least 30 min) enhanced the rate of 32 P-labeling of phosphatidic acid (PA). On the other hand, after a lag time of 5 min, 32 P-labeling of phosphatidylinositol (PI) was also increased also. These sequential 32 P-labeling of PA and PI demonstrated that inositolphospholipid turnover was stimulated in fibroblasts exposed to estradiol. The rapid estrogen-stimulated inositolphospholipid turnover may not be through the mechanism associated with classical action of estrogen

  3. Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

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    Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

    2003-11-05

    Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

  4. Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.

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    Agua Sobrino

    2009-12-01

    Full Text Available Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxygenase (COX1, dimethylarginine dimethylaminohydrolase (DDAH2, phospholipase A2 group IV (PLA2G4 B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes.

  5. Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin surges in ovariectomized rats.

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    Stathopoulos, Andrea M; Helena, Cleyde V; Cristancho-Gordo, Ruth; Gonzalez-Iglesias, Arturo E; Bertram, Richard

    2016-08-01

    Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy maintenance, lactation, and aspects of maternal behavior. In rodents, there is a surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of prolactin surges during early pregnancy, with a diurnal and nocturnal surge every day. Both of these patterns can be replicated in ovariectomized rats. A prior study demonstrated that central antagonism of κ-opioid receptors, the target of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats. We build on this to determine whether dynorphin, perhaps from the arcuate population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons), also contributes to the estradiol- or cervical stimulation-induced surges in ovariectomized rats. Ovariectomized rats were treated with either estradiol or cervical stimulation to induce prolactin surge(s). Blood samples were taken around the expected surge time to determine the effect of either acute κ-opioid receptor antagonism or previous chemical ablation of the KNDy population on prolactin levels. Dynorphin antagonism does significantly disrupt the nocturnal prolactin surge, but it does not contribute to the estradiol-induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while a somewhat larger ablation significantly reduced the size of the estradiol-induced surge. We conclude that dynorphin is likely a controlling factor for the nocturnal surge induced by cervical stimulation, and that other KNDy neuron products must play a role in the estradiol-induced surge.

  6. Impact of growth hormone (GH) and follicle stimulating hormone (FSH) on in vitro canine preantral follicle development and estradiol production.

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    Serafim, M K B; Duarte, A B G; Silva, G M; Souza, C E A; Magalhães-Padilha, D M; Moura, A A A; Silva, L D M; Campello, C C; Figueiredo, J R

    2015-04-01

    Evaluate the effect of different concentrations of growth hormone (GH) on the in vitro development of domestic dog (Canis lupus familiaris) preantral follicles in the presence or absence of follicle stimulating hormone (FSH). Secondary preantral follicles, isolated by microdissection, were cultured in a medium composed of αMEM with bovine serum albumin (BSA), glutamine, hypoxanthine, insulin, transferrin, selenium and ascorbic acid (αMEM(+)-control) added at different concentrations of GH (GH10 ng/ml or GH50 ng/ml) and FSH (GH10+FSH, GH50+FSH). Follicle development was evaluated based on the percentage of intact follicles, antrum formation, follicular diameter, follicular viability using fluorescent markers and estradiol production. GH50 was the only treatment that maintained the same percentage of normal morphologically follicles from day 0 to day 18 of culture (PGH50 supplemented with FSH (GH50+FSH) resulted in the highest average follicular diameter (PGH50+FSH treatment groups actively and increasingly secreted estradiol from day 6 to 18 of culture (PGH benefits the maintenance of follicular morphology in a dose-dependent manner and, in association with FSH, stimulates in vitro follicular growth and estradiol production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Estradiol and corticosterone stimulate the proliferation of a GH cell line, MtT/S: Proliferation of growth hormone cells.

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    Nogami, Haruo; Hiraoka, Yoshiki; Aiso, Sadakazu

    2016-08-01

    Estrogens are known as a potent growth-stimulator of the anterior pituitary cells such as prolactin cells and somatomammotroph cell lines, while glucocorticoids often inhibit cellular proliferation in the pituitary gland as well as in the extra-pituitary tissues. In this study, the involvement of these steroid hormones in the regulation of proliferation was examined in the MtT/S cells, secreting growth hormone (GH). Effects of estrogens and glucocorticoids were examined in MtT/S cells grown in the medium containing dextran-coated charcoal treated serum. The relative cell density after culture was estimated by the Cell Titer-Glo Luminescent Cell Viability Assay System, and the proliferation rate was determined by the BrdU incorporation method. The mRNA levels were determined by real-time PCR. Estradiol and the specific agonist for both estrogen receptor (ER) α and ERβ stimulated MtT/S growth at a dose dependent manner. The membrane impermeable estrogen, 17β-estradiol-bovine serum albumin conjugate also stimulated the MtT/S proliferation. The effects of all estrogens were inhibited by an estrogen receptor antagonist, ICI182780. Corticosterone stimulated the proliferation of MtT/S cells at doses lower than 10nM without stimulating GH gene transcription, whereas it did not change the proliferation rate at 1μM. The effects of corticosterone were inhibited by glucocorticoid receptor inhibitor, RU486, but not by the mineralocorticoid receptor antagonist, spironolactone. Both estrogens and glucocorticoids were found to stimulate the proliferation of MtT/S, increasing the mRNA expression of cyclins D1, D3, and E. The results suggest that estrogens and glucocorticoids may be involved in the mechanisms responsible for the proliferation of GH cells in the course of pituitary development, to maintain the population of GH cells in the adult pituitary gland, and also in the promotion of GH cell tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome.

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    Olivetti, Pedro R; Maheshwari, Atul; Noebels, Jeffrey L

    2014-01-22

    Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate treatment. In patients, mutation of ARX, a transcription factor selectively expressed in neuronal precursors and adult inhibitory interneurons, impairs cell migration and causes a major inherited subtype of the disease X-linked infantile spasms syndrome. Using an animal model, the Arx((GCG)10+7) mouse, we determined that brief estradiol (E2) administration during early postnatal development prevented spasms in infancy and seizures in adult mutants. E2 was ineffective when delivered after puberty or 30 days after birth. Early E2 treatment altered mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and restored depleted interneuron populations without increasing GABAergic synaptic density. Postnatal E2 treatment may induce lasting transcriptional changes that lead to enduring disease modification and could potentially serve as a therapy for inherited interneuronopathies.

  9. Trajectories of estradiol and follicle-stimulating hormone over the menopause transition and early markers of atherosclerosis after menopause.

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    El Khoudary, Samar R; Santoro, Nanette; Chen, Hsiang-Yu; Tepper, Ping G; Brooks, Maria M; Thurston, Rebecca C; Janssen, Imke; Harlow, Sioban D; Barinas-Mitchell, Emma; Selzer, Faith; Derby, Carol A; Jackson, Elizabeth A; McConnell, Daniel; Matthews, Karen A

    2016-05-01

    The purpose of this study was to assess associations between distinct patterns of circulating estradiol (E2) and follicle-stimulating hormone (FSH) over the menopause transition (MT) and subclinical measures of atherosclerosis after menopause. Four temporal patterns of E2 decline (Low: low before and after final menstrual period (FMP); Medium: medium before and high after FMP; High-early decline: high prior to FMP and early decline thereafter; High-late decline: high prior to FMP and late decline thereafter) and three of FSH rise (Low, Medium, High) over 9.6 years across FMP were identified and linked to carotid intima-media-thickness (IMT), adventitial diameter (AD), and presence of carotid plaque (cPlaque) measured after menopause at the 12th annual visit (visit 12). Participants were 856 women (age at visit 12 = 59.5 ± 2.7 years) from the Study of Women's Health Across the Nation (SWAN), who never reported a stroke or a heart attack. In models adjusted for visit 12 or baseline cardiovascular disease (CVD) risk factors, odds of having any cPlaque were ∼43% lower among women with the High-early decline E2 trajectory compared to women with the Low E2 trajectory. In contrast, women with the Medium E2 trajectory had significantly higher IMT than those with the Low E2 trajectory adjusting for visit 12 CVD risk factors. Interestingly, adjusting for baseline CVD risk factors attenuated this association. The Low FSH group had lower IMT than the Medium and High FSH groups (p ≤ 0.05) in all models. During MT, women are subjected to hormonal alterations that could potentially increase their risk of developing CVD after menopause. © The European Society of Cardiology 2015.

  10. Estradiol stimulates glycogen synthesis whereas progesterone promotes glycogen catabolism in the uterus of the American mink (Neovison vison).

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    Bowman, Kole; Rose, Jack

    2017-01-01

    Glycogen synthesis by mink uterine glandular and luminal epithelia (GE and LE) is stimulated by estradiol (E 2 ) during estrus. Subsequently, the glycogen deposits are mobilized to near completion to meet the energy requirements of pre-embryonic development and implantation by as yet undetermined mechanisms. We hypothesized that progesterone (P 4 ) was responsible for catabolism of uterine glycogen reserves as one of its actions to ensure reproductive success. Mink were treated with E 2 , P 4 or vehicle (controls) for 3 days and uteri collected 24 h (E 2 , P 4 and vehicle) and 96 h (E 2 ) later. To evaluate E 2 priming, mink were treated with E 2 for 3 days, then P 4 for an additional 3 days (E 2 →P 4 ) and uteri collected 24 h later. Percent glycogen content of uterine epithelia was greater at E 2 + 96 h (GE = 5.71 ± 0.55; LE = 11.54 ± 2.32) than E 2 +24 h (GE = 3.63 ± 0.71; LE = 2.82 ± 1.03), and both were higher than controls (GE = 0.27 ± 0.15; LE = 0.54 ± 0.30; P glycogen content (GE = 0.61 ± 0.16; LE = 0.51 ± 0.13), to levels not different from controls, while concomitantly increasing catabolic enzyme (glycogen phosphorylase m and glucose-6-phosphatase) gene expression and amount of phospho-glycogen synthase protein (inactive) in uterine homogenates. Interestingly, E 2 →P 4 increased glycogen synthase 1 messenger RNA (mRNA) and hexokinase 1mRNA and protein. Our findings suggest to us that while E 2 promotes glycogen accumulation by the mink uterus during estrus and pregnancy, it is P 4 that induces uterine glycogen catabolism, releasing the glucose that is essential to support pre-embryonic survival and implantation. © 2016 Japanese Society of Animal Science.

  11. Shifting from constant-voltage to constant-current in Parkinson's disease patients with chronic stimulation.

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    Amami, P; Mascia, M M; Franzini, A; Saba, F; Albanese, A

    2017-08-01

    The study aimed to evaluate safety and efficacy of shifting stimulation settings from constant-voltage (CV) to constant-current (CC) programming in patients with Parkinson's disease (PD) and chronic subthalamic nucleus deep brain stimulation (STN DBS). Twenty PD patients with chronic STN DBS set in CV programming were shifted to CC and followed for 3 months; the other stimulation settings and the medication regimen remained unchanged. Side effects, motor, non-motor, executive functions, and impedance were assessed at baseline and during follow-up. No adverse events were observed at time of shifting or during CC stimulation. Motor and non-motor measures remained unchanged at follow-up despite impedance decreased. Compared to baseline, inhibition processes improved at follow-up. The shifting strategy was well tolerated and the clinical outcome was maintained with no need to adjust stimulation settings or medications notwithstanding a decrease of impedance. Improvement of inhibition processes is a finding which needed further investigation.

  12. Comparative Analysis of Proteins with Stimulating Activity on Ovarian Estradiol Biosynthesis from Four Different Dioscorea Species in vitro Using Both Phenotypic and Target-based Approaches: Implication for Treating Menopause.

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    Lu, J; Wong, R N S; Zhang, L; Wong, R Y L; Ng, T B; Lee, K F; Zhang, Y B; Lao, L X; Liu, J Y; Sze, S C W

    2016-09-01

    Rhizomes of Dioscorea species are traditionally used for relieving menopausal syndromes in Chinese medicine. The estrogen-stimulating bioactive principles have been demonstrated in our previous study. In this study, the estrogen-stimulating effects of proteins isolated from four Dioscorea species [D. alata L. (DA), D. zingiberensis C.H. Wright (DH), D. collettii var. hypoglauca (Palib.) S.J. Pei & C.T. Ting (DH), and D. oppositifolia L. (DO)] have been investigated and compared. Microscopic authentication of four Dioscorea species was performed by using paraffin and powder sections of the rhizomes. The potential bioactive proteins of four Dioscorea species have been rapidly isolated by using a DOI-antibody affinity column chromatography on immobilized antibodies against on estradiol-stimulating protein from DO (DOI), and their bioactivity has been rapidly confirmed and compared by phenotypic (i.e., estradiol-stimulating effect) and target-based (i.e., STAR, aromatase, estrogen receptors) screening approaches. The estrogen-stimulating activity of bioactive proteins from DO is the highest. In addition, bioactive proteins from DO upregulated the estradiol-metabolizing enzymes (aromatase and steroidogenic acute regulatory protein). Meanwhile, bioactive proteins from DA, DH and DO upregulated estrogen receptor β (ERβ). All bioactive proteins did not change the expression of estrogen receptor β (ERα). The estrogen-stimulating bioactive proteins isolated from DO increased biosynthesis of estradiol and upregulated the protein expression of aromatase, steroidogenic acute regulatory protein, and ERβ. The results scientifically support the traditional use of DO in Chinese medicine for relieving menopausal syndrome. Besides, proteins from DA and DZ could also upregulate the translational levels of ERβ, and potentially reducing the risk of ovarian cancer, which also support the clinical use of them for treating female aging disorder. Graphical Abstract Comparative

  13. Effectiveness of a recombinant human follicle stimulating hormone on the ovarian follicles, peripheral progesterone, estradiol-17β, and pregnancy rate of dairy cows

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    Mohamed Ali

    2016-07-01

    Full Text Available Aims: This study aimed at elucidating the effects of recombinant human follicle stimulating hormone (r-hFSH on the ovarian follicular dynamics, progesterone, estradiol-17β profiles, and pregnancy of dairy cows. Materials and Methods: Three groups (G, n=5 cows of multiparous dairy cows were used. G1 (C control cows were given controlled internal drug release (CIDR and prostaglandin F2α; G2 (L cows were given low dose (525 IU and G3 (H cows were given high dose (1800 IU of r-hFSH on twice daily basis at the last 3 days before CIDR removal. All cows were ultrasonically scanned for follicular growth and dynamics, and blood samples were collected every other day for two consecutive estrus cycles for the determination of estradiol-17β and progesterone. Results: Estrus was observed in all C and L but not in H cows. Dominant follicle was bigger in L compared to C and H cows. Dominant follicle in C (16.00±2.5 mm and L cows (17.40±2.3 mm disappeared at 72 h after CIDR removal. However, in H cows, no ovulation has occurred during 7 days post-CIDR removal. Progesterone was not different (p>0.10 among groups, whereas estradiol-17β revealed significant (p<0.01 reduction in H (15.96±2.5 pg/ml cows compared to C (112.26±26.1 pg/ml and L (97.49±15.9 pg/ml cows. Pregnancy rate was higher in L cows (60% compared with C cows (20%. However, H cows were not artificially inseminated due to non-ovulation. Only a cow of C group has calved one calf, however, 2 of the L cows gave birth of twins and a cow gave single calf. Conclusion: Administration of a low dose (525 IU of r-hFSH resulted in an optimal size of dominant follicle, normal values of progesterone and estradiol-17β, and 40% twinning rate, howeverusing 1800 IU of r-hFSH, have adverse effects on ovarian follicular dynamics and hormonal profiles with non-pregnancy of dairy cows raised under hot climate.

  14. Transcranial direct current stimulation of the left dorsolateral prefrontal cortex shifts preference of moral judgments.

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    Maria Kuehne

    Full Text Available Attitude to morality, reflecting cultural norms and values, is considered unique to human social behavior. Resulting moral behavior in a social environment is controlled by a widespread neural network including the dorsolateral prefrontal cortex (DLPFC, which plays an important role in decision making. In the present study we investigate the influence of neurophysiological modulation of DLPFC reactivity by means of transcranial direct current stimulation (tDCS on moral reasoning. For that purpose we administered anodal, cathodal, and sham stimulation of the left DLPFC while subjects judged the appropriateness of hard moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal stimulation induced a shift in judgment of personal moral dilemmas towards more non-utilitarian actions. Our results demonstrate that alterations of left DLPFC activity can change moral judgments and, in consequence, provide a causal link between left DLPFC activity and moral reasoning. Most important, the observed shift towards non-utilitarian actions suggests that moral decision making is not a permanent individual trait but can be manipulated; consequently individuals with boundless, uncontrollable, and maladaptive moral behavior, such as found in psychopathy, might benefit from neuromodulation-based approaches.

  15. Structural Organization of the Corpus Callosum Predicts Attentional Shifts after Continuous Theta Burst Stimulation

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    Humphreys, Glyn W.; Sotiropoulos, Stamatios N.; Kennard, Christopher; Cazzoli, Dario

    2015-01-01

    Repetitive transcranial magnetic stimulation (rTMS) applied over the right posterior parietal cortex (PPC) in healthy participants has been shown to trigger a significant rightward shift in the spatial allocation of visual attention, temporarily mimicking spatial deficits observed in neglect. In contrast, rTMS applied over the left PPC triggers a weaker or null attentional shift. However, large interindividual differences in responses to rTMS have been reported. Studies measuring changes in brain activation suggest that the effects of rTMS may depend on both interhemispheric and intrahemispheric interactions between cortical loci controlling visual attention. Here, we investigated whether variability in the structural organization of human white matter pathways subserving visual attention, as assessed by diffusion magnetic resonance imaging and tractography, could explain interindividual differences in the effects of rTMS. Most participants showed a rightward shift in the allocation of spatial attention after rTMS over the right intraparietal sulcus (IPS), but the size of this effect varied largely across participants. Conversely, rTMS over the left IPS resulted in strikingly opposed individual responses, with some participants responding with rightward and some with leftward attentional shifts. We demonstrate that microstructural and macrostructural variability within the corpus callosum, consistent with differential effects on cross-hemispheric interactions, predicts both the extent and the direction of the response to rTMS. Together, our findings suggest that the corpus callosum may have a dual inhibitory and excitatory function in maintaining the interhemispheric dynamics that underlie the allocation of spatial attention. SIGNIFICANCE STATEMENT The posterior parietal cortex (PPC) controls allocation of attention across left versus right visual fields. Damage to this area results in neglect, characterized by a lack of spatial awareness of the side of space

  16. GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.

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    Nitsche, Michael A; Liebetanz, David; Schlitterlau, Anett; Henschke, Undine; Fricke, Kristina; Frommann, Kai; Lang, Nicolas; Henning, Stefan; Paulus, Walter; Tergau, Frithjof

    2004-05-01

    Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.

  17. Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause.

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    Rył, Aleksandra; Jasiewicz, Andrzej; Grzywacz, Anna; Adler, Grażyna; Skonieczna-Żydecka, Karolina; Rotter, Iwona; Sipak-Szmigiel, Olimpia; Rumianowski, Bogdan; Karakiewicz, Beata; Jurczak, Anna; Parczewski, Miłosz; Urbańska, Anna; Grabowska, Marta; Laszczyńska, Maria

    2016-05-28

    Menopause is the permanent cessation of menstruation due to loss of ovarian follicular activity. A review of the available literature indicates that correlations between the changes that take place in a woman's body after menopause and different genetic variants are still being sought. The study was conducted in 252 women who had completed physiological menopause. The women were divided into groups according to the time elapsed since menopause. The total concentrations of estradiol and follicle-stimulating hormone were determined by means of electrochemiluminescence. The apolipoprotein E (APOE) and lepitn (LEP) genotypes were determined by real-time PCR and polymerase chain reaction-restriction fragment length polymorphism, respectively. We observed that people with the APOE3/E3 genotype entered menopause insignificantly later compared to other genotypes. Additionally, in the group of patients with the APOE3/E3 genotypes, differences in the E2 concentration were significantly related to the time since their last menstruation. There is no association found in the literature between these polymorphisms of the LEP gene and hormones. To date, attempts to formulate a model describing the association between E2 and FSH concentration with the polymorphisms of various genes of menopause in women have not been successful. This relationship is difficult to study because of the number of nongenetic factors. Environmental factors can explain variation in postmenopausal changes in hormone levels.

  18. Analysis of the Relationship between Estradiol and Follicle-Stimulating Hormone Concentrations and Polymorphisms of Apolipoprotein E and LeptinGenes in Women Post-Menopause

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    Aleksandra Rył

    2016-05-01

    Full Text Available Background: Menopause is the permanent cessation of menstruation due to loss of ovarian follicular activity. A review of the available literature indicates that correlations between the changes that take place in a woman’s body after menopause and different genetic variants are still being sought. Methods: The study was conducted in 252 women who had completed physiological menopause. The women were divided into groups according to the time elapsed since menopause. The total concentrations of estradiol and follicle-stimulating hormone were determined by means of electrochemiluminescence. The apolipoprotein E (APOE and lepitn (LEP genotypes were determined by real-time PCR and polymerase chain reaction–restriction fragment length polymorphism, respectively. Results: We observed that people with the APOE3/E3 genotype entered menopause insignificantly later compared to other genotypes. Additionally, in the group of patients with the APOE3/E3 genotypes, differences in the E2 concentration were significantly related to the time since their last menstruation. There is no association found in the literature between these polymorphisms of the LEP gene and hormones. Conclusions: To date, attempts to formulate a model describing the association between E2 and FSH concentration with the polymorphisms of various genes of menopause in women have not been successful. This relationship is difficult to study because of the number of nongenetic factors. Environmental factors can explain variation in postmenopausal changes in hormone levels.

  19. Slow-oscillatory transcranial direct current stimulation can induce bidirectional shifts in motor cortical excitability in awake humans

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    Groppa, S; Bergmann, T O; Siems, C

    2010-01-01

    Constant transcranial direct stimulation (c-tDCS) of the primary motor hand area (M1(HAND)) can induce bidirectional shifts in motor cortical excitability depending on the polarity of tDCS. Recently, anodal slow oscillation stimulation at a frequency of 0.75 Hz has been shown to augment intrinsic...

  20. Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms

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    Guo H

    2017-06-01

    Full Text Available Hao Guo,1 Ziming Wang,1 Quanyin Du,1 Pan Li,2 Zhigang Wang,2 Aimin Wang1 1Department of Orthopedics, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China Purpose: Bacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs combined with vancomycin.Materials and methods: We fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria.Results: NDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs

  1. Streptomycin decreases the functional shift to a slow phenotype induced by electrical stimulation in engineered muscle.

    Science.gov (United States)

    Khodabukus, Alastair; Baar, Keith

    2015-03-01

    Chronic low-frequency stimulation (CLFS) has long been used to induce a fast-to-slow phenotype shift in skeletal muscle. In this study, we explore the role of frequency (10 and 20 Hz), active time (15-60%), and streptomycin in inducing a fast-to-slow shift in engineered muscle. We found that C2C12 engineered muscle could respond to CLFS with an adult-like active time of 60% and found that a constant 10 Hz train of 0.6 s, followed by 0.4 s rest, induced a partial fast-to-slow phenotype shift. Following 2 weeks of CLFS, time-to-peak tension (TPT) (control [CTL]=40.9±0.2 ms; 10 Hz=58.5±3.5 ms; 20 Hz=48.2±2.7 ms) and half-relaxation time (1/2RT) (CTL=50.4±0.6 ms; 10 Hz=76.1±3.3 ms; 20 Hz=66.6±2.3 ms) slowed significantly in frequency, but not in an active time-dependent manner. Streptomycin significantly blunted the slowing of TPT and 1/2RT induced by CLFS by minimizing the fast-to-slow shift in SERCA isoform. Streptomycin (Nonstim=-42.8%±2.5%; Stim=-38.1%±3.6%) significantly prevented the improvement in fatigue resistance seen in CTL constructs (Nonstim=-58.4%±3.6%; Stim=-27.8%±1.7%). Streptomycin reduced the increase seen in GLUT4 protein following CLFS (CTL=89.4%±6.7%; STREP=41.0%±4.3%) and prevented increases in the mitochondrial proteins succinate dehydrogenase (SDH) and ATP synthase. These data demonstrate that streptomycin significantly blunts the fast-to-slow shift induced by CLFS. In the absence of streptomycin, CLFS induced slowing of contractile dynamics and improved fatigue resistance and suggests that this model can be used to study the mechanisms underlying CLFS-induced adaptations in muscle phenotype.

  2. Effect of LED light stimulation on sleep latency in night shift people

    Science.gov (United States)

    Wu, Jih-Huah; Chang, Yang-Chyuan; Chiu, Hui-Ling; Fang, Wei; Shan, Yi-Chia; Chen, Ming-Jie; Chang, Yu-Ting

    2014-05-01

    Sleep problems are getting worse and worse in modern world. They have a severe impact on psychological and physical health, as well as social performances. From our previous study, the brainwave α rhythm, θ wave and β wave were affected by radiating the palm of the subjects with low-level laser array. In addition, from other study, the LED array stimulator (LEDAS) also has the similar effects. In the present study, LED light was used to radiate the left palm of the subjects too, and the effects were assessed with the multiple sleep latency test (MSLT) and heart-rate variability (HRV) analysis. The results revealed that it doesn't have significant meaning between these two groups. However, the tendency of the sleep latency (SL) in the LED group was shorter than that in the control group. In addition, the autonomic nervous system (ANS) analysis showed that the sympathetic nervous system was getting larger in the LED group than that in the control group, and total ANS activity were mainly getting larger in the LED group. We infer that this LED stimulation could reduce SL and balance ANS activity of the night-shift people. In the future, the further study will be conducted on normal subjects.

  3. Analytical study of nonlinear phase shift through stimulated Brillouin scattering in single mode fiber with the pump power recycling technique

    International Nuclear Information System (INIS)

    Al-Asadi, H A; Mahdi, M A; Bakar, A A A; Adikan, F R Mahamd

    2011-01-01

    We present a theoretical study of nonlinear phase shift through stimulated Brillouin scattering in single mode optical fiber. Analytical expressions describing the nonlinear phase shift for the pump and Stokes waves in the pump power recycling technique have been derived. The dependence of the nonlinear phase shift on the optical fiber length, the reflectivity of the optical mirror and the frequency detuning coefficient have been analyzed for different input pump power values. We found that with the recycling pump technique, the nonlinear phase shift due to stimulated Brillouin scattering reduced to less than 0.1 rad for 5 km optical fiber length and 0.65 reflectivity of the optical mirror, respectively, at an input pump power equal to 30 mW

  4. Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol

    Directory of Open Access Journals (Sweden)

    Henley Donald C

    2003-02-01

    Full Text Available Abstract Estrogens play an important role in the regulation of placental function, and 17-beta-estradiol (E2 production rises eighty fold during human pregnancy. Although term placenta has been found to specifically bind estrogens, cellular localization of estrogen receptor alpha (ER-alpha in trophoblast remains unclear. We used western blot analysis and immunohistochemistry with h-151 and ID5 monoclonal antibodies to determine the expression and cellular localization of ER-alpha protein in human placentae and cultured trophoblast cells. Western blot analysis revealed a ~65 kDa ER-alpha band in MCF-7 breast carcinoma cells (positive control. A similar band was detected in five normal term placentae exhibiting strong expression of Thy-1 differentiation protein in the villous core. However, five other term placentae, which exhibited low or no Thy-1 expression (abnormal placentae, exhibited virtually no ER-alpha expression. In normal placentae, nuclear ER-alpha expression was confined to villous cytotrophoblast cells (CT, but syncytiotrophoblast (ST and extravillous trophoblast cells were unstained. In abnormal placentae no CT expressing ER-alpha were detected. Normal and abnormal placentae also showed ER-alpha expression in villous vascular pericytes and amniotic (but not villous fibroblasts; no staining was detected in amniotic epithelial cells or decidual cells. All cultured trophoblast cells derived from the same normal and abnormal placentae showed distinct ER-alpha expression in western blots, and the ER-alpha expression was confined to the differentiating CT, but not to the mature ST. Trophoblast cells from six additional placentae were cultured in normal medium with phenol red (a weak estrogen as above (PhR+, or plated in phenol red-free medium (PhR- without or with mid-pregnancy levels of E2 (20 nM. Culture in PhR- medium without E2 caused retardation of syncytium formation and PhR-medium with E2 caused acceleration of syncytium formation

  5. Inhibin A, inhibin B, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels in 473 healthy infant girls

    DEFF Research Database (Denmark)

    Chellakooty, M; Schmidt, I M; Haavisto, A M

    2003-01-01

    The early postnatal regulation of reproductive hormones seems to be more complex in girls than in boys. The aim of this study was to describe inhibins A and B, FSH, LH, estradiol, and SHBG in a large prospective cohort of 473 unselected, healthy, 3-month-old girls. In full term, appropriate-for- ...

  6. Intrafollicular Endocrine Milieu After Addition of hCG to Recombinant FSH During Controlled Ovarian Stimulation for In Vitro Fertilization

    DEFF Research Database (Denmark)

    Thuesen, L L; Andersen, A Nyboe; Loft, A

    2014-01-01

    : 72; D150: 56 (P ratio decreased significantly, with the lowest ratio in D100 and the highest in D0. Large follicles giving rise to good-quality embryos had significantly higher estradiol and progesterone levels and estradiol to T, estradiol to androstenedione...... for controlled ovarian stimulation. SETTING: This was a prospective randomized dose-response study conducted at Copenhagen University Hospital, Rigshospitalet, Denmark. PATIENTS: From 62 in vitro fertilization patients, 334 FFs were selected for analyses. INTERVENTIONS: Patients were treated using a GnRH agonist......, and progesterone to estradiol ratios, compared with small follicles, leading to poor-quality embryos. CONCLUSIONS: Increasing doses of hCG supplementation markedly stimulated the intrafollicular concentration of both estradiol and androgens, with a shift toward a more androgenic milieu. In large follicles...

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

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

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

  8. Estradiol Transdermal Patch

    Science.gov (United States)

    ... itching, and burning in women who are experiencing menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent osteoporosis (a condition in ... experienced menopause. Women who need to use transdermal estradiol for ...

  9. Blood Test: Estradiol

    Science.gov (United States)

    ... For Parents / Blood Test: Estradiol What's in this article? What It Is Why It's Done Preparation The Procedure What to Expect Getting the Results Risks Helping Your Child If You Have Questions Print en español Análisis de sangre: estradiol What It Is An estradiol test measures ...

  10. Effects of shifts in the rate of repetitive stimulation on sustained attention

    Science.gov (United States)

    Krulewitz, J. E.; Warm, J. S.; Wohl, T. H.

    1975-01-01

    The effects of shifts in the rate of presentation of repetitive neutral events (background event rate) were studied in a visual vigilance task. Four groups of subjects experienced either a high (21 events/min) or a low (6 events/min) event rate for 20 min and then experienced either the same or the alternate event rate for an additional 40 min. The temporal occurrence of critical target signals was identical for all groups, irrespective of event rate. The density of critical signals was 12 signals/20 min. By the end of the session, shifts in event rate were associated with changes in performance which resembled contrast effects found in other experimental situations in which shift paradigms were used. Relative to constant event rate control conditions, a shift from a low to a high event rate depressed the probability of signal detections, while a shift in the opposite direction enhanced the probability of signal detections.

  11. Observation of vector and tensor light shifts in 87Rb using near-resonant, stimulated Raman spectroscopy

    Science.gov (United States)

    Hu, Qing-Qing; Freier, Christian; Sun, Yuan; Leykauf, Bastian; Schkolnik, Vladimir; Yang, Jun; Krutzik, Markus; Peters, Achim

    2018-01-01

    We present the derivation of the frequency-dependent scalar, vector, and tensor dynamical polarizabilities for the two hyperfine levels of the 87Rb atom 5 s ground state. Based on the characterization of the dynamical polarizabilities, we analyze and measure the differential vector and tensor light shift between the 5 s ground-state sublevels with near-resonant, stimulated Raman transitions. These results clarify that the tensor polarizabilities for the ground states of alkali atoms are absent when the light field is far detuned from the atomic resonance and the total electronic angular momentum J is a good quantum number. In the near-resonant case, the light shifts are nontrivial and the determination of the frequency-dependent vector and tensor dynamic polarizabilities will help to achieve higher fidelities for applications of neutral atoms in quantum information and precision measurements.

  12. Shifts in connectivity during procedural learning after motor cortex stimulation: A combined transcranial magnetic stimulation/functional magnetic resonance imaging study.

    Science.gov (United States)

    Steel, Adam; Song, Sunbin; Bageac, Devin; Knutson, Kristine M; Keisler, Aysha; Saad, Ziad S; Gotts, Stephen J; Wassermann, Eric M; Wilkinson, Leonora

    2016-01-01

    Inhibitory transcranial magnetic stimulation (TMS), of which continuous theta burst stimulation (cTBS) is a common form, has been used to inhibit cortical areas during investigations of their function. cTBS applied to the primary motor area (M1) depresses motor output excitability via a local effect and impairs procedural motor learning. This could be due to an effect on M1 itself and/or to changes in its connectivity with other nodes in the learning network. To investigate this issue, we used functional magnetic resonance imaging to measure changes in brain activation and connectivity during implicit procedural learning after real and sham cTBS of M1. Compared to sham, real cTBS impaired motor sequence learning, but caused no local or distant changes in brain activation. Rather, it reduced functional connectivity between motor (M1, dorsal premotor & supplementary motor areas) and visual (superior & inferior occipital gyri) areas. It also increased connectivity between frontal associative (superior & inferior frontal gyri), cingulate (dorsal & middle cingulate), and temporal areas. This potentially compensatory shift in coupling, from a motor-based learning network to an associative learning network accounts for the behavioral effects of cTBS of M1. The findings suggest that the inhibitory TMS affects behavior via relatively subtle and distributed effects on connectivity within networks, rather than by taking the stimulated area "offline". Published by Elsevier Ltd.

  13. Estradiol-mediated ERK phosphorylation and apoptosis in vascular smooth muscle cells requires GPR 30.

    Science.gov (United States)

    Ding, Qingming; Gros, Robert; Limbird, Lee E; Chorazyczewski, Jozef; Feldman, Ross D

    2009-11-01

    Recent studies suggest that the rapid and nongenomic effects of estradiol may be mediated through the G protein-coupled receptor dubbed GPR30 receptor. The present study examines the role of GPR30 versus a classical estrogen receptor (ERalpha) in mediating the growth regulatory effects of estradiol. GPR30 is readily detectable in freshly isolated vascular tissue but barely detectable in cultured vascular smooth muscle cells (VSMC). In freshly isolated aortic tissue, estradiol stimulated extracellular signal-regulated kinases (ERK) phosphorylation. In contrast, in cultured VSMC, where GPR30 expression is significantly reduced, estradiol inhibits ERK phosphorylation. Transfer of the genes encoding GPR30 led to estradiol stimulation of ERK phosphorylation, which is opposite the effects of estradiol in the primary culture of VSMCs. Transduction of the mineralocorticoid receptor (MR) had no effect on estradiol effects on ERK. Estradiol-mediated stimulation of ERK subsequent to heterologous GPR30 expression was pertussis toxin sensitive and phosphoinositide 3-kinase (PI3 kinase) dependent; under these conditions, estradiol also inhibited protein kinase A (PKA). In contrast, in the absence of GPR30 expression in cultured VSMC, estradiol stimulated PKA activity and inhibited ERK phosphorylation. To determine the functional effect of GPR30 (vs. estrogen receptor expression), we assessed estradiol-mediated apoptosis. In the absence of GPR30 expression, estradiol inhibited apoptosis. This effect was enhanced with ERalpha expression. In contrast, with GPR30 expression, estradiol stimulated apoptosis in an ERK-dependent manner. Thus the effect of estradiol on vascular smooth muscle cell apoptosis is likely dependent on the balance between ER-mediated PKA activation and GPR30-mediated PKA inhibition and PI3 kinase activation. Taken together, we postulate that modulation of GPR30 expression or activity may be an important determinant of the effects of estradiol in the vasculature.

  14. Dienogest, a selective progestin, reduces plasma estradiol level through induction of apoptosis of granulosa cells in the ovarian dominant follicle without follicle-stimulating hormone suppression in monkeys.

    Science.gov (United States)

    Sasagawa, S; Shimizu, Y; Nagaoka, T; Tokado, H; Imada, K; Mizuguchi, K

    2008-07-01

    Dienogest is a selective progestin that has been shown to arrest ovarian follicular development in women, without affecting gonadotropin secretion. As luteal progesterone or exogeneous progestins are known to suppress ovarian folliculogenesis via the inhibition of gonadotropin secretion, this action of dienogest on ovaries seems to be unique. To examine the underlying mechanism of the antifolliculogenic effect of dienogest, female cynomolgus monkeys were treated with a single oral dose of 0.1 mg/kg dienogest on day 7 of the menstrual cycle. Plasma FSH, estradiol (E2), and progesterone levels were measured up to 15 days after dosing. In an additional experiment, ovaries were excised 24 h after dosing for histological examinations. As a result, plasma E2 level declined within 24 h after dosing, while dienogest did not decreased FSH level prior to E2 decline. After decline of E2 level, the low level of E2 was sustained for more than 11 days. It is considered that a single oral dose of dienogest induced atresia of the dominant follicle. In the histological examination, two out of three animals showed decline in E2 level. The ovarian dominant follicles from these animals showed apoptotic changes in granulosa cells with scattered aromatase expression within 24 h after dosing. These results indicate that the induction of atresia of the ovarian dominant follicle by direct action would be a possible mechanism of dienogest to inhibit plasma E2 level.

  15. Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide.

    Science.gov (United States)

    Shastri, Shefali M; Barbieri, Elizabeth; Kligman, Isaac; Schoyer, Katherine D; Davis, Owen K; Rosenwaks, Zev

    2011-02-01

    To evaluate in vitro fertilization (IVF) cycle outcomes in young poor responders treated with a luteal estradiol/gonadotropin-releasing hormone antagonist (E(2)/ANT) protocol versus an oral contraceptive pill microdose leuprolide protocol (OCP-MDL). Retrospective cohort. Academic practice. Poor responders: 186 women, aged <35 years undergoing IVF with either E(2)/ANT or OCP-MDL protocols. None. Clinical pregnancies, oocytes retrieved, cancellation rate. Patients in the E(2)/ANT group had a greater gonadotropin requirement (71.9 ± 22.2 vs. 57.6 ± 25.7) and lower E(2) level (1,178.6 ± 668 vs. 1,627 ± 889), yet achieved similar numbers of oocytes retrieved and fertilized, and a greater number of embryos transferred (2.3 ± 0.9 vs. 2.0 ± 1.1) with a better mean grade (2.14 ± .06 vs. 2.7 ± 1.8) compared with the OCP/MDL group. The E2/ANT group exhibited a trend toward improved implantation rates (30.5% vs. 21.1%) and ongoing pregnancy rates per started cycle: 44 out of 117 (37%) versus 17 out of 69 (25%). Poor responders aged <35 years may be treated with the aggressive E(2)/ANT protocol to improve cycle outcomes. Both protocols remain viable options for this group. Adequately powered, randomized clinical comparison appears justified. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  16. Deep Brain Stimulation: A Paradigm Shifting Approach to Treat Parkinson's Disease

    Science.gov (United States)

    Hickey, Patrick; Stacy, Mark

    2016-01-01

    Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management. PMID:27199637

  17. 17β-estradiol prevents cardiac diastolic dysfunction by stimulating mitochondrial function: a preclinical study in a mouse model of a human hypertrophic cardiomyopathy mutation.

    Science.gov (United States)

    Chen, Youzhou; Zhang, Zhuoli; Hu, Fenghuan; Yang, Weixian; Yuan, Jiansong; Cui, Jingang; Hao, Shujing; Hu, Jie; Zhou, Ying; Qiao, Shubin

    2015-03-01

    We investigated the effect of ovariectomy (OVX) and 17β-estradiol (E2) replacement on both mitochondrial and myocardial function in cTnT-Q92 transgenic mice generated by cardiac-restricted expression of a human hypertrophic cardiomyopathy (HCM) mutation. The cTnT-Q92 mice were ovariectomized at twenty weeks of age and were treated with either placebo (OVX group) or E2 (OVX+E2 group) for twelve weeks before being sacrificed. Wild-type and cTnT-Q92 female mice receiving sham operation were used as controls. Indices of diastolic function such as mitral early (E) and late (A) inflow as well as isovolumic relaxation time (IVRT) were measured by echocardiography. A Clark-type electrode was used to detect respiratory control, and ATP levels were determined at the mitochondrial level using HPLC. Key components related to mitochondrial energy metabolism, such as peroxisome proliferator-activated receptor α (PPARα), PPARγ coactivator 1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1), were also analyzed using Western blot and RT-PCR. The levels of oxidative stress markers were determined by measuring malondialdehyde (MDA) using the thiobarbituric acid assay. The cTnT-Q92 mice had impaired diastolic function compared with wild-type mice (E/A ratio, 1.39 ± 0.04 vs. 1.21 ± 0.01, penergy metabolism, as determined by ATP levels (3.49 ± 0.31 vs. 5.07 ± 0.47 μmol/g, penergy dysregulation, and reduced myocardial oxidative stress in cTnT-Q92 mice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

    Science.gov (United States)

    Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

    2005-10-01

    Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

  19. Alkaline conditions stimulate the production of 1,3-propanediol in Lactobacillus panis PM1 through shifting metabolic pathways.

    Science.gov (United States)

    Grahame, Douglas A S; Kang, Tae Sun; Khan, Nurul H; Tanaka, Takuji

    2013-07-01

    A novel Lactobacillus panis PM1 isolate was found to be capable of converting glycerol to 1,3-propanediol (1,3-PDO), an increasingly valuable commodity chemical. In this study the effects of various process parameters, including glucose and glycerol concentrations, inoculum size, temperature, aeration, pH, and carbon source were examined to determine the optimal conditions for the production of 1,3-PDO using a culture method simulating late log to early stationary phases. Inoculum size did not influence the production of 1,3-PDO, and temperature variance showed similar 1,3-PDO production between 25 and 37 °C under the examined conditions. Glycerol concentration and pH played a primary role in the final concentration of 1,3-PDO. The highest production occurred at 150-250 mM glycerol when 50 mM glucose was available. Alkaline initial conditions (pH 9-10) stimulated the production of 1,3-PDO which concurrently occurred with increased acetic acid production. Under these conditions, 213.6 mM of 1,3-PDO were produced from 300 mM glycerol (conversion efficiency was 71 %). These observations indicated that the production of 1,3-PDO was associated with the shift of the metabolic end-product ethanol to acetic acid, and that this shift resulted in an excess concentration of NADH available for the processing of glycerol to 1,3-PDO.

  20. Up-regulation of PI3K/Akt signaling by 17β-estradiol through activation of estrogen receptor-α, but not estrogen receptor-β, and stimulates cell growth in breast cancer cells

    International Nuclear Information System (INIS)

    Lee, Young-Rae; Park, Jinny; Yu, Hong-Nu; Kim, Jong-Suk; Youn, Hyun Jo; Jung, Sung Hoo

    2005-01-01

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

  1. Warm Water Bath Stimulates Phase-Shifts of the Peripheral Circadian Clocks in PER2::LUCIFERASE Mouse

    Science.gov (United States)

    Kuriki, Daisuke; Haraguchi, Atsushi; Shibata, Shigenobu

    2014-01-01

    Circadian clocks in the peripheral tissues of mice are known to be entrained by pulse stimuli such as restricted feeding, novel wheel running, and several other agents. However, there are no reports on high temperature pulse-mediated entrainment on the phase-shift of peripheral clocks in vivo. Here we show that temperature treatment of mice for two days at 41°C, instead of 37°C, for 1–2 h during the inactive period, using a temperature controlled water bath stimulated phase-advance of peripheral clocks in the kidney, liver, and submandibular gland of PER2::LUCIFERASE mice. On the other hand, treatment for 2 days at 35°C ambient room temperature for 2 h did not cause a phase-advance. Maintenance of mice at 41°C in a water bath, sustained the core body temperature at 40–41°C. However, the use of 37°C water bath or the 35°C ambient room temperature elevated the core body temperature to 38.5°C, suggesting that at least a core body temperature of 40–41°C is necessary to cause phase-advance under light-dark cycle conditions. The temperature pulse stimulation at 41°C, instead of 37°C water bath for 2 h led to the elevated expression of Per1 and Hsp70 in the peripheral tissue of mice. In summary, the present study demonstrates that transient high temperature pulse using water bath during daytime causes phase-advance in mouse peripheral clocks in vivo. The present results suggest that hot water bath may affect the phase of peripheral clocks. PMID:24933288

  2. Circulating thyrotropin is upregulated by estradiol

    Directory of Open Access Journals (Sweden)

    Salvatore Benvenga

    2018-03-01

    Full Text Available After encountering two women with serum thyrotropin (TSH levels greater in periovulatory phase than in other days of the menstrual cycle, we hypothesized that TSH levels could be sensitive to changes in circulating estrogens in women.The objective of this study was to evaluate whether serum TSH increases after an induced acute increase of serum estradiol, and compare serum TSH increase with that of prolactin (PRL which is a classic estradiol-upregulated pituitary hormone.In this retrospective study, we resorted to stored frozen sera from 55 women who had undergone the GnRH agonist (buserelin-acute stimulation test of ovarian steroidogenesis. This test, that is preceded by dexamethasone administration to suppress adrenal steroidogenesis, had been performed to show an increased buserelin-stimulated response of 17-hydroxyprogesterone, a response that is frequent in polycystic ovary syndrome. Fifty-five women had enough serum volume at pertinent times (first observation early in the follicular phase and all times of the test to permit assay of serum estradiol, TSH and PRL.Before dexamethasone administration, estradiol averaged 26.4 ± 15.5 pg/ml (reference range 23–139, follicular phase, TSH 1.78 ± 0.86 mU/L (reference range 0.3–4.2 and PRL 409.4 ± 356 mU/L (reference range 70.8–556 (mean ± SD.Serum estradiol, TSH and PRL averaged 47.2 ± 27 pg/ml, 0.77 ± 0.48 mU/L and 246.4 ± 206.8 mU/L just prior to the buserelin injection, but they peaked at 253.4 ± 113.5 pg/ml (nv 83–495, midcycle, 3.30 ± 1.65 mU/L and 540.3 ± 695.2 mU/L after injection. The responses to buserelin of estradiol, TSH and PRL were of wide magnitude. There was a significant correlation between TSH peak and serum estradiol peak, betweeen AUC0-24 h-TSH and AUC0-24 h-estradiol, or between PRL peak and estradiol peak and AUC0-24 h -PRL and AUC0-24 h-estradiol in only a subgroup of women.Therefore, women

  3. Estradiol-induced estrogen receptor-alpha trafficking.

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2009-12-02

    Estradiol has rapid actions in the CNS that are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca(2+)](i)) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERalpha has an extracellular portion. In addition to the full-length ERalpha [apparent molecular weight (MW), 66 kDa], surface biotinylation labeled an ERalpha-immunoreactive protein (MW, approximately 52 kDa) identified by both COOH- and NH(2)-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 and 52 kDa ERalpha. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24-48 h reduced ERalpha levels, suggesting receptor downregulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERalpha-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERalpha trafficking to and from the membrane. Estradiol-induced [Ca(2+)](i) flux was also significantly increased at the time of peak ERalpha activation/internalization. These results demonstrate that ERalpha is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERalpha are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERalpha to augment and then terminate membrane-initiated signaling.

  4. Estradiol-induced estrogen receptor-α trafficking

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2010-01-01

    Estradiol has rapid actions in the central nervous system, which are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca2+]i) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERα has an extracellular portion. In addition to the full length ERα (apparent M.W. 66 kDa), surface biotinylation labeled an ERα-immunoreactive protein (M.W. ~ 52 kDa) identified by both COOH- and NH2-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 kDa and 52 kDa ERα. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24–48 hr reduced ERα levels, suggesting receptor down-regulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERα-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERα trafficking to and from the membrane. Estradiol-induced [Ca2+]i flux was also significantly increased at the time of peak ERα activation/internalization. These results demonstrate that ERα is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERα are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERα to augment and then terminate membrane-initiated signaling. PMID:19955385

  5. Estradiol blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003711.htm Estradiol blood test To use the sharing features on this page, ... of estrogens. How the Test is Performed A blood sample is needed . How to Prepare for the Test Your health care provider may tell you to ...

  6. Increased Progesterone/Estradiol Ratio on the Day of hCG Administration Adversely Affects Success of In Vitro Fertilization–Embryo Transfer in Patients Stimulated with Gonadotropin-releasing Hormone Agonist and Recombinant Follicle-stimulating Hormone

    Directory of Open Access Journals (Sweden)

    Yu-Che Ou

    2008-06-01

    Conclusion: Premature luteinization, defined as late follicular P/E2 ratio of > 1 in long GnRHa cycles with rFSH stimulation, adversely affected ovarian responses and clinical outcomes. It seems unrelated to preovulatory luteinizing hormone (LH elevation and LH/hCG content of gonadotropins and could be associated with poor ovarian response and the presence of dysmature follicles. [Taiwan J Obstet Cynecol 2008;47(2:1 68-1 74

  7. EEG-guided transcranial magnetic stimulation reveals rapid shifts in motor cortical excitability during the human sleep slow oscillation

    DEFF Research Database (Denmark)

    Bergmann, Til O; Mölle, Matthias; Schmidt, Marlit A

    2012-01-01

    Evoked cortical responses do not follow a rigid input-output function but are dynamically shaped by intrinsic neural properties at the time of stimulation. Recent research has emphasized the role of oscillatory activity in determining cortical excitability. Here we employed EEG-guided transcrania...... magnetic stimulation (TMS) during non-rapid eye movement sleep to examine whether the spontaneous...

  8. Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation.

    Directory of Open Access Journals (Sweden)

    Stewart Heitmann

    2017-01-01

    Full Text Available Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40-80 Hz oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude-the hallmark of a type II excitable medium-yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields.

  9. Restoring the basal ganglia in Parkinson's disease to normal via multi-input phase-shifted deep brain stimulation.

    Science.gov (United States)

    Agarwal, Rahul; Sarma, Sridevi V

    2010-01-01

    Deep brain stimulation (DBS) injects a high frequency current that effectively disables the diseased basal ganglia (BG) circuit in Parkinson's disease (PD) patients, leading to a reversal of motor symptoms. Though therapeutic, high frequency stimulation consumes significant power forcing frequent surgical battery replacements and causing widespread influence into other brain areas which may lead to adverse side effects. In this paper, we conducted a rigorous study to assess whether low frequency signals can restore behavior in PD patients by restoring neural activity in the BG to the normal state. We used a biophysical-based model of BG nuclei and motor thalamus whose parameters can be set to simulate the normal state and the PD state with and without DBS. We administered pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies ranging from 1-150Hz. For each DBS frequency, we computed statistics on the simulated neural activity to assess whether it is restored to the normal state. In particular, we searched for DBS waveforms that suppress pathological bursting, oscillations, correlations and synchronization prevalent in the PD state and that enable thalamic cells to relay cortical inputs reliably. We found that none of the tested waveforms restores neural activity to the normal state. However, our simulations led us to construct a novel DBS strategy involving low frequency multi-input phaseshifted DBS to be administered into the STN. This strategy successfully suppressed all pathological symptoms in the BG in addition to enabling thalamic cells to relay cortical inputs reliably.

  10. Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells

    Science.gov (United States)

    Lombardi, Maria; Castoria, Gabriella; Migliaccio, Antimo; Barone, Maria Vittoria; Di Stasio, Rosina; Ciociola, Alessandra; Bottero, Daniela; Yamaguchi, Hiroshi; Appella, Ettore; Auricchio, Ferdinando

    2008-01-01

    In breast cancer cells, cytoplasmic localization of the estradiol receptor α (ERα) regulates estradiol-dependent S phase entry. We identified a nuclear export sequence (NES) in ERα and show that its export is dependent on both estradiol-mediated phosphatidylinositol-3-kinase (PI3K)/AKT activation and chromosome region maintenance 1 (CRM1). A Tat peptide containing the ERα NES disrupts ERα–CRM1 interaction and prevents nuclear export of ERα- and estradiol-induced DNA synthesis. NES-ERα mutants do not exit the nucleus and inhibit estradiol-induced S phase entry; ERα-dependent transcription is normal. ERα is associated with Forkhead proteins in the nucleus, and estradiol stimulates nuclear exit of both proteins. ERα knockdown or ERα NES mutations prevent ERα and Forkhead nuclear export. A mutant of forkhead in rhabdomyosarcoma (FKHR), which cannot be phosphorylated by estradiol-activated AKT, does not associate with ERα and is trapped in the nucleus, blocking S phase entry. In conclusion, estradiol-induced AKT-dependent phosphorylation of FKHR drives its association with ERα, thereby triggering complex export from the nucleus necessary for initiation of DNA synthesis and S phase entry. PMID:18644889

  11. Transfer of estradiol to human milk. [Radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, S.; Nygren, K.G.; Johansson, E.D.B.

    1978-11-15

    A radioimmunoassay for the measurement of estradiol in human milk is evaluated. The detection limit was found to be 25 pg of estradiol per milliliter of milk. In milk samples collected from four lactating women during three to four months and from one pregnant and lactating woman, the concentration of estradiol was found to be below the detection limit of the assay. When six lactating women were given vaginal suppositories containing 50 or 100 mg of estradiol, it was possible to estimate the estradiol concentration in milk. A ratio of transfer of estradiol from plasma to milk during physiologic conditions is calculated to be less than 100 : 10.

  12. Transfer of estradiol to human milk

    International Nuclear Information System (INIS)

    Nilsson, S.; Nygren, K.G.; Johansson, E.D.B.

    1978-01-01

    A radioimmunoassay for the measurement of estradiol in human milk is evaluated. The detection limit was found to be 25 pg of estradiol per milliliter of milk. In milk samples collected from four lactating women during three to four months and from one pregnant and lactating woman, the concentration of estradiol was found to be below the detection limit of the assay. When six lactating women were given vaginal suppositories containing 50 or 100 mg of estradiol, it was possible to estimate the estradiol concentration in milk. A ratio of transfer of estradiol from plasma to milk during physiologic conditions is calculated to be less than 100 : 10

  13. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

    2003-01-01

    To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol....... A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month...... before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone...

  14. Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period

    DEFF Research Database (Denmark)

    Andersson, Anna-Maria; Carlsen, Elisabeth; Petersen, Jørgen Holm

    2003-01-01

    To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol......, and SHBG were measured. The intraindividual variation in inhibin B over the study period was, on the average, 10%, corresponding to the assay variation of the inhibin B assay, indicating that most of the observed day to day variation in inhibin B levels in men could be explained by assay variation...... before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone...

  15. Acute treatment with 17beta-estradiol attenuates astrocyte-astrocyte and astrocyte-neuron communication.

    Science.gov (United States)

    Rao, Shilpa P; Sikdar, Sujit Kumar

    2007-12-01

    Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control. (c) 2007 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    1999-10-01

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

  17. Synthesis of 123I-16 iodo estradiol

    International Nuclear Information System (INIS)

    Therain, F.; Gros, J.; Souchu, A.

    1982-01-01

    16α iodo estradiol has been demonstrated to have as good an affinity as estradiol for estrogen-receptors and, labeled with iodine 123, may provide a good scanning agent fot visualisation of tissues containing estrogen-repectors, especially mammary tumors. 123 I-16α iodo estradiol has been synthesized by an halogen exchange of 16ν bromo estradiol according to the procedure described by Hochberg for 125 I-16α iodo estradiol labeling. Radiochemical yields are much lower than with iodine 125 (1 to 30%) and extremely variable. Specific activity range from 1,000 to 2,000 Ci/mmole [fr

  18. Human endometrial milk fat globule-epidermal growth factor 8 (MFGE8) is up regulated by estradiol at the transcriptional level, and its secretion via microvesicles is stimulated by human chorionic gonadotropin (hCG)

    KAUST Repository

    Sarhan, Abbaa

    2013-10-17

    Objective: We have recently showed that MFGE8, a novel epithelial cell protein in the human endometrium, upregulated during the window of implantation. We hypothesized that MFGE8 may act as a key modulator of endometrial remodeling and trophoblast invasion. The aims of this study were (i) to investigate the in vitro regulation of human endometrial epithelial cells MFGE8 transcription, translation, and secretion by sex steroids and hCG; and (ii) to examine the possibility of MFGE8 secretion via microvesicles. Design: Experimental in vitro study using Ishikawa cells. Setting: University center. Interventions: Treatment with estradiol (E2), progesterone (P4), and human chorionic gonatropin (hCG). Main outcome measures: MFGE8 mRNA and protein expression, and identification of secreted microvesicles by mass spectrometry (MS) and immunoblotting. Results: E2, but not P4 or hCG, significantly upregulated MFGE8 mRNA expression. hCG significantly increased MFGE8 secretion. Microvesicels obtained after ultracentrifugation were visualized with atomic force microscopy ranging from ~100 to 200 nm. In addition to the expected 46 kD protein, the microvesicles contained a second form of secreted MFGE8 measuring ~30 kD which was confirmed by MS. Conclusions: We demonstrated (i) dual effects of E2 and hCG on the regulation of MFGE8, and (ii) MFGE8 protein secretion in association with microvesicles. MFGE8 has the potential to modulate endometrial function and implantation via exocrine and/ or paracrine-autocrine effects. To the best of our knowledge, this is the first demonstration of microvesicular secretion of any regulatory protein by endometrial epithelial cells, providing initial evidence suggestive of microvesicular participation in cellular trafficking information in the non-pregnant and pregnant endometrium.

  19. 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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  1. Effects of estradiol on norepinephrine and prostaglandin efflux in medial basal hypothalamus of ovariectomized rats

    International Nuclear Information System (INIS)

    Cardinali, D.P.; Fernandez Pardal, J.; Gimeno, M.F.; Gimeno, A.L.

    1982-01-01

    The spontaneous and K + -stimulated efflux of norepinephrine (NE) and the release of PGE 2 and PGF 2 α were examined in medial basal hypothalamus (MBH) of ovariectomized rats killed before and during the LH release that follows estradiol treatment. As compared to vehicle-treated, ovariectomized rats, estradiol-primed rats exhibited a 60% more increase in K + -stimulated 3 H-overflow of MBH slices preloaded with 3 H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K + -induced 3 H release from MBH slices at the time of LH release (1700 hours), nor affected labelled NE release in occipital cortex slices. A significant difference between K + -stimulated NE release of vehicle-treated spayed rats killed at 1000 and 1700 hours was observed, the latter showing 54% more release upon stimulus. PGE 2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE 2 at the evening as compared to the controls. The release of PGF 2 α remained essentially unchanged regardless of estradiol treatment or time of day. The present results offer additional support to the involvement of MBH catecholamines and prostaglandins in the mechanism of LH secretion in the rat. (author)

  2. Estradiol facilitation of cocaine-induced locomotor sensitization in female rats requires activation of mGluR5.

    Science.gov (United States)

    Martinez, Luis A; Peterson, Brittni M; Meisel, Robert L; Mermelstein, Paul G

    2014-09-01

    In comparison to men, women exhibit enhanced responsiveness to the stimulating and addictive properties of cocaine. A growing body of evidence implicates the steroid hormone estradiol in mediating this sex difference, yet the mechanisms underlying estradiol enhancement of behavioral responses to cocaine in females are not known. Recently, we have found that estrogen receptor alpha (ERα) functionally couples with the metabotropic glutamate receptor 5 (mGluR5) to mediate the effects of estradiol on both cellular activation as well as dendritic spine plasticity in brain regions involved in cocaine-induced behavioral sensitization. Thus, we sought to determine whether mGluR5 activation is required for the facilitative effects of estradiol on locomotor responses to cocaine. To test this hypothesis, ovariectomized (OVX) female rats were tested for locomotor activity on the first and fifth days of daily systemic injections of cocaine. For the 2 days prior to each locomotor test, animals were injected with the mGluR5 antagonist MPEP (or vehicle) and estradiol (or oil). MPEP treatment blocked the facilitative effects of estradiol on cocaine-induced locomotor sensitization, without affecting acute responses to cocaine or the inhibitory actions of estradiol on weight gain. Considered together, these data indicate that mGluR5 activation is critical for the actions of estradiol on cocaine-induced behavioral sensitization. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Oleocanthal Modulates Estradiol-Induced Gene Expression Involving Estrogen Receptor α.

    Science.gov (United States)

    Keiler, Annekathrin Martina; Djiogue, Sefirin; Ehrhardt, Tino; Zierau, Oliver; Skaltsounis, Leandros; Halabalaki, Maria; Vollmer, Günter

    2015-09-01

    Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes. Georg Thieme Verlag KG Stuttgart · New York.

  4. 17β-estradiol and xenoestrogens reveal synergistic effect on mitochondria of human sperm.

    Science.gov (United States)

    Skibińska, Izabela; Jendraszak, Magdalena; Borysiak, Karolina; Jędrzejczak, Piotr; Kotwicka, Małgorzata

    2016-01-01

    The aim of the study was to investigate the influence of 17β-estradiol (main endogenous estrogen) and selected xenoestrogens (genistein, bisphenol-A), individually and in combination, on the mitochondrial function of human sper-matozoa. In natural environment, human beings are exposed to multiple xenoestrogens, so their impact is combined with endogenous steroids. The effects of ligands on human spermatozoa were assessed regarding the following phenomena: spermatozoa vitality (propidium iodide staining), phosphatidylserine membrane translocation (staining with annexin V marked with fluorescein), mitochondrial membrane potential (using JC-1 fluorochrome), and production of superoxide anion in mitochondria (using MitoSOX RED dye). Two-hour incubation of spermatozoa with 17β-estradiol, genistein, and bisphenol-A neither altered cell vitality nor stimulated phosphatidylserine membrane translocation. Incubation of spermatozoa with 17β-estradiol or bisphenol-A sepa-rately, as well as incubation with the three ligands simultaneously, resulted in altered mitochondrial membrane potential. Spermatozoa incubation with the three ligands significantly increased the mitochondrial superoxide anion level. It seems safe to conclude that human spermatozoa mitochondria are target cell structures for both, 17β-estradiol and xenoestrogens. The reaction to the 17β-estradiol and xenoestrogens mixture suggests a synergistic mechanism of action. Xenoestrogens may increase the sensitivity of spermatozoa to 17β-estradiol.

  5. Diet and estradiol level in adolescent girls

    Directory of Open Access Journals (Sweden)

    Ririn Hariani

    2016-07-01

    Conclusion Serum estradiol levels in adolescent girls aged 13-15 years are influenced by diet, especially fat intake. Estradiol levels can be predicted from energy, carbohydrate, protein, and fat intake, as well as BMI. [Paediatr Indones. 2016;56:134-8.].

  6. Estradiol RIA kit in clinical practice

    International Nuclear Information System (INIS)

    Friedrich, W.; Lisse, K.; Bienert, R.; Flentje, H.; Koerner, H.; Wilken, T.; Akademie der Wissenschaften der DDR, Berlin-Buch. Zentralinstitut fuer Isotopen- und Strahlenforschung)

    1985-01-01

    First clinical experience with a estradiol RIA kit developed in the Central Institute for Isotope- and Radiation Research is reported. The kit was used for the daily control of estradiol level in patients, which were treated within the program for in vitro fertilization and embryo transfer. The time of incubation could be shortened by means of a double antibody technique and by use of a precipitation mixture to 2 h. The intraassay variation is 9.2%, the interassay variation is 15.1%, the recovery rate is 94%. The sensitivity of the test (B 0 -3SD) is about 120 pmol/l. The estradiol RIA kit satisfies clinical requirements. (author)

  7. The induction of pro-angiogenic processes within a collagen scaffold via exogenous estradiol and endometrial epithelial cells.

    Science.gov (United States)

    Pence, Jacquelyn C; Clancy, Kathryn B H; Harley, Brendan A C

    2015-10-01

    Nutrient transport remains a major limitation in the design of biomaterials. One approach to overcome this constraint is to incorporate features to induce angiogenesis-mediated microvasculature formation. Angiogenesis requires a temporal presentation of both pro- and anti-angiogenic factors to achieve stable vasculature, leading to increasingly complex biomaterial design scheme. The endometrium, the lining of the uterus and site of embryo implantation, exemplifies a non-pathological model of rapid growth, shedding, and re-growth of dense vascular networks regulated by the dynamic actions of estradiol and progesterone. In this study, we examined the individual and combined response of endometrial epithelial cells and human umbilical vein endothelial cells to exogenous estradiol within a three-dimensional collagen scaffold. While endothelial cells did not respond to exogenous estradiol, estradiol directly stimulated endometrial epithelial cell transduction pathways and resulted in dose-dependent increases in endogenous VEGF production. Co-culture experiments using conditioned media demonstrated estradiol stimulation of endometrial epithelial cells can induce functional changes in endothelial cells within the collagen biomaterial. We also report the effect of direct endometrial epithelial and endothelial co-culture as well as covalent immobilization of estradiol within the collagen biomaterial. These efforts establish the suitability of an endometrial-inspired model for promoting pro-angiogenic events within regenerative medicine applications. These results also suggest the potential for developing biomaterial-based models of the endometrium. © 2015 Wiley Periodicals, Inc.

  8. Ethinyl Estradiol and Norelgestromin Transdermal Patch

    Science.gov (United States)

    ... human immunodeficiency virus (HIV; the virus that causes acquired immunodeficiency syndrome [AIDS]) and other sexually transmitted diseases. ... of energy fever dark-colored urine light-colored stool rash Ethinyl estradiol and norelgestromin contraceptive patch may ...

  9. Neonatal androgenization of hypogonadal (hpg male mice does not abolish estradiol-induced FSH production and spermatogenesis

    Directory of Open Access Journals (Sweden)

    Kerr Jeffrey B

    2005-09-01

    Full Text Available Abstract Background Testicular development is arrested in the hypogonadal (hpg mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Methods Hpg mice were treated with 100 μg testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. Results The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Conclusion The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and

  10. Decreased neural activity and neural connectivity while performing a set-shifting task after inhibiting repetitive transcranial magnetic stimulation on the left dorsal prefrontal cortex

    NARCIS (Netherlands)

    Gerrits, N.J.H.M.; van den Heuvel, O.A.; van der Werf, Y.D.

    2015-01-01

    Background: Sub-optimal functioning of the dorsal prefrontal cortex (PFC) is associated with executive dysfunction, such as set-shifting deficits, in neurological and psychiatric disorders. We tested this hypothesis by investigating the effect of low-frequency 'inhibiting' off-line repetitive

  11. Decreased neural activity and neural connectivity while performing a set-shifting task after inhibiting repetitive transcranial magnetic stimulation on the left dorsal prefrontal cortex

    NARCIS (Netherlands)

    Gerrits, Niels J H M; van den Heuvel, Odile A; van der Werf, Ysbrand D

    2015-01-01

    BACKGROUND: Sub-optimal functioning of the dorsal prefrontal cortex (PFC) is associated with executive dysfunction, such as set-shifting deficits, in neurological and psychiatric disorders. We tested this hypothesis by investigating the effect of low-frequency 'inhibiting' off-line repetitive

  12. Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2015-02-01

    Full Text Available It is firmly believed that the mechanism of action of SSRIs in major depression is to inhibit the serotonin transporter, SERT, and increase extracellular concentration of serotonin. However, this undisputed observation does not prove that SERT inhibition is the mechanism, let alone the only mechanism, by which SSRI’s exert their therapeutic effects. It has recently been demonstrated that 5-HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine in vivo. The ability of all 5 currently used SSRIs to stimulate the 5-HT2B receptor equipotentially incultured astrocyteshas been known for several years,and increasing evidence has shown the importance of astrocytes and astrocyte-neuronal interactions for neuroplasticity and complex brain activity. This paper reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured astrocytes and in astrocytes freshly isolated from brains of mice treated with fluoxetine for 14 daystogether with effects ofanti-depressant therapy on turnover of glutamate and GABA and metabolism of glucose and glycogen. It is suggested that these events are causally related to the mechanism of action of SSRIs and of interest for development of newer antidepressant drugs.

  13. Development of an innovative microcantilever-based biosensor for 17β-estradiol detection in bovine muscles: preliminary results

    Directory of Open Access Journals (Sweden)

    Danilo Pitardi

    2013-06-01

    Full Text Available 17β-estradiol is the most powerful substance with estrogenic effect, commonly used as illegal growth promoter in livestock production. To avoid health risks for consumers, sensitive, reliable and low-cost methods for quantification of extremely low concentrations of such carcinogenic residues in food are needed. Antibody-immobilised microcantilever resonators were proposed as innovative biosensors able to quantify an adsorbed target mass thanks to a shift in resonance frequency. Furthermore, the quantification of masses on the order of few picograms has recently shown to be successfully achievable with very high precision. In this study, we analysed the performance of our microcantilever sensors using extracted samples of bovine muscle from experimental animals, containing variable concentrations of 17β-estradiol (HPLC-MS/MS tested. Preliminary data showed that treated animals are correctly revealed, exhibiting large negative frequency shifts. More experiments, though, are needed to obtain a correct quantification of 17β-estradiol concentration.

  14. Roles of estradiol and gonadotropin-releasing hormone in controlling negative and positive feedback associated with the luteinizing hormone surge in ovariectomized pigs.

    Science.gov (United States)

    Britt, J H; Esbenshade, K L; Ziecik, A J

    1991-09-01

    Ovariectomized gilts (n = 63) were given estradiol benzoate (estradiol), antiserum to neutralize endogenous GnRH, and pulses of a GnRH agonist (GnRH-A) to stimulate release of LH. GnRH-A was given as 200-ng pulses hourly from 0 to 54 h and as 100- or 200-ng pulses every 30 or 60 min from 54 to 96 h after estradiol. Estradiol alone suppressed LH from 6 to 54 h and elicited an LH surge that peaked at 72 h. When GnRH-A was given every 30-60 min from 0 to 96 h, estradiol suppressed LH for 6-12 h, but then LH returned to pre-estradiol concentrations. When pulses of GnRH-A were given only between 54 and 96 h after estradiol, the surge of LH was related positively to dose and frequency of GnRH-A. We conclude that 1) estrogen acts at the hypothalamus to inhibit release of GnRH for 54 h and then causes a synchronous release of GnRH; 2) estrogen acts at the pituitary to block its response to GnRH for 6-12 h and enhances the accumulation of releasable LH; and 3) magnitude of the LH surge is dependent on the amount of GnRH stimulation.

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

    Directory of Open Access Journals (Sweden)

    Azboy İbrahim

    2016-01-01

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

  16. Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

    Science.gov (United States)

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

    2015-12-01

    Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Sukhdeep [Center for Protein Science, Design and Engineering (CPSDE), Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector-81, SAS Nagar, Punjab 140306 (India); Mukherjee, Tapan K. [Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, Haryana 133207 (India); Guptasarma, Purnananda, E-mail: guptasarma@iisermohali.ac.in [Center for Protein Science, Design and Engineering (CPSDE), Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector-81, SAS Nagar, Punjab 140306 (India)

    2016-09-02

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D {sup 1}H and {sup 13}C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl {sup 1}H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters {sup 1}H and {sup 13}C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C{sub 18} reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D 1 H and 13 C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl 1 H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters 1 H and 13 C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C 18 reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.

  19. Estradiol implants in the arcuate nucleus induce lactogenesis in virgin rats. Role of progesterone.

    Science.gov (United States)

    Carón, R W; Deis, R P

    1998-01-01

    The aim of this study was to determine the effect of the centrally administered estradiol, and the effects of the consequent hypersecretion of prolactin (PRL) and progesterone, on lactogenesis as evaluated by mammary accumulation of casein and lactose. Bilateral cannulae containing 17beta-estradiol or cholesterol were implanted in the arcuate nucleus of virgin rats on the day of estrus (Day 0). In the first experiment different groups of rats were killed on Days 6, 9, 15, 17, or 19. Trunk blood was collected and abdominal mammary glands were taken. In the second experiment, estradiol-implanted rats received the progesterone antagonist mifepristone or vehicle at 14.00 h on Day 8 or 16 post-implant, and were killed 28 or 48 h later. Serum PRL and progesterone and mammary casein were measured by RIA and lactose was determined by an enzymatic assay. Estradiol-implanted rats showed a significant increase in both milk components at all time points after implant compared to controls. On Day 9 after estradiol implant, mifepristone had no effect on mammary content of casein or lactose. By contrast, on Day 16, mifepristone markedly increased both casein and lactose contents without modifying serum PRL and progesterone concentrations. In conclusion, 17beta-estradiol implants in the arcuate nucleus of virgin rats results in hyperprolactinaemia and stimulates mammary accumulation of casein and lactose in the absence of feto-placental units. Despite the prolonged luteal activation, the sustained high levels of circulating progesterone become inhibitory to lactogenesis after a relatively long period after implant.

  20. Estradiol valerate/dienogest: in oral contraception.

    Science.gov (United States)

    Hoy, Sheridan M; Scott, Lesley J

    2009-08-20

    Estradiol valerate/dienogest is an oral contraceptive for women that combines the natural estrogen estradiol with the 19-nortestosterone derivative dienogest in a four-phasic formulation. Estradiol valerate/dienogest demonstrated contraceptive efficacy in a large (n = 1377), noncomparative, multicentre study in women aged 18-50 years, with 13 pregnancies over 1797.5 women-years of exposure generating an unadjusted Pearl Index (PI) of 0.73 (upper limit of 95% CI 1.24) [primary endpoint]. Six of the pregnancies were attributed to method failure, resulting in an adjusted PI, based on 1786.5 women-years of exposure, of 0.34 (upper limit of 95% CI 0.73). In a double-blind study in 798 women aged 18-50 years, estradiol valerate/dienogest and ethinylestradiol/levonorgestrel demonstrated an acceptable bleeding pattern and level of cycle control, according to several co-primary endpoints. As reported in the UK manufacturer's summary of product characteristics, the unadjusted PI for women aged 18-35 years or 18-50 years in a pooled analysis of clinical studies was 1.01 (upper limit of 95% CI 1.59) and 0.79 (upper limit of 95% CI 1.23). This pooled analysis of three studies excluded those pregnancies occurring within 14 days of the cessation of therapy. Estradiol valerate/dienogest was generally well tolerated in this population, with the nature of adverse events generally similar across the studies and between estradiol valerate/dienogest and ethinylestradiol/levonorgestrel.

  1. 21 CFR 522.2477 - Trenbolone acetate and estradiol.

    Science.gov (United States)

    2010-04-01

    ... mg trenbolone acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant... estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (F) 80 mg trenbolone acetate... trenbolone acetate and 4 mg estradiol, and 1 pellet containing 29 mg tylosin tartrate) per implant dose. (G...

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

    Science.gov (United States)

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

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

  3. The impact of serum FSH and estradiol on postmenopausal osteoporosis related to time since menopause.

    Science.gov (United States)

    Yoldemir, Tevfik; Erenus, Mithat; Durmusoglu, Fatih

    2012-11-01

    To determine the impact on osteopenia/osteoporosis of serum follicle-stimulating hormone (FSH), estradiol levels and time since menopause in a group of Turkish postmenopausal women. Four hundred and thirty-three healthy postmenopausal women seen at the Marmara University Menopause Outpatient Clinic were enrolled for this prospective cohort study. The women were allocated to one of three groups according to the bone mineral density (BMD) of the lumbar vertebrae and total hip, as measured by dual energy X-ray absorptiometry (DEXA). Serum FSH, estradiol levels, age and time since menopause were compared between the groups. The mean serum FSH, LH, estradiol and testosterone levels for women with normal, osteopenic and osteoporotic BMD at lumbar vertrebra L1-L4 and total hip were comparable. Time since menopause had a stronger predictive value for low BMD (osteopenia or osteoporosis) in the lumbar and hip areas than did serum FSH or estradiol levels. Our study showed that neither FSH nor E2 has a strong impact on postmenopausal BMD. However it appears that time since menopause has a weak non-significant association with postmenopausal osteopenia and osteoporosis.

  4. Clinical comparison of monophasic oral contraceptive preparations of gestodene/ ethinyl estradiol and desogestrel/ethinyl estradiol

    OpenAIRE

    Aguiar, Luis Fernando; Aldrighi, Jose Mendes; Andrade, Rosires Pereira de; Barbosa, Ione Cristina; Barreto, Cristina Maria Vasconcellos

    1994-01-01

    Texto completo: acesso restrito. p.201–214 The efficacy, cycle control, subjective complaints, and safety of monophasic preparations of the oral contraceptives containing gestodene 75 mcg plus ethinyl estradiol 30 mcg versus desogestrel 150 mcg plus ethinyl estradiol 30 mcg were compared in a 6-cycle, open-label, parallel, randomized, multicenter phase IV clinical study in Latin America. Of a total of 176 women in each group, 163 in the gestodene group and 160 in the desogestrel group comp...

  5. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    Directory of Open Access Journals (Sweden)

    Kristensen Vessela N

    2011-08-01

    in turn stimulates aromatase expression and hence increases the local production of estradiol. This is the first report studying such associations in normal breast tissue in humans.

  6. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    International Nuclear Information System (INIS)

    Haakensen, Vilde D; Børresen-Dale, Anne-Lise; Helland, Åslaug; Bjøro, Trine; Lüders, Torben; Riis, Margit; Bukholm, Ida K; Kristensen, Vessela N; Troester, Melissa A; Homen, Marit M; Ursin, Giske

    2011-01-01

    High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the

  7. Shifting Attention

    Science.gov (United States)

    Ingram, Jenni

    2014-01-01

    This article examines the shifts in attention and focus as one teacher introduces and explains an image that represents the processes involved in a numeric problem that his students have been working on. This paper takes a micro-analytic approach to examine how the focus of attention shifts through what the teacher and students do and say in the…

  8. Effect of Estradiol Prescribed during Luteal Phase of Art Cycles and Pregnancy Outcome

    Directory of Open Access Journals (Sweden)

    M Karimzadeh

    2007-01-01

    Full Text Available Introduction: Implantation is one of the most important steps in ART cycles and it depends upon embryo and endometrial reception. Different protocols have been suggested for getting better endometrium. It seems estrogen increases the endometrial reception and pregnancy rate by inducing changes in the hormonal status. The aim of this study was to evaluate the effect of estradiol(E2 on luteal phase support and pregnancy rate in ART cycles Methods: This prospective randomized study was done in Yazd at the IVF center from March until December, 2002. 68 patients who had undergone IVF or ICSI were enrolled in the study. Exclusion criteria was age>40, endometriosis and ovarian hyper stimulation syndrome. Induction ovulation protocol was long suppression with GnRH analogues.After embryo transfer, patients were divided in two groups randomly. Both groups received 100mg progesterone IM daily from the transfer day. Estradiol valerate 2 mg/day was added from the 7th transfer day to progesterone in Group I and continued if the BhCG became positive. Abortion and malformations were measured in all patients. Data analyzed with SPSS 11.0 and P value <0.05 considered statistically significant. Results: Pregnancy rate in the 34 patients of estradiol group (group I was 26.5%which was significantly higher than 11.8 %( 4 cases in the other group (Pvalue=0.034. Abortion rate was higher in estradiol group (3 cases, but there was no abortion in the progesterone group(P=0.119. 2 cases of major fetal malformations were observed in E2 supplementation group (P=0.246 . Conclusions: E2 suplementation to progesterone in the luteal phase of ART cycles, especially in the long GnRH analogues causes higher endometrial receptivity and pregnancy rate.

  9. GnRH Neuron Activity and Pituitary Response in Estradiol-Induced vs Proestrous Luteinizing Hormone Surges in Female Mice.

    Science.gov (United States)

    Silveira, Marina A; Burger, Laura L; DeFazio, R Anthony; Wagenmaker, Elizabeth R; Moenter, Suzanne M

    2017-02-01

    During the female reproductive cycle, estradiol exerts negative and positive feedback at both the central level to alter gonadotropin-releasing hormone (GnRH) release and at the pituitary to affect response to GnRH. Many studies of the neurobiologic mechanisms underlying estradiol feedback have been done on ovariectomized, estradiol-replaced (OVX+E) mice. In this model, GnRH neuron activity depends on estradiol and time of day, increasing in estradiol-treated mice in the late afternoon, coincident with a daily luteinizing hormone (LH) surge. Amplitude of this surge appears lower than in proestrous mice, perhaps because other ovarian factors are not replaced. We hypothesized GnRH neuron activity is greater during the proestrous-preovulatory surge than the estradiol-induced surge. GnRH neuron activity was monitored by extracellular recordings from fluorescently tagged GnRH neurons in brain slices in the late afternoon from diestrous, proestrous, and OVX+E mice. Mean GnRH neuron firing rate was low on diestrus; firing rate was similarly increased in proestrous and OVX+E mice. Bursts of action potentials have been associated with hormone release in neuroendocrine systems. Examination of the patterning of action potentials revealed a shift toward longer burst duration in proestrous mice, whereas intervals between spikes were shorter in OVX+E mice. LH response to an early afternoon injection of GnRH was greater in proestrous than diestrous or OVX+E mice. These observations suggest the lower LH surge amplitude observed in the OVX+E model is likely not attributable to altered mean GnRH neuron activity, but because of reduced pituitary sensitivity, subtle shifts in action potential pattern, and/or excitation-secretion coupling in GnRH neurons. Copyright © 2017 by the Endocrine Society.

  10. Negative regulation of glucose metabolism in human myotubes by supraphysiological doses of 17β-estradiol or testosterone.

    Science.gov (United States)

    Garrido, Pablo; Salehzadeh, Firoozeh; Duque-Guimaraes, Daniella E; Al-Khalili, Lubna

    2014-09-01

    Exposure of skeletal muscle to high levels of testosterone or estrogen induces insulin resistance, but evidence regarding the direct role of either sex hormone on metabolism is limited. Therefore, the aim of this study was to investigate the direct effect of acute sex hormone exposure on glucose metabolism in skeletal muscle. Differentiated human skeletal myotubes were exposed to either 17β-estradiol or testosterone and metabolic characteristics were assessed. Glucose incorporation into glycogen, glucose oxidation, palmitate oxidation, and phosphorylation of key signaling proteins were determined. Treatment of myotubes with either 17β-estradiol or testosterone decreased glucose incorporation into glycogen. Exposure of myotubes to 17β-estradiol reduced glucose oxidation under basal and insulin-stimulated conditions. However, testosterone treatment enhanced basal palmitate oxidation and prevented insulin action on glucose and palmitate oxidation. Acute stimulation of myotubes with testosterone reduced phosphorylation of S6K1 and p38 MAPK. Exposure of myotubes to either 17β-estradiol or testosterone augmented phosphorylation GSK3β(Ser9) and PKCδ(Thr505), two negative regulators of glycogen synthesis. Treatment of myotubes with a PKC specific inhibitor (GFX) restored the effect of either sex hormone on glycogen synthesis. PKCδ silencing restored glucose incorporation into glycogen to baseline in response to 17β-estradiol, but not testosterone treatment. An acute exposure to supraphysiological doses of either 17β-estradiol or testosterone regulates glucose metabolism, possibly via PKC signaling pathways. Furthermore, testosterone treatment elicits additional alterations in serine/threonine kinase signaling, including the ribosomal protein S6K1 and p38 MAPK. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. FSH to estradiol ratio can be used as screening method for mild cognitive impairment in postmenopausal women.

    Science.gov (United States)

    Hestiantoro, A; Wiwie, M; Shadrina, A; Ibrahim, N; Purba, J S

    2017-12-01

    To determine the role of anthropometric measurement, menopausal symptoms and biochemical marker changes as screening methods for mild cognitive impairment (MCI) in postmenopausal women Methods: A cross-sectional study included 282 postmenopausal women in Jakarta, further classified into two groups, with and without MCI. Some related variables such as age, body mass index (BMI), duration of menopause, vasomotor symptoms, hormone levels such as follicle stimulating hormone (FSH), luteinizing hormone, leptin, estradiol, and cognitive status, were assessed and analyzed. The FSH levels significantly correlated with MCI incidence (p = 0.018), along with the ratio of FSH/estradiol levels (p = 0.029) and ratio of FSH/soluble leptin receptor (p = 0.011), while other variables did not. By multivariate analysis, the ratio of FSH/estradiol was known as the most significant factor with a probability of having MCI in menopausal women of 1.15. Using the ROC curve, the threshold of the ratio FSH/estradiol to predict MCI was 1.94, with sensitivity 66.5% and specificity 46.8%. The ratio of FSH to estradiol (>1.94) can be used as a screening method for the occurrence of MCI in postmenopausal women.

  12. Estradiol-mediated hepatocyte growth factor is involved in the implantation of endometriotic cells via the mesothelial-to-mesenchymal transition in the peritoneum.

    Science.gov (United States)

    Ono, Yoshihiro J; Hayashi, Masami; Tanabe, Akiko; Hayashi, Atsushi; Kanemura, Masanori; Terai, Yoshito; Ohmichi, Masahide

    2015-06-01

    The pathogenesis of endometriosis, a chronic painful gynecological disease characterized by the presence of endometrial tissue located outside of the uterus and often adhering to the peritoneum, is known to be estrogen dependent. However, the precise pathophysiology of endometriosis remains elusive. Recent studies indicate that the epithelial-to-mesenchymal transition (EMT) of human endometrial cells is important for the progression of endometriosis, and another previous study has implicated hepatocyte growth factor (HGF) in endometriosis progression. The aim of the present study was to examine the role of estradiol in the regulation of HGF production and progression of peritoneal endometriosis, focusing on the interactions between the peritoneum and endometriotic cells. Consequently, estradiol was found to promote the proliferation, invasion, and migration of immortalized human endometrial epithelial cells (hEECs) via HGF upregulation, and the estradiol-induced direct binding of estrogen receptor-α to the HGF promoter was confirmed on a chromatin immunoprecipitation (ChIP) assay. Estradiol also induced the EMT in hEECs by promoting HGF production. Furthermore, human mesothelial cells underwent the mesothelial-to-mesenchymal transition (MMT) during culture with estradiol-stimulated hEEC conditioned medium. Importantly, estradiol itself did not induce the MMT, and the estradiol-stimulated hEEC-conditioned medium in the presence of HGF antibodies reversed the MMT process. These results, which were obtained using immortalized hEECs, indicate that estradiol-induced HGF production may play a crucial role in the peritoneal implantation of human endometriotic cells by exerting proliferative and invasive effects via the EMT in hEECs and promoting the MMT in mesothelial cells. Copyright © 2015 the American Physiological Society.

  13. Endocrine disrupter - estradiol - in Chesapeake Bay tributaries

    Energy Technology Data Exchange (ETDEWEB)

    Dorabawila, Nelum [University of Maryland Eastern Shore, Princess Anne, MD 21853 (United States); Gupta, Gian [University of Maryland Eastern Shore, Princess Anne, MD 21853 (United States)]. E-mail: gcgupta@umes.edu

    2005-04-11

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

  14. Endocrine disrupter - estradiol - in Chesapeake Bay tributaries

    International Nuclear Information System (INIS)

    Dorabawila, Nelum; Gupta, Gian

    2005-01-01

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

  15. Dose-dependent effect of 17 beta-estradiol determined by growth curves and flow cytometric DNA analysis of a human breast carcinoma (T61) grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Spang-Thomsen, M; Vindeløv, L

    1985-01-01

    An estrogen and progesterone receptor-positive human breast carcinoma (T61) grown in nude mice was exposed to 1.0, 0.1, 0.01, and 0.001 mg 17 beta-estradiol. These doses resulted in serum peak concentrations (day 1) of estradiol ranging from 3.5 X 10(-8) to 6.9 X 10(-10) M. The effect...... fraction of polyploid cells. The results suggest that estradiol induces a dose-dependent cell killing effect in the T61 human breast carcinoma. The correlation between the treatment-induced growth delay and the effect on the cell cycle distribution indicates that the changes in the cell cycle...... are a reflection of the estradiol-induced cell destruction. Since no tumor growth stimulation could be observed even at very low serum estradiol concentrations, the T61 human breast carcinoma may represent a new aspect in the study of human breast cancer....

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Estradiol valerate and dienogest: a new approach to oral contraception

    OpenAIRE

    Kiley, Jessica; Kiley,Jessica

    2011-01-01

    Jessica W Kiley, Lee P ShulmanSection of Family Planning and Contraception, Department of Obstetrics and Gynecology, Feinberg School of Medicine of Northwestern University, Chicago, IL, USAAbstract: Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill c...

  18. Progesterone initiates Wnt-beta-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells.

    Science.gov (United States)

    Rider, Virginia; Isuzugawa, Kazuto; Twarog, Meryl; Jones, Stacy; Cameron, Brent; Imakawa, Kazuhiko; Fang, Jianwen

    2006-12-01

    Progesterone pretreatment of ovariectomized rat uteri increases the number of synchronously proliferating stromal cells in response to estradiol 17-beta. To identify the signals involved in stimulating synchronous proliferation, sexually mature ovariectomized rats were injected with progesterone (2 mg) for 3 consecutive days. Estradiol 17-beta (0.2 microg) was administered to initiate cell cycle entry. Uterine samples were removed at various times after hormone administration and changes in wingless (Wnt) pathway effectors and gene targets were identified by microarray. Progesterone pretreatment decreased glycogen synthase kinase-3beta (GSK-3beta) and increased expression of T-cell factor/lymphoid enhancer factor (TCF/LEF). GSK-3beta protein decreased markedly in the uterine stroma of progesterone-pretreated uteri with the concomitant appearance of beta-catenin in these stromal cells. Translocation of beta-catenin from the cytosol to the nuclei in progesterone-pretreated stromal cells was stimulated in response to estradiol. Beta-catenin binding to TCF/LEF increased (P<0.05) in progesterone-pretreated uteri in response to estradiol. Progesterone stimulated the expression of the Wnt target gene urokinase plasminogen activator receptor (uPA-R) in the periluminal uterine stromal cells. The expression of uPA-R increased in progesterone-pretreated stromal cells in response to estradiol administration. Together, the results indicate that progesterone initiates Wnt signaling in the uterine stroma by down-regulating GSK-3beta. However, nuclear translocation of beta-catenin and sufficient complex formation with TCF/LEF to activate stromal cell cycle entry requires estradiol. Stimulation of a uterine stromal cell line to proliferate and differentiate resulted in beta-catenin accumulation, suggesting that endocrine-dependent Wnt signaling controls proliferation and differentiation (decidualization).

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

    International Nuclear Information System (INIS)

    Jozan, S.; Faye, J.C.; Tournier, J.F.; Tauber, J.P.; David, J.F.; Bayard, F.

    1985-01-01

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

  20. Tough Shift

    DEFF Research Database (Denmark)

    Brewer, Robert S.; Verdezoto, Nervo; Holst, Thomas

    2015-01-01

    people to change their behavior at home. Leveraging prior research on encouraging reductions in residential energy use through game play, we introduce ShareBuddy: a casual mobile game intended to encourage players not only to reduce, but also to shift their electricity use. We conducted two field studies...... real-world resource use into a game....

  1. Different chemo- and endocrino-sensitivity of MCF-7 cells with or without estradiol supplement in vitro.

    Science.gov (United States)

    Tanino, H; Kubota, T; Saikawa, Y; Kuo, T H; Takeuchi, T; Kase, S; Furukawa, T; Kitajima, M; Sakurai, T; Naito, Y

    1993-01-01

    The sensitivity of MCF-7 cells to tamoxifen (TAM) and mitomycin C (MMC) was assessed in rapidly and slowly growing cells with or without estradiol supplementation, respectively. The growth of MCF-7 was inhibited by MMC in a concentration-dependent manner with or without estradiol (E2) supplementation. Preincubation with MMC suppressed subsequent E2 stimulated growth of MCF-7. TAM inhibited the growth of MCF-7 supplemented with E2 and preincubation with TAM prevented subsequent E2 stimulated growth of MCF-7. However, TAM did not inhibit the growth of MCF-7 cells in E2 free medium. These results suggested that MMC may be more effective than TAM on breast cancer cells in the dormant or slow-growth phase.

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Effects of acupuncture and electroacupuncture on estradiol-induced inflammation and oxidative stress in health rodents.

    Science.gov (United States)

    Santos, Elba Lucia Wanderley; Dias, Bruno Hállan Meneses; Andrade, Ana Carolina Rodrigues de; Pascoal, Angélica Maria Holanda; Vasconcelos Filho, Francisco Eugênio de; Medeiros, Francisco das Chagas; Guimarães, Sergio Botelho

    2013-08-01

    To investigate the effects of classical acupuncture (Ac) and electroacupuncture (EAc) on estradiol-induced inflammation and oxidative stress in health rodents. Twenty-four eight-week old female rats were treated with estradiol valerate (EV) 4.0 mg i.m. single dose and randomly assigned to four groups (n=6): G1(control), G2 (Ac), G3 (EAc 2 Hz) and G4 (EAc 100 Hz). After 60 days all rats were anesthetized with chloral hydrate 10% (0.1 ml/30 g weight of the animal) and submitted to Ac/EAc for twenty minutes. The procedures were repeated on days three, five, seven and nine of the study. The equivalent of the human right ST-36 (Zusanli) and SP-6 (Sanyinjiao) acupoints were chosen for needling and electrical stimulation. On the 10th day of the experiment, all rats were anesthetized for collection of blood and tissues (ovaries) samples for biochemical analysis and histological examination. Glutathione (GSH) and malonaldehyde (MDA) concentrations increased significantly in all groups (plasma and ovary) while myeloperoxidase (MPO) activity decreased significantly in all groups compared with control group (G1). Both classical acupuncture and electroacupuncture decrease systemic and local oxidative stress and ovary inflammation in healthy rats exposed to estrogenic stimulation. EAc enhances lipid peroxidation at systemic and local levels in female rats exposed to estrogenic stimulation.

  4. High Estradiol Levels During Postmenopause - Pitfalls in Laboratory Analysis.

    Science.gov (United States)

    Mebes, I; Graf, M; Kellner, M; Keck, C; Segerer, S E

    2015-09-01

    A 54-year-old woman was admitted with a result of high serum estradiol levels (> 4300 pg/ml) and typical postmenopausal symptoms. She had a history of an adnexectomy (normal histopathology) due to the elevated estradiol levels. After surgery, estradiol levels were as high as before. Analyzing the anti-mullerian hormone (AMH), inhibin B, DHEA-S and estrone, typical postmenopausal levels were found. Serum estradiol levels were controlled several times with rabbit-derived polyclonal as well as monoclonal antibodies to optimize the selectivity of the test system. Secondary, a radioimmunoassay was performed to exclude interferences of the detection system where lower, but still elevated estradiol levels (186 pg/ml) were found. Hypothesizing that our patient underwent a cross reaction with irregular antibodies, a control was done using sheep-derived antibodies, which proved a postmenopausal hormone level (estradiol level irregular antibodies (> 200 mg/l; reference < 30 mg/l). This case depicts the pitfalls of estradiol measurement detecting false elevated estradiol levels in a postmenopausal woman.

  5. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate. 522.842 Section 522.842 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in...

  6. Invited commentary: dietary fiber, estradiol, and cholesterol.

    Science.gov (United States)

    Levitan, Emily B

    2011-01-15

    The limitations of examining mediating factors by adjusting for them in standard regression models have been well-documented in the literature. Although alternative analytic models have been suggested, they are rarely used. In the accompanying article, Mumford et al. (Am J Epidemiol. 2010;173(2):145-156) use marginal structural linear mixed models to determine the association between dietary fiber intake and cholesterol through pathways that do not involve estradiol. Their findings suggest that overall high fiber intake decreases levels of total and low density lipoprotein (LDL) cholesterol and that there are multiple pathways through which fiber can act. The estradiol-mediated pathway seems to lead to increases in total and LDL cholesterol which are more than counterbalanced by pathways leading to decreases in total and LDL cholesterol. In addition to answering a scientifically interesting question, this work provides a concrete example of the use of marginal structural models for examination of direct effects and may serve as a guide to future researchers.

  7. Estradiol impairs the Th17 immune response against Candida albicans.

    Science.gov (United States)

    Relloso, Miguel; Aragoneses-Fenoll, Laura; Lasarte, Sandra; Bourgeois, Christelle; Romera, Gema; Kuchler, Karl; Corbí, Angel L; Muñoz-Fernández, M Angeles; Nombela, César; Rodríguez-Fernández, José L; Diez-Orejas, Rosalia

    2012-01-01

    Candida albicans is a commensal opportunistic pathogen that is also a member of gastrointestinal and reproductive tract microbiota. Exogenous factors, such as oral contraceptives, hormone replacement therapy, and estradiol, may affect susceptibility to Candida infection, although the mechanisms involved in this process have not been elucidated. We used a systemic candidiasis model to investigate how estradiol confers susceptibility to infection. We report that estradiol increases mouse susceptibility to systemic candidiasis, as in vivo and ex vivo estradiol-treated DCs were less efficient at up-regulating antigen-presenting machinery, pathogen killing, migration, IL-23 production, and triggering of the Th17 immune response. Based on these results, we propose that estradiol impairs DC function, thus explaining the increased susceptibility to infection during estrus.

  8. Relationship between Estradiol and Antioxidant Enzymes Activity of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Nasrin Sheikh

    2009-01-01

    Full Text Available Some evidence suggests the neuroprotection of estrogen provided by the antioxidant activity of this compound. The main objective of this study was to determine the level of estradiol and its correlation with the activity of antioxidant enzymes, total antioxidant status and ferritin from ischemic stroke subjects. The study population consisted of 30 patients with acute ischemic stroke and 30 controls. There was no significant difference between estradiol in stroke and control group. The activity of superoxide dismutase and level of ferritin was higher in stroke compared with control group (<.05, <.001, resp.. There was no significant correlation between estradiol and glutathione peroxidase, glutathione reductase, catalase, total antioxidant status, and ferritin in stroke and control groups. We observed inverse correlation between estradiol with superoxide dismutase in males of stroke patients (=−0.54, =.029. Our results supported that endogenous estradiol of elderly men and women of stroke or control group has no antioxidant activity.

  9. Estradiol valerate/dienogest: a novel oral contraceptive.

    Science.gov (United States)

    Whalen, Karen L; Rose, Renee

    2011-10-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of the new oral contraceptive estradiol valerate/dienogest. Searches of PubMed (1966-July 2011) and International Pharmaceutical Abstracts (1970-July 2011) were conducted using the key words estradiol valerate, dienogest, Natazia, and Qlaira. Bibliographies of retrieved articles were reviewed to identify additional references. All identified studies published in English and involving efficacy and safety of estradiol valerate/dienogest as an oral contraceptive were reviewed. Estradiol valerate/dienogest is a 4-phasic oral contraceptive approved for the prevention of pregnancy. The 4-phasic design allows for acceptable cycle control with this hormonal combination. In efficacy trials of estradiol valerate/dienogest in women aged 18-35 years, the Pearl Index ranged from 0.40 to 1.64, a range comparable to that of other combination oral contraceptives. The safety profile was also similar to that of other oral contraceptives, with headache, metrorrhagia, breast tenderness, nausea or vomiting, acne, and weight gain reported as the most common adverse effects. Menstrual bleeding patterns and cycle control with estradiol valerate/dienogest were comparable to those of a monophasic oral contraceptive containing ethinyl estradiol/levonorgestrel. Estradiol valerate/dienogest differs from other oral contraceptives in that it necessitates more stringent dosing guidelines for maximum contraceptive efficacy. New starts should be on the first day of menses only, and a back-up method of contraception is required for the first 9 days, as compared to 7 days with other oral contraceptives. Back-up contraception is usually required for any pill taken more than 12 hours later than scheduled. Estradiol valerate/dienogest is an effective oral contraceptive. Because it has more stringent start times and requires a longer duration of backup contraception and stricter adherence, estradiol valerate/dienogest should be reserved

  10. Estradiol determines the effects of PTH on ERα-dependent transcription in MC3T3-E1 cells.

    Science.gov (United States)

    Christensen, Monika H E; Fenne, Ingvild S; Flågeng, Marianne H; Almås, Bjørg; Lien, Ernst A; Mellgren, Gunnar

    2014-07-18

    Bone remodeling is a continuous process regulated by several hormones such as estrogens and parathyroid hormone (PTH). Here we investigated the influence of PTH on estrogen receptor alpha (ERα)-dependent transcriptional activity in MC3T3-E1 osteoblasts. Cells that were transfected with an ER-responsive reporter plasmid and treated with PTH showed increased luciferase activity. However, in the presence of 17β-estradiol, we observed that PTH inhibited ERα-mediated transcription. cAMP mimicked the effects by PTH, and the findings were confirmed in COS-1 cells transfected with expression vector encoding the catalytic subunit of cAMP-dependent protein kinase (PKA). Furthermore, PTH exhibited specific effects on the mRNA expression of the decoy receptor osteoprotegerin (OPG) and the receptor activator of NF kappa-B ligand (RANKL) in MC3T3-E1 osteoblasts. In the absence of 17β-estradiol, PTH and cAMP enhanced the OPG/RANKL ratio, whereas, OPG/RANKL was suppressed when estradiol was present. In conclusion, our results indicate that the presence of estradiol determines whether PTH and cAMP stimulates or inhibits ERα-dependent activity and the OPG/RANKL mRNA expression in an osteoblastic cell line. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Ultrastructural and enzyme-histochemical studies of the prostate of the dog under the effect of estradiol.

    Science.gov (United States)

    Hohbach, C

    1977-07-01

    The prostate of 4 mature pure bred Beagles 12 months old was studied 3 weeks following a single i.m. injection of 1 mg estradiol/kg body weight by means of histochemistry (acid and alcaline phosphatase) and electron microscopy. Four 11 months old Beagles served as controls. Estradiol leads to a variable reaction of glandular epithelium. There is an atrophy of active secretory cells, probably due to an inhibition of the release of ICSH by the anterior pituitary lobe, that in turn leads to a deficiency of androgens. The residual secretory function is not sufficient for normal synthesis of secretory granules, recognizable through the decrease in electron density of secretory granules and the extensive loss of activity of acid phosphatase. Under physiologic conditions it corresponds in its localization to the amount of secretory granules lying in the apical portion of the cytoplasm. The basal reserve cells show an ambivalence. Normally under the predominant influence of androgen they do not show any metaplasia, but they differentiate into the secretorely active epithelial cell. Without stimulation by androgens, estradiol leads to a basal cell proliferation with squamous metaplasia particularly in the dorso-lateral lobes close to the urethra. The activity of alcaline phosphatase shows a minor decrease in the capillary endothelium under estradiol. With increasing maturation of the metaplastic squamous epithelium the activity of alcaline phosphatase increases in the upper cell layer.

  12. Biphasic Estradiol-induced AKT Phosphorylation Is Modulated by PTEN via MAP Kinase in HepG2 Cells

    Science.gov (United States)

    Marino, Maria; Acconcia, Filippo; Trentalance, Anna

    2003-01-01

    We reported previously in HepG2 cells that estradiol induces cell cycle progression throughout the G1–S transition by the parallel stimulation of both PKC-α and ERK signaling molecules. The analysis of the cyclin D1 gene expression showed that only the MAP kinase pathway was involved. Here, the presence of rapid/nongenomic, estradiol-regulated, PI3K/AKT signal transduction pathway, its modulation by the levels of the tumor suppressor PTEN, its cross-talk with the ERK pathway, and its involvement in DNA synthesis and cyclin D1 gene promoter activity have all been studied in HepG2 cells. 17β-Estradiol induced the rapid and biphasic phosphorylation of AKT. These phosphorylations were independent of each other, being the first wave of activation independent of the estrogen receptor (ER), whereas the second was dependent on ER. Both activations were dependent on PI3K activity; furthermore, the ERK pathway modulated AKT phosphorylation by acting on the PTEN levels. The results showed that the PI3K pathway, as well as ER, were strongly involved in both G1–S progression and cyclin D1 promoter activity by acting on its proximal region (-254 base pairs). These data indicate that in HepG2 cells, different rapid/nongenomic estradiol-induced signal transduction pathways modulate the multiple steps of G1–S phase transition. PMID:12808053

  13. Fluid Shifts

    Science.gov (United States)

    Stenger, M. B.; Hargens, A. R.; Dulchavsky, S. A.; Arbeille, P.; Danielson, R. W.; Ebert, D. J.; Garcia, K. M.; Johnston, S. L.; Laurie, S. S.; Lee, S. M. C.; hide

    2017-01-01

    Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid

  14. Shifting Blame?

    DEFF Research Database (Denmark)

    Garofalo, Orsola; Rott, Christina

    2017-01-01

    either the decision maker or a spokesperson communicates the decided allocation to recipients, who then determine whether to punish either of them. We find that receivers punish both the decision maker and the spokesperson more often, and more heavily, for unfair allocations communicated...... by the spokesperson if there is room for shifting blame. The increased punishment results from the messenger’s style of delivery: spokespersons are more likely than decision makers to express emotional regret instead of rational need. Receivers seem to punish the former style of communication because they view...

  15. CONCENTRATION OF ESTRADIOL IN DOGS (BITCHES IN SPRINGTIME

    Directory of Open Access Journals (Sweden)

    Edina Hajdarević

    2013-09-01

    Full Text Available Measuring of estradiol level in the peripheral blood in dog is important for the precise estrus detection. In proestrus, estradiol dominates. In estrus, however, estradiol progressively decreases while progesterone and LH increase, the latter shortly and abruptly. The research of Feldman and Nelson (7 indicates that the beginning of the sexual cycle of the female dog is the result of complex interaction of the environment, general health condition, condition of the ovaries, condition of the uterus, animal age, and some unidentified factors. Estradiol level in the peripheral circulation is starting to rise before the beginning of the proestrus, and during the proestrus the female dog is under the influence of estradiol (4. Our research included 30 female dogs on the territory of Tuzla Municipality, in the springtime. The female dogs were divided in three groups according to the breeding and living conditions: group A (female dogs living in the house environment; group B (female dogs living in the shelter; group C (female stray dogs. For the researched groups, estradiol level varied between 6,265 pg\\ml and 69,734 pg\\ml over the springtime. Of importance is the results can be applied in the evaluation of estrus in the female dogs, and when considering factors crucial for their sustainable reproduction potential.Key words: dogs, estradiol, spring

  16. Involvement of CART in estradiol-induced anorexia.

    Science.gov (United States)

    Dandekar, Manoj P; Nakhate, Kartik T; Kokare, Dadasaheb M; Subhedar, Nishikant K

    2012-01-18

    Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significant decrease in food intake as compared with that in OVX controls. Intracerebroventricular (icv) administration of CART (0.5-1 μg/rat) to OVX rats, resulted in a dose-dependent reduction in the food intake. The lower dose (0.25 μg) had no effect, and was considered subeffective. In estradiol replaced OVX rats, CART at subeffective dose, further reduced food intake. However, CART failed to reduce food intake in estradiol replaced OVX rats pretreated with anti-estrogenic agent tamoxifen (3 mg/kg, subcutaneous). Administration of CART antibody (1:500 dilution/rat, i.c.v.) significantly attenuated estradiol-induced anorexia in the OVX rats. While estradiol replacement significantly increased CART-immunoreactivity in the cells/fibers of paraventricular nucleus (PVN) of OVX rats, fibers in the anteroventral periventricular nucleus (AVPV), and cells/fibers in the arcuate nucleus (ARC) showed considerable reduction. These changes were attenuated following concurrent injection of tamoxifen to the estradiol replaced OVX rats. However, CART-immunoreactive cells/fibers in the periventricular area did not respond to any of the treatments. We suggest that estradiol treatment might influence the hypothalamic CART system in a site specific manner. While increased CART activity in the PVN might produce anorexia, reduction of CART in ARC and AVPV might represent a compensatory homeostatic response. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 17β-estradiol modifies human spermatozoa mitochondrial function in vitro.

    Science.gov (United States)

    Kotwicka, Malgorzata; Skibinska, Izabela; Jendraszak, Magdalena; Jedrzejczak, Piotr

    2016-08-26

    It is assumed that spermatozoa are target cells for estrogens however, the mechanism of their action is not fully understood. The aim of this study was to investigate the influence of 17β-estradiol (E2) on the human spermatozoa mitochondrial function. The effects on spermatozoa of E2 at final concentrations of 10(-10), 10(-8) and 10(-6) M were studied regarding the following phenomena: (1) kinetics of intracellular free calcium ions changes (using Fluo-3), (2) mitochondrial membrane potential ΔΨm (using JC-1 fluorochrome), (3) production of superoxide anion in mitochondria (using MitoSOX RED dye), (4) spermatozoa vitality (propidium iodide staining) and (5) phosphatidylserine membrane translocation (staining with annexin V marked with fluorescein). E2 initiated rapid (within a few seconds) dose dependent increase of intracellular free calcium ions concentration. E2 was changing the mitochondrial membrane potential: 10(-8) M initiated significant increase of percentage of high ΔΨm spermatozoa while the 10(-6) M induced significant decrease of high ΔΨm cells. In spermatozoa stimulated with E2 10(-6) M a significant increase of mitochondrial superoxide anion level was observed. 2 h incubation of spermatozoa with E2 did not alter cells vitality nor stimulated phosphatidylserine membrane translocation, for all three doses. 17β-estradiol affected the human spermatozoa mitochondrial function. E2 in low concentration improved while in high concentration might deteriorate mitochondrial function.

  18. Renewal of conditioned responding to food cues in rats: Sex differences and relevance of estradiol.

    Science.gov (United States)

    Anderson, Lauren C; Petrovich, Gorica D

    2015-11-01

    Cues associated with food can stimulate food anticipation, procurement, and consumption, independently of hunger. These and other behaviors driven by learned cues are persistent and can reappear after extinction, because the original learned associations continue to exist. Renewal, or reinstatement, of extinguished conditioned behavior may explain the inability to change maladaptive eating habits driven by food cues, similar to the mechanisms of drug use relapse. Here, we investigated sex differences in context-induced renewal of responding to food cues, and the role of estradiol in females in a Pavlovian conditioning preparation. We compared adult male and female rats because there is evidence for sex differences in learning and memory and in the control of feeding. Context-induced renewal involves conditioning and extinction in different contexts and the renewal of conditioned behavior is induced by return to the conditioning context ("ABA renewal"; experimental groups). Control groups remain in the same context during conditioning, extinction, and test. In Experiment 1, male and female rats were trained to associate a tone with food pellets during acquisition, and after extinction with tone only presentations, were tested for renewal of responding to the tone. Learning was assessed through the expression of the conditioned response, which included approach and activity directed at food receptacle (food cup behavior). Males and females learned the acquisition and extinction of tone-food associations similarly, but there were sex differences during renewal of the conditioned responses to the food cue. Males showed robust renewal of responding, while renewal in intact females was inconsistent. Males in the experimental group had significantly higher food cup behavior compared to males in the control group, while females in both groups showed similar levels of food cup behavior during the tone. In Experiment 2, we examined a potential role of estradiol in renewal

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

    DEFF Research Database (Denmark)

    Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla

    2009-01-01

    for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents...... agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates......: rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression...

  20. Evaluation of serum estradiol/ progestrone ratio on day of embryo transfer and it’s effect on intra-cytoplasmic sperm induction outcome

    Directory of Open Access Journals (Sweden)

    Masomeh Hagshafiha

    2013-07-01

    Full Text Available Background : One of the important problems in fertilization in vitro (IVF is failure of implantation. This could be the result of estrogen and progesterone effects in endometrial acceptance during ovulation stimulation. Although progesterone has a vital role in primary phase of pregnancy, but the estradiol role in luteal phase is unknown. The aim of this study is assessment of the ratio of estradiol to progesterone in embryo transfer day on Intracytoplasmic sperm injection (ICSI outcomes. Methods : This is a cohort study. The subjects were 311 infertile women referred to Urmia Kosar infertility clinic & Urmia reproductive health research center who treated with ICSI method between August-Jan 2011 . Five cc blood was drawn for determine of estradiol and progesterone in transfer day. Transfer occurred after a variable in vitro culture period ranging from 48 to 72 hours after ovulation induction. Chemiluminescent ELICA the level of mention hormones was used to determine the ratio of the progesterone level to the estradiol serum level and was compared based on treatment outcomes. Results : A total of 311 patients, 115 (37% were pregnant and happened abortion were 18 (5.8% . The mean ratio of estradiol to progesterone in transfer day in two groups of miscarriage/ non miscarriage and pregnant/ non pregnant was 32.26±23.86 , 28.17±26.5 and 28.58±2.4 , 36.09±4.39 respectively. There is no significant difference between two groups in regard of estradiol on progesterone ratio (P=0.5, P= 0.2 . Conclusion: The results of this prospective cohort study show that there is no effect of estradiol to progesterone ratio on day of embryo transfer, successful pregnancy in ICSI cycles and abortion rate following of ICSI .

  1. Dispersal of estradiol-17 beta from the site of injection in the pectoral muscles of Japanese quail

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, G.A.

    1985-09-01

    Exogenous estrogens, if given in sufficient quantity, stimulate vitellogenesis in the males of vitellogenic species. In the present study, ethanolic solutions of estradiol-17 beta (E2), labeled with 16-alpha-( SVI)iodoestradiol (( SVI)E2) or sodium iodide (Na SVI), were injected into the pectoral muscles of male Japanese quail. The rate of dispersal of the estradiol from the site of injection was measured in vivo during 4 days. The curves of radioactivity appeared to be diphasic. The dose percentages forming the second phase of these curves and the half-time for the second phase were: for 16 mumol E2 (( SVI)E2 label)/100 g body weight, 84.6% and 27.6 hr; for 6 pmol ( SVI)E2/100 g, 20.0% and 17.2 hr; for 16 mumol E2 (Na SVI label)/100 g, 6.7% and 99.0 hr, and for Na SVI, 6.1% and 83.1 hr. Thus, in male quail the estradiol-induced stimulation of vitellogenesis apparently resulted from a continuing hormonal pressure on the liver during the period of study and not from a rapid flow of E2 to the liver shortly after injection.

  2. Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca^{2+} efflux in rat caudate nucleus and brain stem

    OpenAIRE

    PETROVIC, SNJEZANA; MILOSEVIC, MAJA; RISTIC-MEDIC, DANIJELA; VELICKOVIC, NATASA; DRAKULIC, DUNJA; GRKOVIC, IVANA; HORVAT, ANICA

    2015-01-01

    Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca^{2+} efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl_2 (0.6?0.75 µCi ^45CaCl_{2}) was used for Ca^{2+} transport monitoring. The results revealed that in the presence of ER antagonist 7\\alpha,17ß-[9[(4,4,5,5,5-...

  3. Shifting Sugars and Shifting Paradigms

    Science.gov (United States)

    Siegal, Mark L.

    2015-01-01

    No organism lives in a constant environment. Based on classical studies in molecular biology, many have viewed microbes as following strict rules for shifting their metabolic activities when prevailing conditions change. For example, students learn that the bacterium Escherichia coli makes proteins for digesting lactose only when lactose is available and glucose, a better sugar, is not. However, recent studies, including three PLOS Biology papers examining sugar utilization in the budding yeast Saccharomyces cerevisiae, show that considerable heterogeneity in response to complex environments exists within and between populations. These results join similar recent results in other organisms that suggest that microbial populations anticipate predictable environmental changes and hedge their bets against unpredictable ones. The classical view therefore represents but one special case in a range of evolutionary adaptations to environmental changes that all organisms face. PMID:25688600

  4. Shifting sugars and shifting paradigms.

    Directory of Open Access Journals (Sweden)

    Mark L Siegal

    2015-02-01

    Full Text Available No organism lives in a constant environment. Based on classical studies in molecular biology, many have viewed microbes as following strict rules for shifting their metabolic activities when prevailing conditions change. For example, students learn that the bacterium Escherichia coli makes proteins for digesting lactose only when lactose is available and glucose, a better sugar, is not. However, recent studies, including three PLOS Biology papers examining sugar utilization in the budding yeast Saccharomyces cerevisiae, show that considerable heterogeneity in response to complex environments exists within and between populations. These results join similar recent results in other organisms that suggest that microbial populations anticipate predictable environmental changes and hedge their bets against unpredictable ones. The classical view therefore represents but one special case in a range of evolutionary adaptations to environmental changes that all organisms face.

  5. 17β-estradiol-induced ACSL4 protein expression promotes an invasive phenotype in estrogen receptor positive mammary carcinoma cells.

    Science.gov (United States)

    Belkaid, Anissa; Ouellette, Rodney J; Surette, Marc E

    2017-04-01

    Long chain acyl-CoA synthase-4 (ACSL4) expression has been associated with an aggressive phenotype in breast carcinoma cells, whereas its role in ERα-positive breast cancer has not been studied. ACSL4 prefers 20-carbon polyunsaturated fatty acid (PUFA) substrates, and along with other ACSLs has been associated with cellular uptake of exogenous fatty acids. 17β-estradiol induces proliferation and invasive capacities in ERα+ve breast carcinoma that is associated with modifications of cellular lipid metabolism. In this study, treatment of steroid-starved ERα-positive MCF-7 and T47D mammary carcinoma cells with 17β-estradiol resulted in increased cellular uptake of the PUFA arachidonic acid (AA) and eicosapentaenoic acid (EPA), important building blocks for cellular membranes, and increased ACSL4 protein levels. There was no change in the expression of the ACSL1, ACSL3 and ACSL6 protein isotypes. Increased ACSL4 protein expression was not accompanied by changes in ACSL4 mRNA expression, but was associated with a significant increase in the protein half-life compared to untreated cells. ERα silencing reversed the impact of 17β-estradiol on ACSL4 protein levels and half-life. Silencing of ACSL4 eliminated the 17β-estradiol-induced increase in AA and EPA uptake, as well as the 17β-estradiol-induced cell migration, proliferation and invasion capacities. ASCL4 silencing also prevented the 17β-estradiol induced increases in p-Akt and p-GSK3β, and decrease in E-cadherin expression, important events in epithelial to mesenchymal transition. Taken together, these results demonstrate that ACSL4 is a target of 17β-estradiol-stimulated ERα and is required for the cellular uptake of exogenous PUFA and the manifestation of a more malignant phenotype in ERα+ve breast carcinoma cells. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Estradiol and cognitive function: Past, present and future

    Science.gov (United States)

    Luine, Victoria N.

    2014-01-01

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

  7. 3D model of amphioxus steroid receptor complexed with estradiol

    International Nuclear Information System (INIS)

    Baker, Michael E.; Chang, David J.

    2009-01-01

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ERα are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ERα in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  8. 3D model of amphioxus steroid receptor complexed with estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Michael E., E-mail: mbaker@ucsd.edu [Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693 (United States); Chang, David J. [Department of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693 (United States)

    2009-08-28

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  9. Estradiol valerate and dienogest: a new approach to oral contraception

    Directory of Open Access Journals (Sweden)

    Kiley JW

    2011-08-01

    Full Text Available Jessica W Kiley, Lee P ShulmanSection of Family Planning and Contraception, Department of Obstetrics and Gynecology, Feinberg School of Medicine of Northwestern University, Chicago, IL, USAAbstract: Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V with dienogest (DNG in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.Keywords: estradiol valerate, dienogest, oral contraception, combination

  10. Impact of peak/mid luteal estradiol on pregnancy outcome after intracytoplasmic sperm injection

    International Nuclear Information System (INIS)

    Rehman, R.; Hussain, Z.; Zahir, H.

    2014-01-01

    Objective: To compare peak to mid estradiol ratio with the probability of successful conception after intra-cytoplasmic sperm injection. Method: The quasi-experimental study was conducted in an infertility clinic at Islamabad from June 2010 till August 2011, and comprised couples subjected to intra-cytoplasmic sperm injection. Down-regulation of ovaries was followed by calculated stimulation, ovulation induction, oocytes retrieval, intra cytoplasmic sperm injection, in vitro maturation of embryos and finally blastocysts transfer. Serum estradiol was measured by enzyme-linked immunosorbent assay on ovulation induction day and the day of embryo transfer. Failure of procedure was detected by beta human chorionic gonadotropin 5-25mIU/ml (Group I; non-pregnant). Females with beta human chorionic gonadotropin>25mIU/ml and no cardiac activity after 4 weeks of transfer were placed in Group II (pre-clinical abortion), and confirmation of foetal heart in the latter comprised Group III (clinical pregnancy). Data was analysed using SPSS 15. Results: Of the 323 couples initially enrolled, embryo transfer was carried out in 282(87.3%) females. Clinical pregnancy was achieved in 101(36%) of the cases, while 61(21.63%) had pre-clinical abortion, and 120(42%) remained non-pregnant. The peak/mid-luteal estradiolratio was low (2.3) in patients who had high oocyte maturity (p=0.001) and fertilisation rate (p=0.003) compared to non-pregnant patients with high peak/mid-luteal estradiolratio (2.56). Conclusion: High peak estradiol with maintenance of optimal levels in mid-luteal phase is required for implantation of fertilised ovum and accomplishment of clinical pregnancy. (author)

  11. 17β-Estradiol enhances sulforaphane cardioprotection against oxidative stress.

    Science.gov (United States)

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

    2017-04-01

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

  12. Nomegestrol acetate/estradiol hormonal oral contraceptive and breast cancer risk.

    Science.gov (United States)

    Del Pup, Lino; Berretta, Massimiliano; Di Francia, Raffaele; Cavaliere, Carla; Di Napoli, Marilena; Facchini, Gaetano; Fiorica, Francesco; Mileto, Mario; Schindler, Adolf E

    2014-08-01

    Combined hormonal contraceptives (CHCs) contain estrogen and progestin, which can stimulate estrogen-sensitive and/or progesterone-sensitive breast cancer growth. Until recently, ethinylestradiol had been almost the only estrogen used for decades, and its dose has been greatly reduced over time. The first generations of birth control pills contained approximately five times more estrogen and four times more progestin than the latest contraceptives. Newer CHCs also contain steroids that more closely mimic the physiological estradiol (E2) and progesterone effects. The newer CHC formulations are thus expected to have less influence on the breast, although it is very difficult to demonstrate any difference among the recent available preparations in human studies. Recently, nomegestrol acetate (NOMAC), a neutral, nonandrogenic, progesterone-like profile progestin, has become available in combination with the 'natural' estrogen, E2. According to the literature, NOMAC/E2 is expected to have either a lesser stimulating effect or a neutral effect on estrogen-sensitive breast cancers. We performed an analysis of the available studies and a bibliographical review. The endocrine and metabolic effects of NOMAC/E2 formulation might lead to a lesser breast tissue stimulation. The data reported, confirmed through clinical studies, should be considered when choosing a hormonal contraceptive, especially when breast stimulation is a concern.

  13. ANTIBODIES TO BENZO[A]PYRENE, ESTRADIOL AND PROGESTERONE IN THE POSTMENOPAUSAL BREAST CANCER WOMEN

    Directory of Open Access Journals (Sweden)

    A. N. Glushkov

    2016-01-01

    Full Text Available The identification of women who are at high risk of developing breast cancer plays a key role in chemoprevention of breast cancer selective estrogen receptor modulators. purpose: To study specific immune responses to chemical carcinogens and sex steroid hormones associated with breast cancer in postmenopausal women. material and methods. Serum IgA-antibodies specific to benzo[a]pyrene, estradiol and progesterone were studied in 203 non-smoking healthy women and 469 non-smoking breast cancer patients (125 with ER– and 344 with ER+ using semi-quantitative enzyme immunoassay. results. The low levels of all three antibodies were revealed in 53.2 % of healthy donors, in 47.2 % of breast cancer patients with ER– and in 40.7 % of patients with ER+. The high levels of all three antibodies were found in 12.3 %, 18.4 % and 26.5 % of cases, respectively. In the studied groups, the levels of antibodies to estradiol and progesterone were correlated with the levels of antibodies to benzo[a]pyrene (rs=0.54–0.7, p<0.0001. Conclusion. Immunoassay of antibodies to exogenous and endogenous antigens could be useful for determining risk of developing ER+ breast cancer and preventing administration of tamoxifen and others selective modulators of estrogen receptors. Active immunization against exogenous chemical carcinogens could increase the levels of antibodies to endogenous steroids, thus stimulating breast cancer.

  14. Bladder function in 17β-estradiol-induced nonbacterial prostatitis model in Wistar rat.

    Science.gov (United States)

    Matsumoto, Seiji; Kawai, Yuko; Oka, Michiko; Oyama, Tatsuya; Hashizume, Kazumi; Wada, Naoki; Hori, Jun-ichi; Tamaki, Gaku; Kita, Masafumi; Iwata, Tatsuya; Kakizaki, Hidehiro

    2013-06-01

    To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17β-estradiol injection. Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

  15. Ovarian Drilling Efficacy, Estradiol Levels and Pregnancy Rate in Females With Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Moramezi

    2015-02-01

    Full Text Available Background Polycystic ovary syndrome (PCOS is the most common cause of oligoovulation and anovulation in general population and in females with infertility. Objectives The purpose of this study was to compare the efficacy of ovarian laparoscopic drilling procedure (LOD in females with PCOS, resistant to treatment with estradiol (E2 level less than 40 pg/mL versus more than 40 pg/mL. Materials and Methods Females with PCOS, resistant to drug for ovary stimulation, were grouped based on the Estradiol levels of ≤ 40 pg/mL (n = 13 and > 40 pg/mL (n = 15. To survey the ovulation, continuing spontaneous ovulation and cumulative pregnancy rate, ovarian laparoscopic drilling was carried out after the analysis of serum E2. Results There was significant difference in the average starting time of ovulation and continuing spontaneous ovulation of cases with PCOS with E2 levels > 40 pg/mL, compared with ones with E2 ≤ 40 pg/mL (P = 0.029, P = 0.05, respectively. Significant differences were also found in pregnancy rates of cases with PCOS with E2 levels > 40 pg/mL compared with ones with E2 ≤ 40 pg/mL (P = 0.05. Conclusions This study revealed that LOD in females with PCOS with a serum E2 > 40 pg/mL was sufficient and safe to trigger development of ovarian follicles followed by clinical pregnancy.

  16. Sex hormone binding globulin, free estradiol index, and lipid profiles in girls with precocious puberty

    Directory of Open Access Journals (Sweden)

    Hyun-Wook Chae

    2013-06-01

    Full Text Available PurposeSex hormone-binding globulin (SHBG modulates the availability of biologically active free sex hormones. The regulatory role of SHBG might be important in the relationship between hormone levels and the modification of lipid profiles in girls with precocious puberty. However, few studies have evaluated the relationship of SHBG, free estradiol index (FEI, and lipid levels in these girls.MethodsOne hundred and nine girls less than 8 years of age with pubertal development were enrolled. FEI was calculated with SHBG and estradiol (E2. We analyzed SHBG between peak luteinizing hormone (LH≥5 (IU/L (group 1 and LH<5 (IU/L (group 2 through a gonadotropin releasing hormone stimulation test.ResultsBody mass index (BMI standard deviation score (SDS was higher in group 2 than in group 1 (P=0.004. Serum SHBG levels did not differ and FEI was not higher in group 1 (P=0.122. Serum cholesterol, HDL, and LDL did not differ; however, triglyceride levels were higher in group 2 (P=0.023. SHBG was negatively correlated with bone age advancement, BMI, BMI SDS, and FEI, and was positively correlated with HDL. However, SHBG was not correlated with E2 or peak LH.ConclusionSerum SHBG itself might not be associated with precocious puberty in girls, but it might be related to BMI and lipid profiles. Further studies are needed to reveal the relationship between sex hormone and obesity in girls with precocious puberty.

  17. Estradiol valerate and dienogest: a new approach to oral contraception

    Science.gov (United States)

    Kiley, Jessica W; Shulman, Lee P

    2011-01-01

    Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol. PMID:21892339

  18. The role of estradiol in male reproductive function

    Directory of Open Access Journals (Sweden)

    Michael Schulster

    2016-01-01

    Full Text Available Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone′s effects on erectile function, spermatogenesis, and libido.

  19. The role of estradiol in male reproductive function

    Science.gov (United States)

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  20. The role of estradiol in male reproductive function.

    Science.gov (United States)

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido.

  1. Estradiol valerate and dienogest: a new approach to oral contraception.

    Science.gov (United States)

    Kiley, Jessica W; Shulman, Lee P

    2011-01-01

    Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.

  2. Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta.

    Science.gov (United States)

    Rossi, Dania V; Dai, Ying; Thomas, Peter; Carrasco, Gonzalo A; DonCarlos, Lydia L; Muma, Nancy A; Li, Qian

    2010-08-01

    Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since desensitization of 5-HT(1A) receptors may be an underlying mechanism by which selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is important to determine which estrogen receptors are capable of desensitizating 5-HT(1A) receptor function. We previously demonstrated that selective activation of the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower binding affinity than estradiol for GPR30. Administration of DPN did not desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by agonist-stimulated hormone release. Second, we used a recombinant adenovirus containing ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in ERbeta did not alter the estradiol-induced desensitization of 5-HT(1A) receptor signaling in oxytocin cells. In contrast, in animals with reduced ERbeta, estradiol administration, instead of producing desensitization, augmented the ACTH response to a 5-HT(1A) agonist. Combined with the results from the DPN treatment experiments, desensitization of 5-HT(1A) receptor signaling does not appear to be mediated by ERbeta in oxytocin cells, but that ERbeta, together with GPR30, may play a complex role in central regulation of 5-HT(1A)-mediated ACTH release. Determining the mechanisms by which estrogens induce desensitization may aid in the development of better treatments for mood disorders. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. IN VITRO STUDY OF THE EFFECT OF 17β-ESTRADIOL AND 4-NONYLPHENOL ON BOVINE SPERMATOZOA

    Directory of Open Access Journals (Sweden)

    Jana Lukáčová

    2012-10-01

    Full Text Available Nonylphenol (NP, an environmental endocrine disruptor, is a final metabolite of nonylphenol ethoxylate (NPE that is able to interfere with hormonal system of numerous organisms. Estrogens play a central role in female reproduction, but also affect the male reproductive system. In males, stimulate mammalian spermatozoa capacitation, acrosome reaction and fertilizing ability. The aim of this in vitro study was to determine the effect of 17β-estradiol and nonylphenol (NP on the spermatozoa motility. Specifically, we examined the dose- and time-dependent effect of nonylphenol (1, 10, 100 and 200 µg/mL with the addition 1 µg/mL of 17β-estradiol on the motility and progressive motility of bovine spermatozoa during two time periods (0 h and 6 h. The spermatozoa motility was determined by CASA (Computer Assisted Semen Analyzer system using the Sperm VisionTM program. The results showed decreased average values of motility in all experimental groups during 0 h of in vitro cultivation. The motility and the progressive motility of bovine spermatozoa increased in the experimental groups using concentrations 10, 100 and 200 µg/mL after 6 h of cultivation and significant differences (P<0.05 were detected between these groups and the control group. The results suggest that the addition of 17β-estradiol could positively affect spermatozoa motility during the short-term cultivation of spermatozoa with NP.

  4. Plasma and faecal testosterone and estradiol in chicken

    International Nuclear Information System (INIS)

    Mekchay, S.; Apichartsrungkoon, T.; Pongpiachan, P.

    1996-01-01

    Identification of sex in some kind of fowls can not be done by using their external appearances. Sex steroid hormone levels may be used as an indicator of sexual dimorphism in birds. The objective of this investigation was to measure plasma and faecal testosterone and estradiol concentrations in 8 male and 15 female chickens by using radioimmunoassay (RIA) technique. The relationship between plasma and faecal testosterone, and plasma and faecal estradiol are positively correlated. The correlation coefficients (r 2 ) between plasma and faecal steroids concentration were 0.621 (p<0.05) for testosterone and 0.692 (p<0.05) for estradiol. The average plasma and faecal sex steroid concentrations in male and female chickens were 10.05 ± 1.97 ng/ml and 511.50 ± 95.89 ng/g (for male testosterone), 24.85 ± 1.60 pg/ml and 49.65 ± 6.01 ng/g (for male estradiol), 0.79 ± 0.05 ng/ml and 134.20 ± 14.70 ng/ml (for female testosterone), 129.91 ± 19.30 pg/ml and 334.80 ± 15.62 ng/g (for female estradiol), respectively. Plasma and faecal testosterone and estradiol levels in male and female chickens are significant difference (p<0.01, p<0.01, p<0.001 and p<0.001 respectively). The results of this investigation suggested that plasma or faecal sex steroid concentrations can be used to discriminate sex of chicken which is show the possibility to use the plasma or faecal sex steroids for identification of sex in other bird species

  5. Dissipation of 17β-estradiol in composted poultry litter.

    Science.gov (United States)

    Hakk, Heldur; Sikora, Lawrence

    2011-01-01

    The excreted estrogen rate of all livestock in the United States is estimated at 134 kg d. The influence of manure treatment on the fate of estrogens is critical in deciding the recycling of over 300 million dry tons of livestock produced annually. The effects of two common manure management practices, heated composting and ambient temperature decomposition, on the fate of 17β-estradiol in poultry litter were determined. A mixture of poultry litter, wood chips, and straw was amended with [C]17β-estradiol and allowed to undergo decomposition with a laboratory-scale heated composter (HC) or room temperature incubation (RTI) for 24 d. Radiolabel in the finished products was fractionated into water-extractable, acetone-extractable, nonextractable, and mineralized fractions. Total 17β-estradiol radioactive residues in the HC and RTI ( = 2) treatments were not different ( > 0.05), except that statistically less 17β-estradiol was mineralized to CO during HC than RTI (1.1 vs. 10.0% for HC and RTI, respectively). Estrone was the major degradation product in extracts of HC and RTI treatments as determined by liquid chromatography/mass spectrometry analyses. The nonextractable residues indicated no quantitative differences among the humins between the treatments. An estimated 3% of the fortified estrogenicity remained after HC treatment, and 15% of the fortified estrogenicity remained after RTI treatment. If reduction of water-removable, biologically active 17β-estradiol is the treatment goal, then HC treatment would be slightly preferred over ambient temperature degradation. However, unmanaged, ambient temperature litter piles are less costly and time consuming for food animal producers and result in greater mineralization and similar immobilization of estradiol. by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  6. Comparison of mild stimulation and conventional stimulation in ART outcome.

    Science.gov (United States)

    Karimzadeh, Mohammad Ali; Ahmadi, Shahnaz; Oskouian, Homa; Rahmani, Elham

    2010-04-01

    To provide a treatment for particular condition that is the most effective treatment with the least risk and cost for the patient we compared the efficacy of using clomiphene 100 mg + delayed low dose gonadotropin + flexible GnRH antagonist administration for ovarian stimulation protocol and GnRH agonist + gonadotropin for stimulation protocol in IVF outcome. Clinical outcome of 243 women with regularly menstruation who were candidate for IVF. They had undergone stimulation with GnRH agonist and gonadotropin (group A) or clomiphene citrate, gonadotropin and GnRH antagonist (group B). Main outcome was ongoing pregnancy. There were no significant difference in mean age, cause of infertility, basal FSH, BMI, duration of infertility, endometrial thickness on the day HCG administration in two groups. The number of recovered oocytes, obtained embryos, transferred embryos, peak of estradiol on the day HCG administration and OHSS were significantly higher in group A. Significantly more patients in control group had embryos for cryopreservation. There were no significant difference in clinical pregnancy rate and ongoing pregnancy rate between two groups. Clomiphene + delayed low dose gonadotropin + flexible GnRH - antagonist stimulation is an acceptable alternative protocol for IVF in patients with regularly menstruation.

  7. Cardiovascular risk markers during treatment with estradiol and trimegestone or dydrogesterone

    NARCIS (Netherlands)

    Hellgren, M.; Conard, J.; Norris, L.; Kluft, C.

    2009-01-01

    Objective: To study cardiovascular risk markers in women taking estradiol/trimegestone or estradiol/dydrogesterone. Design: Multicenter, randomized, prospective, double-blind study of 184 healthy post-menopausal women randomized to 6 cycles of either estradiol (2 mg) + trimegestone (0.5 mg)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  9. A Mouse Model of Hypospadias Induced by Estradiol Benzoate.

    Science.gov (United States)

    He, Hou-Guang; Han, Cong-Hui; Zhang, Wei

    2015-12-01

    We wished to establish a mouse model of hypospadias using injections of estradiol benzoate for investigating the molecular mechanisms of hypospadias. Fifty timed pregnant mice were randomly divided into five study groups: A, B, C, D, and E. These groups were injected subcutaneously with estradiol benzoate mixed with sesame oil at, respectively, the doses of 0, 0.1, 0.5, 2.5, or 12.5 mg kg(-1) days(-1) from gestation day (GD) 12 to GD 16. The pups' mortality was recorded on the day of delivery. Urethras and positions of testes were examined on postnatal day 28. The numbers of live pups were significantly lower in the study groups D and E compared to study group A (p Hypospadias was seen in groups C (3.3 %; 1/30), D (18.2 %; 4/22), and E (21.4 %; 3/14), while cryptorchidism was observed in groups C (10 %; 3/30), D (31.8 %; 7/22), and E (57.1 %; 8/14) on postnatal day 28. The experimental model of hypospadias induced by estradiol benzoate in the group D (2.5 mg kg(-1) days(-1)) was more reliable considering high mortality of the study group E. The dose of estradiol benzoate used in the group D is suitable for establishing mouse model of hypospadias.

  10. 21 CFR 862.1260 - Estradiol test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862...

  11. Response surface method applied to optimization of estradiol ...

    Indian Academy of Sciences (India)

    torial design was built for the determination of the main factors affecting estradiol permeation. The independent factors analysed were: ... lation, waste water treatment, packaging in food industry and textile dyeing (Ravi Kumar 2000; ... Experimental design and optimization are tools that are used to systematically examine ...

  12. Response surface method applied to optimization of estradiol ...

    Indian Academy of Sciences (India)

    An optimization process based on response surface methodology was carried out in order to develop a statistical model which describes the relationship between active independent variables and estradiol flux. This model can be used to find out a combination of factor levels during response optimization. Possible options ...

  13. Estradiol levels in prepubertal boys and girls--analytical challenges

    DEFF Research Database (Denmark)

    Bay, Katrine; Andersson, Anna-Maria; Skakkebaek, Niels E

    2004-01-01

    Increasing evidence points at an important function of low concentrations of estradiol (E2) in prepubertal boys and girls. E2 serum levels in prepubertal children are, however, often immeasurable in conventional E2 assays. This strongly hampers further investigation of the physiological relevance...

  14. Supported liquid membrane extraction of 17ß- estradiol

    African Journals Online (AJOL)

    b- estradiol and its metabolites, namely 17b-estriol and estrone in various biological matrices and water. The biological matrices in which extraction was done included bovine kidney and liver tissues, milk and urine. The liquid membrane used to trap these compounds was made of 5% tri-n-octylphosphine oxide (TOPO) ...

  15. Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus

    Energy Technology Data Exchange (ETDEWEB)

    Mistry, A.; Vijayan, E.

    1985-05-27

    Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of /sup 3/H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis. 18 references, 4 tables.

  16. Interleukin 6, interleukin 1β, estradiol and testosterone ...

    African Journals Online (AJOL)

    Jane

    2011-08-22

    Aug 22, 2011 ... Key words: Oocyte maturation, follicular fluid, interleukin 6, interleukin 1β, testosterone, estradiol. INTRODUCTION. A complex of hormones, growth factors and cytokines regulates the ovarian function. The interaction between immune and endocrine systems is triggered by the action of immune cells within ...

  17. Supported liquid membrane extraction of 17β- estradiol and its ...

    African Journals Online (AJOL)

    Administrator

    2006-10-02

    Oct 2, 2006 ... A sample purification and enrichment technique involving the use of supported liquid membrane (SLM) has been developed for the selective extraction of 17β- estradiol and its metabolites, namely 17β-estriol and estrone in various biological matrices and water. The biological matrices in which extraction ...

  18. Biotransformation of Я-estradiol isolated from Sonchus eruca

    African Journals Online (AJOL)

    Administrator

    2011-06-20

    Jun 20, 2011 ... Key words: Microbial transformation, Я-estradiol (1,3,5-estratriene-3,17,Я-diols), Bacillus subtillus, Aspergillus niger, lipoxygenase. INTRODUCTION ... needed for well defined chemical transformation. An alternative way of structural ... med on Jasco DIP-360 digital polarimeter. Melting point was taken.

  19. Dosage of estradiol, bone and body composition in Turner syndrome

    DEFF Research Database (Denmark)

    Cleemann, Line; Holm, Kirsten; Kobbernagel, Hanne

    2017-01-01

    OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17ß-estradiol in young TS women on bone...

  20. Effect of estradiol and oxytocin on ovine cervical relaxation

    African Journals Online (AJOL)

    Yomi

    2012-02-07

    Feb 7, 2012 ... Key words: Ewes, Estradiol, Oxytocin, Cervical dilation. INTRODUCTION. Artificial insemination (AI) is a good way for the use of superior rams in reproduction ..... tropical sheep using cervical silicone moulds. Anim. Reprod. Sci. 85: 337-344. Salamon S, Maxwell WMC (1995). Frozen storage of ram semen I.

  1. 17 beta-estradiol affects osmoregulation in Fundulus heteroclitus

    NARCIS (Netherlands)

    Mancera, J.M.; Smolenaars, M.; Laiz-Carrion, R.; Rio, M. del; Wendelaar Bonga, S.E.; Flik, G.

    2004-01-01

    The effect of 17beta-estradiol (ED on osmoregulatory performance was examined in the euryhaline killifish, Fundulus heteroclitus. Fish were injected once with 1, 2 and 5 mug g(-1) E-2 and, 6 h after injection, transferred from I ppt seawater (SW) to full strength SW (40 ppt) or from SW to I ppt SW.

  2. Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

    Science.gov (United States)

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W.; Saunders, Philippa T.K.

    2016-01-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1–differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. PMID:26073038

  3. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis.

    Science.gov (United States)

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W; Saunders, Philippa T K

    2015-08-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1-differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Correlation among thermosensitive period, estradiol response, and gonad differentiation in the sea turtle Lepidochelys olivacea.

    Science.gov (United States)

    Merchant-Larios, H; Ruiz-Ramirez, S; Moreno-Mendoza, N; Marmolejo-Valencia, A

    1997-09-01

    Reptile embryos with temperature sex determination have a thermosensitive period (TSP). The finding that exogenous estradiol (E2) overcomes the effect of male-promoting temperature led to the idea that temperature may regulate estrogen concentration in the gonad during TSP. Since interspecific variations in TSP and in the effect of exogenous E2 exist, we undertook a study in the olive ridley Lepidochelys olivacea. Four parameters were correlated: the TSP (time dimension), the thermosensitive stages (rate of development), gonad development (histological aspect), and the estradiol response. Two kinds of experiments were performed: (1) Eggs were shifted once, at different stages of development, from a male-promoting temperature to a female-temperature (or vice versa) for the remainder of development. (2) Eggs at male-promoting temperature were treated once with 6 or 12 microg of estradiol (E2) at various times of incubation. Sex ratio was established around hatching in each experimental series. We found that the temporal dimension of the TSP was around 7 days (Days 20-27 of incubation) at a male-promoting or a female-promoting temperature. The rate of development of the whole embryo and gonadal growth was faster at female-promoting temperature than at male-promoting temperature. Formation of the genital ridge began at stage 21-22 and histological differentiation of the gonads occurred around stage 26-27. Although these stages coincided with the TSP, at male-promoting temperature the thermosensitive stages occurred earlier (from stages 20-21 to stages 23-24) than at female-promoting temperature (from stages 23-24 to stages 26-27). Thus, at male promoting-temperature, sex was determined in embryos with incipient or undifferentiated gonads. In contrast, E2 treatment continued to feminize the gonads of embryos at a male-promoting temperature beyond the TSP up to stage 25-26, but the E2-induced ovaries were significantly smaller than temperature-induced ovaries. It is

  5. Estradiol and reproduction in the South American toad Rhinella arenarum (Amphibian, Anura).

    Science.gov (United States)

    Scaia, María Florencia; Volonteri, María Clara; Czuchlej, Silvia Cristina; Ceballos, Nora Raquel

    2018-03-16

    Rhinella arenarum is a South American toad with wide geographic distribution. Testes of this toad produce high amount of androgens during the non reproductive season and shift steroid synthesis from androgens to 5α-pregnanedione during the breeding. In addition, plasma estradiol (E 2 ) in males of this species shows seasonal variations but, since testes of R. arenarum do not express aromatase, the source of plasma E 2 remained unknown for several years. However, the Bidder's organ (BO), a structure located at one pole of each testis, is proposed to be the main source of E 2 in male's toads since it expresses several steroidogenic enzymes and is able to produce E 2 from endogenous substrates throughout the year. In addition, there were significant correlations between plasma E 2 and total activity of BO aromatase, and between plasma E 2 and the amount of hormone produced by the BO in vitro. In the toad, apoptosis induced by in vitro treatment with E 2 was mostly detected in spermatocytes during the breeding and in spermatids during the post-reproductive season, suggesting that this steroid has an important role in controlling spermatogenesis. However, in vitro treatment with E 2 had no effect on proliferation. This evidence suggests that the mechanism of action of E 2 on amphibian spermatogenesis is complex and more studies are necessary to fully understand the role of estrogens regulating the balance between cellular proliferation and apoptosis. In addition, in R. arenarum in vitro studies suggested that E 2 has no effect on CypP450c17 protein levels or enzymatic activity, while it reduces 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD/I) activity during the post reproductive season. As well, E 2 regulates FSHβ mRNA expression all over the year suggesting a down regulation process carried out by this steroid. The effect on LHβ mRNA is dual, since during the reproductive season estradiol increases the expression of LHβ mRNA while in the non

  6. Involvement of miR-106b in tumorigenic actions of both prolactin and estradiol.

    Science.gov (United States)

    Chen, Kuan-Hui Ethan; Bustamante, Karissa; Nguyen, Vi; Walker, Ameae M

    2017-05-30

    Prolactin promotes a variety of cancers by an array of different mechanisms. Here, we have investigated prolactin's inhibitory effect on expression of the cell cycle-regulating protein, p21. Using a miRNA array, we identified a number of miRNAs upregulated by prolactin treatment, but one in particular that was strongly induced by prolactin and predicted to bind to the 3'UTR of p21 mRNA, miR-106b. By creating a p21 mRNA 3'UTR-luciferase mRNA construct, we demonstrated degradation of the construct in response to prolactin in human breast, prostate and ovarian cancer cell lines. Increased expression of miR-106b replicated, and anti-miR-106b counteracted, the effects of prolactin on degradation of the 3'UTR construct, p21 mRNA levels, and cell proliferation in breast (T47D) and prostate (PC3) cancer cells. Increased expression of miR-106b also stimulated migration of the very epithelioid T47D cell line. By contrast, anti-miR-106b dramatically decreased expression of the mesenchymal markers, SNAIL-2, TWIST-2, VIMENTIN, and FIBRONECTIN. Using signaling pathway inhibitors and the 3'UTR construct, induction of miR-106b by prolactin was determined to be mediated through the MAPK/ERK and PI3K/Akt pathways and not through Jak2/Stat5 in both T47D and PC3 cells. Prolactin activation of MAPK/ERK and PI3K/Akt also activates ERα in the absence of an ERα ligand. 17β-estradiol promoted degradation of the construct in both cell lines and pre-incubation in the estrogen antagonist, Fulvestrant, blocked the ability of both prolactin and 17β-estradiol to induce the construct-degrading activity. Together, these data support a convergence of the prolactin and 17β-estradiol miR-106b-elevating signaling pathways at ERα.

  7. The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

    Directory of Open Access Journals (Sweden)

    Pejic S.

    2003-01-01

    Full Text Available The sensitivity of copper,zinc (CuZn- and manganese (Mn-superoxide dismutase (SOD to exogenous estradiol benzoate (EB was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 µg EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%, 8 (72.7% and 15 (81.7%. In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6% disappeared on day 8 and on days 15 and 45 it became inhibitory (40.3 and 30.5%, respectively. EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8% changed to an inhibitory effect on day 8 (38.4% and disappeared by day 45 when inhibition was detected again (48.7%. In males, the inhibitory effect on this enzyme was observed on days 0 (45.0% and 15 (28.9%, and then disappeared until day 60 when a stimulatory effect was observed (38.4%. EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process.

  8. 17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib.

    Science.gov (United States)

    Girgert, Rainer; Emons, Günter; Gründker, Carsten

    2017-02-01

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

  9. Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region.

    Science.gov (United States)

    Grassi, S; Tozzi, A; Costa, C; Tantucci, M; Colcelli, E; Scarduzio, M; Calabresi, P; Pettorossi, V E

    2011-09-29

    In the hippocampal formation many neuromodulators are possibly implied in the synaptic plasticity such as the long-term potentiation (LTP) induced by high-frequency stimulation (HFS) of afferent fibers. We investigated the involvement of locally synthesized neural 17β-estradiol (nE(2)) in the induction of HFS-LTP in hippocampal slices from male rats by stimulating the Schaffer collateral fibers and recording the evoked field excitatory postsynaptic potential (fEPSP) in the CA1 region. We demonstrated that either the blockade of nE(2) synthesis by the aromatase inhibitor letrozole, or the antagonism of E(2) receptors (ERs) by ICI 182,780 did not prevent the induction of HFS-LTP, but reduced its amplitude by ∼60%, without influencing its maintenance. Moreover, letrozole and ICI 182,780 did not affect the first short-term post-tetanic component of LTP and the paired-pulse facilitation (PPF). These findings demonstrate that nE(2) plays an important role in the induction phase of HFS-dependent LTP. Since the basal responses were not affected by the blocking agents, we suggest that the synthesis of nE(2) is induced or enhanced by HFS through aromatase activation. In this context, the local production of nE(2) seems to be a very effective mechanism to modulate the amplitude of LTP. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Actions and interactions of estradiol and glucocorticoids in cognition and the brain: Implications for aging women.

    Science.gov (United States)

    Ycaza Herrera, Alexandra; Mather, Mara

    2015-08-01

    Menopause involves dramatic declines in estradiol production and levels. Importantly, estradiol and the class of stress hormones known as glucocorticoids exert countervailing effects throughout the body, with estradiol exerting positive effects on the brain and cognition, glucocorticoids exerting negative effects on the brain and cognition, and estradiol able to mitigate negative effects of glucocorticoids. Although the effects of these hormones in isolation have been extensively studied, the effects of estradiol on the stress response and the neuroprotection offered against glucocorticoid exposure in humans are less well known. Here we review evidence suggesting that estradiol-related protection against glucocorticoids mitigates stress-induced interference with cognitive processes. Animal and human research indicates that estradiol-related mitigation of glucocorticoid damage and interference is one benefit of estradiol supplementation during peri-menopause or soon after menopause. The evidence for estradiol-related protection against glucocorticoids suggests that maintaining estradiol levels in post-menopausal women could protect them from stress-induced declines in neural and cognitive integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Actions and interactions of estradiol and glucocorticoids in cognition and the brain: Implications for aging women.

    Science.gov (United States)

    Herrera, Alexandra Ycaza; Mather, Mara

    2015-01-01

    Menopause involves dramatic declines in estradiol production and levels. Importantly, estradiol and the class of stress hormones known as glucocorticoids exert countervailing effects throughout the body, with estradiol exerting positive effects on the brain and cognition, glucocorticoids exerting negative effects on the brain and cognition, and estradiol able to mitigate negative effects of glucocorticoids. Although the effects of these hormones in isolation have been extensively studied, the effects of estradiol on the stress response and the neuroprotection offered against glucocorticoid exposure in humans are less well known. Here we review evidence suggesting that estradiol-related protection against glucocorticoids mitigates stress-induced interference with cognitive processes. Animal and human research indicates that estradiol-related mitigation of glucocorticoid damage and interference is one benefit of estradiol supplementation during peri-menopause or soon after menopause. The evidence for estradiol-related protection against glucocorticoids suggests that maintaining estradiol levels in post-menopausal women could protect them from stress-induced declines in neural and cognitive integrity. PMID:25929443

  12. Effects of Panax ginseng, zearalenol, and estradiol on sperm function

    OpenAIRE

    Gray, Sandra L.; Lackey, Brett R.; Boone, William R.

    2015-01-01

    Background: Estrogen signaling pathways are modulated by exogenous factors. Panax ginseng exerts multiple activities in biological systems and is classified as an adaptogen. Zearalenol is a potent mycoestrogen that may be present in herbs and crops arising from contamination or endophytic association. The goal of this study was to investigate the impact of P. ginseng, zearalenol and estradiol in tests on spermatozoal function. Methods: The affinity of these compounds for estrogen receptor ...

  13. Membrane-Initiated Estradiol Signaling Regulating Sexual Receptivity

    Science.gov (United States)

    Micevych, Paul E.; Dewing, Phoebe

    2011-01-01

    Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs) has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES) component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor), and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH). Using both activation of μ-opioid receptors (MOR) in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX-receptor participate in the required MIES. ERα and the STX-receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a) that augment progesterone synthesis in astrocytes and protein kinase C (PKC) in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX-receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum, and dorsal root ganglias. PMID:22649369

  14. Membrane–initiated estradiol signaling regulating sexual receptivity

    Directory of Open Access Journals (Sweden)

    Paul E Micevych

    2011-09-01

    Full Text Available Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor; GPER, and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH. Using both activation of μ-opioid receptors (MOR in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX receptor participate in the required MIES. ERα and the STX receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a that augment progesterone synthesis in astrocytes and protein kinase C (PKC in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum and DRGs.

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

    Directory of Open Access Journals (Sweden)

    Burke A

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Barzegar

    2017-12-01

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

  17. Estradiol: a rhythmic, inhibitory, indirect control of meal size.

    Science.gov (United States)

    Eckel, Lisa A

    2004-08-01

    The classic analyses of the inhibitory effects of cholecystokinin (CCK) on meal size, conducted by Professor Gerard P. Smith and his colleagues at the Bourne Laboratory, inspired my initial interest in this field. My current research, which investigates the role of estradiol in the control of meal size, continues to be guided by Gerry's thoughtful, scientific approach to the study of ingestive behavior. In 1996, the year I arrived as a Postdoctoral Fellow at the Bourne Laboratory, Gerry published a new theory of the controls of meal size. In this important paper, Gerry proposed that the controls of meal size can be either direct or indirect. He argued that direct controls of meal size interact with peripheral, preabsorptive receptors that are sensitive to the chemical, mechanical, and colligative properties of ingested food and that indirect controls of meal size function to modulate the activity of direct controls. The purpose of this review is to illustrate how Gerry's theory has guided much of what is known about the mechanism by which estradiol inhibits food intake in female rats. I will provide evidence, primarily from behavioral studies of gonadally intact and ovariectomized rats, that estradiol exerts phasic and tonic inhibitory effects on food intake by acting as a rhythmic, inhibitory, indirect control of meal size.

  18. OpenShift Workshop

    CERN Multimedia

    CERN. Geneva; Rodriguez Peon, Alberto

    2017-01-01

    Workshop to introduce developers to the OpenShift platform available at CERN. Several use cases will be shown, including deploying an existing application into OpenShift. We expect attendees to realize about OpenShift features and general architecture of the service.

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

    Science.gov (United States)

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

    2011-01-01

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

  20. The smallest available estradiol transdermal patch: a new treatment option for the prevention of postmenopausal osteoporosis.

    Science.gov (United States)

    Bertonazzi, Abigail; Nelson, Bridgette; Salvador, Jamie; Umland, Elena

    2015-11-01

    Minivelle(®) (Noven Therapeutics, LLC, FL, USA) is an estradiol transdermal delivery system that has recently been approved in the USA for prevention of postmenopausal osteoporosis. The decline in estrogen during menopause leads to bone resorption, increasing the risk of fractures. Transdermal estradiol has been shown to increase bone mineral density. Safety studies of transdermal estradiol have shown a decreased risk in cardiovascular disease as compared with oral estrogen therapy. Minivelle is currently the smallest available transdermal estradiol patch, providing the lowest effective dose of estrogen.

  1. Effects of 17β-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Weichselbaum, R.R.

    1981-01-01

    The effects of 17β-estradiol, given either alone or with X-radiation, on the induction of malignant transformation were investigated in vitro. Treatment with 10 -6 M 17β-estradiol for 6 weeks, or 10 -5 M 17β-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicated an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation. (author)

  2. Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation

    International Nuclear Information System (INIS)

    Gazzerro, Patrizia; Abbondanza, Ciro; D'Arcangelo, Andrea; Rossi, Mariangela; Medici, Nicola; Moncharmont, Bruno; Puca, Giovanni Alfredo

    2006-01-01

    The retinoblastoma protein-interacting zinc-finger (RIZ) gene, a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumor suppressor. Estradiol treatment of MCF-7 cells produced a selective decrease of RIZ1 transcript and an increase of total RIZ mRNA. Experiments of chromatin immunoprecipitation indicated that RIZ2 protein expression was controlled by estrogen receptor and RIZ1 had a direct repressor function on c-myc gene expression. To investigate the role of RIZ gene products as regulators of the proliferation/differentiation transition, we analyzed the effects of forced suppression of RIZ1 induced in MCF-7 cells by siRNA of the PR domain-containing form. Silencing of RIZ1 expression stimulated cell proliferation, similar to the effect of estradiol on these cells, associated with a transient increase of c-myc expression

  3. Local feedback loop of ghrelin-GH in the pig ovary: action on estradiol secretion, aromatase activity and cell apoptosis.

    Science.gov (United States)

    Rak, Agnieszka; Gregoraszczuk, Ewa Łucja

    2008-06-01

    Ghrelin is recognized as an important regulator of growth hormone (GH) secretion, food intake and a factor which controls reproduction. In the present studies, the effect of GH and insulin-like growth factor (IGF-I) on ghrelin synthesis and secretion and the effects of ghrelin on GH synthesis and secretion in cultured whole porcine follicles were studied. Ghrelin and GH levels were measured in the follicular wall and in the culture medium. Moreover, the action of combined treatment with ghrelin and GH on estradiol secretion, aromatase activity and cell apoptosis were examined. We demonstrated that ghrelin increased GH secretion but not GH synthesis by ovarian follicles. GH stimulated both ghrelin synthesis and secretion in the ovarian follicles. The increase in estradiol secretion, aromatase activity and the decrease in caspase-3 activity were noted in ghrelin alone- and ghrelin in combination with GH-treated cells. In culture treated with combination of both these hormones, all investigated parameters were similar to those noted in ghrelin alone-treated cells. In conclusion, our study provides novel evidence for the gonadal feedback loop between GH and ghrelin secretion in the ovary. However, results of the presented research suggest independent action of GH and ghrelin in the ovary.

  4. Implementing OpenShift

    CERN Document Server

    Miller, Adam

    2013-01-01

    A standard tutorial-based approach to using OpenShift and deploying custom or pre-built web applications to the OpenShift Online cloud.This book is for software developers and DevOps alike who are interested in learning how to use the OpenShift Platform-as-a-Service for developing and deploying applications, how the environment works on the back end, and how to deploy their very own open source Platform-as-a-Service based on the upstream OpenShift Origin project.

  5. Effect of cultivation conditions on β-estradiol removal in laboratory and pilot-plant photobioreactors by an algal-bacterial consortium treating urban wastewater.

    Science.gov (United States)

    Parladé, Eloi; Hom-Diaz, Andrea; Blánquez, Paqui; Martínez-Alonso, Maira; Vicent, Teresa; Gaju, Nuria

    2018-03-03

    The use of microalgal consortia for urban wastewater treatment is an increasing trend, as it allows simultaneous nutrient removal and biomass production. Emerging contaminants proposed for the list of priority substances such as the hormone 17β-estradiol are commonly found in urban wastewater, and their removal using algal monocultures has been accomplished. Due to the inherent potential of algae-based systems, this study aimed to assess the capability of native photobioreactor biomass to remove 17β-estradiol under indoor and outdoor conditions. At the same time, the microbial community changes in regular and bioaugmented operations with Scenedesmus were assessed. The results show that almost complete removal (>93.75%) of the hormone 17β-estradiol can be attained in the system under favourable seasonal conditions, although these conditions greatly influence biomass concentrations and microbial diversity. Even under the harsh conditions of low temperatures and solar irradiation, the established consortium removed more than 50% of the pollutant in 24 h. While species from genus Chlorella were stable during the entire operation, the microbial diversity analysis revealed that assorted and evenly distributed populations stimulate the removal rates. Bioaugmentation assays proved that the input of additional biomass results in higher overall removal and decreases the yield per mg of biomass. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. PROGESTERONE/ESTRADIOL RATIO IN THE LATE FOLLICULAR PHASE OF LONG GONADOTROPIN-RELEASING HORMONE AGONIST CYCLES DID NOT DIFFER BETWEEN CONCEIVED AND NOT-CONCEIVED WOMEN

    Directory of Open Access Journals (Sweden)

    L. Safdarian

    2008-04-01

    Full Text Available There is a challenging debate on the effect of premature luteinization on the clinical outcome of ‘controlled ovarian hyperstimulation' (COH using long ‘gonadotropin-releasing hormone agonist' (GnRHa cycles. Premature luteinization is defined as late follicular progesterone/estradiol ratio more than 1 on the day of human chorionic gonadotropin (HCG administration. We carried out a retrospective case-control study on 75 conceived cases versus 75 not-conceived control women, receiving long GnRHa cycles in their first cycle of treatment. Premature luteinization developed in 15% of the case group vs. 22% of the control group. Neither the late follicular progesterone/estradiol (P/E2 ratio was significantly different between the two groups, nor the day 3 follicle stimulating hormone (FSH, serum estradiol level on the HCG day, total amount of human menopausal gonadotropins ampoules, number of follicles, retrieved oocytes and transferred embryos. Endometrial thickness was significantly more in the pregnant women than in the non-pregnant group. Premature luteinization seems not to adversely affect the clinical outcome of COH.

  7. Brain Stimulation Therapies

    Science.gov (United States)

    ... Magnetic Seizure Therapy Deep Brain Stimulation Additional Resources Brain Stimulation Therapies Overview Brain stimulation therapies can play ... for a shorter recovery time than ECT Deep Brain Stimulation Deep brain stimulation (DBS) was first developed ...

  8. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Homogeneous bilateral block shifts. ADAM KORÁNYI. Department of Mathematics, The Graduate Center, City University of New York,. New York, NY 10016, USA. E-mail: Adam.Koranyi@lehman.cuny.edu. MS received 18 January 2013. Abstract. A new 3-parameter family of homogeneous 2-by-2 block shifts is described.

  9. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    A new 3-parameter family of homogeneous 2-by-2 block shifts is described. These are the first examples of irreducible homogeneous bilateral block shifts of block size larger than 1. Author Affiliations. Adam Korányi1. Department of Mathematics, The Graduate Center, City University of New York, New York, NY 10016, USA ...

  10. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  11. Shifting employment revisited

    NARCIS (Netherlands)

    Cremers, Jan; Gramuglia, Alessia

    2014-01-01

    The CLR-network examined in 2006 the phenomenon of undeclared labour, with specific regard to the construction sector. The resulting study, Shifting Employment: undeclared labour in construction (Shifting-study hereafter), gave evidence that this is an area particularly affected by undeclared

  12. OpenShift cookbook

    CERN Document Server

    Gulati, Shekhar

    2014-01-01

    If you are a web application developer who wants to use the OpenShift platform to host your next big idea but are looking for guidance on how to achieve this, then this book is the first step you need to take. This is a very accessible cookbook where no previous knowledge of OpenShift is needed.

  13. Avaliação dos efeitos do estradiol e do FSH nos níveis de leptina em mulheres com supressão da função hipofisária Effects of estradiol and FSH on leptin levels in women with pituitary suppression

    Directory of Open Access Journals (Sweden)

    Selmo Geber

    2005-04-01

    Full Text Available OBJETIVO: identificar a correlação entre os níveis séricos de leptina e os níveis de estradiol e do hormônio folículo-estimulante (FSH em mulheres com supressão da função hipofisária, e suas possíveis interferências no eixo reprodutivo. MÉTODOS: estudamos prospectivamente 64 pacientes submetidas à hiperestimulação ovariana controlada com FSH recombinante para tratamento pela técnica de reprodução assistida, devido a fator masculino ou tubário, e 20 pacientes em uso de valerato de estradiol, para preparo endometrial, em tratamento de doação de óvulos, por falha de resposta ovariana em ciclo prévio. Todas as pacientes utilizaram análogo de GnRH no início do tratamento, de forma a obter a supressão da função hipofisária. Para a análise estatística dos resultados, foram utilizados os testes chi2, t de Student e correlação de Pearson, quando adequado. Os resultados foram considerados significativos quando pPURPOSE: to identify the relationship between serum levels of leptin and the levels of estradiol and follicle-stimulating hormone (FSH in women with pituitary suppression and to evaluate its possible interference on the reproductive axis. METHODS: a total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction, due to a male or tubal factor, and 20 patients using estradiol valerate, for endometrial preparation in order to be submitted to oocyte donation treatment were studied. All patients used GnRH analogues before starting treatment in order to avoid premature LH surge. Data were analyzed statistically by the chi2 test, Student's t-test and the Pearson correlation test, when appropriate, with the level of significance set at p<0,05. RESULTS: it was observed that leptin levels correlated with body mass index (BMI even though they had not influenced growth rate of these hormones. A positive correlation was observed between estradiol and leptin levels in both

  14. α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

    Science.gov (United States)

    Aquino, Nayara S S; Araujo-Lopes, Roberta; Henriques, Patricia C; Lopes, Felipe E F; Gusmao, Daniela O; Coimbra, Candido C; Franci, Celso R; Reis, Adelina M; Szawka, Raphael E

    2017-06-01

    Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge. Copyright © 2017 Endocrine Society.

  15. Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

    Science.gov (United States)

    The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of estradiol on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n = 12), 150 (n = 11) or 210 (n = 12) days of age received estradiol ...

  16. Direct radioimmunoassay of 17. beta. -estradiol in ether extracts of bovine

    Energy Technology Data Exchange (ETDEWEB)

    Medina, M.B.

    Anabolic estrogens such as 17..beta..-estradiol or 17..beta..-estradiol benzoate are used to promote growth and increase feed efficiency in food-producing cattle. This paper describes a technique to produce a more specific antibody to 17..beta..-estradiol by intradermal immunization using microquantities of 6-(carboxymethyl)-17..beta..-estradiol oxime bovine serum albumin and the development of a radioimmunoassay (RIA) procedure to measure directly the amounts of 17..beta..-estradiol in ether extracts of bovine serum without using cleanup procedures. Results demonstrated that a specific and sensitive antibody was produced, and a titer of 1:10,000 was used in the RIA procedure. Antibody cross-reactivity with ..beta..-estradiol metabolites and other anabolic estrogens was negligible. The untreated bovine sera showed 0-24 pg of apparent 17..beta..-estradiol/mL, while 0-31 pg/mL total estrogens had been reported in the literature. This assay can measure 5-100 pg in 20-250..mu..L/sample. This method can be used before or immediately after slaughter to monitor the residual amounts of estradiol used in the treatment of cattle.

  17. Direct radioimmunoassay of 17β-estradiol in ether extracts of bovine

    International Nuclear Information System (INIS)

    Medina, M.B.

    1986-01-01

    Anabolic estrogens such as 17β-estradiol or 17β-estradiol benzoate are used to promote growth and increase feed efficiency in food-producing cattle. This paper describes a technique to produce a more specific antibody to 17β-estradiol by intradermal immunization using microquantities of 6-(carboxymethyl)-17β-estradiol oxime bovine serum albumin and the development of a radioimmunoassay (RIA) procedure to measure directly the amounts of 17β-estradiol in ether extracts of bovine serum without using cleanup procedures. Results demonstrated that a specific and sensitive antibody was produced, and a titer of 1:10,000 was used in the RIA procedure. Antibody cross-reactivity with β-estradiol metabolites and other anabolic estrogens was negligible. The untreated bovine sera showed 0-24 pg of apparent 17β-estradiol/mL, while 0-31 pg/mL total estrogens had been reported in the literature. This assay can measure 5-100 pg in 20-250μL/sample. This method can be used before or immediately after slaughter to monitor the residual amounts of estradiol used in the treatment of cattle

  18. Exogenous estradiol alters gonadal growth and timing of temperature sex determination in gonads of sea turtle.

    Science.gov (United States)

    Díaz-Hernández, Verónica; Marmolejo-Valencia, Alejandro; Merchant-Larios, Horacio

    2015-12-01

    Temperature sex determining species offer a model for investigating how environmental cues become integrated to the regulation of patterning genes and growth, among bipotential gonads. Manipulation of steroid hormones has revealed the important role of aromatase in the regulation of the estrogen levels involved in temperature-dependent sex determination. Estradiol treatment counteracts the effect of male-promoting temperature, but the resulting ovarian developmental pattern differs from that manifested with the female-promoting temperature. Hypoplastic gonads have been reported among estradiol-treated turtles; however the estradiol effect on gonadal size has not been examined. Here we focused on the sea turtle Lepidochelys olivacea, which develops hypoplastic gonads with estradiol treatment. We studied the effect of estradiol on cell proliferation and on candidate genes involved in ovarian pattern. We found this effect is organ specific, causing a dramatic reduction in gonadal cell proliferation during the temperature-sensitive period. Although the incipient gonads resembled tiny ovaries, remodeling of the medullary cords and down-regulation of testicular factor Sox9 were considerably delayed. Contrastingly, with ovarian promoting temperature as a cue, exogenous estradiol induced the up-regulation of the ovary factor FoxL2, prior to the expression of aromatase. The strong expression of estrogen receptor alpha at the time of treatment suggests that it mediates estradiol effects. Overall results indicate that estradiol levels required for gonadal growth and to establish the female genetic network are delicately regulated by temperature. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt.

    Science.gov (United States)

    Barb, C R; Hausman, G J; Kraeling, R R

    2010-12-01

    The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of 17β-estradiol (estradiol) on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n=12), 150 (n=11) or 210 (n=12) days of age received estradiol benzoate (EB) osmotic pump implants 6/group and the remaining animals received vehicle control (C) implants except for 150-day C (n=5) on Day 0. On Day 10 blood samples were collected every 15 min for 8h and serum LH and estradiol concentrations were measured. Serum estradiol concentrations averaged 5 ± 1, 5 ± 1 and 7 ± 2 pg/ml for the 90-, 150- and 210-day-old gilts implanted with estradiol, respectively, whereas, serum estradiol concentrations was undetectable in C gilts. Mean serum LH concentrations, basal LH concentrations and serum LH pulse amplitude were less in EB-treated gilts at all ages compared to control animals. In contrast, LH pulse frequency initially was less in EB-treated gilts but subsequently increased (Pgilts. These results demonstrate an age related reduction in the sensitivity to the negative feedback action of estradiol on LH secretion and support the idea that the gilt conforms to the gonadostat hypothesis. Published by Elsevier B.V.

  20. Effects of estradiol, progestogens, and of tibolone on breast proliferation and apoptosis.

    Science.gov (United States)

    Pompei, L M; Cunha, E P; Steiner, M L; Theodoro, T R; Mader, A M A A; Petri, G; Pinhal, M A S; Fernandes, C E

    2015-01-01

    To study the effects of estrogen therapy, alone or combined with progestogens, and of tibolone on the expression of proliferation and apoptosis markers in normal breast tissue. Thirty 250-day-old Wistar rats were castrated and 3 weeks later received one of the following treatments by gavage for 5 weeks: (1) estradiol benzoate; (2) estradiol benzoate + medroxyprogesterone acetate; (3) estradiol benzoate + norethisterone acetate; (4) estradiol benzoate + dydrogesterone; (5) tibolone; (6) placebo. Following treatment, the expression of proliferating cell nuclear antigen (PCNA) and caspase-3 was analyzed by quantitative immunohistochemistry in the breast tissue, and proliferation and apoptosis were analyzed semiquantitatively by microscopic imaging. There was a statistically significant difference among the groups for PCNA, caspase-3 and the caspase-3 : PCNA ratio. Tibolone was associated with the lowest proliferative activity, followed by estradiol benzoate + dydrogesterone; however, estradiol benzoate + dydrogesterone showed the greatest rate of apoptosis. The various progestogens can have more or less proliferative and pro-apoptotic effects than estradiol alone. Among the treatment schemes analyzed, the estradiol + dydrogesterone combination resulted in a higher apoptosis rate in relation to the proliferation rate and tibolone was associated with the lowest proliferation.

  1. Effects of Panax ginseng, zearalenol, and estradiol on sperm function.

    Science.gov (United States)

    Gray, Sandra L; Lackey, Brett R; Boone, William R

    2016-07-01

    Estrogen signaling pathways are modulated by exogenous factors. Panax ginseng exerts multiple activities in biological systems and is classified as an adaptogen. Zearalenol is a potent mycoestrogen that may be present in herbs and crops arising from contamination or endophytic association. The goal of this study was to investigate the impact of P. ginseng, zearalenol and estradiol in tests on spermatozoal function. The affinity of these compounds for estrogen receptor (ER)-alpha and beta (ERα and ERβ)-was assessed in receptor binding assays. Functional tests on boar spermatozoa motility, movement and kinematic parameters were conducted using a computer-assisted sperm analyzer. Tests for capacitation, acrosome reaction (AR), and chromatin decondensation in spermatozoa were performed using microscopic analysis. Zearalenol-but not estradiol (E2)- or ginseng-treated spermatozoa-decreased the percentage of overall, progressive, and rapid motile cells. Zearalenol also decreased spontaneous AR and increased chromatin decondensation. Ginseng decreased chromatin decondensation in response to calcium ionophore and decreased AR in response to progesterone (P4) and ionophore. Zearalenol has adverse effects on sperm motility and function by targeting multiple signaling cascades, including P4, E2, and calcium pathways. Ginseng protects against chromatin damage and thus may be beneficial to reproductive fitness.

  2. An improved method for estradiol-17B radioimmunoassay

    International Nuclear Information System (INIS)

    El-Banna, I.M.; El-Asrag, H.A.; Gamal, M.H.

    1991-01-01

    This work describes an improved radioimmunoassay (RIA) of serum estradiol-17 B (E) using locally generated immuno-chemicals. Estradiol hemisuccinate (E -3-H S) was prepared and conjugated to bovine serum albumin (BSA). The obtained conjugate; E 3-H S: BSA, hadλ max at 280 mu and the steroid BSA molar ratio was 25:1. The immunogen was injected subcutaneously in New Zealand rabbits and large amount of antiserum was harvested with 1 : 10500 antibody titre. The antibody cross reactions with estrone (E ), estriol (E ) and progesterone (P) were determined. Blood samples were collected from cycling Osemi ewes during follicular phase, pregnant ewes near term and daily from a cycling ewe over two consecutive estrous cycles. Serum samples were analysed for E both directly and after diethyl ether extraction (DE). The higher E values were found in the direct assay for pregnant ewes. The direct serum minnature RIA system, described herein, was found to be specific, sensitive, precise and economic.5 fig. 2 tab

  3. The influence of smoking on bone loss and response to nasal estradiol

    DEFF Research Database (Denmark)

    Bjarnason, N.H.; Nielsen, T.F.; Jørgensen, Henrik Løvendahl

    2009-01-01

    Objective To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. Methods Post-hoc explorator...... estradiol to increase bone mass in early postmenopausal women. In addition, smoking may increase spontaneous bone loss in untreated women Udgivelsesdato: 2009......Objective To investigate the influence of smoking on bone during therapy with nasally administrated estradiol in sequential combination with oral progesterone in early postmenopausal women. In addition, to observe the consequences of smoking on bone in untreated women. Methods Post-hoc exploratory...... analyses of data from 270 postmenopausal women randomized to 2 years' therapy with daily nasal administration of 17-estradiol or placebo sequentially combined with oral micronized progesterone in the active groups or placebo in the placebo group. Results During treatment with nasal estradiol, the bone...

  4. Effects of estradiol on radiation-induced apoptosis in immunocytes of mouse

    International Nuclear Information System (INIS)

    Wu Wei; Yang Rujun; Kong Xiantao; Zhang Lingzhen; Li Bolong; Cai Jianming

    2000-01-01

    Objective: To assess the effects of estradiol on 60 Co γ-radiation induced apoptosis of splenic lymphocytes and thymocytes, and surface molecule expression of splenic lymphocytes. Methods: Mice were whole body irradiated with 4.0 Gy γ-rays. By flow cytometry and electrophoretic analysis of DNA, the changes in apoptosis of mouse immunocytes were determined. The splenic lymphocytes were analyzed by flow cytometry with fluorescent monoclonal antibodies. Results: 10 days after administration of estradiol, the characteristic DNA ladder in mice 8h after irradiation was minor than in mice without estradiol administration,indicating that the apoptotic rate reduced on flow cytometry. CD4+ T cells, CD8+ T cells and IgM+ B cells up regulated Fas, CD25 and CD69 expression, but did not so in the estradiol treated mice. Conclusion: Estradiol can block CD25, CD69 and Fas overexpression, thereby inhibiting Fas mediated apoptosis induced by γ-irradiation

  5. Dose-dependent effects of 17-ß-estradiol on pituitary thyrotropin content and secretion in vitro

    Directory of Open Access Journals (Sweden)

    Moreira R.M.

    1997-01-01

    Full Text Available We studied the basal and thyrotropin-releasing hormone (TRH (50 nM induced thyrotropin (TSH release in isolated hemipituitaries of ovariectomized rats treated with near-physiological or high doses of 17-ß-estradiol benzoate (EB; sc, daily for 10 days or with vehicle (untreated control rats, OVX. One group was sham-operated (normal control. The anterior pituitary glands were incubated in Krebs-Ringer bicarbonate medium, pH 7.4, at 37oC in an atmosphere of 95% O2/5% CO2. Medium and pituitary TSH was measured by specific RIA (NIDDK-RP-3. Ovariectomy induced a decrease (P<0.05 in basal TSH release (normal control = 44.1 ± 7.2; OVX = 14.7 ± 3.0 ng/ml and tended to reduce TRH-stimulated TSH release (normal control = 33.0 ± 8.1; OVX = 16.6 ± 2.4 ng/ml. The lowest dose of EB (0.7 µg/100 g body weight did not reverse this alteration, but markedly increased the pituitary TSH content (0.6 ± 0.06 µg/hemipituitary; P<0.05 above that of OVX (0.4 ± 0.03 µg/hemipituitary and normal rats (0.46 ± 0.03 µg/hemipituitary. The intermediate EB dose (1.4 µg/100 g body weight induced a nonsignificant tendency to a higher TSH response to TRH compared to OVX and a lower response compared to normal rats. Conversely, in the rats treated with the highest dose (14 µg/100 g body weight, serum 17-ß-estradiol was 17 times higher than normal, and the basal and TRH-stimulated TSH release, as well as the pituitary TSH content, was significantly (P<0.05 reduced compared to normal rats and tended to be even lower than the values observed for the vehicle-treated OVX group, suggesting an inhibitory effect of hyperestrogenism. In conclusion, while reinforcing the concept of a positive physiological regulatory role of estradiol on the TSH response to TRH and on the pituitary stores of the hormone, the present results suggest an inhibitory effect of high levels of estrogen on these responses

  6. Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus

    Science.gov (United States)

    Ivanova, Margarita M.; Radde, Brandie N.; Son, Jieun; Mehta, Fabiola F.; Chung, Sang-Hyuk; Klinge, Carolyn M.

    2013-01-01

    Nuclear respiratory factor-1 (NRF-1) stimulates the transcription of nuclear-encoded genes that regulate mitochondrial genome transcription and biogenesis. We reported that estradiol (E2) and 4-hydroxytamoxifen (4-OHT) stimulate NRF-1 transcription in an estrogen receptor α- and β- (ERα, ERβ) dependent manner in human breast cancer cells. The aim of this study was to determine if E2 and 4-OHT increase NRF-1 in vivo. Here we report that E2 and 4-OHT increase NRF-1 expression in mammary gland and uterus of ovariectomized C57BL/6 mice in a time-dependent manner. E2 increased NRF-1 protein in the uterus and mammary gland; however, in mammary gland, 4-OHT increased Nrf1 mRNA but not protein. Chromatin immunoprecipitation (ChIP) assays revealed increased in vivo recruitment of ERα to the Nrf1 promoter and intron 3 in mammary gland and uterus 6 h after E2 and 4-OHT treatment, commensurate with increased NRF-1 expression. E2 and 4-OHT- induced increases in NRF-1 and its target genes Tfam, Tfb1m, and Tfb2m were coordinated in mammary gland but not uterus, due to uterine-selective inhibition of the expression of the NRF-1 coactivators Ppargc1a and Ppargc1b by E2 and 4-OHT. E2 transiently increased NRF-1 and PGC-1α nuclear staining while reducing PGC-1α in uterus. E2, not 4-OHT, activates mitochondrial biogenesis in mammary gland and uterus in a time-dependent manner. E2 increased mitochondrial outer membrane Tom40 protein levels in mammary gland and uterus whereas 4-OHT increased Tom40 only in uterus. These data support the hypothesis of tissue-selective regulation of NRF-1 and its downstream targets by E2 and 4-OHT in vivo. PMID:23892277

  7. Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus.

    Science.gov (United States)

    Ivanova, Margarita M; Radde, Brandie N; Son, Jieun; Mehta, Fabiola F; Chung, Sang-Hyuk; Klinge, Carolyn M

    2013-10-01

    Nuclear respiratory factor-1 (NRF-1) stimulates the transcription of nuclear-encoded genes that regulate mitochondrial (mt) genome transcription and biogenesis. We reported that estradiol (E2) and 4-hydroxytamoxifen (4-OHT) stimulate NRF-1 transcription in an estrogen receptor α (ERα)- and ERβ-dependent manner in human breast cancer cells. The aim of this study was to determine whether E2 and 4-OHT increase NRF-1 in vivo. Here, we report that E2 and 4-OHT increase NRF-1 expression in mammary gland (MG) and uterus of ovariectomized C57BL/6 mice in a time-dependent manner. E2 increased NRF-1 protein in the uterus and MG; however, in MG, 4-OHT increased Nrf1 mRNA but not protein. Chromatin immunoprecipitation assays revealed increased in vivo recruitment of ERα to the Nrf1 promoter and intron 3 in MG and uterus 6 h after E2 and 4-OHT treatment, commensurate with increased NRF-1 expression. E2- and 4-OHT-induced increases in NRF-1 and its target genes Tfam, Tfb1m, and Tfb2m were coordinated in MG but not in uterus due to uterine-selective inhibition of the expression of the NRF-1 coactivators Ppargc1a and Ppargc1b by E2 and 4-OHT. E2 transiently increased NRF-1 and PGC-1α nuclear staining while reducing PGC-1α in uterus. E2, not 4-OHT, activates mt biogenesis in MG and uterus in a time-dependent manner. E2 increased mt outer membrane Tomm40 protein levels in MG and uterus whereas 4-OHT increased Tomm40 only in uterus. These data support the hypothesis of tissue-selective regulation of NRF-1 and its downstream targets by E2 and 4-OHT in vivo.

  8. Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

    Science.gov (United States)

    Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

    2016-12-01

    17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

  9. Nurses' shift reports

    DEFF Research Database (Denmark)

    Buus, Niels; Hoeck, Bente; Hamilton, Bridget Elizabeth

    2017-01-01

    practices were described as highly conventionalised and locally situated, but with occasional opportunities for improvisation and negotiation between nurses. Finally, shift reports were described as multifunctional meetings, with individual and social effects for nurses and teams. CONCLUSION: Innovations...... of nurses' shift reports. BACKGROUND: Nurses' shift reports are routine occurrences in healthcare organisations that are viewed as crucial for patient outcomes, patient safety and continuity of care. Studies of communication between nurses attend primarily to 1:1 communication and analyse the adequacy...... and negotiate care....

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

    Science.gov (United States)

    Fruzzetti, Franca; Trémollieres, Florence; Bitzer, Johannes

    2012-01-01

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

  11. Shift Verification and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Pandya, Tara M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Evans, Thomas M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Davidson, Gregory G [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Johnson, Seth R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Godfrey, Andrew T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-07

    This documentation outlines the verification and validation of Shift for the Consortium for Advanced Simulation of Light Water Reactors (CASL). Five main types of problems were used for validation: small criticality benchmark problems; full-core reactor benchmarks for light water reactors; fixed-source coupled neutron-photon dosimetry benchmarks; depletion/burnup benchmarks; and full-core reactor performance benchmarks. We compared Shift results to measured data and other simulated Monte Carlo radiation transport code results, and found very good agreement in a variety of comparison measures. These include prediction of critical eigenvalue, radial and axial pin power distributions, rod worth, leakage spectra, and nuclide inventories over a burn cycle. Based on this validation of Shift, we are confident in Shift to provide reference results for CASL benchmarking.

  12. Influence of agricultural antibiotics and 17beta-estradiol on the microbial community of soil.

    Science.gov (United States)

    Chun, Soul; Lee, Jaehoon; Radosevich, Mark; White, David C; Geyer, Roland

    2006-01-01

    Agricultural pharmaceuticals are a major environmental concern because of their hazardous effects on human and wildlife. This study analyzed phospholipid ester-linked fatty acids (PLFAs) and quinones to investigate the effects of a steroid (17beta-estradiol) and agricultural antibiotics (chlortetracycline and tylosin) on soil microbes in the laboratory. Two different types of soil were used: Sequatchie loam (0.8% organic matter) and LaDelle silt loam (9.2% organic matter). The soils were spiked with 17beta-estradiol and antibiotics, alone or in combination. In Sequatchie loam, 17beta-estradiol significantly increased the microbial biomass, especially the biomarkers for beta proteobacteria (16:1omega7c, 18:1omega7c, Cy17:0, and UQ-8). The coexistence of antibiotics decreased the stimulatory effect of 17beta-estradiol on the microbial community. In LaDelle silt loam, there were no significant differences in total microbial biomass and their microbial community structure among the treatments. Overall, 17beta-estradiol changed the microbial community of soil and the presence of antibiotics nullified the effect of 17beta-estradiol. However, the effects of 17beta-estradiol and antibiotics on soil microbes were sensitive to the soil properties, as seen in the LaDelle silt loam.

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

    Science.gov (United States)

    Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

    2015-10-30

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

  14. The role of histamine in estradiol-induced conditioned consumption reductions.

    Science.gov (United States)

    Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

    2005-01-31

    Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

  15. Insulin priming effect on estradiol-induced breast cancer metabolism and growth.

    Science.gov (United States)

    Wairagu, Peninah M; Phan, Ai N H; Kim, Min-Kyu; Han, Jeongwoo; Kim, Hyun-Won; Choi, Jong-Whan; Kim, Ki Woo; Cha, Seung-Kuy; Park, Kwang Hwa; Jeong, Yangsik

    2015-01-01

    Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.

  16. Estradiol Regulates Brown Adipose Tissue Thermogenesis via Hypothalamic AMPK

    Science.gov (United States)

    Martínez de Morentin, Pablo B.; González-García, Ismael; Martins, Luís; Lage, Ricardo; Fernández-Mallo, Diana; Martínez-Sánchez, Noelia; Ruíz-Pino, Francisco; Liu, Ji; Morgan, Donald A.; Pinilla, Leonor; Gallego, Rosalía; Saha, Asish K.; Kalsbeek, Andries; Fliers, Eric; Bisschop, Peter H.; Diéguez, Carlos; Nogueiras, Rubén; Rahmouni, Kamal; Tena-Sempere, Manuel; López, Miguel

    2014-01-01

    Summary Estrogens play a major role in the modulation of energy balance through central and peripheral actions. Here, we demonstrate that central action of estradiol (E2) inhibits AMP-activated protein kinase (AMPK) through estrogen receptor alpha (ERα) selectively in the ventromedial nucleus of the hypothalamus (VMH), leading to activation of thermogenesis in brown adipose tissue (BAT) through the sympathetic nervous system (SNS) in a feeding-independent manner. Genetic activation of AMPK in the VMH prevented E2-induced increase in BAT-mediated thermogenesis and weight loss. Notably, fluctuations in E2 levels during estrous cycle also modulate this integrated physiological network. Together, these findings demonstrate that E2 regulation of the VMH AMPK-SNS-BAT axis is an important determinant of energy balance and suggest that dysregulation in this axis may account for the common changes in energy homeostasis and obesity linked to dysfunction of the female gonadal axis. PMID:24856932

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

    Directory of Open Access Journals (Sweden)

    Marcello Maggio

    2015-08-01

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

  18. Loneliness depends on salivary estradiol levels in adolescent females.

    Science.gov (United States)

    Fujisawa, Takashi X; Nishitani, Shota; Obara, Tatsuro; Shinohara, Kazuyuki

    2012-01-01

    Loneliness is one of the psychological characteristics in adolescence, during which sex hormones are elevated. The elevation of sex steroid hormones is known to sculpture and remodel neuronal circuits, which cause behavioral characteristics in adolescence. The aim of the present study is to investigate the relationship between loneliness and sex steroid hormones, testosterone (T) and 17β-estradiol (E2). Fifty-eight adolescents (28 boys and 30 girls) participated in this study. The salivary levels of T and E2 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Loneliness was assessed by the UCLA loneliness scale, which is widely used as a self-administered questionnaire. The results showed that Salivary E2 levels had positive relevance to loneliness in females, whereas there was no relationship in males. Salivary T level was not shown to be relevant with loneliness in either sex group. These findings suggest that E2 has gender specific effects on loneliness in adolescent females.

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

    Science.gov (United States)

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

    2015-08-05

    In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998-2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. After adjustment for age, α-carotene (β ± SE = -0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = -0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = -1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = -0.29 ± 0.08, p = 0.0009), and E2 persisted whereas the

  20. Estradiol partially recapitulates murine pituitary cell cycle response to pregnancy.

    Science.gov (United States)

    Toledano, Yoel; Zonis, Svetlana; Ren, Song-Guang; Wawrowsky, Kolja; Chesnokova, Vera; Melmed, Shlomo

    2012-10-01

    Because pregnancy and estrogens both induce pituitary lactotroph hyperplasia, we assessed the expression of pituitary cell cycle regulators in two models of murine pituitary hyperplasia. Female mice were assessed during nonpregnancy, pregnancy, day of delivery, and postpartum. We also implanted estradiol (E(2)) pellets in female mice and studied them for 2.5 months. Pituitary weight in female mice increased 2-fold after E(2) administration and 1.4-fold at day of delivery, compared with placebo-treated or nonpregnant females. Pituitary proliferation, as assessed by proliferating cell nuclear antigen and/or Ki-67 staining, increased dramatically during both mid-late pregnancy and E(2) administration, and lactotroph hyperplasia was also observed. Pregnancy induced pituitary cell cycle proliferative and inhibitory responses at the G(1)/S checkpoint. Differential cell cycle regulator expression included cyclin-dependent kinase inhibitors, p21(Cip1), p27(Kip1), and cyclin D1. Pituitary cell cycle responses to E(2) administration partially recapitulated those effects observed at mid-late pregnancy, coincident with elevated circulating mouse E(2), including increased expression of proliferating cell nuclear antigen, Ki-67, p15(INK4b), and p21(Cip1). Nuclear localization of pituitary p21(Cip1) was demonstrated at mid-late pregnancy but not during E(2) administration, suggesting a cell cycle inhibitory role for p21(Cip1) in pregnancy, yet a possible proproliferative role during E(2) administration. Most observed cell cycle protein alterations were reversed postpartum. Murine pituitary meets the demand for prolactin during lactation associated with induction of both cell proliferative and inhibitory pathways, mediated, at least partially, by estradiol.

  1. Human pharmacokinetics of ethynyl estradiol 3-sulfate and 17-sulfate.

    Science.gov (United States)

    Goldzieher, J W; Mileikowsky, G; Newburger, J; Dorantes, A; Stavchansky, S A

    1988-01-01

    Pharmacokinetic parameters of ethynyl estradiol 3-sulfate (EE-3) and 17-sulfate (EE-17) were estimated. Each sulfate was administered orally and intravenously to five ovariectomized volunteer women. Blood samples were taken over a period of 24 h. Radioimmunoassay for free and sulfoconjugated ethynyl estradiol (EE) was performed. The analysis of the plasma concentrations obtained after administration of EE-3 and EE-17 indicates significant differences in their pharmacokinetic profiles. EE-3 is cleared more rapidly from the central compartment (systemic circulation), which may indicate that differences in protein binding, tissue binding, metabolism, and distribution exist between EE-3 and EE-17. It has been suggested that these conjugates are a slow-release reservoir for maintenance of blood levels of free EE itself. However, previous studies in baboons have shown that the half-lives of the free and sulfoconjugated EE are similar (ranging from 8.8 to 11.2 h), which is not consistent with this hypothesis. The t1/2 beta (mean 9.28 h) of the 17-sulfate after IV administration was almost identical in women and baboons, and similar to the t1/2 beta of free EE, confirming the previous observation. Only 3.4% of IV and 11.4% of the orally administered 17-sulfate appeared in the blood as free EE; with the 3-sulfate, the conversions were 13.7 and 20.7%, respectively, suggesting that these sulfates are not important slow-release reservoirs. The similarity of pharmacokinetic parameters between women and baboons suggests that this species of nonhuman primate is, in important respects, a suitable animal model for clinical pharmacology.

  2. Adrenalectomy alters regulation of blood pressure and endothelial nitric oxide synthase in sheep: modulation by estradiol.

    Science.gov (United States)

    Li, Feng; Wood, Charles E; Keller-Wood, Maureen

    2007-07-01

    Hypoadrenocorticism produces more severe hypotension during the peripartal period in pregnant ewes and women. We hypothesized that estradiol increases the severity of hypotension after withdrawal of corticosteroids and that this results from combined effects of adrenalectomy and estradiol to increase endothelial nitric oxide synthase (eNOS). In study I, blood pressure and eNOS mRNA and protein in aorta, uterine, renal, and mesenteric arteries were measured in intact ewes or adrenalectomized ewes 18-20 h after cessation of infusion of cortisol and aldosterone; half of each group ewes were treated with estradiol. In study II, adrenalectomized ewes were similarly studied 22-28 h after withdrawal of corticosteroids. Estradiol treatment in both studies significantly increased eNOS mRNA and protein in uterine artery, whereas corticosteroid withdrawal decreased expression of eNOS mRNA and protein in uterine artery. In both studies, adrenalectomy and steroid withdrawal decreased mean arterial pressure. In study II, four of six adrenalectomized ewes not treated with estradiol showed dramatic phasic variations in blood pressure and heart rate with a period of approximately 20 s, developing within 22-28 h after corticosteroid withdrawal. Although there was no effect of estradiol on blood pressure in study I, in study II, ewes treated with estradiol did not develop this pattern. Estradiol also slowed both the decline in plasma sodium and the rise in plasma potassium after corticosteroid withdrawal. These results disprove the hypothesis that estradiol increases the severity of hypotension during hypoadrenocorticism. However, the study reveals an important effect of corticosteroid withdrawal on blood pressure, consistent with corticosteroid modulation of baroreflex responsiveness.

  3. Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

    2013-07-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

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

    Science.gov (United States)

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

    2015-10-01

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

  5. Engagement sensitive visual stimulation

    Directory of Open Access Journals (Sweden)

    Deepesh Kumar

    2016-06-01

    Full Text Available Stroke is one of leading cause of death and disability worldwide. Early detection during golden hour and treatment of individual neurological dysfunction in stroke using easy-to-access biomarkers based on a simple-to-use, cost-effective, clinically-valid screening tool can bring a paradigm shift in healthcare, both urban and rural. In our research we have designed a quantitative automatic home-based oculomotor assessment tool that can play an important complementary role in prognosis of neurological disorders like stroke for the neurologist. Once the patient has been screened for stroke, the next step is to design proper rehabilitation platform to alleviate the disability. In addition to the screening platform, in our research, we work in designing virtual reality based rehabilitation exercise platform that has the potential to deliver visual stimulation and in turn contribute to improving one’s performance.

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

    Science.gov (United States)

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

    1986-07-01

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

  7. 17-β-Estradiol Upregulates the Stress Response in Candida albicans: Implications for Microbial Virulence

    OpenAIRE

    C. O’Connor; M. Essmann; B. Larsen

    1998-01-01

    Objective: The influence of 17-β-estradiol on the stress response of Candida albicans was studied.Methods: The survival of clinical isolates of C. albicans treated with 17-β-estradiol after heat and oxidative stress was measured by viable plate counts. Cellular proteins were analyzed via SDSPAGE.Results: The heat stress response induced by 17-β-estradiol in C. albicans grown at 25 ℃ protected the organisms against the lethal temperature of 48.5 ℃, as shown by viable plate counts. 17-β-estradi...

  8. 17-beta-estradiol upregulates the stress response in Candida albicans: implications for microbial virulence.

    OpenAIRE

    O'Connor, C; Essmann, M; Larsen, B

    1998-01-01

    OBJECTIVE: The influence of 17-beta-estradiol on the stress response of Candida albicans was studied. METHODS: The survival of clinical isolates of C. albicans treated with 17-beta-estradiol after heat and oxidative stress was measured by viable plate counts. Cellular proteins were analyzed via SDS-PAGE. RESULTS: The heat stress response induced by 17-beta-estradiol in C. albicans grown at 25 degrees C protected the organisms against the lethal temperature of 48.5 degrees C, as shown by viabl...

  9. Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial.

    Science.gov (United States)

    Melisko, Michelle E; Goldman, Mindy E; Hwang, Jimmy; De Luca, Amy; Fang, Sally; Esserman, Laura J; Chien, Amy J; Park, John W; Rugo, Hope S

    2017-03-01

    Aromatase inhibitors (AI) are associated with significant urogenital atrophy, affecting quality of life and drug compliance. To evaluate safety of intravaginal testosterone cream (IVT) or an estradiol-releasing vaginal ring (7.5 μg/d) in patients with early-stage breast cancer (BC) receiving an AI. Intervention was considered unsafe if more than 25% of patients had persistent elevation in estradiol (E2), defined as E2 greater than 10 pg/mL (to convert to pmol/L, multiply by 3.671) and at least 10 pg/mL above baseline after treatment initiation on 2 consecutive tests at least 2 weeks apart. Postmenopausal (PM) women with hormone receptor (HR)-positive stage I to III BC taking AIs with self-reported vaginal dryness, dyspareunia, or decreased libido were randomized to 12 weeks of IVT or an estradiol vaginal ring. Estradiol was measured at baseline and weeks 4 and 12 using a commercially available liquid chromatography and tandem mass spectrometry assay; follicle-stimulating hormone levels were measured at baseline and week 4. Gynecologic examinations and sexual quality-of-life questionnaires were completed at baseline and week 12. This randomized noncomparative design allowed safety evaluation of 2 interventions concurrently in the same population of patients, reducing the possibility of E2 assay variability over time and between the 2 interventions. The primary objective of this trial was to evaluate safety of IVT or an estradiol vaginal ring in patients with early-stage BC receiving an AI; secondary objectives included evaluation of adverse events, changes in sexual quality of life using the Cancer Rehabilitation Evaluation System sexuality subscales, changes in vaginal atrophy using a validated 4-point scale, and comparison of E2 levels. Overall, 76 women signed consent (mean [range] age, 56 [37-78] years), 75 started treatment, and 69 completed 12 weeks of treatment. Mean (range) baseline E2 was 20 (10 pg/mL) in 28 of 76 women (37%). Persistent E2 elevation was

  10. Evidence that 17alpha-estradiol is biologically active in the uterine tissue: Antiuterotonic and antiuterotrophic action

    Directory of Open Access Journals (Sweden)

    Navarrete Erika

    2005-07-01

    Full Text Available Abstract Background 17alpha-Estradiol has been considered as the hormonally inactive isomer of 17beta-estradiol. Recently, nongenomic (smooth muscle relaxation and genomic (light estrogenic activity effects of 17alpha-estradiol have been reported, but no reports have yet determined its possible antiestrogenic activity. Therefore, this study investigated: the nongenomic action of 17alpha-estradiol on uterine contractile activity and its potential agonist-antagonist activity on uterine growth. Methods Uterine rings from rats were isometrically recorded. Different concentrations (0.2–200 microM of 17alpha-estradiol were tested on spontaneous contraction and equimolarly compared with 17beta-estradiol. To examine the mechanism of 17alpha-estradiol action, its effect was studied in presence of beta2-antagonist (propranolol, antiestrogens (tamoxifen and ICI 182,780 or inhibitors of protein synthesis (cycloheximide and transcription (actinomycin D. Moreover, contractions induced by high potassium (KCl solution or calcium in depolarized tissues by KCl-calcium free solution were exposed to 17alpha-estradiol. Collaterally, we performed an uterotrophic assay in adult ovariectomized rats measuring the uterine wet weight. The administration for three days of 0.3 microM/day/Kg 17beta-estradiol was equimolarly compared with the response produced by 17alpha-estradiol. Antiuterotrophic activity was assayed by administration of 0.3 microM/day/Kg 17beta-estradiol and various doses ratios (1:1, 1:3, 1:5, and 1:100 of 17alpha-estradiol. Results The estradiol isomers elicited an immediate relaxation, concentration-dependent and reversible on spontaneous contraction. 17alpha-Estradiol presented lower potency than 17beta-estradiol although it did not antagonize 17beta-estradiol-induced relaxation. Relaxation to 17alpha-estradiol was not inhibited by propranolol, tamoxifen, ICI 182,780, cycloheximide or actinomycin D. The KCl contractions were also sensitive to 17alpha-estradiol

  11. Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women.

    Science.gov (United States)

    Norman, Catalina; Rollene, Nanette L; Erickson, Dana; Miles, John M; Bowers, Cyril Y; Veldhuis, Johannes D

    2014-01-01

    Estrogen stimulates pulsatile secretion of GH, via mechanisms that are largely unknown. An untested hypothesis is that estradiol (E₂) drives GH secretion by amplifying interactions among GH-releasing hormone (GHRH), somatostatin (SS), and GH-releasing peptide (GHRP). The design comprised double-blind randomized prospective administration of transdermal E₂ vs placebo to healthy postmenopausal women (n=24) followed by pulsatile GHRH or SS infusions for 13 h overnight with or without continuous GHRP2 stimulation. End points were mean concentrations, deconvolved secretion, and approximate entropy (ApEn; a regularity measure) of GH. By generalized ANOVA models, it was observed that E₂ vs placebo supplementation: i) augmented mean (13-h) GH concentrations (P=0.023), GHRH-induced pulsatile GH secretion over the first 3 h (P=0.0085) and pulsatile GH secretion over the next 10 h (P=0.054); ii) increased GHRP-modulated (P=0.022) and SS-modulated (PGH ApEn; and iii) did not amplify GHRH/GHRP synergy during pulsatile GH secretion. By linear regression, E₂ concentrations were found to be positively correlated with GH secretion during GHRP2 infusion (P=0.022), whereas BMI was found to be negatively correlated with GH secretion during GHRH (P=0.006) and combined GHRH/GHRP (P=0.015) stimulation. E₂ and BMI jointly determined triple (combined l-arginine, GHRH, and GHRP2) stimulation of GH secretion after saline (R²=0.44 and P=0.003) and pulsatile GHRH (R²=0.39 and P=0.013) infusions. In summary, in postmenopausal women, E₂ supplementation augments the amount (mass) and alters the pattern (regularity) of GH secretion via interactions among GHRH, SS, GHRP, and BMI. These outcomes introduce a more complex model of E₂ supplementation in coordinating GH secretion in aging women.

  12. Rapid effects of 17beta-estradiol on epithelial TRPV6 Ca2+ channel in human T84 colonic cells.

    LENUS (Irish Health Repository)

    Irnaten, Mustapha

    2008-11-01

    The control of calcium homeostasis is essential for cell survival and is of crucial importance for several physiological functions. The discovery of the epithelial calcium channel Transient Receptor Potential Vaniloid (TRPV6) in intestine has uncovered important Ca(2+) absorptive pathways involved in the regulation of whole body Ca(2+) homeostasis. The role of steroid hormone 17beta-estradiol (E(2)), in [Ca(2+)](i) regulation involving TRPV6 has been only limited at the protein expression levels in over-expressing heterologous systems. In the present study, using a combination of calcium-imaging, whole-cell patch-clamp techniques and siRNA technology to specifically knockdown TRPV6 protein expression, we were able to (i) show that TRPV6 is natively, rather than exogenously, expressed at mRNA and protein levels in human T84 colonic cells, (ii) characterize functional TRPV6 channels and (iii) demonstrate, for the first time, the rapid effects of E(2) in [Ca(2+)](i) regulation involving directly TRPV6 channels in T84 cells. Treatment with E(2) rapidly (<5 min) enhanced [Ca(2+)](i) and this increase was partially but significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV6 protein expression. These results indicate that when cells are stimulated by E(2), Ca(2+) enters the cell through TRPV6 channels. TRPV6 channels in T84 cells contribute to the Ca(2+) entry\\/signalling pathway that is sensitive to 17beta-estradiol.

  13. H19 lncRNA mediates 17β-estradiol-induced cell proliferation in MCF-7 breast cancer cells.

    Science.gov (United States)

    Sun, Hong; Wang, Guo; Peng, Yan; Zeng, Ying; Zhu, Qiong-Ni; Li, Tai-Lin; Cai, Jia-Qin; Zhou, Hong-Hao; Zhu, Yuan-Shan

    2015-06-01

    Estrogen plays a critical role in breast cancer development and progression. However, the mechanism involved in the promotion of breast cancer development and progression by estrogen remains unclear although it has been intensively studied. In the present study, we investigated the estrogen inducibility and functional significance of H19 lncRNA in breast cancer cells and tumor tissues. The screening of 83 disease-related long non-coding RNAs (lncRNAs) revealed that H19 lncRNA was much higher in estrogen receptor (ER)-positive MCF-7 breast cancer cells than in ER-negative MDA-MB-231 cells. 17β-estradiol produced a dose- and time-dependent induction of H19 expression in MCF-7 cells, which was mediated via ERα as evident by the blockade of this 17β-estradiol effect with ICI 182780, a specific ER antagonist and knockdown of ERα using specific RNAi. Moreover, knockdown of H19 lncRNA decreased cell survival and blocked estrogen-induced cell growth while overexpression of H19 lncRNA stimulated cell proliferation. Quantitation of H19 lncRNA in human breast cancer tissues showed that the level of H19 lncRNA was >10-fold higher in ER-positive than in ER-negative tumor tissues. These results suggest that H19 is an estrogen-inducible gene and plays a key role in cell survival and in estrogen-induced cell proliferation in MCF-7 cells, indicating that H19 lncRNA may serve as a biomarker for breast cancer diagnosis and progression, and as a valuable target for breast cancer therapy.

  14. Shifting Up a Gear.

    Science.gov (United States)

    Palmer, Martin

    1997-01-01

    Shift workers are often excluded from educational opportunities on and off the job. General education and leisure learning needs are addressed less than job-specific training needs. Providers should consider open/distance learning, creative marketing, targeted funding, and consortia of employer-developed programs. (SK)

  15. Understanding regime shifts

    DEFF Research Database (Denmark)

    Heymann, Matthias; Nielsen, Kristian Hvidtfelt

    ”. Danish wind power development is all the more surprising, as the innovation process in wind technology was carried to a large extent by non-academic craftsmen and political activists. Many features of this innovation story have been investigated and that research makes it possible to summarize...... the current understanding of the regime shift....

  16. Shifting employment revisited

    NARCIS (Netherlands)

    Cremers, J.; Gramuglia, A.

    2014-01-01

    The CLR-network examined in 2006 the phenomenon of undeclared labour, with specific regard to the construction sector. The resulting study, Shifting Employment: undeclared labour in construction, gave evidence that this is an area particularly affected by undeclared activities with one of the

  17. Paradigm Shifts into Giftedness.

    Science.gov (United States)

    Meckstroth, Elizabeth

    1992-01-01

    The process of recognizing qualities of giftedness in a child evokes a range of responses in families, affecting the roles and relationships of an entire family system as the whole family constellation shifts to accommodate a child's giftedness, and each family member's reactions differ because of their own particular temperament, personality,…

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

    Science.gov (United States)

    Kusuma, R.; Siregar, Y.; Mardianto

    2018-03-01

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

  19. Effects of estradiol on worm burden and peripheral leukocytes in Parastrongylus malaysiensis-infected rats.

    Science.gov (United States)

    Kamis, A B; Ahmad, R A; Badrul-Munir, M Z

    1994-01-01

    Gonadectomized male laboratory rats were given 0.06 mg/kg estradiol benzoate daily for 14 days before being inoculated with 50 third-stage larvae of Parastrongylus malaysiensis. Hormone treatment was continued until the rats were killed. The numbers of larvae in the brain and of adult worms in the pulmonary area of the rats were determined every 7 days after the inoculation. It was found that the rats treated daily with estradiol benzoate had significantly and consistently higher numbers of larvae and adult worms as compared with the controls. The number of total leukocytes increased significantly after the rats were infected. The results show that estradiol-treated rats become susceptible to P. malaysiensis infection, which may indicate that the immunosuppressive effects of testosterone observed in earlier studies may partly be caused by estradiol that was peripherally aromatized from testosterone.

  20. The pathway of estradiol-induced apoptosis in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Rastin, Maryam; Hatef, Mohammad Reza; Tabasi, Nafisseh; Mahmoudi, Mahmoud

    2012-03-01

    Systemic lupus erythematosus (SLE) is a disease with unknown etiology. The pathologic role of sex hormones and apoptosis in SLE has often been discussed. We studied the effects of estradiol in the pathway of induced apoptosis in Iranian SLE patients. T lymphocytes from 35 SLE patients and 20 age-matched controls were isolated and cultured in the presence of 10(-8) M 17-β estradiol. The expression levels of Fas, Fas ligand (FasL), Bcl-2, caspase-8, and caspase-9 mRNAs were determined semiquantitatively in comparison to the expression level of beta actin RNA. Estradiol exposure did not have any significant effects on the expression levels of Fas, Bcl-2, and caspase-9 in SLE patients and controls. However, the expression levels of FasL and caspase-8 were significantly increased in SLE patients, but not in controls. This suggests the probable involvement of extrinsic apoptosis pathway in estradiol-induced apoptosis in SLE.

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

    Science.gov (United States)

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

    2017-06-01

    17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (pbody weight (pbody weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (pbody weight regulation depending on the presence of isoflavones in rodent chow. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    International Nuclear Information System (INIS)

    Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

    2012-01-01

    Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E ∗ of osteoblasts significantly decreased by 43–46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

  3. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    Energy Technology Data Exchange (ETDEWEB)

    Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

  4. Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling.

    Science.gov (United States)

    Kriszt, Rókus; Winkler, Zsuzsanna; Polyák, Ágnes; Kuti, Dániel; Molnár, Csilla; Hrabovszky, Erik; Kalló, Imre; Szőke, Zsuzsanna; Ferenczi, Szilamér; Kovács, Krisztina J

    2015-11-01

    Xenoestrogens from synthetic or natural origin represent an increasing risk of disrupted endocrine functions including the physiological activity of the hypothalamo-pituitary-gonad axis. Ethinyl estradiol (EE2) is a synthetic estrogen used in contraceptive pills, whereas zearalenone (ZEA) is a natural mycoestrogen found with increasing prevalence in various cereal crops. Both EE2 and ZEA are agonists of estrogen receptor-α and accelerate puberty. However, the neuroendocrine mechanisms that are responsible for this effect remain unknown. Immature female Wistar rats were treated with EE2 (10 μg/kg), ZEA (10 mg/kg), or vehicle for 10 days starting from postnatal day 18. As a marker of puberty, the vaginal opening was recorded and neuropeptide and related transcription factor mRNA levels were measured by quantitative real time PCR and in situ hybridization histochemistry. Both ZEA and EE2 accelerated the vaginal opening, increased the uterine weight and the number of antral follicles in the ovary, and resulted in the increased central expression of gnrh. These changes occurred in parallel with an earlier increase of kiss1 mRNA in the anteroventral and rostral periventricular hypothalamus and an increased kisspeptin (KP) fiber density and KP-GnRH appositions in the preoptic area. These changes are compatible with a mechanism in which xenoestrogens overstimulate the developmentally unprepared reproductive system, which results in an advanced vaginal opening and an enlargement of the uterus at the periphery. Within the hypothalamus, ZEA and EE2 directly activate anteroventral and periventricular KP neurons to stimulate GnRH mRNA. However, GnRH and gonadotropin release and ovulation are disrupted due to xenoestrogen-mediated inhibitory KP signaling in the arcuate nucleus.

  5. 17β-estradiol enhances memory duration in the main olfactory bulb in CD-1 mice.

    Science.gov (United States)

    Dillon, T Samuel; Fox, Laura C; Han, Crystal; Linster, Christiane

    2013-12-01

    Rodents rely heavily on odor detection, discrimination, and memory to locate food, find mates, care for pups, and avoid predators. Estrogens have been shown to increase memory retention in rodents performing spatial memory and object placement tasks. Here we evaluate the extent to which 17β-estradiol modulates memory formation and duration in the olfactory system. Adult CD-1 mice were gonadectomized and given either systemic 17β-estradiol replacement, local 17β-estradiol in the main olfactory bulb, or no replacement. Before performing the behavioral task the mice were given saline or PHTPP (an estrogen receptor β [ER-β] antagonist) via bilateral infusion into the main olfactory bulb. As the beta-type estrogen receptor (ER-β) is more abundant than the alpha-type estrogen receptor in the murine main olfactory bulb, the current study focuses on 17β-estradiol and its interactions with ERβ. Habituation, a simple, nonassociative learning task in which an animal is exposed to the same odor over successive presentations, was used to evaluate the animals' ability to detect odors and form an olfactory memory. To evaluate memory duration, we added a final trial of intertrial interval time (30 or 60 min) in which we presented the habituated odor. Neither surgical nor drug manipulation affected the ability of mice to detect or habituate to an odor. After habituation, gonadectomized 17β-estradiol-treated mice retained memory of an odor for 30 min, whereas non-estradiol-treated, 17β-estradiol+ERβ antagonist (PHTPP), and untreated male mice did not remember an odor 30 min after habituation. The results show that both systemic and local bulbar infusions of 17β-estradiol enhance odor memory duration in mice.

  6. 17 Beta-estradiol, progesterone and testosterone in the normal menstrual cycle of Nigerians.

    Science.gov (United States)

    Dada, O A; Osinusi, B O; Nduka, E U; Osotimehin, B O; Ladipo, O A

    1984-04-01

    Circulating blood levels of estradiol, progesterone and testosterone are reported in 17 normally menstruating Nigerian women. The pattern of secretion and the range of levels of estradiol and progesterone are similar to those reported in other ethnic groups. Testosterone levels were, in general, higher than corresponding values in Caucasian or Asian women, but were of the same order of magnitude as previously reported in Zambian African women.

  7. Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

    International Nuclear Information System (INIS)

    Theron, C.N.

    1985-03-01

    A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

  8. Modulation of SHBG binding to testosterone and estradiol by sex and morbid obesity.

    Science.gov (United States)

    Grasa, María Del Mar; Gulfo, José; Camps, Núria; Alcalá, Rosa; Monserrat, Laura; Moreno-Navarrete, José María; Ortega, Francisco José; Esteve, Montserrat; Remesar, Xavier; Fernández-López, José Antonio; Fernández-Real, José Manuel; Alemany, Marià

    2017-04-01

    Sex hormone-binding globulin (SHBG) binds and transports testosterone and estradiol in plasma. The possibility that SHBG is a mixture of transporting proteins has been postulated. We analyzed in parallel the effects of obesity status on the levels and binding capacity of circulating SHBG and their relationship with testosterone and estradiol. Anthropometric measures and plasma were obtained from apparently healthy young (i.e. 35 ± 7 years) premenopausal women ( n =  32) and men ( n =  30), with normal weight and obesity (BMI >30 kg/m 2 ). SHBG protein (Western blot), as well as the plasma levels of testosterone, estradiol, cortisol and insulin (ELISA) were measured. Specific binding of estradiol and testosterone to plasma SHBG was analyzed using tritium-labeled hormones. Significant differences in SHBG were observed within the obesity status and gender, with discordant patterns of change in testosterone and estradiol. In men, testosterone occupied most of the binding sites. Estrogen binding was much lower in all subjects. Lower SHBG of morbidly obese (BMI >40 kg/m 2 ) subjects affected testosterone but not estradiol. The ratio of binding sites to SHBG protein levels was constant for testosterone, but not for estradiol. The influence of gender was maximal in morbid obesity, with men showing the highest binding / SHBG ratios. The results reported here are compatible with SHBG being a mixture of at least two functionally different hormone-binding globulins, being affected by obesity and gender and showing different structure, affinities for testosterone and estradiol and also different immunoreactivity. © 2017 European Society of Endocrinology.

  9. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    OpenAIRE

    Jensen JT; Bitzer J; Serrani M

    2013-01-01

    Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2)-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA,...

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

    Directory of Open Access Journals (Sweden)

    Sheila Krishnan

    2010-08-01

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

  11. β-ESTRADIOL INDUCES CYTOTOXIC EFFECTS TO HUMAN T-LYMPHOMA (JURKAT) CELLS THROUGH OXIDATIVE STRESS.

    Science.gov (United States)

    Yedjou, Clement; Cameron, Joseph; Mbemi, Ariane T; Tchounwou, Paul

    2015-04-01

    β-estradiol is the most potent estrogen of a group of endogenous estrogen steroids which includes estrone and estriol. This steroid hormone is the most potent natural estrogen, produced mainly by the ovary, placenta, and in smaller amounts by the adrenal cortex, and the male testes. Although β-estradiol protects the renal and cardiovascular systems, the mechanisms involved remain unclear. In this research, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay to evaluate the effect of β-estradiol on human T-lymphoma (Jurkat) cells upon 24 and 48 hours, respectively. Lipid peroxidation assay was also performed to estimate the levels of malondialdehyde (MDA) production in β-estradiol-treated cells. The results of MTT assay demonstrated that low, physiological levels of β-estradiol induce cellular proliferation in Jurkat T-cells. At higher dose of exposure, β-estradiol decreases the viability of Jurkat T-cells compared to the control cells. Data generated from lipid peroxidation assay resulted in a significant increase (p Jurkat T-cells. This cytotoxicity is found to be associated with oxidative stress.

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

    Science.gov (United States)

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

    2017-11-01

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

  13. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

    Science.gov (United States)

    Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

    1998-01-01

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

  14. Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

    Directory of Open Access Journals (Sweden)

    Furlanetto T.W.

    2001-01-01

    Full Text Available Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 ± 0.370 to 2.085 ± 0.364 pmol I-/µg DNA at 1 ng/ml (P<0.02, to 1.970 ± 0.302 pmol I-/µg DNA at 10 ng/ml (P<0.003, and to 2.038 ± 0.389 pmol I-/µg DNA at 100 ng/ml (P<0.02. In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 ± 0.408 to 7.312 ± 0.506 pmol I-/µg DNA (P<0.02. A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

  17. 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.

  18. 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}.

  19. Mechanical spectral shift reactor

    International Nuclear Information System (INIS)

    Wilson, J.F.; Sherwood, D.G.

    1982-01-01

    A mechanical spectral shift reactor comprises a reactive core having fuel assemblies accommodating both water displacer elements and neutron absorbing control rods for selectively changing the volume of water-moderator in the core. The fuel assemblies with displacer and control rods are arranged in alternating fashion so that one displacer element drive mechanism may move displacer elements in more than one fuel assembly without interfering with the movement of control rods of a corresponding control rod drive mechanisms. (author)

  20. The significance of estradiol metabolites in human corpus luteum physiology.

    Science.gov (United States)

    Devoto, Luigi; Henríquez, Soledad; Kohen, Paulina; Strauss, Jerome F

    2017-07-01

    The human corpus luteum (CL) is a temporary endocrine gland derived from the ovulated follicle. Its formation and limited lifespan is critical for steroid hormone production required to support menstrual cyclicity, endometrial receptivity for successful implantation, and the maintenance of early pregnancy. Endocrine and paracrine-autocrine molecular mechanisms associated with progesterone production throughout the luteal phase are critical for the development, maintenance, regression, and rescue by hCG which sustains CL function into early pregnancy. However, the signaling systems driving the regression of the primate corpus luteum in non-conception cycles are not well understood. Recently, there has been interest in the functional roles of estradiol metabolites (EMs), mostly in estrogen-producing tissues. The human CL produces a number of EMs, and it has been postulated that the EMs acting via paracrine-autocrine pathways affect angiogenesis or LH-mediated events. The present review describes advances in understanding the role of EMs in the functional lifespan and regression of the human CL in non-conception cycles. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Fecal estradiol-17β and testosterone in prepubertal domestic cats.

    Science.gov (United States)

    Faya, M; Carranza, A; Miotti, R; Ponchón, T; Furlan, P; Gobello, C

    2013-10-01

    The aim of this article was to describe the time course of prepubertal sexual steroids in domestic cats. Fourteen newborn kittens were followed up until puberty (physical, behavioral, and hormonal changes). Fecal testosterone [T; males] and E estradiol 17-β [E2; females] concentrations were analyzed by repeated measures ANOVA and two consecutive time windows (TWs) were used to compare changes in both male (postnatal weeks 1-4 vs. 5-14) and females (postnatal weeks 1-5 vs. 6-13). Puberty was achieved 14.3 ± 0.3 and 13.3 ± 0.4 weeks after birth in male and female cats, respectively. In both genders, during TW-1 fecal steroids concentrations were similar (males) or even higher (females) to that previously described for mature cats. Fecal T (P cats. It is concluded that in domestic cats there is a sexual steroid surge during the first 4 and 5 postnatal weeks in male and female animals, respectively. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  3. Evaluation of estradiol benzoate as a pre-treatment for oocyte recovery in sheep

    Directory of Open Access Journals (Sweden)

    Marilu Constantino Max

    2014-02-01

    Full Text Available The objective of this study was to compare the number of follicles, oocytes and the recovery rate in sheep submitted to the one-shot protocol with or without ovarian priming with estradiol benzoate (EB. Pluriparous non-lactating sheep (n=33 with an average age of five years (range 4-6 and a body condition score of 3.0±0.3 were divided into three groups. The one-shot group (n=10 was treated with a subcutaneous implant containing 1.5 mg of norgestomet from D0 to D10. The animals in this group were administered 0.04 mg of D-cloprostenol, 200 IU of follicle stimulating hormone (FSH and 300 IU of equine chorionic gonadotropin (eCG on D8. Animals in the EB group (n=11 received the same treatment as one-shot plus the administration of 0.6 mg of EB on D0. In the untreated group (n=12, the animals received no hormone stimulation. The collection of the oocytes was performed by laparotomy 36 h after the administration of gonadotropins (D10. Oocytes were searched and classified based on morphology. An increase was observed (p<0.05 in the number of follicles aspirated in the one-shot vs. the EB and untreated groups (16.3±5.6 vs. 9.5±2.4 and 12.1±4.1, respectively. The average number of oocytes and the recovery rate were higher (p<0.05 in the one-shot and EB groups compared to the untreated group, resulting in 14.2±9.0 and 87.1% (142/163, 11.0±6.2 and 91.4% (122/134 vs. 6.8±3.5 and 71.9% (82/114, respectively. It was concluded that the EB did not improve efficiency in the oneshot protocol, but was significantly better than in untreated animals

  4. Estradiol rapidly activates Akt via the ErbB2 signaling pathway.

    Science.gov (United States)

    Stoica, Gerald E; Franke, Thomas F; Wellstein, Anton; Czubayko, Frank; List, Heinz-Joachim; Reiter, Ronald; Morgan, Elisha; Martin, Mary Beth; Stoica, Adriana

    2003-05-01

    Previously, we have demonstrated that the two mitogenic growth factors epidermal growth factor and IGF-I can activate Akt and estrogen receptor-alpha (ERalpha) in the hormone-dependent breast cancer cell line, MCF-7. In this report we now show that estradiol can also rapidly activate phosphatidylinositol 3-kinase (PI 3-K)/Akt and that this effect is mediated by the ErbB2 signaling pathway. Treatment of cells with estradiol resulted in phosphorylation of Akt and a 9-fold increase in Akt activity in 10 min. Akt activation was blocked by wortmannin and LY 294,002, two inhibitors of PI 3-K; by genistein, a protein tyrosine kinase inhibitor and an ER agonist; by AG825, a selective ErbB2 inhibitor; and by the antiestrogens ICI 182,780 and 4-hydroxy-tamoxifen; but not by rapamycin, an inhibitor of the ribosomal protein kinase p70S6K; nor by AG30, a selective epidermal growth factor receptor inhibitor. Akt activation by estradiol was abrogated by an arginine-to-cysteine mutation in the pleckstrin homology domain of Akt (R25C). Growth factors also activated Akt in the ER-negative variant of MCF-7, MCF-7/ADR, but estradiol did not induce Akt activity in these cells. Transient transfection of ERalpha into these cells restored Akt activation by estradiol, suggesting that estradiol activation of Akt requires the ERalpha. Estradiol did not activate Akt in MCF-7 cells stably transfected with an anti-ErbB2-targeted ribozyme, further confirming a role for ErbB2. In vitro kinase assays using immunoprecipitation and anti-Akt1, -Akt2, and -Akt3-specific antibodies demonstrated that Akt1 is activated by estradiol in MCF-7 cells whereas Akt3 is the activated isoform in ER-negative MDA-MB231 cells, implying that selective activation of Akt subtypes plays a role in the actions of estradiol. Taken together, our data suggest that estradiol, bound to membrane ERalpha, interacts with and activates an ErbB dimer containing ErbB2, inducing activation of PI 3-K/Akt.

  5. Regulation of Na+/K+-ATPase by Estradiol and IGF-1 in Cardio-Metabolic Diseases.

    Science.gov (United States)

    Obradovic, Milan; Stanimirovic, Julijana; Panic, Anastasija; Bogdanovic, Nikola; Sudar-Milovanovic, Emina; Cenic-Milosevic, Desanka; Isenovic, Esma R

    2017-01-01

    The sodium/potassium- adenosine- triphosphatase (Na+/K+-ATPase) is an important mediator in vasculature tone and contractility, and its abnormal regulation has been implicated in many diseases such as obesity, insulin resistance, diabetes, and hypertension. Decreased Na+/K+-ATPase abundance and its altered isoform expression induce cardiomyocytes death and cardiac dysfunction, possibly leading to the development of myocardial dilation and heart failure. Therefore, the regulation of Na+/K+-ATPase activity/expression could be important in treatment and possible prevention of cardio-metabolic diseases. A number of hormones and environmental factors regulate the function of Na+/K+-ATPase in response to changing cellular requirements. Estradiol and insulin like growth factor-1 (IGF-1) are among potent hormones that positively regulate Na+/K+- ATPase activity or de novo synthesis of α - and β - subunits. Both estradiol and IGF-1 have a huge therapeutic potential in treatment of vasculopathy in cardio-metabolic diseases. We searched the MEDLINE and PUBMED databases for all English and non-English articles with an English abstract from April 1978 to May 2016. The main data search terms were: Na+/K+-ATPase; estradiol and Na+/K+-ATPase; estradiol, Na+/K+-ATPase and CVS; estradiol, Na+/K+-ATPase and CVD; estradiol, Na+/K+- ATPase and obesity; estradiol, Na+/K+-ATPase and diabetes; estradiol, Na+/K+-ATPase and hypertension; IGF-1; IGF-1 and Na+/K+-ATPase; IGF-1, Na+/K+-ATPase and CVS; IGF-1, Na+/K+-ATPase and CVD; IGF-1, Na+/K+- ATPase and obesity; IGF-1, Na+/K+-ATPase and diabetes; IGF-1, Na+/K+-ATPase and hypertension. The present review discusses the latest data from animal and human studies which focus on the effects of estradiol and IGF-1 on Na+/K+-ATPase regulation in physiological and pathophysiological conditions in cardiovascular system. Understanding the molecular mechanisms of estradiol and IGF-1 action on Na+/K+-ATPase in humans, may help resolving outstanding

  6. Estradiol-induced vaginal mucus inhibits antigen penetration and CD8(+) T cell priming in response to intravaginal immunization.

    Science.gov (United States)

    Seavey, Matthew M; Mosmann, Tim R

    2009-04-14

    Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8(+) T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APCs) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8(+) T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8(+) T cell priming after insemination or vaginal vaccination.

  7. Estradiol-induced vaginal mucus inhibits antigen penetration and CD8+ T cell priming in response to intravaginal immunization

    Science.gov (United States)

    Seavey, Matthew M.; Mosmann, Tim R.

    2010-01-01

    Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8+ T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APC) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8+ T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8+ T cell priming after insemination or vaginal vaccination. PMID:19428849

  8. Effects of 17 beta-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Weichselbaum, R.R.

    1981-01-01

    We have investigated the effects of 17 beta-estradiol, given both alone and with X-irradiation, on the induction of malignant transformation in vitro. Treatment with 10(-6)M 17 beta-estradiol for 6 weeks, or 10(-5)M 17 beta-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicate an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation

  9. Effects of 17 beta-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A.R.; Weichselbaum, R.R.

    1981-01-01

    We have investigated the effects of 17 beta-estradiol, given both alone and with X-irradiation, on the induction of malignant transformation in vitro. Treatment with 10(-6)M 17 beta-estradiol for 6 weeks, or 10(-5)M 17 beta-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicate an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation.

  10. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2014-05-09

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  11. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Directory of Open Access Journals (Sweden)

    M.F. Souza

    2014-06-01

    Full Text Available Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL, estradiol (0.05 mg/mL, progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  12. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    International Nuclear Information System (INIS)

    Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.

    2014-01-01

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse

  13. Mechanism of Estradiol-Induced Block of Voltage-Gated K+ Currents in Rat Medial Preoptic Neurons

    Science.gov (United States)

    Druzin, Michael; Malinina, Evgenya; Grimsholm, Ola; Johansson, Staffan

    2011-01-01

    The present study was conducted to characterize possible rapid effects of 17-β-estradiol on voltage-gated K+ channels in preoptic neurons and, in particular, to identify the mechanisms by which 17-β-estradiol affects the K+ channels. Whole-cell currents from dissociated rat preoptic neurons were studied by perforated-patch recording. 17-β-estradiol rapidly (within seconds) and reversibly reduced the K+ currents, showing an EC50 value of 9.7 µM. The effect was slightly voltage dependent, but independent of external Ca2+, and not sensitive to an estrogen-receptor blocker. Although 17-α-estradiol also significantly reduced the K+ currents, membrane-impermeant forms of estradiol did not reduce the K+ currents and other estrogens, testosterone and cholesterol were considerably less effective. The reduction induced by estradiol was overlapping with that of the KV-2-channel blocker r-stromatoxin-1. The time course of K+ current in 17-β-estradiol, with a time-dependent inhibition and a slight dependence on external K+, suggested an open-channel block mechanism. The properties of block were predicted from a computational model where 17-β-estradiol binds to open K+ channels. It was concluded that 17-β-estradiol rapidly reduces voltage-gated K+ currents in a way consistent with an open-channel block mechanism. This suggests a new mechanism for steroid action on ion channels. PMID:21625454

  14. Induction of gonadal maturation of eel using PMSG, antidopamine, and estradiol-17β

    Directory of Open Access Journals (Sweden)

    Aprelia Martina Tomasoa

    2015-10-01

    Full Text Available ABSTRACT The study was aimed to induce gonadal maturation of eel Anguilla bicolor bicolor by hormonal treatment using pregnant mare serum gonadotropin (PMSG, antidopamine (AD, dan estradiol-17β (E2. The research used complete randomized design with five hormone combination treatments consisted of PK (NaCl 0.95% as control, P10A (PMSG 10 IU + AD 10 ppm, P20A (PMSG 20 IU + AD 10 ppm, P10BE (PMSG 10 IU + AD 10 ppm + E2 150 µg, and P20BE (PMSG 20 IU + AD 10 ppm + E2 150 µg, with three individual replications for each treatment. Hormonal induction was applied through intramuscular injection weekly during eight weeks at initial body weight of 200 g. The result showed that P10BE treatment has obtained highest level on E2 (0.43 ng/mL, FSH (2.68 mIU/mL has increased in week-4 and level on T (1.2 ng/mL, LH (2.80 mIU/mL has increased in week-8. P10BE has affected spermatogenesis and the increased of GSI (2.46% in fourth and sixth week compared to PK (1.28%, P10A (1.58%, P20A (1.34%, and P20BE (2.12%. In conclusion, combination of PMSG, AD, and E2 hormones could stimulate the gonadal maturation of eel at the size of 200 g into male. Keywords: Anguilla bicolor bicolor, gonadal growth, hormone, maturation  ABSTRAK Penelitian ini dilakukan untuk menginduksi pematangan gonad ikan sidat Anguilla bicolor bicolor secara hormonal dengan menggunakan pregnant mare serum gonadothropin (PMSG, antidopamin (AD, dan estradiol-17β (E2. Metode penelitian ini menggunakan metode eksperimen rancangan acak lengkap dengan lima perlakuan kombinasi hormon, yaitu PK (larutan NaCl 0,95% sebagai kontrol, P10A (PMSG 10 IU + AD 10 ppm, P20A (PMSG 20 IU + AD 10 ppm, P10BE (PMSG 10 IU + AD 10 ppm + E2 150 µg, dan P20BE (PMSG 10 IU+AD 10 ppm+E2 150 µg, dengan tiga ulangan individu pada masing-masing perlakuan. Induksi hormonal dilakukan dengan metode penyutikan secara intramuskuler setiap minggu selama delapan minggu dengan bobot ikan yang berukuran 200 g. Hasil penelitian

  15. Shift rostering using decomposition: assign weekend shifts first

    NARCIS (Netherlands)

    van der Veen, Egbert; Hans, Elias W.; Post, Gerhard F.; Veltman, Bart

    This paper introduces a shift rostering problem that surprisingly has not been studied in literature: the weekend shift rostering problem. It is motivated by our experience that employees’ shift preferences predominantly focus on the weekends, since many social activities happen during weekends. The

  16. Concentrations of 17beta-estradiol in Holstein whole milk.

    Science.gov (United States)

    Pape-Zambito, D A; Magliaro, A L; Kensinger, R S

    2007-07-01

    Some individuals have expressed concern about estrogens in food because of their potential to promote growth of estrogen-sensitive human cancer cells. Researchers have reported concentrations of estrogen in milk but few whole milk samples have been analyzed. Because estrogen associates with the fat phase of milk, the analysis of whole milk is an important consideration. The objectives of this study, therefore, were to quantify 17beta-estradiol (E2) in whole milk from dairy cows and to determine whether E2 concentrations in milk from cows in the second half of pregnancy were greater than that in milk from cows in the first half of pregnancy or in nonpregnant cows. Milk samples and weights were collected during a single morning milking from 206 Holstein cows. Triplicate samples were collected and 2 samples were analyzed for fat, protein, lactose, and somatic cell counts (SCC); 1 sample was homogenized and analyzed for E2. The homogenized whole milk (3 mL) was extracted twice with ethyl acetate and once with methanol. The extract was reconstituted in benzene:methanol (9:1, vol/vol) and run over a Sephadex LH-20 column to separate E2 from cholesterol and estrone before quantification using radioimmunoassay. Cows were classified as not pregnant (NP, n = 138), early pregnant (EP, 1 to 140 d pregnant, n = 47), or midpregnant (MP, 141 to 210 d pregnant, n = 21) at the time of milk sampling based on herd health records. Mean E2 concentration in whole milk was 1.4 +/- 0.2 pg/mL and ranged from nondetectable to 22.9 pg/mL. Milk E2 concentrations averaged 1.3, 0.9, and 3.0 pg/mL for NP, EP, and MP cows, respectively. Milk E2 concentrations for MP cows were greater and differed from those of NP and EP cows. Milk composition was normal for a Holstein herd in that log SCC values and percentages of fat, protein, and lactose averaged 4.9, 3.5, 3.1, and 4.8, respectively. Estradiol concentration was significantly correlated (r = 0.20) with percentage fat in milk. Mean milk yield was

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

    Science.gov (United States)

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

    2001-01-01

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

  18. Curcumin inhibits endometriosis endometrial cells by reducing estradiol production.

    Science.gov (United States)

    Zhang, Ying; Cao, Hong; Yu, Zheng; Peng, Hai-Ying; Zhang, Chang-Jun

    2013-05-01

    Endometriosis is a complex estrogen-dependent disease that is defined as the presence of endometrial gland and stroma outside the uterine cavity. Although the exact mechanism for the development of endometriosis remains unclear, there is a large body of research data and circumstantial evidence that suggests a crucial role of estrogen in the establishment and maintenance of this disease. This study is an attempt to assess the effect of curcumin on inhibiting endometriosis endometrial cells and to investigate whether such an effect is mediated by reducing estradiol production. Endometriotic stromal cells, normal endometrial stromal cells, endometriotic epithelial cells and normal endometrial epithelial cells were isolated and cultured. E2 value of cells and the effect of curcumin on cell proliferation were evaluated. Finally, effect of curcumin on E2 assay was detected. Electrochemiluminescence immunoassay results showed that E2 value of endometriotic epithelial cells was higher than the endometriotic stromal cells (p=0.037), while the expression of E2 in normal endometrial stromal and epithelial cells was extremely low. WST-8 result showed, compared with endometrial stromal cells, ectopic endometriotic stromal cells had a higher growth rate. After intervene with curcumin (10μmol/L, 30μmol/L and 50μmol/L) for 0-96h, the number of endometriotic stromal cells was reduced and cells growth slowed, compared with 0μmol/L group. Compared with 0μmol/L group, E2 level was lower after treatment with curcumin, especially in 30μmol/L and 50μmol/L group. In summary, in this study we found that E2 is important in ectopic endometrium, and epithelial cell is in dominant position with E2 secretion. Curcumin was able to suppress the proliferation of endometrial cells by reducing the E2 value.

  19. Ovarian estradiol production and lipid metabolism in postmenopausal women.

    Science.gov (United States)

    Maruoka, Risa; Tanabe, Akiko; Watanabe, Ayako; Nakamura, Kiyoko; Ashihara, Keisuke; Tanaka, Tomohito; Terai, Yoshito; Ohmichi, Masahide

    2014-10-01

    Menopause is defined as the permanent cessation of menses. Although previous studies demonstrated a slight production of androgens and estrogens by postmenopausal ovaries, the impact of hormone production on lipid metabolism is still uncertain. The aim of this study was to evaluate whether the postmenopausal ovary is hormonally active and whether hormone status contributes to lipid metabolism. This was a prospective study of 87 women who were treated for gynecological diseases (29% had cervical cancer, 49% had endometrial cancer, 7% had fibroid tumors, and 15% had cervical intraepithelial neoplasia). They were categorized as early postmenopausal (n = 40; mean [SD], 56.8 [3.8] y) or late postmenopausal (n = 47; mean [SD], 66.6 [5.7] y) women. Serum specimens were collected from the peripheral and ovarian veins of participants undergoing bilateral oophorectomy. Sex steroid hormone levels and lipid profiles were determined. Statistically significant differences in estradiol (E2) and testosterone were seen between the ovarian samples and the peripheral samples in all groups. E2 and estrone obtained from ovarian venous samples gradually decreased with age in postmenopausal women. There was a significant correlation between ovarian E2 and high-density lipoprotein cholesterol levels and the low-density lipoprotein-to-high-density lipoprotein ratio. However, there was no correlation between peripheral E2 levels and any of the lipid parameters examined. Although this study investigates women with gynecological diseases, the postmenopausal ovary is hormonally active, and the E2 produced by postmenopausal ovaries may therefore contribute to the maintenance of lipid metabolism.

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

    Science.gov (United States)

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

    2002-01-01

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

  1. Repetition and Translation Shifts

    Directory of Open Access Journals (Sweden)

    Simon Zupan

    2006-06-01

    Full Text Available Repetition manifests itself in different ways and at different levels of the text. The first basic type of repetition involves complete recurrences; in which a particular textual feature repeats in its entirety. The second type involves partial recurrences; in which the second repetition of the same textual feature includes certain modifications to the first occurrence. In the article; repetitive patterns in Edgar Allan Poe’s short story “The Fall of the House of Usher” and its Slovene translation; “Konec Usherjeve hiše”; are compared. The author examines different kinds of repetitive patterns. Repetitions are compared at both the micro- and macrostructural levels. As detailed analyses have shown; considerable microstructural translation shifts occur in certain types of repetitive patterns. Since these are not only occasional; sporadic phenomena; but are of a relatively high frequency; they reduce the translated text’s potential for achieving some of the gothic effects. The macrostructural textual property particularly affected by these shifts is the narrator’s experience as described by the narrative; which suffers a reduction in intensity.

  2. Cognitive stimulation in healthy older adults: a cognitive stimulation program using leisure activities compared to a conventional cognitive stimulation program.

    Science.gov (United States)

    Grimaud, Élisabeth; Taconnat, Laurence; Clarys, David

    2017-06-01

    The aim of this study was to compare two methods of cognitive stimulation for the cognitive functions. The first method used an usual approach, the second used leisure activities in order to assess their benefits on cognitive functions (speed of processing; working memory capacity and executive functions) and psychoaffective measures (memory span and self esteem). 67 participants over 60 years old took part in the experiment. They were divided into three groups: 1 group followed a program of conventional cognitive stimulation, 1 group a program of cognitive stimulation using leisure activities and 1 control group. The different measures have been evaluated before and after the training program. Results show that the cognitive stimulation program using leisure activities is as effective on memory span, updating and memory self-perception as the program using conventional cognitive stimulation, and more effective on self-esteem than the conventional program. There is no difference between the two stimulated groups and the control group on speed of processing. Neither of the two cognitive stimulation programs provides a benefit over shifting and inhibition. These results indicate that it seems to be possible to enhance working memory and to observe far transfer benefits over self-perception (self-esteem and memory self-perception) when using leisure activities as a tool for cognitive stimulation.

  3. The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives.

    Science.gov (United States)

    Sinofsky, F E; Pasquale, S A

    1998-02-01

    This open-label, two-period, crossover study was conducted to evaluate the effect of a single 150 mg dose of fluconazole on the pharmacokinetics of ethinyl estradiol in healthy female subjects. Ten subjects regularly taking Ortho-Novum 7/7/7 (Ortho Pharmaceutical, Raritan, N.J.) and 10 subjects regularly taking Triphasil (Wyeth-Ayerst Laboratories, Philadelphia), which contain ethinyl estradiol 35 microg and 30 microg during days 1 to 6, respectively, were randomly assigned to receive a single 150 mg dose of fluconazole 2 hours before the oral contraceptive, on pill day 6 of one of two menstrual cycles. Ethinyl estradiol serum concentrations were measured at baseline and up to 24 hours after oral contraceptive intake. No fluconazole was administered during the other menstrual cycle, which served as the control. Mean serum concentrations of ethinyl estradiol were increased after fluconazole administration in both oral contraceptive groups. Maximum observed serum concentration and area under the concentration-time curve values were significantly (p < 0.05) greater during the fluconazole regimens (vs regimens without fluconazole) for both oral contraceptive groups and for combined values of the two oral contraceptive groups. The mean time to reach the maximum concentration was not altered by concomitant fluconazole administration. These findings suggest that there is a potential for a clinically significant interaction between coadministration of fluconazole and ethinyl estradiol in oral contraceptives.

  4. Utility of salivary enzyme immunoassays for measuring estradiol and testosterone in adolescents: a pilot study.

    Science.gov (United States)

    Amatoury, Mazen; Lee, Jennifer W; Maguire, Ann M; Ambler, Geoffrey R; Steinbeck, Katharine S

    2016-04-09

    We investigated the utility of enzyme immunoassay kits for measuring low levels of salivary estradiol and testosterone in adolescents and objectively assessed prevalence of blood contamination. Endocrine patients provided plasma and saliva for estradiol (females) or testosterone (males) assay. Saliva samples were also tested with a blood contamination kit. Picomolar levels of salivary estradiol in females failed to show any significant correlation with plasma values (r=0.20, p=0.37). The nanomolar levels of salivary testosterone in males showed a strong correlation (r=0.78, p<0.001). A significant number of saliva samples had blood contamination. After exclusion, correlations remained non-significant for estradiol, but strengthened for testosterone (r=0.88, p<0.001). The salivary estradiol enzyme immunoassay is not clinically informative at low levels. Users should interpret clinical saliva with caution due to potential blood contamination. Our data supports the utility of the salivary testosterone enzyme immunoassay for monitoring adolescent boys on hormone developmental therapy.

  5. The effects of estradiol on mood and behavior in human female adolescents: a systematic review.

    Science.gov (United States)

    Balzer, Ben W R; Duke, Sally-Anne; Hawke, Catherine I; Steinbeck, Katharine S

    2015-03-01

    Mood disorders and health risk behaviors increase in adolescence. Puberty is considered to contribute to these events. However, the precise impact of pubertal hormone changes to the emergence of mood disorders and risk behaviors is relatively unclear. It is important that inappropriate attribution is not made. Our aim was to determine what is known about the effect of endogenous estradiol on human adolescent girls' mood and behavior. The databases searched were MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Pre-MEDLINE, Web of Science, and Scopus for all dates to October 2014. For inclusion, contemporaneous hormone and mood or behavioral assessment was required. Data were extracted following a template created by the authors. Fourteen studies met our inclusion criteria. There was some consistency in findings for mood and estradiol levels, with associations between estradiol and depression and emotional tone and risk taking. Results were less consistent for studies assessing other mood and behavioral outcomes. Most studies were cross-sectional in design; assay methodologies used in older studies may lack the precision to detect early pubertal hormone levels. Three longitudinal and several cross-sectional studies indicate potential associations between estradiol and certain mood or affective states, especially depression and mood variability though there are insufficient data to confirm that the rise in estradiol during puberty is causative. We believe that it is important for health professionals to take care when attributing adolescent psychopathology to puberty hormones, as the current data supporting these assertions are limited.

  6. Effects of estradiol and progesterone on the variability of the micronucleus assay

    International Nuclear Information System (INIS)

    Baeyens, Ans; Vandersickel, Veerle; Thierens, Hubert; Ridder, Leo De; Vral, Anne

    2005-01-01

    To investigate chromosomal radiosensitivity of lymphocytes the micronucleus (MN) assay has been used for many years. The results of these studies suggest the use of the MN assay as a biomarker for cancer predisposition. However, the MN assay has still some limitations associated with the reproducibility and sensitivity. Especially a high intra-individual variability has been observed. An explanation for this high intra-individual variability is not yet available. In literature it is suggested that the high variability among females is attributable to hormonal status. In this study we investigated if the high intra-individual variability in micronucleus formation in lymphocytes of females after in vitro exposure to ionising radiation is caused by variations in hormone levels of estradiol (E2) and progesterone (PROG). For this, the MN assay was performed on blood samples of 18 healthy women during 7 consecutive weeks while the estradiol and progesterone levels were determined at the same time. The MN assay was also examined in cultures of isolated blood lymphocytes with estradiol or progesterone levels added in vitro. The results demonstrated that estradiol and progesterone levels have no influence on the variations in radiation-induced MN yields observed in blood samples of healthy women. These conclusions were confirmed by the 'in vitro' experiments as no correlation between the MN yields and the concentrations of hormones (estradiol or progesterone) added in vitro to isolated lymphocytes cultures was observed

  7. Lanthanide shift reagents, binding, shift mechanisms and exchange

    International Nuclear Information System (INIS)

    Boer, J.W.M. de

    1977-01-01

    Paramagnetic lanthanide shift reagents, when added to a solution of a substrate, induce shifts in the nuclear magnetic resonance (NMR) spectrum of the substrate molecules. The induced shifts contain information about the structure of the shift reagent substrate complex. The structural information, however, may be difficult to extract because of the following effects: (1) different complexes between shift reagent and substrate may be present in solution, e.g. 1:1 and 1:2 complexes, and the shift observed is a weighed average of the shifts of the substrate nuclei in the different complexes; (2) the Fermi contact interaction, arising from the spin density at the nucleus, contributes to the induced shift; (3) chemical exchange effects may complicate the NMR spectrum. In this thesis, the results of an investigation into the influence of these effects on the NMR spectra of solutions containing a substrate and LSR are presented. The equations describing the pseudo contact and the Fermi contact shift are derived. In addition, it is shown how the modified Bloch equations describing the effect of the chemical exchange processes occurring in the systems studied can be reduced to the familiar equations for a two-site exchange case. The binding of mono- and bifunctional ethers to the shift reagent are reported. An analysis of the induced shifts is given. Finally, the results of the experiments performed to study the exchange behavior of dimethoxyethane and heptafluorodimethyloctanedionato ligands are presented

  8. Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

    Science.gov (United States)

    Bowman, R E; Ferguson, D; Luine, V N

    2002-01-01

    Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

  9. The shift in windpower

    International Nuclear Information System (INIS)

    Gipe, P.

    1992-01-01

    Despite new production records, the near-term market for new windpower projects in the US remains bleak. Congressional incentives and project proposals in the mid-1990s offer promise, but for now most development has shifted to Europe. During 1992 and 1993 the largest wind projects developed by US companies will not be in the US, but in the United Kingdom and Spain. Indeed, most of the US's windpower industry is going abroad, establishing offices overseas. This move toward Europe comes as little surprise. New project development for US firms has faltered at home while the European market has burgeoned. The topics of the article include the move to Europe, a reduction in California's share of producing wind power plants, a rise in Europe's share of producing wind power plants, the future market for wind power in the US, and reawakening California's market

  10. Final report on key comparison CCQM-K55.a (estradiol): An international comparison of mass fraction purity assignment of estradiol

    Science.gov (United States)

    Westwood, Steven; Josephs, Ralf; Daireaux, Adeline; Wielgosz, Robert; Davies, Stephen; Wang, Hongjie; Rodrigues, Jainana; Wollinger, Wagner; Windust, Anthony; Kang, Ma; Fuhai, Su; Philipp, Rosemarie; Kuhlich, Paul; Wong, Siu-kay; Shimizu, Yoshitaka; Pérez, Melina; Avila, Marco; Fernandes-Whaley, Maria; Prevoo, D.; de Vos, J.; Visser, R.; Archer, M.; LeGoff, Thierry; Wood, Steve; Bearden, Dan; Bedner, Mary; Boroujerdi, Arezue; Duewer, David; Hancock, Diane; Lang, Brian; Porter, Barbara; Schantz, Michele; Sieber, John; White, Edward; Wise, Stephen A.

    2012-01-01

    Under the auspices of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a key comparison, CCQM K55.a, was coordinated by the Bureau International des Poids et Mesures (BIPM) in 2009/2010. Eleven national measurement institutes and the BIPM participated. Participants were required to assign the mass fraction of estradiol present as the main component in the comparison sample (CCQM-K55.a) which consisted of a bulk estradiol hemihydrate material obtained from a commercial supplier that had been extensively but not exhaustively dried prior to sub-division into the units supplied for the comparison. Estradiol was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of organic compounds of medium structural complexity [molar mass range 300-500 Da] and low polarity (pKOW process. The results displaying a positive bias relative to the KCRV (overestimation of estradiol content) were due to underestimation of the water content of the material, while those with a negative bias (underestimation of estradiol) overestimated the total related substance impurities through a failure to detect and control for artefact formation arising from in situ oxidative dimerization of estradiol in neutral solution prior to analysis. There was however good agreement between all participants in the identification and the quantification of the individual related structure impurities actually present in the sample. The comparison also demonstrated the utility of high-field 1H NMR for both quantitative and qualitative analysis of high purity compounds. It is noted that all the participants who used qNMR as a major or contributing technique and included it as part of, combined it or confirmed it with a conventional 'mass balance' data estimate, obtained results consistent with the KCRV. Main text. To reach the main text of this paper, click on Final Report. Note that this text is

  11. Inclusion of 3H-estradiol-17#betta# in the chick embryo ovary in vitro

    International Nuclear Information System (INIS)

    Angelova, P.; Martinova, J.; K''ncheva, L.; Jordonov, Zh.; Bylgarska Akademiya na Naukite, Sofia)

    1982-01-01

    Basing on literature data on experimental investigation of genital differentiation of chick embryonal gonad in vitro, the authors have made their proposal that relationship between extragents and androgens in the favour of estradiol is of a great importance for differentiation of the gonad corti-- cal zone and for interruption of the meiosis process in cortical genital cells both genetically female and male (in the case of testis feminization). The autoradiographic investigation on 3 H-estradiol-17#betta# inclusion in an embryonal chick ovary in the period before the beginning of the meiotic prophase in genital cells has been performed in order to prove this hypothesis. The results obtained complement Gasc data on the presence of receptors for steroid hormones in embryonal chick gonads and confirm a conception that the development of indifferent gonad in female line is the same as the differentiation of cortical genital cells to oocyte conditioned by estradiol

  12. Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Di Paolo, T.; Falardeau, P.

    1987-08-31

    The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p < 0.001). Competition for (/sup 3/H)-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-(..beta..-..gamma..-imino)triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables.

  13. Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

    International Nuclear Information System (INIS)

    Di Paolo, T.; Falardeau, P.

    1987-01-01

    The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p 3 H]-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-[β-γ-imino]triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables

  14. Negative effect of 17-beta-estradiol on growth parameters of goldfish (Carassius auratus

    Directory of Open Access Journals (Sweden)

    Reza Tarkhani

    2015-03-01

    Full Text Available Objective: To evaluate the effects of 17-beta-estradiol on growth factors of goldfish (Carassius auratus. Methods: To perform the test, 17-beta-estradiol was given 3 months period to fish at different doses as followed: control group, Group 1: 10 mg/kg food, Group 2: 25 mg/kg food and Group 3: 50 mg/kg food. For this purpose, a solution of hormone in pure ethanol used to spray on food. Feeding was done 3 times daily as an appetite. Comparing the mean values measured for length and weight using ANOVA. Results: Indicated with increase length and weight, the effects of the hormone get more distinct, so that with increase concentration of hormone, reduce weight and length. Conclusions: Estradiol along with testosterone and progesterone regulates final stages of oocyte maturation and ovulation. Various studies have proven the different concentrations of this hormone has different effects on the growth of different fishes.

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

    Science.gov (United States)

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

    2015-05-01

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

  16. Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

    DEFF Research Database (Denmark)

    Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

    2003-01-01

    arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

  17. Serum estradiol:oocyte ratio as a predictor of reproductive outcome: an analysis of data from >9000 IVF cycles in the Republic of Ireland.

    Science.gov (United States)

    Vaughan, Denis A; Harrity, Conor; Sills, E Scott; Mocanu, Edgar V

    2016-04-01

    The purpose of this study was to evaluate the serum estradiol (E2) per oocyte ratio (EOR) as a function of selected embryology events and reproductive outcomes with IVF. This retrospective analysis included all IVF cycles where oocyte collection and fresh transfer occurred between January 2001 and November 2012 at a single institution. Patients were divided by three age groups (highest in patients with EOR of 250-750 and declined as this ratio increased, independent of patient age. While the odds ratio (OR) for clinical pregnancy where EOR = 250-750 vs. EOR > 1500 was 3.4 (p response to gonadotropin stimulation could optimize IVF treatments going forward.

  18. Mineralocorticoid receptor haplotype, estradiol, progesterone and emotional information processing.

    Science.gov (United States)

    Hamstra, Danielle A; de Kloet, E Ronald; Quataert, Ina; Jansen, Myrthe; Van der Does, Willem

    2017-02-01

    Carriers of MR-haplotype 1 and 3 (GA/CG; rs5522 and rs2070951) are more sensitive to the influence of oral contraceptives (OC) and menstrual cycle phase on emotional information processing than MR-haplotype 2 (CA) carriers. We investigated whether this effect is associated with estradiol (E2) and/or progesterone (P4) levels. Healthy MR-genotyped premenopausal women were tested twice in a counterbalanced design. Naturally cycling (NC) women were tested in the early-follicular and mid-luteal phase and OC-users during OC-intake and in the pill-free week. At both sessions E2 and P4 were assessed in saliva. Tests included implicit and explicit positive and negative affect, attentional blink accuracy, emotional memory, emotion recognition, and risky decision-making (gambling). MR-haplotype 2 homozygotes had higher implicit happiness scores than MR-haplotype 2 heterozygotes (p=0.031) and MR-haplotype 1/3 carriers (pinformation processing and P4 or E2 differed between sessions, as well as the moderating effects of the MR genotype. In the first session the MR-genotype moderated the influence of P4 on implicit anxiety (sr=-0.30; p=0.005): higher P4 was associated with reduction in implicit anxiety, but only in MR-haplotype 2 homozygotes (sr=-0.61; p=0.012). In the second session the MR-genotype moderated the influence of E2 on the recognition of facial expressions of happiness (sr=-0.21; p=0.035): only in MR-haplotype 1/3 higher E2 was correlated with happiness recognition (sr=0.29; p=0.005). In the second session higher E2 and P4 were negatively correlated with accuracy in lag2 trials of the attentional blink task (pinformation processing. This moderating effect may depend on the novelty of the situation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Application of adaptive neuro-fuzzy inference systems (ANFIS) to delineate estradiol, glutathione and homocysteine interactions.

    Science.gov (United States)

    Mohan, Iyyapu Krishna; Khan, Siraj Ahmed; Jacob, Rachel; Sushma Chander, Nooguri; Hussain, Tajamul; Alrokayan, Salman A; Radha Rama Devi, Akella; Naushad, Shaik Mohammad

    2017-08-01

    The rationale of the current study was to elucidate the contributing factors for the gender-based differences in total plasma homocysteine levels. A total of 413 subjects comprising of 293 men and 120 women were enrolled for the study. Chemiluminescence technology for vitamin B 12 , folate and total plasma homocysteine; ELISA for estradiol and 8-oxo-2-deoxyguanosine; Ellman's method for total glutathione; and PCR-RFLP analysis for the detection of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism were employed. No statistically significant differences were observed between the men and women in the distribution of age (p = 0.82), vitamin B 12 (p = 0.23), folate (p = 0.36) and MTHFR C677T polymorphism (p = 0.35). However, the total plasma homocysteine levels were higher in men compared to women (28.4 ± 17.9 vs. 20.6 ± 13.6 μmol/L, p neuro-fuzzy inference systems (ANFIS) were developed to understand trivariate interactions among estradiol, glutathione and homocysteine. In the presence of adequate estradiol levels, inverse association was observed between glutathione and homocysteine. This association is lost when estradiol levels were inadequate. Estradiol was found to quench homocysteine mediated oxidative DNA damage. Irrespective of gender, combined deficiency of vitamin B 12 and folate showed positive association with hyperhomocysteinemia and vice versa. Homocysteine reduction in response to vitamin status varied according to gender with men responding to folate and women responding to B 12 . To conclude, gender-differences in homocysteine are attributable estradiol mediated lowering of homocysteine that prevents inactivation of glutathione mediated oxidative defense in women. Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  20. In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

    International Nuclear Information System (INIS)

    Garvin, Stina; Dabrosin, Charlotta

    2008-01-01

    Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue. Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections. We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF. We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo

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

    Science.gov (United States)

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

    2015-01-01

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

  2. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation.

    Science.gov (United States)

    Lewis, Joan S; Meeke, Kathleen; Osipo, Clodia; Ross, Eric A; Kidawi, Noman; Li, Tianyu; Bell, Eric; Chandel, Navdeep S; Jordan, V Craig

    2005-12-07

    We previously developed an estrogen receptor (ER)-positive breast cancer cell line (MCF-7:5C) that is resistant to long-term estrogen deprivation and undergoes rapid and complete apoptosis in the presence of physiologic concentrations of 17beta-estradiol. Here, we investigated the role of the mitochondrial apoptotic pathway in this process. Apoptosis in MCF-7:5C cells treated with estradiol, fulvestrant, or vehicle (control) was investigated by annexin V-propidium iodide double staining and 4',6-diamidino-2-phenylindole (DAPI) staining. Apoptosis was also analyzed in MCF-7:5C cells transiently transfected with small interfering RNAs (siRNAs) to apoptotic pathway components. Expression of apoptotic pathway intermediates was measured by western blot analysis. Mitochondrial transmembrane potential (psim) was determined by rhodamine-123 retention assay. Mitochondrial pathway activity was determined by cytochrome c release and cleavage of poly(ADP-ribose) polymerase (PARP) protein. Tumorigenesis was studied in ovariectomized athymic mice that were injected with MCF-7:5C cells. Differences between the treatment groups and control group were determined by two-sample t test or one-factor analysis of variance. All statistical tests were two-sided. MCF-7:5C cells treated with estradiol underwent apoptosis and showed increased expression of proapoptotic proteins, decreased psim, enhanced cytochrome c release, and PARP cleavage compared with cells treated with fulvestrant or vehicle. Blockade of Bax, Bim, and p53 mRNA expression by siRNA reduced estradiol-induced apoptosis relative to control by 76% [95% confidence interval (CI) = 73% to 79%, P estradiol-induced apoptosis in long-term estrogen-deprived breast cancer cells. Physiologic concentrations of estradiol could potentially be used to induce apoptosis and tumor regression in tumors that have developed resistance to aromatase inhibitors.

  3. Evidence that the [3H]estradiol-binding protein in pancreas is localized in exocrine cells

    International Nuclear Information System (INIS)

    Grossman, A.; Richardson, S.B.; Altszuler, N.; Lane, B.

    1985-01-01

    Extracts of rat pancreas contain significant amounts of an [ 3 H]estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining [ 3 H]estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of [ 3 H]estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for [ 3 H]estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of [ 3 H]estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in [ 3 H]estradiol-binding activity

  4. In Vitro Interactions between 17β-Estradiol and DNA Result in Formation of the Hormone-DNA Complexes

    Directory of Open Access Journals (Sweden)

    Zbynek Heger

    2014-07-01

    Full Text Available Beyond the role of 17β-estradiol (E2 in reproduction and during the menstrual cycle, it has been shown to modulate numerous physiological processes such as cell proliferation, apoptosis, inflammation and ion transport in many tissues. The pathways in which estrogens affect an organism have been partially described, although many questions still exist regarding estrogens’ interaction with biomacromolecules. Hence, the present study showed the interaction of four oligonucleotides (17, 20, 24 and/or 38-mer with E2. The strength of these interactions was evaluated using optical methods, showing that the interaction is influenced by three major factors, namely: oligonucleotide length, E2 concentration and interaction time. In addition, the denaturation phenomenon of DNA revealed that the binding of E2 leads to destabilization of hydrogen bonds between the nitrogenous bases of DNA strands resulting in a decrease of their melting temperatures (Tm. To obtain a more detailed insight into these interactions, MALDI-TOF mass spectrometry was employed. This study revealed that E2 with DNA forms non-covalent physical complexes, observed as the mass shifts for app. 270 Da (Mr of E2 to higher molecular masses. Taken together, our results indicate that E2 can affect biomacromolecules, as circulating oligonucleotides, which can trigger mutations, leading to various unwanted effects.

  5. The effect of low doses of zearalenone and its metabolites on progesterone and 17β-estradiol concentrations in peripheral blood and body weights of pre-pubertal female Beagle dogs.

    Science.gov (United States)

    Gajęcka, Magdalena; Zielonka, Łukasz; Dąbrowski, Michał; Mróz, Magdalena; Gajęcki, Maciej

    2013-12-15

    The experiment involved 30 clinically healthy female Beagle dogs aged approximately 70 days with estimated initial body weight (BW) of 8 kg. The animals were randomly divided into two experimental groups (EI and EII) and a control group of 10 animals each. Group EI was intoxicated with 50 μg zearalenone/kg BW per os for 42 days, group EII received 75 μg zearalenone/kg BW per os for 42 days, and the control group was administered placebo per os for 42 days. The animals were weighed, and blood samples for analyses of the concentrations of zearalenone, its metabolites, progesterone and 17β-estradiol were collected seven times at seven-day intervals, one hour after mycotoxin administration. Biotransformation of zearalenone was observed in all groups throughout the experiment, and the highest percentage share of α-zearalenol was reported in group EII on the last five sampling dates (0.637-0.788 ng/ml, i.e. percentage share of 57.96-73.64%). The above had a significant influence on the non-physiological concentrations of progesterone and 17β-estradiol in both experimental (E) groups throughout the experiment. The lowest progesterone levels (0.131 ng/ml) were observed in group EII during the last test, and high concentrations of 17β-estradiol were found in group EII on the last two sampling dates (17.434 and 21.581 ng/ml, respectively) in comparison with control. Inhibited proliferation, manifested by a slower rate of body weight gain, was observed on the last but one day of zearalenone administration in both experimental groups. Our results indicate that NOAEL doses have stimulating/adaptive effects, whereas doses above NOAEL values suggest that even very low zearalenone doses can act as endocrine disruptors with regard to progesterone and 17β-estradiol. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. [Estradiol inducible and flower-specific expression of ARGOS and ARGOS-LIKE genes in transgenic tobacco plants].

    Science.gov (United States)

    Kuluev, B R; Kniazev, A V; Nikonorov, Iu M; Cheremis, A V

    2014-08-01

    Transgenic tobacco plants expressing Arabidopsis thaliana ARGOS and ARGOS-LIKE genes under the control of the chalcone synthase promoter of Petunia hybrid L., as well as the estradiol inducible XVE system, have been obtained. The part of transgenic plants with flower-specific expression of the target genes was characterized by increased flower size, caused by an increase in cell size and quantity in the case of the ARGOS gene and by a stimulation of cell growth via stretching in the case of the ARGOS-LIKE gene. An enhanced expression level of the NtEXPA1, NtEXPA4 genes encoding expansins, NtEXGT gene encoding endo-xyloglucan transferase, and the AINTEGUMENTA-like gene was detected in the flowers of transgenic tobacco plants. In the case of inducible expression of ARGOS and ARGOS-LIKE genes, an increase in leaf, stem and flower size was revealed in several lines of transgenic plants as compared to control. Expression of the ARGOS gene also affected cell number and size in this case, while the ARGOS-LIKE gene mainly influenced cell size via stretching. Inducible expression of the ARGOS gene in flowers mainly provided an enhanced containment of AINTEGUMENTA-like mRNA, while ARGOS-LIKE gene expression resulted in the activation of NtEXPA1 and NtEXGT genes.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  8. Innate immunity in the vagina (part I): estradiol inhibits HBD2 and elafin secretion by human vaginal epithelial cells.

    Science.gov (United States)

    Patel, Mickey V; Fahey, John V; Rossoll, Richard M; Wira, Charles R

    2013-05-01

    Vaginal epithelial cells (VEC) are the first line of defense against incoming pathogens in the female reproductive tract. Their ability to produce the anti-HIV molecules elafin and HBD2 under hormonal stimulation is unknown. Vaginal epithelial cells were recovered using a menstrual cup and cultured overnight prior to treatment with estradiol (E₂), progesterone (P₄) or a panel of selective estrogen response modulators (SERMs). Conditioned media were recovered and analyzed for protein concentration and anti-HIV activity. E₂ significantly decreased the secretion of HBD2 and elafin by VEC over 48 hrs, while P4 and the SERMs (tamoxifen, PHTTP, ICI or Y134) had no effect. VEC conditioned media from E₂ -treated cells had no anti-HIV activity, while that from E₂ /P₄ -treated cells significantly inhibited HIV-BaL infection. The menstrual cup allows for effective recovery of primary VEC. Their production of HBD2 and elafin is sensitive to E₂, suggesting that innate immune protection varies in the vagina across the menstrual cycle. © 2013 John Wiley & Sons A/S.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

  11. 76 FR 75886 - Determination That DEMULEN 1/50-28 (Ethinyl Estradiol; Ethynodiol Diacetate) Tablet and Four...

    Science.gov (United States)

    2011-12-05

    ...] Determination That DEMULEN 1/50-28 (Ethinyl Estradiol; Ethynodiol Diacetate) Tablet and Four Other Drug Products... ethynodiol diacetate) Pkwy., Skokie, Tablet, 0.05 mg; 1 mg. IL 60077. NDA 018160 DEMULEN 1/35-28 Do. (ethinyl estradiol; ethynodiol diacetate) Tablet, 0.035 mg; 1 mg. [[Page 75887

  12. Effect of naloxone and morphine on the estradiol induced LH surge in gilts

    OpenAIRE

    Yearwood, H.; Ziecik, A.J.; España España, F.

    1994-01-01

    This study examines the role of endogenous opioids in control of the estradiol-induced luteinizing hormone (LH) surge. In the experiment 1 (Exp.1), fifteen Duroc gills were ovarieclomized at the age of 5 to 6 months and one month later challenged with estradiol benzoate (EB, 25 µg/kg i.m.) at 0 h of the experiment. Control animals (n=5) received continuos i.v. infusion of saline solution (5 ml/h) from 30 to 34 h and from 60 to 64 h preceded by single i.v- injection of 10 ml of saline in each ...

  13. An international study of the relationship between alcohol consumption and postmenopausal estradiol levels

    DEFF Research Database (Denmark)

    Gavaler, J S; Love, K; Van Thiel, D

    1991-01-01

    the generalizability of this finding, 3 comparable study populations of healthy postmenopausal women were recruited: 62 in Copenhagen, 34 in Lisbon and 20 in Madrid. Although no association was detected in the Madrid study sample, in both the Copenhagen and Lisbon study populations, not only were estradiol levels...... significantly increased in alcohol users as compared to abstainers, but also estradiol levels were significantly correlated with total weekly drinks consumed. Based on these findings in study samples of healthy postmenopausal women from Pittsburgh, Copenhagen and Lisbon, we conclude that the increase...

  14. [Zoely, a combined oral contraceptive, monophasic pill containing estradiol and nomegestrol acetate].

    Science.gov (United States)

    Pintiaux, A; Gaspard, U; Nisolle, M

    2012-03-01

    A new combined oral contraceptive called Zoely has just been marketed in Belgium. It contains nomegestrol acetate, a progestin known for its high contraceptive reliability based on its antigonadotropic power and long half-life. This progestin is associated with estradiol and Zoely is devoid of ethinyl estradiol, which is the usual component of the majority of combined oral contraceptives and is primarily responsible for thrombotic side effects of the pill. The compositon and type of regimen of this new oral contraceptive contribute to its efficacy and excellent clinical tolerance.

  15. Chemical shift imaging: a review

    International Nuclear Information System (INIS)

    Brateman, L.

    1986-01-01

    Chemical shift is the phenomenon that is seen when an isotope possessing a nuclear magnetic dipole moment resonates at a spectrum of resonance frequencies in a given magnetic field. These resonance frequencies, or chemical shifts, depend on the chemical environments of particular nuclei. Mapping the spatial distribution of nuclei associated with a particular chemical shift (e.g., hydrogen nuclei associated with water molecules or with lipid groups) is called chemical shift imaging. Several techniques of proton chemical shift imaging that have been applied in vivo are presented, and their clinical findings are reported and summarized. Acquiring high-resolution spectra for large numbers of volume elements in two or three dimensions may be prohibitive because of time constraints, but other methods of imaging lipid of water distributions (i.e., selective excitation, selective saturation, or variations in conventional magnetic resonance imaging pulse sequences) can provide chemical shift information. These techniques require less time, but they lack spectral information. Since fat deposition seen by chemical shift imaging may not be demonstrated by conventional magnetic resonance imaging, certain applications of chemical shift imaging, such as in the determination of fatty liver disease, have greater diagnostic utility than conventional magnetic resonance imaging. Furthermore, edge artifacts caused by chemical shift effects can be eliminated by certain selective methods of data acquisition employed in chemical shift imaging

  16. The nonsteroidal mycoestrogen zearalenone and its five metabolites suppress LH secretion from the bovine anterior pituitary cells via the estradiol receptor GPR30 in vitro.

    Science.gov (United States)

    Nakamura, Urara; Kadokawa, Hiroya

    2015-11-01

    Picomolar concentrations of estradiol produce nongenomic suppression of GnRH-induced LH secretion from the anterior pituitary (AP) of cattle via G-protein-coupled receptor 30 (GPR30). Zearalenone (ZEN) is the nonsteroidal mycoestrogen produced by Fusarium fungi and has been detected in cereal grains, animal feed, and ruminant urine worldwide. Zearalenone has a prolonged blood half-life that results from enterohepatic cycling. There are five metabolites of ZEN: α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), α-zearalenol (α-ZOL), β-zearalenol (β-ZOL), and zearalanone, which may persist for long periods in animals and humans after consumption of ZEN-contaminated feed. We recently reported that GPR30 bound with α-ZAL decreases cytoplasmic cAMP but not gene expression of LHα and LHβ subunits, and GPR30 bound with α-ZAL suppresses GnRH-induced LH release in bovine AP cells in vitro. We tested the hypothesis that GPR30 bound with ZEN or one of the four previously untested metabolites suppresses GnRH-induced LH release from the bovine AP cells in vitro. Anterior pituitary cells were cultured for 3 days under steroid-free conditions and were then incubated with various concentrations (0.001-10 nM) of estradiol or one of the ZEN analogs for 5 minutes before GnRH stimulation. Gonadotropin-releasing hormone-stimulated LH secretion from AP cells was inhibited by all of the test concentrations of ZEN, 0.001 to 1 nM of α-ZAL, and 0.001 to 0.1 nM of the remaining four analogs. Pretreatment for 5 minutes with a GPR30-specific antagonist, G36, inhibited estradiol- and the ZEN analog-induced suppression of LH secretion from cultured AP cells. G36 alone had no significant effect on LH secretion. The estimated order of the nongenomic inhibiting effect was ZEN, α-ZAL, zearalanone, α-ZOL, β-ZOL, and β-ZAL, which is quite different from the reported order for their genomic effects. Therefore, ZEN and all of its metabolites suppress LH secretion from the bovine AP

  17. Perceived shift. South Africa.

    Science.gov (United States)

    Coovadia, H

    1998-01-01

    This speech challenges the global community to commit to reducing HIV/AIDS in Durban, South Africa, where 1 in 4 adults is infected with the virus. A commitment of resources and energy would show good faith in fairness, generate unstoppable momentum in the prevention and control of HIV/AIDS, provide a genuine renewal in the war against this disease, and set an example for other low income, resource poor, and HIV-epidemic countries. In 2000, the 13th Annual International AIDS Conference will be suitably located in Durban in a region with the highest rates of HIV/AIDS. The 1998 UNAIDS report states that 70% of those infected with HIV (21 million) are in Africa. A shift in program effort and political will would mark a turning point in the war against AIDS. There are four "P's" behind prevention and control of the HIV/AIDS epidemic: politicians, people, private sector, and programs. It is suggested that next year's conference should include political will that will become unshakable. Budgets need to be realistic. People should have unquestionable tolerance, acceptance, and generosity. Community organizations should be strengthened. Discrimination should be stopped. Science needs to be advanced. The private sector's involvement should be meaningful and supportive. Programs should be appropriate, affordable, and accessible. Many gaps need to be bridged and many people need to enlist their aid. The author urges that conference participants remember the afflicted poor and plan for a rebirth and renewal of hope.

  18. Dual effect of 17β-estradiol on NMDA-induced neuronal death: involvement of metabotropic glutamate receptor 1.

    Science.gov (United States)

    Spampinato, Simona Federica; Merlo, Sara; Molinaro, Gemma; Battaglia, Giuseppe; Bruno, Valeria; Nicoletti, Ferdinando; Sortino, Maria Angela

    2012-12-01

    Pretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.

  19. In men, peripheral estradiol levels directly reflect the action of estrogens at the hypothalamo-pituitary level to inhibit gonadotropin secretion

    NARCIS (Netherlands)

    G. Raven (Garrett); F.H. de Jong (Frank); J.-M. Kaufman (Jean-Marc); W.A. de Ronde (Willem)

    2006-01-01

    textabstractContext: Estradiol inhibits gonadotropin release in men by an action at the hypothalamus and pituitary. Because of the tissue-specific regulation of aromatase, peripheral estradiol levels may not reflect brain estradiol concentrations. Objective: We evaluated whether local aromatization

  20. Efecto de la leptina en la producción de progesterona y estradiol por el ovario de rata

    Directory of Open Access Journals (Sweden)

    M. B. Rearte

    2003-10-01

    Full Text Available El desequilibrio de factores autocrinos/paracrinos en el ovario conduce a diversas enfermedades. El objetivo del presente trabajo fue evaluar la relación entre el factor de crecimiento insulínico 1 (IGF-1 y la leptina (Lp en la producción de progesterona (P y estradiol (E por el ovario de rata estimulado con hormona folículo estimulante (FSH. Para ello, se incubaron explantes ováricos con FSH, IGF-1 y Lp, evaluándose P y E en el sobrenadante por radioinmunoensayo. La FSH estimuló la producción de P y E por el ovario. El IGF-1 produjo un importante efecto sinérgico con FSH tanto en la síntesis de P como de E. La Lp no tuvo efecto sobre la acción de FSH en el aumento de P y E por el ovario, sin embargo revirtió el efecto sinérgico de IGF-1 sobre FSH tanto para P como para E. Podemos concluir que la Lp podría actuar directamente disminuyendo el efecto sinérgico de IGF-1 sobre FSH. Estos resultados podrían sugerir que niveles anormales de Lp encontrados en mujeres con síndrome de ovario poliquístico provocarían una desensibilización ovárica al IGF-1 que afectaría la producción de P y E.An alteration in the balance of autocrine/paracrine ovarian factors may lead to different diseases. The aim of the present report was to evaluate the relationship between insulin growth factor 1 (IGF-1 and leptin (Lp in the progesterone (P and estradiol (E production after ovarian rat FSH stimulation. Thus, ovarian explants were incubated with FSH, IGF-1 and Lp, and P and E were evaluated by means of specific radioimmunoassays. FSH increased ovarian P and E production. IGF-1 synergized with FSH in P as well as in ovarian E production. Lp had not shown any effect on the FSH capacity to increse P and E in the ovarian tissue; nevertheless it reverted the synergistic effect of IGF-1 on FSH for P as well as for E. These data raise the possibility that abnormal Lp levels may contribute to infertility in women with polycystic ovarian syndrome by

  1. Bisphenol A and 17β-estradiol promote arrhythmia in the female heart via alteration of calcium handling.

    Directory of Open Access Journals (Sweden)

    Sujuan Yan

    Full Text Available There is wide-spread human exposure to bisphenol A (BPA, a ubiquitous estrogenic endocrine disruptor that has been implicated as having potentially harmful effects on human heart health. Higher urine BPA concentrations have been shown to be associated with cardiovascular diseases in humans. However, neither the nature nor the mechanism(s of BPA action on the heart are understood.The rapid (<7 min effects of BPA and 17β-estradiol (E2 in the heart and ventricular myocytes from rodents were investigated in the present study. In isolated ventricular myocytes from young adult females, but not males, physiological concentrations of BPA or E2 (10⁻⁹ M rapidly induced arrhythmogenic triggered activities. The effects of BPA were particularly pronounced when combined with estradiol. Under conditions of catecholamine stimulation, E2 and BPA promoted ventricular arrhythmias in female, but not male, hearts. The cellular mechanism of the female-specific pro-arrhythmic effects of BPA and E2 were investigated. Exposure to E2 and/or BPA rapidly altered myocyte Ca²⁺ handling; in particular, estrogens markedly increased sarcoplasmic reticulum (SR Ca²⁺ leak, and increased SR Ca²⁺ load. Ryanodine (10⁻⁷ M inhibition of SR Ca²⁺ leak suppressed estrogen-induced triggered activities. The rapid response of female myocytes to estrogens was abolished in an estrogen receptor (ER β knockout mouse model.Physiologically-relevant concentrations of BPA and E2 promote arrhythmias in a female-specific manner in rat hearts; the pro-arrhythmic actions of estrogens are mediated by ERβ-signaling through alterations of myocyte Ca²⁺ handling, particularly increases in SR Ca²⁺ leak. Our study provides the first experimental evidence suggesting that exposure to estrogenic endocrine disrupting chemicals and the unique sensitivity of female hearts to estrogens may play a role in arrhythmogenesis in the female heart.

  2. Quantized beam shifts in graphene

    Energy Technology Data Exchange (ETDEWEB)

    de Melo Kort-Kamp, Wilton Junior [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sinitsyn, Nikolai [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dalvit, Diego Alejandro Roberto [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-08

    We predict the existence of quantized Imbert-Fedorov, Goos-Hanchen, and photonic spin Hall shifts for light beams impinging on a graphene-on-substrate system in an external magnetic field. In the quantum Hall regime the Imbert-Fedorov and photonic spin Hall shifts are quantized in integer multiples of the fine structure constant α, while the Goos-Hanchen ones in multiples of α2. We investigate the influence on these shifts of magnetic field, temperature, and material dispersion and dissipation. An experimental demonstration of quantized beam shifts could be achieved at terahertz frequencies for moderate values of the magnetic field.

  3. Feldspar, Infrared Stimulated Luminescence

    DEFF Research Database (Denmark)

    Jain, Mayank

    2014-01-01

    This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars.......This entry primarily concerns the characteristics and the origins of infrared-stimulated luminescence in feldspars....

  4. Growth hormone stimulation test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of the ...

  5. Spinal cord stimulation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

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

    Science.gov (United States)

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

    2014-08-01

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

  7. Estradiol gel : review of the pharmacology, pharmacokinetics, efficacy, and safety in menopausal women

    NARCIS (Netherlands)

    Naunton, M.; Al Hadithy, A.F.Y.; Brouwers, J.R.B.J.; Archer, D.F.

    2006-01-01

    Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of a gel containing estradiol that is applied to the skin. Design: MEDLINE and EMBASE searches were conducted from 1966 to March 2005. Additional references were identified from bibliographies from selected studies in

  8. Estradiol and Testosterone Levels Are Lower after Oophorectomy than after Natural Menopause

    NARCIS (Netherlands)

    Korse, Catharina M.; Bonfrer, Johannes M. G.; van Beurden, Marc; Verheijen, Rene H. M.; Rookus, Matti A.

    2009-01-01

    Objective: The aim of this study was to compare hormone levels between women who became postmenopausal after a prophylactic bilateral salpingo-oophorectomy, and women who became postmenopausal in a natural way. Methods: In this cross-sectional study, we investigated estradiol, testosterone, SHBG,

  9. Simultaneous determination of ethinyl estradiol and drospirenone in oral contraceptive by high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Viviane Benevenuti Silva

    2013-09-01

    Full Text Available A simple, rapid, economical and reliable high performance liquid chromatographic method has been developed and successfully applied in simultaneous determination of ethinyl estradiol and drospirenone in coated tablets. The HPLC method was performed on a LiChroCART® 100RP column (125x4 mm i.d., 5 µm with acetonitrile:water 50:50 (v/v as mobile phase, pumped at a flow rate of 1.0 mL.min-1. The fluorescence detection for ethinyl estradiol was made at λex= 280 nm and λem= 310 nm and a UV detection for drospirenone was made at 200 nm. The elution time for ethinyl estradiol and drospirenone were 4.0 and 5.7 min, respectively. The method was validated in accordance to USP 34 guidelines. The proposed HPLC method presented advantages over reported methods and is suitable for quality control assays of ethinyl estradiol and drospirenone in coated tablets.

  10. Determination of urinary estradiol using an enzymatic method during the menstrual cycle

    International Nuclear Information System (INIS)

    Patricot, M.C.; Mathian, B.; Serpentie, S.; Revol, A.

    1986-01-01

    The aim of this study was to compare the results of enzymatic determination of urinary estradiol with results from a method using isotope dilution-mass fragmentography. Urine samples were collected from women during the menstrual cycle. The results obtained differed in absolute values, but showed good correlation. (Auth.)

  11. 17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

    Science.gov (United States)

    Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

    2013-01-01

    Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…

  12. Differential effects of testosterone, dihydrotestosterone and estradiol on carotenoid deposition in an avian sexually selected signal

    NARCIS (Netherlands)

    Casagrande, Stefania; Dijkstra, Cor; Tagliavini, James; Goerlich, Vivian C.; Groothuis, Ton G. G.

    Recent studies have demonstrated that carotenoid-based traits are under the control of testosterone (T) by up-regulation of carotenoid carriers (lipoproteins) and/or tissue-specific uptake of carotenoids. T can be converted to dihydrotestosterone (DHT) and estradiol (E2), and variation in conversion

  13. The influence of elevated preovulatory estradiol on apoptosis in the trophectoderm of day 16 bovine conceptuses

    Science.gov (United States)

    Preovulatory estradiol impacts follicular growth, oocyte maturation, sperm transport, uterine environment, and embryo survival/development. It has also been reported that cows in standing estrus within 24 hours of fixed-time AI have greater pregnancy success compared to cows that do not exhibit stan...

  14. Pattern recognition of estradiol, testosterone and dihydrotestosterone in children's saliva samples using stochastic microsensors

    NARCIS (Netherlands)

    Stefan-van Staden, R.I.; Gugoaşă, L.A.; Calenic, B.; Legler, J.

    2014-01-01

    Stochastic microsensors based on diamond paste and three types of electroactive materials (maltodextrin (MD), α-cyclodextrin (α-CD) and 5,10,15,20-tetraphenyl-21H,23H porphyrin (P)) were developed for the assay of estradiol (E2), testosterone (T2) and dihydrotestosterone (DHT) in children's saliva.

  15. Triclosan elevates estradiol levels in serum and tissues of cycling and peri-implantation female mice.

    Science.gov (United States)

    Pollock, Tyler; Greville, Lucas J; Tang, Brandon; deCatanzaro, Denys

    2016-10-01

    Triclosan, an antimicrobial agent added to personal care products, can modulate estrogenic actions. We investigated whether triclosan affects concentrations of exogenous and endogenous estradiol. Female mice were given injections of triclosan followed by 1μCi tritium-labeled estradiol. Mice given daily 2-mg triclosan doses (57.9mg/kg/dose) showed significantly elevated radioactivity in tissues and serum compared to controls. A single dose of 1 or 2mg triclosan increased radioactivity in the uterus in both cycling and peri-implantation females. We also measured natural urinary estradiol at 2-12h following triclosan injection. Unconjugated estradiol was significantly elevated for several hours following 1 or 2mg of triclosan. These data are consistent with evidence that triclosan inhibits sulfonation of estrogens by interacting with sulfotransferases, preventing metabolism of these steroids into biologically inactive forms. Elevation of estrogen concentrations by triclosan is potentially relevant to anti-reproductive and carcinogenic actions of excessive estrogen activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Neuroprotective effects of 17β-estradiol in a rat model of neonatal X radiation

    International Nuclear Information System (INIS)

    Caceres, L.G.; Aon, L.; Saraceno, E.; Capani, F.; Guelman, L.R.

    2009-01-01

    Developing Central Nervous System (CNS) is vulnerable to radiation-induced reactive oxygen species (ROS). The consequent oxidative stress has been shown to produce changes at behavioral, biochemical and histological levels in cerebellum (CE) and hippocampus (HIP). The aim of the present work was to test if 17β-estradiol, a potential neuroprotector, was able to counteract these changes. Neonatal male Wistar rats were X-irradiated (5 Gy) in their cephalic ends up to 48hs of postnatal life and a group of this animals was treated with 17β-estradiol (5 g/g). Open field (OF) test, ROS levels, as well as a histological assessment, were performed at 30 postnatal days. Administration of 17β-estradiol improved the short-term habituation and decreased the time spent in the centre in the OF. ROS levels returned to control in HIP and the cytoarchitecture of CE was reconstituted. These results suggest that 17β-estradiol was able to counteract the effects of X-rays at behavioral, biochemical and histological levels, probably acting through an antioxidant mechanism. (authors)

  17. Cortisol Interferes with the Estradiol-Induced Surge of Luteinizing Hormone in the Ewe1

    Science.gov (United States)

    Wagenmaker, Elizabeth R.; Breen, Kellie M.; Oakley, Amy E.; Pierce, Bree N.; Tilbrook, Alan J.; Turner, Anne I.; Karsch, Fred J.

    2008-01-01

    Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was ∼1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge. PMID:19056703

  18. Low dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

    DEFF Research Database (Denmark)

    Nielsen, Mads; Raundahl, Jakob; Pettersen, Paola

    2009-01-01

    Objective: To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density or heterogeneity compared to raloxifene. Secondarily, if these changes relate to changes in bone formation/resorption markers, and if these findings indicate elevation of breast canc...

  19. PTHrP potentiating estradiol-induced vitellogenesis in sea bream (Sparus auratus, L.)

    NARCIS (Netherlands)

    Bevelander, G.S.; Hang, X.; Abbink, W.; Spanings, F.A.T.; Canario, A.V.; Flik, G.

    2006-01-01

    In fish, vitellogenin is an important nutritional precursor protein produced solely in the liver and released into the blood where it binds calcium. In the gilthead sea bream (Sparus auratus) 17beta-Estradiol (E2) plays an important role in the synthesis of vitellogenin, but also the pituitary

  20. Rapid Effects of Estradiol on Aggression in Birds and Mice: The Fast and the Furious

    Science.gov (United States)

    Heimovics, Sarah A.; Trainor, Brian C.; Soma, Kiran K.

    2015-01-01

    Across invertebrates and vertebrates, steroids are potent signaling molecules that affect nearly every cell in the organism, including cells of the nervous system. Historically, researchers have focused on the genomic (or “nuclear-initiated”) effects of steroids. However, all classes of steroids also have rapid non-genomic (or “membrane-initiated”) effects, although there is far less basic knowledge of these non-genomic effects. In particular, steroids synthesized in the brain (“neurosteroids”) have genomic and non-genomic effects on behavior. Here, we review evidence that estradiol has rapid effects on aggression, an important social behavior, and on intracellular signaling cascades in relevant regions of the brain. In particular, we focus on studies of song sparrows (Melospiza melodia) and Peromyscus mice, in which estradiol has rapid behavioral effects under short photoperiods only. Furthermore, in captive Peromyscus, estrogenic compounds (THF-diols) in corncob bedding profoundly alter the rapid effects of estradiol. Environmental factors in the laboratory, such as photoperiod, diet, and bedding, are critical variables to consider in experimental design. These studies are consistent with the hypothesis that locally-produced steroids are more likely than systemic steroids to act via non-genomic mechanisms. Furthermore, these studies illustrate the dynamic balance between genomic and non-genomic signaling for estradiol, which is likely to be relevant for other steroids, behaviors, and species. PMID:25980562

  1. Lipid profiling and transcriptomic analysis reveals a functional interplay between estradiol and growth hormone in liver

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; Mirecki-Garrido, Mercedes de

    2014-01-01

    17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2...

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

    Science.gov (United States)

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

    2017-04-01

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

  3. Physical activity, heart rate, metabolic profile, and estradiol in premenopausal women

    DEFF Research Database (Denmark)

    Emaus, Aina; Veierød, Marit B; Furberg, Anne-Sofie

    2008-01-01

    PURPOSE: To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS: Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical...

  4. Synthesis and evaluation of a new series of 17α-[123I]iodovinyl estradiols

    International Nuclear Information System (INIS)

    Kabalka, George W.; Shoup, Timothy M.; Daniel, Gregory B.; Goodman, Mark M.

    2000-01-01

    A series of 17α-substituted estradiols was synthesized in which the stereochemical characteristics of carbons 20 and 21 were modified. It was found that the (Z)-isomer demonstrated more favorable receptor binding affinity than the corresponding (E)-isomer

  5. Modulating Action of 17β Estradiol on Urinary Volume and Renal ...

    African Journals Online (AJOL)

    This study determined the effect of combined administration of 17β estradiol and dietary salt on some renal parameters. Thirty-two female Albino rats were used for this study and they were assigned into four groups consist of eight rats in each group. The group A served as control while groups B, C and D were given daily ...

  6. Large collective lamb shifts in high pressure noble gases

    International Nuclear Information System (INIS)

    Payne, M.G.; Garrett, W.R.; Hart, R.C.; Datskou, I.; Wray, J.

    1990-01-01

    When three-photon atomic excitation is produced by two laser beams of angular frequencies ω L1 and ω L2 , which are crossed at an angle θ, large cooperative pressure dependent shifts can be produced in the peak position of the excitation lineshape. By studying an experimental situation in xenon the theoretical predictions are shown to be in precise agreement with experiment for several angles and a wide range of pressures. The possibility of observing related shifts in nonlinear processes (such as backward stimulated hyper-Raman generation) is discussed. 14 refs., 2 figs

  7. Biological activity and binding of estradiol to SK-Mel 23 human melanoma cells

    Directory of Open Access Journals (Sweden)

    Sarti M.S.M.V.

    2004-01-01

    Full Text Available Patients expressing estradiol receptors in melanoma cells have been reported to have a better prognosis. We therefore decided to investigate the in vitro effects of ß-estradiol and tamoxifen on the growth and tyrosinase activity of SK-Mel 23 human melanoma cells. Twenty-four-hour treatment with 0.4 nM ß-estradiol inhibited cell proliferation in 30% (0.70 ± 0.03 x 10(5 cells and increased tyrosinase activity in 50% (7130.5 ± 376.5 cpm/10(5 cells, as compared to untreated cells (1.0 ± 0.05 x 10(5 cells and 4769 ± 25.5 cpm/10(5 cells, respectively. Both responses were completely (100% blocked by 1 µM tamoxifen. Higher concentrations (up to 1.6 nM or longer treatments (up to 72 h did not result in a larger effect of the hormone on proliferation or tyrosinase activity. Competition binding assays demonstrated the presence of binding sites to [2,4,6,7-³H]-ß-estradiol, and that the tritiated analogue was displaced by the unlabeled hormone (1 nM to 100 µM, Kd = 0.14 µM, maximal displacement of 93% or by 10 µM tamoxifen (displacement of 60%. ß-estradiol also increased the phosphorylated state of two proteins of 16 and 46 kDa, after 4-h treatment, as determined by Western blot. The absorbance of each band was 1.9- and 4-fold the controls, respectively, as determined with Image-Pro Plus software. Shorter incubation periods with ß-estradiol did not enhance phosporylation; after 6-h treatment with the hormone, the two proteins returned to the control phosphorylation levels. The growth inhibition promoted by estradiol may explain the better prognosis of melanoma-bearing women as compared to men, and open new perspectives for drug therapy.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Low doses of estradiol in combination with gestodene to prevent early postmenopausal bone loss.

    Science.gov (United States)

    Bjarnason, N H; Byrjalsen, I; Hassager, C; Haarbo, J; Christiansen, C

    2000-09-01

    Our purpose was to study combinations of estradiol and gestodene for prevention of bone loss in early postmenopausal women. We randomly assigned 278 healthy, early postmenopausal women to receive either 2 mg 17beta-estradiol sequentially combined with 25 microg gestodene (group 2/25s), 2 mg estradiol sequentially combined with 50 microg gestodene (group 2/50s), 1 mg estradiol sequentially combined with 25 microg gestodene (group 1/25s), 1 mg estradiol continuously combined with 25 mg gestodene (group 1/25c), or placebo. After 3 years the changes in bone mineral density of the spine were as follows (mean +/- SEM): group 2/25s, 7. 41% +/- 0.72%; group 2/50s, 8.53% +/- 0.90%; group 1.25s, 6.67% +/- 0.88%; group 1/25c, 4.44% +/- 0.59%; and placebo group, -2.03% +/- 0. 64%. The changes in bone mineral density were mirrored in the biochemical bone markers. The average responses for the urinary C-terminal telopeptide fragments of type I collagen corrected for creatinine excretion were as follows (mean of baseline +/- SEM): group 2/25s, -68.8% +/- 0.03%; group 2/50s, -72.8% +/- 0.02%; group 1/25s, -60.7% +/- 0.03%; group 1/25c, -52.28% +/- 0.04%; and placebo group, 6.5% +/- 0.09%. Beneficial lipid effects were found in all active groups. The decreases in low-density lipoprotein were as follows (mean +/- SEM): group 2/25s, -13.7% +/- 3.0%; group 2/50s, -14.6% +/- 3.2%; group 1/25s, -9.28% +/- 2.2%; group 1/25c, -9.92% +/- 2.4%; and placebo group, 1.53% +/- 1.9%. These results demonstrate that estradiol therapy with 1 mg estradiol is fully protective against early postmenopausal bone loss.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  11. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Savergnini, S.Q.; Reis, A.M. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, R.A.S. [1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, P.E.B. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-11-01

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E{sub 2}; 5 µg·100 g{sup −1}·day{sup −1}) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E{sub 2} treatment caused an increase in uterine weight. Although E{sub 2} administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E{sub 2}-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

  12. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    International Nuclear Information System (INIS)

    Savergnini, S.Q.; Reis, A.M.; Santos, R.A.S.; Santos, P.E.B.; Ferreira, A.J.; Almeida, A.P.

    2012-01-01

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E 2 ; 5 µg·100 g −1 ·day −1 ) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E 2 treatment caused an increase in uterine weight. Although E 2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E 2 -treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval

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

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

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

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

    Science.gov (United States)

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

    2013-11-18

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

  15. Treatment of labial adhesion with topical estrogen and correlation with serum estradiol level

    Directory of Open Access Journals (Sweden)

    Safaian B

    2013-05-01

    Full Text Available Background: Serum estradiol level is a controversial prognostic factor in the outcome of labial adhesion. The aim of this study was to evaluate serum estradiol levels and topical estrogen response in patients with labial adhesion.Methods: A prospective interventional study was conducted among girls with labial adhesion that referred to Pediatrics clinic in Taleghani University Hospital, Gorgan city, Iran in 2011. One hundred patients entered the study. The diagnosis was conducted by clinical examination of vestibule area. Inclusion criteria were, three months to eight years old prepuberty girls, no ambiguous genitalia, lack of vulvovaginitis symptoms, labial adhesion more than twenty five percent, no history of previous topical estrogen treatment since two weeks ago and previous incomplete treatment. The patients who did not use proper amount and duration of drug and also with adverse drug reactions during treatment period were excluded from the study. Results: The maximum frequency of labial adhesion was in the group of less than one year old. The minimum frequency of labial adhesion was in the 7-8 years old group. Eighty six patients had complete or partial remission. No evidence of an improvement was observed in fourteen children. Severity of adhesions did not worsen in our patients. Serum estradiol levels were lower in patients who had a positive response to treatment. There were significant differences in serum estradiol levels between full or relative improvement with no improvement groups (P=0.044.Conclusion: Findings of this study showed that the labial adhesion patients with low serum estradiol level had better treatment response after using topical estrogen.

  16. A study on the synthesis, labeling and its biodistribution of estradiol derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup [College of Medicine, Dongguk Univ., Seoul (Korea, Republic of)] [and others

    2000-10-01

    Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE) has been prepared from 17{alpha}-ethynyl estradiol. Labeling of E-17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE] was carried out using peracetic acid with [{sup 123}I]Nal and Z-[{sup 123}I]IVE labelling was archived using chloamine T/HCL solution with [{sup 123}I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[{sup 123}I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[{sup 123}I]IVE and Z-[{sup 123}I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[{sup 123}I]IVE. These results suggest the possibility of using E-[{sup 123}I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.

  17. Distribution of estrogens, 17β-estradiol and estrone, in Canadian municipal wastewater treatment plants

    International Nuclear Information System (INIS)

    Servos, M.R.; Bennie, D.T.; Burnison, B.K.; Jurkovic, A.; McInnis, R.; Neheli, T.; Schnell, A.; Seto, P.; Smyth, S.A.; Ternes, T.A.

    2005-01-01

    The distribution of female hormones, 17β-estradiol and estrone, was determined in effluents of 18 selected municipal treatment plants across Canada. Replicate 24-h composite samples were collected from the influent and final effluent of each treatment plant, and the removal efficiency compared to the operational characteristics of the plants. In conventional activated sludge and lagoon treatment systems, the mean concentrations of 17β-estradiol and estrone in influent were 15.6 ng/l (range 2.4-26 ng/l) and 49 ng/l (19-78 ng/l). In final effluents, the mean concentrations of both 17β-estradiol and estrone were reduced to 1.8 ng/l (0.2-14.7 ng/l) and 17 ng/l (1-96 ng/l), respectively. 17β-estradiol was removed effectively, >75% and as high as 98%, in most of the conventional mechanical treatment systems with secondary treatment. The removal of estrone was much more complex with removal varying from 98% to situations where the concentrations in the effluent were elevated above that detected in the influent. The estrogenicity, measured using a transfected estrogen receptor in yeast (YES) assay, was also variable, ranging from high removal to elevations of estrogenicity in final effluent. Although the apparent removals were not statistically correlated with either hydraulic (HRT) or solid (SRT) retention times, plants or lagoons with high SRT were very effective at reducing the levels of hormones. Well-operated plants that achieved nitrification also tended to have higher removal of hormones than those that did not nitrify. Laboratory aerobic reactor experiments confirmed the rapid removal of 17β-estradiol, estrone, and estrogenicity when exposed to sewage slurries

  18. Work shifts in Emergency Medicine

    Directory of Open Access Journals (Sweden)

    Roberto Recupero

    2007-06-01

    Full Text Available Emergency Medicine is known as a high stress specialty. The adverse effect of constantly rotating shifts is the single most important reason given for premature attrition from the field. In this work problems tied with night shift work will be taken into account and some solutions to reduce the impact of night work on the emergency physicians will be proposed.

  19. Fate of 17β-estradiol and 17α-ethinylestradiol in batch and column studies simulating managed aquifer recharge

    KAUST Repository

    Maeng, Sungkyu

    2013-11-01

    Laboratory-scale batch and soil columns experiments were conducted to investigate the attenuation of estrogens (17β-estradiol and 17α-ethinylestradiol) during managed aquifer recharge. The role of microbial activity in the removal of selected estrogens was evaluated by comparing the results from biotic and abiotic batch experiments. Moreover, batch experiments were carried out using the sand media prepared over different acclimation periods to investigate the impact of acclimation periods on the removal of selected estrogens. Batch studies showed that adsorption was the dominant removal mechanism in the removal of 17β-estradiol and 17α-ethinylestradiol. 17β-estradiol and 17α-ethinylestradiol were attenuated by 99% and 96%, respectively, in batch experiments under oxic conditions. Redox conditions did not show any significant effect on the attenuation of 17β-estradiol. However, the net estrogenicity of 17β-estradiol remaining was lower under oxic conditions (130 ng estradiol-equivalents/L) than anoxic conditions (970 ng estradiol-equivalents/L) . Column studies operated at 17 h of empty bed contact time also demonstrated that removal mechanism of 17α-ethinylestradiol was more dependent on adsorption than biodegradation. © IWA Publishing 2013.

  20. Metabolic impact of shift work.

    Science.gov (United States)

    Zimberg, Ioná Zalcman; Fernandes Junior, Silvio A; Crispim, Cibele Aparecida; Tufik, Sergio; de Mello, Marco Tulio

    2012-01-01

    In developing countries, shift work represents a considerable contingent workforce. Recently, studies have shown that overweight and obesity are more prevalent in shift workers than day workers. In addition, shift work has been associated with a higher propensity for the development of many metabolic disorders, such as insulin resistance, diabetes, dislipidemias and metabolic syndrome. Recent data have pointed that decrease of the sleep time, desynchronization of circadian rhythm and alteration of environmental aspects are the main factors related to such problems. Shortened or disturbed sleep is among the most common health-related effects of shift work. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changes in lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The present review will discuss the impact of shift work on obesity and metabolic disorders and how disruption of sleep and circadian misalignment may contribute to these metabolic dysfunctions.

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

    International Nuclear Information System (INIS)

    Gupta, Rupesh K.; Singh, Jeffery M.; Leslie, Tracie C.; Meachum, Sharon; Flaws, Jodi A.; Yao, Humphrey H-C

    2010-01-01

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

  2. Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

    Science.gov (United States)

    Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

    2011-07-01

    Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

  3. Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

    International Nuclear Information System (INIS)

    Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K.; Lord, Peter

    2006-01-01

    Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury. Repeated administration of ethinyl estradiol (500 mg/kg/day for 4 days, po) resulted in no detectable liver injury or dysfunction. Using RT-PCR analysis, we demonstrate that HO-1 gene expression in whole liver tissue is elevated (> 20-fold) after the single dose of ethinyl estradiol. The number and intensity of HO-1 immunoreactive macrophages were increased after the single dose of ethinyl estradiol. HO-1 expression was undetectable in hepatic parenchymal cells from rats receiving Methocel control or a single dose of ethinyl estradiol, however cytosolic HO-1 immunoreactivity in these cells after repeated dosing of ethinyl estradiol was pronounced. The increases in HO-1 mRNA and HO-1 immunoreactivity following administration of a single dose of ethinyl estradiol suggested that this enzyme might be responsible for the observed protection of the liver during repeated dosing. To investigate the effect of HO-1 expression on ethinyl estradiol-induced hepatotoxicity, rats were pretreated with hemin (50 μmol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 μmol/kg, ip, an HO-1 inhibitor), or with gadolinium chloride (10 mg/kg, iv, an inhibitor/toxin of Kupffer cells) 24 h before ethinyl estradiol treatment. Pretreatment with modulators of HO-1 expression and activity had generally minimal effects on ethinyl estradiol-induced liver injury. These data suggest that HO-1 plays a limited role in antioxidant defense against ethinyl estradiol-induced oxidative stress and hepatotoxicity, and suggests that other coordinately induced enzymes are responsible for protection observed with

  4. Comparison of the effects of Origanum vulgare with LHRH-A2 and 17β-estradiol on the ultrastructure of gonadotroph cells and ovarian oogenesis in immature Trichogaster trichopterus.

    Science.gov (United States)

    Bagheri Ziari, Sedigheh; Naji, Tahereh; Hosseinzadeh Sahafi, Homayoun

    2015-10-01

    Origanum vulgare is a plant of the mint family that contains phytoestrogens. This study compared the effects of O. vulgare, LHRH-A2, and 17β-estradiol on the ultrastructure of gonadotroph cells and ovarian oogenesis in immature Trichogaster trichopterus. Fish (5.1±0.032cm and 2.1±0.043g, n=150) were randomly divided into four treatment groups (three hormonal treatments and control) and treated intramuscularly at four levels with 17β-estradiol or O. vulgare at 10, 20, 30 and 50mg/kg body weight and with LHRH-A2 at 0.001, 0.002, 0.003, and 0.005mg/kg body weight. There were three control treatments: saline, ethanol and placebo. Fish were kept in 15 tanks, with 10 fish per tank, injected a total of seven doses over 13 days. Gonadosomatic index (GSI) and oocyte diameter were lower (P≤0.05) in the control than in the three hormonal treatments. The highest GSI and oocyte diameter responses were observed in fish treated with 17β-estradiol (2.76±0.23%, 149.8±15.43mm) followed by O. vulgare (1.86±0.18%, 104.3±11.5mm) and LHRH-A2 (1.52±0.12%, 91.75±9.02mm) (P≤0.05). Moreover, there was a significant effect of dose level within all the hormonal treatments (P≤0.05). The effect of treatment on the length and weight was likely GSI. Ovarian tissue results showed faster oogenesis of oocytes in fish treated with O. vulgare, after 17β-estradiol. Ultrastructure of gonadotroph cells demonstrated less stimulation by O. vulgare than by 17β-estradiol and LHRH-A2. This study suggests that compared with the two hormonal treatments, O. vulgare dose-dependently affects ovarian oogenesis and gonadotroph cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Effects of estradiol benzoate, raloxifen and an ethanolic extract of Cimicifuga racemosa in nonclassical estrogen regulated organs of ovariectomized rats.

    Science.gov (United States)

    Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

    2009-10-01

    The special extract of Cimicifuga racemosa (CR) BNO 1055 was shown to have bone protective effects without exerting estrogenic effects in the uterus or mammary gland. Whether the effects of CR BNO 1055 would be exerted in other organs that also express estrogen receptors (ERs) but in which the effects of estrogens and of the selective estrogen receptor modulator raloxifen (Ral) were not thoroughly studied was therefore investigated in the present contribution. Rats were ovariectomized (ovx) and their food immediately substituted with estradiol benzoate (EB), Ral or 2 doses of CR BNO 1055 for 3 months. Expressions of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta) and of insulin-like growth factor-1 (IGF-1) genes were determined in the vagina, liver, thyroid gland, lung, spleen, colon and kidney by means of quantitative RT-PCRs. Body weights in all treatment groups were significantly reduced and uterine weights in the EB treated animals were largely and in the Ral treated animals slightly but significantly increased. CR BNO 1055 was without effects in the uterus. We tested 3 genes: ERalpha gene expression was significantly reduced in the vagina, liver and kidney and remained unaffected in all other organs with the exception of the thyroid gland where ERalpha gene expression was stimulated by EB, Ral had--if any--similar effects in these organs. The CR extract BNO 1055 was devoid of any effect on ERalpha gene expression. ERbeta gene expression was suppressed in the vagina and colon by EB and this effect was shared by Ral in the colon. In the thyroid, EB and Ral stimulated ERbeta gene expression. Expression of IGF-1 gene was stimulated by EB and CR BNO 1055 in the vagina and kidney and inhibited by EB and Ral in the liver. No effects were observed by CR BNO 1055 in these organs. The effects of Ral, if occurring, were similar to those of EB while CR BNO 1055 was ineffective in all organs but the vagina. In the colon, reduced ERbeta gene activity may

  6. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    International Nuclear Information System (INIS)

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

    1990-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1990-08-01

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

  8. Pathways of translation: deep brain stimulation.

    Science.gov (United States)

    Gionfriddo, Michael R; Greenberg, Alexandra J; Wahegaonkar, Abhijeet L; Lee, Kendall H

    2013-12-01

    Electrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high-frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench-to-bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench. © 2013 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2014-06-01

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

  10. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  11. Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin

    Directory of Open Access Journals (Sweden)

    Telleria Carlos M

    2005-08-01

    Full Text Available Abstract Background In pregnant rats, structural luteal regression takes place after parturition and is associated with cell death by apoptosis. We have recently shown that the hormonal environment is responsible for the fate of the corpora lutea (CL. Changing the levels of circulating hormones in post-partum rats, either by injecting androgen, progesterone, or by allowing dams to suckle, was coupled with a delay in the onset of apoptosis in the CL. The objectives of the present investigation were: i to examine the effect of exogenous estradiol on apoptosis of the rat CL during post-partum luteal regression; and ii to evaluate the post-partum luteal expression of the estrogen receptor (ER genes. Methods In a first experiment, rats after parturition were separated from their pups and injected daily with vehicle or estradiol benzoate for 4 days. On day 4 post-partum, animals were sacrificed, blood samples were taken to determine serum concentrations of hormones, and the ovaries were isolated to study apoptosis in situ. In a second experiment, non-lactating rats after parturition received vehicle, estradiol benzoate or estradiol benzoate plus bromoergocryptine for 4 days, and their CL were isolated and used to study apoptosis ex vivo. In a third experiment, we obtained CL from rats on day 15 of pregnancy and from non-lactating rats on day 4 post-partum, and studied the expression of the messenger RNAs (mRNAs encoding the ERalpha and ERbeta genes. Results Exogenous administration of estradiol benzoate induced an increase in the number of apoptotic cells within the CL on day 4 post-partum when compared with animals receiving vehicle alone. Animals treated with the estrogen had higher serum prolactin and progesterone concentrations, with no changes in serum androstenedione. Administration of bromoergocryptine blocked the increase in serum prolactin and progesterone concentrations, and DNA fragmentation induced by the estrogen treatment. ERalpha and

  12. [Ovarian stimulation monitoring: past, present and perspectives].

    Science.gov (United States)

    Salama, S; Torre, A; Paillusson, B; Thomin, A; Ben Brahim, F; Muratorio, C; Bailly, M; Wainer, R

    2011-04-01

    Since the inception of Assisted Reproductive Technology (ART), knowing the moment of ovulation has always been a priority. Initially, the monitoring was accomplished by observing the luteinizing hormone (LH) surge just before ovulation. Currently, in all ART facilities, the monitoring of all stimulated ovulatory cycles is done by using the conventional two-dimensional (2D) ultrasound to measure follicle diameter and by drawing blood tests that measure estradiol, progesterone, and luteinizing hormone levels. These exams allow determination of the numbers and quality of growing ovarian follicles and evaluation of follicle maturity before choosing the appropriate time for ovulation triggering. The monitoring of ovulatory cycles has now become enhanced with the arrival of new software called SonoAVC. This software allows the utilization of 3D blocks to immediately calculate the total number and volume of the follicles inside the ovary. This automatic approach is faster, precise, and more efficient. It also has better reproducibility than the classical 2D diameters. Furthermore, certain ART professionals envision that by using the SonoVac technology, patients will no longer need to be monitored with regular ultrasounds and with systematic hormonal testing. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  13. Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation

    International Nuclear Information System (INIS)

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

    2012-01-01

    Highlights: ► TNF-α augments neointimal hyperplasia in human saphenous vein. ► TNF-α induces detrimental effects on endothelial and smooth muscle cell function. ► Estradiol exerts modulatory effects on TNF-induced vascular cell functions. ► The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-α on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-α (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α increased SV–SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1–50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV–SMC proliferation to a level comparable to that of TNF-α alone. SV–EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV–EC to migrate and repair the wound. In contrast, TNF-α increased SV–SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α potently induced ICAM-1 and VCAM-1 expression in both SV–EC and SV–SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-α induced SV neointima formation, increased SMC proliferation and migration, impaired

  14. Successful pregnancy and live birth from a hypogonadotropic hypogonadism woman with low serum estradiol concentrations despite numerous oocyte maturations: a case report.

    Science.gov (United States)

    Matsumoto, Kaori; Imakawa, Kazuhiko; Hayashi, Chuyu

    2017-09-20

    The increase in serum estradiol (E 2 ) concentrations during the follicular phase becomes the index of oocyte maturation in vivo. When ovarian stimulation is performed to hypogonadotropic hypogonadism (HH) patients with only follicle stimulating hormone (FSH), proper increase in serum E 2 concentrations is not observed. Even if oocytes are obtained, which usually have low fertilization rate. In this report, we would like to present an unique case, in which under low E 2 concentrations and without luteinizing hormone (LH) administration, numerous mature oocytes could be obtained and a healthy baby delivered. During controlled ovarian stimulation (COS) with only recombinant follicular stimulating hormone (rFSH) administrations, a 26-year-old Japanese woman with hypothalamic amenorrhea (i.e., hypogonadotropic hypogonadism) developed numerous follicles despite low serum E 2 , 701 pg/ml, and high progesterone (P 4 ) concentrations, 2.11 ng/ml, on the day of induced ovulation. However, 33 cumulus-oocyte complexes (COCs) were successfully obtained; following the embryo culture, four early embryos and six blastocysts were cryopreserved. This patient received hormone replacement therapy (HRT), during which one of six cryopreserved blastocysts was thawed and transferred into the uterine lumen. The patient became pregnant from the first transfer, went through her pregnancy without any complications, and delivered a healthy male baby in the 39th week. Low E 2 concentrations in follicular fluids (FFs) are suggestive that aromatase and/or 17β-hydroxysteroid dehydrogenase (17β-HSD) could be low. Serum E 2 concentrations may not be the most important index for oocyte maturation during COS, and suggested that oocyte maturation was in progress even under low serum E 2 and high P 4 conditions. Even if serum E 2 concentrations did not properly increase, numerous mature oocytes could be obtained, resulting in the birth of a healthy baby.

  15. Evidence for gating roles of protein kinase A and protein kinase C in estradiol-induced luteinizing hormone receptor (lhcgr) expression in zebrafish ovarian follicle cells.

    Science.gov (United States)

    Liu, Ka-Cheuk; Ge, Wei

    2013-01-01

    Estradiol (E2) stimulates luteinizing hormone receptor (lhcgr) expression in zebrafish follicle cells via nuclear estrogen receptors (nERs) that are likely expressed on the membrane, and lhcgr responds to E2 in a biphasic manner during 24-h treatment. These observations raise an interesting question on the signaling mechanism underlying E2 regulation, in particular the biphasic response of lhcgr expression. In the present study, we demonstrated that E2 regulation of lhcgr was significantly influenced by the activity of cAMP-PKA pathway. Activation of cAMP-PKA pathway by forskolin or db-cAMP suppressed E2-stimulated lhcgr expression in short-term (3 h) but enhanced its effect in long-term (24 h), suggesting differential roles of PKA at these two phases of lhcgr response. PKA inhibitor H89 showed reversed effects. In contrast, PKC pathway had consistent permissive effect on E2-induced lhcgr expression as evidenced by strong inhibition of E2 effect by PKC inhibitors GF109203X and Ro-31-8220 at both 3 and 24 h. One of the mechanisms by which PKA and PKC gated E2 effect might be through regulating nERs, particularly esr2a. Despite the strong influence of PKA and PKC, our data did not suggest direct mediating roles for these two pathways in E2 stimulation of lhcgr expression; yet they likely play critical gating roles in E2 signal transduction. As a follow-up study to our previous report on E2 regulation of gonadotropin receptors in the zebrafish ovary, the present study provides further evidence for the involvement of classical intracellular signal transduction pathways in E2 stimulation of lhcgr expression in the follicle cells.

  16. Reduced estradiol-induced vasodilation and poly-(ADP-ribose polymerase (PARP activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Gabriella Masszi

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT. After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE. Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose polymerase (PARP activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  17. Reduced estradiol-induced vasodilation and poly-(ADP-ribose) polymerase (PARP) activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Masszi, Gabriella; Horvath, Eszter Maria; Tarszabo, Robert; Benko, Rita; Novak, Agnes; Buday, Anna; Tokes, Anna-Maria; Nadasy, Gyorgy L; Hamar, Peter; Benyó, Zoltán; Varbiro, Szabolcs

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  18. Explaining (Missing) Regulator Paradigm Shifts

    DEFF Research Database (Denmark)

    Wigger, Angela; Buch-Hansen, Hubert

    2014-01-01

    The global financial and economic crisis has prompted some scholars to suggest that a fundamental regulatory shift away from neoliberalism will take place – both in general and in the field of EU competition regulation. This paper shows that so far no radical break with the neoliberal type...... of competition regulation is heaving into sight. It sets out to explain this from the vantage point of a critical political economy perspective, which identifies the circumstances under which a crisis can result in a regulatory paradigm shift. Contrasting the current situation with the shift in EC/EU competition...... regulation after the crisis in the 1970s, the paper argues that the preconditions for a fundamental shift in this issue area are not present this time around. Several reasons account for this: the current crisis has been construed by economic and political elites as a crisis within and not of neoliberal...

  19. The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells.

    Science.gov (United States)

    Neubauer, Hans; Yang, Yang; Seeger, Harald; Fehm, Tanja; Cahill, Michael A; Tong, Xiaowen; Ruan, Xiangyan; Mueck, Alfred O

    2011-08-01

    Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.

  20. Adenosine monophosphate activated protein kinase (AMPK), a mediator of estradiol-induced apoptosis in long-term estrogen deprived breast cancer cells.

    Science.gov (United States)

    Chen, Haiyan; Wang, Ji-Ping; Santen, Richard J; Yue, Wei

    2015-06-01

    Estrogens stimulate growth of hormone-dependent breast cancer but paradoxically induce tumor regress under certain circumstances. We have shown that long-term estrogen deprivation (LTED) enhances the sensitivity of hormone dependent breast cancer cells to estradiol (E2) so that physiological concentrations of estradiol induce apoptosis in these cells. E2-induced apoptosis involve both intrinsic and extrinsic pathways but precise mechanisms remain unclear. We found that exposure of LTED MCF-7 cells to E2 activated AMP activated protein kinase (AMPK). In contrast, E2 inhibited AMPK activation in wild type MCF-7 cells where E2 prevents apoptosis. As a result of AMPK activation, the transcriptional activity of FoxO3, a downstream factor of AMPK, was up-regulated in E2 treatment of LTED. Increased activity of FoxO3 was demonstrated by up-regulation of three FoxO3 target genes, Bim, Fas ligand (FasL), and Gadd45α. Among them, Bim and FasL mediate intrinsic and extrinsic apoptosis respectively and Gadd45α causes cell cycle arrest at the G2/M phase. To further confirm the role of AMPK in apoptosis, we used AMPK activator AICAR in wild type MCF-7 cells and examined apoptosis, proliferation and expression of Bim, FasL, and Gadd45α. The effects of AICAR on these parameters recapitulated those observed in E2-treated LTED cells. Activation of AMPK by AICAR also increased expression of Bax in MCF-7 cells and its localization to mitochondria, which is a required process for apoptosis. These results reveal that AMPK is an important factor mediating E2-induced apoptosis in LTED cells, which is implicative of therapeutic potential for relapsing breast cancer after hormone therapy.

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

    Science.gov (United States)

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

    2017-07-28

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

  2. Estradiol induces dendritic spines by enhancing glutamate release independent of transcription: A mechanism for organizational sex differences

    Science.gov (United States)

    Schwarz, Jaclyn M.; Liang, Shu-Ling; Thompson, Scott M.; McCarthy, Margaret M.

    2008-01-01

    SUMMARY The naturally occurring sex difference in dendritic spine number on hypothalamic neurons offers a unique opportunity to investigate mechanisms establishing synaptic patterning during perinatal sensitive periods. A major advantage of the model is the ability to treat neonatal females with estradiol to permanently induce the male phenotype. During the development of other systems, exuberant innervation is followed by activity-dependent pruning necessary for elimination of spurious synapses. In contrast, we demonstrate that estradiol-induced organization in the hypothalamus involves the induction of new synapses on dendritic spines. Activation of estrogen receptors by estradiol triggers a non-genomic activation of PI3 kinase that results in enhanced glutamate release from presynaptic neurons. Subsequent activation of ionotropic glutamate receptors activates MAP kinases inducing dendritic spine formation. These results reveal a trans-neuronal mechanism by which estradiol acts during a sensitive period to establish a profound and lasting sex difference in hypothalamic synaptic patterning. PMID:18498739

  3. 17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

    Science.gov (United States)

    Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

    2015-12-01

    Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

  4. Modulating the brain at work using noninvasive transcranial stimulation.

    Science.gov (United States)

    McKinley, R Andy; Bridges, Nathaniel; Walters, Craig M; Nelson, Jeremy

    2012-01-02

    This paper proposes a shift in the way researchers currently view and use transcranial brain stimulation technologies. From a neuroscience perspective, the standard application of both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has been mainly to explore the function of various brain regions. These tools allow for noninvasive and painless modulation of cortical tissue. In the course of studying the function of an area, many studies often report enhanced performance of a task during or following the stimulation. However, little follow-up research is typically done to further explore these effects. Approaching this growing pool of cognitive neuroscience literature with a neuroergonomics mindset (i.e., studying the brain at work), the possibilities of using these stimulation techniques for more than simply investigating the function of cortical areas become evident. In this paper, we discuss how cognitive neuroscience brain stimulation studies may complement neuroergonomics research on human performance optimization. And, through this discussion, we hope to shift the mindset of viewing transcranial stimulation techniques as solely investigatory basic science tools or possible clinical therapeutic devices to viewing transcranial stimulation techniques as interventional tools to be incorporated in applied science research and systems for the augmentation and enhancement of human operator performance. Published by Elsevier Inc.

  5. Are intracytoplasmic sperm injection and high serum estradiol compounding risk factors for adverse obstetric outcomes in assisted reproductive technology?

    Science.gov (United States)

    Royster, Greene Donald; Krishnamoorthy, Kavitha; Csokmay, John M; Yauger, Belinda J; Chason, Rebecca J; DeCherney, Alan H; Wolff, Erin F; Hill, Micah J

    2016-08-01

    To evaluate whether intracytoplasmic sperm injection (ICSI) use and E2 on the final day of assisted reproductive technology (ART) stimulation are associated with adverse obstetric complications related to placentation. Retrospective cohort study. Large private ART practice. A total of 383 women who underwent ART resulting in a singleton live birth. None. Adverse placental outcomes composed of placenta accreta, placental abruption, placenta previa, intrauterine growth restriction, preeclampsia, gestational hypertension, and small for gestational age infants. Patients with adverse placental outcomes had higher peak serum E2 levels and were three times more likely to have used ICSI. Adverse placental outcomes were associated with increasing E2 (odds ratio 1.36, 95% confidence interval 1.13-1.65) and ICSI (odds ratio 3.86, 95% confidence interval 1.61-9.27). Adverse outcomes increased when E2 was >3,000 pg/mL and continued to increase in a linear fashion until E2 was >5,000 pg/mL. The association of ICSI with adverse outcomes was independent of male factor infertility. Interaction testing suggested the adverse effect of E2 was primarily seen in ICSI cycles, but not in conventional IVF cycles. Estradiol >5,000 pg/mL was associated with adverse placental events in 36% of all ART cycles and 52% of ICSI cycles. ICSI and elevated E2 on the day of hCG trigger were associated with adverse obstetric outcomes related to placentation. The finding of a potential interaction of E2 and ICSI with adverse placental events is novel and warrants further investigation. Published by Elsevier Inc.

  6. Pharmacokinetic and pharmacodynamic interactions between the hepatitis C virus protease inhibitor, boceprevir, and the oral contraceptive ethinyl estradiol/norethindrone.

    Science.gov (United States)

    Lin, Wen H; Feng, Hwa-Ping; Shadle, Craig R; O'Reilly, Terry; Wagner, John A; Butterton, Joan R

    2014-09-01

    The purpose of this study was to examine drug interactions between boceprevir, a hepatitis C virus NS3/4A protease inhibitor, and a combined oral contraceptive containing ethinyl estradiol (EE) and norethindrone (NE). A single-center, open-label study was conducted in 20 healthy female volunteers. In three consecutive 28-day treatment periods, subjects received EE/NE (0.035 mg/1 mg; 21 days on, 7 days off). During period 3, subjects also received boceprevir (800 mg three times daily) for 28 days. Coadministration of boceprevir with EE/NE did not affect NE AUC0-24 but slightly reduced NE C max. Geometric mean ratios (GMRs) for NE AUC0-24 and C max with EE/NE alone and EE/NE plus boceprevir were 0.96 (90% confidence interval (CI), 0.87-1.06) and 0.83 (90% CI, 0.76-0.90). Coadministration of boceprevir with EE/NE reduced EE AUC0-24 and C max by 26 and 21%, with GMRs of 0.74 (90% CI, 0.68-0.80) and 0.79 (90% CI, 0.75-0.84). Boceprevir had no effect on mid-cycle luteinizing hormone (LH), follicle-stimulating hormone (FSH), or sex hormone-binding globulin levels, and progesterone concentrations remained Adverse events reported in this study were consistent with the well-established safety profile of boceprevir. Serum progesterone, LH, and FSH levels indicate that ovulation was suppressed during coadministration of boceprevir with EE/NE. Coadministration of boceprevir with combined oral contraceptives containing EE and ≥1 mg of NE is therefore unlikely to alter contraceptive effectiveness. The ovulation suppression activity of oral contraceptives containing lower doses of NE, and of other forms of hormonal contraception during coadministration with boceprevir, has not been established.

  7. Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes.

    Science.gov (United States)

    Salehzadeh, Firoozeh; Rune, Anna; Osler, Megan; Al-Khalili, Lubna

    2011-08-01

    Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E(2)) in metabolism and investigated whether either hormone may mediate a sex-specific effect. Myotubes from postmenopausal women and age-matched male donors were treated with 10 nM testosterone or E(2) for 4 days, and assays were performed to measure metabolic readouts, signal transduction, and mRNA expression. Testosterone and E(2) treatment enhanced insulin-stimulated glucose incorporation into glycogen and AKT phosphorylation in myotubes from female donors, highlighting a sex-specific role of sex hormone in glucose metabolism. Testosterone treatment increased palmitate oxidation in myotubes from both female and male donors, while E(2) enhanced palmitate oxidation in myotubes from male donors only. Testosterone-mediated increase in palmitate oxidation was attenuated at the presence of androgen receptor antagonist, which may indicate a role of nuclear steroid receptor in muscle lipid oxidation. Testosterone treatment increased mRNA expression of the insulin receptor substrate 2 in myotubes from male and female donors, whereas it increased mRNA expression of glycogen synthase 1 only in myotubes from male donors. E(2) treatment increased pyruvate dehydrogenase kinase 4 mRNA expression in myotubes from female donors. Thus, our data suggest that testosterone or E(2) modulates muscle glucose and lipid metabolism and may play a role in metabolism in a sex-dependent manner.

  8. Tamoxifen induces regression of estradiol-induced mammary cancer in ACI.COP-Ept2 rat model

    OpenAIRE

    Ruhlen, Rachel L.; Willbrand, Dana M.; Besch-Williford, Cynthia L.; Ma, Lixin; Shull, James D.; Sauter, Edward R.

    2008-01-01

    The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5–7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonan...

  9. Prostaglandin receptors EP and FP are regulated by estradiol and progesterone in the uterus of ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Blesson Chellakkan S

    2012-01-01

    Full Text Available Abstract Background Prostaglandins are important for female reproduction. Prostaglandin-E2 acts via four different receptor subtypes, EP1, EP2, EP3 and EP4 whereas prostaglandin-F2alpha acts through FP. The functions of prostaglandins depend on the expression of their receptors in different uterine cell types. Our aim was to investigate the expression of EPs and FP in rat uterus and to identify the regulation by estradiol, progesterone and estrogen receptor (ER selective agonists. Methods We performed four different rat experiments involving treatments with estradiol, progesterone and ER agonists. Real-time PCR and immunohistochemistry were employed to evaluate receptor expression. Results Our results showed that all mRNAs and proteins of EPs and FP are expressed in the rat uterus. The expression pattern and intensity of immunostaining vary between different cell types and treatments. The mRNA expression of all EPs and FP are downregulated by estradiol and the ERalpha specific agonist PPT, whereas the ERbeta specific agonist DPN downregulates only EP2 and EP4. The protein expression however, showed an increase in EP2 and EP3 after estradiol treatment. When treated with estradiol and progesterone in combination, the expressions of EP1 and EP3 are upregulated. Conclusions Regulation of EPs and FP expression by estradiol appears to be mainly modulated via ERalpha for EP1, EP3 and FP, while EP2 and EP4 also are affected by the ERbeta selective ligand. Our immunohistochemical data shows a cell specific regulation of prostaglandin receptors under the influence of ovarian steroids, where EP2 is estrogen regulated in all uterine tissues examined. EP1 and EP3 are upregulated by the combination of estradiol and progesterone. Thus, our observations indicate that estradiol and progesterone regulate the mRNA and protein expression of EPs and FP in a receptor and tissue specific way.

  10. Estradiol Facilitation of Cocaine Self-Administration in Female Rats Requires Activation of mGluR5.

    Science.gov (United States)

    Martinez, Luis A; Gross, Kellie S; Himmler, Brett T; Emmitt, Nicole L; Peterson, Brittni M; Zlebnik, Natalie E; Foster Olive, M; Carroll, Marilyn E; Meisel, Robert L; Mermelstein, Paul G

    2016-01-01

    In comparison to men, women initiate drug use at earlier ages and progress from initial use to addiction more rapidly. This heightened intake and vulnerability to drugs of abuse is regulated in part by estradiol, although the signaling mechanisms by which this occurs are not well understood. Recent findings indicate that within the nucleus accumbens core, estradiol induces structural plasticity via membrane-localized estrogen receptor α, functionally coupled to metabotropic glutamate receptor subtype 5 (mGluR5). Hence, we sought to determine whether mGluR5 activation was essential for estradiol-mediated enhancement of cocaine self-administration. Ovariectomized (OVX) female rats were allowed to freely self-administer cocaine under extended access conditions (6 h/d) for 10 consecutive days. The mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) or vehicle was administered before estradiol (or oil), on a 2 d on/2 d off schedule throughout the extended access period. MPEP treatment prevented the estradiol-dependent enhancement of cocaine self-administration in OVX females. In a separate experiment, potentiation of mGluR5 function with the positive allosteric modulator 3-cyano- N -(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (in the absence of estradiol treatment) failed to increase cocaine self-administration. These data suggest that mGluR5 activation is necessary for estradiol-mediated enhancement of responses to cocaine, but that direct mGluR5 activation is insufficient to mimic the female response to estradiol. Building on previous studies in male animals, these findings further highlight the therapeutic potential of mGluR5 antagonism in the treatment of addiction and suggest that there may be added therapeutic benefit in females.

  11. Disruption of male reproductive behavior in threespine stickleback asterosteus aculeatus exposed to 17β-estradiol

    International Nuclear Information System (INIS)

    Wibe, Asa Espmark; Rosenqvist, Gunilla; Jenssen, Bjoern Munro

    2002-01-01

    In past years we have witnessed decreased reproductive capacity in many wildlife species due to exposure to chemicals with endocrine-disrupting properties. In this laboratory experiment male three spine sticklebacks asterosteus aculeatus exposed to 17β-estradiol (2.0 μg/g) dispersed in peanut oil, on days 1, 7, 14, and 21, showed impaired paternal care compared to control fish that were exposed to peanut oil only. There were no differences between the two groups in number of males that built nests or in courtship displays. However, exposed males started nest building significantly later than control males. This study suggests that some but not all essential traits of male reproductive behavior may be altered as a result of exposure to 17β-estradiol. To reveal harmful effects of chemicals with suggested reproductive-disrupting properties it is thus important to take a wide variety of variables related to reproductive behavior into consideration

  12. Progesterone after Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

    Directory of Open Access Journals (Sweden)

    Darryl J. Mayeaux

    2015-01-01

    Full Text Available In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action.

  13. Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

    International Nuclear Information System (INIS)

    Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

    1981-01-01

    The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations

  14. [The influence of estradiol on histomorphology of skin flaps with ischemia reperfusion injury].

    Science.gov (United States)

    Jianlong, Wu; Ruixing, Hou; Guangliang, Zhou; Jihui, Ju

    2015-09-01

    To study the influence of estradiol on histomorphology of skin flaps with ischemia reperfusion injury. 48 adult male Wistar rats aged 12-14 weeks old, were randomly divided into control group (group I), ischemia-reperfusion group (group II), saline group (group III), estradiol group (group IV). Superficial epigastric artery axial flap, 3 cm x 6 cm in size, was made in the left lower quadrant abdominal of each rat. Flap model with ischemia-reperfusion injury was established by using the nondestructive micro vascular clamp to clamp the superficial epigastric artery. The general condition of the flap was observed after operation. At 7 days after operation, the survival rate of the flap was detected, the flaps were harvested to receive histology and ultrastructural observation. The neutrophils level of the superficial epigastric vein were tested. 7 days after operation, the survival rate of the flap in group IV was significantly higher than that in group II, III (P organization structure in flap.

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

    Directory of Open Access Journals (Sweden)

    Xiaoyan Ma

    2015-09-01

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

  16. Brain-generated estradiol drives long-term optimization of auditory coding to enhance the discrimination of communication signals.

    Science.gov (United States)

    Tremere, Liisa A; Pinaud, Raphael

    2011-03-02

    Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species, including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real time, by controlling the strength of inhibitory transmission via a nongenomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homolog of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency, and the neural discrimination of songs. These effects are mediated by estradiol's modulation of both the rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely behaving animals disrupts behavioral responses to songs, but not to other behaviorally relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain.

  17. Negative feedback as an obligatory antecedent to the estradiol-induced luteinizing hormone surge in ovariectomized pigs.

    Science.gov (United States)

    Kesner, J S; Price-Taras, E A; Kraeling, R R; Rampacek, G B; Barb, C R

    1989-09-01

    In ovariectomized pigs, estradiol treatment induces a preovulatory-like luteinizing hormone (LH) surge, but only after serum LH concentrations are suppressed for 48 h. This inhibition of LH release is attributable in large part to inhibition of gonadotropin-releasing hormone (GnRH) release. The present report examines the dependency of the estradiol-induced LH surge on this preceding phase of negative feedback. Ten ovariectomized gilts were given an i.m. injection of estradiol benzoate (10 micrograms/kg BW). Beginning at the time of estradiol treatment, 5 of these gilts received 1-microgram GnRH pulses i.v. every 45 min for 48 h, i.e. during the period of negative feedback. The remaining 5 control gilts received comparable infusions of vehicle. Estradiol induced the characteristic biphasic LH response in control gilts. On the other hand, the inhibitory LH response to estradiol was prevented and the ensuing LH surge was blocked in 4 of the 5 gilts given GnRH pulses during the negative feedback phase. These results indicate that suppressing release of GnRH and/or LH is an important antecedent to full expression of the LH surge in ovariectomized pigs. Assimilation of this observation with the existing literature provides novel insights into the neuroendocrine control of LH secretion in castrated and ovary-intact gilts.

  18. Effect of 17β-estradiol on the elasticity of MCF-7 cells by atomic force microscopy

    Science.gov (United States)

    Wang, Yuhua; Jiang, Ningcheng; Zheng, Liqin; Yang, Hongqin; Xie, Shusen

    2016-10-01

    Estrogen plays an important role in the development and progression of breast cancer, and it promotes proliferation, invasion and metastasis of breast cancer cells. In this paper, we investigated the effect of estrogen on the elasticity of breast cancer cells. 17β-estradiol, one of the most active estrogens in the human body was applied to MCF-7 living cells and the elasticity of breast cancer cells was measured by atomic force microscopy. The force spectroscopy was performed on the center of the cell and the Hertz model was used to calculate the elasticity modulus. Furthermore, the confocal fluorescence imaging was taken to observe the effect of 17β-estradiol on the actin distribution in the cells. The results show that the elasticity of the cells decreases rapidly after the addition of 17β-estradiol, which indicates that the cells appear softer for 17β-estradiol's treatment. From the confocal imaging, it can be observed that the actin filament rearranged for 17β-estradiol's treatment, which may lead to the alteration of the cell elasticity. Our findings may deepen our understanding on the rapid effect of 17β-estradiol to MCF-7 cells.

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

    Science.gov (United States)

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

    2011-07-01

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

  20. Percutaneous 17ß-estradiol replacement therapy in hypertensive postmenopausal women

    Directory of Open Access Journals (Sweden)

    M.C. Osório-Wender

    1997-09-01

    Full Text Available The present study evaluated the short-term effects of percutaneous 17ß-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17ß-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued. Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 ± 27.21 to 35.09 ± 20.44 IU/l, P<0.05, and an increase in estradiol levels (15.06 ± 8.76 to 78.7 ± 44.6 pg/ml, P<0.05. There was no effect on LH (18.0 ± 9.5 to 14.05 ± 8.28 IU/l. Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17ß-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women

  1. Synthesis and cytotoxic activities of estrone and estradiol cis-dichloroplatinum(II) complexes

    Czech Academy of Sciences Publication Activity Database

    Kvasnica, Miroslav; Rárová, L.; Oklešťková, Jana; Buděšínský, Miloš; Kohout, Ladislav

    2012-01-01

    Roč. 20, č. 24 (2012), s. 6969-6978 ISSN 0968-0896 R&D Projects: GA MŠk 1M06030; GA AV ČR IAA400550801 Grant - others:GA MŠk(CZ) ED0007/01/01 Program:ED Institutional support: RVO:61388963 ; RVO:61389030 Keywords : steroids * estrone * estradiol * platinum complex * cytotoxicity Subject RIV: CC - Organic Chemistry Impact factor: 2.903, year: 2012

  2. Treatment of heavy menstrual bleeding with a new combination of estradiol valerate and dienogest

    Directory of Open Access Journals (Sweden)

    Luis Bahamondes

    2010-11-01

    Full Text Available Luis Bahamondes, Ilza Monteiro, Arlete FernandesHuman Reproduction Unit, Department of Obstetrics and Gynecology, School of Medical Sciences and National Institute of Hormones and Women’s Health, University of Campinas, Campinas, BrazilAbstract: The first combined oral contraceptive (OC was launched in the US 50 years ago and was followed by another formulation introduced in Germany one year later. The most common estrogen component in current formulations is ethinylestradiol; however, many concerns have been raised with respect to this estrogen. Although the natural estrogen produced by the ovary, 17-beta estradiol, is the most potent of the estrogens, it is poorly absorbed orally, and previous attempts to use it in combined OCs have been unsuccessful due to the occurrence of irregular bleeding. Recently, a new combined OC was developed containing a natural estrogen, estradiol valerate, and a new progestin, dienogest, in a dynamic 26-day, four-phasic (estrogen stepdown and progestin stepup scheme of administration. In clinical trials, its contraceptive performance was excellent, with good cycle control and bleeding patterns compared with other combined OCs or with placebo. This review focuses predominantly on the use of an estradiol valerate-dienogest combined OC for the treatment of heavy menstrual bleeding. The findings of two large, randomized, controlled trials have shown that this combined OC constitutes an effective treatment for women with heavy menstrual bleeding, representing a new therapeutic option to reduce menstrual blood loss. Further studies are necessary to confirm these data.Keywords: dienogest, estradiol valerate, heavy menstrual bleeding, menorrhagia, contraception

  3. Enzyme immunoassay for progesterone and estradiol. A study of factors influencing sensitivity

    International Nuclear Information System (INIS)

    Joyce, B.G.; Read, G.F.; Riad-Fahmy, D.

    1978-01-01

    Enzyme immunoassays (EIA) for progesterone and estradiol have been developed at the Tenovus Institute using horseradish peroxidase conjugates and a solid-phase system for separation of free and bound steroid. The sensitivity of these assays was inadequate and precluded their use for the assay of low-titre samples. Attempts to increase the sensitivity of the assay by reducing the affinity of the conjugate for the antiserum by altering the bridge groups were unsuccessful. Decrease in the molar incorporation of the steroid into the enzyme conjugate effected a significant improvement, increasing the sensitivity in the progesterone assay by 50% and in that of estradiol by 70%. Initial attempts to replace the solid-phase separation technique by a second antibody procedure based on a sheep, anti-rabbit IgG serum were of limited success. Increased sensitivity in the progesterone radioimmunoassay (RIA) was achieved but severe problems with high non-specific binding remained. The apparent specific binding in the estradiol assay did not exceed 30% and a viable system could not therefore be established. An improved second antibody produced in guinea-pigs to a wider spectrum of immunoglobulins, when used in the EIA of progesterone, increased sensitivity 50-fold compared with the solid-phase assay. The sensitivity of the estradiol assay was increased 8-fold compared with the solid-phase system, and is now comparable with that of the RIA (2.0pg/0.7pg). The significant improvement in sensitivity in EIA associated with the use of double antibody separation procedures, and the importance of tailoring the affinity of the second antibody to the immunoglobulin profile of the first antibody are emphasized. (author)

  4. 17β-estradiol regulates the differentiation of cementoblasts via Notch signaling cascade

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Jing; Zhou, Zeyuan; Huang, Li; Li, Yuyu [Department of Orthodontics, The State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province (China); Li, Jingtao [Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province (China); Zou, Shujuan, E-mail: drzsj@scu.edu.cn [Department of Orthodontics, The State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province (China)

    2016-08-12

    Estrogen has been well recognized as a key factor in the homeostasis of bone and periodontal tissue, but the way it regulates the activities of cementoblasts, the cell population maintaining cementum has not been fully understood. In this study, we examined the expression of estrogen receptor in OCCM-30 cells and the effect of 17β-estradiol (E2) on the proliferation and differentiation of OCCM-30 cells. We found that both estrogen receptor α and β were expressed in OCCM-30 cells. E2 exerted no significant influence on the proliferation of OCCM-30 cells, but inhibited the transcription and translation of BSP and Runx2 in the early phase of osteogenic induction except the BSP mRNA. Afterwards in the late phase of osteogenic induction, E2 enhanced the transcription and translation of BSP and Runx2 and promoted the calcium deposition. In addition, the expression level of Notch1, NICD and Hey1 mRNAs responded to exogenous E2 in a pattern similar to that of the osteoblastic markers. DAPT could attenuate the effect of E2 on the expression of osteoblastic markers. These findings indicated that E2 might regulate the differentiation of cementoblasts via Notch signaling. - Highlights: • 17β-estradiol showed no significant effect on the proliferation of cementoblasts. • 17β-estradiol promoted the osteoblastic differentiation of cementoblasts despite of an early transient inhibition. • Notch signaling was regulated by 17β-estradiol and was responsible for mediating the effect of E2 on cementoblasts. • Hey1 might display an opposite expression pattern to Notch signaling in certain circumstances.

  5. In vivo expusure to 17β-estradiol triggers premature sperm capacitation in cauda epididymis

    Czech Academy of Sciences Publication Activity Database

    Děd, Lukáš; Šebková, N.; Černá, M.; Elzeinová, Fatima; Dostálová, Pavla; Pěknicová, Jana; Dvořáková-Hortová, K.

    2013-01-01

    Roč. 145, March 2013 (2013), s. 255-263 ISSN 1470-1626 R&D Projects: GA ČR(CZ) GA523/09/1793; GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : 17β-estradiol * sperm capacitation * RTqPCR * tyrosine phosphorylation Subject RIV: CE - Biochemistry Impact factor: 3.262, year: 2013

  6. In vivo exposure to 17beta-estradiol triggers premature sperm capacitation in cauda epididymis

    Czech Academy of Sciences Publication Activity Database

    Děd, Lukáš; Šebková, N.; Černá, M.; Elzeinová, Fatima; Dostálová, Pavla; Pěknicová, Jana; Dvořáková-Hortová, K.

    2013-01-01

    Roč. 145, č. 3 (2013), s. 255-263 ISSN 1470-1626 R&D Projects: GA ČR(CZ) GA523/09/1793; GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : Estrogen * Estrogen receptor * 17β-estradiol * Sperm capacitation Subject RIV: EI - Biotechnology ; Bionics Impact factor: 3.262, year: 2013

  7. A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol-17b

    OpenAIRE

    Fuentes, J.; Guerreiro, P. M.; Modesto, Teresa; Rotllant, J.; Canario, Adelino V. M.; Power, Deborah

    2007-01-01

    Estradiol (E2) increases circulating calcium and phosphate levels in fish, thus acting as a hypercalcemic and hyperphosphatemic factor during periods of high calcium requirements, such as during vitellogenesis. Since parathyroid hormone (PTH)-related protein (PTHrP) has been shown to be calciotropic in fish, we hypothesized that the two hormones could be mediating the same process. Sea bream (Sparus auratus) juveniles receiving a single intraperitoneal injection of piscin...

  8. Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland.

    Science.gov (United States)

    Lin, Man; Wang, Na; Yao, Bei; Zhong, Yao; Lin, Yan; You, Tianhui

    2018-04-19

    Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α-ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α-ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of β-casein, stearoyl-CoA desaturase, fatty acid synthase, and α-lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen-like quercetin promotes mammary gland development and lactation yield in milk-deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells. Copyright © 2018 John Wiley & Sons, Ltd.

  9. Lack of support for relation between woman's masculinity preference, estradiol level and mating context.

    Science.gov (United States)

    Marcinkowska, Urszula M; Ellison, Peter T; Galbarczyk, Andrzej; Milkowska, Karolina; Pawlowski, Boguslaw; Thune, Inger; Jasienska, Grazyna

    2016-02-01

    It has been proposed that women's preferences for male facial sexual dimorphism are positively correlated with conception probability and differ between short- and long-term mating contexts. In this study, we tested this assumption by analyzing relationships between estradiol levels to the women's preferences of male faces that were manipulated to vary in masculinity. Estradiol was measured in daily saliva samples throughout the entire menstrual cycle collected by Polish women with regular menstrual cycles. In our analyses, we included the three most commonly used definitions of the fertile window in the literature. After computing the overall masculinity preference of each participant and measuring hormone levels, we found that i) the timing of ovulation varied greatly among women (between -11 and -17days from the onset of the next menses, counting backwards), ii) there was no relationship between daily, measured during the day of the test (N=83) or average for the cycle (N=115) estradiol levels and masculinity preferences, iii) there were no differences in masculinity preferences between women in low- and high-conception probability phases of the cycle, and iv) there were no differences in masculinity preferences between short- and long-term mating contexts. Our results do not support the idea that women's preferences for a potential sexual partner's facial masculinity fluctuate throughout the cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Efficacy of Topical Estradiol Compared to Topical Glycolic Acid for Skin Aging Treatment in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Shannaz Nadia Yusharyahya

    2017-12-01

    Full Text Available Skin aging is a complex biological process in human being, as a result from intrinsic factors (genetic, hormonal, metabolism and extrinsic factors (UV exposure, pollution, smoking, life style. In postmenopausal women, physiologically, the amount of estrogen are decreased, causing deterioration of their skin’s appearance. Along with the changes that occur, skin care require more attention. A holistic approach can increase epidermal thickness, therefore, reducing the depth of wrinkles, as well as improving skin texture and moisture. There are various treatments available to improve skin appearance due to aging. This EBCR is aimed to compare the efficacy of topical estradiol and topical glycolic acid as skin treatment in postmenopausal women. Articles were searched through Pubmed/MEDLINE, EBSCO, and Cochrane. One randomized-controlled trial by Fuchs KO, et al was obtained and critically appraised. Based on the appraisal, study by Fuchs KO, et al is considered valid, important, and applicable. Both estradiol and glycolic acid show good efficacy and safety for postmenopausal women with signs of skin aging, however estradiol is not considered to have better efficacy than glycolic acid.

  11. Selective modulation of ER-beta by estradiol and xenoestrogens in human breast cancer cell lines.

    Science.gov (United States)

    Cappelletti, V; Saturno, G; Miodini, P; Körner, W; Daidone, M G

    2003-03-01

    In the last decades, substances with estrogenic activity have been dispersed into the environment. Xenoestrogens act by binding to estrogen receptors, ligand-regulated transcription factors, for which two subtypes have been described, ER-alpha and ER-beta, which are often coexpressed at variable amounts in different tissues. We investigated variations in the expression of ER-alpha and ER-beta mRNAs following treatment with four xenoestrogens (bisphenol A, 4-tert octylphenol, 2-hydroxybiphenyl, 4-hydroxybiphenyl) and with 17beta-estradiol in estrogen-sensitive (T47D) and estrogen-insensitive (BT20) breast cancer cell lines. Although to a variable extent, both estradiol and the tested xenoestrogens increased the expression of ER-beta mRNA, whereas a slight effect on ER-alpha was observed only in T47D cells. Upregulation of ER-beta expression by estradiol and xenoestrogens was observed only in the presence of detectable ER-alpha protein levels. These findings indicate a regulatory role for ER-beta in ER-alpha-mediated transcription and a role for ER-beta in mediating xenoestrogen toxicity.

  12. High estradiol and low progesterone are associated with high assertiveness in women.

    Science.gov (United States)

    Blake, Khandis R; Bastian, Brock; O'Dean, Siobhan M; Denson, Thomas F

    2017-01-01

    Sexual selection theory posits that women are more selective than men are when choosing a mate. This evolutionary theory suggests that "choosiness" increases during the fertile window because the costs and benefits of mate selection are highest when women are likely to conceive. Little research has directly investigated reproductive correlates of choice assertion. To address this gap, in the present research we investigated whether fertility, estradiol, and progesterone influenced general assertiveness in women. We recruited 98 naturally cycling, ethnically diverse women. Using a within-subjects design and ovarian hormone concentrations at fertile and non-fertile menstrual cycle phases, we measured implicit assertiveness and self-reported assertive behavior. To see if fertility-induced high assertiveness was related to increased sexual motivation, we also measured women's implicit sexual availability and interest in buying sexy clothes. Results showed that high estradiol and low progesterone predicted higher assertiveness. Sexual availability increased during periods of high fertility. Low progesterone combined with high estradiol predicted greater interest in buying sexy clothes. Results held when controlling for individual differences in mate value and sociosexual orientation. Our findings support the role of fluctuating ovarian hormones in the expression and magnitude of women's assertiveness. High assertiveness during the fertile window may be a psychological adaptation that promotes mate selectivity and safeguards against indiscriminate mate choice when conception risk is highest. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. 17β-Estradiol inhibits estrogen binding protein-mediated hypha formation in Candida albicans.

    Science.gov (United States)

    Kurakado, Sanae; Kurogane, Rie; Sugita, Takashi

    2017-08-01

    Candida albicans is one of the most prevalent and clinically important fungal pathogens. The ability to change form depending on environmental stress is an important microbial virulence factor. A survey of compounds that inhibit this morphological change identified various steroids, including 17β-estradiol. Interestingly, C. albicans has proteins capable of binding to steroids, including estrogen binding protein (Ebp1). Estrogens regulate cell differentiation and proliferation in humans through estrogen receptor proteins. To determine whether EBP1 regulates a virulence factor, we investigated the effect of 17β-estradiol on the morphological transition of C. albicans using an ebp1 deletion mutant. Treatment with 10 μg/mL of 17β-estradiol inhibited hypha formation, whereas its effect on the ebp1 deletion mutant was decreased compared to that on the wild-type and revertant strains. These data suggest a new pathway for the yeast-to-hypha transition via EBP1 in C. albicans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. 17β-Estradiol induces supernumerary primordial germ cells in embryos of the polychaete Platynereis dumerilii.

    Science.gov (United States)

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

    2014-01-15

    In the polychaete Platynereis dumerilii exactly four primordial germ cells (PGCs) arise in early development and are subject to a transient mitotic arrest until the animals enter gametogenesis. In order to unravel the mechanisms controlling the number of PGCs in Platynereis, we tested whether the steroid 17β-estradiol (E2) is able to induce PGC proliferation, as it had been described in other species. Our data provide strong support for such a mechanism, showing that E2 significantly increases the occurrence of larvae with supernumerary PGCs in Platynereis in a dose dependent manner. E2 responsiveness is restricted to early developmental stages, when the PGCs are specified. During these stages, embryos exhibit high expression levels of the estradiol receptor (ER). The ER transcript localizes to the yolk-free cytoplasm of unfertilized eggs and segregates into the micromeres during cleavage stages. Nuclear ER protein is found asymmetrically distributed between daughter cells. Neither transcript nor protein is detectable in PGCs at larval stages. Addition of the specific estradiol receptor inhibitor ICI-182,780 (ICI) abolishes the proliferative effect of E2, suggesting that it is mediated by ER signaling. Our study reports for the first time an ER mediated proliferative effect of E2 on PGCs in an invertebrate organism. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Estradiol-treated female mice as surrogate hosts for Neisseria gonorrhoeae genital tract infections

    Directory of Open Access Journals (Sweden)

    Ann E. Jerse

    2011-07-01

    Full Text Available Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrheae to humans. Genital tract infection can be established in female mice that are treated with 17β-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, TLR4, and T-regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrate a role for sialyltransferase and the MtrC-MtrD-MtrE active efflux pump in evading innate defenses in vivo, but not for several factors hypothesized to protect against the phagocytic respiratory burst and H2O2-producing lactobacilli. Experimental infection of estradiol-treated mice has also revealed the existence of non-host restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model.

  16. 17 beta-estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Breinholt, V.; Dalsgaard, T.

    2001-01-01

    The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.20% nari...... and its antiatherogenic effect. - Mortensen, A., V. Breinholt, T. Dalsgaard, H. Frandsen, S. T. Lauridsen, J. Laigaard, B. Ottesen, and J-J. Larsen. 17 beta -Estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits.......The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.......20% naringenin, for 16 weeks. The uterine weight was increased (P 17 beta -E-2 group compared with the controls. Total plasma cholesterol and triglycerides were not different from those in the controls, In lipoproteins, HDL...

  17. Technological Advances in Deep Brain Stimulation.

    Science.gov (United States)

    Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

    2015-01-01

    Functional and stereotactic neurosurgery has always been regarded as a subspecialty based on and driven by technological advances. However until recently, the fundamentals of deep brain stimulation (DBS) hardware and software design had largely remained stagnant since its inception almost three decades ago. Recent improved understanding of disease processes in movement disorders as well clinician and patient demands has resulted in new avenues of development for DBS technology. This review describes new advances both related to hardware and software for neuromodulation. New electrode designs with segmented contacts now enable sophisticated shaping and sculpting of the field of stimulation, potentially allowing multi-target stimulation and avoidance of side effects. To avoid lengthy programming sessions utilising multiple lead contacts, new user-friendly software allows for computational modelling and individualised directed programming. Therapy delivery is being improved with the next generation of smaller profile, longer-lasting, re-chargeable implantable pulse generators (IPGs). These include IPGs capable of delivering constant current stimulation or personalised closed-loop adaptive stimulation. Post-implantation Magnetic Resonance Imaging (MRI) has long been an issue which has been partially overcome with 'MRI conditional devices' and has enabled verification of DBS lead location. Surgical technique is considering a shift from frame-based to frameless stereotaxy or greater role for robot assisted implantation. The challenge for these contemporary techniques however, will be in demonstrating equivalent safety and accuracy to conventional methods. We also discuss potential future direction utilising wireless technology allowing for miniaturisation of hardware.

  18. Optically stimulated luminesence dosimeter

    International Nuclear Information System (INIS)

    Liu Qiujiang; Zhu Lei; Zhu Lei; Chinese Academy of Sciences, Beijing; Chen Zhaoyang; Fan Yanwei; Ba Weizhen; Cong Xiuyun; Tang Xinqiang; Guo Qi; Lu Wu

    2007-01-01

    In this paper, the principle and makeup of optically stimulated luminescence dosimeter is described, and a measurement for radiation is carried, some actual problem is discussed. The dosimeter has high sensitive and can be reseted in-flight by stimulated light. (authors)

  19. SAT in shift manager training

    International Nuclear Information System (INIS)

    Lecuyer, F.

    1995-01-01

    EDF has improved the organization of the operation shift teams with the replacement of shift supervisor in shift manager function. The shift manager is not only responsible for tasks associated to plant operation (production), but he is also responsible for safety of these tasks and for management of shift team members. A job analysis of this new job position has been performed in order to design the training programme. It resulted in a 10-month training programme that includes 8 weeks in safety-related topics and 12 weeks in soft-skills related topics. The safety related training courses are mandatory, the other courses are optional courses depending on individual trainee needs. The training also includes the development of management competencies. During the 10 month period, each trainee develops an individual project that is evaluated by NPP manager. As well, as group project is undertaken by the trainees and overseen by a steering committee. The steering committee participates in the evaluation process and provides operational experience feedback to the trainee groups and to the overall programme

  20. [Transcranial magnetic stimulation].

    Science.gov (United States)

    Tormos, J M; Catalá, M D; Pascual-Leone, A

    Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS. The magnetic stimulator is composed of a series of capacitors that store the voltage necessary to generate a stimulus of the sufficient intensity of generate an electric field in the stimulation coil. The safety of TMS is supported by the considerable experience derived from studies involving electrical stimulation of the cortex in animals and humans, and also specific studies on the safety of TMS in humans. In this article we review historical and technical aspects of TMS, describe its adverse effects and how to avoid them, summarize the applications of TMS in the investigation of different cerebral functions, and discuss the possibility of using TMS for the treatment of neuropsychiatric disorders.

  1. Effects of estradiol benzoate on 5'-iodothyronine deiodinase activities in female rat anterior pituitary gland, liver and thyroid gland

    Directory of Open Access Journals (Sweden)

    Lisbôa P.C.

    1997-01-01

    Full Text Available There is little information on the possible effects of estrogen on the activity of 5'-deiodinase (5'-ID, an enzyme responsible for the generation of T3, the biologically active thyroid hormone. In the present study, anterior pituitary sonicates or hepatic and thyroid microsomes from ovariectomized (OVX rats treated or not with estradiol benzoate (EB, 0.7 or 14 µg/100 g body weight, sc, for 10 days were assayed for type I 5'-ID (5'-ID-I and type II 5'-ID (5'-ID-II, only in pituitary activities. The 5'-ID activity was evaluated by the release of 125I from deiodinated 125I rT3, using specific assay conditions for type I or type II. Serum TSH and free T3 and free T4 were measured by radioimmunoassay. OVX alone induced a reduction in pituitary 5'-ID-I (control = 723.7 ± 67.9 vs OVX = 413.9 ± 26.9; P<0.05, while the EB-treated OVX group showed activity similar to that of the normal group. Thyroid 5'-ID-I showed the same pattern of changes, but these changes were not statistically significant. Pituitary and hepatic 5'-ID-II did not show major alterations. The treatment with the higher EB dose (14 µg, contrary to the results obtained with the lower dose, had no effect on the reduced pituitary 5'-ID-I of OVX rats. However, it induced an important increment of 5'-ID-I in the thyroid gland (0.8 times higher than that of the normal group: control = 131.9 ± 23.7 vs ovx + EB 14 µg = 248.0 ± 31.2; P<0.05, which is associated with increased serum TSH (0.6-fold vs OVX, P<0.05 but normal serum free T3 and free T4. The data suggest that estrogen is a physiological stimulator of anterior pituitary 5'-ID-I and a potent stimulator of the thyroid enzyme when employed at high doses

  2. Cellular proliferation rate and insulin-like growth factor binding protein (IGFBP)-2 and IGFBP-3 and estradiol receptor alpha expression in the mammary gland of dairy heifers naturally infected with gastrointestinal nematodes during development.

    Science.gov (United States)

    Perri, A F; Dallard, B E; Baravalle, C; Licoff, N; Formía, N; Ortega, H H; Becú-Villalobos, D; Mejia, M E; Lacau-Mengido, I M

    2014-01-01

    Mammary ductal morphogenesis during prepuberty occurs mainly in response to insulin-like growth factor-1 (IGF-1) and estradiol stimulation. Dairy heifers infected with gastrointestinal nematodes have reduced IGF-1 levels, accompanied by reduced growth rate, delayed puberty onset, and lower parenchyma-stroma relationship in their mammary glands. Immunohistochemical studies were undertaken to determine variations in cell division rate, IGF-1 system components, and estradiol receptors (ESR) during peripubertal development in the mammary glands of antiparasitic-treated and untreated Holstein heifers naturally infected with gastrointestinal nematodes. Mammary biopsies were taken at 20, 30, 40, and 70 wk of age. Proliferating cell nuclear antigen immunolabeling, evident in nuclei, tended to be higher in the parenchyma of the glands from treated heifers than in those from untreated. Insulin-like growth factor binding proteins (IGFBP) type 2 and type 3 immunolabeling was cytoplasmic and was evident in stroma and parenchyma. The IGFBP2-labeled area was lower in treated than in untreated heifers. In the treated group, a maximal expression of this protein was seen at 40 wk of age, whereas in the untreated group the labeling remained constant. No differences were observed for IGFBP3 between treatment groups or during development. Immunolabeling for α ESR (ESR1) was evident in parenchymal nuclei and was higher in treated than in untreated heifers. In the treated group, ESR1 peaked at 30 wk of age and then decreased. These results demonstrate that the parasite burden in young heifers negatively influence mammary gland development, affecting cell division rate and parameters related to estradiol and IGF-1 signaling in the gland. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  3. A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant, Implanon®.

    Science.gov (United States)

    Weisberg, Edith; Croxatto, Horatio B; Findlay, John K; Burger, Henry G; Fraser, Ian S

    2011-12-01

    Mifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel-releasing contraceptive implant, Implanon® but could impair contraceptive efficacy. To examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon. Women using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2-5. Measurements of serum estradiol (E(2)), progesterone (P(4)), luteinizing hormone (LH), follicle-stimulating hormone (FSH), cervical mucus examination and maximal follicle size (by vaginal ultrasound) were carried out at various times. Following mifepristone intake, there was a dramatic increase in E(2) levels ranging from 543 to 1183 pmol/L (p=.000), which was not correlated with maximal follicle size or preceded by LH or FSH increase. The increase in E(2) triggered an LH increase resulting in development of a luteinized follicle in four women with no evidence of ovulation. One of these women had estradiol and progesterone levels suggestive of ovulation, but no corpus luteum was seen. Almost all women had very low mucus scores, which did not correlate with E(2) levels. Despite a transient increase in E(2) levels after mifepristone, there was no evidence of subsequent ovulation irrespective of whether they also received EE. The mechanism by which mifepristone in the presence of etonogestrel results in a rapid increase in E(2) levels remains unclear and could not be related to any significant changes in FSH, LH, ovarian follicle dynamics or subsequent possible ovulation. Pregnancy is very unlikely to occur if mifepristone and EE are given during use of Implanon to stop an episode of bleeding. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. shift

    African Journals Online (AJOL)

    during the course of an academic year at the University of Witwatersrand following recent reforms in training and assessment methods Method: All fifth ... Assessment of Psychiatry in medical education at the. University of Witwatersrand ... or two examiners, to assess mainly clinical competence; multiple-choice questions ...

  5. Response shift en retrospectie. / Response shift in retrospect.

    NARCIS (Netherlands)

    Hoogstraten, J.; de Meijer, E.; Sprangers, M.

    1986-01-01

    Discusses the relationship between response shift and the concept of "artifact" with reference to W. K. Hofstee's (1986) arguments. The use of retrospective posttests instead of retrospective pretests is rejected, and some empirical approaches for assessing the impact of social desirability and

  6. Paradigm Shifts in Ophthalmic Diagnostics.

    Science.gov (United States)

    Sebag, J; Sadun, Alfredo A; Pierce, Eric A

    2016-08-01

    Future advances in ophthalmology will see a paradigm shift in diagnostics from a focus on dysfunction and disease to better measures of psychophysical function and health. Practical methods to define genotypes will be increasingly important and non-invasive nanotechnologies are needed to detect molecular changes that predate histopathology. This is not a review nor meant to be comprehensive. Specific topics have been selected to illustrate the principles of important paradigm shifts that will influence the future of ophthalmic diagnostics. It is our impression that future evaluation of vision will go beyond visual acuity to assess ocular health in terms of psychophysical function. The definition of disease will incorporate genotype into what has historically been a phenotype-centric discipline. Non-invasive nanotechnologies will enable a paradigm shift from disease detection on a cellular level to a sub-cellular molecular level. Vision can be evaluated beyond visual acuity by measuring contrast sensitivity, color vision, and macular function, as these provide better insights into the impact of aging and disease. Distortions can be quantified and the psychophysical basis of vision can be better evaluated than in the past by designing tests that assess particular macular cell function(s). Advances in our understanding of the genetic basis of eye diseases will enable better characterization of ocular health and disease. Non-invasive nanotechnologies can assess molecular changes in the lens, vitreous, and macula that predate visible pathology. Oxygen metabolism and circulatory physiology are measurable indices of ocular health that can detect variations of physiology and early disease. This overview of paradigm shifts in ophthalmology suggests that the future will see significant improvements in ophthalmic diagnostics. The selected topics illustrate the principles of these paradigm shifts and should serve as a guide to further research and development. Indeed

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

    Science.gov (United States)

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

    2010-11-01

    The personal care product Triclosan, 5-chloro-2(2,4-dichlorophenoxy)-phenol, is widely used in consumer products as an antibacterial agent and is increasingly found in the environment as a contaminant of sewage sludge and wastewater. This compound has been identified in plasma and urine of people in the United States, Sweden and Australia. Triclosan is known to inhibit sulfonation of phenolic xenobiotics and is structurally related to inhibitors of estrogen sulfotransferase, such as polychlorobiphenylols. In pregnancy, the placenta is an important source of estrogen, which is needed for normal fetal development and successful parturition, and estrogen sulfotransferase is thought to play an important role in regulation of estrogen availability. In this study, we examined the effect of Triclosan on sheep placental cytosolic sulfotransferase activity with 17-beta-estradiol and estrone as substrates. For comparison, we studied the effects of 4-hydroxy-3,3',4',5-tetrachlorobiphenyl and 2'-hydroxytriclocarban on estradiol sulfonation. The apparent K(m) for placental cytosolic sulfotransferase activity with estradiol as substrate was 0.27 ± 0.06 nM (mean ± S.D., n = 3 individuals) and with estrone as substrate was 1.86 ± 0.22 nM. Partial substrate inhibition was observed with estradiol at concentrations higher than 10-20 nM, as is typical of estrogen sulfotransferases (SULT1E1) in other species. Studies of the effect of Triclosan on estrogen sulfotransferase activity were conducted with several concentrations (0.1-6 nM) of estradiol and with 2 nM estrone. Triclosan was a very potent inhibitor of both estradiol and estrone sulfonation. For estradiol the inhibition was shown to be mixed competitive/uncompetitive, with K(ic) of 0.09 ± 0.01 nM and K(iu) of 5.2 ± 2.9 nM. The IC(50) for inhibition of estrone sulfonation was 0.60 ± 0.06 nM. At an environmentally relevant concentration of 1 µM, Triclosan was not a substrate for glucuronidation in sheep placental microsomes

  8. VP Anaphors and Object Shift

    DEFF Research Database (Denmark)

    Ørsnes, Bjarne

    2013-01-01

    The article discusses the placement of the VP anaphor det ‘it’ as a complement of verbs selecting VP complements in Danish. With verbs that only allow a VP complement, the VP anaphor must be in SpecCP regardless of its information structure properties. If SpecCP is occupied by an operator, the an...... be in situ. The article argues that a shifted pronominal in Danish must be categorially licensed by the verb and extends this analysis to shifting locatives. An Optimality Theory analysis is proposed that accounts for the observed facts....

  9. Impact of Equine Chorionic Gonadotropin Associated with Temporary Weaning, Estradiol Benzoate, or Estradiol Cypionate on Timed Artificial Insemination in Primiparous Bos Indicus Cows

    Directory of Open Access Journals (Sweden)

    Andre Luis Bastos Souza

    Full Text Available The study aimed to determine the impact of equine chorionic gonadotropin (eCG associated with different timed artificial insemination (TAI protocols on the pregnancy rate (PR in Bos indicus cows previously treated with progesterone. Five hundred and fifty-seven primiparous cows were subjected to the following treatments: on day 0 (d0, GeCGTW (group equine Chorionic Gonadotropin+Temporary Weaning;n=178 received 0,558 g intravaginal progesterone (P4+1.0 mg of estradiol benzoate (EB (IM; on d8 (P4 removal+0,075 mg D-cloprostenol + 400 IU eCG + TW for 48 h; on d10, TAI + calves return to dam; GeCGEB (group equine Chorionic Gonadotropin+Estradiol benzoate; n=176 the same as GeCGTW without TW + application of 1.0 mg of EB on d9; GeCGEC (group equine Chorionic Gonadotropin+Estradiol Cypionate; n=203, the same as GeCGTW without TW+1.5 mg EC (IM. On d35, post TAI, pregnancy diagnosis (PD was performed. Non-pregnant animals remained under clean-up bulls for 90 days. After this period, the animals were subjected to PD using ultrasound. The PR of TAI was 51.1%, 47.1%, and 47.8% for GeCGTW, GeCGEB24, and GeCGEC (P>0.05 respectively. The PR under clean-up bulls was 88.3%, 47.3%, and 31.1% (P<0.05. The final PR (TAI+clean-up bulls of the groups was 94.4%, 72.1%, and 64.0%, respectively (P<0.05. It was concluded that no differences in PR among the protocols related to TAI were detected; PR in the GeCGTW protocol under clean-up bulls was higher compared to others (P<0.05; the overall PR of cows subjected to TAI+clean-up bulls was significantly higher in GeCGTW than in the other groups.

  10. Metformin inhibits 17?-estradiol-induced epithelial-to-mesenchymal transition via ?Klotho-related ERK1/2 signaling and AMPK? signaling in endometrial adenocarcinoma cells

    OpenAIRE

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

    2016-01-01

    The potential role of metformin in treating endometrial cancer remains to be explored. The current study investigated the role of metformin in 17?-estradiol-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells. We found that 17?-estradiol promoted proliferation and migration, attenuated apoptosis in both estrogen receptor (ER) positive and ER negative endometrial adenocarcinoma cells (Ishikawa and KLE cells, respectively). Metformin abolished 17?-estradiol-induc...

  11. Transient human auditory cortex activation during volitional attention shifting.

    Directory of Open Access Journals (Sweden)

    Christian Harm Uhlig

    Full Text Available While strong activation of auditory cortex is generally found for exogenous orienting of attention, endogenous, intra-modal shifting of auditory attention has not yet been demonstrated to evoke transient activation of the auditory cortex. Here, we used fMRI to test if endogenous shifting of attention is also associated with transient activation of the auditory cortex. In contrast to previous studies, attention shifts were completely self-initiated and not cued by transient auditory or visual stimuli. Stimuli were two dichotic, continuous streams of tones, whose perceptual grouping was not ambiguous. Participants were instructed to continuously focus on one of the streams and switch between the two after a while, indicating the time and direction of each attentional shift by pressing one of two response buttons. The BOLD response around the time of the button presses revealed robust activation of the auditory cortex, along with activation of a distributed task network. To test if the transient auditory cortex activation was specifically related to auditory orienting, a self-paced motor task was added, where participants were instructed to ignore the auditory stimulation while they pressed the response buttons in alternation and at a similar pace. Results showed that attentional orienting produced stronger activity in auditory cortex, but auditory cortex activation was also observed for button presses without focused attention to the auditory stimulus. The response related to attention shifting was stronger contralateral to the side where attention was shifted to. Contralateral-dominant activation was also observed in dorsal parietal cortex areas, confirming previous observations for auditory attention shifting in studies that used auditory cues.

  12. 17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

    Science.gov (United States)

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

    2016-12-01

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

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

    Science.gov (United States)

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

    2018-03-07

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

  14. Pharmacokinetics of the first combination 17β-estradiol/progesterone capsule in clinical development for menopausal hormone therapy.

    Science.gov (United States)

    Pickar, James H; Bon, Charles; Amadio, Julia M; Mirkin, Sebastian; Bernick, Brian

    2015-12-01

    This study aims to compare the pharmacokinetics and oral bioavailability of a capsule combining 17β-estradiol and progesterone in a non-peanut oil-containing formulation with those of widely used and approved separate formulations of estradiol and progesterone coadministered to healthy postmenopausal women. This was an open-label, balanced, randomized, single-dose, two-treatment, three-period, three-sequence, cross-over, partial-replicate, reference-scaled study. Postmenopausal women (aged 40-65 y) were randomly assigned to one of three dosing sequences of test and reference products (TRR, RTR, or RRT, where T is the test drug and R is the coadministered reference product), with each of the three periods separated by a 14-day washout. The primary pharmacokinetic endpoints were Cmax, AUC(0-t), and AUC(0-inf) for the test and reference products, assessed for bioequivalence using the scaled average bioequivalence or unscaled average bioequivalence method. Safety was assessed by clinical observation, participant-reported adverse events, and laboratory data, including blood levels of hormones. Sixty-six women were randomly assigned, and 62 women (94.0%) completed all three study periods. All AUC and Cmax parameters met bioequivalence criteria for all analytes (estradiol, progesterone, and estrone), except Cmax for total estrone. The extent of estradiol and progesterone absorption was similar between the test product and the reference products. Four adverse events--all considered mild and unrelated to the study drugs--were reported. The combination 17β-estradiol/progesterone product demonstrates bioavailability similar to those of the respective reference products of estradiol and progesterone. If regulatory approval is obtained, this new hormone therapy would be the first treatment of menopause symptoms to combine progesterone with 17β-estradiol in an oral formulation.

  15. Does the ARFIMA really shift?

    DEFF Research Database (Denmark)

    Monache, Davide Delle; Grassi, Stefano; Santucci de Magistris, Paolo

    Short memory models contaminated by level shifts have long-memory features similar to those associated to processes generated under fractional integration. In this paper, we propose a robust testing procedure, based on an encompassing parametric specification, that allows to disentangle the level...

  16. Shift Work: Improving Daytime Sleep

    Science.gov (United States)

    ... Good daytime sleep is possible, though, if shift work is a necessary part of your work life. To promote better sleep during the day: ... Take naps. Napping late in the day before work might help you make up your sleep debt. ...

  17. Leadership Shifts in Changing Field

    Science.gov (United States)

    Zubrzycki, Jaclyn

    2013-01-01

    As groups representing local and state education players struggle to remain relevant in a policy conversation often dominated by foundations, think tanks, new advocacy groups, and political and business figures, a shift in leadership has been under way at major associations. Most of the changes have come as part of the natural churn; former…

  18. Shift register neutron coincidence module

    International Nuclear Information System (INIS)

    Stephens, M.M.; Swansen, J.E.; East, L.V.

    1975-11-01

    A neutron coincidence module was designed using multistage shift registers to produce the coincidence gates and a crystal controlled oscillator with variable clock outputs to change the gate lengths. The advantage of this system over the conventional, thermal-neutron coincidence gates is a decrease in deadtime by more than an order of magnitude

  19. The Shift Needed for Sustainability

    Science.gov (United States)

    Smith, Peter A. C.; Sharicz, Carol

    2011-01-01

    Purpose: The purpose of this action research is to begin to assess to what extent organizations have in practice begun to make the shift towards triple bottom line (TBL) sustainability. Design/methodology/approach: A definition of TBL sustainability is provided, and key elements of TBL sustainability considered necessary to success are identified…

  20. Environmental Protection: a shifting focus

    NARCIS (Netherlands)

    Dr. ir. Jan Venselaar

    2004-01-01

    The last two decades have seen a fundamental change in the way chemistry handles environmental issues. A shift in focus has occurred from 'end-of-pipe' to prevention and process integration. Presently an even more fundamental change is brought about by the need for sustainable development. It is

  1. Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa, E-mail: nebojsa.andric@dbe.uns.ac.rs

    2013-07-01

    Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

  2. Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

    International Nuclear Information System (INIS)

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa

    2013-01-01

    Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

  3. Clinical comparison of monophasic oral contraceptive preparations of gestodene/ethinyl estradiol and desogestrel/ethinyl estradiol. Latin American Oral Contraceptive Study Group.

    Science.gov (United States)

    1994-09-01

    The efficacy, cycle control, subjective complaints, and safety of monophasic preparations of the oral contraceptives containing gestodene 75 mcg plus ethinyl estradiol 30 mcg versus desogestrel 150 mcg plus ethinyl estradiol 30 mcg were compared in a 6-cycle, open-label, parallel, randomized, multicenter phase IV clinical study in Latin America. Of a total of 176 women in each group, 163 in the gestodene group and 160 in the desogestrel group completed 6 cycles, providing data for 1,015 and 1,006 cycles, respectively. Subject compliance was excellent; pills were missed during only 6.9% of the cycles in each group. No woman became pregnant during the study. Gestodene group exhibited significantly better cycle control as evidenced by the lower incidence of breakthrough bleeding and spotting. Spotting in some cycles was reported by 11.9% of women taking the gestodene-combination compared with 21% of women taking the desogestrel-combination. Based on number of women, 86.4% of the gestodene group reported all cycles were normal (no BTB) compared with 76.7% of the desogestrel group. Also, the women in the gestodene group reported a significantly lower incidence of nuisance side effects during treatment cycles. No amenorrhea was observed for either group. There were no clinically significant differences between groups with respect to body weight, blood pressure, or laboratory evaluations. Seven women withdrew from the gestodene group and 8 women withdrew from the desogestrel group because of adverse reactions. The results of this study indicate that, although both OCs provided effective contraception, in comparison to the desogestrel-combination, the gestodene-containing OC is associated with better cycle control, less bleeding, and fewer subjective complaints.

  4. Plasma concentrations of estradiol and testosterone, gonadal aromatase activity and ultrastructure of the testis in Xenopus laevis exposed to estradiol or atrazine

    International Nuclear Information System (INIS)

    Hecker, Markus; Kim, Wan Jong; Park, June-Woo; Murphy, Margaret B.; Villeneuve, Daniel; Coady, Katherine K.; Jones, Paul D.; Solomon, Keith R.; Kraak, Glen van der; Carr, James A.; Smith, Ernest E.; Preez, Louis du; Kendall, Ronald J.; Giesy, John P.

    2005-01-01

    The ultrastructure of testicular cells of adult male African clawed frogs (Xenopus laevis) exposed to either estradiol (0.1 μg/L) or 2-chloro-4-ethylamino-6-isopropyl-amino-s-triazine (atrazine; 10 or 100 μg/L) was examined by electron microscopy and compared to plasma concentrations of the steroid hormones, testosterone (T) and estradiol (E2), testicular aromatase activity and gonad growth expressed as the gonado-somatic index (GSI). Exposure to E2 caused significant changes both at the sub-cellular and biochemical levels. Exposure to E2 resulted in significantly fewer sperm cells, inhibition of meiotic division of germ cells, more lipid droplets that are storage compartments for the sex steroid hormone precursor cholesterol, and lesser plasma T concentrations. Although not statistically significant, frogs exposed to E2 had slightly smaller GSI values. These results may be indicative of an inhibition of gonad growth and disrupted germ cell development by E2. Concentrations of E2 in plasma were greater in frogs exposed to E2 in water. Exposure to neither concentration of atrazine caused effects on germ cell development, testicular aromatase activity or plasma hormone concentrations. These results suggest that atrazine does not affect testicular function. In contrast, exposure of male X. laevis to E2 led to sub-cellular events that are indicative of disruption of testicular development, and demasculinization processes (decrease of androgen hormone titers). These results indicate that atrazine does not cause responses that are similar to those caused by exposure to E2

  5. Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell.

    Science.gov (United States)

    Zhang, Hui; Guo, Qiufen; Wang, Chong; Yan, Lei; Fu, Yibing; Fan, Mingjun; Zhao, Xingbo; Li, Mingjiang

    2013-08-25

    Dual-specificity phosphatase 6 (Dusp6) is a negative feedback mechanism of fibroblast growth factors (FGFs)/mitogen-activated protein kinase (MAPK)/ERK1/2 signaling. The aim of this study was to explore the expression of Dusp6 in human endometrial adenocarcinomas and the role of Dusp6 expression in the growth regulation of endometrial adenocarcinoma cell. We found that Dusp6 was over-expressed in human endometrial adenocarcinomas. In Ishikawa cells, plasmid-driven Dusp6 expression efficiently blocked the activity of FGF2-induced MAPK/ERK1/2 signaling. Unexpectedly, Dusp6 expression significantly enhanced the growth of Ishikawa cells. In Dusp6 forced-expression cells, 17β-estradiol stimulation increased the cell growth by all most threefolds. In addition, progesterone treatment reduced the cell growth to about half both in Ishikawa cells with and without forced-Dusp6-expression. Dusp6 over-expression is involved in the pathogenesis and development of human endometrial adenocarcinomas. Dusp6 functions as a negative regulator of FGF2/ERK1/2 signaling but enhances the growth and 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Copyright © 2013. Published by Elsevier Ireland Ltd.

  6. Stimulant-induced trichotillomania.

    Science.gov (United States)

    Hamalian, Gareen; Citrome, Leslie

    2010-01-01

    A prior report described the presentation of cocaine-induced trichotillomania, which resolved with the cessation of cocaine use. Here the authors describe the case of stimulant-induced trichotillomania that resolved with the discontinuation of stimulants and initiation of olanzapine. To the authors' knowledge this is the first reported adult case of stimulant-induced trichotillomania. The case is of a patient with a previous diagnosis of attention deficit hyperactivity disorder whose symptoms of trichotillomania coincide with abuse of amphetamine and with the resolution of symptoms in the absence of amphetamine use. Given the increase in exposure of prescription amphetamines among adults, further study into the association between stimulants and adverse events such as trichotillomania is needed.

  7. Vagus Nerve Stimulation

    Science.gov (United States)

    ... you do certain activities such as public speaking, singing or exercising, or when you're eating if ... of life. Research is still mixed on the benefits of vagus nerve stimulation for the treatment of ...

  8. Multipolar intrafascicular stimulation

    NARCIS (Netherlands)

    Meier, Jan H.; Meier, J.H.; Rutten, Wim

    1992-01-01

    The suppressing effect of two intrafascicular anodes on the neural recruitment elicited by one intrafascicular cathode has been studied. Recruitment curves are calculated with a nerve stimulation model and are compared to experimental curves for the peroneal nerve of rat.

  9. Mixtures of xenoestrogens disrupt estradiol-induced non-genomic signaling and downstream functions in pituitary cells.

    Science.gov (United States)

    Viñas, René; Watson, Cheryl S

    2013-03-26

    Our study examines the effects of xenoestrogen mixtures on estradiol-induced non-genomic signaling and associated functional responses. Bisphenol-A, used to manufacture plastic consumer products, and nonylphenol, a surfactant, are estrogenic by a variety of assays, including altering many intracellular signaling pathways; bisphenol-S is now used as a bisphenol-A substitute. All three compounds contaminate the environment globally. We previously showed that bisphenol-S, bisphenol-A, and nonylphenol alone rapidly activated several kinases at very low concentrations in the GH3/B6/F10 rat pituitary cell line. For each assay we compared the response of individual xenoestrogens at environmentally relevant concentrations (10-15 -10-7 M), to their mixture effects on 10-9 M estradiol-induced responses. We used a medium-throughput plate immunoassay to quantify phosphorylations of extracellular signal-regulated kinases (ERKs) and c-Jun-N-terminal kinases (JNKs). Cell numbers were assessed by crystal violet assay to compare the proliferative effects. Apoptosis was assessed by measuring caspase 8 and 9 activities via the release of the fluorescent product 7-amino-4-trifluoromethylcoumarin. Prolactin release was measured by radio-immunoassay after a 1 min exposure to all individual and combinations of estrogens. Individual xenoestrogens elicited phospho-activation of ERK in a non-monotonic dose- (fM-nM) and mostly oscillating time-dependent (2.5-60 min) manner. When multiple xenoestrogens were combined with nM estradiol, the physiologic estrogen's response was attenuated. Individual bisphenol compounds did not activate JNK, while nonylphenol did; however, the combination of two or three xenoestrogens with estradiol generated an enhanced non-monotonic JNK dose-response. Estradiol and all xenoestrogen compounds induced cell proliferation individually, while the mixtures of these compounds with estradiol suppressed proliferation below that of the vehicle control, suggesting a

  10. Functional connectivity between prefrontal and parietal cortex drives visuo-spatial attention shifts.

    Science.gov (United States)

    Heinen, Klaartje; Feredoes, Eva; Ruff, Christian C; Driver, Jon

    2017-05-01

    It is well established that the frontal eye-fields (FEF) in the dorsal attention network (DAN) guide top-down selective attention. In addition, converging evidence implies a causal role for the FEF in attention shifting, which is also known to recruit the ventral attention network (VAN) and fronto-striatal regions. To investigate the causal influence of the FEF as (part of) a central hub between these networks, we applied thetaburst transcranial magnetic stimulation (TBS) off-line, combined with functional magnetic resonance (fMRI) during a cued visuo-spatial attention shifting paradigm. We found that TBS over the right FEF impaired performance on a visual discrimination task in both hemifields following attention shifts, while only left hemifield performance was affected when participants were cued to maintain the focus of attention. These effects recovered ca. 20min post stimulation. Furthermore, particularly following attention shifts, TBS suppressed the neural signal in bilateral FEF, right inferior and superior parietal lobule (IPL/SPL) and bilateral supramarginal gyri (SMG). Immediately post stimulation, functional connectivity was impaired between right FEF and right SMG as well as right putamen. Importantly, the extent of decreased connectivity between right FEF and right SMG correlated with behavioural impairment following attention shifts. The main finding of this study demonstrates that influences from right FEF on SMG in the ventral attention network causally underly attention shifts, presumably by enabling disengagement from the current focus of attention. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. A novel 17β-hydroxysteroid dehydrogenase in Rhodococcus sp. P14 for transforming 17β-estradiol to estrone.

    Science.gov (United States)

    Ye, Xueying; Wang, Hui; Kan, Jie; Li, Jin; Huang, Tongwang; Xiong, Guangming; Hu, Zhong

    2017-10-01

    17β-hydroxysteroid dehydrogenases (17β-HSD) are a group of oxidoreductase enzymes that exhibit high specificity for 17C reduction/oxidation. However, the mechanism of 17β-HSD in oxidizing steroid hormone 17β-estradiol to estrone in bacterium is still unclear. In this work, a functional bacterium Rhodococcus sp. P14 was identified having rapid ability to oxidize estradiol into estrone in mineral salt medium (MSM) within 6 h. The functional genes encoding NADH-dependent oxidoreductase were successfully detected with the help of bioinformatics, and it was identified that it contained two consensus regions affiliated to the short-chain dehydrogenase/reductase (SDR) superfamily. Expression of 17β-HSD could be induced by estradiol in strain P14. The 17β-HSD gene from Rhodococcus sp. P14 was expressed in Escherichia coli strain BL21. Furthermore, recombinant 17β-HSD-expressing BL21 cells showed a high transformation rate, they are capable of transforming estradiol to estrone up to 94%. The purified His-17β-HSD protein also exhibited high catalyzing efficiency. In conclusion, this study provides the first evidence that a novel 17β-HSD in Rhodococcus sp. P14 can catalyze the oxidation of estradiol. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

    International Nuclear Information System (INIS)

    Okamoto, Mayumi; Naka, Kyosuke; Kitagawa, Yuya; Ishiwata, Kiichi; Yoshimoto, Mitsuyoshi; Shimizu, Isao; Toyohara, Jun

    2015-01-01

    Introduction: Several lines of evidence suggest that C-7α-substituted estradiol derivatives are well tolerated by estrogen receptor (ER). In line with this hypothesis, we are interested in the design and synthesis of C-7α-substituted estrogens as molecular probes to visualize ER function. Methods: We have synthesized 7α-(3-[ 18 F]fluoropropyl) estradiol (C3-7α-[ 18 F]FES) as a potential radiopharmaceutical for ER imaging by positron emission tomography (PET). In vitro receptor binding and in vivo biodistribution and blocking studies in mature female mice, and in vivo metabolite analysis were carried out. Furthermore, in vivo ER-selective uptake was confirmed using ER-positive T-47D and ER-negative MDA-MB-231 tumor-bearing mice. We also compared the in vivo biodistribution of C3-7α-[ 18 F]FES with 16α-[ 18 F]FES. Results: C3-7α-[ 18 F]FES was produced in moderate yields (30.7% ± 15.1%, decay corrected) with specific activity of 32.0 ± 18.1 GBq/μmol (EOS). The in vitro binding affinity of C3-7α-FES to the ERα isoform was sufficient and equivalent to that of estradiol. C3-7α-[ 18 F]FES showed selective uptake in ER-rich tissues, such as the uterus (4.7%ID/g ± 1.2%ID/g at 15 minutes) and ovary (4.0%ID/g ± 1.0%ID/g at 5 minutes). The tissue time activity curves of these organs showed reversible kinetics, indicating suitability for quantitative analysis. The highest contrast was obtained at 120 minutes after injection of C3-7α-[ 18 F]FES in the uterus (uterus/blood = 18, uterus/muscle = 17.3) and ovary (ovary/blood = 6.3, ovary/muscle = 6.0). However, the level of selective uptake of C3-7α-[ 18 F]FES was significantly lower than that of 16α-[ 18 F]FES. Most radioactivity in the uterus was detected in unchanged form, although peripherally C3-7α-[ 18 F]FES was rapidly degraded to hydrophilic metabolites. In accordance with this peripheral metabolism, gradual increases in bone radioactivity were observed, indicating defluorination. Coinjection with

  13. Impact of optokinetic stimulation on mental arithmetic.

    Science.gov (United States)

    Masson, Nicolas; Pesenti, Mauro; Dormal, Valérie

    2017-07-01

    Solving arithmetic problems has been shown to induce shifts of spatial attention, subtraction problems orienting attention to the left side, and addition problems to the right side of space. At the neurofunctional level, the activations elicited by the solving of arithmetical problems resemble those elicited by horizontal eye movements. Whether overt orientation of attention (i.e., eye movements) can be linked to the solving procedure is, however, still under debate. In the present study, we used optokinetic stimulation (OKS) to trigger automatic eye movements to orient participants' overt attention to the right or to the left of their visual field while they were solving addition or subtraction problems. The results show that, in comparison to leftward OKS and a control condition, rightward OKS facilitates the solving of addition problems that necessitate a carrying procedure. Subtraction solving was unaffected by leftward or rightward OKS. These results converge with previous findings to show that attentional shifts are functionally related to mental arithmetic processing.

  14. Stimulated Brillouin processes in crystals and glasses

    International Nuclear Information System (INIS)

    Faris, G.W.; Hickman, A.P.

    1992-02-01

    The basic physics and material properties needed to describe and predict the Brillouin gain for a variety of materials have been investigated. Lawrence Livermore National Laboratory (LLNL) has identified transverse stimulated Brillouin scattering (SBS) as an important limiting mechanism in high power laser fusion systems. At sufficiently high laser intensities, SBS drives acoustic vibrations that can damage optical components. SRI has performed measurements and developed the corresponding theory for stimulated Brillouin gain spectroscopy in anisotropic crystals. Absolute Brillouin steady-state gain coefficients, linewidths, and frequency shifts have been determined at 532 nm for a number of optical materials of interest to LLNL. This knowledge can be used to select optical materials and devise suppression schemes that will allow much higher laser fluences to be used in laser fusion

  15. Stokes and anti-stokes stimulated Mie scattering on nanoparticle suspensions of latex

    Science.gov (United States)

    Burkhanov, I. S.; Krivokhizha, S. V.; Chaikov, L. L.

    2016-12-01

    Stokes and anti-Stokes shifts of stimulated concentration light scattering (SCLS, stimulated Mie scattering) in suspensions of various-sized latex nanoparticles in water were measured by the light guide scheme, under conditions of backscattering in the presence of convection.

  16. Mimicking of Estradiol Binding by Flame Retardants and Their Metabolites: A Crystallographic Analysis

    Science.gov (United States)

    Gosavi, Rajendrakumar A.; Knudsen, Gabriel A.; Birnbaum, Linda S.

    2013-01-01

    Background: Brominated flame retardants (BFRs), used in many types of consumer goods, are being studied because of concerns about possible health effects related to endocrine disruption, immunotoxicity, reproductive toxicity, and neurotoxicity. Tetrabromobisphenol A (TBBPA), the most widely used BFR, and human metabolites of certain congeners of polybrominated diphenyl ether (e.g., 3-OH-BDE-47) have been suggested to inhibit estrogen sulfotransferase, potentially affecting estrogen metabolism. Objectives: Our primary goal was to understand the structural mechanism for inhibition of the hormone-metabolizing enzyme estrogen sulfotransferase by certain BFRs. We also sought to understand various factors that facilitate the binding of flame retardants in the enzyme binding pocket. Methods: We used X-ray crystallography to obtain atomic detail of the binding modes of TBBPA and 3-OH-BDE-47 to estrogen sulfotransferase for comparison with binding of the endogenous substrate estradiol. Results: The crystal structures reveal how BFRs mimic estradiol binding as well as the various interactions between the compounds and protein residues that facilitate its binding. In addition, the structures provide insights into the ability of the sulfotransferase substrate binding pocket to accommodate a range of halogenated compounds that satisfy minimal structural criteria. Conclusions: Our results show how BFRs or their metabolites can bind to and inhibit a key hormone-metabolizing enzyme, potentially causing endocrine disruption. Citation: Gosavi RA, Knudsen GA, Birnbaum LS, Pedersen LC. 2013. Mimicking of estradiol binding by flame retardants and their metabolites: a crystallographic analysis. Environ Health Perspect 121:1194–1199; http://dx.doi.org/10.1289/ehp.1306902 PMID:23959441

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-06-01

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

  18. Effects of ethinyl estradiol plus desogestrel on premenstrual symptoms in Iranian women.

    Directory of Open Access Journals (Sweden)

    Abbas Norouzi Javidan

    2014-11-01

    Full Text Available Marvelon®, a combined oral contraceptive, contains 30 μg ethinyl estradiol (EE and 150 μg desogestrel (DE, and has been shown to be a well-tolerated and effective combination that provides high contraceptive reliability and good cycle control. However, its efficacy has not been yet evaluated among Iranian women. Thus, the study aimed to determine the effect of oral contraceptive pill on treating premenstrual symptoms and on various parameters associated with well-being and health in a sample of Iranian. This clinical trial (before- after study was performed at the family-planning clinic of the centers under the supervision of Tehran University of Medical Sciences on sixty-one women. The study protocol was approved by the Ethics Committee of Tehran University of Medical Sciences and all participants received a 21/7-day regimen of oral contraceptive containing 150 μg desogestrel (DE and 30 μg ethinyl estradiol (EE for six cycles. Efficacy parameters included changes in premenstrual symptoms were also assessed. Clinical data was collected by calendar of premenstrual experiences (COPE at baseline and treatment cycles 1,2, 3 and 6. Clinical variables were measured including low-density lipoprotein (LDL, high-density lipoprotein (HDL and triglyceride levels for two timing periods (baseline and last visit. Linear mixed model analyses were used to analyze differences in changes of the four factors of premenstrual syndrome (PMS, weight and blood pressure during these timing periods. The mean age of the women was 28.52 (SD=6.75 years. Participants on average had been pregnant 1.13 (SD=1.16 times. The linear mixed model analyses indicated that premenstrual syndrome symptoms reduced significantly over time (P0.05. A combined oral contraceptive containing ethinyl estradiol and desogestrel has a positive effect on women's health and reduces premenstrual symptoms.

  19. Fate of 4-nonylphenol and 17β-estradiol in the Redwood River of Minnesota

    Science.gov (United States)

    Writer, Jeffrey H.; Ryan, Joseph N.; Keefe, Steffanie H.; Barber, Larry B.

    2012-01-01

    The majority of previous research investigating the fate of endocrine-disrupting compounds has focused on single processes generally in controlled laboratory experiments, and limited studies have directly evaluated their fate and transport in rivers. This study evaluated the fate and transport of 4-nonylphenol, 17β-estradiol, and estrone in a 10-km reach of the Redwood River in southwestern Minnesota. The same parcel of water was sampled as it moved downstream, integrating chemical transformation and hydrologic processes. The conservative tracer bromide was used to track the parcel of water being sampled, and the change in mass of the target compounds relative to bromide was determined at two locations downstream from a wastewater treatment plant effluent outfall. In-stream attenuation coefficients (kstream) were calculated by assuming first-order kinetics (negative values correspond to attenuation, whereas positive values indicate production). Attenuation of 17β-estradiol (kstream = −3.2 ± 1.0 day–1) was attributed primarily due to sorption and biodegradation by the stream biofilm and bed sediments. Estrone (kstream = 0.6 ± 0.8 day–1) and 4-nonylphenol (kstream = 1.4 ± 1.9 day–1) were produced in the evaluated 10-km reach, likely due to biochemical transformation from parent compounds (17β-estradiol, 4-nonylphenolpolyethoxylates, and 4-nonyphenolpolyethoxycarboxylates). Despite attenuation, these compounds were transported kilometers downstream, and thus additive concentrations from multiple sources and transformation of parent compounds into degradates having estrogenic activity can explain their environmental persistence and widespread observations of biological disruption in surface waters.

  20. Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions.

    Science.gov (United States)

    Elger, W; Wyrwa, R; Ahmed, G; Meece, F; Nair, H B; Santhamma, B; Killeen, Z; Schneider, B; Meister, R; Schubert, H; Nickisch, K

    2017-01-01

    Oral compared to parenteral estrogen administration is characterized by reduced systemic but prominent hepatic estrogenic effects on lipids, hemostatic factors, GH-/IGF I axis, angiotensinogen. In order to avoid such adverse metabolic effects of oral treatment, estradiol (E2) prodrugs (EP) were designed which bypass the liver tissue as inactive molecules. Carbone17-OH sulfonamide [-O 2 -NH 2 ] substituted esters of E2 (EC508, others) were synthesized and tested for carbonic anhydrase II (CA-II) binding. CA II in erythrocytes is thought to oppose extraction of EP from portal vein blood during liver passage. Ovariectomized (OVX, day minus 14) rats were orally treated once daily from day 1-3. Sacrifice day 4. Uteri were dissected and weighed. Cholesterol fractions and angiotensinogen were determined in plasma. Oral E2 and ethinyl estradiol (EE) generated dose related uterine growth and important hepatic estrogenic effects. EP induced uterine growth at about hundred-fold lower doses. This was possible with almost absent effects on plasma cholesterol or angiotensinogen. Preliminary pharmacokinetic studies with EC508 used intravenous and oral administration in male rats. Resulting blood levels revealed complete oral bioavailability. Further high blood- but low plasma concentrations indicated erythrocyte binding of EC508 in vivo as potential mechanism of low extraction at liver passage. Very high systemic estrogenicity combined with markedly lower or absent adverse hepatic estrogenic effects is evidence for a systemic release of E2 from sulfonamide EP. In conclusion, tested oral EP bypass the liver in erythrocytes furnishing systemic estradiol at hydrolysis. This mechanism avoids the hepatic estrogenic impact of conventional oral estrogen therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Female Japanese quail with high levels of estradiol demonstrate cocaine-induced conditioned place preference.

    Science.gov (United States)

    Gill, Karin E; Reynolds, Anna R; Prendergast, Mark A; Akins, Chana K

    2016-06-01

    Preclinical research has indicated that females may be more sensitive to the rewarding properties of cocaine. However, the majority of this research has been done in rodent species. Environmental cues associated with human drug-taking behavior tend to be visual. Because rodents do not rely on the visual system as their primary sense modality, the use of a visually oriented species may add to our understanding of cue-elicited drug cravings and relapse. The present study examined the potential role of the steroid hormone, estradiol, in the rewarding properties of cocaine in female Japanese quail using a conditioned place preference (CPP) procedure. In the current experiment, female quail were housed on either an 8L:16D (light:dark) or 16L:8D (light:dark) cycle for 21 days to induce photoregression or photostimulation, respectively. They then received 10, 20, or 30 mg/kg cocaine, or saline during conditioning. Conditioning trials were carried out for 8 days, once per day for 30 min, for a total of 4 cocaine and 4 saline alternating conditioning trials. Results indicated that female quail housed in long-light conditions (16L:8D) had significantly higher levels of estradiol than short-cycle females. Additionally, photostimulated female quail developed a CPP to 10 and 20 mg/kg cocaine. Short-cycle females did not show cocaine-induced CPP to any dose tested. Results indicate that cocaine is dose-dependently rewarding to photostimulated female Japanese quail. Furthermore, the current findings suggest that estradiol may enhance the rewarding properties of cocaine in female quail. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  2. Sexual Dimorphism of Growth Hormone in the Hypothalamus: Regulation by Estradiol

    Science.gov (United States)

    Addison, Melisande L.

    2012-01-01

    GH is best known as an anterior pituitary hormone fundamental in regulating growth, differentiation, and metabolism. GH peptide and mRNA are also present in brain, in which their functions are less well known. Here we describe the distribution of GH neurons and fibers and sex differences in Gh mRNA in adult mouse brain. Cell bodies exhibiting GH immunoreactivity are distributed in many brain regions, particularly in the hypothalamus in which retrograde labeling suggests that some of these cells project to the median eminence. To determine whether Gh mRNA is sexual dimorphic, we carried out quantitative RT-PCR on microdissected brain nuclei. Ovary-intact mice had elevated Gh mRNA in the arcuate nucleus and medial preoptic area (MPOA) compared with gonad-intact males. In males, castration increased Gh mRNA in the MPOA, whereas ovariectomy decreased Gh mRNA in both regions. When gonadectomized adults of both sexes were treated with estradiol Gh mRNA increased in females but had no effect in castrated males. Tamoxifen was able to blunt the rise in Gh mRNA in response to estradiol in females. In addition, we found that estrogen receptor-α is coexpressed in GH neurons in the MPOA and arcuate nucleus. In summary, the findings reveal sexual dimorphisms in Gh gene expression in areas of the brain associated with reproduction and behavior. Interestingly, estradiol enhances Gh mRNA in females only, suggesting that multiple factors orchestrate this sexual dimorphism. PMID:22315455

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

    Science.gov (United States)

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

    2015-09-01

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

  4. Preventive effects of oligomerized polyphenol on estradiol-induced prostatitis in rats.

    Science.gov (United States)

    Kim, Dong Suk; Lee, Eun Jin; Cho, Kang Su; Yoon, So Jung; Lee, Young Hoon; Hong, Sung Joon

    2009-06-30

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.

  5. Biodistribution and metabolism of 16α-([/sup 18/F]-fluoro)-17β-estradiol

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  6. Serum estradiol and progesterone profiles during estrus, pseudopregnancy, and active gestation in Steller sea lions.

    Science.gov (United States)

    Sattler, Renae; Polasek, Lori

    2017-09-01

    While the proximate driver behind the decline of the Western stock of Steller sea lions (Eumetopias jubatus, >80% since 1970s) is likely multifactorial, the population reduction may have been powered by a decrease in fecundity. A harvest of Steller sea lions in the 1970s and 80s revealed a 30% reduction in the proportion of pregnant females from early (October-November) to late gestation (April-May). Identification and quantification of these reproductive failures are difficult when we lack species-specific data on endocrinology associated with discrete stages of the reproductive cycle (i.e., estrus, implantation, and gestation). We tracked changes in serum estradiol and progesterone in three adult female Steller sea lions from 2011 to 2015. In all years and most females, a discrete increase in estradiol was observed during the breeding season (June-August), indicative of estrus. Estradiol concentrations from October to May in a pregnant female compared to her corresponding values when non-pregnant did not consistently differ through gestation. An elevation in progesterone was observed in all females and all years beginning approximately in June and lasting through November. This likely results from progesterone production by the corpus luteum in both pregnant and pseudopregnant females. Serum progesterone shows promise as a diagnostic tool to identify pregnancy during months 3-5 (December-February) of the 8-month active gestation following embryonic implantation. This study provides ranges of key hormones during estrus, embryonic diapause/pseudopregnancy, and gestation in pregnant and non-pregnant females for studying reproduction in Steller sea lions. © 2017 Wiley Periodicals, Inc.

  7. Special training of shift personnel

    International Nuclear Information System (INIS)

    Martin, H.D.

    1981-01-01

    The first step of on-the-job training is practical observation phase in an operating Nuclear Plant, where the participants are assigned to shift work. The simulator training for operating personnel, for key personnel and, to some extent, also for maintenance personnel and specialists give the practical feeling for Nuclear Power Plant behaviour during normal and abnormal conditions. During the commissioning phase of the own Nuclear Power Plant, which is the most important practical training, the participants are integrated into the commissioning staff and assisted during their process of practical learning by special instructors. The preparation for the licensing exams is vitally important for shift personnel and special courses are provided after the first non-nuclear trial operation of the plant. Personnel training also includes performance of programmes and material for retraining, training of instructors and assistance in building up special training programmes and material as well as training centers. (orig./RW)

  8. Contraception containing estradiol valerate and dienogest--advantages, adherence and user satisfaction.

    Science.gov (United States)

    Graziottin, A

    2014-10-01

    The contraceptive pill containing estradiol valerate and dienogest meets women's requests for: a more natural contraceptive, that is reliable and easy to use, with positive cosmetic effects; less intense and shorter bleeding, reduced anaemia and increased vital energy; reduced dysmenorrhoea and all the specific cycle-related symptoms linked to a drop in oestrogen and the related systemic inflammation, the result of a hormone free interval (HFI) of just two days; with a good impact on sexuality and overall well-being, all associated with a high level of efficacy: (uncorrected Pearl Index: 0.79; corrected: 0.42). Women would prefer more natural hormonal contraception, with high reliability, good tolerability, a simple dosing schedule and possibly some health advantages. To evaluate what the pill containing estradiol valerate and dienogest can offer women and the best way to communicate this opportunity, after 4 years of growing clinical use. A review of literature plus the Author's clinical experience. The new pill containing estradiol valerate and dienogest may satisfy women's need for: a more natural hormonal contraceptive with a low hormone dosage, high reliability and good tolerability; a simple dosing schedule (one pill per day for 28 days); a positive cosmetic effect on the skin; lighter and shorter withdrawal bleeding, improved anaemia, less fatigue and higher vital energy; reduced dysmenorrhoea and a dramatic reduction in all symptoms thanks to a shorter Hormone Free Interval (HFI) of just two days. The new pill is an option for all women taking hormonal contraception who would like a more natural choice; for those who have never used hormonal contraception and may consider this new opportunity positively, for those who suffer from various menstrual symptoms, related inflammation ("a shorter HFI means much fewer or no symptoms") and, possibly for pre-menopausal women, an opportunity to combine excellent contraception with a definite improvement in their well

  9. Acciones neuroprotectoras del estradiol y los receptores de estrógenos

    OpenAIRE

    García Segura, Luis Manuel

    2016-01-01

    El estradiol y la progesterona regulan el desarrollo y la función de los sistemas nerviosos central y periférico. Además, las hormonas ováricas, actuando a través de las células endoteliales, las células de glía y las neuronas, ejercen acciones neuroprotectoras en varios modelos animales de patología neural. Sin embargo, las implicaciones clínicas de las acciones neuroprotectoras de las hormonas ováricas en el hombre, son objeto de debate. Universidad de Málaga. Campus de...

  10. Effects of estrogen antagonists on estradiol-enhanced radiation transformation in vitro

    International Nuclear Information System (INIS)

    Umans, R.S.; Kenneddy, A.R.

    1988-01-01

    We have previously reported that radiation and 17β-estrediol can induce transformation in vitro in C3H 10T1/2 cells. In the present series of experiments, we have observed that antagonists of estrogen action, such as c-AMP activating agents(Theophylinne and dibutylc-AMP) and the antiestrogens tamoxifen, suppress radiation/17β-estradiol enhanced transformation in vitro. None of these known estrogen antagonists had a significant effect on transformation induced by radiation alone. Our results with added dibutyl c-AMP, theophylline and tamoxifen suggest that estrogen receptor complex formation may play a role in estrogen-enhanced radiation transformation in vitro (author)

  11. Kisspeptin Expression in Guinea Pig Hypothalamus: Effects of 17β-Estradiol

    OpenAIRE

    Bosch, Martha A.; Xue, Changhui; Rønnekleiv, Oline K.

    2012-01-01

    Kisspeptin is essential for reproductive functions in humans. As a model for the human we have used the female guinea pig, which has a long ovulatory cycle similar to that of primates. Initially, we cloned a guinea pig kisspeptin cDNA sequence and subsequently explored the distribution and 17β-estradiol (E2) regulation of kisspeptin mRNA (Kiss1) and protein (kisspeptin) by using in situ hybridization, real-time PCR and immunocytochemistry. In ovariectomized females, Kiss1 neurons were scatter...

  12. Debt Shifting and Ownership Structure

    OpenAIRE

    Dirk Schindler; Guttorm Schjelderup

    2011-01-01

    Previous theoretical studies on the debt shifting behavior of multinationals have assumed affiliates of multinationals to be wholly owned. We develop a model that allows a multinational firm to determine both the leverage and ownership structure in affiliates endogenously. A main finding is that affiliates with minority owners have less debt than wholly owned affiliates and therefore a less tax efficient financing structure. This is due to an externality that arises endogenously in our model,...

  13. Into the Era of shifts

    DEFF Research Database (Denmark)

    Dencik, Lars

    2005-01-01

    Globalization and new communication technologies shape new increasingly unpredictable living conditions. Societies as individuals face a world og growing predictive impotence. Traditions loose their power as guides for maneuvering - where traditions was reflection will be. At the same time people......, life styles, experiences and sexuality. Even thougts and feelings.In the era of shifts we shall be living with ever more design in an ever less designed world....

  14. Hadronic shift in pionic hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Hennebach, M.; Gotta, D. [Forschungszentrum Juelich, Institut fuer Kernphysik, Juelich (Germany); Anagnostopoulos, D.F. [University of Ioannina, Department of Materials Science and Engineering, Ioannina (Greece); Dax, A.; Liu, Y.W.; Markushin, V.E.; Simons, L.M. [Paul Scherrer Institut, Laboratory for Particle Physics, Villigen (Switzerland); Fuhrmann, H.; Gruber, A.; Hirtl, A.; Zmeskal, J. [Austrian Academy of Sciences, Stefan Meyer Institute for Subatomic Physics, Vienna (Austria); Indelicato, P. [UPMC Univ. Paris 06, Laboratoire Kastler Brossel, Sorbonne Universites, Paris (France); CNRS, Laboratoire Kastler Brossel, Paris (France); Departement de Physique de l' Ecole Normale Superieure, Laboratoire Kastler Brossel, Paris (France); Manil, B. [UPMC Univ. Paris 06, Laboratoire Kastler Brossel, Sorbonne Universites, Paris (France); Rusi el Hassani, A.J. [Universite Abdelmalek Essaadi, Faculte des Sciences et Techniques, Tanger (Morocco); Trassinelli, M. [Sorbonne Universites, Institut des NanoSciences de Paris, Paris (France); CNRS, Institut des NanoSciences de Paris, Paris (France)

    2014-12-01

    The hadronic shift in pionic hydrogen has been redetermined to be ε {sub 1s} = 7.086 ± 0.007(stat) ± 0.006(sys) eV by X-ray spectroscopy of ground-state transitions applying various energy calibration schemes. The experiment was performed at the high-intensity low-energy pion beam of the Paul Scherrer Institut by using the cyclotron trap and an ultimate-resolution Bragg spectrometer with bent crystals. (orig.)

  15. Multicolor Holography With Phase Shifting

    Science.gov (United States)

    Vikram, Chandra S.

    1996-01-01

    Prototype apparatus constructed to test feasibility of two-color holographic interferometric scheme in which data for reconstructing holographic wavefront obtained with help of phase-shifting technique. Provides two sets of data needed to solve equations for effects of temperature and concentration. Concept extended to holography at three or more wavelengths to measure three or more phenomena associated with significant variations in index of refraction

  16. Shift Work and Endocrine Disorders

    Directory of Open Access Journals (Sweden)

    M. A. Ulhôa

    2015-01-01

    Full Text Available The objective of this review was to investigate the impact of shift and night work on metabolic processes and the role of alterations in the sleep-wake cycle and feeding times and environmental changes in the occurrence of metabolic disorders. The literature review was performed by searching three electronic databases for relevant studies published in the last 10 years. The methodological quality of each study was assessed, and best-evidence synthesis was applied to draw conclusions. The literature has shown changes in concentrations of melatonin, cortisol, ghrelin, and leptin among shift workers. Melatonin has been implicated for its role in the synthesis and action of insulin. The action of this hormone also regulates the expression of transporter glucose type 4 or triggers phosphorylation of the insulin receptor. Therefore, a reduction in melatonin can be associated with an increase in insulin resistance and a propensity for the development of diabetes. Moreover, shift work can negatively affect sleep and contribute to sedentarism, unhealthy eating habits, and stress. Recent studies on metabolic processes have increasingly revealed their complexity. Physiological changes induced in workers who invert their activity-rest cycle to fulfill work hours include disruptions in metabolic processes.

  17. Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

    Science.gov (United States)

    Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

    2013-04-01

    Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI

  18. Exogenous cortisol causes a shift from deliberative to intuitive thinking.

    Science.gov (United States)

    Margittai, Zsofia; Nave, Gideon; Strombach, Tina; van Wingerden, Marijn; Schwabe, Lars; Kalenscher, Tobias

    2016-02-01

    People often rely on intuitive judgments at the expense of deliberate reasoning, but what determines the dominance of intuition over deliberation is not well understood. Here, we employed a psychopharmacological approach to unravel the role of two major endocrine stress mediators, cortisol and noradrenaline, in cognitive reasoning. Healthy participants received placebo, cortisol (hydrocortisone) and/or yohimbine, a drug that increases noradrenergic stimulation, before performing the cognitive reflection test (CRT). We found that cortisol impaired performance in the CRT by biasing responses toward intuitive, but incorrect answers. Elevated stimulation of the noradrenergic system, however, had no effect. We interpret our results in the context of the dual systems theory of judgment and decision making. We propose that cortisol causes a shift from deliberate, reflective cognition toward automatic, reflexive information processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Local estrogen replacement therapy in postmenopausal atrophic vaginitis: efficacy and safety of low dose 17beta-estradiol vaginal tablets.

    Science.gov (United States)

    Mainini, G; Scaffa, C; Rotondi, M; Messalli, E M; Quirino, L; Ragucci, A

    2005-01-01

    To verify the effectiveness and safety of low-dose 17beta-estradiol vaginal tablets in the treatment of the postmenopausal atrophic vaginitis. 325 postmenopausal women with atrophic vaginitis in estrogenic replacement therapy with 0.025 mg 17beta-estradiol vaginal tablets, one application each day for two weeks, and a single application two times a week for the following 22 weeks (total treatment period: 24 weeks). Most of the women reported an improvement of symptoms just after two weeks and minimal incidence of adverse reactions. No patients showed abnormal endometrial thickness and no one had to interrupt the treatment for abnormal uterine bleeding because of systemic absorption. Low-dose 17beta-estradiol vaginal tablets in the treatment of the postmenopausal atrophic vaginitis constitutes an extremely valid approach in terms of effectiveness and safety.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

    Science.gov (United States)

    Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

    2015-01-01

    Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

  2. Circulating sclerostin and estradiol levels are associated with inadequate response to bisphosphonates in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Morales-Santana, Sonia; Díez-Pérez, Adolfo; Olmos, José M; Nogués, Xavier; Sosa, Manuel; Díaz-Curiel, Manuel; Pérez-Castrillón, José L; Pérez-Cano, Ramón; Torrijos, Antonio; Jodar, Esteban; Rio, Luis Del; Caeiro-Rey, José R; Reyes-García, Rebeca; García-Fontana, Beatriz; González-Macías, Jesús; Muñoz-Torres, Manuel

    2015-12-01

    The biological mechanisms associated with an inadequate response to treatment with bisphosphonates are not well known. This study investigates the association between circulating levels of sclerostin and estradiol with an inadequate clinical outcome to bisphosphonate therapy in women with postmenopausal osteoporosis. This case-control study is based on 120 Spanish women with postmenopausal osteoporosis being treated with oral bisphosphonates. Patients were classified as adequate responders (ARs, n=66, mean age 68.2±8 years) without incident fractures during 5 years of treatment, or inadequate responders (IRs, n=54, mean age 67±9 years), with incident fractures between 1 and 5 years of treatment. Bone mineral density (DXA), structural analysis of the proximal femur and structural/fractal analysis of the distal radius were assessed. Sclerostin concentrations were measured by ELISA and 17β-estradiol levels by radioimmunoassay based on ultrasensitive methods. In the ARs group, sclerostin serum levels were significantly lower (p=0.02) and estradiol concentrations significantly higher (p=0.023) than in the IRs group. A logistic regression analysis was performed, including as independent variables in the original model femoral fracture load, 25 hydroxyvitamin D, previus history of fragility fracture, sclerostin and estradiol. Only previous history of fragility fracture (OR 14.04, 95% CI 2.38-82.79, p=0.004) and sclerostin levels (OR 1.11, 95% CI 1.02-1.20, p=0.011), both adjusted by estradiol levels remained associated with IRs. Also, sclerostin concentrations were associated with the index of resistance to compression (IRC) in the fractal analysis of the distal radius, a parameter on bone microstructure. Sclerostin and estradiol levels are associated with the response to bisphosphonate therapy in women with postmenopausal osteoporosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. 17-β estradiol and testosterone mineralization and incorporation into organic matter in broiler litter-amended soils.

    Science.gov (United States)

    Durant, Michelle B; Hartel, Peter G; Cabrera, Miguel L; Vencill, William K

    2012-01-01

    The presence of the hormones estradiol and testosterone in the environment is of concern because they adversely affect vertebrate sexual characteristics. Land spreading broiler litter introduces these hormones into the environment. We conducted two studies. The first study determined the mineralization of C-labeled estradiol and testosterone at three water potentials and three temperatures in four broiler litter-amended soils. With a few exceptions, the mineralization of each hormone either stayed the same or increased with increasing water content (both hormones) and increasing (estradiol) or decreasing (testosterone) temperature. Mineralization was dependent on soil type. The second study determined the incorporation of C-labeled estradiol and testosterone into (i) three soil organic matter (SOM) fractions (fulvic acid, humic acid, and humin) at two water potentials, two temperatures, and one sampling time, and (ii) at one water potential, one temperature, and seven sampling times. As time increased, higher temperature and water potential decreased percentages of C estradiol and testosterone in water- and acetone-soluble fractions and increased percentages in SOM fractions. However, the distribution of the two hormones in SOM fractions differed. For estradiol, higher temperature and water potential increased the percentage in all three SOM fractions. For testosterone, higher temperature and water potential increased the percentage of hormone in fulvic acid and humin. Although the mineralization studies suggest the potential for these hormones to still have environmental effects, the incorporation of the two hormones into SOM suggest that land spreading these hormones may actually be less of an environmental concern. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  4. The effect of 17β-estradiol on gene expression of calcitonin gene-related peptide and some pro-inflammatory mediators in peripheral blood mononuclear cells from patients with pure menstrual migraine

    Directory of Open Access Journals (Sweden)

    Azam Karkhaneh

    2015-09-01

    Results:Treatment with 17β-estradiol had a biphasic effect on expression of CGRP. We found that 17β-estradiol treatment at pharmacological dose significantly increases mRNA expression of CGRP in both groups (P

  5. Serum estradiol should be monitored not only during the peri-menopausal period but also the post-menopausal period at the time of aromatase inhibitor administration

    Directory of Open Access Journals (Sweden)

    Zembutsu Hitoshi

    2009-11-01

    Full Text Available Abstract Background Aromatase inhibitor (AI therapy is being extensively used as postoperative adjuvant therapy in patients with hormone receptor-positive postmenopausal breast cancer. On the other hand, it has been reported that ovarian function was restored when AI was administered to patients who had undergone chemical menopause with chemotherapy or tamoxifen. However, there have been no reports of comprehensive monitoring of estradiol (E2 in breast cancer patients with ordinary menopause who were being administered AI. Patients and Methods Beginning in March 2008, regular monitoring of the serum levels of E2, luteinizing hormone (LH and follicle-stimulating hormone (FSH was performed for 66 postmenopausal breast cancer patients who had been started on AI therapy. For this study, we chose anastrozole as the AI. The assays of those hormones were outsourced to a commercial clinical laboratory. Results In 4 of the 66 patients the serum E2 level was decreased at 3 months but had then increased at 6 months, while in 2 other patients E2 was decreased at both 3 and 6 months but had increased at 9 months. Conclusion The results indicate that, in some breast cancer patients with ordinary menopause, E2 rebounds following AI therapy. In the future, E2 monitoring should be performed for a larger number of patients being administered AI therapy. Trial registration Our trial registration number is 19-11-1211.

  6. Baicalein suppresses 17-β-estradiol-induced migration, adhesion and invasion of breast cancer cells via the G protein-coupled receptor 30 signaling pathway.

    Science.gov (United States)

    Shang, Dandan; Li, Zheng; Zhu, Zhuxia; Chen, Huamei; Zhao, Lujun; Wang, Xudong; Chen, Yan

    2015-04-01

    Flavonoids are structurally similar to steroid hormones, particularly estrogens, and therefore have been studied for their potential effects on hormone-dependent cancers. Baicalein is the primary flavonoid derived from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the effects of baicalein on 17β-estradiol