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Estradiol
Kinds of Estradiol Terms modified by Estradiol Selected AbstractsGlutamate AMPA/kainate receptors, not GABAA receptors, mediate estradiol-induced sex differences in the hypothalamusDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Brigitte J. Todd Abstract Sex differences in brain morphology underlie physiological and behavioral differences between males and females. During the critical perinatal period for sexual differentiation in the rat, gonadal steroids act in a regionally specific manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just dorsal and just lateral to the VMN that there was a sex difference in total dendritic spine number (males greater) that was abolished by treating female neonates with exogenous testosterone. Dendritic branching was similarly sexually differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then used spinophilin, a protein that positively correlates with the amount of dendritic spines, to investigate the mechanisms underlying these sex differences. Estradiol, which mediates most aspects of masculinization and is the aromatized product of testosterone, increased spinophilin levels in female PN2 rats to that of males. Muscimol, an agonist at GABAA receptors, did not affect spinophilin protein levels in either male or female neonates. Kainic acid, an agonist at glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol-induced increase in spinophilin in females but did not affect spinophilin level in males. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Aqueous exposure to 4-nonylphenol and 17,-estradiol increases stress sensitivity and disrupts ion regulatory ability of juvenile Atlantic salmonENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2007Darren T. Lerner Abstract Population declines of wild Atlantic salmon have been attributed to an array of anthropogenic disturbances, including dams, commercial and recreational fishing, habitat loss, and pollution. Environmental contaminants in particular, can act as environmental stressors on fish, typically causing disruption of ion homeostasis due to their close association with the aquatic environment. To examine the effects of the xenoestrogen 4-nonylphenol (NP) or 17,-estradiol (E2) on stress sensitivity and ion regulation, we exposed juvenile Atlantic salmon continuously for 21 d to either 10 or 100 ,g/L NP (NP-L or NP-H), 2 ,g/L E2 (positive control), or vehicle control during the parr-smolt transformation in April. After treatment, fish were sampled in freshwater (FW), transferred to 30, seawater (SW) for 24 h, or subjected to a handling stress. Estradiol and NP-H increased plasma vitellogenin in males and females, and E2 increased gonadosomatic index only in males. In FW, E2 reduced sodium potassium,activated adenosine triphosphatase activity as well as plasma levels of growth hormone, insulin-like growth factor I, and triiodothyronine. Both E2 and NP-H reduced plasma sodium in FW and increased plasma chloride in SW. Plasma Cortisol levels pre- and poststressor were significantly elevated by all treatments relative to controls, but only E2 increased plasma glucose before and after the stressor. These results indicate that exposure of anadromous salmonids to environmental estrogens heightens sensitivity to external stressors, impairs ion regulation in both FW and SW, and disrupts endocrine pathways critical for smolt development. [source] Plasma sex steroid concentrations and gonadal aromatase activities in African clawed frogs (Xenopus laevis) from South AfricaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2004Markus Hecker Abstract Adult African clawed frogs (Xenopus laevis) were collected from a corn-growing region (CGR) and a non-corn-growing region (NCGR) with different exposure profiles for atrazine and related triazines. Physical, chemical, and biological parameters from the catchment areas were also measured. Frogs were surveyed for possible effects of exposure to triazine herbicides on plasma testosterone (T) and estradiol (E2) titers, gonadal aromatase activity, and gonad growth (GSI). Concentrations of both T and E2 varied among locations and were correlated to some accessory factors, such as pH, several ions, and metals. Greatest median plasma T concentrations (males: 19 ng/ml; females: 16 ng/ml) occurred in frogs inhabiting NCGR as compared to those from the CGR (males: 4 ng/ml; females: 1 ng/ml). Median E2 concentrations were also greater in frogs collected from the NCGR (males: 3 ng/ml; females: 28 ng/ml) than those in frogs from the CGR (males: 2 ng/ml; females: 5 ng/ml). Because some exposure to agricultural chemicals at both regions occurred, as did simultaneous exposures to multiple chemicals, a regression analysis was employed. Negative correlations were observed between plasma T concentrations and concentrations of atrazine, deisopropylatrazine, deethylatrazine, and tertbuthylazine in females and between T and diaminochlorotriazine in males. Estradiol in females exhibited a significant negative correlation with atrazine and deethylatrazine. No correlations were observed between gonadal aromatase activity or GSI and any of the agricultural chemicals measured. Median aromatase activities in ovaries varied among sampling sites ranging from 7 to >3,000 times greater than those in males when measurable. Testicular aromatase activity was below the detection limit of the assay in male frogs at most of the sites. Although exposure to agricultural inputs did not affect aromatase activities, effects of atrazine or coapplied pesticides on sex steroid homeostasis cannot be excluded at this point. [source] Timing of exposure to a pulp and paper effluent influences the manifestation of reproductive effects in rainbow troutENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2002Michael R. Van den Heuvel Abstract Rainbow trout were exposed to a secondary treated, thermomechanical/bleached kraft pulp and paper effluent in 12,000-L, flow-through exposure tanks at an environmental research facility located at a pulp and paper mill in Kawerau, New Zealand. Trout (age, 2+ years) were obtained from a local hatchery and exposed either to upstream river water or a nominal concentration of 12% (v/v) effluent diluted in upstream river water. Three treatment groups were used: Effluent exposure that started approximately three months before gonadal growth (eight-month total exposure), effluent exposure that started approximately halfway through gonadal development (two-month total exposure), and trout exposed to reference water alone for the total duration of the experiment. Trout were sacrificed just before spawning; exposure, growth, and reproductive endpoints were assessed during and at the termination of the experiment. Reduction in growth was observed in both sexes in the eight-month treatment group relative to the river water reference treatment group. No differences were observed in condition factor or liver size in either treatment. Females in the eightmonth exposure group also had significantly lower ovary weight. The two-month exposure group showed no differences from the reference group in growth or somatic indices. Estradiol and testosterone were reduced in blood samples taken from the eight-month exposure group by four months into the experiment as compared to the reference treatment. Steroid and vitellogenin levels in individual female trout from this treatment were significantly correlated with gonadosomatic indices (GSI) measured at the termination of the experiment. The GSI was not correlated strongly or consistently with pregnenolone, nor were any treatment-related pregnenolone differences observed, indicating that the steroid hormone reductions likely were not related to cholesterol side-chain cleavage. Male trout showed significant induction of vitellogenin and lower 11-ketotestosterone during the experiment (only the eight-month group was examined), but this did not result in any significant differences in testes development. Thus, this study has shown an impact of pulp mill effluent exposure on the reproductive physiology of female trout that appeared to be hormonally mediated. Furthermore, the effect could only be manifest when the exposure was initiated before the start of gonad development. [source] Substances with estrogenic activity in effluents of sewage treatment plants in southwestern Germany.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2001Abstract The proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-Screen assay) was applied for quantitative determination of total estrogenic activity in 24-h composite effluent samples from 16 municipal and two industrial sewage treatment plants (STPs) in the state of Baden-Württemberg, southwestern Germany. The estrogenic efficacy relative to the positive control, 17,-estradiol, was between 26 and 74% (median, 48%) for the 16 municipal STPs. Estradiol equivalent concentrations (EEQs) were between 0.2 and 7.8 ng/L (median, 1.6 ng/L) and, thereby, were lower than those found in a pilot study, which revealed EEQs of greater than 10 ng/L in the effluents of two other STPs. The EEQs in 14 of the 16 effluent samples were very similar (0.9,3.3 ng/L), indicating a rather constant input of estrogenic substances via STPs into rivers. Additional activated charcoal filtration turned out to be very efficient in further eliminating estrogenic activity from effluents. The EEQs of the E-Screen assay and those calculated from the results of extensive chemical analysis using the estradiol equivalency factors determined for 13 natural and synthetic estrogenic substances were comparable for most of the effluent samples. 17,-Estradiol, 17,-ethinylestradiol, and, to a lesser extent, estrone contributed to 90% or more of the EEQ value. [source] Ethinyl Estradiol, Not Progestogens, Reduces Lamotrigine Serum ConcentrationsEPILEPSIA, Issue 9 2005Arne Reimers Summary:,Purpose: To study the interaction between lamotrigine (LTG) and hormonal contraception. Methods: LTG serum concentrations of female patients using either no hormonal contraception (n = 18), an ethinyl estradiol (EE)-containing (n = 11), or a progestogen (PG)-only,containing compound (n = 16) were analyzed. Patients were recruited prospectively, and blood samples were drawn during drug fasting and at steady-state conditions. Comedication with enzyme inducers, valproate, topiramate, or sertraline was not allowed. Some patients changed groups and thus served as their own controls. Samples were analyzed by a gas chromatography/ mass spectroscopy method. The Mann,Whitney U test was used for statistical comparison of the groups. Results: The LTG serum concentration-to-dose ratio (CDR), expressed as (mg/L)/(mg/d) was significantly lower in women using EE than in the control group (mean ± SD, 0.010 ± 0.004 vs. 0.017 ± 0.006; p = 0.003). The CDR in women using PG was 0.02 ± 0.007, which was not statistically different from controls. No difference was found in CDR between women using either oral, topical, or parenteral PG. Five women switched from the control to the EE group and experienced a considerable reduction in CDR. An increase of the CDR toward control level was seen in the two women who changed from EE to PG. Conclusions: It is the EE component of oral contraceptives that interacts with LTG. The PG-only compounds did not alter LTG serum concentrations in this study. These findings should be considered when counselling women with epilepsy in the childbearing ages. [source] Protection of estrogens against the progression of chronic liver diseaseHEPATOLOGY RESEARCH, Issue 4 2007Ichiro Shimizu Hepatitis C virus infections are recognized as a major causative factor of chronic liver disease. A characteristic feature of chronic hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory and oxidative stimuli, and to produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. Estradiol is a potent endogenous antioxidant. Hepatic steatosis was reported to become evident in an aromatase-deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures. Variant estrogen receptors were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. A better understanding of the basic mechanisms underlying the gender-associated differences observed in the progression of chronic liver disease would provide valuable information relative to the search for effective antifibrogenic therapies. [source] Estradiol enhances long term potentiation in hippocampal slices from aged apoE4-TR miceHIPPOCAMPUS, Issue 12 2007Sung Hwan Yun Abstract Hormone replacement therapy to treat or prevent Alzheimer Disease (AD) in postmenopausal women is controversial because it may pose other health risks such as cancer and thromboembolism. ApoE status is thought to influence the nootropic efficacy of hormone therapy, but findings are neither consistent nor well understood. We used a known in vitro memory model (long-term potentiation, LTP) in aged (24,27 month) female targeted replacement mice expressing human apoE3 or E4 to compare the effects of exogenous estradiol. Recording medial perforant path evoked field potentials in dentate gyrus of hippocampal slices, we found that both strains exhibited comparable basal synaptic transmission as assessed by input/output functions and paired pulse depression, and that these measures were not affected by estradiol. Vehicle-treated groups from both strains showed comparable LTP. Estradiol had no effect on LTP in apoE3-TR, but selectively increased LTP magnitude in apoE4-TR. The estradiol induced enhancement of LTP in aged female apoE4-TR is consistent with recent clinical observations that estrogen replacement decreases AD risk in some women with apoE4. Elucidating the mechanism of this selective enhancement may lead to more informed treatment decisions as well as to the development of safer alternatives to hormone therapy. © 2007 Wiley-Liss, Inc. [source] Gonadal hormone modulation of hippocampal neurogenesis in the adultHIPPOCAMPUS, Issue 3 2006Liisa A.M. Galea Abstract Gonadal hormones modulate neurogenesis in the dentate gyrus (DG) of adult rodents in complex ways. Estradiol, the most potent estrogen, initially enhances and subsequently suppresses cell proliferation in the dentate gryus of adult female rodents. Much less is known about how estradiol modulates neurogenesis in the adult male rodent; however, recent evidence suggests that estradiol may have a moderate effect on cell proliferation but enhances cell survival in the DG of newly synthesized cells but only when estradiol is administered during a specific stage in the cell maturation cycle in the adult male rodent. Testosterone likely plays a role in adult neurogenesis, although there have been no direct studies to address this. However, pilot studies from our laboratory suggest that testosterone up-regulates cell survival but not cell proliferation in the DG of adult male rats. Progesterone appears to attenuate the estradiol-induced enhancement of cell proliferation. Neurosteroids such as allopregnalone decrease neurogenesis in adult rodents, while pregnancy and motherhood differentially regulate adult neurogenesis in the adult female rodent. Very few studies have investigated the effects of gonadal hormones on male rodents; however, studies have indicated that there is a gender difference in the response to hormone-regulated hippocampal neurogenesis in the adult. Clearly, more work needs to be done to elucidate the effects of gonadal hormones on neurogenesis in the DG of both male and female rodents. © 2006 Wiley-Liss Inc. [source] Low-risk factor profile, estrogen levels, and breast cancer risk among postmenopausal womenINTERNATIONAL JOURNAL OF CANCER, Issue 8 2009Naja Hulvej Rod Abstract Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI , 30 kg/m2, alcohol <1 drink/week, physically active and no current hormone use) and to evaluate their associations with estrogen. The 5,054 postmenopausal women in the Copenhagen City Heart Study were asked about risk factors at baseline in 1981,3 and were followed until 2002 in the Danish Cancer Registry, with <0.1% loss to follow-up. Estradiol was measured in a subset of 1,042 women. During follow-up, 263 women developed breast cancer. Twenty-six percent of the women had a favourable risk factor profile, and their breast cancer rates were markedly lower (154 per 100,000 years) than women with 3+ risk factors (460 per 100,000 years). One, two and three risk factors were associated with hazard ratios of 1.38 (95% CI: 0.99; 1.92), 1.84 (1.26; 2.67) and 2.79 (1.59; 4.88) compared to women with a favourable profile. Each of the risk factors was associated with estrogen. In conclusion, the risk of breast cancer was markedly lower for women with a favourable risk profile than for other women and lower estrogen levels is a possible explanation. © 2008 Wiley-Liss, Inc. [source] Association Between Testosterone and Estradiol and Age-Related Decline in Physical Function in a Diverse Sample of MenJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2008Andre B. Araujo PhD OBJECTIVES: To examine the association between aging and physical function in men by testing a theoretically based model of aging, hormones, body composition, strength, and physical function with data obtained from men enrolled in the Boston Area Community Health/Bone (BACH/Bone) Survey. DESIGN: Cross-sectional, observational survey. SETTING: Population-based. PARTICIPANTS: Eight hundred ten black, Hispanic, and white randomly selected men from the Boston area aged 30 to 79. MEASUREMENTS: Testosterone, estradiol, sex hormone,binding globulin, lean and fat mass, grip strength, and summated index of physical function (derived from walk and chair stand tests). RESULTS: Measures of grip strength and physical function declined strongly with age. For instance, 10 years of aging was associated with a 0.49-point difference (scale 0,7) in physical function. Age differences in total testosterone and estradiol concentrations were smaller than age differences in their free fractions. Weak or nonsignificant age-adjusted correlations were observed between hormones and measures of physical function, although path analysis revealed a positive association between testosterone and appendicular lean mass and a strong negative association between testosterone and total fat mass. Lean and fat mass, in turn, were strongly associated with grip strength and physical function, indicating the possibility that testosterone influences physical function via indirect associations with body composition. CONCLUSION: The age-related decline in serum testosterone concentration in men has a weak association with physical strength and functional outcomes through its associations with lean and fat mass. [source] Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: Relationship to Morris water maze performanceJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2004Nahid K. El-Bakri Abstract Estrogen modulates NMDA receptors function in the brain. It increases both dendritic spine density and synapse number in the hippocampus, an effect that can be blocked by NMDA antagonist. In this study, we investigated the effect of 17,-estradiol and progesterone treatment on NMDA receptors in ovariectomized rats. Two different doses were used for 10 weeks. Receptor autoradiography was done on brain sections using [3H] MK-801 as a ligand. Our results showed a significant increase in [3H] MK-801 binding in the dentate gyrus, CA3 and CA4 areas of the hippocampus of ovariectomized compared to sham operated rats. In addition, we observed similar changes in CA1. 17,-estradiol treatment in both doses reduced the binding back to the normal level while progesterone treatment did not show any effect. Spatial reference memory was tested on Morris water maze task. Ovariectomy severely impaired spatial reference memory. Estradiol but not progesterone treatment significantly improved the memory performance of the ovariectomized rats. Low dose treatment showed better learning than high dose estrogen treatment. The decrease in the antagonist sites by estradiol treatment could result in an increase in the sensitivity of the hippocampus to the excitatory stimulation by glutamate system and hence the effect of estradiol on learning and memory. The changes of NMDA receptors in the hippocampus support the concept that estrogen-enhancing effect on spatial reference memory could be through the enhancing of NMDA function. [source] 2-methoxyestradiol-induced cell death in osteosarcoma cells is preceded by cell cycle arrestJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Avudaiappan Maran Abstract 2-Methoxyestradiol (2-ME), a naturally occurring mammalian metabolite of 17,-Estradiol (E2), induces cell death in osteosarcoma cells. To further understand the molecular mechanisms of action, we have investigated cell cycle progression in 2-ME-treated human osteosarcoma (MG63, SaOS-2 and LM8) cells. At 5 µM, 2-ME induced growth arrest by inducing a block in cell cycle; 2-ME-treatment resulted in 2-fold increases in G1 phase cells and a decrease in S phase cells in MG63 and SaOS-2 osteosarcoma cell lines, compared to the appropriate vehicle controls. 2-ME-treatment induced a threefold increase in the G2 phase in LM8 osteosarcoma cells. The results demonstrated steroid specificity, as the tumorigenic metabolite, 16,-hydroxyestradiol (16-OHE), did not have any effect on cell cycle progression in osteosarcoma cells. The cell cycle arrest coincided with an increase in expression of the cell cycle markers p21, p27 and p53 proteins in 2-ME-treated osteosarcoma cells. Also, MG63 cells, transiently transfected with cDNA for a ,loss of function mutant' RNA-dependent protein kinase (PKR) protein, were resistant to 2-ME-induced cell cycle arrest. These results suggest that 2-ME works in concert with factors regulating cell cycle progression, and cell cycle arrest precedes cell death in 2-ME-treated osteosarcoma cells. J. Cell. Biochem. 104: 1937,1945, 2008. © 2008 Wiley-Liss, Inc. [source] 17,-estradiol prevents cytotoxicity from hydrophobic bile acids in HepG2 and WRL-68 cell culturesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2006Matteo Ricchi Abstract Background:, Epidemiological and clinical studies suggest the possibility that estrogens might have a cytoprotective effect on the liver. The aim of the present study was to test the hypothesis that 17,-estradiol (E2) prevents hepatocellular damage induced by deoxycholic acid (DCA), a hydrophobic bile acid. Methods:, HepG2 cells were exposed for 24 h to DCA (350 µmol/L). Cell viability, aspartate aminotransferase and lactate dehydrogenase activity and apoptosis were measured as indices of cell toxicity. The effect of DCA was compared to that observed using either a hydrophilic bile acid, ursodeoxycholic acid (UDCA; 100 µmol/L), or E2 at different concentrations (1 nmol/L, 10 nmol/L, 50 nmol/L and 50 µmol/L) or mixtures of E2/DCA or UDCA/DCA. The same experiments were performed using WRL-68 cells that, at variance with HepG2, express a higher level of nuclear estrogen receptor. Results:, High concentrations of E2 and UDCA prevented DCA-induced decrease in cell viability, increase in enzyme activity and apoptosis evaluated both by 4,,6-diamidino-2-phenylindole dihydrochloride (DAPI) and TdT-mediated dUTP nick-end labeling (TUNEL) assays. In addition, DCA-related apoptosis, assessed by caspase activity, was also prevented by E2 (P < 0.01) in physiological (1,10 nmol/L) doses. The cytoprotective effects of E2 and UDCA was also observed in the WRL-68 cell line. Conclusions:, 17,-Estradiol prevents DCA-induced cell damage in HepG2 and WRL-68 cell lines to an extent comparable to UDCA. The hypothesis that the protective effect of E2 may be mediated by a mechanism that is nuclear estrogen receptor independent, deserves further verification. [source] Estrogens inhibit l -glutamate uptake activity of astrocytes via membrane estrogen receptor ,JOURNAL OF NEUROCHEMISTRY, Issue 6 2003Kaoru Sato Abstract We investigated the effects of estrogen-related compounds including xenoestrogens [17,-estradiol (E2), 17,-ethynylestradiol (EE), diethylstilbestrol (DES), p-nonylphenol (PNP), bisphenol A (BPA) and 17,-estradiol (17,)] on l -glu uptake by cultured astrocytes via glutamate-aspartate transporter (GLAST). After 24 h treatment, E2 inhibited the l -glu uptake at 1 µm and higher concentrations. EE and DES also inhibited the l -glu uptake at 1 nm and higher concentrations. The other four compounds had no effect. The effects of E2, EE and DES were completely blocked by 10 nm of ICI182 780 (ICI). ,-Estradiol 17-hemisuccinate : bovine serum albumin (E2-BSA), a membrane-impermeable conjugate of E2, also elicited the inhibition of l -glu uptake at 1 nm and higher concentrations, and the effect was blocked by ICI. 16,-Iodo-17,-estradiol (16,IE2), an estrogen receptor , (ER,) selective ligand, revealed an inhibitory effect at 10 nm, while genistein, an ER, selective ligand, failed to reveal such an effect at this concentration. Western blot analysis showed that the predominant ER of cultured astrocytes was ER,. The colocalization of ER, with GLAST on plasma membranes was immunohistochemically detected in these cells. From these results, we concluded that estrogens down-regulate l -glu uptake activity of astrocytes via membrane ER,. [source] Effects of caudal hindbrain lactate infusion on insulin-induced hypoglycemia and neuronal substrate transporter glucokinase and sulfonylurea receptor-1 gene expression in the ovariectomized female rat dorsal vagal complex: Impact of estradiolJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2008Kamlesh V. Vavaiya Abstract The monocarboxylate, lactate, is produced by astrocytic glycolysis and is trafficked to neurons as a substrate fuel for aerobic respiration. This molecule is a critical monitored metabolic variable in hindbrain detection of cellular energy imbalance, because diminished uptake and/or oxidative catabolism of lactate in this part of the brain activates neural mechanisms that increase systemic glucose availability. Lactate-sensitive chemosensory neurons occur in the hindbrain dorsal vagal complex (DVC). Estradiol (E) enhances expression of the neuronal monocarboxylate transporter MCT2 in the DVC during insulin-induced hypoglycemia (IIH), evidence that this hormone may promote local lactate utilization during systemic glucose shortages. We investigated the hypothesis that E regulates basal and IIH-associated patterns of DVC MCT2 and neuronal glucose transporter gene expression and that caudal fourth ventricular (CV4) lactate infusion exerts divergent effects on blood glucose levels and DVC energy transducer gene profiles in hypoglycemic E- vs. oil (O)-implanted ovariectomized (OVX) rats. Insulin-induced decrements in circulating glucose were significantly augmented by lactate, albeit to a greater extent in the presence of E. DVC MCT2, GLUT3, GLUT4, glucokinase (GCK), and sulfonylurea receptor-1 (SUR1) mRNA levels did not differ between saline-injected OVX + E and OVX + O rats. IIH elevated MCT2 and GLUT3 gene profiles in both E- and O-implanted groups, but up-regulation of MCT2 transcripts was reversed by CV4 lactate infusion during hypoglycemia in E- but not O-implanted animals. DVC GLUT4 and GK mRNA were decreased by insulin alone in OVX + O but not OVX + E, but were suppressed by lactate plus insulin treatment in the latter group. Expression of the SUR1 subunit of the energy-dependent potassium channel KATP was significantly decreased by IIH in both E- and O-treated rats and further suppressed in response to lactate delivery during hypoglycemia in OVX + E. These data reveal that E does not control baseline DVC substrate fuel transporter or energy transducer gene profiles or local MCT2, GLUT3, or SUR1 transcriptional responses to IIH but prevents IIH-associated decreases in GLUT4 and GCK mRNA in this brain site. The results also show that, in the presence of E, intensifying effects of CV4 lactate infusion on hypoglycemia are correlated with reversal of IIH enhancement of DVC MCT2 gene expression, augmented IIH inhibition of SUR1 transcripts, and reductions in GLUT4 and GCK mRNA levels relative to baseline. This work implies that IIH may enhance specific neuronal lactate and glucose transport mechanisms in the female rat DVC and that, in the presence of E, caudal hindbrain lactate repletion may normalize neuronal lactate but not glucose internalization by local neurons. The results also suggest that putative IIH-associated reductions in KATP -mediated regulation of membrane voltage in this brain site may be causally related to diminished glucose availability. © 2007 Wiley-Liss, Inc. [source] Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2005Yo Kishi Abstract To investigate the effect of estrogen on neuronal differentiation, especially on dopaminergic (DA) neurons, human neural stem cells (NSCs) were differentiated in the presence of 17,-estradiol. NSCs gave rise to tyrosine hydroxylase (TH)-positive neurons in vitro, the proportion of which was increased by 17,-estradiol. Increase in TH-positive neurons was abrogated by an estrogen receptor (ER) antagonist, ICI182780, suggesting ERs play a role in differentiation of DA neurons. The observation that ERs were expressed in both proliferating NSCs and postmitotic DA neurons suggested that increase in TH-positive neurons was due to induction and support of DA neurons. 17,-Estradiol also increased the number of DA neurons derived from human NSCs in vivo when the cells were grafted into mouse brains. These results support a possible role for estrogen in the transplantation of NSCs for Parkinson's disease. © 2004 Wiley-Liss, Inc. [source] Alcohol-Induced Disruption of Endocrine SignalingALCOHOLISM, Issue 8 2007Martin J. J. Ronis This article contains the proceedings of a symposium at the 2006 ISBRA Meeting in Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M. Badger. The presentations were (1) Effect of Long-Term Ethanol Consumption on Liver Injury and Repair, by Jack R. Wands; (2) Alcohol-Induced Insulin Resistance in Liver: Potential Roles in Regulation of ADH Expression, Ethanol Clearance, and Alcoholic Liver Disease, by Thomas M. Badger; (3) Chronic Gestational Exposure to Ethanol Causes Brain Insulin and Insulin-Like Growth Factor Resistance, by Suzanne M de la Monte; (4) Disruption of IGF-1 Signaling in Muscle: A Mechanism Underlying Alcoholic Myopathy, by Charles H. Lang; (5) The Role of Reduced Plasma Estradiol and Impaired Estrogen Signaling in Alcohol-Induced Bone Loss, by Martin J. Ronis; and (6) Short-Term Influence of Alcohol on Appetite-Regulating Hormones in Man, by Jan Calissendorff. [source] c - fos and estrogen receptor gene expression pattern in the rat uterine epithelium during the estrous cycleMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2003C. Adriana Mendoza-Rodríguez Abstract Different studies in ovariectomized estrogen treated animals support the idea that c - fos plays a role in the proliferation of uterine epithelial cells. However, these studies invite us to reassess the role played by c - fos in epithelial cell types of the endometrium during the estrous cycle. The present study was undertaken to determine the c - fos and estrogen receptor (ER) gene expression pattern in the rat uterine epithelium during the estrous cycle in which natural and cyclic changes of steroid hormones occur, and correlate these changes with the proliferation status of this cellular types. Proliferation was assessed during the estrous cycle using bromodeoxyuridine incorporation to DNA. ER, and , proteins were assessed by immunohistochemistry. The regulation of c - fos gene expression in the uterus of intact animals during the estrous cycle was evaluated using both in situ hybridization and immunohistochemistry. Estradiol (E2) and progesterone (P4) plasma levels were assessed by radioimmunoassay. The results indicated that luminal (LE) and glandular epithelia (GE) presented maximal proliferation during the metestrus (M) and the diestrus (D) days. However, during the proestrus (P) day only LE presented proliferation, and during the estrus (E) day only the stromal cells proliferated. A marked immunostaining for ER, was detected in both LE and GE cells during the early phases of the cycle but diminished on the P and the E day. In contrast, ER, was undetectable in both epithelia during all stages of the cycle. The highest c - fos mRNA level was detected in both epithelia on the M day, followed by a significant reduction during the other days of the cycle. The highest protein content was observed on the M and D days, and the minimal value was detected on the E day. The c-Fos protein level in LE was increased during M and D days, presenting a high correlation with the cellular proliferation pattern of this cell type. In conclusion, the overall results indicate that c-Fos protein presented a good correlation with uterine epithelial cell proliferation of LE. In the case of GE, the same tendency was observed, although no significant correlation was found. Both in LE and GE, c - fos mRNA did not strictly correlate with its protein levels. c - fos seems to have a postranscriptional regulation in uterine epithelial cells during the rat's estrous cycle. Mol. Reprod. Dev. 64: 379,388, 2003. © 2003 Wiley-Liss, Inc. [source] Relationship between urinary profile of the endogenous steroids and postmenopausal women with stress urinary incontinenceNEUROUROLOGY AND URODYNAMICS, Issue 3 2003S.W. Bai Abstract Aims The aims of this study were to investigate whether endogenous steroid hormones are (1) related to pathogenesis of stress urinary incontinence after menopause, (2) are related to severity of stress urinary incontinence, and (3) are related to prognostic parameters of stress urinary incontinence. Methods Twenty post-partum women with clinically diagnosed stress urinary incontinence and 20 age-matched postmenopausal women without stress urinary incontinence (control group) were evaluated. We compared urinary profile of the endogenous steroid hormones patients with stress urinary incontinence and controls, and between grade I and grade II of stress urinary incontinence. We also in vestigated the relationship between urinary profile of the endogenous steroid hormones and prognostic parameters of stress urinary incontinence (maximal urethral closure pressure, functional urethral length, Valsalva leak point pressure, cough leak point pressure, posterior urethrovesical angle, bladder neck descent, and stress urethral axis). The ages of the patients and those in the control group were 64.3,±,5.6 and 57.5,±,3.8 years old and the body mass indexes were 24.96,±,3.14 and 22.11,±, 2.73 kg/m2 in patients and in normal subjects, respectively. Nine patients were grade I and 11 were grade II. Estrone and 17,-estradiol only were detected in all subjects, regardless of control or patient group. It is noteworthy that there were no significant differ ences (P,>,0.05) in the levels of estrone and 17,-estradiol in the urine of postmenopausal normal subjects compared with in the urine of postmenopausal patients with urinary incontinence. E2/E1 ratio was not different between the two groups (P,>,0.05). Among the objective steroids, DHEA, ,4 -dione, ,5 -diol, Te, DHT, 16,-DHT, 11-keto An, THDOC, and THB were not detected either in the urine of normal subjects and nor in the urine of the patients. After comparing androgen levels between normal subjects and patients, no significant differences (P>0.05) were detected, except for 5,-THB and 5,-THF. Neither 5,-THB or 5,-THF were detected in the patients' urine. Et/An (11,-OH Et/11,-OH An) concentration ratios were not significantly different between the two groups, either (P,>,0.05). There were not significant differences of concentrations (,mol/g creatinine) of urinary steroids between grade I and grade II of stress urinary incontinence. Pregnanediol was significantly related to bladder neck descent in supine and sitting positions (R,=,0.79, P,=,0.01, and R,=,0.73, P,=,0.03, respectively), and pregnanetriol was significantly related to maximal urethral closure pressure and functional urethral length (R,=,0.68, P,=,0.04, and R,=,,0.79, P,=,0.01, respectively). Androsterone was significantly related to bladder neck descent in supine and sitting positions (R,=,0.68, P,=,0.04, and R,=,0.78, P,=,0.01, respectively). 5-AT was significantly related to bladder neck descent in sitting position and stress urethral axis (R,=,0.72, P,=,0.03, and R,=,,0.71, P,=,0.03). 11-Keto Et was significantly related to bladder neck descent in supine and sitting positions and related to stress ure thral axis (R,=,0.82, P,=,0.01, and R,=,0.81, P,=,0.01, R,=,,0.67, P,=,0.04, respectively). THS was signi ficantly related to bladder neck descent in supine and sitting positions and related to stress urethral axis (R,=,0.76, P,=,0.02, and R,=,0.74, P,=,0.02, R,=,,0.68, P,=,0.04, respectively). THE was significantly related to bladder neck descent in sitting position (R,=,0.67, P,=,0.04).,-Tetrahydrocortisol/,-tetrahydrocortisol (,-THF/,-THF) and ,-cortol were significantly related to maximal urethral closure pressure and functional urethral length (R,=,0.74, P,=,0.02, and R,=,,0.92, P,=,0.01; R,=,0.71, P,=,0.36, and R,=,,0.87, P,=,0.000, respectively). 17,-Estradiol (E2) was significantly related to bladder neck descent in supine position (R,=,,0.62, P,=,0.04) and 17,-estradiol/estrone (E2/E1) was significantly related to cough leak point pressure (R,=,0.79, P,=,0.01). In conclusion, the urinary concentrations of endogenous steroid metabolites in postmenopausal patients with stress urinary incontinence were not significantly different from normal patients and were not significantly different between grade I and grade II patients with stress urinary incontinence. Some endogenous steroid metabolites were positively or negatively significantly related to prognostic parameters of stress urinary incontinence. Neurourol. Urodynam. 22:198,205, 2003. © 2003 Wiley-Liss, Inc. [source] Follicle Dynamics and its Relation with Plasma Concentrations of Progesterone, Luteinizing Hormone and Estradiol during the Egg-Laying Cycle in OstrichesREPRODUCTION IN DOMESTIC ANIMALS, Issue 4 2009RGG Bronneberg Contents The aims of this study were (i) to describe the changes in the volume of large ovarian follicles (diameter >3 cm) during the 48 h egg laying cycle in farmed ostriches, and (ii) to quantify factors affecting the volume of the largest measured follicle and the plasma concentrations of progesterone (P4) and estradiol-17, (E2,). In eight egg-producing birds, which all ovulated during the study period, transcutaneous ultrasound scanning and blood sampling was performed at 3 h intervals. The average volume of the total number of visualized large follicles (Vtotal), the largest measured follicle (VF1), the second largest follicle (VF2) and of all follicles smaller than F2 (VF3,Fn) were each higher before than after oviposition. Vtotal, VF2 and VF3,Fn nearly doubled in the 24-h period before oviposition, while VF1 remained at an equal, rather high level until oviposition. Immediately after oviposition Vtotal, as well as the volume of the other follicle categories, decreased within 6 h, i.e. around the moment of ovulation. By performing statistical analysis on the basis of linear mixed-effects modelling, we quantified that: (i) VF1 was 13.2% higher before than after oviposition and increased with 6.5% when LH increased with 1 ng/ml; (ii) P4 levels were 93.2% higher before than after oviposition and increased with 43.1% for every 3 h closer to oviposition; when LH and E2, levels and VF1 increased with 1 ng/ml, 10 pg/ml and 10 ml, respectively, P4 increased with 116.6%, 50% and 6.1%; and (iii) E2, levels were 35.6% higher before than after oviposition, increased with 2.7% for every 3 h closer to oviposition and increased with 14.6% when LH increased with 1 ng/ml. It is concluded that during the egg-laying cycle in ostriches: (i) follicular mass, as estimated by the volume of visualized follicles larger than 3 cm, increases before and decreases after ovulation, and (ii) follicular dynamics and its accompanying endocrine plasma hormone profiles during the egg-laying cycle in ostriches follow a pattern similar to that in chickens. [source] Relationship Among Follicular Growth, Oestrus, Time of Ovulation, Endogenous Estradiol 17, and Luteinizing Hormone in Bos Indicus Cows After a Synchronization ProgramREPRODUCTION IN DOMESTIC ANIMALS, Issue 6 2007M Maquivar Contents To determine the pattern of follicular growth during oestrus and the relationship with estradiol and luteinizing hormone in ovulating and non-ovulating cows, three groups of (n = 10), thirty cyclic, Bos indicus cows were synchronized with CIDR, consecutively at 9-day intervals. Twenty-four hours after implant withdrawal, all cows synchronized in the same group with other cows displaying estrous behaviour after implant withdrawal were subjected to an intensive period of ultrasonographic observations (every 6 h for 120 h). Blood samples were taken to evaluate LH surge and 17- , estradiol. No differences were observed in follicular growth, ovulatory diameter and growth average in the three groups of synchronized cows. Cows ovulating (CO) had a better growth average in comparison with the group of cows not ovulating (CNO) (1.4 ± 0.7 mm vs 0.7 ± 0.5 mm, p < 0.06). The average time from estradiol release to LH surge was 39.3 ± 24.6 h. Differences were also observed between CO and CNO with respect to both the first concentration (27.7 ± 5.2 vs 58.6 ± 31.9, p < 0.004) and last concentration (79.3 ± 23.3 vs 99.2 ± 27.3, p < 0.05) of estradiol above 5 pg/ml. The average time from overt signs of oestrus to LH release was 8.4 ± 7.7 h. In the CNO, the increase in LH concentration was never above two SD from the basal average. In conclusion, there is a wide variability in follicular growth and ovulatory diameter between CO and CNO, which can affect the intervals of LH release, estradiol peak and ovulation. Yet, LH surge might be a good marker for timing ovulation in Zebu cows. [source] Changes in Plasma Concentrations of LH, FSH, Estradiol 17- , and Progesterone During Oestrus in Mithun (Bos frontalis)REPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2006A Dhali Contents The objective of the present study was to establish the changes in plasma concentrations of LH, FSH, estradiol 17- , (E2) and progesterone (P4), as well as to understand their temporal relationships during oestrus in mithun (Bos frontalis). The experiment was conducted on 11 mithuns during third or fourth postpartum oestrous cycle. Since oestrus onset the jugular vein blood samples were collected every 2 h for 72 and 96 h, respectively from the animals without and with standing heat. The LH, FSH, E2 and P4 concentrations were estimated in plasma. The P4 concentration was fluctuated throughout the oestrus period and the average P4 concentration was found significantly (p < 0.05) lower on the day of oestrus onset. The multiple rises in LH and FSH concentrations above the basal level in spike like fashion were observed throughout the oestrus period irrespective of the occurrence of standing heat. A significant (p < 0.01) gradual increase in the average daily E2 concentration was observed till day 2 following oestrus onset irrespective of the occurrence of standing heat. A significant (p < 0.05) simultaneous increase in LH, FSH and E2 concentrations and a transient increase in P4 concentration at approximately the time of standing heat onset were observed. During investigation a definite temporal coupling between LH and FSH rises was absent throughout the oestrus period. The results suggest that (1) the multiple short-duration low-amplitude LH and FSH surges during oestrus may be crucial for the final maturation of ovulatory follicle and subsequent ovulation in mithun; (2) a differential mechanism for controlling LH and FSH secretions probably exists in mithun. [source] ORIGINAL ARTICLE: Estradiol Limits Viral Replication Following Intravaginal Immunization Leading to Diminished Mucosal IgG Response and Non-sterile Protection Against Genital Herpes ChallengeAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2010Amy Gillgrass Citation Gillgrass A, Chege D, Bhavanam S, Kaushic C. Estradiol limits viral replication following intravaginal immunization leading to diminished mucosal IgG response and non-sterile protection against genital herpes challenge. Am J Reprod Immunol 2010; 63: 299,309 Problem, Previously we reported that ovariectomized (OVX) mice receiving estradiol (E) prior to immunization with an attenuated strain of HSV-2 (TK-HSV-2) were not protected. Lack of protection in the E group was because of the inability of TK-HSV-2 to penetrate the thick keratinized epithelium. In this study, we determined the outcome of immunization after the thickening of vaginal epithelium following E-treatment waned. OVX, C57BL/6 mice were given Progesterone (P), E or saline (S) for 3 days and immunized with IVAG TK-HSV-2. Method of study, To determine the time point at which E-treated mice could be successfully immunized, the mice were inoculated with TK-HSV-2 between days 1 and 7 (ED1,ED7) post-E-treatment and challenged with IVAG HSV-2 three weeks later. Results, The level of infection post-immunization correlated with HSV-2-specific IgG antibody level, which correlated with sterile protection. No viral infection was observed in ED1,ED3 groups and no specific antibodies were detected, resulting in no protection. Moderate infection was seen in ED5 group, resulting in low antibody production and non-sterile protection in 87.5% of mice. High antibody titers and sterile protection were observed in all groups that experienced robust infection post-immunization. Conclusion, The results show that estradiol leads to limited viral replication and diminished mucosal IgG response, resulting in non-sterile immune protection against genital herpes infection. [source] SHORT COMMUNICATION: Increased Expression of Glutathione by Estradiol, Tumor Necrosis Factor-Alpha, and Interleukin 1-Beta in Endometrial Stromal CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Sa Ra Lee Problem, The intracellular antioxidant system, based on glutathione (GSH), plays a key role in endometrial detoxification reactions and has been proposed to be involved in the pathogenesis endometriosis. This study was designed to evaluate whether estradiol (E2) and proinflammatory cytokines have any effects on expression of glutathione in endometrial stromal cells (ESCs). Method of study, Glutathione levels were measured utilizing high-performance liquid chromatography following in vitro culture and treatment of ESCs with estradiol, tumor necrosis factor-alpha (TNF-,) and interleukin 1-beta (IL-1,). Results, The GSH level in E2 (10,8 m) treatment group was significantly higher than in the control group at 48 h (P < 0.05). In vitro treatment of ESCs with TNF-, 10 ng/mL as well as E2 (10,8 m) plus TNF-, 10 ng/mL for 48 hr also led to a significant increase in GSH level (P < 0.05; P < 0.05, respectively). Both IL-1, 10 ng/mL and E2 (10,8 m) plus IL-1, 10 ng/mL for 48 hr increased GSH level significantly (P < 0.05; P < 0.05, respectively) as well. Conclusions, These findings might suggest that increased production of estradiol and proinflammatory cytokines in the peritoneal cavity possibly leads to the establishment of endometriosis through increased level of GSH. [source] ORIGINAL RESEARCH,WOMEN'S SEXUAL HEALTH: Comparison of the Effects of Hormone Therapy Regimens, Oral and Vaginal Estradiol, Estradiol + Drospirenone and Tibolone, on Sexual Function in Healthy Postmenopausal WomenTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2008Filiz Çayan MD ABSTRACT Introduction., Sexual dysfunction is more prevalent in postmenopausal women. Aims., To prospectively evaluate and compare the effects of hormone therapy (HT) regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. Methods., The study included 169 consecutive healthy postmenopausal women, and the women were divided into two groups: 111 women received HT, and 58 women received no treatment and served as a control group. As an HT, 23 women with surgically induced menopause received oral 17-, estradiol. The rest of the women with natural menopause were prospectively randomized: 22 received oral 17-, estradiol + drospirenone daily, 42 received oral tibolone, and 24 received vaginal 17-, estradiol. Sexual function was evaluated with a detailed 19-item questionnaire, the female sexual function index, including sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. Main Outcome Measures., The differences in sexual function were compared before and 6 months after the treatment in all women. Results., Total sexual function score increased from 19.81 ± 7.15 to 22.9 ± 6.44 in the HT group and decreased from 21.6 ± 8.69 to 17.6 ± 5.7 in the control group, revealing a significant difference from baseline to post-treatment between the two groups (P = 0.000). The highest improvement in total score and arousal was achieved with the oral 17-, estradiol (P = 0.000 and P = 0.000, respectively). The highest improvement in lubrication was achieved with the oral and vaginal 17-, estradiol groups (P = 0.000). The highest improvement in orgasm was achieved with the tibolone group (P = 0.000). The highest improvement in pain was achieved with the oral and vaginal 17-, estradiol groups (P = 0.000). Conclusions., HT provided significant improvement in sexual function compared to women receiving no treatment, and therefore, HT regimens should be suggested for improvement in sexual functioning of postmenopausal women. Çayan F, Dilek U, Pata Ö, and Dilek S. Comparison of the effects of hormone therapy regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. J Sex Med 2008;5:132,138. [source] The Alchemy of Jargon: Etymologies of Urologic Neologisms.THE PROSTATE, Issue 3 2009Number 3: The genesis of steroid terminology Abstract Background As the scientific community is increasingly severed from the study of linguistics, the underlying significance of their common technical words is becoming blurred. This article will focus on the genesis of terminology in the field of sexual steroids. Methods These notes will give a detailed background of the history of technical terms, including how they came into being, whence they were derived, and how they impacted the scientific community through the ages. Results In this installment, following terms are analyzed: Steroid, Cholesterol, Estrogen, Estrous, Progesterone, Estradiol, Androgen, and Testosterone. Conclusions This analysis of the history and significance of scientific terms common to the urological community works towards a fortification of their power by offering a reminder of their origins. Prostate 69:228,230, 2009. © 2008 Wiley-Liss, Inc. [source] Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via nonclassic signalingARTHRITIS & RHEUMATISM, Issue 4 2010Zsuzsa Jenei-Lanzl Objective We undertook this study to examine the effects of estradiol on chondrogenesis of human bone marrow,derived mesenchymal stem cells (MSCs), with consideration of sex-dependent differences in cartilage repair. Methods Bone marrow was obtained from the iliac crest of young men. Density-gradient centrifugation,separated human MSCs proliferated as a monolayer in serum-containing medium. After confluence was achieved, aggregates were created and cultured in a serum-free differentiation medium. We added different concentrations of 17,-estradiol (E2) with or without the specific estrogen receptor inhibitor ICI 182.780, membrane-impermeable E2,bovine serum albumin (E2-BSA), ICI 182.780 alone, G-1 (an agonist of G protein,coupled receptor 30 [GPR-30]), and G15 (a GPR-30 antagonist). After 21 days, the aggregates were analyzed histologically and immunohistochemically; we quantified synthesized type II collagen, DNA content, sulfated glycosaminoglycan (sGAG) concentrations, and type X collagen and matrix metalloproteinase 13 (MMP-13) expression. Results The existence of intracellular and membrane-associated E2 receptors was shown at various stages of chondrogenesis. Smaller aggregates and significantly lower type II collagen and sGAG content were detected after treatment with E2 and E2-BSA in a dose-dependent manner. Furthermore, E2 enhanced type X collagen and MMP-13 expression. Compared with estradiol alone, the coincubation of ICI 182.780 with estradiol enhanced suppression of chondrogenesis. Treatment with specific GPR-30 agonists alone (G-1 and ICI 182.780) resulted in a considerable inhibition of chondrogenesis. In addition, we found an enhancement of hypertrophy by G-1. Furthermore, the specific GPR-30 antagonist G15 reversed the GPR-30,mediated inhibition of chondrogenesis and up-regulation of hypertrophic gene expression. Conclusion The experiments revealed a suppression of chondrogenesis by estradiol via membrane receptors (GPR-30). The study opens new perspectives for influencing chondrogenesis on the basis of classic and nonclassic estradiol signaling. [source] ,3-Tubulin is induced by estradiol in human breast carcinoma cells through an estrogen-receptor dependent pathwayCYTOSKELETON, Issue 7 2009Jennifer Saussede-Aim Abstract Microtubules are involved in a variety of essential cell functions. Their role during mitosis has made them a target for anti-cancer drugs. However development of resistance has limited their use. It has been established that enhanced ,3-tubulin expression is correlated with reduced response to antimicrotubule agent-based chemotherapy or worse outcome in a variety of tumor settings. However little is known regarding the regulation of ,3-tubulin expression. We investigated the regulatory mechanisms of expression of ,3-tubulin in the MCF-7 cell line, a model of hormone-dependent breast cancer. Exposure of MCF-7 cells to estradiol was found to induce ,3-tubulin mRNA as well as ,3-tubulin protein expression. Conversely, we did not observe induction of ,3-tubulin mRNA by estradiol in MDA-MB-231 cells which are negative for the estrogen receptor (ER). In order to determine whether ,3-tubulin up-regulation is mediated through the ER pathway, MCF-7 cells were exposed to two ER modulators. Exposure to tamoxifen, a selective estrogen receptor modulator, completely abolished the ,3-tubulin mRNA induction due to estradiol in MCF-7 cells. This result was confirmed with fulvestrant, a pure antagonist of ER. These results demonstrate that the effect of estradiol on ,3-tubulin transcription is mediated through an ER dependent pathway. Cell Motil. Cytoskeleton 66:378,388, 2009. © 2009 Wiley-Liss, Inc. [source] Role for primary cilia in the regulation of mouse ovarian functionDEVELOPMENTAL DYNAMICS, Issue 8 2008Ellen T. Johnson Abstract Ift88 is a component of the intraflagellar transport complex required for formation and maintenance of cilia. Disruption of Ift88 results in depletion of cilia. The goal of the current study was to determine the role of primary cilia in ovarian function. Deletion of Ift88 in ovary using Cre-Lox recombination in mice resulted in a severe delay in mammary gland development including lack of terminal end bud structures, alterations in the estrous cycle, and impaired ovulation. Because estrogen drives the formation of end buds and Cre was expressed in the granulosa cells of the ovary, we tested the hypothesis that addition of estradiol to the mutant mice would compensate for defects in ovarian function and rescue the mammary gland phenotype. Mammary gland development including the formation of end bud structures resumed in mutant mice that were injected with estradiol. Together the results suggest that cilia are required for ovarian function. Developmental Dynamics 237:2053,2060, 2008. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||