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Sample records for ovarian steroid hormones

  1. Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development.

    PubMed

    Jeon, So-Ye; Hwang, Kyung-A; Choi, Kyung-Chul

    2016-04-01

    As the primary female sex steroid hormones, estrogens and progesterone play important roles to regulate growth, differentiation, and function of a broad range of target tissues in the human body and maintain the function of female reproductive tissues. Ovarian cancer is the most cause of cancer death in gynecological malignancy. Despite enormous outcomes in the understanding of ovarian cancer pathology, this disease has resulted in poor survival rates since most patients are asymptomatic until the disease has been metastasized. The exact molecular events leading to metastasis of ovarian tumor cells have not yet been well elucidated, although it is recognized that the acquisition of capacity for migration and invasiveness would be a necessary prerequisite. During metastasis, epithelial-mesenchymal transition (EMT) is an important process, in which epithelial cells lose their intracellular adhesion and cell polarity and acquire increased motility and invasive properties to become mesenchymal like cells. The process of cancer cells to undergo EMT is regulated through the up- and down- regulation of a multiple cellular markers and signaling proteins. In this review, we focused the roles of women sex steroid hormones, estrogen and progesterone, in ovarian cancer, especially the ovarian cancer undergoing EMT and metastatic process. All things considered, we may suggest that progesterone is a potent hormone which inhibits the growth of human ovarian cancer cells and development to metastasis whereas estrogen may act as a risk factor of ovarian cancer progression and that progesterone therapy may be an alternative clinically effective tool for the treatment of human ovarian cancer.

  2. Ovarian steroidogenesis and the role of sex steroid hormones on ovarian growth and maturation of the Japanese eel.

    PubMed

    Kazeto, Yukinori; Tosaka, Ryota; Matsubara, Hajime; Ijiri, Shigeho; Adachi, Shinji

    2011-11-01

    Three sex steroid hormones, estradiol-17β (E2), 11-ketotestosterone (11-KT), and 17α,20β-dihydroxy-4-pregnen-3-one (DHP), are well established as primary estrogen, androgen, and progestin, respectively, in teleost fish. Japanese eel, Anguilla japonica, would be a suitable candidate to study ovarian steroid physiology of fish because the ovarian growth and steroidogenesis is dormant under laboratory condition but can be induced by administration of exogenous gonadotropic reagents. In this review, we summarized our work on the function and production of sex steroid hormones in the ovary of the Japanese eel during ovarian growth and oocyte maturation artificially induced by treatment with extract of salmon pituitary. In vitro and in vivo assays suggest that 11-KT and E2 play primary roles in previtellogenic and vitellogenic growth of oocytes, respectively, whereas DHP is essential for induction of final oocyte maturation. We also reviewed the correlation between ovarian steroidogenesis to produce these sex steroid hormones, serum titers and gene expression.

  3. Morphologic responses of the mouse ovarian surface epithelium to ovulation and steroid hormonal milieu.

    PubMed

    Gotfredson, Garry S; Murdoch, William J

    2007-02-01

    Ovarian cancer of surface epithelial origin is an ovulation- and endocrine-related disease. It appears that a cell transformed by genotoxins generated at follicular rupture is propagated during postovulatory wound repair. A consequent steroid hormonal imbalance favoring the mitogenic estrogens is a prospective predisposing factor in ovarian neoplasia. Protection against epithelial ovarian cancer is conferred by progesterone. The objective of this study was to characterize the acute effects of ovulation and steroid hormonal exposure on morphologic responses of surface epithelial cells of mouse ovaries. Follicular development and ovulation were induced in immature animals with equine and human (=Day 0) choriogonadotropins, respectively. On Day 2 (approximately 36 hrs after ovulation), surface epithelial classifications presented in histologic sections were altered from simple (single-layered) squamous and cuboidal toward stratification; this trend was reversed (i.e., reverted to the control status) on Days 4-8. Shifts in the ovarian epithelium from simple to stratified were accentuated following postovulatory (Days 1-8) treatment with estradiol. Surface epithelia of ovaries obtained after 1 week of progesterone administration were exclusively of a simple phenotype. We conclude that the proliferative/procarcinogenic reaction of the ovarian surface epithelium to ovulation is exacerbated by estrogen and counteracted by progesterone.

  4. Correlation between steroid hormonal levels and cardiac function in women during controlled ovarian hyperstimulation.

    PubMed

    Li, Yiran; Sun, Xiuhua; Zang, Lili; Zhang, Quan; Li, Jichun; Zou, Shuhua

    2013-12-01

    During in vitro fertilization-embryo transfer (IVF-ET) treatment, most women require controlled ovarian hyperstimulation (COH). COH with gonadotropins results in an increase in steroid hormonal levels; however, it is unclear what impact these high concentrations of steroid hormones have on cardiac heart function. The purpose of this study was to examine the effect of high levels of estradiol (E2) and progesterone (P) during COH treatment on cardiac function in women undergoing IVF-ET. A total of 34 women with infertility due to tubal or male factors treated with COH and 28 women with normal menstrual cycles who underwent ovulation monitoring only were enrolled in this study. The serum levels of steroid hormones and the parameters of echocardiography at different time points during the natural menstrual cycles of the control group and the corresponding time points during COH treatment of the study group were compared. The independent sample with the t test, the paired sample with t test, χ(2) test, and Pearson correlation analysis were applied. The steroid hormonal levels were significantly different between natural menstrual cycles and COH treatment cycles. Left ventricular end-diastolic volume (LVEDV) reached the highest level on day 7 after oocyte pickup; in contrast, ejection fraction (LVEF) was the lowest level on the same day. On day 16 after ET, E2 and P levels were maintained in the pregnant women in the study group; however, the levels of those hormones returned to those of a natural menstrual cycle in non-pregnant women. The parameters of LVEF and LVEDV significantly correlated with E2 concentrations. High levels of E2 during COH treatment may temporarily affect cardiac function, suggesting that COH intervention is relatively safe; however, a certain level of risk might exist.

  5. Steroid and metabolic hormonal profile of porcine serum vis-à-vis ovarian follicular fluid

    PubMed Central

    Naskar, Soumen; Borah, S.; Vashi, Y.; Thomas, R.; Sarma, D. K.; Goswami, J.; Dhara, S. K.

    2016-01-01

    Aim: This study was conducted to understand whether serum level of the steroid and metabolic hormones may be indicative of their level in ovarian follicular fluid (FF) in porcine, and its influence on fertility. Materials and Methods: Ovaries from pigs (n=32) of two genetic groups, namely, native (Ghungroo; n=16) and crossbred (Hampshire × Ghungroo; n=16) were collected. Both the genetic groups comprised gilts (n=8) and sows (n=8), and sows were in luteal phase of estrus cycle. FF was aspirated from small, medium and large follicles, and centrifuged for the collection of supernatant for further analysis. Blood samples were collected from the same animals, and serum was separated. Hormones, namely, cortisol, T3, T4 and testosterone were estimated by radioimmunoassay. Two-way ANOVA was used for analysis of data considering genetic background (native or crossbred), stage of reproductive life (gilt or sow), and source of sample (serum or FF) as fixed effects. Results: It was observed that all the hormones except cortisol differed significantly (p<0.01) based on genetic background. Stage of reproductive life and source of sample did not affect the studied hormonal level. Within the genetic groups, stage of reproductive life influenced T3 (p<0.01), cortisol (p<0.05) and testosterone (p<0.01) level in crossbred pigs as compared to T3 (p<0.01) only in native pigs. The level of T3 in serum, as well as FF, was higher (p<0.01) in Ghungroo gilts compared to sows. However, a reverse of this was observed in the case of crossbred pigs. The level of cortisol (p<0.05) and testosterone (p<0.01) was higher in crossbred sows than gilts in both serum and FF. Conclusion: The study revealed that serum level of the steroid and metabolic hormones is indicative of their level in the ovarian FF. Further, varying level of steroid and metabolic hormones in pigs based on genetic background may be due to variation in body size, rate of energy metabolism and stage of (re)productive life. PMID

  6. Comparative aspects of steroid hormone metabolism and ovarian activity in felids, measured noninvasively in feces.

    PubMed

    Brown, J L; Wasser, S K; Wildt, D E; Graham, L H

    1994-10-01

    Noninvasive fecal assays were used to study steroid metabolism and ovarian activity in several felid species. Using the domestic cat (Felis catus) as model, the excretory products of injected [14C]estradiol (E2) and [14C]progesterone (P4) were determined. Within 2 days, 97.0 +/- 0.6% and 96.7 +/- 0.5% of recovered E2 and P4 radioactivity, respectively, was found in feces. E2 was excreted as unconjugated estradiol and estrone (40%) and as a non-enzyme-hydrolyzable conjugate (60%). P4 was excreted primarily as non-enzyme-hydrolyzable, conjugated metabolites (78%) and as unconjugated pregnenolone epimers. A simple method for extracting fecal steroid metabolites optimized extraction efficiencies of the E2 and P4 excretion products (90.1 +/- 0.8% and 87.2 +/- 1.4%, respectively). Analysis of HPLC fractions of extracted fecal samples from the radiolabel-injected domestic cats revealed that E2 immunoreactivity coincided primarily with the unconjugated metabolized [14C]E2 peak, whereas progestogen immunoreactivity coincided with a single conjugated epimer and multiple unconjugated pregnenolone epimers. After HPLC separation, similar immunoreactive E2 and P4 metabolite profiles were observed in the leopard cat (F. bengalensis), cheetah (Acinonyx jubatus), clouded leopard (Neofelis nebulosa), and snow leopard (Panthera uncia). Longitudinal analyses demonstrated that changes in fecal E2 and P4 metabolite concentrations reflected natural or artificially induced ovarian activity. For example, severalfold increases in E2 excretion were associated with overt estrus or exogenous gonadotropin treatment, and elevated fecal P4 metabolite concentrations occurred during pregnant and nonpregnant (pseudopregnant) luteal phases. Although overall concentrations were similar, the duration of elevated fecal P4 metabolites during pseudopregnancy was approximately half that observed during pregnancy. In summary, steroid metabolism mechanisms appear to be conserved among these physically

  7. Bisphenol A Exposure, Ovarian Follicle Numbers, and Female Sex Steroid Hormone Levels: Results From a CLARITY-BPA Study.

    PubMed

    Patel, Shreya; Brehm, Emily; Gao, Liying; Rattan, Saniya; Ziv-Gal, Ayelet; Flaws, Jodi A

    2017-06-01

    Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. Copyright © 2017 Endocrine Society.

  8. Synthetic Steroid Hormones Regulated Cell Proliferation Through MicroRNA-34a-5p in Human Ovarian Endometrioma.

    PubMed

    Hsu, Chia-Yi; Hsieh, Tsung-Hua; Tsai, Cheng-Fang; Chen, Hung-Sheng; Liang, Peir-In; Hsu, Ya-Ling; Tsai, Eing-Mei

    2016-03-01

    Endometriosis is the hormone-dependent product of endometrial tissue found outside the uterus. Recently, micro-RNAs (miRNAs) were shown to play a role in endometriotic lesion development. However, the mechanism of steroid hormones responsible for miRNA remains obscure. In the present study, we assayed for the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate [MPA]) on miRNAs in endometriosis. We used a global miRNA expression profile microarray to evaluate miRNA expression in endometrial mesenchymal stem cells (EN-MSCs) of ovarian endometrioma following treatment with 1 μM danazol, progesterone, or MPA. Furthermore, we selected candidate miRNAs whose expression changed more than fivefold and compared the effects of danazol, progesterone, and MPA treatments and also compared those results with controls in EN-MSCs. Among those with a fivefold change, we found 13 ectopically upregulated miRNAs in EN-MSCs. To understand the function of these 13 miRNAs, we subjected their sequences to Ingenuity Pathway Analysis. According to both the etiology and pathogenesis of endometriosis, we found that miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Steroid hormone treatment elevated the levels of miR-199a-5p and miR-34a-5p. An inhibitor of miR-34a-5p also reduced the synthetic steroid hormones effects on cell proliferation. In vivo data revealed that miRNA levels in endometriotic lesions correlated with findings following in vitro synthetic hormone treatment. Our data show the effects of synthetic steroid hormones on miRNA regulation. These findings contribute to our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment. © 2016 by the Society for the Study of Reproduction, Inc.

  9. Effects of ovarian steroid hormones and thyroxine on calcitonin secretion in pregnant rats.

    PubMed

    Lu, C C; Tsai, S C; Wang, S W; Tsai, C L; Lau, C P; Shih, H C; Chen, Y H; Chiao, Y C; Liaw, C; Wang, P S

    1998-02-01

    In the present study, the roles of ovarian steroid hormones and thyroxine (T4) in regulating the secretion of calcitonin (CT) in pregnant rats were examined. The levels of plasma progesterone, pre- and post-CaCl2 plasma CT, and recovery time of plasma CT and calcium after calcium challenge were greatest in midterm pregnant rats. The levels of basal plasma progesterone, CT, calcium, and recovery time of plasma CT after calcium challenge were less in late pregnant rats, but basal plasma estradiol was highest in late pregnancy. The concentrations of plasma T4 were gradually decreased in rats during pregnancy. Regardless of the presence of estradiol, administration of progesterone in ovariectomized (Ovx) rats resulted in an increase of plasma T4 as well as the basal and calcium-induced secretion of CT. Administration of estradiol alone did not alter the CaCl2-induced levels but decreased the post-CaCl2 levels of plasma calcium in Ovx rats. The basal levels of plasma CT were decreased in Ovx rats treated with T4. These results suggest that the hypercalcitoninemia in midterm pregnant rats is due to an increased secretion of progesterone. Hypocalcitoninemia in late pregnant rats, however, is due in part to lower plasma calcium.

  10. Effect of ovarian steroid hormones and the presence of the fetus on oxytocin gene expression in the uterus.

    PubMed

    Higuchi, T; Liu, C X; Saito, H; Negoro, H; Matsukawa, S

    1995-07-01

    Oxytocin (OT) is a neurohypophysial hormone with potent stimulating activity of the pregnant uterus, but its physiological role in parturition is still unclear. Recently, OT was found to be synthesized in the pregnant uterus, indicating that OT originating from the uterus, not from the posterior pituitary gland, may trigger the onset of labour. In order to define the factors responsible for the induction of uterine OT, the effect of ovarian steroid hormones and conceptus on the induction of OT mRNA in the rat uterus was examined by Northern and dot blot hybridization analysis. OT mRNA in the uterus started to increase on day 14 of pregnancy and showed very high levels at the time of parturition. Uterine OT mRNA was not altered by any steroid treatment, oestradiol-17 beta (0.2 microgram), progesterone (4 mg) or both in combination, for 6 days. The gravid horn of the uterus had 3.6-fold as much OT mRNA as the non-gravid horn on day 21 of pregnancy in hemipregnant rats with one ligated oviduct. The ovarian steroid hormones could not induce accumulation of OT mRNA in the uterus of ovariectomized rats, at least under the conditions used, but the presence of a conceptus may be critical for the very high levels of OT mRNA.

  11. Proliferation of rhesus ovarian surface epithelial cells in culture: Lack of mitogenic response to steroid or gonadotropic hormones

    SciTech Connect

    Wright, Jay W.; Toth-Fejel, Suellen; Stouffer, Richard L.; Rodland, Karin D.

    2002-06-30

    Ovarian cancer is the most lethal gynecological cancer and approximately 90% of ovarian cancers derive from the ovarian surface epithelium (OSE), yet the biology of the OSE is poorly understood. Factors associated with increased risk of non-hereditary ovarian cancer include the formation of inclusion cysts, effects of reproductive hormones cytokeratin, vimentin, N-cadherin, E-cadherin, estrogen receptor-a, and progesterone receptor. We show that these cells activate MAP Kinase and proliferate in response to extracellular calcium, as do human and rat OSE. In contrast, the gonadotropic hormones FSH (4-400 IU/L), LH (8.5-850 IU/l), and hCG (10-1000 IU/l) fail to stimulate proliferation. We find that concentrations of progesterone and estrogen normally present in follicles just prior to ovulation ( ~1000 ng/ml) significantly decrease the number of mitotically active RhOSE cells as determined by PCNA labelling, total cell count, and 3H-thymidine uptake, while lower steroid concentrations have no effect.

  12. Urinary concentrations of ovarian steroid hormone metabolites and bioactive follicle-stimulating hormone in killer whales (Orcinus orchus) during ovarian cycles and pregnancy.

    PubMed

    Walker, L A; Cornell, L; Dahl, K D; Czekala, N M; Dargen, C M; Joseph, B; Hsueh, A J; Lasley, B L

    1988-12-01

    Reproductive hormone profiles of six captive killer whales (Orcinu orcus) from three Sea World aquaria were studied for intervals up to 2 yr. Daily urine samples and bimonthly blood samples were collected and analyzed for hormone concentration. Immunoreactive estrone conjugates, pregnanediol-3-glucoruonide, 20-alpha-hydroxyprogesterone as well as bioactive follicle-stimulating hormone (FSH) were measured in urine samples and indexed by creatinine concentrations of the same sample. In selected cases, serum progesterone concentrations were also measured. Three of the animals in the study became pregnant during the study period and two of these animals were evaluated during the time of conception and throughout most of gestation. From the data of the three animals that conceived, hormone profiles of the complete ovarian cycle, early pregnancy, and mid- to late gestation are described. The remaining three animals did not conceive and only one of these demonstrated hormone changes that indicated regular ovarian activity. The female reproductive pattern of the killer whale is characterized by a gestation of 17 mo and an ovarian cycle of 6-7 wk in duration. The hormone changes associated with the ovarian cycle of the killer whale are similar to those of most other mammalian species. A bimodal pattern of bioactive FSH with a pronounced rise of estrogen predominates the preovulatory hormone profile. After ovulation, increased progesterone production is observed for approximately 4 wk in the nonconceptive ovarian cycle. During the luteal phase and early pregnancy, when progesterone metabolites are elevated, estrogen metabolite excretion remains low. These data extend the application of urine collections for longitudinal studies involving hormone changes, particularly those involving nondomesticated species.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. The influence of deoxynivalenol and zearalenone on steroid hormone production by porcine ovarian granulosa cells in vitro.

    PubMed

    Kolesarova, Adriana; Medvedova, Marina; Halenar, Marek; Sirotkin, Alexander V; Bulla, Jozef

    2017-09-25

    Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEA) are frequently occurring in feed of pigs together. The aim of this study was to evaluate the possible in vitro effects of DON and ZEA, alone or their combination on steroid secretion of porcine ovarian granulosa cells (GCs). A species-specific model with porcine ovarian GCs was used to study the potential endocrine disrupting effects of DON and ZEA alone and in co-exposure. Progesterone (P4) and estradiol (E2) were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). The results of this study demonstrate that DON alone at the higher concentrations may act to stimulate P4 (at 1,000, 2,000, 3,000 and 5,000 ng mL(-1) but not 10 and 100 ng mL(-1)) and E2 (at 2,000, 3,000 and 5,000 ng mL(-1) but not 10, 100 and 1000 ng mL(-1)) secretion. The effects of ZEA on P4 and E2 secretion were not confirmed. DON in combination with the other fusariotoxin ZEA may impair steroidogenesis. Results aslo demonstrate different toxicological effects of fusariotoxins on follicle stimulating hormone-induced secretion of P4 and E2. All these results taken together suggest that fusariotoxin and their interactions can impact ovarian steroidogenesis, thereby demonstrating their potential reproductive effects in pigs.

  14. Expression of focal adhesion kinase in endometrial stromal cells of women with endometriosis was adjusted by ovarian steroid hormones.

    PubMed

    Mu, Lin; Ma, Yan-Yan

    2015-01-01

    The aim of our study is to investigate the effects of ovarian steroid hormones on focal adhesion kinase (FAK) expression in ESCs and whether there is alteration in women with endometriosis. FAK expression was assessed by western blotting analysis. Elevated expression of FAK was seen in the cultured ESCs treated with estrogen (P < 0.05). Expression of FAK protein was not changed in ESCs after treated by progesterone or treated by estrogen and progesterone. The level of up-regulation by estrogen in endometriosis is significantly higher than that from women without endometriosis (P < 0.05). FAK expression in endometrial stromal cells from endometriosis was more sensitive to estrogen, which might contribute to the pathogenesis and progress of endometriosis.

  15. Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.

    PubMed

    Watson, H; Kiddy, D S; Hamilton-Fairley, D; Scanlon, M J; Barnard, C; Collins, W P; Bonney, R C; Franks, S

    1993-06-01

    Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels.

  16. Regulation of object recognition and object placement by ovarian sex steroid hormones.

    PubMed

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

    2015-05-15

    The ovarian hormones 17β-estradiol (E2) and progesterone (P4) are potent modulators of hippocampal memory formation. Both hormones have been demonstrated to enhance hippocampal memory by regulating the cellular and molecular mechanisms thought to underlie memory formation. Behavioral neuroendocrinologists have increasingly used the object recognition and object placement (object location) tasks to investigate the role of E2 and P4 in regulating hippocampal memory formation in rodents. These one-trial learning tasks are ideal for studying acute effects of hormone treatments on different phases of memory because they can be administered during acquisition (pre-training), consolidation (post-training), or retrieval (pre-testing). This review synthesizes the rodent literature testing the effects of E2 and P4 on object recognition (OR) and object placement (OP), and the molecular mechanisms in the hippocampus supporting memory formation in these tasks. Some general trends emerge from the data. Among gonadally intact females, object memory tends to be best when E2 and P4 levels are elevated during the estrous cycle, pregnancy, and in middle age. In ovariectomized females, E2 given before or immediately after testing generally enhances OR and OP in young and middle-aged rats and mice, although effects are mixed in aged rodents. Effects of E2 treatment on OR and OP memory consolidation can be mediated by both classical estrogen receptors (ERα and ERβ), and depend on glutamate receptors (NMDA, mGluR1) and activation of numerous cell signaling cascades (e.g., ERK, PI3K/Akt, mTOR) and epigenetic processes (e.g., histone acetylation, DNA methylation). Acute P4 treatment given immediately after training also enhances OR and OP in young and middle-aged ovariectomized females by activating similar cell signaling pathways as E2 (e.g., ERK, mTOR). The few studies that have administered both hormones in combination suggest that treatment can enhance OR and OP, but that effects

  17. Regulation of object recognition and object placement by ovarian sex steroid hormones

    PubMed Central

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

    2014-01-01

    The ovarian hormones 17β-estradiol (E2) and progesterone (P4) are potent modulators of hippocampal memory formation. Both hormones have been demonstrated to enhance hippocampal memory by regulating the cellular and molecular mechanisms thought to underlie memory formation. Behavioral neuroendocrinologists have increasingly used the object recognition and object placement (object location) tasks to investigate the role of E2 and P4 in regulating hippocampal memory formation in rodents. These one-trial learning tasks are ideal for studying acute effects of hormone treatments on different phases of memory because they can be administered during acquisition (pre-training), consolidation (post-training), or retrieval (pre-testing). This review synthesizes the rodent literature testing the effects of E2 and P4 on object recognition (OR) and object placement (OP), and the molecular mechanisms in the hippocampus supporting memory formation in these tasks. Some general trends emerge from the data. Among gonadally intact females, object memory tends to be best when E2 and P4 levels are elevated during the estrous cycle, pregnancy, and in middle age. In ovariectomized females, E2 given before or immediately after testing generally enhances OR and OP in young and middle-aged rats and mice, although effects are mixed in aged rodents. Effects of E2 treatment on OR 7and OP memory consolidation can be mediated by both classical estrogen receptors (ERα and ERβ), and depend on glutamate receptors (NMDA, mGluR1) and activation of numerous cell signaling cascades (e.g., ERK, PI3K/Akt, mTOR) and epigenetic processes (e.g., histone H3 acetylation, DNA methylation). Acute P4 treatment given immediately after training also enhances OR and OP in young and middle-aged ovariectomized females by activating similar cell signaling pathways as E2 (e.g., ERK, mTOR). The few studies that have administered both hormones in combination suggest that treatment can enhance OR and OP, but that

  18. Effects of acute unilateral ovariectomy to pre-pubertal rats on steroid hormones secretion and compensatory ovarian responses

    PubMed Central

    2011-01-01

    In the present study we analyzed the existence of asymmetry in the secretion of steroid hormones in pre-pubertal female rats treated with unilateral ovariectomy (ULO) or unilateral perforation of the abdominal wall (sham-surgery). Treated rats were sacrificed at different times after surgery. Since sham-surgery had an apparent effect on the age of first vaginal estrous (FVE) and serum levels hormone, the results of the sham surgery groups were used to assess the effects of their respective surgery treatment groups. On the day of FVE, compensatory ovulation (CO) and compensatory ovarian hypertrophy (COH) were similar in animals with ULO, regardless of the ovary remaining in situ. In ULO treated animals, progesterone (P4) levels were higher than in animals with sham-surgery one hour after treatment but lower in rats sacrificed at FEV. Left-ULO resulted in lower testosterone (T) concentration 48 and 72 hours after surgery. In rats with Right-ULO lower T concentrations were observed in rats sacrificed one or 72 hours after surgery, and at FVE. ULO (left or right) resulted in lower estradiol (E2) concentrations one or 72 hours after treatment. In rats with Left-ULO, E2 levels were higher 48 hours after surgery and at FVE. Left-ULO resulted in higher levels of follicle stimulating hormone (FSH) five hours after surgery and at FVE. FSH levels were higher in rats with Right-ULO sacrificed on FVE. The present results suggest that in the pre-pubertal rat both ovaries have similar capacities to secrete P4, and that the right ovary has a higher capacity to secrete E2. Taken together, the present results support the idea that the effects of ULO result from the decrease in glandular tissue and changes in the neural information arising from the ovary. PMID:21450102

  19. Ovarian steroid hormones modulate the expression of progesterone receptors and histone acetylation patterns in uterine leiomyoma cells.

    PubMed

    Sant'Anna, Gabriela Dos Santos; Brum, Ilma Simoni; Branchini, Gisele; Pizzolato, Lolita Schneider; Capp, Edison; Corleta, Helena von Eye

    2017-03-16

    Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.

  20. Alligators, contaminants and steroid hormones.

    PubMed

    Guillette, Louis J; Edwards, Thea M; Moore, Brandon C

    2007-01-01

    Steroids are essential for successful reproduction in all vertebrate species. Over the last several decades, extensive research has indicated that exposure to various environmental pollutants can disrupt steroidogenesis and steroid signaling. Although steroidogenesis is regulated by the hypothalamic-pituitary axis, it is also modified by various paracrine and autocrine factors. Furthermore, the classical two-cell model of steroidogenesis in the developing ovarian follicle, involving the granulosa and theca cells in mammals, may not be universal. Instead, birds and probably reptiles use the two thecal compartments (theca interna and theca externa) as sites of steroid production. We have documented that embryonic or juvenile exposure to a complex mixture of contaminants from agricultural and storm water runoff leads to altered steroid hormone profiles in American alligators. Our observations suggest that alterations in plasma steroid hormone concentrations are due in part to altered gene expression, modified hepatic biotransformation and altered gonadal steroidogenesis. Future studies must examine the interplay between endocrine and paracrine regulation in the development and expression of gonadal steroidogenesis in individuals exposed to endocrine disrupting contaminants at various life stages if we are to fully understand potential detrimental outcomes.

  1. Effects on steroid hormones secretion resulting from the acute stimulation of sectioning the superior ovarian nerve to pre-pubertal rats

    PubMed Central

    2012-01-01

    In the adult rat, neural signals arriving to the ovary via the superior ovarian nerve (SON) modulate progesterone (P4), testosterone (T) and estradiol (E2) secretion. The aims of the present study were to analyze if the SON in the pre-pubertal rat also modulates ovarian hormone secretion and the release of follicle stimulating hormone (FSH) and luteinizing (LH) hormone. P4, T, E2, FSH and LH serum levels were measured 30 or 60 minutes after sectioning the SON of pre-pubertal female rats. Our results indicate that the effects on hormone levels resulting from unilaterally or bilaterally sectioning the SON depends on the analyzed hormone, and the time lapse between surgery and autopsy, and that the treatment yielded asymmetric results. The results also suggest that in the pre-pubertal rat the neural signals arriving to the ovaries via the SON regulate the enzymes participating in P4, T and E2 synthesis in a non-parallel way, indicating that the mechanisms regulating the synthesis of each hormone are not regulated by the same signals. Also, that the changes in the steroids hormones are not explained exclusively by the modifications in gonadotropins secretion. The observed differences in hormone levels between rats sacrificed 30 and 60 min after surgery reflect the onset of the compensatory systems regulating hormones secretion. PMID:23110668

  2. Alteration of gonadotrophin and steroid hormone release, and of ovarian function by a GnRH antagonist in gilts.

    PubMed

    Brüssow, K P; Schneider, F; Nürnberg, G

    2001-04-30

    This study examined the impact of the gonadotrophin-releasing hormone (GnRH) antagonist Antarelix on LH, FSH, ovarian steroid hormone secretion, follicular development and pituitary response to LHRH in cycling gilts. Oestrous cycle of 24 Landrace gilts was synchronised with Regumate (for 15 days) followed by 800 IU PMSG 24h later. In experiment 1, Antarelix (n=6 gilts) was injected i.v. (0.5mg per injection) twice daily on four consecutive days from day 3 to 6 (day 0=last day of Regumate feeding). Control gilts (n=6) received saline. Blood was sampled daily, and every 20 min for 6h on days 2, 4, 6, 8 and 10. In experiment 2, gilts (n=12) were assigned to the following treatments: Antarelix; Antarelix + 50 microg LHRH on day 4; Antarelix + 150 microg LHRH on day 4 or control, 50 microg LHRH only on day 4. Blood samples were collected daily and every 20 min for 6h on days 2, 4 and 6 to assess LH pulsatility. Ovarian follicular development was evaluated at slaughter. Antarelix suppressed (P<0.05) serum LH concentrations. The amount of LH released on days 4-9 (experiment 1) was 8.80 versus 36.54 ngml(-1) (S.E.M.=6.54). The pattern of FSH, and the preovulatory oestradiol rise was not affected by GnRH antagonist. Suppression of LH resulted in a failure (P<0.05) of postovulatory progesterone secretion. Exogenous LHRH (experiment 2) induced a preovulatory-like LH peak, however in Antarelix treated gilts the LH surge started earlier and its duration was less compared to controls (P<0.01). Furthermore, the amount of LH released from day 4 to 5 was lower (P<0.01) in Antarelix, Antarelix + 50 and Antarelix + 150 treated animals compared to controls. No differences were estimated in the number of LH pulses between days and treatment. Pulsatile FSH was not affected by treatment. Mean basal LH levels were lower (P<0.05) after antagonist treatment compared to controls. Antarelix blocked the preovulatory LH surge and ovulation, but the effects of Antarelix were reduced by exogenous

  3. Assessment of pituitary and steroid hormones and members of the TGF-beta superfamily for ovarian function in patients with congenital uterus and vaginal aplasia (MRKH syndrome).

    PubMed

    Strissel, P L; Oppelt, P; Cupisti, S; Stiegler, E; Beckmann, M W; Strick, R

    2009-05-01

    Patients with Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome have congenital uterine and vaginal aplasia. The main question of this study was, if the absence of a uterus along with other genital and organ malformations could contribute to hormone or other growth factor protein fluctuations involved in communication between the hypothalamus-pituitary axis, ovaries and uterus. Serum from 56 MRKH patients (mean 27.6 years) and 22 female controls (mean 30.7 years) were analyzed using ELISA to determine levels of pituitary and steroid hormones (LH, FSH, estradiol, progesterone), growth factors of the TGF-beta superfamily like activin A, inhibin B, and anti-Müllerian hormone (AMH). All serum levels were analyzed in relation to other organ malformations. Compared to controls, all 56 patients, including 5% with streak ovaries or unilateral ovarian aplasia, were generally similar in hormone and growth factor levels and could be grouped into hormonal phases. However, compared to controls LH/FSH and FSH/LH ratios of patients had significantly higher and lower mean values, of 2.75-fold (p=0.015) and 1.9-fold (p=0.002), respectively. Undetectable inhibin B levels of<10 pg/ml (p=0.05) were noted in 41.1% of MRKH patients, resulting in significantly higher activin A/inhibin B ratios (p<0.001). MRKH patients have hormonal phases supporting ovarian function, but patients with low FSH/LH ratios and undetectable inhibin B levels (<10 pg/ml) could represent cycle phasing irregularities. A model is discussed regarding our findings and the loss of ovarian-uterine communication.

  4. Inhibin-non-steroidal regulation of follicle stimulating hormone secretion

    SciTech Connect

    Burger, H.G.; Findlay, J.K. ); de Kretser, D.M. ); Igarashi, M. )

    1987-01-01

    This book contains the proceedings of inhibin non-steroidal regulation of follicle stimulating hormone secretion. Topics covered include: FSH regulation, Molecular biology, Radioimmunoassay, Physiology - Testocular inhibin, Physiology - ovarian inhibin, and local actions.

  5. The strength of B cell immunity in female rhesus macaques is controlled by CD8+ T cells under the influence of ovarian steroid hormones

    PubMed Central

    LÜ, F X; ABEL, K; MA, Z; ROURKE, T; LU, D; TORTEN, J; MCCHESNEY, M; MILLER, C J

    2002-01-01

    To understand more clearly how mucosal and systemic immunity is regulated by ovarian steroid hormones during the menstrual cycle, we evaluated the frequency of immunoglobulin- and antibody-secreting cells (ISC, AbSC) in genital tract and systemic lymphoid tissues of normal cycling female rhesus macaques. The frequency of ISC and AbSC was significantly higher in tissues collected from animals in the periovulatory period of the menstrual cycle than in tissues collected from animals at other stages of the cycle. The observed changes were not due to changes in the relative frequency of lymphocyte subsets and B cells in tssues, as these did not change during the menstrual cycle. In vitro, progesterone had a dose-dependent inhibitory effect, and oestrogen had a dose-dependent stimulatory effect on the frequency of ISC in peripheral blood mononuclear cell (PBMC) cultures. The in vitro effect of progesterone and oestrogen on ISC frequency could not be produced by incubating enriched B cells alone with hormone, but required the presence of CD8+ T cells. Following oestrogen stimulation, a CD8+ enriched cell population expressed high levels of IFN-gamma and IL-12. The changes in B cell Ig secretory activity that we document in the tissues of female rhesus macaques during the menstrual cycle is due apparently to the action of ovarian steroid hormones on CD8+ T cells. Thus, CD8+ T cells control B cell secretory activity in both mucosal and systemic immune compartments. Understanding, and eventually manipulating, the CD8+ regulatory cell–B cell interactions in females may produce novel therapeutic approaches for autoimmune diseases and new vaccine strategies to prevent sexually transmitted diseases. PMID:11982585

  6. Anabolic steroids and growth hormone.

    PubMed

    Haupt, H A

    1993-01-01

    Athletes are generally well educated regarding substances that they may use as ergogenic aids. This includes anabolic steroids and growth hormone. Fortunately, the abuse of growth hormone is limited by its cost and the fact that anabolic steroids are simply more enticing to the athlete. There are, however, significant potential adverse effects regarding its use that can be best understood by studying known growth hormone excess, as demonstrated in the acromegalic syndrome. Many athletes are unfamiliar with this syndrome and education of the potential consequences of growth hormone excess is important in counseling athletes considering its use. While athletes contemplating the use of anabolic steroids may correctly perceive their risks for significant physiologic effects to be small if they use the steroids for brief periods of time, many of these same athletes are unaware of the potential for habituation to the use of anabolic steroids. The result may be incessant use of steroids by an athlete who previously considered only short-term use. As we see athletes taking anabolic steroids for more prolonged periods, we are likely to see more severe medical consequences. Those who eventually do discontinue the steroids are dismayed to find that the improvements made with the steroids generally disappear and they have little to show for hours or even years of intense training beyond the psychological scars inherent with steroid use. Counseling of these athletes should focus on the potential adverse psychological consequences of anabolic steroid use and the significant risk for habituation.

  7. Steroid hormones and BDNF.

    PubMed

    Pluchino, N; Russo, M; Santoro, A N; Litta, P; Cela, V; Genazzani, A R

    2013-06-03

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.

  8. Ovarian hormones and obesity.

    PubMed

    Leeners, Brigitte; Geary, Nori; Tobler, Philippe N; Asarian, Lori

    2017-05-01

    Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a

  9. Ovarian hormones and gingivitis.

    PubMed

    Zachariasen, R D

    1991-01-01

    Elevated plasma concentrations of the ovarian hormones--estrogen and progestins--during pregnancy, puberty, the menstrual cycle, and oral contraceptive (OC) use are associated with an increased incidence of gingival inflammation and exudate. Gingivitis is induced by the micro- organisms that compose subgingival plaque, particularly anaerobic organisms. The ovarian hormones both stimulate bacterial growth and promote the inflammatory process. In the presence of sex hormones, the metabolic breakdown of folate is increased, leading to a folate deficiency that enhances the inflammatory destruction of oral tissue. Gingivitis occurs in an estimated 60-75% of pregnancy women, but the numbers of gingivitis-producing bacteria decrease toward the end of pregnancy and the gingival tissues return to their previous state. In OC users, on the other hand, inflammation of the gingiva is chronic and may increase over time. If gingivitis is already present at the onset of pregnancy or OC use, the inflammation will become progressively more severe. Although these effects cannot be avoided, ovarian hormone- induced gingivitis can be substantially minimized of low plaque levels exist at the beginning of pregnancy or pill initiation.

  10. Concentrations of steroid hormones, estrous, ovarian and reproductive responses in sheep estrous synchronized with different prostaglandin-based protocols.

    PubMed

    Fierro, S; Viñoles, C; Olivera-Muzante, J

    2016-04-01

    To determine estrous, ovarian and reproductive responses after different prostaglandin (PG)-based protocols, ewes were assigned to groups PG10, PG12, PG14 or PG16 (twoPG injections administered 10, 12, 14 or 16 days apart; respectively). Experiment I (n=132) was conducted to evaluate the estrous response, ovulation rate (OR), conception and fertility. Experiment II (n=24) was conducted to evaluate ovarian follicle growth, steroid concentrations and the interval from the second PG injection to estrus (PG-estrus) and ovulation (PG-ovulation). Estrous response was less with the PG16 (P<0.05) treatment, and the extent of estrous synchrony was greater with the PG10 and PG12 treatments. Ovarian follicle growth and the intervals for the variables PG-estrus, PG-ovulation and OR were similar among groups (P>0.05). From 8 to 4 days before estrus, progesterone (P4) concentrations were greater for the PG14 and PG16 than for the PG10 and PG12 (P<0.05) groups. There were more days where concentrations of P4 were above 3.18 nmol/L with the PG14 and PG16 than PG10 and PG12 (P<0.05) treatments. Use of the PG14 and PG16 treatments resulted in greater estradiol (E2) at estrus and 12h later than use of the PG10 and PG12 treatments. A positive correlation was observed between the duration of the luteal phase and maximum E2 concentrations, and between duration of the luteal phase and days with E2 concentrations above 10 pmol/L. Conception and fertility were greater with use of the PG14 compared with PG10 and PG12 (P<0.05) treatments. The administration of two PG injections 10, 12, 14 or 16 days apart resulted in different durations of the luteal phase that were positively associated with E2 concentrations and the reproductive outcome. The shorter luteal phases were associated with greater synchrony in time of estrus. The intervals for the variables PG-estrus, PG-ovulation and OR were similar among groups. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Ovarian activity and pregnancy in the Siberian tiger, Panthera tigris altaica, assessed by fecal gonadal steroid hormones analyses.

    PubMed

    Putranto, Heri Dwi; Kusuda, Satoshi; Inagaki, Kayo; Kumagai, Gaku; Ishii-Tamura, Rie; Uziie, Yoko; Doi, Osamu

    2007-05-01

    Feces were collected from two female and one male Siberian tigers, Panthera tigris altaica. Steroid hormones were extracted from lyophilized feces and quantified by enzyme immunoassay. The fecal contents of estradiol-17beta (E(2)) and testosterone in the females and male, respectively, changed markedly throughout the year. The fecal E(2) contents of females Nos. 179 and 238 increased at 26.4 +/- 8.0 and 28.0 +/- 14.2 day intervals, respectively. However, the fecal contents of progesterone (P(4)) in the female kept alone did not change. In contrast, the other female, which was kept with a male, had increased fecal P(4) contents after copulation. The fecal progesterone levels of the pregnant female remained high during her 106-day pregnancy.

  12. Plasma anti-Müllerian hormone as a biomarker for bovine granulosa-theca cell tumors: comparison with immunoreactive inhibin and ovarian steroid concentrations.

    PubMed

    El-Sheikh Ali, Hossam; Kitahara, Go; Nibe, Kazumi; Yamaguchi, Ryoji; Horii, Yoichiro; Zaabel, Samy; Osawa, Takeshi

    2013-11-01

    Granulosa-theca cell tumors (GTCTs) are the most frequently reported ovarian tumors in cattle. Clinically, GTCTs could be confused with other ovarian abnormalities; therefore, the only definitive diagnosis for such tumors is histopathology of a biopsy from the affected ovary. However, this is an invasive technique and unsuitable for farm conditions. As a result, the key aim of this study was to evaluate the diagnostic value of anti-Müllerian hormone (AMH), a glycoprotein hormone that is synthesized exclusively by ovarian granulosa cells, as a sensitive noninvasive biomarker for diagnosing GTCTs in cattle. To achieve this aim, we conducted two experiments. In experiment 1, four clinically healthy Japanese Black cows had blood samples taken daily over one estrous cycle to characterize their AMH profiles throughout the estrous cycle. Additionally, single blood samples were collected from 21 cyclic cows to clarify the physiological range of AMH. In experiment 2, cows with histologically confirmed GTCT (GTCT group, n = 9) and cows affected with cystic ovarian disease (COD group, n = 8) had one blood sample taken before extraction of the tumorous ovary or therapeutic treatment for the COD. Blood samples (n = 105) from cyclic cows (n = 25) in experiment 1 were assigned as a physiologically cyclic group (PC group). Plasma AMH, immunoreactive inhibin (ir-INH), estradiol-17β (E2), testosterone (T), and progesterone (P4) concentrations were assayed in all samples. In experiment 1, the mean plasma AMH concentration was 0.09 ± 0.003 ng/mL and did not show substantial fluctuation throughout the estrous cycle. In experiment 2, plasma AMH, ir-INH, and E2 concentrations were significantly elevated in the GTCT group in comparison with the PC group; among these parameters, only the AMH concentrations were significantly higher in the GTCT group than in the COD group. The area under the receiver operating characteristic curve of AMH for diagnosis of GTCT was 0.99 and was

  13. Steroid hormone pretreatments in assisted reproductive technology.

    PubMed

    Nassar, Jean; Tadros, Teddy; Adda-Herzog, Elodie; Ayoubi, Jean Marc; Fanchin, Renato

    2016-12-01

    Adequate availability and FSH sensitivity of ovarian antral follicles and coordination of their growth during controlled ovarian hyperstimulation (COH) rank among factors that may determine outcome, particularly in patients presenting ovarian function defects and so-called "poor responders." Growing evidence indicates that both factors are positively influenced by steroid hormone pretreatments. First, data from studies conducted in both animals and in women exposed to virilizing androgen doses indicate that androgen pretreatments may increase follicle responsiveness to FSH and/or the number of growing follicles in the ovary, thereby constituting an interesting perspective in the management of "poor responders." Second, overcoming pre-COH heterogeneities in antral follicle sizes, which are more pronounced in "poor responders," to achieve adequate coordination of multiple follicular growth during COH also is contributive. For this, suppression or attenuation of the premature FSH increase during the preceding late luteal phase using sex steroid pretreatments (oral contraceptives, synthetic progestogens, or estradiol), or additional strategies such as premenstrual GnRH antagonist administration has been shown to be effective. The present paper will critically review proposed mechanisms and clinical results of sex steroid hormone pretreatments in these two different indications as an effort to optimizing COH outcome. Copyright © 2016. Published by Elsevier Inc.

  14. Gonadotrophin-inhibitory hormone receptor expression in the chicken pituitary gland: potential influence of sexual maturation and ovarian steroids.

    PubMed

    Maddineni, S; Ocón-Grove, O M; Krzysik-Walker, S M; Hendricks, G L; Proudman, J A; Ramachandran, R

    2008-09-01

    Gonadotrophin-inhibitory hormone (GnIH), a hypothalamic RFamide, has been found to inhibit gonadotrophin secretion from the anterior pituitary gland originally in birds and, subsequently, in mammalian species. The gene encoding a transmembrane receptor for GnIH (GnIHR) was recently identified in the brain, pituitary gland and gonads of song bird, chicken and Japanese quail. The objectives of the present study are to characterise the expression of GnIHR mRNA and protein in the chicken pituitary gland, and to determine whether sexual maturation and gonadal steroids influence pituitary GnIHR mRNA abundance. GnIHR mRNA quantity was found to be significantly higher in diencephalon compared to either anterior pituitary gland or ovaries. GnIHR mRNA quantity was significantly higher in the pituitaries of sexually immature chickens relative to sexually mature chickens. Oestradiol or a combination of oestradiol and progesterone treatment caused a significant decrease in pituitary GnIHR mRNA quantity relative to vehicle controls. GnIHR-immunoreactive (ir) cells were identified in the chicken pituitary gland cephalic and caudal lobes. Furthermore, GnIHR-ir cells were found to be colocalised with luteinising hormone (LH)beta mRNA-, or follicle-stimulating hormone (FSH)beta mRNA-containing cells. GnIH treatment significantly decreased LH release from anterior pituitary gland slices collected from sexually immature, but not from sexually mature chickens. Taken together, GnIHR gene expression is possibly down regulated in response to a surge in circulating oestradiol and progesterone levels as the chicken undergoes sexual maturation to allow gonadotrophin secretion. Furthermore, GnIHR protein expressed in FSHbeta or LHbeta mRNA-containing cells is likely to mediate the inhibitory effect of GnIH on LH and FSH secretion.

  15. Plasma prorenin response to human chorionic gonadotropin in ovarian-hyperstimulated women: correlation with the number of ovarian follicles and steroid hormone concentrations.

    PubMed Central

    Itskovitz, J; Sealey, J E; Glorioso, N; Rosenwaks, Z

    1987-01-01

    Plasma prorenin and active renin were measured before and after human chorionic gonadotropin (hCG) administration in two groups of patients undergoing ovarian stimulation for 4-6 days with follicle-stimulating hormone alone or in combination with luteinizing hormone, for in vitro fertilization. Baseline total plasma renin (prorenin plus active renin; n = 12) averaged 25 +/- 8 ng/ml per hr (mean +/- SD). Total renin did not change during ovarian stimulation but it increased to 46 +/- 16 ng/ml per hr (P less than 0.05) 1 or 2 days later, just before hCG administration. Thirty-six hours after hCG administration, just before laparoscopy and egg retrieval, total renin was 123 +/- 97 ng/ml per hr; a peak of 182 +/- 143 ng/ml per hr occurred 2-6 days later--i.e., during the luteal phase of the menstrual cycle. In eight of the patients who did not conceive, total renin returned to baseline 14 days after hCG administration. In four who conceived, a nadir was reached (57 +/- 13 ng/ml per hr) 8-12 days after hCG administration and then total renin increased again as the plasma beta hCG measurement began to rise. By day 16 it averaged 225 +/- 157 ng/ml per hr. In a second group of five patients active renin and prorenin were measured separately. Active renin comprised less than 20% of the total renin at all times. It was unchanged until day 4 after hCG administration and then increased significantly only when plasma progesterone was high. Thus, the initial response to hCG was entirely due to an increase in prorenin. A highly significant correlation was observed between the number of follicles and the total renin increases on the day of aspiration (r = 0.93, P less than 0.001) and at the peak (r = 0.89, P less than 0.001). After hCG administration, a temporal relationship was observed between the rise in total renin and plasma estradiol and progesterone levels. These results demonstrate that plasma prorenin increases markedly after administration of hCG and that the rise is

  16. Involvement of adrenoceptors in the ovarian vascular pedicle in the regulation of counter current transfer of steroid hormones to the arterial blood supplying the oviduct and uterus of pigs

    PubMed Central

    Stefańczyk-Krzymowska, S; Grzegorzewski, W; Skipor, J; Wasowska, B; Krzymowski, T

    1997-01-01

    On Day 10 of the oestrous cycle in pigs, after laparotomy noradrenaline (NA), methoxamine (α1-adrenomimetic, M), Prazosin (α1-adrenolytic, Pr) in total doses of 4 μmol, and saline were infused (10 min) into the superficial layer of mesovarium on both sides of the ovarian pedicle vasculature, close to the ovary.Blood flow in the ovarian artery, heart rate and progesterone (P4) and androstenedione (A4) secretion from the ovary and their concentrations in the ovarian venous effluent, as well as the concentrations of P4 and A4 in the blood supplying the oviduct and the uterus, were determined.A significant increase of P4 and A4 secretion after NA and M infusion and increased concentrations of P4 and A4 in the ovarian venous effluent were found, but these changes did not influence the counter current transfer of hormones from the venous effluent into arterial blood supplying the oviduct and the uterus.Infusion of Pr caused a significant decrease of P4 and A4 secretion and their concentrations in the ovarian venous effluent and significantly increased A4 concentration in the blood supplying the oviduct and uterus.The results indicate that stimulation of α1-adrenoceptors in the area of ovarian vasculature did not influence, whereas block of α1-adrenoceptors affected, the local concentration of steroid hormones in the blood supplying the oviduct and the part of the uterus proximal to the ovary, despite the changes in the concentrations of steroid hormones in the ovarian effluent. PMID:9138679

  17. Residual ovarian activity during oral steroid contraception.

    PubMed

    van Heusden, A M; Fauser, B C J M

    2002-01-01

    Steroid drugs with contraceptive properties have been available in the clinical setting for over four decades and are still subject to improvement. Estrogens, progestins and anti-progestins have been used alone or in various combinations, regimens and routes of administration to favour the balance between efficacy and undesirable effects. One of the most important changes in this respect is the gradual lowering of steroid dosage in commercially available contraceptives. Current steroid contraceptive pills still achieve the goal of suppression of pituitary-ovarian activity, but the margins for error are minimal. In this review the available data on modes of action and the effects on suppressing pituitary-ovarian activity by different forms of oral contraception are reassessed. Although pregnancy rates provide a crude measure of contraceptive efficacy, no benchmark for pituitary-ovarian inhibition is available to test the suppressive potential of contraceptive drugs. Consequently, many studies provide incomplete and/or incomparable results. For the further study of those forms of steroid contraception that rely predominantly on suppression of ovarian activity, prevention of dominant follicles selection should be the objective.

  18. Ovarian Steroids: The Good, the Bad, and the Signals that Raise Them

    PubMed Central

    Jamnongjit, Michelle; Hammes, Stephen R

    2006-01-01

    Ovarian steroid production and subsequent local steroid-mediated signaling are critical for normal ovarian processes, including follicle growth, oocyte maturation, and ovulation. In contrast, elevated steroidogenesis and/or increased steroid signaling in the ovary can lead to profound ovarian pathology, such as polycystic ovarian syndrome, the leading cause of infertility in reproductive age women. Through the use of several in vitro and animal models, great strides have been made toward characterizing the mechanisms regulating local steroid production and action in the ovary. Examples of this progress include insights into luteinizing hormone (LH)- and growth factor-mediated signaling, steroidogenic acute regulatory protein (StAR) activation, and both genomic and nongenomic steroid-mediated signaling in somatic and germ cells, respectively. The following review will address these advances, focusing on how this rapidly expanding knowledge base can be used to better understand female reproduction, and to further improve treatments for common diseases of infertility. PMID:16760656

  19. Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications

    PubMed Central

    Moravek, Molly B.; Yin, Ping; Ono, Masanori; Coon V, John S.; Dyson, Matthew T.; Navarro, Antonia; Marsh, Erica E.; Chakravarti, Debabrata; Kim, J. Julie; Wei, Jian-Jun; Bulun, Serdar E.

    2015-01-01

    BACKGROUND Uterine leiomyoma is the most common benign tumor in women and is thought to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a cellular insult. Leiomyomas cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are the most common indication for hysterectomy in the USA. A slow rate of cell proliferation, combined with the production of copious amounts of extracellular matrix, accounts for tumor expansion. A common salient feature of leiomyomas is their responsiveness to steroid hormones, thus providing an opportunity for intervention. METHODS A comprehensive search of PUBMED was conducted to identify peer-reviewed literature published since 1980 pertinent to the roles of steroid hormones and somatic stem cells in leiomyoma, including literature on therapeutics that target steroid hormone action in leiomyoma. Reviewed articles were restricted to English language only. Studies in both animals and humans were reviewed for the manuscript. RESULTS Estrogen stimulates the growth of leiomyomas, which are exposed to this hormone not only through ovarian steroidogenesis, but also through local conversion of androgens by aromatase within the tumors themselves. The primary action of estrogen, together with its receptor estrogen receptor α (ERα), is likely mediated via induction of progesterone receptor (PR) expression, thereby allowing leiomyoma responsiveness to progesterone. Progesterone has been shown to stimulate the growth of leiomyoma through a set of key genes that regulate both apoptosis and proliferation. Given these findings, aromatase inhibitors and antiprogestins have been developed for the treatment of leiomyoma, but neither treatment results in complete regression of leiomyoma, and tumors recur after treatment is stopped. Recently, distinct cell populations were discovered in leiomyomas; a small population showed stem

  20. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2003-08-01

    NFl is characterized by benign Schwann cell tumors called neurofibromas; complex forms can become malignant ( MPNST ). Little is known about...neurofibroma (and/or MPNST ) Schwann cells have increased growth or decreased apoptosis related to steroid hormones. Specific Aim 1 is examining steroid...hormone receptor expression in human normal, NFl neurofibroma and MPNST Schwann cells. Real-time PCR shows very low levels of these receptor

  1. Ovarian hormones and drug abuse.

    PubMed

    Moran-Santa Maria, Megan M; Flanagan, Julianne; Brady, Kathleen

    2014-11-01

    There are significant gender differences in course, symptomology, and treatment of substance use disorders. In general data from clinical and preclinical studies of substance use disorders suggest that women are more vulnerable than men to the deleterious consequences of drug use at every phase of the addiction process. In addition data from epidemiologic studies suggest that the gender gap in the prevalence of substance use is narrowing particularly among adolescence. Therefore, understanding the role of estrogen and progesterone in mediating responses to drugs of abuse is of critical importance to women's health. In this review we will discuss findings from clinical and preclinical studies of (1) reproductive cycle phase; (2) endogenous ovarian hormones; and (3) hormone replacement on responses to stimulants, nicotine, alcohol, opioids, and marijuana. In addition, we discuss data from recent studies that have advanced our understanding of the neurobiologic mechanisms that interact with estrogen and progesterone to mediate drug-seeking behavior.

  2. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2002-08-01

    hypothesis is that human neurofibroma (and/or MPNST ) Schwann cells have increased hormone response compared to normal Schwann cells, leading to tumor...growth. Specific Aim 1 will determine steroid hormone receptor expression in human normal, NFl neurofibroma and MPNST Schwann cells. Real-time PCR has...and rat Schwann cells, as well as an MPNST line so far (which showed no proliferative response) Specific Aim 3 involves in vivo hormone response of

  3. [The secretion of the main ovarian steroids during bleeding in the premenopause].

    PubMed

    Rachev, E; Kŭnchev, L; Stankov, B

    1989-01-01

    The authors study the secretion of the basic ovarian steroids (estradiol, progesterone and testosterone) during dysfunctional bleedings in 46 women at the premenopausal phase of climacteric (mean age of 47.02 years). The results show that the premenopausal bleeding occurs on the background of manifested hypoestradiolemia (2.5 times lower than that at the early follicular phase), hypoprogesteronemia (relatively higher that at the early follicular early follicular phase) and relatively high testosteronemia. Determination of the hormones during three successive days show lack of definite dynamics in the secretion of these ovarian steroids. Considerable individual differences are described.

  4. Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

    SciTech Connect

    Shimizu, Takashi; Hirai, Yuko; Murayama, Chiaki; Miyamoto, Akio; Miyazaki, Hitoshi; Miyazaki, Koyomi

    2011-08-19

    Highlights: {yields} Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. {yields}Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. {yields} Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. {yields}Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. {yields} The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.

  5. Comparison between lactating and non-lactating dairy cows on follicular growth and corpus luteum development, and endocrine patterns of ovarian steroids and luteinizing hormone in the estrous cycles.

    PubMed

    Endo, Natsumi; Nagai, Kiyosuke; Tanaka, Tomomi; Kamomae, Hideo

    2012-10-01

    The dynamics of ovarian follicle, corpus luteum (CL), and peripheral plasma ovarian steroids were compared between lactating and non-lactating cows, and a possible association of pulsatile luteinizing hormone (LH) secretion with the dynamics was examined. Lactating (n=5) and non-lactating (n=5) cows were monitored daily for follicle and CL throughout two consecutive estrous cycles (Day 0: day of ovulation). Blood samples were collected daily and at 15 min intervals for 8h on Days 2, 4, 6, 8, and 14 of the second cycle. Lactating cows had larger CL (25.4 ± 1.8mm vs. 23.5 ± 1.5mm, P<0.01) and greater progesterone concentrations (4.6 ± 1.0ng/ml vs. 3.9 ± 0.9 ng/ml, P<0.01) during mid-luteal phase compared with non-lactating cows. Maximal diameters of the first wave dominant follicle (17.2 ± 1.8mm vs. 15.5 ± 0.8mm) and the ovulatory follicle (17.9 ± 1.2mm vs. 15.2 ± 0.8mm) were greater (P<0.05) in lactating cows than in non-lactating cows during the estrous cycles with two follicular waves, but no significant differences were detected between the groups during the estrous cycles with three follicular waves. Plasma estradiol concentrations did not differ between the groups throughout the experiment. Lactating cows had more LH pulses from Days 2 to 14 than non-lactating cows. These results imply that differences in ovarian dynamics may exist between lactating and non-lactating cows, for which the increased number of LH pulses observed in lactating cows may have responsibility.

  6. Rapid steroid hormone actions via membrane receptors.

    PubMed

    Schwartz, Nofrat; Verma, Anjali; Bivens, Caroline B; Schwartz, Zvi; Boyan, Barbara D

    2016-09-01

    Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Steroid plant hormones: effects outside plant kingdom.

    PubMed

    Zhabinskii, Vladimir N; Khripach, Natalia B; Khripach, Vladimir A

    2015-05-01

    Brassinosteroids (BS) are the first group of steroid-hormonal compounds isolated from and acting in plants. Among numerous physiological effects of BS growth stimulation and adaptogenic activities are especially remarkable. In this review, we provide evidence that BS possess similar types of activity also beyond plant kingdom at concentrations comparable with those for plants. This finding allows looking at steroids from a new point of view: how common are the mechanisms of steroid bioregulation in different types of organisms from protozoa to higher animals.

  8. Modulation of appetite by gonadal steroid hormones.

    PubMed

    Asarian, Lori; Geary, Nori

    2006-07-29

    Several sex differences in eating, their control by gonadal steroid hormones and their peripheral and central mediating mechanisms are reviewed. Adult female rats and mice as well as women eat less during the peri-ovulatory phase of the ovarian cycle (estrus in rats and mice) than other phases, an effect under the control of cyclic changes in estradiol secretion. Women also appear to eat more sweets during the luteal phase of the cycle than other phases, possibly due to simultaneous increases in estradiol and progesterone. In rats and mice, gonadectomy reveals further sex differences: orchiectomy decreases food intake by decreasing meal frequency and ovariectomy increases food intake by increasing meal size. These changes are reversed by testosterone and estradiol treatment, respectively. A variety of peripheral feedback controls of eating, including ghrelin, cholecystokinin (CCK), glucagon, hepatic fatty acid oxidation, insulin and leptin, has been shown to be estradiol-sensitive under at least some conditions and may mediate the estrogenic inhibition of eating. Of these, most progress has been made in the case of CCK. Neurons expressing estrogen receptor-alpha in the nucleus tractus solitarius of the brainstem appear to increase their sensitivity to CCK-induced vagal afferent input so as to lead to an increase in the satiating potency of CCK, and consequently decreased food intake, during the peri-ovulatory period in rats. Central serotonergic mechanisms also appear to be part of the effect of estradiol on eating. The physiological roles of other peripheral feedback controls of eating and their central mediators remain to be established.

  9. Steroid Hormones in NF1 Tumorigenesis

    DTIC Science & Technology

    2004-08-01

    This work is testing the hypothesis that human NF1 neurofibroma (and/or MPNST ) Schwann cells have increased growth or decreased apoptosis in response...to estrogen and progesterone. Specific Aim 1 measured steroid hormone receptor expression in human normal, NF1 neurofibroma and MPNST Schwann cells...responses of the neurofibroma/ MPNST Schwann cell cultures to hormones or antagonists, but no global patterns, indicating tumors behave individually as

  10. Steroid hormone sulphation in lead workers.

    PubMed Central

    Apostoli, P; Romeo, L; Peroni, E; Ferioli, A; Ferrari, S; Pasini, F; Aprili, F

    1989-01-01

    The metabolism of steroid hormones has been investigated in 10 workers exposed to lead and in 10 non-exposed subjects to determine whether lead interferes with the first or second phase reactions of steroid hormone biotransformation, or both. In the exposed workers blood lead concentrations (PbB) ranged from 45 to 69 micrograms/100 ml; in the controls PbB was less than 25 micrograms/100 ml. No statistical differences were found for the total amount of the urinary hormone metabolites, but a drop of about 50% was observed for the sulphated portion. It is suggested that lead interferes with the mechanisms of sulphoconjugation through an effect on the cytosol enzymes sulphotransferase and sulphokinase. PMID:2930732

  11. Steroids

    MedlinePlus

    ... steroids (say: STARE-oydz), they often mean illegal anabolic steroids. Anabolic steroids are artificially produced hormones that are the ... these is testosterone (say: tes-TOSS-tuh-rone). Anabolic steroids can be taken in the form of ...

  12. Risk factors for ovarian cancer: an overview with emphasis on hormonal factors.

    PubMed

    Salehi, Fariba; Dunfield, Lesley; Phillips, Karen P; Krewski, Daniel; Vanderhyden, Barbara C

    2008-03-01

    Ovarian cancer is the fifth most frequently occurring cancer among women and leading cause of gynecological cancer deaths in North America. Although the etiology of ovarian cancer is not clear, certain factors are implicated in the etiology of this disease, such as ovulation, gonadotropic and steroid hormones, germ cell depletion, oncogenes and tumor suppressor genes, growth factors, cytokines, and environmental agents. Family history of breast or ovarian cancer is a prominent risk factor for ovarian cancer, with 5-10% of ovarian cancers due to heritable risk. Reproductive factors such as age at menopause and infertility contribute to greater risk of ovarian cancer, whereas pregnancy, tubal ligation, and hysterectomy reduce risk. Oral contraceptive (OC) use has clearly been shown to be protective against ovarian cancer. In contrast, large epidemiologic studies found hormone replacement therapy (HRT) to be a greater risk factor for ovarian cancer. The marked influence of hormones and reproductive factors on ovarian cancer suggests that endocrine disrupters may impact risk; however, there is a notable lack of research in this area. Lifestyle factors such as cigarette smoking, obesity, and diet may affect ovarian cancer risk. Exposure to certain environmental agents such as talc, pesticides, and herbicides may increase risk of ovarian cancer; however, these studies are limited. Further research is needed to strengthen the database of information from which an assessment of environmental and toxicological risk factors for ovarian cancer can be made.

  13. Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective

    PubMed Central

    2012-01-01

    This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABAA receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of

  14. Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective.

    PubMed

    Mahesh, Virendra B

    2012-01-01

    This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABA(A) receptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of

  15. Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice.

    PubMed

    Ezoe, Kenji; Daikoku, Takiko; Yabuuchi, Akiko; Murata, Nana; Kawano, Hiroomi; Abe, Takashi; Okuno, Takashi; Kobayashi, Tamotsu; Kato, Keiichi

    2014-11-01

    Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear. In this study, we first demonstrated that ovarian stimulation using hCG alone impairs implantation, decidualization and fetal development of mice by generating abnormal ovarian hormone levels. We also showed that ovarian hormone levels were altered because of changes in the levels of the enzymes involved in their synthesis in the follicles and corpora lutea. Furthermore, we determined that anomalous ovarian hormone secretion induced by ovarian stimulation alters the spatiotemporal expression of progesterone receptors and their downstream genes, especially in the uterine epithelium. Epithelial estrogenic signaling and cell proliferation were promoted on the day of implantation in stimulated mice and these changes led to the failure of uterine transition from the prereceptive to the receptive state. Collectively, our findings indicate that ovarian stimulation using hCG induces an imbalance in steroid hormone secretion, which causes a failure of the development of uterine receptivity and subsequent implantation and decidualization by altering the expression of steroid receptors and their downstream signaling associated with embryo implantation.

  16. Accessory corpora lutea formation in pregnant Hokkaido sika deer (Cervus nippon yesoensis) investigated by examination of ovarian dynamics and steroid hormone concentrations

    PubMed Central

    YANAGAWA, Yojiro; MATSUURA, Yukiko; SUZUKI, Masatsugu; SAGA, Shin-ichi; OKUYAMA, Hideto; FUKUI, Daisuke; BANDO, Gen; NAGANO, Masashi; KATAGIRI, Seiji; TAKAHASHI, Yoshiyuki; TSUBOTA, Toshio

    2014-01-01

    Generally, sika deer conceive a single fetus, but approximately 80% of pregnant females have two corpora lutea (CLs). The function of the accessory CL (ACL) is unknown; moreover, the process of ACL formation is unclear, and understanding this is necessary to know its role. To elucidate the process of ACL formation, the ovarian dynamics of six adult Hokkaido sika deer females were examined ultrasonographically together with peripheral estradiol-17β and progesterone concentrations. ACLs formed in three females that conceived at the first estrus of the breeding season, but not in those females that conceived at the second estrus. After copulation, postconception ovulation of the dominant follicle of the first wave is induced by an increase in estradiol-17β, which leads to formation of an ACL. A relatively low concentration of progesterone after the first estrus of the breeding season is considered to be responsible for the increase in estradiol-17β after copulation. PMID:25482110

  17. Accessory corpora lutea formation in pregnant Hokkaido sika deer (Cervus nippon yesoensis) investigated by examination of ovarian dynamics and steroid hormone concentrations.

    PubMed

    Yanagawa, Yojiro; Matsuura, Yukiko; Suzuki, Masatsugu; Saga, Shin-Ichi; Okuyama, Hideto; Fukui, Daisuke; Bando, Gen; Nagano, Masashi; Katagiri, Seiji; Takahashi, Yoshiyuki; Tsubota, Toshio

    2015-01-01

    Generally, sika deer conceive a single fetus, but approximately 80% of pregnant females have two corpora lutea (CLs). The function of the accessory CL (ACL) is unknown; moreover, the process of ACL formation is unclear, and understanding this is necessary to know its role. To elucidate the process of ACL formation, the ovarian dynamics of six adult Hokkaido sika deer females were examined ultrasonographically together with peripheral estradiol-17β and progesterone concentrations. ACLs formed in three females that conceived at the first estrus of the breeding season, but not in those females that conceived at the second estrus. After copulation, postconception ovulation of the dominant follicle of the first wave is induced by an increase in estradiol-17β, which leads to formation of an ACL. A relatively low concentration of progesterone after the first estrus of the breeding season is considered to be responsible for the increase in estradiol-17β after copulation.

  18. Brassinosteroids. Plant counterparts to animal steroid hormones?

    PubMed

    Clouse, Steven D

    2002-01-01

    Brassinosteroids are polyhydroxylated derivatives of common plant membrane sterols such as campesterol. They occur throughout the plant kingdom and have been shown by genetic and biochemical analyses to be essential for normal plant growth and development. Numerous reviews have detailed the recent progress in our understanding of the biosynthesis, physiological responses, and molecular modes of action of brassinosteroids. It is clear that like their animal steroid counterparts, brassinosteroids have a defined receptor, can regulate the expression of specific genes, and can orchestrate complex physiological responses involved in growth. This review summarizes the current status of BR research, pointing out where appropriate the similarities and differences between the mechanism of action of brassinosteroids and the more thoroughly studied animal steroid hormones.

  19. Minireview: Nuclear Receptor-Controlled Steroid Hormone Synthesis and Metabolism

    PubMed Central

    He, Jinhan; Cheng, Qiuqiong; Xie, Wen

    2010-01-01

    Steroid hormones are essential in normal physiology whereas disruptions in hormonal homeostasis represent an important etiological factor for many human diseases. Steroid hormones exert most of their functions through the binding and activation of nuclear hormone receptors (NRs or NHRs), a superfamily of DNA-binding and often ligand-dependent transcription factors. In recent years, accumulating evidence has suggested that NRs can also regulate the biosynthesis and metabolism of steroid hormones. This review will focus on the recent progress in our understanding of the regulatory role of NRs in hormonal homeostasis and the implications of this regulation in physiology and diseases. PMID:19762543

  20. Endometriosis as a model for inflammation-hormone interactions in ovarian and breast cancers.

    PubMed

    Ness, Roberta B; Modugno, Francesmary

    2006-04-01

    Chronic inflammation has been implicated in a variety of cancers. In this review, we consider associations between endometriosis and cancers both local (ovarian) and distant (breast). We review the epidemiological data linking endometriosis to ovarian and breast cancers. We then consider evidence for a role for sex steroid hormones and for inflammation in the aetiology of each of these cancers. Finally, we consider that endometriosis may promote alterations in sex steroid hormones and inflammatory mediators. A possible explanation for the association between endometriosis and these reproductive cancers may then be local and systemic enhancement of aberrant inflammatory and hormonal mediators. If this hypothesis is true, endometriosis may need to be considered as a risk factor for ovarian and breast cancers, triggering increasingly intensive surveillance. Moreover, treatments for endometriosis may require consideration of the impact on long-term cancer risk.

  1. Ovarian activity in the scimitar-horned oryx (Oryx dammah) determined by faecal steroid analysis.

    PubMed

    Morrow, C J; Monfort, S L

    1998-10-01

    Ultrasonography and radioimmunoassay (RIA) of serum oestradiol-17beta, luteinizing hormone (LH) and progesterone, and faecal oestrogen and progestin was used to assess ovarian activity in the scimitar-horned oryx (Oryx dammah). Ovarian examination using ultrasonography revealed maximal follicle and corpus luteum (CL) diameters of 15 and 32 mm, respectively. Steroid hormone metabolite distribution among individual faecal pellets within the same defaecation was relatively homogeneous with coefficients of variation averaging 10.2+/-1.8% and 16.2+/-4.6% for oestrogens and progestins, respectively. Elevated faecal oestrogen concentrations were associated with large (> 10 mm) antral follicles detected by ultrasonography. Periovulatory peaks in faecal oestrogen excretion, coincident with nadirs in progestin excretion, were detected in three females. Faecal progestin excretion exhibited a similar temporal pattern to serum progesterone concentrations, with a time lag of approximately 16 h. Faecal progestin concentrations corresponded with the presence of functional CL and proved useful for monitoring luteal function, spontaneous and prostaglandin-F2alpha analogue-induced luteolysis and anovulation. In summary, faecal steroid monitoring is a practical, noninvasive method for characterising ovarian steroid excretion and has potential for facilitating the application of assisted reproductive technologies in scimitar-horned oryx.

  2. Regulation of rat ovarian cell growth and steroid secretion

    PubMed Central

    Johnson, CC; Dawson, WE; Turner, JT; Wyche, JH

    1980-01-01

    A cultured rat ovarian cell line (31 A-F(2)) was used to study the effect of growth factors (epidermal growth factor [EGF] and fibroblast growth factor [FGF]), a survival factor (ovarian growth factor [OGF]), a hormone (insulin), and an iron-binding protein (transferring) on cell proliferation and steroid production under defined culture conditions. EGF and insulin were shown to be mitogenic (half-maximal response at 0.12 nM and 0.11 muM, respectively) for 31A-F(2) cells incubated in serum-free medium. EGF induced up to three doublings in the cell population, whereas insulin induced an average of one cell population doubling. FGF, OGF, and transferrin were found not to have any prominent effect on cell division when incubated individually with 31A-F(2) cells in serum-free medium. However, a combination of EGF, OGF, insulin, and transferrin stimulated cell division to the same approximate extent as cells incubated in the presence of 5 percent fetal calf serum. EGF or insulin did not significantly affect total cell cholesterol levels (relative to cells incubated in serum-free medium) when incubated individually with 31A-F(2) cells. However, cell cholesterol levels were increased by the addition of OGF (250 percent), FGF (370 percent), or a combination of insulin and EGF (320 percent). Progesterone secretion from 31A-F(2) cells was enhanced by EGF (25 percent), FGF (80 percent), and insulin (115 percent). However, the addition of a mitogenic mixture of EGF, OGF, insulin, and transferrin suppressed progesterone secretion 150 percent) below that of control cultures. These studies have permitted us to determine that EGF and insulin are mitogenic factors that are required for the growth of 31A-F(2) cells and that OGF and transferrin are positive cofactors that enhance growth. Also, additional data suggest that cholesterol and progesterone production in 31A-F(2) cells can be regulated by peptide growth factors and the hormone insulin. PMID:6995465

  3. Overlapping nongenomic and genomic actions of thyroid hormone and steroids

    PubMed Central

    Hammes, Stephen R.; Davis, Paul J.

    2016-01-01

    The genomic actions of thyroid hormone and steroids depend upon primary interactions of the hormones with their specific nuclear receptor proteins. Formation of nuclear co-activator or co-repressor complexes involving the liganded receptors subsequently result in transcriptional events—either activation or suppression—at genes that are specific targets of thyroid hormone or steroids. Nongenomic actions of thyroid hormone and steroids are in contrast initiated at binding sites on the plasma membrane or in cytoplasm or organelles and do not primarily require formation of intranuclear receptor protein-hormone complexes. Importantly, hormonal actions that begin nongenomically outside the nucleus often culminate in changes in nuclear transcriptional events that are regulated by both traditional intranuclear receptors as well as other nuclear transcription factors. In the case of thyroid hormone, the extranuclear receptor can be the classical “nuclear” thyroid receptor (TR), a TR isoform, or integrin αvβ3. In the case of steroid hormones, the membrane receptor is usually, but not always, the classical “nuclear” steroid receptor. This concept defines the paradigm of overlapping nongenomic and genomic hormone mechanisms of action. Here we review some examples of how extranuclear signaling by thyroid hormone and by estrogens and androgens modulates intranuclear hormone signaling to regulate a number of vital biological processes both in normal physiology and in cancer progression. We also point out that nongenomic actions of thyroid hormone may mimic effects of estrogen in certain tumors. PMID:26303085

  4. Steroid hormone receptors in cancer development: a target for cancer therapeutics.

    PubMed

    Ahmad, Nihal; Kumar, Raj

    2011-01-01

    The steroid hormone receptors (SHRs) are ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. SHRs pass signals from a steroid/hormone to the target genes by interacting with specific response element DNA sequences and various coregulatory proteins that consists of activators and/or corepressors. Disruptions in physiological functions of SHRs leads to several types of malignancies such as breast cancer, leukemia and lymphoma, prostate cancer, ovarian cancer, and lung cancer among others. Steroids/hormones/SHRs and their coregulators have opened up a unique window for novel steroid-based targeted therapies for cancer. Thus, dysregulation of SHR signaling in cancers compared with normal tissues can be exploited to target drugs that prevent and treat human cancers. In recent years, hormonal therapy has made a major contribution to the treatment of several cancers including reduced recurrence rates and longer survival rates. Development of various steroid receptor modulators and their potential therapeutic efficacies has provided us a great opportunity to effectively manage diseases like cancer in future. In this review article, we have summarized up-to-date knowledge of the role of SHRs in the development and progression of cancers, and potential endocrine-based therapeutic approaches to tackle these diseases.

  5. Organized for sex – steroid hormones and the developing hypothalamus

    PubMed Central

    Lenz, Kathryn M.; McCarthy, Margaret M.

    2017-01-01

    Steroid hormones of gonadal origin act on the neonatal brain, particularly the hypothalamus, to produce sex differences that underlie copulatory behavior. Neuroanatomical sex differences include regional volume, cell number, connectivity, morphology, physiology, neurotransmitter phenotype and molecular signaling, all of which are determined by the action of steroid hormones, particularly by estradiol in males, and are established by diverse downstream effects. Sex differences in distinct hypothalamic regions can be organized by the same steroid hormone, but the direction of a sex difference is often specific to one region or cell type, illustrating the wide range of effects that steroid hormones have on the developing brain. Substantial progress has been made in elucidating the downstream mechanisms through which gonadal hormones sexually differentiate the brain, but gaps remain in establishing the precise relationship between changes in neuronal morphology and behavior. A complete understanding of sexual differentiation will require integrating the diverse mechanisms across multiple brain regions into a functional network that regulates behavioral output. PMID:21143664

  6. Fifty years ago: the quest for steroid hormone receptors.

    PubMed

    Rousseau, Guy G

    2013-08-15

    In 1963 Peter Karlson put forward the revolutionary "hormone-gene" hypothesis, which would change drastically the way in which steroid hormones were thought to act at the time. From a historical perspective, this review relates the acceptance of this initially controversial idea, the discovery of the steroid receptors and the key experiments that have led to the current understanding of the mechanism of steroid hormone action. It shows how, over 50years, the field has widened beyond all expectation and has contributed to major advances not only in endocrinology, but also in molecular biology, pharmacology and therapeutics. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Steroid hormones as biomarkers of endocrine disruption in wildlife

    SciTech Connect

    Guillette, L.J. Jr.; Rooney, A.A.; Crain, D.A.; Orlando, E.F.

    1999-07-01

    Xenobiotic compounds introduced into the environment by human activity have been shown to adversely affect the endocrine system of wildlife. Various species exhibit abnormalities of (1) plasma sex steroid hormones, (2) altered steroid synthesis form the gonad in vitro and (3) altered steroidogenic enzyme function. These endpoints are sensitive and relatively easy to measure quantitatively with reliability and precision. These observations have led to the conclusion that sex steroid hormones could be markers of exposure to, and altered function from, endocrine disrupting contaminants (EDCs). However, there are serious limitations in the use of steroid hormones as generalized markers of EDC exposure. Steroid hormones exhibit seasonal, ontogenetic, gender and species-specific variation. Moreover, the regulation of sex steroid plasma concentrations is a relatively complex phenomenon capable of short-term (minutes-hours) alteration due to environmental inputs, such as acute stress--an activational response. Alterations in steroids synthesis and degradation also can be a response to altered embryonic development due to EDC exposure--an organizational response. If steroid hormones are to be used as biomarkers, then closely controlled, well designed sampling has to be performed. Additionally, an appreciation of the variation possible in endocrine responses among the species to be studied must be obtained.

  8. Plasma steroid hormone concentrations and blood flow of the ovarian structures of the female dromedary (Camelus dromedarius) during growth, dominance, spontaneous ovulation, luteinization and regression of the follicular wave.

    PubMed

    Rawy, M S; Derar, R I; El-Sherry, T M; Megahed, G A

    2014-08-01

    The objectives of this study were to investigate the ovarian follicular waves and their corresponding hormonal changes in she-camels and to elucidate blood perfusion of the ovarian structures. Three reproductively sound, non-pregnant female camels were examined daily using B-mode and color Doppler to detect changes in their ovarian structures and blood vasculature for 22 follicular waves. Blood area (BA) and percentage (BA%) were determined for the ovarian structures. Three phases of follicular development, those of growth, maturation, and regression, were observed during each follicular wave. Deviation occurred on Day 6.1±1.08. Estradiol increased from basal levels of 27.4±0.4pg/ml to peak concentrations of 134.4±47.5pg/ml as the follicle reached a diameter of 13.2mm. Peripheral progesterone concentrations remained low (<0.4ng/ml) throughout the follicular waves. The blood flow to the dominant follicles increased gradually with follicular growth. The BA and BA% reached the maximum values of 18.4±11.6mm(2) and 6.04±2.03%, respectively, when the diameter of the dominant follicle was 17.5±3.4mm. The blood flow to the corpus luteum rose markedly after ovulation to reach a maximum BA% and BA at Days 5 and 7, respectively, post ovulation. In conclusion, the follicular wave pattern in dromedaries consists of individually variable periods of growth, maturation and regression. Deviation occurs 6.1±1.08d from emergence. Transrectal color-Doppler sonography is a useful technique for noninvasive evaluation of follicular vascularity in camels during various stages of the follicular wave. It provides additional information to assess the developmental stage and activity of the ovarian structures.

  9. Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer

    PubMed Central

    Schock, Helena; Surcel, Heljä-Marja; Zeleniuch-Jacquotte, Anne; Grankvist, Kjell; Lakso, Hans-Åke; Fortner, Renée Turzanski; Kaaks, Rudolf; Pukkala, Eero; Lehtinen, Matti; Toniolo, Paolo; Lundin, Eva

    2014-01-01

    Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited prior studies have evaluated circulating androgens and risk of EOC, and estrogens and progesterone have been investigated in only one prior study. Further, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histologic subgroup. Therefore, we conducted a nested case-control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations with the histologic subtypes of EOC. We identified 1,052 EOC cases among cohort members diagnosed after recruitment (1975-2008) and before March 2011. Up to three controls were individually matched to each case (n=2,694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol, and sex hormone-binding globulin were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals [CI]. Associations between hormones and EOC differed by tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors, however, doubling of testosterone and 17-OHP concentration was associated with ~40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% risk increase for mucinous tumors. Risk of endometrioid tumors increased with higher estradiol concentrations (OR: 1.89 [1.20-2.98]). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries. PMID:25270324

  10. Hormonal and histologic findings in human cryopreserved ovarian autografts.

    PubMed

    Dittrich, Ralf; Mueller, Andreas; Maltaris, Theodoros; Hoffmann, Inge; Magener, Achim; Oppelt, Patricia G; Beckmann, Matthias W

    2009-04-01

    This is the first report showing a hormonal and histologic discrepancy in cryopreserved human ovarian tissue 11 months after orthotopic autotransplantation. The presence of antral follicles was observed although the hormonal values had returned to castrated levels.

  11. Relationships between plasma concentrations of sex steroid hormones and gonadal development in the brown hagfish, Paramyxine atami.

    PubMed

    Nishiyama, Maki; Chiba, Hiroaki; Uchida, Katsuhisa; Shimotani, Toyokazu; Nozaki, Masumi

    2013-11-01

    The relationship between sex steroid hormone profiles in plasma and gonadal function in hagfish is poorly understood. In the present study, plasma concentrations of estradiol, testosterone, and progesterone were examined with respect to gonadal development, sexual differences, and possible function of atretic follicles in the brown hagfish, Paramyxine atami, using a time-resolved fluoroimmunoassay. Plasma concentrations of these three hormones were low in juveniles of both sexes. In females, plasma estradiol showed a significant correlation with ovarian development, with the highest concentrations in late vitellogenic adults. Plasma testosterone and progesterone also increased significantly in non-vitellogenic adult females; however, plasma testosterone showed no significant differences among adult females at different ovarian developments, while plasma progesterone was significantly lower in late vitellogenic adults than it was in non-vitellogenic adults. Vitellogenic females that possessed atretic follicles showed significantly lower concentrations of all three hormones than females that only possessed normal follicles. In males, no significant differences were found in plasma estradiol or testosterone levels among groups of different developmental stages of the testis, while plasma progesterone showed a clear inverse relationship with testicular development. Thus, differences were found in plasma sex steroid hormone profiles between male and female P. atami. Moreover, plasma estradiol showed a significant correlation with ovarian development, which suggests that estradiol is involved in the regulation of ovarian development. The present study also revealed that steroid hormone production was strongly suppressed in females that possessed atretic follicles in their ovaries.

  12. Symptomatic Ovarian Steroid Cell Tumor not Otherwise Specified in a Post-Menopausal Woman

    PubMed Central

    Sood, Neha; Desai, Kaniksha; Chindris, Ana-Maria; Lewis, Jason; Dinh, Tri A.

    2016-01-01

    Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging. PMID:27441075

  13. Anxiolytic effect of music depends on ovarian steroid in female mice.

    PubMed

    Chikahisa, Sachiko; Sano, Atsuko; Kitaoka, Kazuyoshi; Miyamoto, Ken-Ichi; Sei, Hiroyoshi

    2007-04-16

    Music is known to be able to elicit emotional changes, including anxiolytic effects. The gonadal steroid hormones estradiol and progesterone have also been reported to play important roles in the modulation of anxiety. In the present study, we examined whether the effect of music on anxiety is related to ovarian steroid in female mice. Behavioral paradigms measuring anxiety were tested in gonadally intact (SHAM) and ovariectomized (OVX) female mice chronically treated with either placebo (OVX/Placebo), 17beta-estradiol (OVX/E), or progesterone (OVX/P). In the elevated plus maze, light-dark transition, and marble burying tests, SHAM and OVX/P mice exposed to music showed less anxiety than those exposed to white noise or silence while OVX/placebo mice did not show these effects at all. OVX/E mice showed the anxiolytic effect of music only in the marble burying test. Furthermore, pretreatment with progesterone's metabolite inhibitor completely prevented the anxiolytic effect of music in behavioral tests, while pretreatment with a progesterone receptor blocker did not prevent the anxiolytic effect of music. These results suggest that exposure to music reduces anxiety levels, and ovarian steroids, mainly progesterone, may be involved in the anxiolytic effect of music observed in female mice.

  14. The Interaction between Steroid Hormones and Lipid Monolayers on Water

    PubMed Central

    Gershfeld, N. L.; Muramatsu, M.

    1971-01-01

    The interaction of progesterone, testosterone, androsterone, and etiocholanolone with insoluble lipid films (cholesterol and saturated hydrocarbons containing either alcohol, ester, acetamide, phosphate, amine, or carboxyl groups) was studied. In addition to surface pressure and surface potential measurements of the surface films, radioactive tracers were used to measure the concentration of adsorbed steroid in the lipid films. In general, steroids form mixed films with the insoluble lipid films. Compression of the insoluble lipid films to their most condensed state leads to complete ejection of adsorbed steroid from the surface in all cases except with the amine, for which a small amount of steroid is still retained in the surface. Interactions between the steroids and insoluble lipids are primarily due to van der Waals or dispersion forces; there were no significant contributions from dipole-dipole interactions (except possibly with the amine). Specific interactions between cholesterol and the soluble steroids were not observed. Evidence suggests that low steroid concentrations influence structure of lipid films by altering the hydration layer in the surface film. In contrast to a specific site of action, it is proposed that steroid hormones initiate structural changes in a variety of biological sites; this model of steroid action is consistent with the ubiquity of many steroid hormones. PMID:5120392

  15. Advances in bioanalytical techniques to measure steroid hormones in serum.

    PubMed

    French, Deborah

    2016-06-01

    Steroid hormones are measured clinically to determine if a patient has a pathological process occurring in the adrenal gland, or other hormone responsive organs. They are very similar in structure making them analytically challenging to measure. Additionally, these hormones have vast concentration differences in human serum adding to the measurement complexity. GC-MS was the gold standard methodology used to measure steroid hormones clinically, followed by radioimmunoassay, but that was replaced by immunoassay due to ease of use. LC-MS/MS has now become a popular alternative owing to simplified sample preparation than for GC-MS and increased specificity and sensitivity over immunoassay. This review will discuss these methodologies and some new developments that could simplify and improve steroid hormone analysis in serum.

  16. Ovarian hormones and oral health: pregnancy gingivitis.

    PubMed

    Zachariasen, R D

    1989-09-01

    The most common oral manifestation of increased levels of ovarian hormones is an increase in gingival inflammation with an accompanying increase in gingival exudate. Although plaque has been identified as the major etiologic agent of gingivitis, there are a number of known situations that exacerbate the condition. It is well-documented that pregnancy, puberty, menstrual cycle, and oral contraceptives all have been coupled with transient, self-limiting periods of gingivitis. A common feature these conditions share is an elevation in the plasma concentration of estrogens and progestins. This article will review the basic physiology of the estrogens and progestins and discuss the possible role these hormones play in the gingivitis occurring during pregnancy or oral contraceptive usage.

  17. [The effect of steroid hormone doses after ovariectomy on the peripheral hormone processes and uterine development in gilts. 2. Effects on gilts during early pregnancy].

    PubMed

    Lampe, B; Schneider, F; Brüssow, K P; Blödow, G; Wollenhaupt, K; Spitschak, K; Hühn, U

    1990-01-01

    Experimental studies were conducted into ovariectomized pregnant gilts to establish effects of exogenic hormone administration, with endogenic ovarian steroids excluded, upon uterus and fetus development as well as on hormone levels in blood plasma, endometrium, and allantoic fluid. Hormone concentrations in blood plasma were found to depend clearly on hormone doses applied after ovariectomy to preserve pregnancy. 2 to 3 weeks of smooth gravidity, following ovariectomy, were ensured on the 6th or 14th day after KB1 by daily application of very low doses of progesterone only (80 mg) or in combination with estrogens, the ratio being 480:1.

  18. CMKLR1 deficiency maintains ovarian steroid production in mice treated chronically with dihydrotestosterone

    PubMed Central

    Tang, Mi; Huang, Chen; Wang, Yu-Fei; Ren, Pei-Gen; Chen, Li; Xiao, Tian-Xia; Wang, Bao-Bei; Pan, Yan-Fei; Tsang, Benjamin K.; Zabel, Brian A; Ma, Bao-Hua; Zhao, Hui-Ying; Zhang, Jian V.

    2016-01-01

    Elevated serum chemerin levels correlate with increased severity of polycystic ovary syndrome (PCOS). However, the role of CMKLR1 signaling in ovarian biology under conditions of excess DHT remains unclear. In this study we compared the effects of continuous 90-day high dose DHT exposure (83.3 □g/day) on wild type and CMKLR1-deficient mice. DHT induced PCOS-like clinical signs in wild type mice as well as significant changes in the expression of hormone receptors, steroid synthesis enzymes, and BMPs and their receptors. In contrast, CMKLR1-deficient mice significantly attenuated DHT-induced clinical signs of PCOS and alterations in ovarian gene expression. To determine whether the BMP4 signaling pathway was involved in the pathogenic effects of CMKLR1 signaling in DHT-induced ovarian steroidogenesis, antral follicles were isolated from wild type and CMKLR1 knockout (KO) mice and treated in vitro with combinations of hCG, DHT, and BMP4 inhibitors. BMP4 inhibition attenuated the induction effects of hCG and DHT on estrogen and progesterone secretion in CMKLR1 KO mice, but not in WT mice, implicating the BMP4 signaling pathway in the CMKLR1-dependent response to DHT. In conclusion, CMKLR1 gene deletion attenuates the effects of chronic DHT treatment on ovarian function in experimental PCOS, likely via BMP4 signaling. PMID:26893072

  19. Steroid Hormone Analysis by Tandem Mass Spectrometry

    PubMed Central

    Soldin, Steven J.; Soldin, Offie P.

    2013-01-01

    BACKGROUND New high-performance liquid chromatography/ tandem mass spectrometry (LC-MS/MS) methods are among the most successful approaches to improve specificity problems inherent in many immunoassays. CONTENT We emphasize problems with immunoassays for the measurement of steroids and review the emerging role of LC-MS/MS in the measurement of clinically relevant steroids. The latest generation of tandem mass spectrometers has superior limits of quantification, permitting omission of previously employed derivatization steps. The measurement of steroid profiles in the diagnosis and treatment of congenital adrenal hyperplasia, adrenal insufficiency, chronic pelvic pain and prostatitis, oncology (breast cancer), and athletes has important new applications. CONCLUSIONS LC-MS/MS now affords the specificity, imprecision, and limits of quantification necessary for the reliable measurement of steroids in human fluids, enhancing diagnostic capabilities, particularly when steroid profiles are available. PMID:19325015

  20. Steroid Hormones and Uterine Vascular Adaptation to Pregnancy

    PubMed Central

    Chang, Katherine; Zhang, Lubo

    2008-01-01

    Pregnancy is a physiological state that involves a significant decrease in uterine vascular tone and an increase in uterine blood flow, which is mediated in part by steroid hormones, including estrogen, progesterone, and cortisol. Previous studies have demonstrated the involvement of these hormones in the regulation of uterine artery contractility through signaling pathways specific to the endothelium and the vascular smooth muscle. Alterations in endothelial nitric oxide synthase expression and activity, nitric oxide production, and expression of enzymes involved in PGI2 production contribute to the uterine artery endothelium-specific responses. Steroid hormones also have an effect on calcium-activated potassium channel activity, PKC signaling pathway and myogenic tone, and alterations in pharmacomechanical coupling in the uterine artery smooth muscle. This review addresses current understanding of the molecular mechanisms by which steroid hormones including estrogen, progesterone, and cortisol modulate uterine artery contractility to alter uterine blood flow during pregnancy with an emphasis on the pregnant ewe model. PMID:18497342

  1. Steroid hormones, stress and the adolescent brain: a comparative perspective.

    PubMed

    Brown, G R; Spencer, K A

    2013-09-26

    Steroid hormones, including those produced by the gonads and the adrenal glands, are known to influence brain development during sensitive periods of life. Until recently, most brain organisation was assumed to take place during early stages of development, with relatively little neurogenesis or brain re-organisation during later stages. However, an increasing body of research has shown that the developing brain is also sensitive to steroid hormone exposure during adolescence (broadly defined as the period from nutritional independence to sexual maturity). In this review, we examine how steroid hormones that are produced by the gonads and adrenal glands vary across the lifespan in a range of mammalian and bird species, and we summarise the evidence that steroid hormone exposure influences behavioural and brain development during early stages of life and during adolescence in these two taxonomic groups. Taking a cross-species, comparative perspective reveals that the effects of early exposure to steroid hormones depend upon the stage of development at birth or hatching, as measured along the altricial-precocial dimension. We then review the evidence that exposure to stress during adolescence impacts upon the developing neuroendocrine systems, the brain and behaviour. Current research suggests that the effects of adolescent stress vary depending upon the sex of the individual and type of stressor, and the effects of stress could involve several neural systems, including the serotonergic and dopaminergic systems. Experience of stressors during adolescence could also influence brain development via the close interactions between the stress hormone and gonadal hormone axes. While sensitivity of the brain to steroid hormones during early life and adolescence potentially leaves the developing organism vulnerable to external adversities, developmental plasticity also provides an opportunity for the developing organism to respond to current circumstances and for behavioural

  2. Albumin, steroid hormones and the origin of vertebrates.

    PubMed

    Baker, M E

    2002-10-01

    Albumin, the major serum protein, binds a wide variety of lipophilic compounds including steroids, other lipophilic hormones and various phytochemicals and xenobiotics that bind to receptors for steroids and other lipophilic hormones. Despite albumin's low affinity (K(d) approximately 10(-4) M to 10(-6) M) for these lipophilic compounds, the high concentration of albumin in serum makes this protein a major carrier of steroids and lipophilic hormones and a regulator of their access to receptors. Albumin also functions as a sink for xenobiotics, diminishing the binding of xenobiotics to hormone receptors and other cellular proteins. This protects animals from endocrine disruption by xenobiotics. We propose that these properties of albumin were important in protochordates and primitive vertebrates, such as jawless fish, about 600 to 530 million years ago, just before and during the Cambrian period. It is at that time that the ancestral receptors of adrenal and sex steroids - androgens, estrogens, glucocorticoids, mineralocorticoids, and progestins - arose in multicellular animals. Albumin regulated access of steroids to their receptors, as well as protecting animals from endocrine disruptors, such as phytochemicals, fungal chemicals and phenolics, and other chemicals formed at hydrothermal vents by geochemical processes. Thus, animals in which albumin expression was high had a selective advantage in regulating the steroid response and avoiding endocrine disruption by xenobiotics.

  3. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action

    PubMed Central

    2016-01-01

    Biologically active steroids are transported in the blood by albumin, sex hormone-binding globulin (SHBG), and corticosteroid-binding globulin (CBG). These plasma proteins also regulate the non-protein-bound or ‘free’ fractions of circulating steroid hormones that are considered to be biologically active; as such, they can be viewed as the ‘primary gatekeepers of steroid action’. Albumin binds steroids with limited specificity and low affinity, but its high concentration in blood buffers major fluctuations in steroid concentrations and their free fractions. By contrast, SHBG and CBG play much more dynamic roles in controlling steroid access to target tissues and cells. They bind steroids with high (~nM) affinity and specificity, with SHBG binding androgens and estrogens and CBG binding glucocorticoids and progesterone. Both are glycoproteins that are structurally unrelated, and they function in different ways that extend beyond their transportation or buffering functions in the blood. Plasma SHBG and CBG production by the liver varies during development and different physiological or pathophysiological conditions, and abnormalities in the plasma levels of SHBG and CBG or their abilities to bind steroids are associated with a variety of pathologies. Understanding how the unique structures of SHBG and CBG determine their specialized functions, how changes in their plasma levels are controlled, and how they function outside the blood circulation provides insight into how they control the freedom of steroids to act in health and disease. PMID:27113851

  4. Overlapping nongenomic and genomic actions of thyroid hormone and steroids.

    PubMed

    Davis, Paul J; Lin, Hung-Yun; Mousa, Shaker A; Luidens, Mary K; Hercbergs, Aleck A; Wehling, Martin; Davis, Faith B

    2011-08-01

    Nuclear receptors for thyroid hormone and steroids are members of a receptor superfamily with similar molecular organization, but discrete transcriptional functions that define genomic actions of these nonpeptide hormones. Nongenomic actions of thyroid hormone and estrogens and androgens are initiated outside the nucleus, at receptors in the plasma membrane or in cytoplasm; these actions are largely regarded to be unique to the respective hormones. However, there is an increasing number of descriptions of overlapping nongenomic and genomic effects of thyroid hormone and estrogens and testosterone. These effects are concentrated in tumor cells, where, for example, estrogens and thyroid hormone have similar mitogen-activate protein kinase (MAPK)-dependent proliferative actions on ERα-positive human breast cancer cells, and where dihydrotestosterone also can stimulate proliferation. Steroids and thyroid hormone have similar anti-apoptotic effects in certain tumors. But thyroid hormone and steroids also have overlapping or interacting nongenomic and genomic actions in heart and brain cells. These various effects of thyroid hormone and estrogens and androgens are reviewed here and their possible clinical consequences are enumerated. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Steroid hormones control on nucleic acid biosynthesis in skeletal muscle.

    PubMed

    Burtea, C; Lefter, C; Butnaru, F; David, A

    1992-01-01

    The medical, agricultural and scientific interest of the muscular tissue is well established in the literature. Its formation and function are essential for survival. It is also known that steroid hormones are involved in the growth, development and maturation of skeletal muscles (sexual hormones) as well as in the process of body adjustment to the stress factors in the environment (glucocorticoid hormones). Starting from these considerations, our experiment has made an attempt to clarify part of the mechanisms involved in the action of steroid hormones at muscle level. On this purpose, 3H thymidine and 3H uridine incorporation was followed up in various types of skeletal muscles (femoral biceps, diaphragmatic, psoas) from rats treated with steroid hormones. Though known as anabolic hormones, sexual hormones did not induce significant and persistent changes in the nucleic acid synthesis (NAS), except for testosterone which enhanced RNA synthesis only in the level femoral muscle after 21 days of administration. Progesterone and the glucocorticoid hormones are known as hormones of proteic catabolism but it seems that this effect is more marked in muscles whose structure predominantly consists of white fibres (rapid muscles), as confirmed by our experiment.

  6. Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes

    PubMed Central

    SIVILS, JEFFREY C.; GONZALEZ, IVEN; BAIN, LISA J.

    2010-01-01

    The multidrug resistance-associated protein 1 (MRP1/ABCC1) is a member of the ABC active transporter family that can transport several steroid hormone conjugates, including 17β-estradiol glucuronide, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate. The present study investigated the role that MRP1 plays in maintaining proper hormone levels in the serum and testes. Serum and testicular steroid hormone levels were examined in both wild-type mice and Mrp1 null mice. Serum testosterone levels were reduced 5-fold in mice lacking Mrp1, while testicular androstenedione, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were significantly reduced by 1.7- to 4.5-fold in Mrp1 knockout mice. Investigating the mechanisms responsible for the reduction in steroid hormones in Mrp1-/- mice revealed no differences in the expression or activity of enzymes that inactivate steroids, the sulfotransferases or glucuronosyltransferases. However, steroid biosynthetic enzyme levels in the testes were altered. Cyp17 protein levels were increased by 1.6-fold, while Cyp17 activity using progesterone as a substrate was also increased by 1.4-2.0-fold in mice lacking Mrp1. Additionally, the ratio of 17β-hydroxysteroid dehydrogenase to 3β-hydroxysteroid dehydrogenase, and steroidogenic factor 1 to 3βhydroxysteroid dehydrogenase were significantly increased in the testes of Mrp1-/- mice. These results indicate that Mrp1-/- mice have lowered steroid hormones levels, and suggests that upregulation of steroid biosynthetic enzymes may be an attempt to maintain proper steroid hormone homeostasis. PMID:20178799

  7. Role of Sex Steroid Hormones in Bacterial-Host Interactions

    PubMed Central

    García-Gómez, Elizabeth; González-Pedrajo, Bertha; Camacho-Arroyo, Ignacio

    2013-01-01

    Sex steroid hormones play important physiological roles in reproductive and nonreproductive tissues, including immune cells. These hormones exert their functions by binding to either specific intracellular receptors that act as ligand-dependent transcription factors or membrane receptors that stimulate several signal transduction pathways. The elevated susceptibility of males to bacterial infections can be related to the usually lower immune responses presented in males as compared to females. This dimorphic sex difference is mainly due to the differential modulation of the immune system by sex steroid hormones through the control of proinflammatory and anti-inflammatory cytokines expression, as well as Toll-like receptors (TLRs) expression and antibody production. Besides, sex hormones can also affect the metabolism, growth, or virulence of pathogenic bacteria. In turn, pathogenic, microbiota, and environmental bacteria are able to metabolize and degrade steroid hormones and their related compounds. All these data suggest that sex steroid hormones play a key role in the modulation of bacterial-host interactions. PMID:23509808

  8. Negative regulation of parathyroid hormone-related protein expression by steroid hormones.

    PubMed

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-04-15

    Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  9. Aging influences steroid hormone release by mink ovaries and their response to leptin and IGF-I.

    PubMed

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karin; Harrath, Abdel Halim; Kotwica, Jan

    2016-01-21

    The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings) and old (3-5 years of age) minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml). We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a) reduction in basal progesterone release and (b) alterations in the response of estradiol but not of progesterone to leptin and IGF-I.

  10. Aging influences steroid hormone release by mink ovaries and their response to leptin and IGF-I

    PubMed Central

    Sirotkin, Alexander V.; Mertin, Dušan; Süvegová, Karin; Harrath, Abdel Halim; Kotwica, Jan

    2016-01-01

    ABSTRACT The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings) and old (3-5 years of age) minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml). We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a) reduction in basal progesterone release and (b) alterations in the response of estradiol but not of progesterone to leptin and IGF-I. PMID:26794607

  11. Introduction: Noncontraceptive use of steroid sex hormones in reproductive medicine.

    PubMed

    Barnhart, Kurt T

    2016-12-01

    The use of estrogens and progestins in reproductive medicine is widespread and has spanned decades. Often the effect is therapeutic, but sometimes its use has unintended consequences. In this Views and Reviews, old and new indications for the use of ovarian sex steroids are examined with attention to updating knowledge, breaking bad habits, and providing evidence for use (or nonuse). Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Stem cells with neurogenic potential and steroid hormones.

    PubMed

    Velasco, Iván

    2011-01-01

    Pluripotent and multipotent stem cells with differentiation potential to neural phenotypes have been described and characterized in the last decades. Embryonic stem cells, as well as neural stem cells from developing and adult nervous system, can differentiate into different types of neurons, astrocytes or oligodendrocytes. Although the initially identified actions of estradiol, progesterone and testosterone are related to sexual reproductive functions, recent evidence shows that these steroid hormones modulate development, physiology and survival of nerve cells. Furthermore, neurosteroids can be synthesized in the developing and adult nervous system. A description of the molecular modulatory actions of sex steroid hormones on the Central Nervous System is presented. The main focus of this review is to summarize the described effects of steroid hormones (progesterone, allopregnanolone, dehydroepiandrosterone, estradiol and androgens) on cell parameters relevant to stem cells, both in vitro and in vivo. The overall conclusion is that steroid hormones influence stem cell behavior by several mechanisms, namely regulation of gene expression by binding to their cognate receptors, activation of intracellular pathways involving kinases or intracellular calcium signaling, and modulation of receptors for neurotransmitters; in some instances, these hormones can substitute or modulate the action of growth factors, and also directly influence self-renewal, proliferation, differentiation or cell death of neurogenic stem cells.

  13. Negative regulation of parathyroid hormone-related protein expression by steroid hormones

    SciTech Connect

    Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

    2011-04-15

    Highlights: {yields} Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. {yields} Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. {yields} Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor {alpha}, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

  14. Occurrence and fate of hormone steroids in the environment.

    PubMed

    Yin, Guang-Guo; Kookana, Rai S; Ru, Ying-Jun

    2002-12-01

    Hormone steroids are a group of endocrine disruptors, which are excreted by humans and animals. In this paper, we briefly review the current knowledge on the fate of these steroids in the environment. Natural estrogenic steroids estrone (E1), 17beta-estradiol (E2) and estriol (E3) all have a solubility of approximately 13 mg/l, whereas synthetic steroids 17alpha-ethynylestradiol (EE2) and mestranol (MeEE2) have a solubility of 4.8 and 0.3 mg/l, respectively. These steroids have a moderate binding on sediments and are reported to degrade rapidly in soil and water. Estrogenic steroids have been detected in effluents of sewage treatment plants (STPs) in different countries at concentrations ranging up to 70 ng/l for E1, 64 ng/l for E2, 18 ng/l for E3 and 42 ng/l for EE2. E2 concentrations in river waters from Japan, Germany, Italy and the Netherlands ranged up to 27 ng/l. In addition, E2 concentrations ranging from 6 to 66 ng/l have also been measured in mantled karst aquifers in northwest Arkansas. This contamination of ground water has been associated with poultry litter and cattle manure waste applied on the land. Although hormone steroids have been detected at a number of sources worldwide, currently, there is limited data on the environmental behaviour and fate of these hormone steroids in different environmental media. Consequently, the exposure and risk associated with these chemicals are not adequately understood.

  15. Regulation of Steroid Hormone Biosynthesis by the Cytoskeleton

    PubMed Central

    Li, Donghui

    2009-01-01

    Steroid hormones are synthesized in response to signaling cascades initiated by the trophic peptide hormones derived from the anterior pituitary. The mechanisms by which these peptide hormones regulate steroid hormone production are multifaceted and include controlling the transcription of steroidogenic genes, regulating cholesterol (substrate) uptake and transport, modulating steroidogenic enzyme activity, and controlling electron availability. Cytoskeletal polymers such as microfilaments and microtubules have also been implicated in regulating steroidogenesis. Of note, steroidogenesis is a multi-step process that occurs in two organelles, the endoplasmic reticulum (ER) and the mitochondrion. However, the precise mechanism by which substrates are delivered back and forth between these two organelles is unknown. In this review we will discuss the role of components of the cytoskeleton in conferring optimal steroidogenic potential. Finally, we present data that identifying a novel mechanism by which sphingosine-1-phosphate induces mitochondrial trafficking to promote steroidogenesis. PMID:18726632

  16. Ovarian steroids alter mu opioid receptor trafficking in hippocampal parvalbumin GABAergic interneurons.

    PubMed

    Torres-Reveron, Annelyn; Williams, Tanya J; Chapleau, Jeanette D; Waters, Elizabeth M; McEwen, Bruce S; Drake, Carrie T; Milner, Teresa A

    2009-09-01

    The endogenous hippocampal opioid systems are implicated in learning associated with drug use. Recently, we showed that ovarian hormones regulate enkephalin levels in the mossy fiber pathway. This pathway overlaps with parvalbumin (PARV)-basket interneurons that contain the enkephalin-activated mu opioid receptors (MORs) and are important for controlling the "temporal timing" of granule cells. Here, we evaluated the influence of ovarian steroids on the trafficking of MORs in PARV interneurons. Two groups of female rats were analyzed: cycling rats in proestrus (relatively high estrogens) or diestrus; and ovariectomized rats euthanized 6, 24 or 72 h after estradiol benzoate (10 microg, s.c.) administration. Dorsal hippocampal sections were dually immunolabeled for MOR and PARV and examined by light and electron microscopy. As in males, in females MOR-immunoreactivity (-ir) was in numerous PARV-labeled perikarya, dendrites and terminals in the dentate hilar region. Variation in ovarian steroid levels altered the subcellular distribution of MORs in PARV-labeled dendrites but not terminals. In normal cycling rats, MOR-gold particles on the plasma membrane of small PARV-labeled dendrites (area <1 microm2) had higher density in proestrus rats than in diestrus rats. Likewise, in ovariectomized rats MORs showed higher density on the plasma membrane of small PARV-labeled dendrites 72 h after estradiol exposure. The number of PARV-labeled cells was not affected by estrous cycle phase or estrogen levels. These results demonstrate that estrogen levels positively regulate the availability of MORs on GABAergic interneurons in the dentate gyrus, suggesting cooperative interaction between opioids and estrogens in modulating principal cell excitability.

  17. Sex steroids and growth hormone interactions.

    PubMed

    Fernández-Pérez, Leandro; de Mirecki-Garrido, Mercedes; Guerra, Borja; Díaz, Mario; Díaz-Chico, Juan Carlos

    2016-04-01

    GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of sex hormones on the liver may be direct, through hepatic receptors, or indirect by modulating endocrine, metabolic, and gender-differentiated functions of GH. Sex hormones can modulate GH actions by acting centrally, regulating pituitary GH secretion, and peripherally, by modulating GH signaling pathways. The endocrine and/or metabolic consequences of long-term exposure to sex hormone-related compounds and their influence on the GH-liver axis are largely unknown. A better understanding of these interactions in physiological and pathological states will contribute to preserve health and to improve clinical management of patients with growth, developmental, and metabolic disorders. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  18. Hormone response in ovarian cancer: time to reconsider as a clinical target?

    PubMed Central

    Modugno, Francesmary; Laskey, Robin; Smith, Ashlee L; Andersen, Courtney L; Haluska, Paul; Oesterreich, Steffi

    2013-01-01

    Ovarian cancer is the sixth most common cancer worldwide among women in developed countries and the most lethal of all gynecologic malignancies. There is a critical need for the introduction of targeted therapies to improve outcome. Epidemiological evidence suggests a critical role for steroid hormones in ovarian tumorigenesis. There is also increasing evidence from in vitro studies that estrogen, progestin, and androgen regulate proliferation and invasion of epithelial ovarian cancer cells. Limited clinical trials have shown modest response rates; however, they have consistently identified a small subset of patients that respond very well to endocrine therapy with few side effects. We propose that it is timely to perform additional well-designed trials that should include biomarkers of response. PMID:23045324

  19. Towards the emerging crosstalk: ERBB family and steroid hormones.

    PubMed

    D'Uva, Gabriele; Lauriola, Mattia

    2016-02-01

    Growth factors acting through receptor tyrosine kinases (RTKs) of ERBB family, along with steroid hormones (SH) acting through nuclear receptors (NRs), are critical signalling mediators of cellular processes. Deregulations of ERBB and steroid hormone receptors are responsible for several diseases, including cancer, thus demonstrating the central role played by both systems. This review will summarize and shed light on an emerging crosstalk between these two important receptor families. How this mutual crosstalk is attained, such as through extensive genomic and non-genomic interactions, will be addressed. In light of recent studies, we will describe how steroid hormones are able to fine-tune ERBB feedback loops, thus impacting on cellular output and providing a new key for understanding the complexity of biological processes in physiological or pathological conditions. In our understanding, the interactions between steroid hormones and RTKs deserve further attention. A system biology approach and advanced technologies for the analysis of RTK-SH crosstalk could lead to major advancements in molecular medicine, providing the basis for new routes of pharmacological intervention in several diseases, including cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. [Clinical, hormonal and histological features in ovarian stromal hyperthecosis].

    PubMed

    Abuladze, M V; Sharabidze, N G

    2006-10-01

    The aim of our study was to investigate clinical, hormonal and histological features of ovarian stromal hyperthecosis We have studied 104 patients with a histological diagnosis of ovarian stromal hyperthecosis and hyperplasia. Analyzing the results we can conclude that clinical features of ovarian stromal hyperthecosis and hyperplasia with polycystic ovarian disease and without it were identical and characterised by virilization syndrome, disorders of menstrual cycle and reproductive function; metabolic and vegeto-vascular disorders; breast and endometrial hyperplasias, high blood level of testosterone . The histological study of ovarian stromal hyperthecosis has showed that superficial part of ovarian cortex is hypocellular and fibrotic, contains scattered follicles with few granulosa cells, luteinized internal theca cells, hyperplasia of deep cortex and medulla, corpus luteus is absent.

  1. Psychological, social, and spiritual effects of contraceptive steroid hormones

    PubMed Central

    Klaus, Hanna; Cortés, Manuel E.

    2015-01-01

    Governments and society have accepted and enthusiastically promoted contraception, especially contraceptive steroid hormones, as the means of assuring optimal timing and number of births, an undoubted health benefit, but they seldom advert to their limitations and side effects. This article reviews the literature on the psychological, social, and spiritual impact of contraceptive steroid use. While the widespread use of contraceptive steroid hormones has expanded life style and career choices for many women, their impact on the women's well-being, emotions, social relationships, and spirituality is seldom mentioned by advocates, and negative effects are often downplayed. When mentioned at all, depression and hypoactive sexual desire are usually treated symptomatically rather than discontinuing their most frequent pharmacological cause, the contraceptive. The rising incidence of premarital sex and cohabitation and decreased marriage rates parallel the use of contraceptive steroids as does decreased church attendance and/or reduced acceptance of Church teaching among Catholics. Lay summary: While there is wide, societal acceptance of hormonal contraceptives to space births, their physical side effects are often downplayed and their impact on emotions and life styles are largely unexamined. Coincidental to the use of “the pill” there has been an increase in depression, low sexual desire, “hook-ups,” cohabitation, delay of marriage and childbearing, and among Catholics, decreased church attendance and reduced religious practice. Fertility is not a disease. Birth spacing can be achieved by natural means, and the many undesirable effects of contraception avoided. PMID:26912936

  2. Hydroxylation and sulfation of sex steroid hormones in inflammatory liver.

    PubMed

    Lee, Sang R; Lee, Seung-Yeon; Kim, Sang-Yun; Ryu, Si-Yun; Park, Bae-Kuen; Hong, Eui-Ju

    2017-09-26

    Sex steroids, also known as gonadal steroids, are oxidized with hydroxylation by cytochrome P450, glucuronidation by UDP-glucuronosyltransferase, sulfation by sulfotransferase, andO-methylation by catechol O-methyltransferase. Thus, it is important to determine the process by which inflammation influences metabolism of gonadal hormones. Therefore, we investigated the mechanism of metabolic enzymes against high physiologic inflammatory responsein vivo to study their biochemical properties in liver diseases. In this study, C57BL/6N mice were induced with hepatic inflammation by diethylnitrosamine (DEN) exposure. We observed upregulation of Cyp19a1, Hsd17b1, Cyp1a1, Sult1e1 in the DEN-treated livers compared to the control-treated livers using real time PCR. Moreover, the increased Cyp19a1 and Hsd17b1 levels support the possibility that estrogen biosynthesis from androgens are accumulated during inflammatory liver diseases. Furthermore, the increased levels of Cyp1a1 and Cyp1b1 in the hydroxylation of estrogen facilitated the conversion of estrogen to 2- or 4-hydroxyestrogen, respectively. In addition, the substantial increase in the Sult1e1 enzyme levels could lead to sulfate conjugation of hydroxyestrogen. The present information supports the concept that inflammatory response can sequester sulfate conjugates from the endogenous steroid hormones and may suppress binding of sex steroid hormones to their receptors in the whole body.

  3. Changes in steroid hormones during an international powerlifting competition.

    PubMed

    Le Panse, Bénédicte; Labsy, Zakaria; Baillot, Aurélie; Vibarel-Rebot, Nancy; Parage, Gaston; Albrings, Detlev; Lasne, Françoise; Collomp, Katia

    2012-11-01

    The purpose of this study was to assess changes in the steroid hormone levels of elite athletes during an international powerlifting competition. Baseline cortisol, DHEA and testosterone were determined in saliva samples in 19 (8 men, 11 women) junior and sub-junior athletes on the day before competition, and then on the competition day during the official weighing and in the hour after competition. Performance was determined by total output and the Wilks formula. No change in saliva steroid concentrations was observed between samples collected on the day before competition and the weighing samples. There was no gender effect on cortisol concentrations but saliva testosterone levels were always significantly higher in men than in women (p<0.01), as was end-competition DHEA (p<0.05). Cortisol and DHEA were significantly increased in male and female athletes after the competition (respectively, p<0.01 and p<0.05), whereas end-competition testosterone concentrations were only significantly increased in men (p<0.01). Significant relationships were demonstrated between performance and end-competition cortisol levels in women and end-competition testosterone levels in men. These data indicate that workouts during an international powerlifting competition produce a significant increase in adrenal steroid hormones in both genders, with an increase in male gonadal steroid hormone. Further studies are necessary to examine the changes in oestradiol and progesterone in women and their potential impact on performance during international powerlifting competition.

  4. Sex steroid hormones and circulating IgE levels.

    PubMed

    Mathur, S; Mathur, R S; Goust, J M; Williamson, H O; Fudenberg, H H

    1977-12-01

    The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies.

  5. Psychological, social, and spiritual effects of contraceptive steroid hormones.

    PubMed

    Klaus, Hanna; Cortés, Manuel E

    2015-08-01

    Governments and society have accepted and enthusiastically promoted contraception, especially contraceptive steroid hormones, as the means of assuring optimal timing and number of births, an undoubted health benefit, but they seldom advert to their limitations and side effects. This article reviews the literature on the psychological, social, and spiritual impact of contraceptive steroid use. While the widespread use of contraceptive steroid hormones has expanded life style and career choices for many women, their impact on the women's well-being, emotions, social relationships, and spirituality is seldom mentioned by advocates, and negative effects are often downplayed. When mentioned at all, depression and hypoactive sexual desire are usually treated symptomatically rather than discontinuing their most frequent pharmacological cause, the contraceptive. The rising incidence of premarital sex and cohabitation and decreased marriage rates parallel the use of contraceptive steroids as does decreased church attendance and/or reduced acceptance of Church teaching among Catholics. Lay summary: While there is wide, societal acceptance of hormonal contraceptives to space births, their physical side effects are often downplayed and their impact on emotions and life styles are largely unexamined. Coincidental to the use of "the pill" there has been an increase in depression, low sexual desire, "hook-ups," cohabitation, delay of marriage and childbearing, and among Catholics, decreased church attendance and reduced religious practice. Fertility is not a disease. Birth spacing can be achieved by natural means, and the many undesirable effects of contraception avoided.

  6. Gonadotropin stimulation of steroid synthesis and metabolism in the Rana pipiens ovarian follicle: sequential changes in endogenous steroids during ovulation, fertilization and cleavage stages.

    PubMed

    Morrill, Gene A; Schatz, Frederick; Kostellow, Adele; Bloch, Eric

    2006-05-01

    Steroid synthesis and metabolism have been followed in Rana pipiens ovarian follicles, denuded oocytes and eggs during ovulation, fertilization and cleavage stages (blastula formation). Under physiological conditions, gonadotropin stimulation of the fully grown follicle leads to progesterone synthesis from [(3)H]acetate as well as formation of much smaller amounts of 17alpha-hydroxyprogesterone, androstenedione, pregnanedione and pregnanediol. Progesterone levels increase during completion of the first meiotic division, but by ovulation progesterone disappears from the egg. Plasma membrane-bound progesterone is taken up into the oocyte cortical granules and is largely metabolized to 5alpha-pregnane-3alphaol,20-one and 5beta-pregnane-3alpha,17alpha,20beta-triol coincident with internalization of 60% of the oocyte surface (and >90% of bound progesterone) by the end of the hormone-dependent period. The principal steroid in the ovulated egg is 5beta-pregnane-3alpha,17alpha,20beta-triol. There is a rapid efflux of 5beta-pregnane-3alpha,17alpha,20beta-triol into the medium immediately following fertilization and residual steroid levels remain low in the developing blastula. Dissociated blastulae cells prepared from stage 9 1/2 embryos concentrate both pregnenolone and progesterone from the medium with minimal metabolism. The results indicate that the ovarian follicle has the ability to synthesize and metabolize progesterone but that this ability disappears in the ovulated egg. The progesterone metabolites formed during meiosis are largely released at fertilization.

  7. Ovarian Steroids Increase Spinogenetic Proteins in the Macaque Dorsal Raphe

    PubMed Central

    Rivera, Heidi M.; Bethea, Cynthia L.

    2012-01-01

    Dendritic spines are the basic structural units of neuronal plasticity. Intracellular signaling cascades that promote spinogenesis have centered on RhoGTPases. We found that ovarian steroids increase gene expression of RhoGTPases (RhoA, Cdc42 and Rac) in laser-captured serotonin neurons. We sought to confirm that the increases observed in gene expression translate to the protein level. In addition, a preliminary study was conducted to determine whether an increase in spines occurs via detection of the spine marker protein, PSD-95. Adult ovariectomized (Ovx) monkeys were treated with estradiol (E), progesterone (P) or E+P for 1 month. Sections through the dorsal raphe nucleus were immunostained for RhoA and Cdc42 (n = 3-4/group). The number and positive pixel area of RhoA-positive cells, and the positive pixel area of Cdc42-positive fibers were determined. Upon combining E and E+P treated groups, there was a significant increase in the average and total cell number and positive pixel area of RhoA-positive cells. E, P and E+P treatments individually or combined, also increased the average and total positive pixel area of Cdc42-positive fibers. With remaining sections from 2 animals in each group, we conducted a preliminary examination of the regulation of PSD-95 protein expression. PSD-95, a postsynaptic scaffold protein, was examined with immunogold silver staining (n = 2/group) and the total number of PSD-95-positive puncta was determined with stereology across 4 levels of the dorsal raphe. E, P and E+P treatment significantly increased the total number of PSD-95-positive puncta. Together, these findings indicate that ovarian steroids act to increase gene and protein expression of two pivotal RhoGTPases involved in spinogenesis and preliminarily indicate that an increased number of spines and/or synapses result from this action. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and in turn, increase serotonin neuronal

  8. Noninvasive Measurement of Steroid Hormones in Zebrafish Holding-Water

    PubMed Central

    Félix, Ana S.; Faustino, Ana I.; Cabral, Eduarda M.

    2013-01-01

    Abstract Zebrafish (Danio rerio) has recently emerged as a new animal model in neuroendocrinology and behavior (e.g., stress physiology and ecotoxicology studies). In these areas, the concentrations of steroid hormones in the blood are often used to study the endocrinological status of individuals. However, due to the small body size of zebrafish, blood sampling is difficult to perform and the amount of plasma obtained per sample for assaying hormones is very small (ca. 1–5 μL), and therefore most studies have been using whole-body hormone concentrations, which implies sacrificing the individuals and hampers sequential sampling of the same individual. Here a noninvasive method to assay steroid hormones from zebrafish holding-water, based on the fact that steroids are released into the fish holding-water through the gills by passive diffusion, is validated. Cortisol and the androgen 11-ketotestosterone (KT) were measured in water samples and compared to plasma levels in the same individuals. Cortisol released to holding-water correlates positively with plasma concentrations, but there was a lack of correlation between KT water and circulating levels. However, KT levels showed a highly significant sex difference that can be used to noninvasively sex individuals. An ACTH challenge test demonstrated that an induced increase in circulating cortisol concentration can be reliably detected in holding-water levels, hence attesting the responsiveness of holding-water levels to fluctuations in circulating levels. PMID:23445429

  9. Noninvasive measurement of steroid hormones in zebrafish holding-water.

    PubMed

    Félix, Ana S; Faustino, Ana I; Cabral, Eduarda M; Oliveira, Rui F

    2013-03-01

    Zebrafish (Danio rerio) has recently emerged as a new animal model in neuroendocrinology and behavior (e.g., stress physiology and ecotoxicology studies). In these areas, the concentrations of steroid hormones in the blood are often used to study the endocrinological status of individuals. However, due to the small body size of zebrafish, blood sampling is difficult to perform and the amount of plasma obtained per sample for assaying hormones is very small (ca. 1-5 μL), and therefore most studies have been using whole-body hormone concentrations, which implies sacrificing the individuals and hampers sequential sampling of the same individual. Here a noninvasive method to assay steroid hormones from zebrafish holding-water, based on the fact that steroids are released into the fish holding-water through the gills by passive diffusion, is validated. Cortisol and the androgen 11-ketotestosterone (KT) were measured in water samples and compared to plasma levels in the same individuals. Cortisol released to holding-water correlates positively with plasma concentrations, but there was a lack of correlation between KT water and circulating levels. However, KT levels showed a highly significant sex difference that can be used to noninvasively sex individuals. An ACTH challenge test demonstrated that an induced increase in circulating cortisol concentration can be reliably detected in holding-water levels, hence attesting the responsiveness of holding-water levels to fluctuations in circulating levels.

  10. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals.

    PubMed

    Sanderson, J Thomas

    2006-11-01

    Various chemicals found in the human and wildlife environments have the potential to disrupt endocrine functions in exposed organisms. Increasingly, the enzymes involved in the steroid biosynthesis pathway are being recognized as important targets for the actions of various endocrine-disrupting chemicals. Interferences with steroid biosynthesis may result in impaired reproduction, alterations in (sexual) differentiation, growth, and development and the development of certain cancers. Steroid hormone synthesis is controlled by the activity of several highly substrate-selective cytochrome P450 enzymes and a number of steroid dehydrogenases and reductases. Particularly aromatase (CYP19), the enzyme that converts androgens to estrogens, has been the subject of studies into the mechanisms by which chemicals interfere with sex steroid hormone homeostasis and function, often related to (de)feminization and (de)masculinazation processes. Studies in vivo and in vitro have focussed on ovarian and testicular function, with less attention given to other steroidogenic organs, such as the adrenal cortex. This review aims to provide a comprehensive overview of the state of knowledge regarding the mechanisms by which chemicals interfere with the function of steroidogenic enzymes in various tissues and organisms. The endocrine toxicities and mechanisms of action related to steroidogenesis of a number of classes of drugs and environmental contaminants are discussed. In addition, several potential in vitro bioassays are reviewed for their usefulness as screening tools for the detection of chemicals that can interfere with steroidogenesis. Analysis of the currently scattered state of knowledge indicates that still relatively little is known about the underlying mechanisms of interference of chemicals with steroidogenesis and their potential toxicity in steroidogenic tissues, neither in humans nor in wildlife. Considerably more detailed and systematic research in this area of

  11. Placental steroid hormone biosynthesis in primate pregnancy.

    PubMed

    Albrecht, E D; Pepe, G J

    1990-02-01

    Substantial advances in our understanding of placental function have resulted from recent establishment of in vitro approaches, such as cell culture, and application of molecular methods to study placental steroidogenesis. Insight into the processes of placental cell differentiation and hormonal function has been gained from culture of relatively pure preparations of cytotrophoblast. Various factors, e.g. cAMP and peptide growth factors, have been shown to have striking effects on progesterone and estrogen formation by placental tissue under in vitro conditions. Using advanced molecular approaches, the genes governing specific enzymes critical to placental steroidogenesis have been identified. Regulation of the mRNAs encoding specific enzyme peptides and thus expression of the genes by factors, such as cAMP, have been elucidated by Northern analysis and other techniques. It is critical that these contemporary approaches continue to be implemented aggressively to further elucidate placental function. However, it is clear from a survey of the literature, particularly of the past decade, that the vast majority of investigation in the area has been conducted in vitro. It is essential to determine whether the factors that have been observed to regulate placental endocrine function in vitro are operable in vivo. It is only with in vivo study that the dynamics of steroidogenesis and the complex functional relationships between placenta, fetus, and mother will be uncovered and understood. It is increasingly evident that the regulation of placental steroidogenesis involves autocrine and/or paracrine mechanisms, similar to those integral to hormone biosynthesis within other reproductive organs, e.g. ovary and testis. For example, as discussed above, estrogen regulates LDL uptake and P-450scc, and thus apparently is involved in generating substrate for progesterone production within the placenta. Conversely, progesterone has effects on 17 beta-hydroxysteroid oxidoreductase

  12. Cellular and molecular effects of steroid hormones on CNS excitability.

    PubMed

    Smith, Sheryl S; Woolley, Catherine S

    2004-02-01

    The steroid hormones 17beta-estradiol (estradiol) and progesterone not only regulate the reproductive system but have other central nervous system effects that can directly affect a variety of behaviors. Generally, estradiol has been shown to have activating effects, including the ability to increase seizure activity, while progesterone has been shown to have depressant effects, including anticonvulsant properties. Because levels of these hormones fluctuate across the menstrual cycle, it is important to understand how changes in these hormone levels may influence levels of excitability in the brain, especially in women who have seizure patterns that are related to their menstrual cycle, a phenomenon known as catamenial epilepsy. This paper reviews the effects of estradiol and progesterone on excitatory and inhibitory neurotransmitters, respectively, and the possible cellular and molecular mechanisms underlying the changes in brain excitability mediated by these hormones.

  13. Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

    PubMed Central

    Ide, Hiroki; Miyamoto, Hiroshi

    2015-01-01

    There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression. PMID:26770009

  14. Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence.

    PubMed

    Riman, T; Persson, I; Nilsson, S

    1998-12-01

    Epithelial ovarian cancer is fairly common with high rates in Scandinavia, intermediate rates in western Europe and North America and low rates in the developing countries and in Japan. The 5-year survival rate is less than 40%. Increasing parity consistently gives a strong protection against epithelial ovarian cancer. A lesser degree of protection is probably derived from incomplete pregnancies and lactation. Ages at menarche and menopause are most probably weak predictors of epithelial ovarian cancer risk. Ever users of oral contraceptives (OC) have 30% lower risk compared to never users. The protection increases with duration of OC use, being about 50% after 5 years. The reduced risk among past OC users persists for at least 10 years after cessation of use. Results concerning hormone replacement therapy (HRT) and epithelial ovarian cancer risk are conflicting, but most data point to a weak or no association, but as an increasing number of women use HRT it still seems important to resolve any potential effect. Infertility adds to epithelial ovarian cancer risk in nulliparous women, while temporary fertility problems in parous women do not appear to increase risk. A possible independent risk effect of fertility drug use has not been easy to assess and remains unresolved. It has been particularly difficult to separate the effects of fertility drugs from those of infertility. Tubal ligation and hysterectomy convey protection against epithelial ovarian cancer, possibly through a suppressed ovarian hormone production. The causes of epithelial ovarian cancer are poorly understood, but reproductive hormones are thought to be involved in the aetiology. For a long time the 'incessant' and 'gonadotrophin' hypotheses have been promoted in relation to carcinogenesis. Both hypotheses find support in ovarian cancer epidemiology, and recent progress in molecular biology adds to the understanding of possible aetiological mechanisms. Another hypothesis focuses on the retrograde

  15. Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors.

    PubMed

    Kallak, Theodora Kunovac; Baumgart, Juliane; Göransson, Emma; Nilsson, Kerstin; Poromaa, Inger Sundström; Stavreus-Evers, Anneli

    2014-04-01

    Women with breast cancer who are treated with aromatase inhibitors often experience vaginal atrophy symptoms and sexual dysfunction. This work aims to study proliferation and the presence and distribution of steroid hormone receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in women with breast cancer who are on adjuvant endocrine treatment and in healthy postmenopausal women. This is a cross-sectional study that compares postmenopausal aromatase inhibitor-treated women with breast cancer (n = 15) with tamoxifen-treated women with breast cancer (n = 16) and age-matched postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy (n = 16). Immunohistochemistry was used to study proliferation and steroid hormone receptor staining intensity. Data was correlated with estrogen and androgen levels, vaginal atrophy scores, and vaginal pH. Aromatase inhibitor-treated women had a lower grade of proliferation, weaker progesterone receptor staining, and stronger androgen receptor staining, which correlated with plasma estrone levels, vaginal atrophy scores, and vaginal pH. Women with aromatase inhibitor-treated breast cancer exhibit reduced proliferation and altered steroid hormone receptor staining intensity in the vagina, which are related to clinical signs of vaginal atrophy. Although these effects are most probably attributable to estrogen suppression, a possible local inhibition of aromatase cannot be ruled out.

  16. Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.

    PubMed

    Mather, K J; Kim, C; Christophi, C A; Aroda, V R; Knowler, W C; Edelstein, S E; Florez, J C; Labrie, F; Kahn, S E; Goldberg, R B; Barrett-Connor, E

    2015-10-01

    Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.

  17. Correlation between plasma steroid hormones and vitellogenin profiles and lunar periodicity in the female golden rabbitfish, Siganus guttatus (Bloch).

    PubMed

    Rahman, M D; Takemura, A; Takano, K

    2000-09-01

    Characteristics of the lunar reproductive cycle in the golden rabbitfish, Siganus guttatus, were determined by histological observations of ovarian development, and immunological measurements of plasma steroid hormones, estradiol-17beta (E2), testosterone (T), 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) and 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S), and vitellogenin (VTG). Ovarian and plasma samples were collected every week according to the lunar phases from May to July. Weekly change of gonadosomatic index (GSI) showed two peaks at the first lunar quarter in June and July. Yolky oocytes were also observed around this time. Histological observations revealed that the vitellogenic oocytes appeared again 1 week after spawning and developed synchronously. These results suggest that this species is a multiple spawner and the oocyte development is in a group-synchronous manner. Plasma steroid hormones (E2, T, DHP and 20beta-S) and VTG levels changed in parallel with changes in GSI. The peak of plasma VTG level occurred prior to spawning. These cyclic changes of plasma steroid hormones and VTG support the hypothesis that lunar periodicity is the major factor in stimulating reproductive activity of S. guttatus.

  18. Effects of Steroid Hormone in Avian Follicles

    PubMed Central

    Caicedo Rivas, R. E.; Nieto, M. Paz-Calderón; Kamiyoshi, M.

    2016-01-01

    The aim of the present study was to examine the effects of testosterone (T) and estradiol-17β (E2) on the production of progesterone (P4) by granulosa cells, and of the E2 on the production of P4 and T by theca internal cells. In the first experiment, granulosa cells isolated from the largest (F1) and third largest (F3) preovulatory follicle were incubated for 4 h in short-term culture system, P4 production by granulosa cells of both F1 and F3 was increased in a dose-dependent manner by ovine luteinizing hormone (oLH), but not T or E2. In the second experiment, F1 and F3 granulosa cells cultured for 48 h in the developed monolayer culture system were recultured for an additional 48 h with increasing doses of various physiological active substances existing in the ovary, including T and E2. Basal P4 production for 48 h during 48 to 96 h of the cultured was about nine fold greater by F1 granulosa cells than by F3 granulosa cells. In substances examined oLH, chicken vasoactive intestinal polypeptide (cVIP) and T, but not E2, stimulated in a dose-dependent manner P4 production in both F1 and F3 granulosa cells. In addition, when the time course of P4 production by F1 granulosa cells in response to oLH, cVIP, T and E2 was examined for 48 h during 48 to 96 h of culture, although E2 had no effect on P4 production by granulosa cells of F1 during the period from 48 to 96 h of culture, P4 production with oLH was found to be increased at 4 h of the culture, with a maximal 9.14 fold level at 6 h. By contrast, P4 production with cVIP and T increased significantly (p<0.05) from 8 and 12 h of the culture, respectively, with maximal 6.50 fold response at 12 h and 6, 48 fold responses at 36 h. Furthermore, when F1 granulosa cells were precultured with E2 for various times before 4 h culture with oLH at 96 h of culture, the increase in P4 production in response to oLH with a dose-related manner was only found at a pretreatment time of more than 12 h. In the third experiment, theca

  19. Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids.

    PubMed Central

    McLaren, J; Prentice, A; Charnock-Jones, D S; Millican, S A; Müller, K H; Sharkey, A M; Smith, S K

    1996-01-01

    Angiogenesis is important in the pathophysiology of endometriosis, a condition characterized by implantation of ectopic endometrium in the peritoneal cavity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis. Our aim was to investigate the site of expression and regulation of VEGF in endometriosis. VEGF immunoreactivity was found in tissue macrophages present in ectopic endometrium and in activated peritoneal fluid macrophages. Macrophage activation was highest in women with endometriosis, and media conditioned by peritoneal fluid macrophages from these women caused a VEGF-dependent increase in endothelial cell proliferation above that seen from normal women. Peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, and this secretion was enhanced after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain receptor) were also detected, suggesting autocrine regulation. During the menstrual cycle, expression of flt was constant but that of KDR was increased in the luteal phase, at which time the cells migrated in response to VEGF. KDR expression and the migratory response were significantly higher in patients with endometriosis. This study demonstrates that activated macrophages are a major source of VEGF in endometriosis and that this expression is regulated directly by ovarian steroids. PMID:8755660

  20. Steroid binding sites in liver membranes: interplay between glucocorticoids, sex steroids, and pituitary hormones.

    PubMed

    Fernández-Pérez, L; Flores-Morales, A; Chirino-Godoy, R; Díaz-Chico, J C; Díaz-Chico, B N

    2008-04-01

    Steroid hormones activate target cells through specific receptors that discriminate among ligands based upon recognition of distinct structural features. For most known steroids, membrane and nuclear receptors co-exist in many target cells. However, while the structure of the nuclear receptors and their function as transcriptional activators of specific target genes is generally well understood, the identity of the membrane receptors remains elusive. Using pharmacological and biochemical approaches, we are beginning to characterize receptors for glucocorticoids and anabolic-androgenic steroids in male rat liver membranes. Male rat liver endoplasmic reticulum contains two steroid binding sites which are functionally related and associated with a 90-134 kDa oligomeric protein: (1) the low-affinity glucocorticoid binding site (LAGS), composed at least in part of two peptides (37 and 53 kDa) that bind glucocorticoids and (2) the stanozolol binding protein (STBP), composed at least in part of three peptides (22, 31, and 55 kDa) that bind the synthetic androgen stanozolol. These steroid binding proteins have many properties different from those of classical nuclear receptors, with the salient differences being a failure to recognize "classical" ligands for nuclear receptors together with marked differences in biochemical properties and physiological regulation. The mechanism of interaction of glucocorticoids with the LAGS can be clearly distinguished from that with STBP. Moreover, STBP shows an extremely narrow pharmacological profile, being selective for ST and its analog, danazol, among more than 100 steroids and non-steroidal compounds that were assayed, including those that are able to displace glucocorticoids from the LAGS. The level of LAGS activity undergoes dramatic variations following changes from the physiological serum levels of thyroid hormones, glucocorticoids, GH, vitamin A, and E2. However, neither thyroid hormones nor GH have a critical role on STBP

  1. Ovarian hormones and chronic pain: A comprehensive review.

    PubMed

    Hassan, Samah; Muere, Abi; Einstein, Gillian

    2014-12-01

    Most chronic noncancer pain (CNCP) conditions are more common in women and have been reported to worsen, particularly during the peak reproductive years. This phenomenon suggests that ovarian hormones might play a role in modulating CNCP pain. To this end, we reviewed human literature aiming to assess the potential role of ovarian hormones in modulating the following CNCP conditions: musculoskeletal pain, migraine headache, temporal mandibular disorder, and pelvic pain. We found 50 relevant clinical studies, the majority of which demonstrated a correlation between hormone changes or treatments and pain intensity, threshold, or symptoms. Taken together, the findings suggest that changes in hormonal levels may well play a role in modulating the severity of CNCP conditions. However, the lack of consistency in study design, methodology, and interpretation of menstrual cycle phases impedes comparison between the studies. Thus, while the literature is highly suggestive of the role of ovarian hormones in modulating CNCP conditions, serious confounds impede a definitive understanding for most conditions except menstrual migraine and endometriosis. It may be that these inconsistencies and the resulting lack of clarity have contributed to the failure of hormonal effects being translated into medical practice for treatment of CNCP conditions.

  2. First attempt to monitor luteinizing hormone and reproductive steroids in urine samples of the Amazonian manatee (Trichechus inunguis).

    PubMed

    Amaral, Rodrigo S; Rosas, Fernando C W; Graham, Laura H; da Silva, Vera M F; Oliveira, Claudio A

    2014-12-01

    The aims of this study were to validate an enzyme immunoassay (EIA) for the measurement of luteinizing hormone (LH) in urine samples of Amazonian manatees (Trichechus inunguis; Mammalia: Sirenia) and to monitor urinary LH and reproductive steroids during the ovarian cycle in this species. Urine samples were collected from two captive males following a hormonal challenge with a gonadotropin-releasing hormone (GnRH) analogue. The urinary LH results from hormonal challenge were compared with urinary androgens for the purpose of EIA validation. Furthermore, urine samples were collected daily, over a 12-wk period, from two captive adult females, for 2 consecutive yr. The urinary LH pattern from females was compared with the patterns of urinary progestagens and estrogen conjugates throughout the ovarian cycle. An LH peak was observed in both male Amazonian manatees after the hormonal challenge, occurring prior to or together with peak androgen levels. In the females, the ovarian cycle ranged from 40 to 48 days (mean of 43.7 days). Two distinct peaks of estrogen conjugates were observed across all cycles analyzed, and the urinary LH peaks observed were accompanied by peaks of urinary estrogen conjugates. The EIA was validated as a method for the quantification of urinary LH from Amazonian manatees, as it was able to detect variations in the levels of LH in urine samples. These results suggest that T. inunguis exhibits a peculiar hormonal pattern during the ovarian cycle. Therefore, further studies are desirable and necessary to clarify the relationship between this hormonal pattern and morphological changes, as well as mating behavior, in Amazonian manatee.

  3. Conserved steroid hormone homology converges on nuclear factor κB to modulate inflammation in asthma.

    PubMed

    Payne, Asha S; Freishtat, Robert J

    2012-01-01

    Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity, yet it has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing (Pediatr Pulmonol Suppl. 1997;15:9-12). Despite the complex pathogenesis of asthma, steroid hormones (eg, glucocorticoids) are ubiquitous in the short-term and long-term management of all types of asthma. Overall, steroid hormones are a class of widely relevant, biologically active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they use rapid, nongenomic actions to affect cellular products. Steroid hormones comprise several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggests that each of these is part of a dynamic system of hormone interaction, likely involving an overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these 3 groups of steroid hormones (ie, glucocorticoids, sex steroid hormones, and secosteroids), identifying nuclear factor κB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (eg, glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be a better understanding of the interplay of classic, nonclassic, and nongenomic steroid hormone functions. However, clues from the conserved homology steroid hormone structure and function and signaling pathways offer

  4. Conserved steroid hormone homology converges on NFκB to modulate inflammation in asthma

    PubMed Central

    Payne, Asha S.; Freishtat, Robert J.

    2012-01-01

    Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity [1], yet has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing. Despite the complex pathogenesis of asthma, steroid hormones (e.g. glucocorticoids) are ubiquitous in the acute and chronic management of all types of asthma. Overall, steroid hormones are a class of widely-relevant, biologically-active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they employ rapid, non-genomic actions to affect cellular products. Steroid hormones are comprised of several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggest that each of these is part of dynamic system of hormone interaction, likely involving overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these three groups of steroid hormones (i.e. glucocorticoids, sex steroid hormones, and secosteroids), identifying NFκB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (e.g. glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be better understanding of the interplay of classical, non-classical, and non-genomic steroid hormone function. However, clues from the conserved homology steroid hormone structure and function and signaling pathways, offer insight into a possible model of steroid

  5. Independent elaboration of steroid hormone signaling pathways in metazoans

    PubMed Central

    Markov, Gabriel V.; Tavares, Raquel; Dauphin-Villemant, Chantal; Demeneix, Barbara A.; Baker, Michael E.; Laudet, Vincent

    2009-01-01

    Steroid hormones regulate many physiological processes in vertebrates, nematodes, and arthropods through binding to nuclear receptors (NR), a metazoan-specific family of ligand-activated transcription factors. The main steps controlling the diversification of this family are now well-understood. In contrast, the origin and evolution of steroid ligands remain mysterious, although this is crucial for understanding the emergence of modern endocrine systems. Using a comparative genomic approach, we analyzed complete metazoan genomes to provide a comprehensive view of the evolution of major enzymatic players implicated in steroidogenesis at the whole metazoan scale. Our analysis reveals that steroidogenesis has been independently elaborated in the 3 main bilaterian lineages, and that steroidogenic cytochrome P450 enzymes descended from those that detoxify xenobiotics. PMID:19571007

  6. Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion

    PubMed Central

    Ghisleni, Carmen; Bollmann, Steffen; Biason-Lauber, Anna; Poil, Simon-Shlomo; Brandeis, Daniel; Martin, Ernst; Michels, Lars; Hersberger, Martin; Suckling, John

    2015-01-01

    Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women. PMID:26356576

  7. Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion.

    PubMed

    Ghisleni, Carmen; Bollmann, Steffen; Biason-Lauber, Anna; Poil, Simon-Shlomo; Brandeis, Daniel; Martin, Ernst; Michels, Lars; Hersberger, Martin; Suckling, John; Klaver, Peter; O'Gorman, Ruth L

    2015-01-01

    Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.

  8. Steroid hormones in the development of postpartum depression.

    PubMed

    Pařízek, A; Mikešová, M; Jirák, R; Hill, M; Koucký, M; Pašková, A; Velíková, M; Adamcová, K; Šrámková, M; Jandíková, H; Dušková, M; Stárka, L

    2014-01-01

    Postpartum depression affects 10-15 % women after childbirth. There is no currently generally accepted theory about the causes and mechanisms of postpartum mental disorders. The principal hypothesis concerns the association with sudden changes in the production of hormones affecting the nervous system of the mother and, on the other hand, with the ability of receptor systems to adapt to these changes. We observed changes in steroidogenesis in the period around spontaneous delivery. We collected three samples of maternal blood. The first sampling was 4 weeks prior to term; the second sampling was after the onset of uterine contractions (the beginning of spontaneous labour); the third sampling was during the third stage of labour (immediately after childbirth). Additionally, we collected mixed umbilical cord blood. The almost complete steroid metabolome was analyzed by gas chromatography-mass spectrometry followed by RIA for some steroids. Mental changes in women in the peripartum period were observed using the Hamilton Depression Rating Scale. The local Ethics Committee approved the study. We found already the changes in androgens levels correlating with postpartum mood disorders four weeks prior to childbirth. The strongest correlations between steroid and postpartum mood change were found in venous blood samples collected from mothers after childbirth and from umbilical cord blood. The main role played testosterone, possibly of maternal origin, and estrogens originating from the fetal compartment. These results suggest that changes in both maternal and fetal steroidogenesis are involved in the development of mental changes in the postpartum period. Descriptions of changes in steroidogenesis in relation to postpartum depression could help clarify the causes of this disease, and changes in some steroid hormones are a promising marker of mental changes in the postpartum period.

  9. Influence of Ovarian Endometrioma on Expression of Steroid Receptor RNA Activator, Estrogen Receptors, Vascular Endothelial Growth Factor, and Thrombospondin 1 in the Surrounding Ovarian Tissues

    PubMed Central

    Lin, Kaiqing; Ma, Junyan; Wu, Ruijin; Zhou, Caiyun

    2014-01-01

    This study investigates the influence of ovarian endometrioma on expression of steroid receptor RNA activator (SRA), estrogen receptors (ERs), vascular endothelial growth factor (VEGF), and thrombospondin 1 (TSP-1) in the surrounding ovarian tissues. Taken from the women with ovarian endometrioma and mature teratoma during laparoscopy, the biopsies were analyzed by real-time polymerase chain reaction and Western blot. Our results indicated that ovarian tissues surrounding endometrioma had lower SRA and ER-α levels but higher SRA protein (SRAP) and ER-β levels than ovarian endometrioma. With lower VEGF levels and higher TSP-1 levels, the surrounding ovarian tissues showed higher expression levels of SRA, SRAP, ER-α, and ER-β in the ovarian endometrioma group when compared to the controls. These data showed that ovarian endometrioma increases SRA, ERs, and TSP-1 but decreases VEGF levels in the surrounding ovarian tissues, suggesting that abnormal expression of these molecules may affect biological behaviors of ovarian endometrioma. PMID:23749764

  10. Relationship between dioxin and steroid hormones in sera of Vietnamese men.

    PubMed

    Sun, Xian Liang; Kido, Teruniko; Okamoto, Rie; Manh, Ho Dung; Maruzeni, Shoko; Nishijo, Muneko; Nakagawa, Hideaki; Honma, Seijiro; Nakano, Takeshi; Takasuga, Takumi; Nhu, Dang Duc; Hung, Nguyen Ngoc; Son, Le Ke

    2014-05-01

    A recent study found an inverse correlation between serum TCDD levels and serum testosterone in the US veterans, while there is little known on the dioxin and steroid hormones about Vietnamese men. We collected blood samples from 48 men who had resided in a hotspot when exposure happened and 38 men in a non-sprayed area. Some steroid hormones levels showed significant differences between two areas. There were no correlations between steroid hormones and dioxin TEQ, after ajusting for age and other factors. Our findings indicate that steroid hormones of Vietnamese men did not correlate with dioxin TEQ in two areas.

  11. Association between ovarian hormones and smoking behavior in women.

    PubMed

    Schiller, Crystal Edler; Saladin, Michael E; Gray, Kevin M; Hartwell, Karen J; Carpenter, Matthew J

    2012-08-01

    Studies examining the association between menstrual cycle phases and smoking behavior in women have yielded mixed results. The purpose of this study was to elucidate the associations between ovarian hormones and smoking by directly measuring ovarian hormone levels and obtaining a laboratory assessment of smoking behaviors. Four hypotheses were tested: Increased smoking will be associated with (1) low absolute levels of estradiol and progesterone; (2) decreasing (i.e., dynamic changes in) estradiol and progesterone; (3) lower ratios of progesterone to estradiol; and (4) higher ratios of estradiol to progesterone. Female smokers (≥10 cigarettes/day) with regular menstrual cycles were recruited as part of a larger, ongoing study examining the influence of ovarian hormones on smoking cessation treatment. Participants completed 2 study visits, including a 1-hr ad lib smoking topography session, which provided a detailed assessment of smoking behavior. Both the change in hormone levels over time and the relative ratios of ovarian hormones were associated with smoking behavior, but each to a limited extent. Decreases in estradiol (r = -.21, p = .048) and decreases in progesterone (r = -.23, p = .03) were associated with increased puff intensity. Lower ratios of progesterone to estradiol were associated with a greater number of puffs (r = -.26, p = .01) and weight of cigarettes smoked (r = -.29, p = .005). The best predictors of smoking behavior were the ratio of progesterone to estradiol (z = -2.7, p = .004) and the change in estradiol and progesterone over time (z = -2.1, p = .02). This pattern of results may help to explain inconsistent findings in previous studies and suggest potential mechanisms by which hormones influence nicotine addiction.

  12. The Association Between Ovarian Hormones and Smoking Behavior in Women

    PubMed Central

    Schiller, Crystal Edler; Saladin, Michael E.; Gray, Kevin M.; Hartwell, Karen J.; Carpenter, Matthew J.

    2013-01-01

    Studies examining the association between menstrual cycle phases and smoking behavior in women have yielded mixed results. The purpose of this study was to elucidate the associations between ovarian hormones and smoking by directly measuring ovarian hormone levels and obtaining a laboratory assessment of smoking behaviors. Four hypotheses were tested: increased smoking will be associated with 1) low absolute levels of estradiol and progesterone; 2) decreasing (i.e., dynamic changes in) estradiol and progesterone; 3) lower ratios of progesterone to estradiol, and 4) higher ratios of estradiol to progesterone. Female smokers (≥10 cigarettes/day) with regular menstrual cycles were recruited as part of a larger, ongoing study examining the influence of ovarian hormones on smoking cessation treatment. Participants completed two study visits, including a one-hour adlib smoking topography session, which provided a detailed assessment of smoking behavior. Both the change in hormone levels over time and the relative ratios of ovarian hormones were associated with smoking behavior, but each to a limited extent. Decreases in estradiol (r=−.21, p=.048), and decreases in progesterone (r=−.23, p=.03) were associated with increased puff intensity. Lower ratios of progesterone to estradiol were associated with a greater number of puffs (r=−.26, p=.01) and weight of cigarettes smoked (r=−.29, p=.005). The best predictors of smoking behavior were the ratio of progesterone to estradiol (z=−2.7, p=.004) and the change in estradiol and progesterone over time (z=−2.1, p=.02). This pattern of results may help to explain inconsistent findings in previous studies and suggest potential mechanisms by which hormones influence nicotine addiction. PMID:22545725

  13. Thecal cell sensitivity to luteinizing hormone and insulin in polycystic ovarian syndrome.

    PubMed

    Cadagan, David; Khan, Raheela; Amer, Saad

    2016-03-01

    This study examined whether a defect of steroid synthesis in ovarian theca cells may lead to the development of PCOS, through contributions to excess androgen secretion. Polycystic ovarian syndrome (PCOS) is one of the leading causes of infertility worldwide affecting around 1 in 10 of women of a reproductive age. One of the fundamental abnormalities in this syndrome is the presence of hormonal irregularities, including hyperandrogenemia, hyperinsulinemia and hypersecretion of luteinizing hormone (LH). Studies suggest that insulin treatment increases progesterone and androstenedione secretion in PCOS theca cells when compared to insulin treated normal theca cells. Furthermore the augmented effects of LH and insulin have been seen to increase ovarian androgen synthesis in non-PCOS theca cultures whilst also increasing the expression of steroidogenic enzymes specific to the PI3-K pathway. Our examination of primary thecal cultures showed an increase in both the expression of the steroidogenic enzyme CYP17 and androgen secretion in PCOS theca cells under basal conditions, when compared to non-PCOS cells. This was increased significantly under treatments of LH and insulin combined. Our results support the previous reported hypothesis that a dysfunction may exist within the PI3-K pathway. Specifically, that sensitivity exists to physiological symptoms including hyperinsulinemia and hyper secretion of LH found in PCOS through co-stimulation. The impact of these findings may allow the development of a therapeutic target in PCOS.

  14. Glucose transporters in sex steroid hormone related cancer.

    PubMed

    Nualart, Francisco; Los Angeles García, Maríade; Medina, Rodolfo A; Owen, Gareth I

    2009-10-01

    Cancer cells, as with most mammalian cells, depend on a continuous supply of glucose; not only as a precursor of glycoproteins, triglycerides and glycogen, but also as an important source of energy. This review concentrates on GLUT transporter expression in both normal and cancerous classical sex-steroid hormone tissues (i.e. breast, uterus, ovary, testis and prostate, among others). Given the importance of estrogen, progesterone and androgens in carcinogenesis, as well as in survival and propagation of these cancers, this review also highlights the current literature on hormone regulation of glucose transporters and on the role of hypoxia in their expression. Given the recent explosion of information on the newer GLUT6-12 family members, a brief overview on their function and general expression has been included. Finally, an insight into the use of glucose transporters as markers of cancer progression and clinical outcome is also discussed.

  15. Phosphoconjugation and dephosphorylation reactions of steroid hormone in insects.

    PubMed

    Sonobe, Haruyuki; Ito, Yoichi

    2009-08-13

    In insects, the major products of phase II metabolism of ecdysteroids, which include the molting hormone, are phosphate esters. The phosphoconjugation pathway is a reversible process, comprising two enzyme systems: ecdysteroid 22-kinase (EcKinase) and ecdysteroid-phosphate phosphatase (EPPase). We report here that: (1) the biochemical characteristics of EcKinase and EPPase, (2) the physiological significance of the reciprocal conversion of ecdysteroids and ecdysteroid phosphates in the ovary-egg system in insects, (3) the biochemical mechanism by which ecdysteroid phosphates are synthesized in the ovary, transferred to eggs, and finally dephosphorylated in eggs, and (4) the possible catalytic steps of EcKinase and EPPase on the basis of the data obtained by an in silico study. From these studies, it is obvious that ecdysteroid phosphates as well as steroid sulfates, which are major products of phase II metabolism in mammals, function as precursors for the formation of biologically active hormones.

  16. Deciduoma growth in the ovariectomized guinea pig: steroid hormone-mediated vascular support of endometrial differentiation.

    PubMed

    Garris, D R

    1988-05-01

    The ability of ovarian steroid hormones to modulate experimentally induced decidual tissue (DT) growth and the associated changes in uterine blood flow rates (UBF) was examined in ovariectomized guinea pigs after uterine trauma (designated day 0 of the studies). Uteri that were exposed, but not manipulated, served as controls. Uterine and DT weights as well as UBF, rates, were subsequently recorded on either day 5 or 10 posttrauma. Oil treatment failed to induce an increase in either control or traumatized uterine weights between days 5 and 10, and trauma had no effect on UBF rates in either group. Daily progesterone (P; 2 mg) treatment induced a significant elevation in DT weight by day 10 and elevated UBF rates between days 5 and 10 relative to control values. Daily P treatment augmented by estradiol (E2; 1 microgram) therapy on days 0 and 1 induced a significant increase in DT weights and UBF rates between days 5 and 10 in both control and DT groups relative to those in oil-treated animals. Combined P and E2 (P/E2) treatment induced a moderate increase in DT weight by day 10 posttrauma and elevated UBF rates in both control and DT groups. Acute treatment (i.e. days -3 to 0) with these steroid regimens indicated that neither P nor P/E2 treatment maintained DT growth. However, day -3 to 0 treatment with P in combination with a single day 0 injection of E2 allowed for maximal DT growth by day 10 and maintained elevated UBF rates relative to control values. P/E2 treatment between days -3 and 0 also induced an increase in UBF rates in both control and DT uteri relative to those in oil-treated animals. These results indicate that E2 is essential for supporting the P-directed differentiation and proliferation of stimulated guinea pig endometrium into DT. The ability of decidualization to occur in the absence of chronic steroid support indicates that uterine sensitization for cellular differentiation in this species only requires that the endometrium be initially primed

  17. Steroid sex hormone dynamics during estradiol-17β induced gonadal differentiation in Paralichthys olivaceus (Teleostei)

    NASA Astrophysics Data System (ADS)

    Sun, Peng; You, Feng; Liu, Mengxia; Wu, Zhihao; Wen, Aiyun; Li, Jun; Xu, Yongli; Zhang, Peijun

    2010-03-01

    Steroid sex hormones, such as estradiol-17β (E2) and testosterone (T), are important regulators of sex change in fish. In this study, we examined the effects of E2 treatment on the dynamics of E2 and T during gonadal differentiation in the olive flounder Paralichthys olivaceus using histology and radioimmunoassay (RIA). Flounder larvae were divided into five groups (G0-G4), and fed with 0 (control), 0.2, 2, 20 and 100 mg E2/kg feed from 35 to 110 day post hatching (dph). Fish growth in the G1 and G2 groups was not significantly different from that of the control group ( P>0.05), while fish in the G3 and G4 groups were less active and showed growth depression and high mortality. The gonads of fish in the G3 and G4 groups were smaller and surrounded by hyperplastic connective tissue. The frequency of females in the G0-G4 groups was 54.5%, 75.0%, 100%, 100% and 93.3%, respectively. The RIA analyses of E2 and T showed that T levels decreased during gonadal differentiation, and increased slightly at the onset of ovarian differentiation, while E2 levels increased gradually and peaked at the onset of ovarian differentiation in the control group. In the E2-treated groups, T levels decreased before the onset of ovarian differentiation. E2 levels were high on the 48 dph, but declined to a lower level on the 54 dph, and then increased gradually during gonadal differentiation. And a sharp increase of E2 levels were observed in all E2-treated groups at the onset of ovarian differentiation. The data suggest that T and E2 play important roles during gonadal differentiation, and an E2 dose of 2 mg/kg feed could induce sex reversal in P. olivaceus.

  18. Decreased ovarian hormones during a soya diet: implications for breast cancer prevention.

    PubMed

    Lu, L J; Anderson, K E; Grady, J J; Kohen, F; Nagamani, M

    2000-08-01

    luteal phase 17beta-estradiol levels were positively associated with urinary isoflavone excretion, an association affected by age, and were inversely associated with decreases in protein intake. Decreases in progesterone levels during the soya diet were inversely associated with increases in intakes of genistein and were affected by the interaction of the intakes of daidzein with energy or with fiber. Consumption of an isoflavone-containing soya diet reduced levels of ovarian steroids in normal women over the entire menstrual cycle without affecting gonadotropins. This suggests that at least under the conditions of this study, soya-induced reductions of circulating ovarian steroids are not mediated by gonadotropins. Decreases in ovarian hormones are related to isoflavones contained in soy and also to energy intake and other components such as protein and fiber but not fat. Our results may explain decreased ovarian hormone levels and decreased risk of breast cancer in populations consuming soya diets and have implications for reducing breast cancer risk by dietary intervention.

  19. Direct effects of sex steroid hormones on adipose tissues and obesity.

    PubMed

    Mayes, J S; Watson, G H

    2004-11-01

    Sex steroid hormones are involved in the metabolism, accumulation and distribution of adipose tissues. It is now known that oestrogen receptor, progesterone receptor and androgen receptor exist in adipose tissues, so their actions could be direct. Sex steroid hormones carry out their function in adipose tissues by both genomic and nongenomic mechanisms. In the genomic mechanism, the sex steroid hormone binds to its receptor and the steroid-receptor complex regulates the transcription of given genes. Leptin and lipoprotein lipase are two key proteins in adipose tissues that are regulated by transcriptional control with sex steroid hormones. In the nongenomic mechanism, the sex steroid hormone binds to its receptor in the plasma membrane, and second messengers are formed. This involves both the cAMP cascade and the phosphoinositide cascade. Activation of the cAMP cascade by sex steroid hormones would activate hormone-sensitive lipase leading to lipolysis in adipose tissues. In the phosphoinositide cascade, diacylglycerol and inositol 1,4,5-trisphosphate are formed as second messengers ultimately causing the activation of protein kinase C. Their activation appears to be involved in the control of preadipocyte proliferation and differentiation. In the presence of sex steroid hormones, a normal distribution of body fat exists, but with a decrease in sex steroid hormones, as occurs with ageing or gonadectomy, there is a tendency to increase central obesity, a major risk for cardiovascular disease, type 2 diabetes and certain cancers. Because sex steroid hormones regulate the amount and distribution of adipose tissues, they or adipose tissue-specific selective receptor modulators might be used to ameliorate obesity. In fact, hormone replacement therapy in postmenopausal women and testosterone replacement therapy in older men appear to reduce the degree of central obesity. However, these therapies have numerous side effects limiting their use, and selective receptor

  20. Steroid hormone activity of flavonoids and related compounds.

    PubMed

    Zand, R S; Jenkins, D J; Diamandis, E P

    2000-07-01

    Soy isoflavones have been studied extensively for estrogenic and antiestrogenic properties. Other flavonoids, found in fruits, vegetables, tea and wine, have been much less tested for steroid hormone activity. We therefore assessed the estrogenic, androgenic and progestational activities of 72 flavonoids and structurally-related compounds. These compounds were tested on BT-474 human breast cancer cells at concentrations of 10(8)-10(-5) M, with estradiol (estrogen), norgestrel (progestin) and dihydrotestosterone (androgen) used as positive controls, and ethanol (solvent) as a negative control. pS2, an estrogen-regulated protein, and prostate-specific antigen (PSA), regulated by androgens and progestins, were quantified in tissue culture supernatants using ELISA-type immunofluorometric assays developed in-house. Of the 72 compounds tested, 18 showed estrogenic activity at 10(-5) M. Of this subset, seven also showed progestational activity at this concentration. The soy isoflavones, biochanin A and genistein, showed the most potent estrogenic activity, with a dose-response effect up to 10(-7) M. Of all other flavonoids, luteolin and naringenin displayed the strongest estrogenicity, while apigenin had a relatively strong progestational activity. Based on our data, we have formulated a set of structure/function relationships between the tested compounds. Flavonoids, therefore, exhibit significant steroid hormone activity, and may have an effect in the modification of cancer risk by diet, or in cancer therapeutics and prevention.

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

    SciTech Connect

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

    1991-01-01

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

  2. Steroid hormone abnormalities in women with severe idiopathic constipation.

    PubMed Central

    Kamm, M A; Farthing, M J; Lennard-Jones, J E; Perry, L A; Chard, T

    1991-01-01

    Patients with severe idiopathic constipation are almost exclusively women of reproductive age. To investigate the possibility of a sex hormone abnormality in this condition, we have compared a range of sex hormones during the follicular and luteal phases of the menstrual cycle in 23 healthy women (mean age 33 years) with those in 26 patients with severe idiopathic constipation (mean age 32 years, spontaneous bowel frequency less than one per week). In the patients there was a reduction in the follicular phase of progesterone (4.5 v 4 nmol/l, p = 0.006, median value, controls v patients), 17 hydroxyprogesterone (9.7 v 5.8 nmol/l, p = 0.01), cortisol (387 v 245 nmol/l, p = 0.008), testosterone (2.3 v 1.8 nmol/l, p less than 0.001), androstenedione (10.3 v 8.4 nmol/l, p = 0.02), and dehydroepiandrosterone sulphate (5.1 v 3.0 mumol/l, p = 0.03). In the luteal phase there was a reduction of oestradiol (483 v 350 pmol/l, p = 0.015), cortisol (322 v 242 nmol/l, p = 0.047), and testosterone (2.4 v 1.7 nmol/l, p = 0.003). The concentrations of sex hormone binding globulin, prolactin, luteinising hormone, and follicle stimulating hormone were not significantly different in either phase of the cycle. Women with severe idiopathic constipation have a consistent reduction in steroid hormones. PMID:1825076

  3. Lonidamine affects testicular steroid hormones in immature mice

    SciTech Connect

    Traina, Maria Elsa . E-mail: Traina@iss.it; Guarino, Maria; Natoli, Alessia; Romeo, Antonella; Urbani, Elisabetta

    2007-05-15

    The effects on the hypothalamus-pituitary-testicular axis of the well-known antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the present study, the possible changes of the testicular steroid hormones were evaluated in immature mice for a better characterization of the LND adverse effects both in its use as antitumoral agent and male contraceptive. Male CD1 mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or 100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on PND42 (1 and 2 weeks after the administration, respectively). Severe testicular effects were evidenced in the LND treated groups, including: a) significant testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease (more than 50% of the control) on PND29-32; c) damage of the tubule morphology primarily on the Sertoli cell structure and germ cell exfoliation. All these reproductive endpoints were recovered on PND42. At the same time, a significant impairment of the testicular steroid balance was observed in the treated mice, as evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while the testicular content of 17{beta}-estradiol (E2) was unchanged. The hormonal balance was not completely restored afterwards, as levels of T, ADIONE and 17OH-P4 tended to be higher in the treated mice than in the controls, on PND35 and PND42. These data showed for the first time that LND affects intratesticular steroids in experimental animals. However further data are needed both to elucidate the mechanism responsible for the impairment of these metabolic pathways and to understand if the androgens decrease observed after LND administration could be partially involved in the testicular damage.

  4. Sex steroid hormone metabolism takes place in human ocular cells.

    PubMed

    Coca-Prados, Miguel; Ghosh, Sikha; Wang, Yugang; Escribano, Julio; Herrala, Annakaisa; Vihko, Pirkko

    2003-08-01

    Steroids are potentially important mediators in the pathophysiology of ocular diseases. In this study, we report on the gene expression in the human eye of a group of enzymes, the 17beta-hydroxysteroid dehydrogenases (17HSDs), involved in the biosynthesis and inactivation of sex steroid hormones. In the eye, the ciliary epithelium, a neuroendocrine secretory epithelium, co-expresses the highest levels of 17HSD2 and 5 mRNAs, and in lesser level 17HSD7 mRNA. The regulation of gene expression of these enzymes was investigated in vitro in cell lines, ODM-C4 and chronic open glaucoma (GCE), used as cell models of the human ciliary epithelium. The estrogen, 17beta-estradiol (10(-7) M) and androgen agonist, R1881 (10(-8) M) elicited in ODM-C4 and GCE cells over a 24 h time course a robust up-regulation of 17HSD7 mRNA expression. 17HSD2 was up-regulated by estradiol in ODM-C4 cells, but not in GCE cells. Under steady-state conditions, ODM-C4 cells exhibited a predominant 17HSD2 oxidative enzymatic activity. In contrast, 17HSD2 activity was low or absent in GCE cells. Our collective data suggest that cultured human ciliary epithelial cells are able to metabolize estrogen, androgen and progesterone, and that 17HSD2 and 7 in these cells are sex steroid hormone-responsive genes and 17HSD7 is responsible to keep on intra/paracrine estrogenic milieu.

  5. Ganglionic adrenergic action modulates ovarian steroids and nitric oxide in prepubertal rat.

    PubMed

    Delgado, Silvia Marcela; Casais, Marilina; Sosa, Zulema; Rastrilla, Ana María

    2006-08-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. The purpose of this work was to analyse the ganglionic adrenergic influence on the ovarian release of steroids and NO and the possible steroids/NO relationship. The experiments were carried out in the ex vivo coeliac ganglion-superior ovarian nerve (SON)-ovary system of prepubertal rats. The coeliac ganglion-SON-ovary system was incubated in Krebs Ringer-bicarbonate buffer in presence of adrenergic agents in the ganglionic compartment. The accumulation of progesterone, androstenedione, oestradiol and NO in the ovarian incubation liquid was measured. Norepinephrine in coeliac ganglion inhibited the liberation of progesterone and increased androstenedione, oestradiol and NO in ovary. The addition of alpha and beta adrenergic antagonists also showed different responses in the liberation of the substances mentioned before, which, from a physiological point of view, reveals the presence of adrenergic receptors in coeliac ganglion. In relation to propranolol, it does not revert the effect of noradrenaline on the liberation of progesterone, which leads us to think that it might also have a "per se" effect on the ganglion, responsible for the ovarian response observed for progesterone. Finally, we can conclude that the ganglionic adrenergic action via SON participates on the regulation of the prepubertal ovary in one of two ways: either increasing the NO, a gaseous neurotransmitter with cytostatic characteristics, to favour the immature follicles to remain dormant or increasing the liberation of androstenedione and oestradiol, the steroids necessary for the beginning of the near first estral cycle.

  6. Building a better hormone therapy?: How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline

    PubMed Central

    Frick, Karyn M.

    2012-01-01

    A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women. PMID:22289043

  7. Building a better hormone therapy? How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline.

    PubMed

    Frick, Karyn M

    2012-02-01

    A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women.

  8. Hormone replacement therapy and risk of epithelial ovarian cancer

    PubMed Central

    Purdie, D M; Bain, C J; Siskind, V; Russell, P; Hacker, N F; Ward, B G; Quinn, M A; Green, A C

    1999-01-01

    It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case–control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32–4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% Cl 1.54–5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours. © 1999 Cancer Research Campaign PMID:10507786

  9. Hormone replacement therapy and risk of epithelial ovarian cancer.

    PubMed

    Purdie, D M; Bain, C J; Siskind, V; Russell, P; Hacker, N F; Ward, B G; Quinn, M A; Green, A C

    1999-10-01

    It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.

  10. Prenatal alcohol exposure results in long-term serotonin neuron deficits in female rats: modulatory role of ovarian steroids.

    PubMed

    Sliwowska, Joanna H; Song, Hyun Jung; Bodnar, Tamara; Weinberg, Joanne

    2014-01-01

    Previous studies on male rodents found that prenatal alcohol exposure (PAE) decreases the number of serotonin immunoreactive (5-HT-ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5-HT system and known effects of estrogen (E2 ) and progesterone (P4 ) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females. Adult females from 3 prenatal groups (Prenatal alcohol-exposed [PAE], Pair-fed [PF], and ad libitum-fed Controls [C]) were ovariectomized (OVX), with or without hormone replacement, or underwent Sham OVX. 5-HT-ir cells were examined in key brainstem areas. Our data support the hypothesis that PAE has long-term effects on the 5-HT system of females and that ovarian steroids have a modulatory role in these effects. Intact (Sham OVX) PAE females had marginally lower numbers of 5-HT-ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became significant following removal of hormones by OVX. Replacement with E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2 . Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups. These data demonstrate long-term, adverse effects of PAE on the 5-HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5-HT neurons. Our findings have important implications for understanding sex differences in 5-HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder. Copyright © 2013 by the Research Society on Alcoholism.

  11. Anti-Mullerian Hormone: A Marker of Ovarian Reserve and its Association with Polycystic Ovarian Syndrome

    PubMed Central

    Verma, Anil Kumar; Rajbhar, Sarita; Gupta, Mayank; Sharma, Mratunjai; Deshmukh, Geeta; Ali, Wahid

    2016-01-01

    Introduction Anti-Mullerian Hormone (AMH) is a useful endocrine marker for assessing the ovarian reserve. AMH serum level reflects the number of follicles that have made the transition from the primordial pool into the growing follicle pool, and it is not controlled by gonadotropins. Aim The present study was conducted to correlate serum AMH levels with Polycystic Ovarian Syndrome (PCOS) and type of treatment protocol. Materials and Methods Serum AMH levels were performed in the early follicular phase (on 2nd day of menstrual cycle) both in infertile females including PCOS and control women. The results were analyzed in relation to age, Body Mass Index (BMI), ovarian volume, serum Follicle Stimulating Hormone (FSH) levels, Antral Follicle Count (AFC), type of treatment protocols and also in association with PCOS patients. The serum levels of AMH were measured in all the participants on 2nd day of menstrual cycle using ultra sensitive Enzyme Linked Immunosorbent Assay (ELISA). Results The plasma AMH levels were significantly higher in women with polycystic ovarian syndrome. The significant association was seen between FSH and AFC with AMH. However, no significant association was observed between AMH levels with age, BMI, ovarian volume and type of treatment protocols. Conclusion The serum AMH measurement was significantly higher in PCOS patients. No association with type of treatment protocol was obtained. PMID:28208941

  12. Effects of PCB 126 and PCB 153 on secretion of steroid hormones and mRNA expression of steroidogenic genes (STAR, HSD3B, CYP19A1) and estrogen receptors (ERα, ERβ) in prehierarchical chicken ovarian follicles.

    PubMed

    Sechman, Andrzej; Batoryna, Marta; Antos, Piotr A; Hrabia, Anna

    2016-12-15

    The objective of this study was to assess the in vitro effects of dioxin-like PCB 126 and non-dioxin-like PCB 153 on basal and ovine LH (oLH)-stimulated testosterone (T) and estradiol (E2) secretion and expression of steroidogenic genes (STAR, HSD3B and CYP19A1) and estrogen receptors α (ERα) and β (ERβ) in white (WF) and yellowish (YF) prehierarchical follicles of the hen ovary. Steroid concentrations in a medium and gene expression in follicles following 6h of exposition were determined by RIA and real-time qPCR, respectively. Both PCBs increased basal and oLH-stimulated T secretion by the WF follicles. PCB 126 reduced basal E2 secretion by the WF follicles. PCB 153 elevated but PCB 126 reduced oLH-stimulated E2 secretion by the prehierarchical follicles. PCB 126 increased basal STAR and HSD3B and reduced CYP19A1 mRNA expression in these follicles. PCB 153 increased basal expression of STAR and HSD3B in YF follicles, but diminished HSD3B mRNA levels in the WF. The studied PCBs had an opposite effect on basal and oLH-stimulated CYP19A1 mRNA expression in prehierarchical follicles. Both PCBs modulated basal and inhibited oLH-stimulated ERα and ERβ gene expression in the prehierarchical follicles. In conclusion, data of the current study demonstrate the congener-specific effects of PCBs on sex steroid secretion by prehierarchical follicles of the chicken ovary, which are at least partly related to STAR, HSD3B and CYP19A1 gene expression. It is suggested that PCBs, by influencing follicular steroidogenesis and expression of estrogen receptors, may impair development and selection of yellowish follicles to the preovulatory hierarchy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Ovarian hormones and reproductive risk factors for breast cancer in premenopausal women: the Norwegian EBBA-I study

    PubMed Central

    Iversen, A.; Thune, I.; McTiernan, A.; Emaus, A.; Finstad, S.E.; Flote, V.; Wilsgaard, T.; Lipson, S. F.; Ellison, P.T.; Jasienska, G.; Furberg, A.-S.

    2011-01-01

    BACKGROUND Ovarian hormones, parity and length of ‘menarche-to-first birth’ time interval are known risk factors for breast cancer, yet the associations between 17β-estradiol, progesterone and these reproductive factors remain unclear. METHODS A total of 204 women (25–35 years) who participated in the Norwegian EBBA-I study collected daily saliva samples for one complete menstrual cycle, and filled in a reproductive history questionnaire. Anthropometry was measured and saliva samples were analyzed for ovarian hormones. Associations between parity, the interval and ovarian hormones, and effects of hormone-related lifestyle factors were studied in linear regression models. RESULTS Mean age was 30.7 years, and age of menarche 13.1 years. Parous women had on average 1.9 births, and age at first birth was 24.5 years. No association was observed between parity and ovarian steroids. In nulliparous women, higher waist circumference (≥77.75 cm) and longer oral contraceptive (OC) use (≥3 years) were associated with higher levels of 17β-estradiol. Short (<10 years) versus long (>13.5 years) ‘menarche-to-first birth’ interval was associated with higher overall mean (Ptrend = 0.029), 47% higher maximum peak and 30% higher mid-cycle levels of 17β-estradiol. We observed a 2.6% decrease in overall mean salivary 17β-estradiol with each 1-year increase in the interval. CONCLUSIONS Nulliparous women may be more susceptible to lifestyle factors, abdominal overweight and past OC use, influencing metabolic and hormonal profiles and thus breast cancer risk. Short time between ‘menarche-to-first birth’ is linked to higher ovarian hormone levels among regularly cycling women, suggesting that timing of first birth is related to fecundity. PMID:21467202

  14. Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels.

    PubMed

    Marcondes, Rodrigo R; Carvalho, Kátia C; Duarte, Daniele C; Garcia, Natália; Amaral, Vinícius C; Simões, Manuel J; Lo Turco, Edson G; Soares, José M; Baracat, Edmund C; Maciel, Gustavo A R

    2015-02-01

    Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Ovarian steroid cell tumor, not otherwise specified: A case report and literature review

    PubMed Central

    Qian, Lili; Shen, Zhen; Zhang, Xuefen; Wu, Dabao; Zhou, Ying

    2016-01-01

    Steroid cell tumors (SCT), not otherwise specified (NOS) are particularly rare ovarian sex cord-stromal tumors, which comprise <0.1% of all ovarian tumors. These tumors are uncommon in patients' prior to puberty without any typical syndromes involving hirsutism, virilization and hypertension. We here in present the case of a 5-year-old female patient who presented with sudden abdominal pain, repeated vomiting and a pelvic mass. Our patient underwent urgent exploratory laparotomy and right salpingo-oophorectomy and the histopathological examination revealed an ovarian SCT-NOS. The patient has been followed up for 5 years since the surgery, without evidence of disease recurrence. The purpose of this study was to discuss the available information on the presentation, diagnosis and recommended treatment of ovarian SCT-NOS; and describes the immunohistochemical characteristics of these tumors. PMID:28105366

  16. Correlation between tumor histology, steroid receptor status, and adenosine deaminase complexing protein immunoreactivity in ovarian cancer.

    PubMed

    Rao, B R; Slotman, B J; Geldof, A A; Dinjens, W N

    1990-01-01

    Adenosine deaminase complexing protein (ADCP) immunoreactivity was investigated in 40 ovarian tumors and correlated with clinicopathologic parameters, including tumor steroid receptor content. Ten (29%) of 34 common epithelial ovarian carcinomas showed ADCP reactivity. Reactivity for ADCP was seen more frequently in mucinous (100%; p less than 0.001), well-differentiated (73%; p less than 0.001) and Stage I (56%; p less than 0.05) ovarian carcinomas. Furthermore, tumors that contained high levels of androgen receptors and tumors that did not contain estrogen receptors were more frequently ADCP positive (p less than 0.05). However, after stratifying for histologic grade, no correlation between ADCP reactivity and receptor status was found. Determination of ADCP reactivity appears to be of limited value in ovarian cancer.

  17. Perception of Plant Steroid Hormones at the Cell Surface

    SciTech Connect

    Li, Jianming

    2013-03-25

    The proposed research had two main objectives: 1) investigating the molecular mechanism by which BRs activate the BRI1-containing steroid receptor; and 2) to investigate the molecular mechanism of BRI1 function. During the course of this project, several research papers were published from other laboratories, which reported studies similar to our proposed experiments. We therefore changed our research direction and focused our research efforts on 1) molecular genetic studies of several extragenic suppressors of a weak bri1-9 mutant (which were named as EMS-mutagenized bri1 suppressor or ebs) and 2) biochemical characterization of the protein products of the cloned EBS genes. This switch turned out to be extremely successful and led to a surprising discovery that the dwarf phenotype of the well-studied bri1-9 mutant is not due to the failure of the bri1 receptor to bind the plant steroid hormone but rather caused by the retention of a structurally-imperfect but biochemically-competent bri1-9 and its subsequent degradation in the endoplasmic reticulum. This initial discovery coupled with subsequent cloning and further studies of additional EBS genes significantly increased our understanding of the protein quality control mechanisms in plants, a severely under-studied research topic in plant biology.

  18. Cobalt-induced hormonal and intracellular alterations in rat ovarian fragments in vitro.

    PubMed

    Roychoudhury, Shubhadeep; Sirotkin, Alexander V; Toman, Robert; Kolesarova, Adriana

    2014-01-01

    The objective of this in vitro study was to examine dose-dependent changes in the secretion activity (progesterone, 17β-estradiol and insulin-like growth factor-I) of rat ovarian fragments after experimental cobalt (Co) administration including the apoptotic potential of Co on rat ovarian fragments by evaluating the expression of apoptotic markers Bax and caspase-3. Ovarian fragments were incubated with cobalt sulphate (CoSO4.7H2O) at the doses 90, 170, 330 and 500 μg.mL(-1) for 24 h and compared with control group without Co addition. Release of progesterone (P4) 17β-estradiol and insulin-like growth factor-I (IGF-I) by ovarian fragments was assessed by RIA, expression of Bax and caspase-3 by SDS-PAGE and Western blotting. Observations show that P4 release by ovarian fragments was significantly (P < 0.05) inhibited after cobalt sulphate addition at higher doses 170-500 μg.mL(-1) used in the study in comparison to control. However, cobalt sulphate addition did not cause any significant change in the release of 17β-estradiol by ovarian fragments at all the doses used in the study (90-500 μg.mL(-1)) in comparison to control. On the contrary, IGF-I release by ovarian fragments was significantly (P < 0.05) stimulated after cobalt sulphate addition at the lowest dose 90 μg.mL(-1) in comparison to control, while other doses did not cause any significant change. Also, addition of cobalt sulphate decreased the expression of both the apoptotic peptides Bax and caspase-3 at the higher doses 170, 330 and 500 μg.mL(-1), but not at the lowest dose 90 μg.mL(-1) used in the study. Obtained results suggest Co induced (1) inhibition in secretion of steroid hormone progesterone, (2) dose-dependent increase in the release of growth factor IGF-I, and (3) decrease in the expression of markers of apoptosis (Bax and caspase-3) of rat ovarian fragments.

  19. Regulation of rat luteinizing hormone subunit messenger ribonucleic acids by gonadal steroid hormones.

    PubMed Central

    Gharib, S D; Bowers, S M; Need, L R; Chin, W W

    1986-01-01

    Little is known about the hormonal regulation of luteinizing hormone (LH) biosynthesis. We have studied the regulation of LH messenger RNA (mRNA) levels by gonadal-steroid hormones in the rat. In one set of experiments, male and female rats were surgically gonadectomized (GDX) and killed 1, 3, 7, 14, 22, and 31 d postoperatively. In another set of experiments, male and female rats were surgically GDX and were injected subcutaneously with testosterone propionate (500 micrograms/100 g body wt per d) or 17 beta-estradiol 3-benzoate (10 micrograms/100 g body wt per d), respectively, beginning 3 wk postoperatively. Levels of serum LH were determined by radioimmunoassay and levels of LH subunit mRNAs in single pituitary glands were determined by blot hybridization analysis using labeled synthetic oligodeoxyribonucleotide probes that correspond to portions of the coding regions of the rat alpha- and LH beta-subunit mRNAs. 4 wk after gonadectomy, serum LH levels rose nine- and 20-fold, while alpha-subunit mRNA levels rose six- and 10-fold, and LH beta-subunit levels rose seven- and 14-fold, compared with controls in males and females, respectively. In gonadal-steroid hormone-treated male and female GDX rats, serum LH levels fell to 8 and 36% of control values, while alpha-subunit mRNA levels declined to 22 and 19%, and LH beta-subunit mRNA levels declined to 6 and 10% of control values, 48 h after injections were initiated, in males and females, respectively. We conclude that gonadal-steroid hormones negatively regulate the levels of both subunit mRNAs in GDX rats in a pattern that parallels the changes in serum LH values. These data suggest that gonadal-steroid hormone regulation of LH biosynthesis occurs, at least in part, at the level of LH subunit mRNAs due to effects at the transcriptional and/or RNA stability levels. Images PMID:2418065

  20. Ovarian steroids and modulation of morphine-induced analgesia and catalepsy in female rats.

    PubMed

    Banerjee, P; Chatterjee, T K; Ghosh, J J

    1983-12-23

    The influence of ovarian steroids on modulation of antinociceptive and cataleptic responses to morphine in female rats was evaluated. The sensitivity of the animals to morphine varied at different stages of the estrous cycle. The responses of postpartum and ovariectomized rats to morphine was attenuated. The test doses of estradiol-17 beta or progesterone, either alone or in combination, did not alter this attenuated morphine sensitivity. Testosterone, however, sensitized post-partum as well as ovariectomized rats to morphine. Unlike progesterone, 17-alpha-hydroxy progesterone antagonized testosterone. Collectively these data implicate ovarian testosterone as a physiological modulator of actions of morphine in female rats.

  1. [Balance of steroid hormones among children and teenagers with epilepsies].

    PubMed

    Gol'tvanitsa, G A; Shirshov, Iu A; Marueva, N A; Kritskaia, Iu A; Leont'eva, E V; Temnikova, I V

    2012-01-01

    The level of steroid hormones (cortisol, cortisone, aldosterone) in children with epilepsy, aged from 4 to 18 years, was investigated. The levels of cortisol, cortisone and aldosterone were changed in 58.0%, 32.0% and 62.0% of patients with pharmacoresistant epilepsy, respectively, compared to age-matched controls. In case of epilepsy with positive effect of antiepileptic treatment, the changes of aldosterone were found only in 40.6% of patients. The level of hormones was, to a certain extent, age-dependent only in pharmacoresistant epilepsy. The greatest changes are registered in the following periods: at the age 4-7 years, the cortisone level corresponded to the norm in 33.3%, aldosterone in 44.4%; at the age 12-16 years, the indexes of cortisol corresponded to the norm in 26.7%, aldosterone in 20.0%; at the age 8 − 11 years, only the level of aldosterone was changed, it corresponded to the norm in 35.3% of cases.

  2. Dual role for ubiquitin in plant steroid hormone receptor endocytosis

    PubMed Central

    Martins, Sara; Dohmann, Esther M. N.; Dompierre, Jim; Fischer, Wolfgang; Pojer, Florence; Jaillais, Yvon; Satiat-Jeunemaître, Béatrice; Chory, Joanne; Geldner, Niko; Vert, Grégory

    2015-01-01

    Brassinosteroids (BRs) are plant steroid hormones that control many aspects of plant growth and development. BRs are perceived at the cell-surface by the plasma membrane-localized receptor complex composed of the receptor kinase BRI1 and its co-receptor BAK1. Here we show that BRI1 is post-translationally modified by K63 polyubiquitin chains in vivo. Artificially ubiquitinated BRI1 is recognized at the trans-Golgi Network/Early Endosomes (TGN/EE) and rapidly routed for vacuolar degradation. Mass spectrometry analyses identified residue K866 as an in vivo ubiquitination target in BRI1 involved in the negative regulation of BRI1. Model prediction revealed several redundant ubiquitination sites required for the endosomal sorting and vacuolar targeting of BRI1. Using total internal reflection fluorescence microscopy (TIRF), we also uncovered a role for BRI1 ubiquitination in promoting internalization from the cell-surface. Finally, we demonstrate that the control of BRI1 protein dynamics by ubiquitination is a fundamental control mechanism for BR responses in plants. Altogether, our results identify K63-linked polyubiquitin chain formation as a dual targeting signal for BRI1 internalization and sorting along the endocytic pathway, and highlight its role in hormonally controlled plant development. PMID:25608221

  3. Influence of sex steroid hormones on the adolescent brain and behavior: An update.

    PubMed

    Vigil, Pilar; Del Río, Juan Pablo; Carrera, BÁrbara; ArÁnguiz, Florencia C; Rioseco, Hernán; Cortés, Manuel E

    2016-08-01

    This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical "organizational window" for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary : The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental "organizational window" during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders.

  4. Influence of sex steroid hormones on the adolescent brain and behavior: An update

    PubMed Central

    Vigil, Pilar; del Río, Juan Pablo; Carrera, BÁrbara; ArÁnguiz, Florencia C.

    2016-01-01

    This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical “organizational window” for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary: The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental “organizational window” during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders. PMID:27833209

  5. Ovarian control of pituitary hormone secretion in early human pregnancy.

    PubMed

    Emmi, A M; Skurnick, J; Goldsmith, L T; Gagliardi, C L; Schmidt, C L; Kleinberg, D; Weiss, G

    1991-06-01

    To determine the influence of ovarian relaxin on the secretion of pituitary GH and PRL in vivo, we evaluated circulating serum hormone levels in 17 pregnant patients with functional corpora lutea (group I) and compared them to levels in 10 patients with premature ovarian failure (POF; group II) who became pregnant with egg donation and did not have corpora lutea. Group II patients had exogenous hormonal support. Serum relaxin (RLX), GH, PRL, estradiol (E2), and progesterone levels were measured weekly by RIA from weeks 4-8 of pregnancy. Analysis of variance and covariance were used to determine hormonal relationships. Serum RLX was present in the natural pregnancy group, with a mean of 1.94 micrograms/L over the study period. Serum RLX was undetectable in the POF patients (less than 0.16 micrograms/L). No significant difference in PRL or progesterone levels between the two groups was noted. E2 levels showed an upward trend in both groups with time and were significantly higher in patients of the POF group than in group I women (P = 0.001). GH levels were significantly higher in the natural cycle patients (P = 0.02) despite lower E2 levels. These data provide additional support for the concept that RLX production in early pregnancy originates from the corpus luteum. They suggest that a luteal product, probably RLX, stimulates GH secretion in early pregnancy. This is a previously undescribed role for RLX in pituitary physiology during human pregnancy.

  6. Effect of ovarian hormones on serum adiponectin and resistin concentrations.

    PubMed

    Chalvatzas, Nektarios; Dafopoulos, Konstantinos; Kosmas, Georgios; Kallitsaris, Athanasios; Pournaras, Spyros; Messinis, Ioannis E

    2009-04-01

    To investigate the effect of ovarian hormones on adiponectin and resistin levels in women. Experimental study. University hospital. Thirteen normally cycling women (7 in group 1 and 6 in group 2) and 8 postmenopausal women (group 3). Women of group 1 were investigated in a control cycle and in a subsequent cycle in which total abdominal hysterectomy plus bilateral salpingooophorectomy (TAH+BSO) was performed on day 3. In both cycles, the women received increasing doses of E(2) from days 3 to 5. Women of group 2 underwent TAH+BSO on day 3 without receiving any hormonal treatment. Women of group 3 received increasing doses of E(2) for 15 days. Adiponectin, resistin, and E(2) concentrations. In group 1, serum adiponectin and resistin levels did not show any significant changes for the week following day 3 and were similar in the two cycles. In group 2, adiponectin and resistin levels were similar before and after TAH+BSO and remained stable during the first postoperative week. In group 3, no significant changes in adiponectin and resistin levels were seen during the 15 days of E(2) administration. Adiponectin and resistin values were not affected either by estrogen treatment or after ovariectomy in women. It is suggested that ovarian hormones are not involved in the regulation of adiponectin and resistin secretion in women.

  7. Mink aging is associated with a reduction in ovarian hormone release and the response to FSH and ghrelin.

    PubMed

    Sirotkin, Alexander V; Mertin, Dušan; Süvegová, Karina; Lauričik, Jozef; Morovič, Martin; Harrath, Abdel Halim; Kotwica, Jan

    2016-09-15

    The endocrine mechanisms of mink ovarian hormones release and reproductive aging are poorly investigated. The aims of our study were to: (1) identify hormones produced by mink ovaries (the steroids progesterone [P] and estradiol [E], the peptide hormone oxytocin [OT], and the prostaglandin F [PGF] and prostaglandin E [PGE]); (2) examine the effect of FSH and ghrelin on the release of the hormones listed previously; and (3) understand whether these hormones can be involved in the control of mink reproductive aging, i.e., whether aging can be associated with changes (a) in the basal release of P, E, OT, PGF, or PGE and (b) their response to FSH and ghrelin. Fragments of ovaries of young (yearlings) and old (3-5 years of age) minks were cultured with and without FSH and ghrelin (0, 1, 10, or 100 ng/mL), and the release of hormones was analyzed by EIA/RIA. We found that isolated ovaries were able to release P, E, OT, PGF, and PGE, and the levels of P produced in the ovaries of old animals were lower than those produced in the ovaries of young animals, whereas the levels of other hormones did not differ. FSH was able to stimulate P and E and suppress OT and PGF and did not affect PGE release. Aging was associated with the inhibition of the effect of FSH on ovarian P and E, the appearance of the inhibitory action of FSH on OT, and the disappearance of this action on ovarian PGF. PGE was not affected by FSH, irrespective of animal age. Ghrelin was able to promote E (but not P) and suppress OT, PGF, and PGE output. Aging was associated with the appearance of an inhibitory influence of ghrelin on ovarian OT and PGE and with the disappearance of this influence on PGF output. Aging did not affect the action of ghrelin on ovarian P and E. Our observations (1) confirm the production of P and E and show that OT, PGF, and PGE are released from mink ovaries, (2) confirm the involvement of FSH and demonstrate the involvement of ghrelin in the control of mink ovarian hormone

  8. Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism.

    PubMed

    Muderris, Iptisam Ipek; Boztosun, Abdullah; Oner, Gokalp; Bayram, Fahri

    2011-01-01

    Primary hypothyroidism may be associated with ovarian enlargement and/ or cyst formation. We evaluated the effect of thyroid hormone replacement therapy on hormonal changes, ovarian volume and sonographic appearance. Open, prospective study of women admitted to university gynecology clinic. The study included 26 patients with untreated hypothyroidism who had polycystic (n=10) or normal-appearing (n=16) ovaries and 20 euthyroidic controls. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandosterone-sulfate, prolactin, estradiol, luteinizing hormone, follicle-stimulating hormone, free T3, free T4 and thyroid-stimulating horone, together with ovarian volumes, were determined and repeated after euthyroidism was achieved. Ovarian volumes of patients with hypothyroidism were significantly greater compared with controls, and their magnitudes diminished significantly during thyroid hormone replacement therapy. Hypothyroidic patients with polycystic ovaries had significantly higher serum free testosterone and dehydroepiandosterone-sulfate, but lower androstenodione levels compared with those who had normal-appearing ovaries. Serum total testosterone concentrations were significantly higher in hypothyroidic patients without polycystic ovaries, and thyroid hormone replacement therapy achieved a significant reduction in total as well as free testosterone. Severe longstanding hypothyroidism leads to increased ovarian volume and/or cyst formation. A decrease in ovarian volume, resolution of ovarian cysts and reversal of the polycystic ovary syndrome-like appearance, together with improvement in serum hormone levels, occurred after euthyroidism was achieved.

  9. The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

    PubMed

    Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

    2016-09-20

    Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

  10. The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

    PubMed Central

    Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

    2016-01-01

    Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors. PMID:27589836

  11. Associations between hormone receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study

    PubMed Central

    Sieh, Weiva; Köbel, Martin; Longacre, Teri A.; Bowtell, David D.; deFazio, Anna; Goodman, Marc T.; Høgdall, Estrid; Deen, Suha; Wentzensen, Nicolas; Moysich, Kirsten B.; Brenton, James D.; Clarke, Blaise; Menon, Usha; Gilks, C. Blake; Kim, Andre; Madore, Jason; Fereday, Sian; George, Joshy; Galletta, Laura; Lurie, Galina; Wilkens, Lynne R.; Carney, Michael E.; Thompson, Pamela J.; Matsuno, Rayna K.; Kjær, Susanne Krüger; Jensen, Allan; Høgdall, Claus; Kalli, Kimberly R.; Fridley, Brooke L.; Keeney, Gary L.; Vierkant, Robert A.; Cunningham, Julie M.; Brinton, Louise A.; Yang, Hannah P.; Sherman, Mark E.; Garcia-Closas, Montserrat; Lissowska, Jolanta; Odunsi, Kunle; Morrison, Carl; Lele, Shashikant; Bshara, Wiam; Sucheston, Lara; Jimenez-Linan, Mercedes; Blows, Fiona M.; Alsop, Jennifer; Mack, Marie; McGuire, Valerie; Rothstein, Joseph H.; Rosen, Barry P.; Bernardini, Marcus Q.; Mackay, Helen; Oza, Amit; Wozniak, Eva L.; Benjamin, Elizabeth; Gentry-Maharaj, Aleksandra; Gayther, Simon A.; Tinker, Anna V.; Prentice, Leah M.; Chow, Christine; Anglesio, Michael S.; Johnatty, Sharon E.; Chenevix-Trench, Georgia; Whittemore, Alice S.; Pharoah, Paul D. P.; Goode, Ellen L.; Huntsman, David G.; Ramus, Susan J.

    2014-01-01

    Background Ovarian cancer is a lethal disease comprised of distinct histopathological types. There are few established biomarkers of ovarian cancer prognosis, in part because subtype-specific associations may have been obscured in studies combining all subtypes. We examined whether progesterone receptor (PR) and estrogen receptor (ER) protein expression were associated with subtype-specific survival in the international Ovarian Tumor Tissue Analysis (OTTA) consortium. Methods PR and ER were assessed by central immunohistochemical analysis of tissue microarrays for 2933 women with invasive epithelial ovarian cancer from 12 study sites. Negative, weak, and strong expression were defined as positive staining in <1%, 1–50%, and ≥50% of tumor cell nuclei, respectively. Hazard ratios (HRs) for ovarian cancer death were estimated using Cox regression stratified by site and adjusted for age, stage, and grade. Results PR expression was associated with improved survival for endometrioid (EC; p<0·0001) and high-grade serous carcinoma (HGSC; p=0·0006), and ER expression was associated with improved EC survival (p<0·0001); no significant associations were found for mucinous, clear cell, or low-grade serous carcinoma. EC patients with hormone receptor (PR and/or ER) positive (weak or strong) versus negative tumors had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·33; 95% CI, 0·21–0·51; p<0·0001). HGSC patients with strong versus weak or negative tumor PR expression had significantly reduced risk of dying from their disease, independent of clinical factors (HR, 0·71; 95% CI, 0·55–0·91; p=0·0061). Interpretation PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to determine whether hormone receptor status predicts response to endocrine therapy, and can guide personalized treatment for ovarian cancer

  12. Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion.

    PubMed

    Toth, Michael J; Cooper, Brian C; Pratley, Richard E; Mari, Andrea; Matthews, Dwight E; Casson, Peter R

    2008-06-01

    Several lines of evidence suggest that ovarian hormones influence glucose homeostasis, although their exact role in humans has not been clearly defined. In the present study, we sought to test the hypothesis that ovarian hormones regulate glucose homeostasis by examining the effect of pharmacologically induced ovarian hormone deficiency on glucose disposal and insulin secretion. Young, healthy women with regular menstrual patterns were studied during the follicular and luteal phases of their cycle at baseline and after 2 mo of treatment with gonadotropin-releasing hormone agonist (GnRHa; n = 7) or placebo (n = 6). Using hyperglycemic clamps, in combination with stable isotope-labeled (i.e., (13)C and (2)H) glucose tracers, we measured glucose disposal and insulin secretion. Additionally, we assessed body composition and regional fat distribution using radiologic imaging techniques as well as glucoregulatory hormones. Ovarian hormone suppression with GnRHa did not alter body composition, abdominal fat distribution, or thigh tissue composition. There was no effect of ovarian suppression on total, oxidative, or nonoxidative glucose disposal expressed relative to plasma insulin level. Similarly, no effect of ovarian hormone deficiency was observed on first- or second-phase insulin secretion or insulin clearance. Finally, ovarian hormone deficiency was associated with an increase in circulating adiponectin levels but no change in leptin concentration. Our findings suggest that a brief period of ovarian hormone deficiency in young, healthy, eugonadal women does not alter glucose disposal index or insulin secretion, supporting the conclusion that ovarian hormones play a minimal role in regulating glucose homeostasis. Our data do, however, support a role for ovarian hormones in the regulation of plasma adiponectin levels.

  13. The role of alcohol and steroid hormones in human aggression.

    PubMed

    von der Pahlen, Bettina

    2005-01-01

    The association between alcohol and aggressive behavior is well established although a direct causal relationship has proven hard to demonstrate. There are, however, indications that alcohol facilitates aggression in individuals who already have a predisposition to behave aggressively. Aggressive personality disorders have in turn been explained by elevated testosterone level. A one-to-one relation between increased levels of testosterone and aggression has been, nevertheless, difficult to reveal. Two metabolites of testosterone, estradiol and 5alpha-dihydrotestosterone (DHT), have been studied much less in human aggressive behavior. Estradiol might reduce androgenic effects and have a counterbalancing influence on aggression. DHT, again, has a much higher affinity than testosterone to androgen receptors, and there are indications that some of the effects of testosterone-mediating aggressive behavior occur after aromatization. Disregard of seasonal and circadian fluctuations in male testosterone production might be responsible for some of the inconclusive testosterone-aggression results. In addition, increasing age decreases both aggressive behavior and testosterone production in males. Cortisol has yielded conflicting results as a mediator in aggressive behavior. Both higher and lower levels have been reported in aggressive and abusive men. Finally, the acute and chronic effects of alcohol influence the steroid hormone levels in various ways. The present understanding of the etiology of aggression is still vague. It is clear that a multidimensional approach, combining both biological and psychosocial factors, will be necessary for the development of a more general concept of human aggression in the future.

  14. Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action

    PubMed Central

    2009-01-01

    Biochemical tests have been the basis for investigations of disorders affecting steroid hormones. In recent years it has been possible however to study the genes that determine functional enzymes, cofactors, receptors, transcription factors and signaling systems that are involved in the process. Analyses of mutations are available as a diagnostic service for only a few of these genes although research laboratories may be able to provide a service. Both biochemical and genetic research have brought to light new disorders. Some genes for transcription factors involved in the development of the endocrine organs have also been identified and patients with defects in these processes have been found. This paper will review general aspects of adrenal disorders with emphasis on clinical and laboratory findings. As with all endocrine investigations there are few single measurements that provide a definitive answer to a diagnosis. Timing of samples in relation to age, gender and time of day needs to be considered. Conflict of interest:None declared. PMID:21274298

  15. From molecule to market: steroid hormones and financial risk-taking.

    PubMed

    Coates, John M; Gurnell, Mark; Sarnyai, Zoltan

    2010-01-27

    Little is known about the role of the endocrine system in financial decision-making. Here, we survey research on steroid hormones and their cognitive effects, and examine potential links to trader performance in the financial markets. Preliminary findings suggest that cortisol codes for risk and testosterone for reward. A key finding of this endocrine research is the different cognitive effects of acute versus chronic exposure to hormones: acutely elevated steroids may optimize performance on a range of tasks; but chronically elevated steroids may promote irrational risk-reward choices. We present a hypothesis suggesting that the irrational exuberance and pessimism observed during market bubbles and crashes may be mediated by steroid hormones. If hormones can exaggerate market moves, then perhaps the age and sex composition among traders and asset managers may affect the level of instability witnessed in the financial markets.

  16. From molecule to market: steroid hormones and financial risk-taking

    PubMed Central

    Coates, John M.; Gurnell, Mark; Sarnyai, Zoltan

    2010-01-01

    Little is known about the role of the endocrine system in financial decision-making. Here, we survey research on steroid hormones and their cognitive effects, and examine potential links to trader performance in the financial markets. Preliminary findings suggest that cortisol codes for risk and testosterone for reward. A key finding of this endocrine research is the different cognitive effects of acute versus chronic exposure to hormones: acutely elevated steroids may optimize performance on a range of tasks; but chronically elevated steroids may promote irrational risk-reward choices. We present a hypothesis suggesting that the irrational exuberance and pessimism observed during market bubbles and crashes may be mediated by steroid hormones. If hormones can exaggerate market moves, then perhaps the age and sex composition among traders and asset managers may affect the level of instability witnessed in the financial markets. PMID:20026470

  17. Corticosterone metabolism by chicken follicle cells does not affect ovarian reproductive hormone synthesis in vitro

    PubMed Central

    Rettenbacher, Sophie; Henriksen, Rie; Groothuids, Ton G.; Lepschy, Michael

    2013-01-01

    Glucocorticoids affect reproductive hormone production in many species. In chickens, elevated plasma corticosterone down-regulates testosterone and progesterone concentrations in plasma, but also in egg yolk. This suppression could be mediated via the hypothalamic-pituitary system but also via local inhibition of gonadal activity by glucocorticoids. As the latter has not been tested in birds yet, we tested if corticosterone directly inhibits ovarian steroid synthesis under in vitro conditions. We hypothesized that degradation of corticosterone by follicular cells impairs their ability to synthesize reproductive hormones due to either inhibition of enzymes or competition for common co-factors. Therefore, we first established whether follicles degrade corticosterone. Follicular tissue was harvested from freshly euthanized laying hens and incubated with radiolabelled corticosterone. Radioactive metabolites were visualized and quantified by autoradiography. Follicles converted corticosterone in a time-dependent manner into metabolites with a higher polarity than corticosterone. The predominant metabolite co-eluted with 20β-dihydrocorticosterone. Other chicken tissues mostly formed the same metabolite when incubated with corticosterone. In a second experiment, follicles were incubated with either progesterone or dehydroepiandrosterone. Corticosterone was added in increasing dosages up to 1000 ng per ml medium. Corticosterone did not inhibit the conversion of progesterone and dehydroepiandrosterone into a number of different metabolites, including 17α-hydroxyprogesterone, androstenedione and testosterone. In conclusion, avian tissues degrade corticosterone mostly to 20β-dihydrocorticosterone and even high corticosterone dosages do not affect follicular hormone production under in vitro conditions. PMID:23333751

  18. The role of ovarian sex steroids in metabolic homeostasis, obesity, and postmenopausal breast cancer: molecular mechanisms and therapeutic implications.

    PubMed

    Boonyaratanakornkit, Viroj; Pateetin, Prangwan

    2015-01-01

    Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.

  19. The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

    PubMed Central

    2015-01-01

    Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer. PMID:25866757

  20. Ovarian hormones through Wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions

    PubMed Central

    Nagendra, Prathima B.; Goad, Jyoti; Nielsen, Sarah; Rassam, Loui; Lombard, Janine M.; Nahar, Pravin; Tanwar, Pradeep S.

    2016-01-01

    Ovarian cancer (OC) is the most deadly gynaecological disease largely because the majority of patients are asymptomatic and diagnosed at later stages when cancer has spread to other vital organs. Therefore, the initial stages of this disease are poorly characterised. Women with BRCA1/2 mutations have a genetic predisposition for developing OC, but not all of these women develop the disease. Epidemiological findings show that lifestyle factors such as contraceptive use and pregnancy, a progesterone dominant state, decrease the risk of getting OC. How ovarian hormones modify the risk of OC is currently unclear. Our study identifies activated Wnt signalling to be a marker for precursor lesions of OC and successfully develops a mouse model that mimics the earliest events in pathogenesis of OC by constitutively activating βcatenin. Using this model and human OC cells, we show that oestrogen promotes and progesterone suppresses the growth of OC cells. PMID:27588493

  1. Progesterone increased β-endorphin innervation of the locus coeruleus, but ovarian steroids had no effect on noradrenergic neurodegeneration.

    PubMed

    Lima, Fernanda B; Leite, Cristiane M; Bethea, Cynthia L; Anselmo-Franci, Janete A

    2017-05-15

    With the decline of ovarian steroids levels at menopause, many women experience an increase in anxiety and stress sensitivity. The locus coeruleus (LC), a central source of noradrenaline (NE), is activated by stress and is inhibited by β-endorphin. Moreover, increased NE has been implicated in pathological anxiety syndromes. Hormone replacement therapy (HRT) in menopause appears to decrease anxiety and vulnerability to stress. Therefore, we questioned the effect of HRT on the inhibitory β-endorphin innervation of the LC. In addition, we found that progesterone protects serotoninergic neurons in monkeys, leading us to question whether ovarian steroids are also neuroprotective in LC neurons in monkeys. Adult Rhesus monkeys (Macaca mulatta) were ovariectomized, and either treated with Silastic capsules that contained estradiol, estradiol+progesterone, progesterone alone or that were empty (ovariectomized; control). After 1month, the LC was obtained and processed for immunohistochemistry for β-endorphin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The density of β-endorphin axons was determined with image analysis using ImageJ. The TUNEL-positive neurons were counted in the entire LC. Progesterone-alone significantly increased the density of the β-endorphin axons in the LC (p<0.01). No significant differences between groups in the number of TUNEL-positive cells in the LC were found. In conclusion, we found that HRT increases the inhibitory influence of β-endorphin in the LC, which could, in turn, contribute to reduce anxiety and increase stress resilience. In addition, we did not find compelling evidence of neurodegeneration or neuroprotection by HRT in the LC of Rhesus monkeys.

  2. Do mollusks use vertebrate sex steroids as reproductive hormones? II. Critical review of the evidence that steroids have biological effects.

    PubMed

    Scott, Alexander P

    2013-02-01

    In assessing the evidence as to whether vertebrate sex steroids (e.g. testosterone, estradiol, progesterone) have hormonal actions in mollusks, ca. 85% of research papers report at least one biological effect; and 18 out of 21 review papers (published between 1970 and 2012) express a positive view. However, just under half of the research studies can be rejected on the grounds that they did not actually test steroids, but compounds or mixtures that were only presumed to behave as steroids (or modulators of steroids) on the basis of their effects in vertebrates (e.g. Bisphenol-A, nonylphenol and sewage treatment effluents). Of the remaining 55 papers, some can be criticized for having no statistical analysis; some for using only a single dose of steroid; others for having irregular dose-response curves; 40 out of the 55 for not replicating the treatments; and 50 out of 55 for having no within-study repetition. Furthermore, most studies had very low effect sizes in comparison to fish-based bioassays for steroids (i.e. they had a very weak 'signal-to-noise' ratio). When these facts are combined with the fact that none of the studies were conducted with rigorous randomization or 'blinding' procedures (implying the possibility of 'operator bias') one must conclude that there is no indisputable bioassay evidence that vertebrate sex steroids have endocrinological or reproductive roles in mollusks. The only observation that has been independently validated is the ability of estradiol to trigger rapid (1-5 min) lysosomal membrane breakdown in hemocytes of Mytilus spp. This is a typical 'inflammatory' response, however, and is not proof that estradiol is a hormone - especially when taken in conjunction with the evidence (discussed in a previous review) that mollusks have neither the enzymes necessary to synthesize vertebrate steroids nor nuclear receptors with which to respond to them. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. In Vivo Regulation of Steroid Hormones by the Chst10 Sulfotransferase in Mouse*

    PubMed Central

    Suzuki-Anekoji, Misa; Suzuki, Atsushi; Wu, Sz-Wei; Angata, Kiyohiko; Murai, Keith K.; Sugihara, Kazuhiro; Akama, Tomoya O.; Khoo, Kay-Hooi; Nakayama, Jun; Fukuda, Michiko N.; Fukuda, Minoru

    2013-01-01

    Chst10 adds sulfate to glucuronic acid to form a carbohydrate antigen, HNK-1, in glycoproteins and glycolipids. To determine the role of Chst10 in vivo, we generated systemic Chst10-deficient mutant mice. Although Chst10−/− mice were born and grew to adulthood with no gross defects, they were subfertile. Uteri from Chst10−/− females at the pro-estrus stage were larger than those from wild-type females and exhibited a thick uterine endometrium. Serum estrogen levels in Chst10−/− females were higher than those from wild-type females, suggesting impaired down-regulation of estrogen. Because steroid hormones are often conjugated to glucuronic acid, we hypothesized that Chst10 sulfates glucuronidated steroid hormone to regulate steroid hormone in vivo. Enzymatic activity assays and structural analysis of Chst10 products by HPLC and mass spectrometry revealed that Chst10 indeed sulfates glucuronidated estrogen, testosterone, and other steroid hormones. We also identified an HPLC peak corresponding to sulfated and glucuronidated estradiol in serum from wild-type but not from Chst10 null female mice. Estrogen-response element reporter assays revealed that Chst10-modified estrogen likely did not bind to its receptor. These results suggest that subfertility exhibited by female mice following Chst10 loss results from dysregulation of estrogen. Given that Chst10 transfers sulfates to several steroid hormones, Chst10 likely functions in widespread regulation of steroid hormones in vivo. PMID:23269668

  4. Variation with semilunar periodicity of plasma steroid hormone production in the mudskipper Boleophthalmus pectinirostris.

    PubMed

    Wang, Qiong; Hong, Wanshu; Chen, Shixi; Zhang, Qiyong

    2008-02-01

    Variation in the production of the plasma steroid hormones E(2), 17alpha-OHP and T in females and T and 11-KT in males, was investigated in the mudskipper Boleophthalmus pectinirostris during the spawning season. Females with oocytes at the vitellogenic stage (GSI 5.97-6.86%) and mature males with GSI of 0.255-0.288% were collected at intervals of 3-4 days within the two complete semilunar cycles from May 31 to June 30, 2006. The results showed that variations in the levels of plasma steroid hormones were synchronized obviously with semilunar periodicity in both females and males. Each steroid hormone level exhibited two cycles, each cycle with a peak. In females, the first peaks in plasma E(2), 17alpha-OHP and T levels were observed 3 days after the first lunar quarter, and the second ones, 4 days after the last lunar quarter. In males, the first peaks of plasma T and 11-KT levels occurred 3 days after the first lunar quarter, and the second ones, at the last lunar quarter. The fact that, in the present study, changes in the levels of plasma steroid hormones were synchronized with semilunar periodicity, although the fish were at the same stages of gonadal development, suggests that variation of plasma steroid hormones is basically regulated by biological rhythms (Zeitgebers), and that tidal movement (with its semilunar periodicity) is the major environmental factor stimulating steroid hormone production in B. pectinirostris.

  5. Differential Responses to Steroid Hormones in Fibroblasts From the Vocal Fold, Trachea, and Esophagus

    PubMed Central

    Mukudai, Shigeyuki; Matsuda, Ken Ichi; Nishio, Takeshi; Sugiyama, Yoichiro; Bando, Hideki; Hirota, Ryuichi; Sakaguchi, Hirofumi; Hisa, Yasuo

    2015-01-01

    There is accumulating evidence that fibroblasts are target cells for steroids such as sex hormones and corticoids. The characteristics of fibroblasts vary among tissues and organs. Our aim in this study is to examine differences in responses to steroid hormones among fibroblasts from different cervicothoracic regions. We compared the actions of steroid hormones on cultured fibroblasts from the vocal folds, which are considered to be the primary target of steroid hormones, and the trachea and esophagus in adult male rats. Expression of steroid hormone receptors (androgen receptor, estrogen receptor α, and glucocorticoid receptor) was identified by immunofluorescence histochemistry. Androgen receptor was much more frequently expressed in fibroblasts from the vocal fold than in those from the trachea and esophagus. Cell proliferation analysis showed that administration of testosterone, estradiol, or corticosterone suppressed growth of all 3 types of fibroblasts. However, mRNA expression for extracellular matrix–associated genes, including procollagen I and III and elastin, and hyaluronic acid synthase I was elevated only by addition of testosterone to fibroblasts from the vocal fold. These results indicate that each steroid hormone exerts region-specific effects on cervicothoracic fibroblasts with different properties through binding to specific receptors. PMID:25514085

  6. Tissue expression of steroid hormone receptors is associated with differential immune responsiveness

    PubMed Central

    Butts, Cherié L.; Jones, Yava L.; Lim, Jean K.; Salter, Caroline E.; Belyavskaya, Elena; Sternberg, Esther M.

    2010-01-01

    Glucocorticoids and other steroid hormones have been used as treatments against a number of diseases, especially inflammatory conditions in which the immune system is overactive. These treatments have varying degrees of responsiveness among individuals and in different tissues (including brain); therefore, it is important to determine what could account for these differences. In this study, we evaluated expression of steroid hormone receptors in immune cells from lymphoid and non-lymphoid tissues as a possible explanation for tissue-specific differences. We analyzed leukocytes (CD45+) in kidney, liver, spleen, and thymus tissues from healthy mice for expression of the receptor for stress hormone (glucocorticoid - GR) as well as other steroid hormones (androgen - AR, progesterone - PR) and found that all tissues expressed these steroid hormone receptors but with varying expression patterns. To determine whether tissue-specific differences were related to immune cell composition, we examined steroid hormone receptor expression in T lymphocytes from each of these tissues and found similar patterns of expression in these cells regardless of tissue source. Because glucocorticoids can also impact brain function, we further examined expression of the stress hormone receptor in brain tissue and found GR expressed in immune cells at this site. In order to investigate the potential impact in an area of neuropathology, we utilized a mouse model of West Nile Virus (WNV). We observed pathological changes in brains of WNV-infected animals and T lymphocytes in the areas of inflammation; however, these cells did not express GR. These data indicate that tissue-specific differences in steroid hormone receptor expression by immune cells could determine responsiveness with steroid hormone treatment. PMID:21074604

  7. Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease.

    PubMed

    Jeong, Jae-Wook; Lee, Hee Sun; Lee, Kevin Y; White, Lisa D; Broaddus, Russell R; Zhang, Yu-Wen; Vande Woude, George F; Giudice, Linda C; Young, Steven L; Lessey, Bruce A; Tsai, Sophia Y; Lydon, John P; DeMayo, Francesco J

    2009-05-26

    Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence of Mig-6 in mice results in the inability of P4 to inhibit E2-induced uterine weight gain and E2-responsive target genes expression. At 5 months of age, the absence of Mig-6 results in endometrial hyperplasia. Ovariectomized Mig-6(d/d) mice exhibit this hyperplastic phenotype in the presence of E2 and P4 but not without ovarian hormone. Ovariectomized Mig-6(d/d) mice treated with E2 developed invasive endometrioid-type endometrial adenocarcinoma. Importantly, the observation that endometrial carcinomas from women have a significant reduction in MIG-6 expression provides compelling support for an important growth regulatory role for Mig-6 in the uterus of both humans and mice. This demonstrates the Mig-6 is a critical regulator of the response of the endometrium to E2 in regulating tissue homeostasis. Since Mig-6 is regulated by both PR and SRC-1, this identifies a PR, SRC-1, Mig-6 regulatory pathway that is critical in the suppression of endometrial cancer.

  8. Perfluoroalkyl substances and ovarian hormone concentrations in naturally cycling women.

    PubMed

    Barrett, Emily S; Chen, Chongshu; Thurston, Sally W; Haug, Line Småstuen; Sabaredzovic, Azemira; Fjeldheim, Frøydis Nyborg; Frydenberg, Hanne; Lipson, Susan F; Ellison, Peter T; Thune, Inger

    2015-05-01

    To examine associations between environmental exposure to perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women. E2 and P were measured in saliva samples collected daily for a single menstrual cycle and concentrations of PFASs (including perfluoroctane sulfonate [PFOS] and perfluoroctanoic acid) were measured in serum samples collected during the same cycle. Not applicable. A total of 178 healthy, naturally cycling women, aged 25-35 years. None. Mean follicular E2 (cycle days -7 to -1, where 0 is the day of ovulation); mean luteal P (cycle days +2 to 10). Among nulliparous, but not parous women, PFOS concentrations were inversely associated with E2 (β = -0.025, 95% CI -0.043, -0.007) and P (β = -0.027, 95% CI -0.048, -0.007). Similar, but weaker results were observed for perfluorooctanesulfonic acid. No associations were observed between other PFASs (including perfluoroctanoic acid) and ovarian steroid concentrations, nor were any associations noted in parous women. Our results demonstrate that PFOS and perfluorooctanesulfonic acid may be associated with decreased production of E2 and P in reproductive age women. These results suggest a possible mechanism by which PFASs affect women's health, and underscore the importance of parity in research on PFASs and women's reproductive health. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women

    PubMed Central

    Barrett, Emily S.; Chen, Chongshu; Thurston, Sally W.; Haug, Line Småstuen; Sabaredzovic, Azemira; Fjeldheim, Frøydis Nyborg; Frydenberg, Hanne; Lipson, Susan F.; Ellison, Peter T.; Thune, Inger

    2015-01-01

    Objective To examine associations between environmental exposure to perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women. Design Estradiol and progesterone were measured in saliva samples collected daily for a single menstrual cycle and concentrations of PFASs (including perfluoroctane sulfonate [PFOS] and perfluoroctanoic acid [PFOA]) were measured in serum samples collected during the same cycle. Setting Tromsø, Norway. Patients 178 healthy, naturally cycling women, ages 25-35. Intervention None. Main outcome measures(s) Mean follicular estradiol (cycle days −7 to −1, where 0 is the day of ovulation); mean luteal progesterone (cycle days +2 to 10). Results Among nulliparous, but not parous women, PFOS concentrations were inversely associated with estradiol (β=−0.025, 95% CI: −0.043, −0.007) and progesterone (β=−0.027, 95% CI: −0.048, −0.007). Similar, but weaker results were observed for perfluorooctanesulfonic acid (PFOSA). No associations were observed between other PFASs (including PFOA) and ovarian steroid concentrations, nor were any associations noted in parous women. Conclusions Our results demonstrate that PFOS and PFOSA may be associated with decreased production of estradiol and progesterone in reproductive age women. These results suggest a possible mechanism by which PFASs affect women's health, and underscore the importance of parity in research on PFASs and women's reproductive health. PMID:25747128

  10. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    SciTech Connect

    Hannon, Patrick R. Brannick, Katherine E. Wang, Wei Gupta, Rupesh K. Flaws, Jodi A.

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  11. Therapeutic uses of contraceptive steroids.

    PubMed

    Starks, G C

    1984-09-01

    During the past 20 years, contraceptive steroids have undergone significant changes as the result of an increased understanding of their metabolic, pharmacologic, and hormonal activities. During this time, prospective and retrospective epidemiologic studies have elucidated several noncontraceptive health benefits of oral contraceptive steroids, including their therapeutic effects for endometriosis, dysmenorrhea, polycystic ovarian disease, and benign breast disease. From this review it appears that the benefits of oral contraceptive steroids in young, healthy, nonsmoking women far outweigh their more publicized, infrequent risks.

  12. Parasites and steroid hormones: corticosteroid and sex steroid synthesis, their role in the parasite physiology and development.

    PubMed

    Romano, Marta C; Jiménez, Pedro; Miranda-Brito, Carolina; Valdez, Ricardo A

    2015-01-01

    In many cases parasites display highly complex life cycles that include the penetration and permanence of the larva or adults within host organs, but even in those that only have one host, reciprocal, intricate interactions occur. Evidence indicates that steroid hormones have an influence on the development and course of parasitic infections. The host gender's susceptibility to infection, and the related differences in the immune response are good examples of the host-parasite interplay. However, the capacity of these organisms to synthesize their own steroidogenic hormones still has more questions than answers. It is now well-known that many parasites synthesize ecdysteroids, but limited information is available on sex steroid and corticosteroid synthesis. This review intends to summarize some of the existing information in the field. In most, but not all parasitosis the host's hormonal environment determines the susceptibility, the course, and severity of parasite infections. In most cases the infection disturbs the host environment, and activates immune responses that end up affecting the endocrine system. Furthermore, sex steroids and corticosteroids may also directly modify the parasite reproduction and molting. Available information indicates that parasites synthesize some steroid hormones, such as ecdysteroids and sex steroids, and the presence and activity of related enzymes have been demonstrated. More recently, the synthesis of corticosteroid-like compounds has been shown in Taenia solium cysticerci and tapeworms, and in Taenia crassiceps WFU cysticerci. In-depth knowledge of the parasite's endocrine properties will contribute to understand their reproduction and reciprocal interactions with the host, and may also help designing tools to combat the infection in some clinical situations.

  13. Parasites and steroid hormones: corticosteroid and sex steroid synthesis, their role in the parasite physiology and development

    PubMed Central

    Romano, Marta C.; Jiménez, Pedro; Miranda-Brito, Carolina; Valdez, Ricardo A.

    2015-01-01

    In many cases parasites display highly complex life cycles that include the penetration and permanence of the larva or adults within host organs, but even in those that only have one host, reciprocal, intricate interactions occur. Evidence indicates that steroid hormones have an influence on the development and course of parasitic infections. The host gender's susceptibility to infection, and the related differences in the immune response are good examples of the host-parasite interplay. However, the capacity of these organisms to synthesize their own steroidogenic hormones still has more questions than answers. It is now well-known that many parasites synthesize ecdysteroids, but limited information is available on sex steroid and corticosteroid synthesis. This review intends to summarize some of the existing information in the field. In most, but not all parasitosis the host's hormonal environment determines the susceptibility, the course, and severity of parasite infections. In most cases the infection disturbs the host environment, and activates immune responses that end up affecting the endocrine system. Furthermore, sex steroids and corticosteroids may also directly modify the parasite reproduction and molting. Available information indicates that parasites synthesize some steroid hormones, such as ecdysteroids and sex steroids, and the presence and activity of related enzymes have been demonstrated. More recently, the synthesis of corticosteroid-like compounds has been shown in Taenia solium cysticerci and tapeworms, and in Taenia crassiceps WFU cysticerci. In-depth knowledge of the parasite's endocrine properties will contribute to understand their reproduction and reciprocal interactions with the host, and may also help designing tools to combat the infection in some clinical situations. PMID:26175665

  14. Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

    PubMed Central

    Auger, Catherine J.; Coss, Dylan; Auger, Anthony P.; Forbes-Lorman, Robin M.

    2011-01-01

    Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems. PMID:21368111

  15. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

    PubMed

    Nykjaer, A; Fyfe, J C; Kozyraki, R; Leheste, J R; Jacobsen, C; Nielsen, M S; Verroust, P J; Aminoff, M; de la Chapelle, A; Moestrup, S K; Ray, R; Gliemann, J; Willnow, T E; Christensen, E I

    2001-11-20

    Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D(3) complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D(3) in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid-carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D(3). This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.

  16. SDR-type human hydroxysteroid dehydrogenases involved in steroid hormone activation.

    PubMed

    Wu, Xiaoqiu; Lukacik, Petra; Kavanagh, Kathryn L; Oppermann, Udo

    2007-02-01

    Hydroxysteroid dehydrogenases catalyze the NAD(P)(H)-dependent oxidoreduction of hydroxyl and oxo-functions at distinct positions of steroid hormones. This reversible reaction constitutes an important pre-receptor control mechanism for nuclear receptor ligands of the androgen, estrogen and glucocorticoid classes, since the conversion "switches" between receptor ligands and their inactive metabolites. The major reversible activities found in mammals acting on steroid hormones comprise 3alpha-, 11beta- and 17beta-hydroxysteroid dehydrogenases, and for each group several distinct isozymes have been described. The enzymes differ in their expression pattern, nucleotide cofactor preference, steroid substrate specificity and subcellular localization, and thus constitute a complex system ensuring cell-specific adaptation and regulation of steroid hormone levels. Several isoforms constitute promising drug targets, of particular importance in cancer, metabolic diseases, neurodegeneration and immunity.

  17. Music increase altruism through regulating the secretion of steroid hormones and peptides.

    PubMed

    Fukui, Hajime; Toyoshima, Kumiko

    2014-12-01

    Music is well known for its effect on human behavior especially of their bonding and empathy towards others. Music provokes one's emotion and activates mirror neurons and reward system. It also regulates social hormones such as steroid hormones or peptides, and increases empathy, pro-sociality and altruism. As a result, it improves one's reproductive success. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. INTERLABORATORY STUDY ON THE USE OF STEROID HORMONES IN EXAMINING ENDOCRINE DISRUPTION.

    EPA Science Inventory

    In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among ...

  19. AN INTERLABORATORY STUDY ON THE USE OF STEROID HORMONES IN EVALUATING ENDOCRINE DISRUPTION

    EPA Science Inventory

    In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among a...

  20. INTERLABORATORY STUDY ON THE USE OF STEROID HORMONES IN EXAMINING ENDOCRINE DISRUPTION.

    EPA Science Inventory

    In recent years, there has been an increased use of the measurement of sex steroid hormone levels in the blood of animals exposed to chemicals as an indicator of reproductive impairment or an alteration in endocrine function. Although levels of hormones are often compared among ...

  1. Oocyte production and ovarian steroid concentrations of immature rats in response to some commercial gonadotrophin preparations.

    PubMed

    Henderson, K M; Weaver, A; Wards, R L; Ball, K; Lun, S; Mullin, C; McNatty, K P

    1990-01-01

    Four commercial gonadotrophin preparations, namely Folligon, F.S.H.-P., Folltropin and Ovagen, were examined for their effects on oocyte production and ovarian steroid concentrations in immature rats. The ratios of the FSH to LH concentrations of the preparations, determined by radioreceptor assays, were Folligon 5, F.S.H.-P. 18, Folltropin 49 and Ovagen 1090. Forty-eight hours after administering each gonadotrophin preparation to immature rats, ovulation was induced by injection of chorionic gonadotrophin. Twenty-four hours later, oocytes were recovered from the oviducts and counted. Oocytes were produced after injection of chorionic gonadotrophin following a single injection of Folligon (10-50 i.u.). However, no oocytes were produced in response to the other gonadotrophin preparations unless they were administered by continuous infusion (30-1000 micrograms day-1). When given by injection (Folligon) or infusion (others), the gonadotrophin preparations all promoted a dose-dependent increase in mean oocyte production, except at the highest doses when mean oocyte numbers either remained unchanged or declined significantly in the cases of Folligon and F.S.H.-P. The highest mean numbers of oocytes produced in response to Folltropin (48 +/- 9 oocytes, mean +/- s.e.m.) and Ovagen (47 +/- 7) were greater than those attained with Folligon (21 +/- 6) or F.S.H.-P. (31 +/- 5). Mean ovarian weights also increased in a dose-dependent fashion in response to each of the gonadotrophin preparations. Measurements of ovarian steroid concentrations 48 h after the onset of gonadotrophin treatment (i.e. immediately prior to ovulation induction with chorionic gonadotrophin) showed that the gonadotrophin preparations markedly influenced the ratios of ovarian oestradiol-17 beta and androgen (androstenedione plus testosterone) concentrations. At low doses the gonadotrophin preparations increased the ratio of oestradiol-17 beta to androgens, but at the highest doses, with the exception of

  2. Monoamines and ovarian hormone-linked sexual and emotional changes: A review.

    PubMed

    Janowsky, D S; Fann, W E; Davis, J M

    1971-09-01

    , progesterone exhibits sedative and soporific effects. Sexual behavior in female rats is reported linked to changes in brain monoamines. Agents increasing brain monoamine levels and availability decrease mating responses, and monoamine depletors, such as reserpine may be substituted for progesterone in activating mating behavior. Serotonin and dopamine appear to be important in the regulation of ovulation. Brain norepinephrine varies with the phases of the rat estrus cycle. Castration increases brain norepinephrine and decreases brain dopamine. Exogenous estrogen decreases rat brain norepinephrine content. The monoamine-destroying enzymes, monoamine oxidase, and catechol O-methyl transferase are affected by ovarian steroids and show fluctuating levels during the reproductive cycle. The effects of reserpine, monoamine oxidase inhibitors, tricyclic antidepressants, and lithium on monoamines in neurophysiological preparations have been used as evidence supporting theories linking monoamine changes with human affective disorders. Estrogen, progesterone, and angiotensin also exhibit effects on in vitromonoamine systems. Like the tricyclic antidepressants, uptake of norepinephrine and dopamine by nerve endings is inhibited in the presence of estrogen, progesterone, and angiotensin. As with reserpine, the flow of these monoamines from nerve endings is increased by progesterone. Estrogen slows the flow of norepinephrine from nerve endings and decreases the electrically induced release of serotonin and norepinephrine from brain slices. The above information provides clues that ovarian hormone-linked psychopathology, like affective disorders in general, may be related to alterations in brain monoamines.

  3. The effect of elevated ovarian hormones on periodontal health: oral contraceptives and pregnancy.

    PubMed

    Zachariasen, R D

    1993-01-01

    The most common oral manifestation of elevated levels of ovarian hormones, as seen in pregnancy or oral contraceptive usage, is an increase in gingival inflammation with an accompanying increase in gingival exudate. This gingivitis can be avoided or at least minimized by establishing low plaque levels at the beginning of pregnancy or the beginning of oral contraceptive therapy. It would appear that bacteria are not solely responsible for the gingivitis seen during these times, nor are the ovarian hormones solely responsible for the condition. Data from numerous studies suggest that the ovarian hormones alter the microenvironment of the oral bacteria so as to promote their growth and shifts in their populations. The present article reviews the current state of knowledge concerning the relationship of gingivitis to elevated levels of ovarian hormones, and describes the role that these hormones may play in the gingivitis associated with pregnancy or oral contraceptive usage.

  4. Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities.

    PubMed

    Bartelt-Hunt, Shannon; Snow, Daniel D; Damon-Powell, Teyona; Miesbach, David

    2011-04-25

    Wastewater impoundments at concentrated animal feeding operations (CAFOs) represent a potential source of veterinary pharmaceuticals and steroid hormone contamination to shallow groundwater. This study investigates the occurrence of seventeen veterinary pharmaceuticals and thirteen steroid hormones and hormone metabolites in lagoons and adjacent groundwater at operating swine and beef cattle facilities. These sites were chosen because subsurface geology and previous monitoring of nitrate, ammonia and chloride levels in shallow ground water strongly indicated direct infiltration, and as such represent worst cases for ground water contamination by waste water. Pharmaceutical compounds detected in samples obtained from cattle facilities include sulfamerazine; sulfamethazine; erythromycin; monensin; tiamulin; and sulfathiazole. Lincomycin; ractopamine; sulfamethazine; sulfathiazole; erythromycin; tiamulin and sulfadimethoxine were detected in wastewater samples obtained from swine facilities. Steroid hormones were detected less frequently than veterinary pharmaceuticals in this study. Estrone, testosterone, 4-androstenedione, and androsterone were detected in wastewater impoundments at concentrations ranging from 30 to 3600ng/L, while only estrone and testosterone were detected in groundwater samples at concentrations up to 390ng/L. The co-occurrence of veterinary pharmaceutical and steroid hormone contamination in groundwater at these locations and the correlation between pharmaceutical occurrence in lagoon wastewater and hydraulically downgradient groundwater indicates that groundwater underlying some livestock wastewater impoundments is susceptible to contamination by veterinary pharmaceuticals and steroid hormones originating in wastewater lagoons. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities

    NASA Astrophysics Data System (ADS)

    Bartelt-Hunt, Shannon; Snow, Daniel D.; Damon-Powell, Teyona; Miesbach, David

    2011-04-01

    Wastewater impoundments at concentrated animal feeding operations (CAFOs) represent a potential source of veterinary pharmaceuticals and steroid hormone contamination to shallow groundwater. This study investigates the occurrence of seventeen veterinary pharmaceuticals and thirteen steroid hormones and hormone metabolites in lagoons and adjacent groundwater at operating swine and beef cattle facilities. These sites were chosen because subsurface geology and previous monitoring of nitrate, ammonia and chloride levels in shallow ground water strongly indicated direct infiltration, and as such represent worst cases for ground water contamination by waste water. Pharmaceutical compounds detected in samples obtained from cattle facilities include sulfamerazine; sulfamethazine; erythromycin; monensin; tiamulin; and sulfathiazole. Lincomycin; ractopamine; sulfamethazine; sulfathiazole; erythromycin; tiamulin and sulfadimethoxine were detected in wastewater samples obtained from swine facilities. Steroid hormones were detected less frequently than veterinary pharmaceuticals in this study. Estrone, testosterone, 4-androstenedione, and androsterone were detected in wastewater impoundments at concentrations ranging from 30 to 3600 ng/L, while only estrone and testosterone were detected in groundwater samples at concentrations up to 390 ng/L. The co-occurrence of veterinary pharmaceutical and steroid hormone contamination in groundwater at these locations and the correlation between pharmaceutical occurrence in lagoon wastewater and hydraulically downgradient groundwater indicates that groundwater underlying some livestock wastewater impoundments is susceptible to contamination by veterinary pharmaceuticals and steroid hormones originating in wastewater lagoons.

  6. Ovarian activity in Arabian leopards (Panthera pardus nimr): sexual behaviour and faecal steroid monitoring during the follicular cycle, mating and pregnancy.

    PubMed

    de Haas van Dorsser, Florine J; Green, Daphne I; Holt, William V; Pickard, Amanda R

    2007-01-01

    The Arabian leopard is a critically endangered subspecies endemic to the Arabian Peninsula. A fundamental understanding of the ovarian activity of the leopard is important to enhance the success with which it breeds in captivity. The objective of the present study was to characterise the endocrinology of the follicular cycle, ovulation and pregnancy in captive females using faecal steroid hormone analyses and observations of sexual behaviour. The follicular cycle of the leopard was shown to last 18-23 days based on the interval between consecutive peaks of faecal oestrogen conjugates, and the occurrence of silent heats was high. Puberty had commenced at 2 years of age, but faecal steroid profiles did not match those of the adult female until 3 years of age. No seasonal change in ovarian steroid excretion was observed, although behavioural oestrus was suppressed in summer. Significant rises in faecal progestagen concentrations were only recorded in mated leopards, indicating that these females were strictly induced ovulators. However, only 60% of these mating periods were ovulatory. Progestagen concentrations during pregnancy were significantly higher than those of the non-pregnant luteal phase. The average duration of the non-pregnant and pregnant luteal phases was 39 and 97 days, respectively. The basic features of the reproductive cycle of the Arabian leopard described here form an important foundation for further study into its reproduction.

  7. Yeast-based reporter assays for the functional characterization of cochaperone interactions with steroid hormone receptors.

    PubMed

    Balsiger, Heather A; Cox, Marc B

    2009-01-01

    Steroid hormone receptor-mediated reporter assays in the budding yeast Saccharomyces cerevisiae have been an invaluable tool for the identification and functional characterization of steroid hormone receptor-associated chaperones and cochaperones. This chapter describes a hormone-inducible androgen receptor-mediated beta-galactosidase reporter assay in yeast. In addition, the immunophilin FKBP52 is used as a specific example of a receptor-associated cochaperone that acts as a positive regulator of receptor function. With the right combination of receptor and cochaperone expression plasmids, reporter plasmid, and ligand, the assay protocol described here could be used to functionally characterize a wide variety of nuclear receptor-cochaperone interactions. In addition to the functional characterization of receptor regulatory proteins, a modified version of this assay is currently being used to screen compound libraries for selective FKBP52 inhibitors that represent attractive therapeutic candidates for the treatment of steroid hormone receptor-associated diseases.

  8. Synthesis and chemical reactions of the steroidal hormone 17α-methyltestosterone.

    PubMed

    El-Desoky, El-Sayed Ibrahim; Reyad, Mahmoud; Afsah, Elsayed Mohammed; Dawidar, Abdel-Aziz Mahmoud

    2016-01-01

    Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry of the steroidal hormone 17α-methyltestosterone that is approved by Food and Drug Administration (FDA) in the United States as an androgen for estrogen-androgen hormone replacement therapy treatment. The analog also offers special possibilities for the prevention/treatment of hormone-sensitive cancers. The testosterone skeleton has important functionalities in the molecule that can act as a carbonyl component, an active methylene compound, α,β-unsaturated enone and tertiary hydroxyl group in various chemical reactions to access stereoisomeric steroidal compounds with potent activity. In addition, microbiological methods of synthesis and transformation of this hormone are presented.

  9. Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus.

    PubMed

    Codner, Ethel; Iñíguez, Germán; Villarroel, Claudio; Lopez, Patricia; Soto, Néstor; Sir-Petermann, Teresa; Cassorla, Fernando; Rey, Rodolfo A

    2007-12-01

    Anti-Müllerian hormone (AMH) levels are increased in polycystic ovarian syndrome (PCOS), but it is not known whether other forms of hyperandrogenism, such as PCOS observed in women with type 1 diabetes mellitus (DM1), are also associated with elevated AMH levels. Our objective was to compare AMH and steroid levels in women with PCOS with and without DM1. We compared the clinical, hormonal, and ultrasonographic characteristics of 17 women with PCOS and DM1 (DM1+PCOS), 20 women with PCOS without DM1 (PCOS), and 35 normal women (control) in a cross-sectional study. The Ferriman-Gallwey score, serum testosterone, free androgen index, 17OH-progesterone, and ovarian volume were elevated in both groups of PCOS women compared with controls. Serum androstenedione, LH/FSH ratio, and follicle number, however, were higher and SHBG was lower in PCOS compared with DM1+PCOS and controls. AMH levels were higher in PCOS (76.0 +/- 36.3 pmol/liter) than in DM1+PCOS (18.8 +/- 7.4 pmol/liter) and controls (13.9 +/- 8.3 pmol/liter). AMH levels correlated with follicle number in the three groups. Serum AMH/follicle number ratio was higher in PCOS than in DM1+PCOS and controls. Women with DM1+PCOS have normal levels of AMH, inhibin B, estradiol, SHBG, and LH/FSH, suggesting that the pathophysiology of hyperandrogenism in PCOS patients with DM1 appears to be different from that in PCOS without DM1. However, hirsutism score and androgen levels were similar in both groups of women with PCOS. We postulate that insulin treatment acts as a co-gonadotropin increasing follicle recruitment, hence not increasing AMH levels.

  10. Retracted: Differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids.

    PubMed

    2015-10-01

    The above article, published online on 20 December 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Professor L Popescu and John Wiley and Sons Ltd. The retraction has been requested by the University of Florida, Office of Research, in response to their investigation which concluded fabrication of data in Figures 2, 3 and 4. Reference Pan Q, Luo X, Chegini N. Retracted: differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids. J Cell Mol Med 12: 227-240. Doi: 10.1111/j.1582-4934.2007.00207.x.

  11. Interactions of xenobiotics with steroid hormone receptors and the sex-steroid binding protein in spotted seatrout

    SciTech Connect

    Thomas, P.; Ghosh, S.; Pinter, J.; Sperry, T.; Breckenridge-Miller, D.; Laidley, C.W.

    1995-12-31

    A variety of xenobiotics, such as DDT, methoxychlor and PCB mixtures and Kepone have estrogenic actions and disrupt reproduction in mammals by binding to nuclear estrogen receptors (ER). These xenobiotics were tested for their ability to bind to the hepatic ER of a marine fish, spotted seatrout (Cynoscion nebulosus). Several of the DDT derivatives, Kepone and PCB mixtures also bound to the seatrout ER over a range of 10{sup {minus}5}--10{sup {minus}3}M. Moreover, Kepone was shown to have both estrogenic and antiestrogenic actions in an in vitro liver slice vitellogenesis assay. These estrogenic compounds were also tested for their ability to bind to nuclear and plasma membrane progestogen (20{beta}-S) receptors in ovarian tissues and to the sex-steroid binding protein in seatrout plasma. Kepone, methoxychlor and o,p{prime}-DDT caused concentration dependent displacement of {sup 3}H2O{beta}-S from its plasma membrane receptor and inhibition of 20{beta}-S induced final maturation in an in vitro assay over the range of 10{sup {minus}7}--10{sup {minus}3}M, but did not alter steroid binding to the nuclear progestogen receptor. Significant binding of methoxychlor and the other organochlorines to the sex steroid binding protein was also observed. It is concluded from these studies that a variety of xenobiotics with estrogenic actions can also bind to other steroid receptors and binding proteins to influence other endocrine-mediated processes.

  12. Steroid metabolism by ovarian follicles and extrafollicular tissue of the guppy (Poecilia reticulata) during oocyte growth and gestation.

    PubMed

    Venkatesh, B; Tan, C H; Kime, D E; Loy, G L; Lam, T J

    1992-06-01

    In the viviparous guppy, fertilization and gestation are intrafollicular. Fully developed embryos are ovulated at the end of gestation just prior to parturition. The metabolism in vitro of various radiolabeled steroid precursors by isolated ovarian follicles at various stages of the reproductive cycle and extrafollicular (EF) tissue of the guppy was investigated. While estradiol-17 beta was one of the end products of metabolism in vitellogenic follicles, 17 alpha, 20 beta-P and several 5-reduced metabolites were synthesized by postvitellogenic follicles. The yield of 17 alpha, 20 beta-P, however, was much lower than some 5 beta-reduced metabolites synthesized by postvitellogenic follicles. Gestation stage follicles rapidly converted the precursors into 5-reduced and polar 7-hydroxylated steroids, and their glucuronides. Although postpartum follicles showed very poor potential for steroid metabolism, they synthesized estradiol-17 beta from testosterone. These results demonstrate distinct changes occurring in the steroidogenic potential of the follicles during the reproductive cycle. Unlike in other viviparous vertebrates, no particular steroid seems to be involved in maintaining gestation in the guppy; all the steroid precursors are converted into highly polar metabolites and their conjugates during gestation, thereby facilitating their excretion. The EF ovarian tissue also synthesized 7-hydroxylated steroids and their glucuronides, providing evidence for the first time that the teleost ovarian EF tissue plays a role in steroidogenesis. The possible physiological significance of the synthesis of the novel polar steroids by the follicles and the EF tissue is discussed.

  13. Fine-needle aspiration cytology of ovarian steroid cell tumor: A rare case report

    PubMed Central

    Agrawal, Nidhi; Vardhan, Harsh; Khokhar, Singh; Rai, Naresh; Saxena, Rajeev; Riyaz, Shahida

    2015-01-01

    Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors that account for less than 0.1% of all ovarian tumors. These tumors can produce steroids, especially testosterone, which produces symptoms such as hirsutism, amenorrhea/oligomenorrhea, and male patterned voice. For evaluation of the androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S) are the first laboratory tests to be measured. Abdominal ultrasound and magnetic resonance imaging (MRI) are useful radiologic imaging techniques. Although SCTs are generally benign, the risk of malignant transformation is always present. Surgical excision of tumor is the most important and hallmark treatment. The present case signifies the early preoperative diagnosis of a virilizing SCT, based on cytological features and its careful correlation with clinicopathological and radiological findings. PMID:26811582

  14. Effects of an isoflavone-free soy diet on ovarian hormones in premenopausal women.

    PubMed

    Lu, L J; Anderson, K E; Grady, J J; Nagamani, M

    2001-07-01

    circulating ovarian steroids without altering gonadotropins. Our results are consistent with previous studies showing decreased ovarian hormone levels and decreased risk of breast cancer in populations consuming soya diets and an inverse relationship between animal protein intake and breast cancer risk and, therefore, may have implications for breast cancer prevention.

  15. Anabolic Steroids

    MedlinePlus

    Anabolic steroids are man-made substances related to male sex hormones. Doctors use anabolic steroids to treat some hormone problems in men, ... from some diseases. Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. ...

  16. The Insect Prothoracic Gland as a Model for Steroid Hormone Biosynthesis and Regulation.

    PubMed

    Ou, Qiuxiang; Zeng, Jie; Yamanaka, Naoki; Brakken-Thal, Christina; O'Connor, Michael B; King-Jones, Kirst

    2016-06-28

    Steroid hormones are ancient signaling molecules found in vertebrates and insects alike. Both taxa show intriguing parallels with respect to how steroids function and how their synthesis is regulated. As such, insects are excellent models for studying universal aspects of steroid physiology. Here, we present a comprehensive genomic and genetic analysis of the principal steroid hormone-producing organs in two popular insect models, Drosophila and Bombyx. We identified 173 genes with previously unknown specific expression in steroid-producing cells, 15 of which had critical roles in development. The insect neuropeptide PTTH and its vertebrate counterpart ACTH both regulate steroid production, but molecular targets of these pathways remain poorly characterized. Identification of PTTH-dependent gene sets identified the nuclear receptor HR4 as a highly conserved target in both Drosophila and Bombyx. We consider this study to be a critical step toward understanding how steroid hormone production and release are regulated in all animal models. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. In vitro binding of steroid hormones by natural and purified fibers

    SciTech Connect

    Shultz, T.D.; Howie, B.J.

    1986-03-01

    The in vitro binding of estrone, estradiol-17..beta.., estriol, testosterone, dihydrotestosterone, and estrone-3-glucuronide by wheat, oat and corn brans, oat hulls, cellulose, lignin, and cholestyramine resin was measured. Steroid binding was carried out by mixing 50 mg of binding substance with varying substrate quantities (0.037 ..mu..Ci; 0.50-2.51 pmol/incubation) of /sup 3/H-estrone, /sup 3/H-estradiol-17..beta.., /sup 3/H-estriol, /sup 3/H-estrone-3-glucuronide, /sup 4/H-testosterone, and /sup 370/C for 1 hr with shaking. Following centrifugation of the reaction mixture, a 1 ml aliquot was analyzed for radioactivity. The extent of steroid sequestration was characteristic and reproducible for each hormone. Cholestyramine bound an average of 90% of all the steroids tested, whereas cellulose bound the least (12%). Of the other substances tested, lignin bound 87%; wheat and oat grans, 45% each; corn bran, 44%; and oat hulls, 32% of the unconjugated hormones. The conjugated steroid was less likely to bind than the unconjugated steroids. Lignin appeared to be an important component in the interaction with steroid hormones. The results support the hydrophobic of nature of adsorption and suggest that the components of the fiber in diet should be considered separately when evaluating in vivo metabolic effects. Implications include the possible modification of hormone-dependent cancer risk through dietary intervention.

  18. Symptomatic Cushing's syndrome and hyperandrogenemia in a steroid cell ovarian neoplasm: a case report.

    PubMed

    Sedhom, Ramy; Hu, Sophia; Ohri, Anupam; Infantino, Dorian; Lubitz, Sara

    2016-10-12

    Malignant steroid cell tumors of the ovary are rare and frequently associated with hormonal abnormalities. There are no guidelines on how to treat rapidly progressive Cushing's syndrome, a medical emergency. A 67-year-old white woman presented to our hospital with rapidly developing signs and symptoms of Cushing's syndrome secondary to a steroid-secreting tumor. Her physical and biochemical manifestations of Cushing's syndrome progressed, and she was not amenable to undergoing conventional chemotherapy secondary to the debilitating effects of high cortisol. Her rapidly progressive Cushing's syndrome ultimately led to her death, despite aggressive medical management with spironolactone, ketoconazole, mitotane, and mifepristone. We report an unusual and rare case of Cushing's syndrome secondary to a malignant steroid cell tumor of the ovary. The case is highlighted to discuss the complications of rapidly progressive Cushing's syndrome, an underreported and often unrecognized endocrine emergency, and the best available evidence for treatment.

  19. The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors in mitochondria of animal cells.

    PubMed

    Psarra, A-M G; Solakidi, S; Sekeris, C E

    2006-02-26

    Mitochondria are key cellular organelles that regulate events related to energy production and apoptosis. These processes are modulated, in turn, by steroid and thyroid hormones in the course of their actions on metabolism, growth and development. In this context, a direct effect of these hormones on the mitochondrial-linked processes, possibly by way of cognate mitochondrial receptors, has been proposed. In this paper we review data from the literature and present new findings supporting this concept. Receptors for steroid hormones, glucocorticoids and estrogens, and for T(3), have been detected in mitochondria by immunofluorescence labeling and confocal laser microscopy, by Western blotting of mitochondrial proteins and by immunogold electron microscopy. Furthermore, the mitochondrial genome contains nucleotide sequences with high similarity to known hormone-responsive elements, which interact with the appropriate receptors to confer hormone-dependent activation of reporter genes in transfection experiments. Thus, thyroid hormone stimulates mitochondrial transcription mediated by the cognate receptor when added to an in organello mitochondrial system, capable of faithful transcription.

  20. The role of hormonal factors and endocrine therapy in ovarian cancer

    PubMed Central

    Sinacki, Marcin; Jassem, Jacek

    2013-01-01

    The efficacy of the second-line chemotherapy commonly used in both relapsed ovarian cancer patients and those with primary treatment failure remains unsatisfactory. This therapy has a small effect on survival, whereas associated toxicity may diminish the patient's quality of life. Hormonal factors play a role in ovarian tumorigenesis, and inhibition of the stimulating effects of estrogens may exert a clinical benefit. The role of hormonal therapy as a palliative therapeutic alternative for ovarian cancer remains undetermined. This modality may result in long-term stabilization of disease in individual patients and less frequently in tumor remission. In this article the role of hormonal factors and recent literature of various forms of hormonal therapy for ovarian cancer are presented. PMID:23788955

  1. Ovarian hormones and fasting differentially regulate pituitary receptors for estrogen and gonadotropin-releasing hormone in rabbit female.

    PubMed

    Parillo, F; Zerani, M; Maranesi, M; Dall'Aglio, C; Galeati, G; Brecchia, G; Boiti, C; González-Mariscal, G

    2014-03-01

    To investigate the mechanisms by which caloric restriction affects reproductive function in female rabbits, we measured, in animals intact or ovariectomized (OVX) estrogen-primed and fed ad libitum or fasted for 48 h, the adenohypophysial expression of estrogen receptor-alpha (ESR1) and gonadotropin releasing hormone receptor (GnRHR) and the dynamic secretion of LH following GnRH stimulation. Fasting increased the number of GnRHR-immunoreactive (-IR) cells in intact animals, whereas reduced the density of ESR1-IR cells in OVX rabbits. Estrogen priming decreased the number of ESR1-IR cells in fasted and OVX animals. Ovariectomy increased the number of ESR1-IR cells in fed rabbits, but caused an opposite effect in both fed and fasted animals treated with estrogen. Fasting down regulated the mRNA levels for ESR1 and GnRHR. Estrogen-priming reduced the abundance for ESR1 mRNA in both fed and fasted rabbits, and that for GnRHR in fasted rabbits. Ovariectomy halved ESR1 mRNA levels independently of treatment and feeding condition, whereas increased (P < 001) that for GnRHR in estrogen-primed rabbits. In all rabbits, an LH surge occurred 30 min after GnRH injection but the lowest levels were found in intact fasted rabbits and the highest in fasted, estrogen-primed animals. The LH profile was similar in intact and OVX rabbits and neither fasting nor estrogen priming modified it. In conclusion, fasting differentially modifies the ESR1 and GnRHR expression in the pituitary, depending on the presence of gonadal hormones, indicating complex interactions between metabolic signals and ovarian steroids. Copyright © 2013 Wiley Periodicals, Inc.

  2. Postmigratory body condition and ovarian steroid production predict breeding decisions by female gray-headed albatrosses.

    PubMed

    Crossin, Glenn T; Phillips, Richard A; Wynne-Edwards, Katherine E; Williams, Tony D

    2013-01-01

    Carryover effects have been documented in many migratory bird species, but we know little about the physiological mechanisms that mediate those effects. Here we show that the energetic, endocrine, and aerobic characteristics of postmigratory female gray-headed albatrosses (Thalassarche chrysostoma) can affect their decision to breed. All females in this study, whether breeding or not, were secreting ovarian steroids when they arrived at the breeding colony at Bird Island, South Georgia, which suggests that all were responding to seasonal cues. However, deferring, nonbreeding birds were characterized by a steroid profile of high progesterone (P4) and low testosterone (T), whereas breeding birds showed the opposite pattern. Deferring birds also had low body mass, hematocrit, and hemoglobin. These results suggest that postmigratory condition can influence patterns of ovarian steroidogenesis and that the maintenance of high P4 without subsequent conversion to T favors breeding deferral. Whereas breeding females normally convert P4 to T, which is a key deterministic step toward 17β-estradiol synthesis, vitellogenesis, and follicle development, deferring females did not make this conversion and instead maintained high levels of P4, perhaps due to inhibition of the hydroxylase-lyase enzyme complex, thus rendering them infertile for the current season. Results are discussed within the context of the biennial breeding system of this species, and comparisons with other biennially and annually breeding albatrosses are made.

  3. Interleukins affect equine endometrial cell function: modulatory action of ovarian steroids.

    PubMed

    Szóstek, Anna Z; Galvão, Antonio M; Hojo, Takuo; Okuda, Kiyoshi; Skarzynski, Dariusz J

    2014-01-01

    The aim of the present study was to investigate the interaction between ovarian steroids, interleukins and prostaglandins (PG) in equine epithelial and stromal cells in vitro. In Experiment 1, cells were exposed to IL-1α (10 ng/mL), IL-1β (10 ng/mL) or IL-6 (10 ng/mL) for 24 h and cell proliferation was determined using MTT. In Experiment 2, cells were exposed to progesterone (P4; 10(-7) M); 17-β estradiol (E2; 10(-9) M) or P4+E2 for 24 h and later medium was replaced with a fresh one treated with IL-1α, IL-1β or IL-6 (10 ng/mL, each) for 24 h. The oxytocin (OT; 10(-7) M) was used as a positive control. In Experiment 3, cells were exposed to P4 (10(-7) M), E2 (10(-9) M) or P4+E2 for 24 h and the IL receptor mRNAs transcription was determined using Real-time PCR. Prostaglandins concentration was determined using the direct enzyme immunoassay (EIA) method. Our findings reveal a functional linking between ovarian steroids and IL-stimulated PG secretion by equine endometrial cells. This interaction could be one of the mechanisms responsible for endometrial local orchestrating events during the estrous cycle and early pregnancy.

  4. Do steroid hormones play a role in the etiology of glioma?

    PubMed

    Kabat, Geoffrey C; Etgen, Anne M; Rohan, Thomas E

    2010-10-01

    Gliomas are the most common type of primary malignant brain tumor and have a very poor prognosis. Little is known, however, about the etiology of these tumors. Evidence from a number of sources suggests that endogenous steroid hormones may play a role in the development of gliomas. First, the descriptive epidemiology of glioma suggests a relative protection of females compared with males, particularly during the premenopausal years. Second, some gliomas and glioblastomas express estrogen receptors (ER), especially ERβ, as well as aromatase, the enzyme responsible for the conversion of testosterone to estradiol, and possibly other steroid hormone receptors. Third, experimental studies indicate that glioblastomas transplanted into animals grow at a slower rate in females compared with males. Finally, experimental studies show that estradiol, 2-methoxyestradiol, and a number of selective estrogen receptor modulators inhibit proliferation of gliomas and induce cell death. These hormonal agonists and antagonists may act either through classical steroid hormone receptors or independently of such receptors. In view of these findings, further clinical, experimental, and epidemiologic studies are needed to elucidate the role of steroid hormone agonists and antagonists in the development and proliferation of glioma. If hormonal pathways are involved in gliomagenesis, this could eventually lead to the design of preventive strategies.

  5. Maximal expression of Foxl2 in pituitary gonadotropes requires ovarian hormones.

    PubMed

    Herndon, Maria K; Nilson, John H

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) and activin regulate synthesis of FSH and ultimately fertility. Recent in vivo studies cast SMAD4 and FOXL2 as master transcriptional mediators of activin signaling that act together and independently of GnRH to regulate Fshb gene expression and female fertility. Ovarian hormones regulate GnRH and its receptor (GNRHR) through negative and positive feedback loops. In contrast, the role of ovarian hormones in regulating activin, activin receptors, and components of the activin signaling pathway, including SMAD4 and FOXL2, remains understudied. The widespread distribution of activin and many of its signaling intermediates complicates analysis of the effects of ovarian hormones on their synthesis in gonadotropes, one of five pituitary cell types. We circumvented this complication by using a transgenic model that allows isolation of polyribosomes selectively from gonadotropes of intact females and ovariectomized females treated with or without a GnRH antagonist. This paradigm allows assessment of ovarian hormonal feedback and distinguishes responses that are either independent or dependent on GnRH. Surprisingly, our results indicate that Foxl2 levels in gonadotropes decline significantly in the absence of ovarian input and independently of GnRH. Expression of the genes encoding other members of the activin signaling pathway are unaffected by loss of ovarian hormonal feedback, highlighting their selective effect on Foxl2. Expression of Gnrhr, a known target of FOXL2, also declines upon ovariectomy consistent with reduced expression of Foxl2 and loss of ovarian hormones. In contrast, Fshb mRNA increases dramatically post-ovariectomy due to increased compensatory input from GnRH. Together these data suggest that ovarian hormones regulate expression of Foxl2 thereby expanding the number of genes controlled by the hypothalamic-pituitary-gonadal axis that ultimately dictate reproductive fitness.

  6. Maximal Expression of Foxl2 in Pituitary Gonadotropes Requires Ovarian Hormones

    PubMed Central

    Herndon, Maria K.; Nilson, John H.

    2015-01-01

    Gonadotropin-releasing hormone (GnRH) and activin regulate synthesis of FSH and ultimately fertility. Recent in vivo studies cast SMAD4 and FOXL2 as master transcriptional mediators of activin signaling that act together and independently of GnRH to regulate Fshb gene expression and female fertility. Ovarian hormones regulate GnRH and its receptor (GNRHR) through negative and positive feedback loops. In contrast, the role of ovarian hormones in regulating activin, activin receptors, and components of the activin signaling pathway, including SMAD4 and FOXL2, remains understudied. The widespread distribution of activin and many of its signaling intermediates complicates analysis of the effects of ovarian hormones on their synthesis in gonadotropes, one of five pituitary cell types. We circumvented this complication by using a transgenic model that allows isolation of polyribosomes selectively from gonadotropes of intact females and ovariectomized females treated with or without a GnRH antagonist. This paradigm allows assessment of ovarian hormonal feedback and distinguishes responses that are either independent or dependent on GnRH. Surprisingly, our results indicate that Foxl2 levels in gonadotropes decline significantly in the absence of ovarian input and independently of GnRH. Expression of the genes encoding other members of the activin signaling pathway are unaffected by loss of ovarian hormonal feedback, highlighting their selective effect on Foxl2. Expression of Gnrhr, a known target of FOXL2, also declines upon ovariectomy consistent with reduced expression of Foxl2 and loss of ovarian hormones. In contrast, Fshb mRNA increases dramatically post-ovariectomy due to increased compensatory input from GnRH. Together these data suggest that ovarian hormones regulate expression of Foxl2 thereby expanding the number of genes controlled by the hypothalamic-pituitary-gonadal axis that ultimately dictate reproductive fitness. PMID:25955311

  7. SEX-STEROID AND THYROID HORMONE CONCENTRATIONS IN JUVENILE ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS) FROM CONTAMINATED AND REFERENCE LAKES IN FLORIDA, USA

    EPA Science Inventory

    Sex-steroid and thyroid hormones are critical regulators of growth and reproduction in all vertebrates, and several recent studies suggest that environmental chemicals can alter circulating concentrations of these hormones. This study examines plasma concentrations of estradiol-...

  8. SEX-STEROID AND THYROID HORMONE CONCENTRATIONS IN JUVENILE ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS) FROM CONTAMINATED AND REFERENCE LAKES IN FLORIDA, USA

    EPA Science Inventory

    Sex-steroid and thyroid hormones are critical regulators of growth and reproduction in all vertebrates, and several recent studies suggest that environmental chemicals can alter circulating concentrations of these hormones. This study examines plasma concentrations of estradiol-...

  9. Comparison of the effects of human and chicken ghrelin on chicken ovarian hormone release.

    PubMed

    Sirotkin, Alexander V; Harrath, Abdel Halim; Grossmann, Roland

    2016-11-01

    The aim of the present experiments was to examine the species-specific and cell-specific effects of ghrelin on chicken ovarian hormone release. For this purpose, we compared the effects of chicken and human ghrelin on the release of estradiol (E), testosterone (T), progesterone (P) and arginine-vasotocin (AVT) by cultured fragments of chicken ovarian follicles and on the release of T and AVT by cultured ovarian granulosa cells. In cultured chicken ovarian fragments, both human and chicken ghrelin promoted E release. T output was stimulated by chicken ghrelin but not by human ghrelin. No effect of either human or chicken ghrelin on P release was observed. Human ghrelin promoted but chicken ghrelin suppressed AVT release by chicken ovarian fragments. In cultured ovarian granulosa cells, human ghrelin inhibited while chicken ghrelin stimulated T release. Both human and chicken ghrelin suppressed AVT output by chicken granulosa cells. These data confirm the involvement of ghrelin in the control of ovarian secretory activity and demonstrate that the effect of ghrelin is species-specific. The similarity of avian ghrelin on avian ovarian granulosa cells and ovarian fragments (containing both granulosa and theca cells) suggests that ghrelin can influence chicken ovarian hormones primarily by acting on granulosa cells.

  10. Effects of steroid hormones on five functional parameters of Tetrahymena: evolutionary conclusions.

    PubMed

    Kohidai, László; Katona, Júlia; Csaba, György

    2003-03-01

    The unicellular Tetrahymena pyriformis was studied for chemotaxis, chemotactic selection, phagocytosis, growth and body shape changes in the presence of water soluble (beta-cyclodextrin-coupled) steroid hormones (testosterone, estradiol, progesterone, hydrocortisone and dexamethasone). Testosterone was chemoattractant over a wide range of concentrations, while progesterone and dexamethasone were active only at one concentration (10(-5) and 10(-6) mg ml(-1) respectively) and were either neutral or repellent at other concentrations. Hydrocortisone and estradiol were unambiguously chemorepellent. Chemotactic selection enhanced the effect of testosterone and estradiol, while in the case of hydrocortisone the action was reversed. The other parameters were mildly influenced by the steroid hormones. The results call attention to the fine molecular recognition capacity of Tetrahymena and to the possible rapid effects of steroid hormones at membrane receptors at a very low evolutionary eukaryotic level.

  11. Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome.

    PubMed

    Maliqueo, Manuel; Benrick, Anna; Alvi, Asif; Johansson, Julia; Sun, Miao; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2015-09-05

    Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Steroid hormones and persistent organic pollutants in plasma from North-eastern Atlantic pilot whales.

    PubMed

    Hoydal, Katrin S; Styrishave, Bjarne; Ciesielski, Tomasz M; Letcher, Robert J; Dam, Maria; Jenssen, Bjørn M

    2017-09-14

    Persistent organic pollutants (POPs) are known to have endocrine disruptive effects, interfering with endogenous steroid hormones. The present study examined nine steroid hormones and their relationships with the concentrations of selected POPs in pilot whales (Globicephala melas) from the Faroe Islands, NE Atlantic. The different steroids were detected in 15 to all of the 26 individuals. High concentrations of progesterone (83.3-211.7pmol/g) and pregnenolone (PRE; 4.68-5.69pmol/g) were found in three adult females indicating that they were pregnant or ovulating. High androgen concentrations in two of the males reflected that one was adult and that one (possibly) had reached puberty. In males a significant positive and strong correlation between body length and testosterone (TS) levels was identified. Furthermore, positive and significant correlations were found between 4-OH-CB107/4'-OH-CB108 and 17β-estradiol in males. In adult females significant positive correlations were identified between PRE and CB149 and t-nonachlor, between estrone and CB138, -149, -187 and p,p'-DDE, between androstenedione and CB187, and between TS and CB-99 and -153. Although relationships between the POPs and the steroid hormones reported herein are not evidence of cause-effect relationships, the positive correlations between steroids and POPs, particularly in females, suggest that POPs may have some endocrine disrupting effects on the steroid homeostasis in this species. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle-Aged Men

    PubMed Central

    Emeville, Elise; Giton, Frank; Giusti, Arnaud; Oliva, Alejandro; Fiet, Jean; Thomé, Jean-Pierre; Blanchet, Pascal; Multigner, Luc

    2013-01-01

    Background Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern

  14. New insights into the role of sex steroid hormones in pregnancy: possible therapeutic approach by sex steroid hormones for the treatment of both preeclampsia and preterm labor.

    PubMed

    Mizutani, S; Mizutani, E

    2015-03-01

    Fetal peptide hormones are essential for the development of fetus, which increase in accordance with pregnancy term. Concentration of these hormones within the feto-placental unit is normally higher than that of maternal circulation. Since these hormones are biologically active, the leakage of these hormones into the maternal circulation is regulated by degradation activity by placental aminopeptidases, in order to maintain the balance between carriage of pregnancy and onset of labor.Because the concentration of these hormones, being regulated by the amount of endogenous production and by physiological degradation by enzymes in the blood and tissue, the balance between production and degradation is a definitive element for maintaining normal gestation and term delivery.The changes of the balance between fetal angiotensin II (A-II) and vasopressin (AVP) andA-II and AVP degrading enzymes, between aminopeptidase A (APA) and placental leucine aminopeptidase( P-LAP) - in the placenta and maternal blood due to fetal stress such as hypoxia - are the provable causes of preeclampsia or preterm labor.Induction of APA and P-LAP by estradiol benzoate (E2) and progesterone (P) from placenta has been demonstrated. They are involved in the regulation of fetal peptide hormones via placental aminopeptidases in homeostasis of pregnancy.Recently it was shown that both APA and P-LAP could be potentially safe and effective drugs for preeclampsia and preterm labor. The authors' proposed sex steroid treatment with dose increasing manner by gestational week (sex steroid treatment) for severe preeclampsia and preterm labor could be candidates replacing conventional treatments. In light of lacking safe and effective medication, the proposed sex steroid treatment is worthwhile for the prospective controlled studies for the treatment of both preeclampsia and preterm labor. © Georg Thieme Verlag KG Stuttgart · New York.

  15. The Circadian Clock Is a Key Driver of Steroid Hormone Production in Drosophila.

    PubMed

    Di Cara, Francesca; King-Jones, Kirst

    2016-09-26

    Biological clocks allow organisms to anticipate daily environmental changes such as temperature fluctuations, abundance of daylight, and nutrient availability. Many circadian-controlled physiological states are coordinated by the release of systemically acting hormones, including steroids and insulin [1-7]. Thus, hormones relay circadian outputs to target tissues, and disrupting these endocrine rhythms impairs human health by affecting sleep patterns, energy homeostasis, and immune functions [8-10]. It is largely unclear, however, whether circadian circuits control hormone levels indirectly via central timekeeping neurons or whether peripheral endocrine clocks can modulate hormone synthesis directly. We show here that perturbing the circadian clock, specifically in the major steroid hormone-producing gland of Drosophila, the prothoracic gland (PG), unexpectedly blocks larval development due to an inability to produce sufficient steroids. This is surprising, because classic circadian null mutants are viable and result in arrhythmic adults [4, 11-14]. We found that Timeless and Period, both core components of the insect clock [15], are required for transcriptional upregulation of steroid hormone-producing enzymes. Timeless couples the circadian machinery directly to the two canonical pathways that regulate steroid synthesis in insects, insulin and PTTH signaling [16], respectively. Activating insulin signaling directly modulates Timeless function, suggesting that the local clock in the PG is normally synced with systemic insulin cues. Because both PTTH and systemic insulin signaling are themselves under circadian control, we conclude that de-synchronization of a local endocrine clock with external circadian cues is the primary cause for steroid production to fail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Mechanisms of prenatal programing: identifying and distinguishing the impact of steroid hormones.

    PubMed

    O'Connor, Thomas G; Barrett, Emily S

    2014-01-01

    Developmental programing is gaining considerable leverage as a conceptual framework for understanding individual variability in human behavioral and somatic health. The current mini-review examines some of the key conceptual and methodological challenges for developmental programing research focused on fetal sex steroid exposure and physical, behavioral, physiological, and health outcomes. Specifically, we consider the bases for focusing on sex steroids, methods for assessing prenatal steroid hormone exposure, confounding factors, and the most relevant postnatal outcomes. We conclude with a brief consideration, based on current knowledge, of the applications of the existing findings for further research and practice.

  17. Both ovarian hormones estrogen and progesterone are necessary for hormonal mammary carcinogenesis in ovariectomized ACI rats.

    PubMed

    Blank, Edward W; Wong, Po-Yin; Lakshmanaswamy, Rajkumar; Guzman, Raphael; Nandi, Satyabrata

    2008-03-04

    August-Copenhagen-Irish (ACI) rats are unique in that the ovary-intact females develop high incidence of mammary cancers induced solely by hormones upon prolonged exposure to high levels of estrogen alone. Studies have also shown that such prolonged exposure to high-dose estrogen results in human-like aneuploid mammary cancers in ovary-intact ACI rats. To determine the role of progesterone in mammary carcinogenesis, six-week-old intact and ovariectomized ACI rats were continuously exposed to low- and high-dose estrogen alone, progesterone alone, low-dose estrogen plus progesterone, and ovariectomized ACI rats with high-dose estrogen plus progesterone. Also, ovariectomized ACI rats were treated with high-dose estrogen plus progesterone plus testosterone to determine the role of the androgen, testosterone, if any, in hormonal mammary carcinogenesis. The results indicate that continuous exposure to high, but not low, concentrations of estrogen alone can induce mammary carcinogenesis in intact but not in ovariectomized rats. Mammary carcinogenesis in ovariectomized ACI rats requires continuous exposure to high concentrations of estrogen and progesterone. The addition of testosterone propionate does not affect tumor incidence in such rats. These results suggest that both ovarian hormones estrogen and progesterone are necessary for mammary carcinogenesis induced solely by hormones in ovariectomized ACI rats. Our results are in agreement with the Women's Health Initiative studies, where treatment of postmenopausal women with estrogen (ERT) alone did not increase the risk of breast cancer, but estrogen and progesterone (HRT) did.

  18. Mechanisms of crosstalk between endocrine systems: regulation of sex steroid hormone synthesis and action by thyroid hormones.

    PubMed

    Duarte-Guterman, Paula; Navarro-Martín, Laia; Trudeau, Vance L

    2014-07-01

    Thyroid hormones (THs) are well-known regulators of development and metabolism in vertebrates. There is increasing evidence that THs are also involved in gonadal differentiation and reproductive function. Changes in TH status affect sex ratios in developing fish and frogs and reproduction (e.g., fertility), hormone levels, and gonad morphology in adults of species of different vertebrates. In this review, we have summarized and compared the evidence for cross-talk between the steroid hormone and thyroid axes and present a comparative model. We gave special attention to TH regulation of sex steroid synthesis and action in both the brain and gonad, since these are important for gonad development and brain sexual differentiation and have been studied in many species. We also reviewed research showing that there is a TH system, including receptors and enzymes, in the brains and gonads in developing and adult vertebrates. Our analysis shows that THs influences sex steroid hormone synthesis in vertebrates, ranging from fish to pigs. This concept of crosstalk and conserved hormone interaction has implications for our understanding of the role of THs in reproduction, and how these processes may be dysregulated by environmental endocrine disruptors.

  19. Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells.

    PubMed

    Piccinato, Carla A; Neme, Rosa M; Torres, Natália; Sanches, Lívia Renta; Derogis, Priscilla Bento Mattos Cruz; Brudniewski, Heloísa F; Rosa e Silva, Júlio C; Ferriani, Rui A

    2016-04-01

    Endometriosis is an estrogen-dependent disease that afflicts about 10% of women in their reproductive age, causing severe pain and infertility. The potential roles of female steroid hormones in modulating key estrogen-metabolizing enzymes, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), were investigated. The expression of STS and SULT1E1 mRNA in biopsy samples (n=78) of superficial and deep endometriotic lesions, eutopic endometrium of women with endometriosis and endometrium from control patients were compared according to the menstrual cycle phase. Increased STS gene expression was detected in superficial and deep-infiltrating lesions and a reduced SULT1E1 expression was also observed in the eutopic endometrium relative to the superficial lesions. Additionally, a significantly positive correlation was detected between STS and SULT1E1 mRNA expression levels in biopsy specimens collected from the endometriosis patients, and not in control individuals. The actions of female steroid hormones on SULT1E1 and STS expression were evidenced in endometriosis, revealed by increased expression levels in the luteal phase of the cycle. There was an increased STS expression in primary eutopic and ectopic endometrial stromal cells treated with estradiol and progesterone (representative of the luteal phase, n=3). Although an increased STS mRNA expression was observed in hormone-induced endometrial stromal cells in vitro, no difference could be detected between the hormone treatment groups in estradiol formation from estradiol sulfate measured by LC-MS-MS. Interestingly, a greater expression of STS was observed in stromal cells from eutopic endometrium with an agreement in estradiol formation originated from estradiol sulfate. The differential regulation of STS and SULT1E1 could provide insights for novel studies of the therapeutic use of STS inhibitors.

  20. Hormones in the mentally disturbed brain: steroids and peptides in the development and treatment of psychopathology.

    PubMed

    Taylor, George Townsend; Maloney, Susan; Dearborn, Joshua; Weiss, Juergen

    2009-12-01

    One of the more fascinating recent discoveries in neuroscience is the widespread influence of hormones on brain regions and functions underlying pathological behaviors. A story is unfolding that points to critical roles played by hypothalamic - pituitary - gonadal (HPG) and hypothalamic - pituitary - adrenal (HPA) axes on a startling array of mental disorders, from depression to dementia. The influence of peptides and steroids does not end with hormones released from the two axes, however. It is now clear that the brain has adapted, "highjacked" is more descriptive, HPG and HPA hormones for uses unrelated to their original functions in reproduction and responses to stress. Findings of neuromodulatory effects of HPA and HPG hormones on monoamine, GABA, glutamate and opioid pathways and of hormone receptors and enzymes involved in hormone synthesis, particularly of steroids, in the hippocampus, amygdala and other subcortical brain regions provide the brain with multiple evolutionary means to adapt to new functions. The complexity of the metabolic cascade for the steroids also leaves open mechanisms by which endogenous errors and exogenous chemicals could be involved in the etiology of psychopathologies. The planned review will examine the recent literature for evidence of steroidal and peptidergic influences on basic biological functions and on mood disorders, anxiety and PTSD, schizophrenia, substance abuse and dementia. Emphasis will be placed on animal models, although findings with patient populations will be prominently included. Special attention will be paid to novel pathways by which the precursors and metabolites of sex steroids can influence psychopathologies. We also will speculate on promising treatments with hormone modulators that may be useful in mollifying the symptomology of the mental disorders.

  1. A KINETIC ANALYSIS OF THE CONFORMATIONAL FLEXIBILITY OF STEROID HORMONES

    EPA Science Inventory

    For a set of 10 androgen steroids and estradiol (E2), the kinetic feasibility of conformation flexibility of the cyclic moieties was studied under the constraint of maintaining the B/C trans and C/D trans ring fusion of the natural and biologically active enantiomer. To this end,...

  2. A KINETIC ANALYSIS OF THE CONFORMATIONAL FLEXIBILITY OF STEROID HORMONES

    EPA Science Inventory

    For a set of 10 androgen steroids and estradiol (E2), the kinetic feasibility of conformation flexibility of the cyclic moieties was studied under the constraint of maintaining the B/C trans and C/D trans ring fusion of the natural and biologically active enantiomer. To this end,...

  3. Growth and obesity and its association with plasma level of steroid hormones and insulin-like growth factor-I (IGF-I) in Slovak female students.

    PubMed

    Zatko, T; Matejovicova, B; Boledovicova, M; Vondrakova, M; Bezakova, A; Sirotkin, A V

    2013-01-01

    The aim of the present study was to examine the possible role of steroid hormones and insulin-like growth factor 1 (IGF-I) in the control of human growth and obesity. We measured plasma level of progesterone, testosterone, estradiol and IGF-I in 301 young women at different stages of their ovarian cycle, and compared them to the standard morphometric indexes of their growth and obesity - body height, body weight, abdomen circumstance and waist to hip ratio (WHR). The ovarian cycle-dependent changes in plasma progesterone and estradiol, but not in testosterone and IGF-I level were found. Young women with higher body height had significantly higher plasma level of estradiol, testosterone and IGF-I, but not of progesterone, compared to subjects with lower body height in both follicular and luteal phases of the ovarian cycle. Subjects with a higher body weight had significantly higher plasma estradiol and progesterone, but not testosterone and IGF-I than subjects with lower body weight in both follicular and luteal phases of ovarian cycle. Women with a higher abdomen circumference had significantly lower plasma estradiol, but not the other hormones than the subjects with lower abdomen circumference. Women with higher WHR index had significantly higher plasma level of estradiol, but not other hormones than subjects with lower WHR index in both follicular and luteal phases of ovarian cycle. The present observations suggests: (1) that luteal phase of the women ovarian cycle is characterised by a dramatically increase in both progesterone and estradiol, but not in testosterone and IGF-I release, (2) that in human females growth can be up-regulated by testosterone, estradiol and IGF-I, but not by progesterone, (3) that body mass can be up-regulated by progesterone and estradiol, but not by testosterone or IGF-I, and (4) that women obesity (high WHR, but not abdomen circumference) can be promoted by estradiol, but not by other steroid hormones or IGF-I (Tab. 1, Fig. 4, Ref

  4. Assessment of ovarian reserve: Anti-Mullerian hormone versus follicle stimulating hormone

    PubMed Central

    Jamil, Zehra; Fatima, Syeda Sadia; Cheema, Zahra; Baig, Safia; Choudhary, Roha Ahmed

    2016-01-01

    Background: This study aimed to evaluate the strength of anti-Mullerian hormone (AMH) and follicle stimulating hormone (FSH) in reflecting the antral follicle count (AFC) in infertile females. Materials and Methods: This cross-sectional study was conducted on 160 females, visiting infertility clinic for assisted reproduction. Serum samples collected on the 3rd day of the cycle were assayed for FSH, luteinizing hormone, and AMH while AFC was assessed via transvaginal ultrasound. The study cohort was segregated into three groups based on AFC. Results: Chronological age and FSH was significantly high in females with very low AFC (P < 0.01 and 0.009, respectively), yet they failed to discriminate patients with normal and higher follicle count (P = 0.65 and 0.84). Conversely, AMH reported highly significant difference between very low AFC and with those having either normal AFC (P = 0.002) or higher AFC (P = 0.001). Moreover, a significant difference in AMH was observed between normal and higher AFC group (P = 0.04). Conclusion: Compared to female’s age and FSH, AMH is superior in clustering study cohort on the bases of antral follicular pool, especially in setups with nonavailability of technological expertise to assess AFC. Incorporation of AMH along with other biomarkers improves estimation of baseline ovarian reserve, required to standardize dose for optimum response; avoiding the risk of failure to retrieve oocyte or inappropriate stimulation leading to ovarian hyperstimulation syndrome. Further prospective studies are required to ascertain its role in predicting the outcomes of ART in such patients. PMID:28163746

  5. Biogas final digestive byproduct applied to croplands as fertilizer contains high levels of steroid hormones.

    PubMed

    Rodriguez-Navas, Carlos; Björklund, Erland; Halling-Sørensen, Bent; Hansen, Martin

    2013-09-01

    In this study we evaluate and demonstrate the occurrence of nine natural and one synthetic steroid hormone, including estrogens, androgens and progestagens in biogas final digestate byproduct (digestion liquid) commonly used as an agricultural fertilizer. We investigated two biogas sites that utilize different anaerobic digestion technologies (mesophilic and thermophilic) from swine manure and other organic wastes. Individual hormone concentration levels were observed up to 1478 ng g(-1) dry weight or 22.5 mg kg(-1) N with estrone and progesterone reaching highest concentration levels. Evaluation of the potential environmental burden through the application in agriculture was also assessed on the basis of predicted environmental concentrations. This study indicates that the biogas digestion process does not completely remove steroid hormones from livestock manure and use of final digestate byproduct on croplands contributes to the environmental emission of hormones. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Ovarian hormones, sleep and cognition across the adult female lifespan: An integrated perspective.

    PubMed

    Gervais, Nicole J; Mong, Jessica A; Lacreuse, Agnès

    2017-10-01

    Loss of ovarian function in women is associated with sleep disturbances and cognitive decline, which suggest a key role for estrogens and/or progestins in modulating these symptoms. The effects of ovarian hormones on sleep and cognitive processes have been studied in separate research fields that seldom intersect. However, sleep has a considerable impact on cognitive function. Given the tight connections between sleep and cognition, ovarian hormones may influence selective aspects of cognition indirectly, via the modulation of sleep. In support of this hypothesis, a growing body of evidence indicates that the development of sleep disorders following menopause contributes to accelerated cognitive decline and dementia in older women. This paper draws from both the animal and human literature to present an integrated view of the effects of ovarian hormones on sleep and cognition across the adult female lifespan. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Effects of sub-lethal levels of dichlorodiphenyltrichloroethane and dichlorodiphenyldichloroethylene on in vitro steroid biosynthesis by ovarian follicles or steroid metabolism by embryos of rainbow trout (Oncorhynchus mykiss).

    PubMed

    Petkam, Rakpong; Renaud, Rick; Lin, Lucy; Boermans, Herman; Leatherland, John

    2005-07-01

    This study examined the possibility that DDT and DDE, at sub-lethal exposure levels, exert direct effects on the biotransformation of gonadal steroids by rainbow trout (Oncorhynchus mykiss) ovarian follicles and embryos. Ovarian follicles were co-incubated with DDT or DDE at 0.01 or 1 mg l-1 to examine effects of the pesticides on basal or cAMP-activated steroidogenesis. Ovarian preparations were incubated with radiolabelled [3H]pregnenolone ([3H]P5), and the tritiated metabolites of [3H]P5 metabolism were separated using high-performance liquid chromatography (HPLC). Testosterone (T) and 17beta-estradiol (E2) production were also measured using radioimmunoassay (RIA). Embryos were either exposed to the pesticides in ovo, or co-incubated in vitro with the pesticides. The effect of the pesticides on embryo steroid biotransformation was examined using a range of radioactively labelled substrates, including [3H]P5, [3H]progesterone ([3H]P4), [3H]T and [3H]E2. At the concentrations used, the pesticides had no significant effect on the relative amounts of unconjugated radiolabelled steroids formed by the biotransformation of [3H]P5 under conditions of basal or cAMP-stimulated ovarian steroidogenesis. However, DDT and DDE appeared to reduce the basal accumulation of androgen as a product of P5 biotransformation by ovarian follicles. Basal or cAMP-stimulated total estrogen production was not affected. In addition, DDT at 1 mg l-1 and DDE at 0.01 mg l-1 significantly increased and decreased cAMP-stimulated T accumulation, respectively. Also DDT at 0.01 mg l-1 and DDE at 1 mg l-1 significantly increased and decreased basal E2 accumulation, respectively. The steroid metabolites synthesized from the different substrates by embryos were essentially similar in both controls and pesticide-exposed groups, and the survival of embryos to hatch was not significantly affected by pesticide exposure, in ovo, with an approximately 90% hatchability in all treatment groups. This study

  8. A factor analysis approach to examining relationships among ovarian steroid concentrations, gonadotrophin concentrations and menstrual cycle length characteristics in healthy, cycling women

    PubMed Central

    Barrett, E.S.; Thune, I.; Lipson, S.F.; Furberg, A.-S.; Ellison, P.T.

    2013-01-01

    STUDY QUESTION How are ovarian steroid concentrations, gonadotrophins and menstrual cycle characteristics inter-related within normal menstrual cycles? SUMMARY ANSWER Within cycles, measures of estradiol production are highly related to one another, as are measures of progesterone production; however, the two hormones also show some independence from one another, and measures of cycle length and gonadotrophin concentrations show even greater independence, indicating minimal integration within cycles. WHAT IS KNOWN ALREADY The menstrual cycle is typically conceptualized as a cohesive unit, with hormone levels, follicular development and ovulation all closely inter-related within a single cycle. Empirical support for this idea is limited, however, and to our knowledge, no analysis has examined the relationships among all of these components simultaneously. STUDY DESIGN, SIZE, DURATION A total of 206 healthy, cycling Norwegian women participated in a prospective cohort study (EBBA-I) over the duration of a single menstrual cycle. Of these, 192 contributed hormonal and cycle data to the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects provided daily saliva samples throughout the menstrual cycle from which estradiol and progesterone concentrations were measured. FSH and LH concentrations were measured in serum samples from three points in the same menstrual cycle and cycle length characteristics were calculated based on hormonal data and menstrual records. A factor analysis was conducted to examine the underlying relationships among 22 variables derived from the hormonal data and menstrual cycle characteristics. MAIN RESULTS AND THE ROLE OF CHANCE Six rotated factors emerged, explaining 80% of the variance in the data. Of these, factors representing estradiol and progesterone concentrations accounted for 37 and 13% of the variance, respectively. There was some association between measures of estradiol and progesterone production within cycles; however

  9. Translocator Protein/Peripheral Benzodiazepine Receptor Is Not Required for Steroid Hormone Biosynthesis

    PubMed Central

    Morohaku, Kanako; Pelton, Susanne H.; Daugherty, Daniel J.; Butler, W. Ronald

    2014-01-01

    Molecular events that regulate cellular biosynthesis of steroid hormones have been a topic of intense research for more than half a century. It has been established that transport of cholesterol into the mitochondria forms the rate-limiting step in steroid hormone production. In current models, both the steroidogenic acute regulatory protein (StAR) and the translocator protein (TSPO) have been implicated to have a concerted and indispensable effort in this cholesterol transport. Deletion of StAR in mice resulted in a critical failure of steroid hormone production, but deletion of TSPO in mice was found to be embryonic lethal. As a result, the role of TSPO in cholesterol transport has been established only using pharmacologic and genetic tools in vitro. To allow us to explore in more detail the function of TSPO in cell type-specific experimental manipulations in vivo, we generated mice carrying TSPO floxed alleles (TSPOfl/fl). In this study we made conditional knockout mice (TSPOcΔ/Δ) with TSPO deletion in testicular Leydig cells by crossing with an anti-Mullerian hormone receptor type II cre/+ mouse line. Genetic ablation of TSPO in steroidogenic Leydig cells in mice did not affect testosterone production, gametogenesis, and reproduction. Expression of StAR, cytochrome P450 side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase type I, and TSPO2 in TSPOcΔ/Δ testis was unaffected. These results challenge the prevailing dogma that claims an essential role for TSPO in steroid hormone biosynthesis and force reexamination of functional interpretations made for this protein. This is the first study examining conditional TSPO gene deletion in mice. The results show that TSPO function is not essential for steroid hormone biosynthesis. PMID:24174323

  10. Chemometric evaluation of urinary steroid hormone levels as potential biomarkers of neuroendocrine tumors.

    PubMed

    Plenis, Alina; Miękus, Natalia; Olędzka, Ilona; Bączek, Tomasz; Lewczuk, Anna; Woźniak, Zofia; Koszałka, Patrycja; Seroczyńska, Barbara; Skokowski, Jarosław

    2013-10-16

    Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL-1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1-300 ng mL-1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  11. Steroid hormones alter neuroanatomy and aggression independently in the tree lizard

    PubMed Central

    Kabelik, David; Weiss, Stacey L.; Moore, Michael C.

    2008-01-01

    KABELIK, D., Weiss S. L. AND MOORE M. C. Steroid hormones alter neuroanatomy and aggression independently in the tree lizard. PHYSIOL BEHAV 00(0) 000-000, 0000. –Steroid hormones affect changes in both neuroanatomy and aggressive behavior in animals of various taxa. However, whether changes in neuroanatomy directly underlie changes in aggression is unknown. We investigate this relationship among steroid hormones, neuroanatomy, and aggression in a free-living vertebrate with a relatively simple nervous system, the tree lizard (Urosaurus ornatus). Weiss and Moore [1] manipulated testosterone and progesterone levels in adult male tree lizards and found that both hormones facilitated aggressive behavior toward a conspecific. In this study, we examined the brains of a subset of these animals to determine whether changes in limbic morphology were associated with hormone-induced changes in aggressive behavior. Specifically, we tested the hypothesis that testosterone and/or progesterone cause changes in neural morphology that are necessary for the expression of testosterone’s effects on aggressive behavior. We found that both hormones increased aggression; however, only testosterone induced changes in neuroanatomy. Testosterone increased the size of both the amygdala and nucleus sphericus. However, we could detect no individual correlations between neuroanatomy and aggression levels suggesting that the observed large-scale changes in neuroanatomy are not precisely reflective of changes in mechanisms underlying aggression. PMID:17996258

  12. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate

    PubMed Central

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-01-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin–testosterone–oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin–testosterone–oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes. PMID:21039986

  13. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate.

    PubMed

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-12-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin-testosterone-oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin-testosterone-oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes.

  14. Dairy Wastewater, Aquaculture, and Spawning Fish as Sources of Steroid Hormones in the Aquatic Environment

    NASA Astrophysics Data System (ADS)

    Kolodziej, E. P.; Harter, T.; Sedlak, D. L.

    2004-12-01

    A suite of androgens, estrogens, and progestins were measured in samples from dairy farms, aquaculture facilities, and surface waters with actively spawning fish using gas chromatography-tandem mass spectrometry (GC/MS/MS) to assess the potential importance of these sources of steroid hormones to surface waters. In a dairy waste lagoon, the endogenous estrogens 17beta-estradiol and estrone, and the androgens testosterone and androstenedione were detected at concentrations as high as 650 ng/L. Samples from nearby groundwater monitoring wells demonstrated removal of steroid hormones in the subsurface. Samples from nearby surface waters and tile drains likely impacted by animal wastes demonstrated the sporadic presence of the steroids 17beta-estradiol, estrone, testosterone, and medroxyprogesterone, usually at concentrations near or below 1 ng/L. The endogenous steroids estrone, testosterone, and androstenedione were detected in the raceways and effluents of three fish hatcheries at concentrations near 1 ng/L. Similar concentrations were detected in a river containing spawning adult Chinook salmon. These results indicate that dairy wastewater, aquaculture effluents, and even spawning fish are sources that can lead to detectable concentrations of steroid hormones in surface waters and that the concentrations of these compounds exhibit considerable temporal and spatial variation.

  15. Dairy wastewater, aquaculture, and spawning fish as sources of steroid hormones in the aquatic environment.

    PubMed

    Kolodziej, Edward P; Harter, Thomas; Sedlak, David L

    2004-12-01

    A suite of androgens, estrogens, and progestins were measured in samples from dairy farms, aquaculture facilities, and surface waters with actively spawning fish using gas chromatography-tandem mass spectrometry (GC/MS/ MS) to assess the potential importance of these sources of steroid hormones to surface waters. In a dairywaste lagoon, the endogenous estrogens 17beta-estradiol and estrone and the androgens testosterone and androstenedione were detected at concentrations as high as 650 ng/L. Samples from nearby groundwater monitoring wells demonstrated removal of steroid hormones in the subsurface. Samples from nearby surface waters and tile drains likely impacted by animal wastes demonstrated the sporadic presence of the steroids 17beta-estradiol, estrone, testosterone, and medroxyprogesterone, usually at concentrations near or below 1 ng/L. The endogenous steroids estrone,testosterone, and androstenedione were detected in the raceways and effluents of three fish hatcheries at concentrations near 1 ng/L. Similar concentrations were detected in a river containing spawning adult Chinook salmon. These results indicate that dairy wastewater, aquaculture effluents, and even spawning fish can lead to detectable concentrations of steroid hormones in surface waters and that the concentrations of these compounds exhibit considerable temporal and spatial variation.

  16. Pentachlorophenol disrupts steroid hormone metabolism at concentrations that reduce survival and fecundity of Daphnia magna

    SciTech Connect

    Parks, L.G.; LeBlanc, G.A.

    1995-12-31

    Alterations in steroid metabolism by environmental endocrine disrupters can significantly affect steroid hormone-dependent processes such as growth and reproduction. Exposure to pentachlorophenol (PCP) has been shown to elicit a variety of endocrine-related adverse effects. The present study was undertaken to establish whether concentrations of PCP that adversely affect survival, growth, or reproduction of Daphnia magna during chronic exposure also elicit changes in steroid hormone metabolism. Survival and/or reproduction of daphnids was significantly reduced from exposure to 1.0, 0.50 and 0.25 mg/L PCP. Following chronic exposure to PCP, daphnids were incubated with [{sup 14}C]testosterone and the testosterone metabolites eliminated were identified and quantified. The rate of testosterone hydroxyl-metabolite elimination was not significantly different from controls. However, elimination of two of the glucose-conjugated metabolites of testosterone decreased in a PCP concentration-dependent manner. Adult daphnids were next exposed to these concentrations of PCP for only 48 hours and effects on steroid metabolism assessed. As observed following chronic exposure, PCP had no effect on the elimination of hydroxyl-metabolites. However, elimination of glucose and sulfate conjugates of testosterone were inhibited in a concentration-dependent manner. These results demonstrate that, (1) PCP alters steroid biotransformation activities at concentrations that affect survival and reproduction, and (2) effects on steroid metabolism can be detected following short-term exposure to PCP. Thus, this biochemical parameter may serve as a biomarker of chronic toxicity associated with PCP.

  17. Steroid Hormone (20-Hydroxyecdysone) Modulates the Acquisition of Aversive Olfactory Memories in Pollen Forager Honeybees

    ERIC Educational Resources Information Center

    Geddes, Lisa H.; McQuillan, H. James; Aiken, Alastair; Vergoz, Vanina; Mercer, Alison R.

    2013-01-01

    Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, "Apis mellifera." 20-E impaired the bees' ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive…

  18. Drug Structure-Activity Algorithms as Tools for Student Learning: An Example Using Steroid Hormone Structures.

    ERIC Educational Resources Information Center

    Roche, Victoria F.

    1990-01-01

    An algorithm presenting questions allowing prediction of the major type of biological activity elicited by a steroid hormone structure is designed to help students organize their approach to the interpretation of the complex structures and permit independent application of logical thought processes in pharmacological identification of other drug…

  19. Steer responses to feeding soybean hulls and steroid hormone implantation on toxic tall fescue pasture

    USDA-ARS?s Scientific Manuscript database

    Yearling steers were grazed on endophyte-infected ‘Kentucky-31’ tall fescue (Lolium arundinaceum) pastures for 77 days in 2007 and for 86 days in 2008 to evaluate effects of feeding pelleted soybean hulls (PSBH) and steroid hormone implants (SHI) on steer performance and physiology. Steers were str...

  20. Steroid Hormone (20-Hydroxyecdysone) Modulates the Acquisition of Aversive Olfactory Memories in Pollen Forager Honeybees

    ERIC Educational Resources Information Center

    Geddes, Lisa H.; McQuillan, H. James; Aiken, Alastair; Vergoz, Vanina; Mercer, Alison R.

    2013-01-01

    Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, "Apis mellifera." 20-E impaired the bees' ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive…

  1. Fate of steroid hormones in sewage sludge and poultry litter prior to land application

    USDA-ARS?s Scientific Manuscript database

    Steroid hormones can act as potent endocrine disruptors when released into the environment. The main sources of these chemicals are thought to be wastewater treatment plant discharges and waste from animal feeding operations. While these compounds have frequently been found in wastewater effluents...

  2. Steroid hormones in biosolids and poultry litter: A comparison of potential environmental inputs

    USDA-ARS?s Scientific Manuscript database

    Steroid hormones can act as potent endocrine disruptors when released into the environment. The main sources of these chemicals are thought to be wastewater treatment plant discharges and waste from animal feeding operations. While these compounds have frequently been found in wastewater effluents...

  3. Reassessing the role of growth hormone and sex steroids in thymic involution.

    PubMed

    Min, Hyeyoung; Montecino-Rodriguez, Encarnacion; Dorshkind, Kenneth

    2006-01-01

    The concomitant decline in growth hormone (GH) and increase in sex steroid production with age is thought to be responsible for thymic involution. If changes in the production of these hormones trigger or sustain thymic involution, that process should be accelerated in little mice, which have a genetic deficiency resulting in reduced production of thymopoietic GH, and delayed in the hypogonadal strain, which fails to produce thymocytotoxic sex steroids. The results indicated that thymic involution in both strains progressed in a manner similar to their normal littermates. That blocking sex steroid production did not delay thymic involution was surprising since castration reportedly increases thymus cellularity. Re-examination of that phenomenon revealed that, while gonadectomy results in increased thymus size, its effects are transient, and the thymus ultimately undergoes involution. Taken together, these data suggest that age-related changes in the endocrine system do not underlie thymic involution.

  4. Steroid hormones and the stroma-vascular cells of the adipose tissue.

    PubMed

    Volat, Fanny; Bouloumié, Anne

    2013-09-01

    The stroma-vascular fraction (SVF) of adipose tissue (AT) is a heterogeneous cell fraction composed of progenitor cells, endothelial cells, and immune cells. SVF plays a key role in AT homeostasis and growth as well as in obesity-associated pathologies. The SVF cell composition and phenotype are distinct according to AT location and adiposity. Such discrepancies influence AT function and are involved in obesity-associated disorders such as chronic inflammation. Investigations performed in recent years in rodents and humans provided evidence that the stroma-vascular cells contribute to the conversion of steroid hormones in AT and are also steroid targets. This review describes the link between steroids and SVF depending on gender, adiposity, and AT location and highlights the potential role of sex and corticosteroid hormones in adipogenesis, angiogenesis, and their contributions in AT inflammation.

  5. Association Between Single-Nucleotide Polymorphisms in Hormone Metabolism and DNA Repair Genes and Epithelial Ovarian Cancer: Results from Two Australian Studies and an Additional Validation Set

    PubMed Central

    Beesley, Jonathan; Jordan, Susan J.; Spurdle, Amanda B.; Song, Honglin; Ramus, Susan J.; Kjaer, Suzanne Kruger; Hogdall, Estrid; DiCioccio, Richard A.; McGuire, Valerie; Whittemore, Alice S.; Gayther, Simon A.; Pharoah, Paul D.P.; Webb, Penelope M.; Chenevix-Trench, Georgia

    2009-01-01

    Although some high-risk ovarian cancer genes have been identified, it is likely that common low penetrance alleles exist that confer some increase in ovarian cancer risk. We have genotyped nine putative functional single-nucleotide polymorphisms (SNP) in genes involved in steroid hormone synthesis (SRD5A2, CYP19A1, HSB17B1, and HSD17B4) and DNA repair (XRCC2, XRCC3, BRCA2, and RAD52) using two Australian ovarian cancer case-control studies, comprising a total of 1,466 cases and 1,821 controls of Caucasian origin. Genotype frequencies in cases and controls were compared using logistic regression. The only SNP we found to be associated with ovarian cancer risk in both of these two studies was SRD5A2 V89L (rs523349), which showed a significant trend of increasing risk per rare allele (P = 0.00002). We then genotyped another SNP in this gene (rs632148; r2 = 0.945 with V89L) in an attempt to validate this finding in an independent set of 1,479 cases and 2,452 controls from United Kingdom, United States, and Denmark. There was no association between rs632148 and ovarian cancer risk in the validation samples, and overall, there was no significant heterogeneity between the results of the five studies. Further analyses of SNPs in this gene are therefore warranted to determine whether SRD5A2 plays a role in ovarian cancer predisposition. PMID:18086758

  6. Effect of exogenous ovarian steroids on the uterine luminal prostaglandins in ovariectomised mares with experimental endometritis.

    PubMed

    Watson, E D; Stokes, C R; Bourne, F J

    1988-05-01

    Prostaglandins (PGs) F and E2 were measured in lavage fluid from the uterus of ovariectomised mares after experimental induction of uterine inflammation. Treatment with progesterone alone, or progesterone followed by oestradiol, significantly increased the concentrations of these PGs in the lavage compared with mares treated with oestradiol or control mares. Ovarian steroids, therefore, influenced uterine PG synthesis in response to an inflammatory stimulus. To determine whether the uterine lavage procedure might contribute to the concentrations of prostaglandins in the lavage, the procedure was also performed on six intact mares. With the exception of washings obtained at luteolysis, uterine concentrations of PGF (measured as the plasma metabolite 15-keto-13,14-dihydro PGF2 alpha) had returned to prewashing levels within 30 minutes of the start of uterine lavage. Lavage was therefore unlikely to have influenced the concentrations of prostaglandins in the lavage fluid.

  7. Sex steroid hormones in relation to Barrett's esophagus: an analysis of the FINBAR Study.

    PubMed

    Cook, M B; Wood, S; Hyland, P L; Caron, P; Drahos, J; Falk, R T; Pfeiffer, R M; Dawsey, S M; Abnet, C C; Taylor, P R; Guillemette, C; Murray, L J; Anderson, L A

    2017-03-01

    Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol ORcontinuous per ½IQR  = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone ORcontinuous per ½IQR  = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis.

  8. Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

    PubMed

    Nath, S; Kadasi, A; Grossmann, R; Sirotkin, A V; Kolesarova, A; Talukdar, A D; Choudhury, M D

    2015-01-01

    Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.

  9. Effect of Adrenal steroid hormones on the response of the toad's urinary bladder to vasopressin

    PubMed Central

    Handler, J. S.; Preston, A. S.; Orloff, J.

    1969-01-01

    This study was designed to examine the effect of adrenal steroid hormones on the response of the toad bladder to vasopressin. Aldosterone enhanced the short-circuit current response, the osmotic water flow response, and the urea permeability response to vasopressin. Since aldosterone also enhanced the short-circuit current response and the osmotic water flow response to adenosine 3′,5′-monophosphate, the steroid effect on the bladder's response to vasopressin appears to be at a step beyond the stimulation of adenyl cyclase. Indirect evidence was obtained that the effect of adrenal steroid hormones on the osmotic water flow response to vasopressin is mediated by a different hormone-tissue interaction than that mediating the effect of adrenal steroid hormones on sodium transport. In experiments with three different pairs of mineralocorticoid and glucocorticoid analogues, the former had a greater effect on short-circuit current, the latter on the osmotic water flow response to vasopressin. In addition, the spirolactone SC-14266 markedly inhibited the short-circuit current effect of dexamethasone and had little or no inhibitory effect on the dexamethasone enhancement of the osmotic water flow response to vasopressin. Aldosterone and dexamethasone stimulate the oxidation by the bladder of glucose-6-14C and depress the rate of oxidation of glucose-1-14C compared with glucose-6-14C. SC-14266 inhibited the effect of dexamethasone on the oxidation of glucose-6-14C but did not alter the effect of the steroid on the rate of oxidation of glucose-1-14C compared with glucose-6-14C, suggesting that the latter is a glucocorticoid effect and the stimulation of glucose-6-14C oxidation a mineralocorticoid effect. Under conditions in which aldosterone has produced a marked enhancement of short-circuit current and the permeability response to vasopressin, the steroid had no detectable effect on cell water content or on cell sodium, potassium, or chloride. PMID:5780194

  10. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones

    PubMed Central

    2010-01-01

    Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are unique in that they require cholesterol not only for membrane biogenesis, maintenance of membrane fluidity and cell signaling, but also as the starting material for the biosynthesis of steroid hormones. It is not surprising, then, that cells of steroidogenic tissues have evolved with multiple pathways to assure the constant supply of cholesterol needed to maintain optimum steroid synthesis. The cholesterol utilized for steroidogenesis is derived from a combination of sources: 1) de novo synthesis in the endoplasmic reticulum (ER); 2) the mobilization of cholesteryl esters (CEs) stored in lipid droplets through cholesteryl ester hydrolase; 3) plasma lipoprotein-derived CEs obtained by either LDL receptor-mediated endocytic and/or SR-BI-mediated selective uptake; and 4) in some cultured cell systems from plasma membrane-associated free cholesterol. Here, we focus on recent insights into the molecules and cellular processes that mediate the uptake of plasma lipoprotein-derived cholesterol, events connected with the intracellular cholesterol processing and the role of crucial proteins that mediate cholesterol transport to mitochondria for its utilization for steroid hormone production. In particular, we discuss the structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites, where P450scc (CYP11A) is localized and where the conversion of cholesterol to pregnenolone (the common

  11. Sex steroid hormone levels in breast adipose tissue and serum in postmenopausal women.

    PubMed

    Falk, Roni T; Gentzschein, Elisabet; Stanczyk, Frank Z; Garcia-Closas, Montserrat; Figueroa, Jonine D; Ioffe, Olga B; Lissowska, Jolanta; Brinton, Louise A; Sherman, Mark E

    2012-01-01

    Elevated levels of circulating estrogens and androgens are linked to higher breast cancer risk among postmenopausal women; however, little is known about hormone levels within the breast. Hormone concentrations within the breast may not be reflected in the blood and are likely important contributors to breast carcinogenesis. We used a previously validated method to measure levels of estrone, estradiol, androstenedione, and testosterone in adipose tissue removed as part of breast excisions performed for cancer in 100 postmenopausal women (69 ER/PR +/+ and 31 ER/PR -/-) participating in a breast cancer case-control study. We also measured the same steroid hormones, as well as estrone sulfate, and sex hormone-binding globulin (SHBG) in serum from these patients and 100 controls matched on ages at blood collection and on menopause. Overall, concentrations of serum hormones did not vary significantly between controls and cases. However, women with ER-/PR- breast cancers had lower circulating levels of all measured sex steroid hormones and higher SHBG levels than women with ER+/PR+ breast cancers and controls. Similarly, hormone concentrations in breast adipose tissue were higher among women with ER+/PR+ compared to ER-/PR- breast cancer, although differences were only significant for testosterone. These data demonstrate that high sex steroid concentrations in both serum and adipose tissues are more strongly related to ER+/PR+ than ER-/PR- breast cancers. Measurement of sex hormones in serum and in the microenvironment may help in understanding the hormonal etiology of breast cancer, suggest methods for prevention, and have value in gauging treatment response and prognosis.

  12. Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids

    PubMed Central

    Szóstek, Anna Z.; Galvão, Antonio M.; Hojo, Takuo; Okuda, Kiyoshi; Skarzynski, Dariusz J.

    2014-01-01

    The aim of the present study was to investigate the interaction between ovarian steroids, interleukins and prostaglandins (PG) in equine epithelial and stromal cells in vitro. In Experiment 1, cells were exposed to IL-1α (10 ng/mL), IL-1β (10 ng/mL) or IL-6 (10 ng/mL) for 24 h and cell proliferation was determined using MTT. In Experiment 2, cells were exposed to progesterone (P4; 10−7 M); 17-β estradiol (E2; 10−9 M) or P4+E2 for 24 h and later medium was replaced with a fresh one treated with IL-1α, IL-1β or IL-6 (10 ng/mL, each) for 24 h. The oxytocin (OT; 10−7 M) was used as a positive control. In Experiment 3, cells were exposed to P4 (10−7 M), E2 (10−9 M) or P4+E2 for 24 h and the IL receptor mRNAs transcription was determined using Real-time PCR. Prostaglandins concentration was determined using the direct enzyme immunoassay (EIA) method. Our findings reveal a functional linking between ovarian steroids and IL-stimulated PG secretion by equine endometrial cells. This interaction could be one of the mechanisms responsible for endometrial local orchestrating events during the estrous cycle and early pregnancy. PMID:24719522

  13. Coordinated steroid hormone-dependent and independent expression of multiple kallikreins in breast cancer cell lines.

    PubMed

    Paliouras, Miltiadis; Diamandis, Eleftherios P

    2007-03-01

    The regulation of gene expression by steroid hormones plays an important role in the normal development and function of many organs, as well in the pathogenesis of endocrine-related cancers. Previous experiments have shown that many kallikrein genes are under steroid hormone regulation in breast cancer cell lines. We here examine the coordinated expression of multiple kallikrein genes in several breast cancer cell lines after steroid hormone stimulation. Breast cancer cell lines were treated with various steroid hormones and kallikrein (KLK/hK) expression of hK3 (prostate-specific antigen, PSA), hK5, hK6, hK7, hK8, hK10, hK11, hK13, and hK14 was analyzed at the RNA level via RT-PCR and at the protein level by immunofluorometric ELISA assays. We identified several distinct hK hormone-dependent and hormone-independent expression patterns. Hormone-specific modulation of expression was seen for several kallikreins in BT-474, MCF-7, and T-47D cell lines. hK6 was specifically up-regulated upon estradiol treatment in all three cell lines whereas PSA expression was induced by dihydrotestosterone (DHT) and norgestrel stimulation in BT-474 and T-47D. hK10, hK11, hK13, and hK14 were specifically up-regulated by DHT in T-47D and by estradiol in BT-474 cells. Bioinformatic analysis of upstream proximal promoter sequences for these hKs did not identify any recognizable hormone-response elements (HREs), suggesting that the coordinated activation of these four hKs represents a unique expression "cassette", utilizing a common hormone-dependent mechanism. We conclude that groups of human hKs are coordinately expressed in a steroid hormone-dependent manner. Our data supports clinical observations linking expression of multiple hKs with breast cancer prognosis.

  14. Gonadotropin-induced changes in oviducal mRNA expression levels of sex steroid hormone receptors and activin-related signaling factors in the alligator.

    PubMed

    Moore, Brandon C; Forouhar, Sara; Kohno, Satomi; Botteri, Nicole L; Hamlin, Heather J; Guillette, Louis J

    2012-01-15

    Oviducts respond to hormonal cues from ovaries with tissue proliferation and differentiation in preparation of transporting and fostering gametes. These responses produce oviducal microenvironments conducive to reproductive success. Here, we investigated changes in circulating plasma sex steroid hormones concentrations and ovarian and oviducal mRNA expression to an in vivo gonadotropin (FSH) challenge in sexually immature, five-month-old alligators. Further, we investigated differences in these observed responses between alligators hatched from eggs collected at a heavily-polluted (Lake Apopka, FL) and minimally-polluted (Lake Woodruff, FL) site. In oviducts, we measured mRNA expression of estrogen, progesterone, and androgen receptors and also beta A and B subunits which homo- or heterodimerize to produce the transforming growth factor activin. In comparison, minimal inhibin alpha subunit mRNA expression suggests that these oviducts produce a primarily activin-dominated signaling milieu. Ovaries responded to a five-day FSH challenge with increased expression of steroidogenic enzyme mRNA which was concomitant with increased circulating sex steroid hormone concentrations. Oviducts in the FSH-challenged Lake Woodruff alligators increased mRNA expression of progesterone and androgen receptors, proliferating cell nuclear antigen, and the activin signaling antagonist follistatin. In contrast, Lake Apopka alligators displayed a diminished increase in ovarian CYP19A1 aromatase expression and no increase in oviducal AR expression, as compared to those observed in Lake Woodruff alligators. These results demonstrate that five-month-old female alligators display an endocrine-responsive ovarian-oviducal axis and environmental pollution exposure may alter these physiological responses.

  15. Gonadotropin-induced changes in oviducal mRNA expression levels of sex steroid hormone receptors and activin-related signaling factors in the alligator

    PubMed Central

    Moore, Brandon C.; Forouhar, Sara; Kohno, Satomi; Botteri, Nicole L.; Hamlin, Heather J.; Guillette, Louis J.

    2011-01-01

    Oviducts respond to hormonal cues from ovaries with tissue proliferation and differentiation in preparation of transporting and fostering gametes. These responses produce oviducal microenvironments conducive to reproductive success. Here we investigated changes in circulating plasma sex steroid hormones concentrations and ovarian and oviducal mRNA expression to an in vivo gonadotropin (FSH) challenge in sexually immature, five-month-old alligators. Further, we investigated differences in these observed responses between alligators hatched from eggs collected at a heavily-polluted (Lake Apopka, FL) and minimally-polluted (Lake Woodruff, FL) site. In oviducts, we measured mRNA expression of estrogen, progesterone, and androgen receptors and also beta A and B subunits which homo- or heterodimerize to produce the transforming growth factor activin. In comparison, minimal inhibin alpha subunit mRNA expression suggests that these oviducts produce a primarily activin-dominated signaling milieu. Ovaries responded to a five-day FSH challenge with increased expression of steroidogenic enzyme mRNA which was concomitant with increased circulating sex steroid hormone concentrations. Oviducts in the FSH-challenged Lake Woodruff alligators increased mRNA expression of progesterone and androgen receptors, proliferating cell nuclear antigen, and the activin signaling antagonist follistatin. In contrast, Lake Apopka alligators displayed a diminished increase in ovarian CYP19A1 aromatase expression and no increase in oviducal AR expression, as compared to those observed in Lake Woodruff alligators. These results demonstrate that five-month-old female alligators display an endocrine-responsive ovarian-oviducal axis and environmental pollution exposure may alter these physiological responses. PMID:22154572

  16. The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions.

    PubMed

    Vasconcelos, Andrea Rodrigues; Cabral-Costa, João Victor; Mazucanti, Caio Henrique; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

    2016-01-01

    Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain. The hypothalamic-pituitary-adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer's and Parkinson's diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, while metabolic syndromes, such as diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, such as calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes.

  17. Transport of Steroid Hormones, Phytoestrogens, and Estrogenic Activity across a Swine Lagoon/Sprayfield System

    PubMed Central

    Yost, Erin E.; Meyer, Michael T.; Dietze, Julie E.; Williams, C. Michael; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W.

    2017-01-01

    The inflow, transformation, and attenuation of natural steroid hormones, phytoestrogens, and estrogenic activity was assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet; particularly daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at two months post-application. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a lagoon/sprayfield system, and provides global insight into the fate of these analytes in this widely used waste management system. PMID:25148584

  18. The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions

    PubMed Central

    Vasconcelos, Andrea Rodrigues; Cabral-Costa, João Victor; Mazucanti, Caio Henrique; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

    2016-01-01

    Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain. The hypothalamic–pituitary–adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer’s and Parkinson’s diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, while metabolic syndromes, such as diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, such as calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes. PMID:26869995

  19. Transport of steroid hormones, phytoestrogens, and estrogenic activity across a swine lagoon/sprayfield system.

    PubMed

    Yost, Erin E; Meyer, Michael T; Dietze, Julie E; Williams, C Michael; Worley-Davis, Lynn; Lee, Boknam; Kullman, Seth W

    2014-10-07

    The inflow, transformation, and attenuation of natural steroid hormones and phytoestrogens and estrogenic activity were assessed across the lagoon/sprayfield system of a prototypical commercial swine sow operation. Free and conjugated steroid hormones (estrogens, androgens, and progesterone) were detected in urine and feces of sows across reproductive stages, with progesterone being the most abundant steroid hormone. Excreta also contained phytoestrogens indicative of a soy-based diet, particularly, daidzein, genistein, and equol. During storage in barn pits and the anaerobic lagoon, conjugated hormones dissipated, and androgens and progesterone were attenuated. Estrone and equol persisted along the waste disposal route. Following application of lagoon slurry to agricultural soils, all analytes exhibited attenuation within 2 days. However, analytes including estrone, androstenedione, progesterone, and equol remained detectable in soil at 2 months postapplication. Estrogenic activity in the yeast estrogen screen and T47D-KBluc in vitro bioassays generally tracked well with analyte concentrations. Estrone was found to be the greatest contributor to estrogenic activity across all sample types. This investigation encompasses the most comprehensive suite of natural hormone and phytoestrogen analytes examined to date across a livestock lagoon/sprayfield and provides global insight into the fate of these analytes in this widely used waste management system.

  20. Resistance training restores muscle sex steroid hormone steroidogenesis in older men.

    PubMed

    Sato, Koji; Iemitsu, Motoyuki; Matsutani, Kenji; Kurihara, Toshiyuki; Hamaoka, Takafumi; Fujita, Satoshi

    2014-04-01

    Skeletal muscle can synthesize testosterone and 5α-dihydrotestosterone (DHT) from dehydroepiandrosterone (DHEA) via steroidogenic enzymes in vitro, but hormone levels and steroidogenic enzyme expression decline with aging. Resistance exercise has been shown to increase in plasma sex steroid hormone levels. However, it remains unclear whether resistance training can restore impaired steroidogenic enzyme expressions in older individuals. Six young and 13 older men were recruited, and muscle biopsies were taken from the vastus lateralis at basal state. The same group of older subjects underwent resistance training involving knee extension and flexion exercises for 12 wk, and post-training biopsies were performed 4-5 d after the last exercise session. Muscular sex steroid hormone levels and sex steroidgenesis-related enzyme expressions were significantly lower in older subjects than younger ones at baseline, but 12 wk of resistance training significantly restored hormone levels (DHEA: 432±26 at baseline, 682±31 pg/μg protein, DHT: 6.2±0.9 at baseline, 9.8±1.4 pg/μg protein). Furthermore, the steroidogenesis-related enzymes such as 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and 5α-reductase expressions were significantly restored by resistance training. We conclude progressive resistance training restores age-related declines in sex steroidogenic enzyme and muscle sex steroid hormone levels in older men.

  1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    SciTech Connect

    Karman, Bethany N. Basavarajappa, Mallikarjuna S. Craig, Zelieann R. Flaws, Jodi A.

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 μM) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ►TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ►Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ►TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  2. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion.

    PubMed

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  3. Gonadotropins in the Russian Sturgeon: Their Role in Steroid Secretion and the Effect of Hormonal Treatment on Their Secretion

    PubMed Central

    Yom-Din, Svetlana; Hollander-Cohen, Lian; Aizen, Joseph; Boehm, Benjamin; Shpilman, Michal; Golan, Matan; Hurvitz, Avshalom; Degani, Gad; Levavi-Sivan, Berta

    2016-01-01

    In the reproduction process of male and female fish, pituitary derived gonadotropins (GTHs) play a key role. To be able to specifically investigate certain functions of Luteinizing (LH) and Follicle stimulating hormone (FSH) in Russian sturgeon (Acipenser gueldenstaedtii; st), we produced recombinant variants of the hormones using the yeast Pichia pastoris as a protein production system. We accomplished to create in vitro biologically active heterodimeric glycoproteins consisting of two associated α- and β-subunits in sufficient quantities. Three dimensional modelling of both GTHs was conducted in order to study the differences between the two GTHs. Antibodies were produced against the unique β-subunit of each of the GTHs, in order to be used for immunohistochemical analysis and to develop an ELISA for blood and pituitary hormone quantification. This detection technique revealed the specific localization of the LH and FSH cells in the sturgeon pituitary and pointed out that both cell types are present in substantially higher numbers in mature males and females, compared to immature fish. With the newly attained option to prevent cross-contamination when investigating on the effects of GTH administration, we compared the steroidogeneic response (estradiol and 11-Keto testosterone (11-KT) in female and males, respectively) of recombinant stLH, stFSH, and carp pituitary extract in male and female sturgeon gonads at different developmental stages. Finally, we injected commercially available gonadotropin releasing hormones analog (GnRH) to mature females, and found a moderate effect on the development of ovarian follicles. Application of only testosterone (T) resulted in a significant increase in circulating levels of 11-KT whereas the combination of GnRH + T did not affect steroid levels at all. The response pattern for estradiol demonstrated a similar situation. FSH levels showed significant increases when GnRH + T was administered, while no changes were present in

  4. The bifunctional role of steroid hormones: implications for therapy in prostate cancer.

    PubMed

    Mathew, Paul

    2014-05-01

    Ablation of the androgen-signaling axis is currently a dominant theme in developmental therapeutics in prostate cancer. Highly potent inhibitors of androgen biosynthesis and androgen receptor (AR) function have formally improved survival in castration-resistant metastatic disease. Resistance to androgen-ablative strategies arises through diverse mechanisms. Strategies to preserve and extend the success of hormonal therapy while mitigating the emergence of resistance have long been of interest. In preclinical models, intermittent hormonal ablative strategies delay the emergence of resistant stem-cell-driven phenotypes, but clinical studies in hormone-naive disease have not observed more than noninferiority over continual androgen ablation. In castration-resistant disease, response and improvement in subjective quality of life with therapeutic testosterone has been observed, but so too has symptomatic and life-threatening disease acceleration. The multifunctional and paradoxical role of steroid hormones in regulating proliferation and differentiation, as well as cell death, requires deeper understanding. The lack of molecular biomarkers that predict the outcome of hormone supplementation in a particular clinical context remains an obstacle to individualized therapy. Biphasic patterns of response to hormones are identifiable in vitro, and endocrine-regulated neoplasms that proliferate after prolonged periods of hormone deprivation appear preferentially sex steroid-suppressible. This review examines the relevance of a translational framework for studying therapeutic androgens in prostate cancer.

  5. [Hormone modulation of organ donor. Utility of the steroids].

    PubMed

    Michelena, Juna C; Chamorro, Carlos; Falcón, Juan A; Garcés, Sandra

    2009-01-01

    Recently, the work group made up of the National Transplant Organization (Organización Nacional de Trasplantes, ONT), Spanish Society of Intensive, Critical Medicine and Coronary Units (Sociedad Española de Medicina Intensiva, Crítica y de Unidades Coronarias, SEMICYUC) and other Scientific Societies have recommended using 15 mg/kg of methyl prednisolone during the management of lung donors after brain death. This recommendation is based on descriptive and retrospective studies. However, the review of different experimental and clinical studies also suggests a potential benefit of using steroids in either thoracic or abdominal organ donors during management strategies. In brain death management, early steroid administration may decrease cytokine production and also may prevent alterations induced by proinflammatoy mediators, stabilize cell membranes, reduce expression of cell surface adhesion molecules and avoid lipid peroxidation after the ischemic period. This could be beneficial in increasing number and quality of organs harvested and in decreasing rejection episodes after transplant. It would be very recommendable to carry out prospective and comparative studies to demonstrate these potential utilities. Meanwhile and knowing the deleterious effects of inflammatory activity arising during and after brain death, we recommend using 15 mg/kg of methyl prednisolone in the organ donor management, as soon as possible. The potential benefit of its immunomodulation effects, its low cost and the absence of major side effects can justify this recommendation.

  6. Salivary steroid hormone response to whole-body cryotherapy in elite rugby players.

    PubMed

    Grasso, D; Lanteri, P; Di Bernardo, C; Mauri, C; Porcelli, S; Colombini, A; Zani, V; Bonomi, F G; Melegati, G; Banfi, G; Lombardi, G

    2014-01-01

    Saliva represents a low stress, not-invasively collected matrix that allows steroid hormone monitoring in athletes by reflecting type, intensity and duration of exercise. Whole body cryotherapy (WBC) consists of short whole-body exposures to extremely cold air (-110° to -140°C) which, despite being initially used to treat inflammatory diseases, is currently acquiring increasing popularity in sports medicine. Cryostimulation practice is now widely accepted as an effective treatment to accelerate muscle recovery in rugby players. The aim of this work was to study the changes of steroid hormones in saliva of rugby players after both 2 and 14 consecutive WBC sessions, in order to investigate the effects of the treatment on their salivary steroid hormonal profile. Twenty-five professional rugby players, belonging to the Italian National Team, underwent a 7-day cryotherapy protocol consisting of 2 daily sessions. Saliva samples were taken in the morning prior to the start of the WBC, in the evening after the end of the second WBC, and in the morning of the day after the last WBC session. The samples were analyzed for cortisol, DHEA, testosterone and estradiol using competitive enzyme-linked immunosorbent assays. Cortisol and DHEA showed a reduction already after the 2 WBC sessions of the first day; after 14 consecutive WBC sessions cortisol, DHEA, and estradiol levels decreased, while testosterone increased as did the testosterone to cortisol ratio. These results were confirmed by the fact that the majority of subjects showed variations exceeding the critical difference (CD). In conclusion, we found that WBC acutely affects the salivary steroid hormone profile, and the results are evident already after only one twice-daily session. Most significantly, after one-week of consecutive twice-daily WBC sessions, all the hormones were modified. This is the first experimental report that links changes in the hormonal asset to WBC.

  7. Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver

    PubMed Central

    Cheng, Jie; Gonzalez, Frank J.

    2013-01-01

    CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17β-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1α, β-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states. PMID:23548611

  8. Steroids

    MedlinePlus

    ... about being the very best in your favorite sport, not to mention earning a big salary. But ... t the kind of steroids getting attention in sports. When people say steroids (say: STARE-oydz), they ...

  9. Ovarian transcriptomes as a tool for a global approach of genes modulated by gonadotropic hormones in human ovarian granulosa cells.

    PubMed

    Friedmann, Sarit; Sarit, Freimann; Dantes, Ada; Ada, Dantes; Amsterdam, Abraham; Abraham, Amsterdam

    2005-04-01

    Follicle-stimulating hormone (FSH) is a key stimulant for the development of the ovarian follicle, while luteinizing hormone (LH) plays a major role in triggering ovulation and luteinization. Both FSH and LH are glycoprotein hormones that share the same alpha subunit but bind to specific seven transmembrane-domain G coupled receptors located on the cell membrane of the granulosa cells, which comprise the main somatic population of the ovarian follicle. These hormone-receptor complexes may trigger different signaling cascades, but the entire repertoire of genes modulated by these hormones is far from being understood, in particular on the transcriptional level. The development of DNA micro-arrays technique, using the entire genome profile of some mammalian species, allows a global approach and screening of multiple signal transduction pathways. This method opened new insights into the cellular and molecular events that control ovulation and desensitization of the corpus luteum to hyperstimulation by gonadotropic hormones. In addition, this technique permitted the discovery of novel members of the EGF family, such as epiregulin and amphiregulin, that were found to be expressed in the gonadotropin-stimulated cells and were discovered to play a crucial role in the mechanism of ovulation. However, because of the pitfalls in interpreting the data other approaches, for example, Northern blots and RT-PCR must be conducted in parallel to verify the validity of the data.

  10. Modulatory effects of sex steroid hormones on brain-derived neurotrophic factor-tyrosine kinase B expression during adolescent development in C57Bl/6 mice.

    PubMed

    Hill, R A; Wu, Y W C; Kwek, P; van den Buuse, M

    2012-05-01

    Sex steroid hormones and neurotrophic factors are involved in pruning and shaping the adolescent brain and have been implicated in the pathogenesis of neurodevelopmental disorders, including mental illness. We aimed to determine the association between altered levels of sex steroid hormones during adolescent development and neurotrophic signalling in the C57Bl/6 mouse. We first performed a week by week analysis from pre-pubescence to adulthood in male and female C57Bl/6 mice, measuring serum levels of testosterone and oestradiol in conjunction with western blot analysis of neurotrophin expression in the forebrain and hippocampal regions. Second, we manipulated adolescent sex steroid hormone levels by gonadectomy and hormone replacement at the pre-pubescent age of 5 weeks. Young-adult forebrain and hippocampal neurotrophin expression was then determined. Male mice showed significant changes in brain-derived neurotrophic factor (BDNF) expression in the forebrain regions during weeks 7-10, which corresponded significantly with a surge in serum testosterone. Castration and testosterone or di-hydrotestosterone replacement experiments revealed an androgen receptor-dependent effect on BDNF-tyrosine kinase (Trk) B signalling in the forebrain and hippocampal regions during adolescence. Female mice showed changes in BDNF-TrkB signalling at a much earlier time point (weeks 4-8) in the forebrain and hippocampal regions and these did not correspond with changes in serum oestradiol. Ovariectomy actually increased BDNF expression but decreased TrkB phosphorylation in the forebrain regions. 17β-Oestradiol replacement had no effect, suggesting a role for other ovarian hormones in regulating BDNF-TrkB signalling in the adolescent female mouse brain. These results suggest the differential actions of sex steroid hormones in modulating BDNF-TrkB signalling during adolescence. These data provide insight into how the male and female brain changes in response to altered levels of

  11. Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome

    PubMed Central

    Moore, Aleisha M.; Prescott, Mel; Marshall, Christopher J.; Yip, Siew Hoong; Campbell, Rebecca E.

    2015-01-01

    Polycystic ovarian syndrome (PCOS), the leading cause of female infertility, is associated with an increase in luteinizing hormone (LH) pulse frequency, implicating abnormal steroid hormone feedback to gonadotropin-releasing hormone (GnRH) neurons. This study investigated whether modifications in the synaptically connected neuronal network of GnRH neurons could account for this pathology. The PCOS phenotype was induced in mice following prenatal androgen (PNA) exposure. Serial blood sampling confirmed that PNA elicits increased LH pulse frequency and impaired progesterone negative feedback in adult females, mimicking the neuroendocrine abnormalities of the clinical syndrome. Imaging of GnRH neurons revealed greater dendritic spine density that correlated with increased putative GABAergic but not glutamatergic inputs in PNA mice. Mapping of steroid hormone receptor expression revealed that PNA mice had 59% fewer progesterone receptor-expressing cells in the arcuate nucleus of the hypothalamus (ARN). To address whether increased GABA innervation to GnRH neurons originates in the ARN, a viral-mediated Cre-lox approach was taken to trace the projections of ARN GABA neurons in vivo. Remarkably, projections from ARN GABAergic neurons heavily contacted and even bundled with GnRH neuron dendrites, and the density of fibers apposing GnRH neurons was even greater in PNA mice (56%). Additionally, this ARN GABA population showed significantly less colocalization with progesterone receptor in PNA animals compared with controls. Together, these data describe a robust GABAergic circuit originating in the ARN that is enhanced in a model of PCOS and may underpin the neuroendocrine pathophysiology of the syndrome. PMID:25550522

  12. Divergence in Sex Steroid Hormone Signaling between Sympatric Species of Japanese Threespine Stickleback

    PubMed Central

    Kitano, Jun; Kawagishi, Yui; Mori, Seiichi; Peichel, Catherine L.; Makino, Takashi; Kawata, Masakado; Kusakabe, Makoto

    2011-01-01

    Sex steroids mediate the expression of sexually dimorphic or sex-specific traits that are important both for mate choice within species and for behavioral isolation between species. We investigated divergence in sex steroid signaling between two sympatric species of threespine stickleback (Gasterosteus aculeatus): the Japan Sea form and the Pacific Ocean form. These sympatric forms diverge in both male display traits and female mate choice behaviors, which together contribute to asymmetric behavioral isolation in sympatry. Here, we found that plasma levels of testosterone and 17β-estradiol differed between spawning females of the two sympatric forms. Transcript levels of follicle-stimulating hormone-β (FSHβ) gene were also higher in the pituitary gland of spawning Japan Sea females than in the pituitary gland of spawning Pacific Ocean females. By contrast, none of the sex steroids examined were significantly different between nesting males of the two forms. However, combining the plasma sex steroid data with testis transcriptome data suggested that the efficiency of the conversion of testosterone into 11-ketotestosterone has likely diverged between forms. Within forms, plasma testosterone levels in males were significantly correlated with male body size, a trait important for female mate choice in the two sympatric species. These results demonstrate that substantial divergence in sex steroid signaling can occur between incipient sympatric species. We suggest that investigation of the genetic and ecological mechanisms underlying divergence in hormonal signaling between incipient sympatric species will provide a better understanding of the mechanisms of speciation in animals. PMID:22216225

  13. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

    SciTech Connect

    Martinez, Elisabeth D.; Pattabiraman, Nagarajan; Danielsen, Mark . E-mail: dan@bc.georgetown.edu

    2005-08-15

    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increased ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids.

  14. Steroid hormone metabolizing enzymes in benign and malignant human bone tumors.

    PubMed

    Svoboda, Martin; Hamilton, Gerhard; Thalhammer, Theresia

    2010-04-01

    IMPORTANCE IN THE FIELD: Primary bone tumors are considered as (sex steroid) hormone-dependent tumors. Osteosarcoma, osteoblastoma and bone cysts are preferentially found in males, while giant cell tumors are more common in females. Indeed, bone tumor development and progression are influenced by sex steroid hormones derived from in situ synthesis in bone cells. This review describes intracrine mechanisms for local formation of the biologically most active estrogen, 17beta-estradiol (E2), from circulating steroid precursors through the 'aromatase' (aromatization of androgens) and the 'sulfatase' (conversion of inactive estrone-sulfate) pathway. The reader gains knowledge on both pathways and the enzymes, which contribute to the in situ availability of active hormones, namely 3beta-hydroxysteroid dehydrogenases, 17beta-hydroxysteroid dehydrogenases, aromatase, steroid sulfatases and sulfotransferases. An overview is given and the expression and function of these enzymes in bone tumors are discussed. Knowledge on pathways for the in situ formation of E2 in bone cells may allow the identification of potential targets for i) novel endocrine therapeutic options in primary bone tumors and ii) future preventive interventions.

  15. Steroid hormones are novel nucleoside transport inhibitors by competition with nucleosides for their transporters.

    PubMed

    Kaneko, Masahiro; Hakuno, Fumihiko; Kamei, Hiroyasu; Yamanaka, Daisuke; Chida, Kazuhiro; Minami, Shiro; Coe, Imogen R; Takahashi, Shin-Ichiro

    2014-01-10

    Nucleoside transport is important for nucleic acid synthesis in cells that cannot synthesize nucleosides de novo, and for entry of many cytotoxic nucleoside analog drugs used in chemotherapy. This study demonstrates that various steroid hormones induce inhibition of nucleoside transport in mammalian cells. We analyzed the inhibitory effects of estradiol (E2) on nucleoside transport using SH-SY5Y human neuroblastoma cells. We observed inhibitory effects after acute treatment with E2, which lasted in the presence of E2. However, when E2 was removed, the effect immediately disappeared, suggesting that E2 effects are not mediated through the canonical regulatory pathway of steroid hormones, such as transcriptional regulation. We also discovered that E2 could competitively inhibit thymidine uptake and binding of the labeled nucleoside transporter inhibitor, S-[4-nitrobenzyl]-6-thioinosine (NBTI), indicating that E2 binds to endogenous nucleoside transporters, leading to inhibition of nucleoside transport. We then tested the effects of various steroids on nucleoside uptake in NBTI-sensitive cells, SH-SY5Y and NBTI-insensitive cells H9c2 rat cardiomyoblasts. We found E2 and progesterone clearly inhibited both NBTI-sensitive and insensitive uptake at micromolar concentrations. Taken together, we concluded that steroid hormones function as novel nucleoside transport inhibitors by competition with nucleosides for their transporters. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Hydrophilic cyclodextrin derivatives enable effective oral administration of steroidal hormones.

    PubMed

    Pitha, J; Harman, S M; Michel, M E

    1986-02-01

    Condensation products of beta-cyclodextrin with propylene oxide or epichlorohydrin, which are amorphous and thus very soluble in water, were used to form complexes with testosterone, progesterone, and estradiol. Sublingual/buccal administration of tablets of these complexes led to effective absorption and entry of the hormones into the systemic circulation, followed by gradual elimination; rapid first-pass loss was avoided. beta-Cyclodextrin itself, its 2,6-dimethyl derivative, and a nonionic detergent did not enable effective buccal absorption. Absorption from the GI tract of hormones complexed with hydrophilic cyclodextrins was also less effective. Effective absorption of drugs from the oral cavity requires (a) that the drug and solubilizer form a complex of the inclusion type which dissolves completely and rapidly and (b) that the solubilizer neither enters nor damages oral tissue.

  17. UTX coordinates steroid hormone-mediated autophagy and cell death

    PubMed Central

    Denton, Donna; Aung-Htut, May T.; Lorensuhewa, Nirmal; Nicolson, Shannon; Zhu, Wenying; Mills, Kathryn; Cakouros, Dimitrios; Bergmann, Andreas; Kumar, Sharad

    2014-01-01

    Correct spatial and temporal induction of numerous cell type-specific genes during development requires regulated removal of the repressive histone H3 lysine 27 trimethylation (H3K27me3) modification. Here we show that the H3K27me3 demethylase dUTX is required for hormone-mediated transcriptional regulation of apoptosis and autophagy genes during ecdysone-regulated programmed cell death of Drosophila salivary glands. We demonstrate that dUTX binds to the nuclear hormone receptor complex Ecdysone Receptor/Ultraspiracle, and is recruited to the promoters of key apoptosis and autophagy genes. Salivary gland cell death is delayed in dUTX mutants, with reduced caspase activity and autophagy that coincides with decreased apoptosis and autophagy gene transcripts. We further show that salivary gland degradation requires dUTX catalytic activity. Our findings provide evidence for an unanticipated role for UTX demethylase activity in regulating hormone-dependent cell death and demonstrate how a single transcriptional regulator can modulate a specific complex functional outcome during animal development. PMID:24336022

  18. Structural and functional relationships of the steroid hormone receptors’ N-terminal transactivation domain

    PubMed Central

    Kumar, Raj; Litwack, Gerald

    2009-01-01

    Steroid hormone receptors are members of a family of ligand inducible transcription factors, and regulate the transcriptional activation of target genes by recruiting coregulatory proteins to the pre-initiation machinery. The binding of these coregulatory proteins to the steroid hormone receptors is often mediated through their two activation functional domains, AF1, which resides in the N-terminal domain, and the ligand-dependent AF2, which is localized in the C-terminal ligand binding domain. Compared to other important functional domains of the steroid hormone receptors, our understanding of the mechanisms of action of the AF1 are incomplete, in part, due to the fact that, in solution, AF1 is intrinsically disordered (ID). However, recent studies have shown that AF1 must adopt a functionally active and folded conformation for its optimal activity under physiological conditions. In this review, we summarize and discuss current knowledge regarding the molecular mechanisms of AF1-mediated gene activation, focusing on AF1 conformation and coactivator binding. We further propose models for the binding/folding of the AF1 domains of the steroid hormone receptors and their protein-protein interactions. The population of ID AF1 can be visualized as a collection of many different conformations, some of which may be assuming the proper functional folding for other critical target binding partners that result in ultimate assembly of AF1:coactivator complexes and subsequent gene regulation. Knowledge of the mechanisms involved therein will significantly help in understanding how signals from a steroid to a specific target gene are conveyed. PMID:19666041

  19. Degradation and behavior of natural steroid hormones in cow manure waste during biological treatments and ozone oxidation.

    PubMed

    Ermawati, Rahyani; Morimura, Shigeru; Tang, Yueqin; Liu, Kai; Kida, Kenji

    2007-01-01

    An efficient treatment process for screened cow manure waste, particularly for the degradation of natural steroid hormones, was developed. The first step in this process was a draw-and-fill process for thermophilic anaerobic digestion. After fourfold dilution with tap water, continuous feeding was performed for the aerobic treatment of the effluent from the anaerobic treatment. Batchwise ozone oxidation was then carried out for the degradation of the natural steroid hormones that remained in the effluent from the aerobic treatment. A yeast two-hybrid assay was performed to evaluate hormonal degradation. Significant reductions in the concentrations of total VFA, BOD(5), COD(Cr), TOC, TS, VSS, and natural steroid hormones were demonstrated in the effluent from the biological treatments. The removal ratios of such concentrations were 99.7%, 90%, 79%, 84%, 51%, 58%, and 99%, respectively. Although the concentrations of the remaining TOC and COD(Cr) remained constant, natural steroid hormones were completely removed by ozone oxidation.

  20. Association of Hormone Receptor Expression with Survival in Ovarian Endometrioid Carcinoma: Biological Validation and Clinical Implications

    PubMed Central

    Rambau, Peter; Kelemen, Linda E.; Steed, Helen; Quan, May Lynn; Ghatage, Prafull; Köbel, Martin

    2017-01-01

    This paper aims to validate whether hormone receptor expression is associated with longer survival among women diagnosed with ovarian endometrioid carcinoma (EC), and whether it identifies patients with stage IC/II tumors with excellent outcome that could be spared from toxic chemotherapy. Expression of estrogen receptor (ER) and progesterone receptor (PR) was assessed on 182 EC samples represented on tissue microarrays using the Alberta Ovarian Tumor Type (AOVT) cohort. Statistical analyses were performed to test for associations with ovarian cancer specific survival. ER or PR expression was present in 87.3% and 86.7% of cases, respectively, with co-expression present in 83.0%. Expression of each of the hormonal receptors was significantly higher in low-grade tumors and tumors with squamous differentiation. Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08–0.42, p = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10–0.53, p = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease. However, the five-year ovarian cancer specific survival among women with ER positive stage IC/II EC was 89.0% (standard error 3.3%) and for PR positive tumors 89.9% (standard error 3.2%), robustly below the 95% threshold where adjuvant therapy could be avoided. We validated the association of hormone receptor expression with ovarian cancer specific survival independent of standard predictors in an independent sample set of EC. The high ER/PR co-expression frequency and the survival difference support further testing of the efficacy of hormonal therapy in hormone receptor-positive ovarian EC. The clinical utility to identify a group of women diagnosed with EC at stage IC/II that could be spared from adjuvant therapy is limited. PMID:28264438

  1. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

    PubMed Central

    2014-01-01

    Background Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. Methods Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. Results The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement

  2. Ovarian steroids alter dopamine receptor populations in the medial preoptic area of female rats: implications for sexual motivation, desire, and behaviour.

    PubMed

    Graham, M Dean; Gardner Gregory, James; Hussain, Dema; Brake, Wayne G; Pfaus, James G

    2015-12-01

    Dopamine (DA) transmission in the medial preoptic area (mPOA) plays a critical role in the control of appetitive sexual behaviour in the female rat. We have shown previously that a DA D1 receptor (D1R)-mediated excitatory state appears to occur in females primed with estradiol benzoate (EB) and progesterone (P), whereas a DA D2 receptor (D2R)-mediated inhibitory state appears to occur in females primed only with EB. The present experiment employed three techniques to better understand what changes occur to DA receptors (DARs) in the mPOA under different hormonal profiles. Ovariectomized females were randomly assigned to one of three steroid treatment groups: EB + P (10 and 500 μg, respectively), EB + Oil, or the control (Oil + Oil), with hormone injections administered at 48 and 4 h prior to euthanizing. First, the number of neurons in the mPOA that contained D1R or D2R was assessed using immunohistochemistry. Second, the mPOA and two control areas (the prelimbic cortex and caudate putamen) were analysed for DAR protein levels using western blot, and DAR functional binding levels using autoradiography. Ovarian steroid hormones affected the two DAR subtypes in opposite ways in the mPOA. All three techniques supported previous behavioural findings that females primed with EB have a lower D1R : D2R ratio, and thus a D2R-mediated system, and females primed with EB + P have a higher D1R : D2R ratio, and thus a D1R-mediated system. This provides strong evidence for a DA-driven pathway of female sexual motivation, desire, and behaviour that is modified by different hormone priming regimens. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Colonic transit in rats: effect of ovariectomy, sex steroid hormones, and pregnancy

    SciTech Connect

    Ryan, J.P.; Bhojwani, A.

    1986-07-01

    In vitro studies suggest that the female sex steroid hormones (estrogen (E) and progesterone (P)) can affect the myoelectric and mechanical activity of colonic smooth muscle. The present study was designed to examine the influence of the hormones on colonic transit in vivo. Transit was assessed by quantifying the distribution within the colon of a radiolabeled marker (0.5 Ci Na2V CrO4), using the geometric center method of analysis. Studies were performed with adult male rats and the following groups of female rats: nonpregnant, ovariectomized, ovariectomy plus hormone pretreatment, and pregnant (day 18). Hormone-pretreated animals were studied 24 h following the fourth injection. The data can be summarized as follows. 1) Colonic transit was affected by the timing of the estrus cycle. 2) Ovariectomy eliminated the biphasic transit pattern observed in estruscycling females and resulted in a geometric center value comparable with that of the metestrus-diestrus animals. 3) E + P pretreatment of ovariectomized rats resulted in a significant decrease in the geometric center compared with the untreated ovariectomized rats. 4) The geometric center value in pregnant anials and hormone-pretreated animals. 5) Adult male rats had a geometric center value of 4.12 +/- 0.29. The results suggest that a relation exists between colonic transit and the circulating levels of the steroid hormones.

  4. WHO scientific group meeting on cardiovascular disease and steroid hormone contraceptives.

    PubMed

    1997-11-28

    More than 100 million women worldwide are thought to use steroid hormone contraceptive methods, with an estimated 93 million women using combined oral contraceptives (COCs). The composition and use of these contraceptive preparations, especially those of COCs, have changed dramatically over the years. The World Health Organization (WHO) convened a Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception during November 3-7, 1997, to review current scientific data on the use of steroid hormone contraception as they relate to the risk of myocardial infarction, ischemic and hemorrhagic stroke, and venous thromboembolic disease. The group also reviewed the incidence of cardiovascular disease among women of reproductive age in general, how the effect of risk factors for cardiovascular disease may be changed using hormonal contraceptives, and whether different compositions of COCs have different cardiovascular risk profiles. The group was comprised of the authors of background papers prepared for the meeting and experts from around the world. The scientific group's conclusions are presented. The incidence and mortality rates of all cardiovascular diseases are very low among reproductive-age women. For women who do not smoke, who have their blood pressure checked, and who do not have hypertension or diabetes, the risk of myocardial infarction in COC users is not increased regardless of age. While current users of COCs have a low absolute risk of venous thromboembolism, their risk is still 3-6 times greater than that of nonusers, with the risk probably being highest during the first year of use.

  5. Evaluation of steroid hormones and their receptors in development and progression of renal cell carcinoma

    PubMed Central

    Bennett, Nigel C; Rajandram, Retnagowri; Ng, Keng Lim

    2014-01-01

    Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC), with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC. PMID:28326246

  6. [Sex steroid hormones and brain serotonin in the estrous cycle of silver foxes].

    PubMed

    Osadchuk, L V; Voĭtenko, N N

    1992-04-01

    A significant increase in hypothalamic serotonin and estradiol levels was found in silver foxes during proestrus. During estrus, the plasma estradiol concentration was reduced and a significant increase in progesterone level was correlated with a decrease in the brain serotonin content. The data obtained suggest that the brain serotonin plays a mediating role in the control of ovarian hormonal activity and ovulation in silver foxes.

  7. DIFFERENTIAL REGULATION OF THE BUMETANIDE-SENSITIVE COTRANSPORTER (NKCC2) BY OVARIAN HORMONES

    PubMed Central

    Musselman, Teddy M; Zhang, Zheng; Masilamani, Shyama ME

    2010-01-01

    The Na-K-2Cl cotransporter (NKCC2) regulates sodium transport along the thick ascending limb of Henle’s loop and is important in control of sodium balance, renal concentrating ability and renin release. To determine if there are sex differences in NKCC2 abundance and/or distribution, and to evaluate the contribution of ovarian hormones to any such differences, we performed semiquantitative immunoblotting and immunoperoxidase immunohistochemistry for NKCC2 in the kidney of Sprague Dawley male, female and ovariectomized (OVX) rats with and without 17-β estradiol or progesterone supplementation. Intact females demonstrated greater NKCC2 protein in homogenates of whole kidney (334%±29), cortex (219%±20) and outer medulla (133%±9) compared to males. Ovarian hormone supplementation to OVX rats regulated NKCC2 in the outer medulla only, with NKCC2 protein abundance decreasing slightly in response to progesterone but increasing in response to 17-β estradiol. Immunohistochemistry demonstrated prominent NKCC2 labeling in the apical membrane of thick ascending limb cells. Kidney section NKCC2 labeling confirmed regionalized regulation of NKCC2 by ovarian hormones. Localized regulation of NKCC2 by ovarian hormones may have importance in controlling sodium and water balance over the lifetime of women as the milieu of sex hormones varies. PMID:20580730

  8. Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.

    PubMed

    Johann, Sonja; Beyer, Cordian

    2013-09-01

    The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production.

    PubMed

    Sandoval, Hector; Yao, Chi-Kuang; Chen, Kuchuan; Jaiswal, Manish; Donti, Taraka; Lin, Yong Qi; Bayat, Vafa; Xiong, Bo; Zhang, Ke; David, Gabriela; Charng, Wu-Lin; Yamamoto, Shinya; Duraine, Lita; Graham, Brett H; Bellen, Hugo J

    2014-10-14

    Mitochondrial fusion and fission affect the distribution and quality control of mitochondria. We show that Marf (Mitochondrial associated regulatory factor), is required for mitochondrial fusion and transport in long axons. Moreover, loss of Marf leads to a severe depletion of mitochondria in neuromuscular junctions (NMJs). Marf mutants also fail to maintain proper synaptic transmission at NMJs upon repetitive stimulation, similar to Drp1 fission mutants. However, unlike Drp1, loss of Marf leads to NMJ morphology defects and extended larval lifespan. Marf is required to form contacts between the endoplasmic reticulum and/or lipid droplets (LDs) and for proper storage of cholesterol and ecdysone synthesis in ring glands. Interestingly, human Mitofusin-2 rescues the loss of LD but both Mitofusin-1 and Mitofusin-2 are required for steroid-hormone synthesis. Our data show that Marf and Mitofusins share an evolutionarily conserved role in mitochondrial transport, cholesterol ester storage and steroid-hormone synthesis.

  10. Generation of breast cancer stem cells by steroid hormones in irradiated human mammary cell lines.

    PubMed

    Vares, Guillaume; Cui, Xing; Wang, Bing; Nakajima, Tetsuo; Nenoi, Mitsuru

    2013-01-01

    Exposure to ionizing radiation was shown to result in an increased risk of breast cancer. There is strong evidence that steroid hormones influence radiosensitivity and breast cancer risk. Tumors may be initiated by a small subpopulation of cancer stem cells (CSCs). In order to assess whether the modulation of radiation-induced breast cancer risk by steroid hormones could involve CSCs, we measured by flow cytometry the proportion of CSCs in irradiated breast cancer cell lines after progesterone and estrogen treatment. Progesterone stimulated the expansion of the CSC compartment both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A normal epithelial PR-negative cells, progesterone-treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c expression), which resulted in increased proportions of radiation-resistant tumor-initiating CSCs.

  11. The role of steroid hormone supplementation in non-assisted reproductive technology treatments for unexplained infertility.

    PubMed

    Quaas, Alexander M; Hansen, Karl R

    2016-12-01

    Fertility treatment strategies are evolving, with a more rapid transition to assisted reproductive technology (ART) treatments after unsuccessful non-ART treatments. This trend increases the potential importance of adjuvant treatments in non-ART cycles, such as steroid hormone supplementation. It has been established that success rates of ART treatments are increased with the use of luteal support with progesterone. In the setting of non-ART cycles, however, the evidence is less clear, and clinical practices vary widely between providers and clinics. In this review, we aimed to provide an overview of the current evidence for the use of steroid hormone supplementation, including progesterone for luteal support, estrogens, androgens, and mineralocorticoids, in the setting of non-ART treatments for ovulatory women. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Growth factors and steroid hormones: a complex interplay in the hypothalamic control of reproductive functions.

    PubMed

    Melcangi, Roberto C; Martini, Luciano; Galbiati, Mariarita

    2002-08-01

    The mechanisms through which LHRH-secreting neurons are controlled still represent a crucial and debated field of research in the neuroendocrine control of reproduction. In the present review, we have specifically considered two potential signals reaching these hypothalamic neurons: steroid hormones and growth factors. Examples of the relevant physiological role of the interactions between these two families of biologically acting molecules have been provided. In many cases, these interactions occur at the level of hypothalamic astrocytes, which are presently accepted as functional partners of the LHRH-secreting neurons. On the basis of the observations here summarized, we have formulated the hypothesis that a functional co-operation of steroid hormones and growth factors occurring in the hypothalamic astrocytic compartment represents a key factor in the neuroendocrine control of reproductive functions.

  13. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    SciTech Connect

    Hansen, R K; Bissell, M J

    2000-06-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

  14. Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones

    PubMed Central

    Hansen, R K; Bissell, M J

    2010-01-01

    The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function. PMID:10903527

  15. Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors

    PubMed Central

    Schülke, Jan-Philip; Wochnik, Gabriela Monika; Lang-Rollin, Isabelle; Gassen, Nils Christian; Knapp, Regina Theresia; Berning, Barbara; Yassouridis, Alexander; Rein, Theo

    2010-01-01

    Background Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet. Methodology and Principal Findings We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action. Conclusion and Significance The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on

  16. Embryonic sex steroid hormones accumulate in the eggshell of loggerhead sea turtle (Caretta caretta).

    PubMed

    Kobayashi, Shohei; Saito, Yoshimichi; Osawa, Akihisa; Katsumata, Etsuko; Karaki, Isuke; Nagaoka, Kentaro; Taya, Kazuyoshi; Watanabe, Gen

    2015-12-01

    Steroids hormones such as estradiol-17β (E2) and testosterone (T) are involved in gonadal differentiation of oviparous animals with temperature-dependent sex determination (TSD), and are greatly distributed. This hypothesizes that these embryonic steroid hormones probably accumulate in the eggshell throughout blood or/and chorioallantoic fluid in sea turtle species with TSD, producing females at higher temperature. To demonstrate this hypothesis, concentrations of E2 and T in the blood plasma from the hatchling loggerhead sea turtle (Caretta caretta) and in their eggshells were measured by radioimmunoassay. In the present study we propose that both concentrations of E2 and T in the blood plasma are correlated with amounts of these sex steroids in the eggshell. Moreover, contents of E2 in the eggshell showed a significant positive correlation with mean incubation temperatures during a thermosensitive period in the experimental nests, whereas T contents in the eggshell did not. Taken together, these findings indicated that embryonic E2 and T that accumulated in the eggshell can be extracted and measured. Furthermore, the present study suggested that contents of E2 in the eggshell may differ between male and female, and monitoring of these steroids is a useful method to identify the sex of loggerhead sea turtle hatchling. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Causes and consequences of age-related steroid hormone changes: insights gained from nonhuman primates

    PubMed Central

    Sorwell, K.G.; Urbanski, H.F.

    2013-01-01

    Like humans, rhesus macaques (Macaca mulatta) are large, long-lived diurnal primates, and show similar age-related changes in the secretion of many steroid hormones, including oestradiol, testosterone, cortisol, and dehydroepiandrosterone (DHEA). Consequently, they represent a pragmatic animal model in which to examine the mechanisms by which these steroidal changes contribute to perturbed sleep-wake cycles and cognitive decline in the elderly. Using remote serial blood sampling we have found the circulating levels of DHEA sulphate, as well as oestradiol and testosterone, decline markedly in old monkeys. Furthermore, using real-time PCR, we have shown that genes associated with the conversion of DHEA to oestradiol and testosterone (e.g., 3BHSD, 17BHSD, and aromatase) are highly expressed in brain areas associated with cognition and behavior, including the hippocampus, prefrontal cortex, and amygdala. Taken together, these findings suggest that administration of supplementary DHEA in the elderly may have therapeutic potential for cognitive and behavioral disorders, but with fewer negative side effects outside of the central nervous system. To test this we have developed a novel steroid supplementation paradigm for use in old animals; this involves oral administration of DHEA and testosterone at physiologically relevant times of the day to mimic the circadian hormone patterns observed in young adults. We are currently evaluating the efficacy of this steroid supplementation paradigm at reversing age-associated disorders, including perturbed sleep-wake cycles and cognitive decline as well as impaired immune response. PMID:23796387

  18. The effect of steroid hormones on the mRNA expression of oct4 and sox2 in uterine tissue of the ovariectomized mice model of menopause

    PubMed Central

    Davoudi, Marzieh; Zavareh, Saeed; Ghorbanian, Mohammad Taghi; Paylakhi, Seyed Hassan; Mohebbi, Seyed Reza

    2016-01-01

    Background: The uterus is a dynamic tissue responding to hormonal changes during reproductive cycles. As such, uterine stem cells have been studied in recent years. Transcription factors oct4 and sox2 are critical for effective maintenance of pluripotent cell identity. Objective: The present research evaluated the mRNA expression of oct4 and sox2 in the uterine tissues of ovariectomized mice treated with steroid hormones. Materials and Methods: In this experimental study, adult virgin female mice were ovariectomized and treated with estradiol 17β (E2), progesterone (P4), and a combination of E2 and P4 (E2 & P4) for 5 days. Uterine tissues were removed, and immunofluorescent (IF) staining and quantitative real-time PCR of oct4 and sox2 markers were performed. Results: IF showed oct4 and sox2 expression in the uterine endometrium and myometrium among all groups. The mRNA expression of oct4 (p=0.022) and sox2 (p=0.042) in the E2-treated group significantly were decreased compared to that in the control group. By contrast, the mRNA expression of oct4 and sox2 in the P4 (p=0.641 and 0.489 respectively) and E2 & P4-treated groups (p=0.267 and 0.264 respectively) did not show significant differences compared to the control group. Conclusion: The results indicate ovarian steroid hormones change the expression of oct4 and sox2 in the mice uterine tissues, which suggest the involvement of steroid hormonal regulation in uterine stem cells. PMID:27525332

  19. Effect of Ovarian Hormones on Genes Promoting Dendritic Spines In Laser Captured Serotonin Neurons From Macaques

    PubMed Central

    Bethea, Cynthia L.; Reddy, Arubala P.

    2009-01-01

    Dendritic spines are the elementary structural units of neuronal plasticity and the cascades that promote dendrite spine remodeling center on Rho GTPases and downstream effectors of actin dynamics. In a model of hormone replacement therapy (HT), we sought the effect of estradiol (E) and progesterone (P) on gene expression in these cascades in laser captured serotonin neurons from rhesus macaques with cDNA array analysis. Spayed rhesus macaques were treated with either placebo, E or E+P via Silastic implant for 1 month prior to euthanasia after which the midbrain was obtained, sectioned and immunostained for TPH. TPH-positive neurons were laser captured using an Arcturus Laser Dissection Microscope (PixCell II). RNA from laser captured serotonin neurons (n=2 animals/treatment) was hybridized to Rhesus Affymetrix GeneChips. There was a significant change in 744 probe sets (ANOVA, p < 0.05), but 10,493 probe sets exhibited a 2-fold or greater change. Pivotal changes in pathways leading to dendrite spine proliferation and transformation included 2-fold or greater increases in expression of the Rho GTPases called CDC42, Rac1 and RhoA. In addition, 2-fold or greater increases occurred in downstream effectors of actin dynamics including PAK1, ROCK, PIP5K, IRSp53, WASP, WAVE, MLC, cofilin, gelsolin, profilin and 3 subunits of ARP2/3. Finally, 2-fold or greater decreases occurred in CRIPAK, LIMK2 and MLCK. The regulation of RhoA, Rac1, CDC42, ROCK, PIP5k, IRSp53, WASP, WAVE, LIMK2, CRIPAK1, MLCK, ARP2/3 subunit 3, gelsolin, profilin and cofilin was confirmed with nested qRT-PCR on laser captured RNA (n=3 animals/treatment). The data indicate that ovarian steroids target gene expression of the Rho GTPases and pivotal downstream proteins that in turn, would promote dendritic spine proliferation and stabilization on serotonin neurons of the dorsal raphe nucleus. PMID:19687787

  20. Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue.

    PubMed

    Prohaska, Bianca K; Tsang, Paul C W; Driggers, William B; Hoffmayer, Eric R; Wheeler, Carolyn R; Brown, A Christine; Sulikowski, James A

    2013-01-01

    Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs.

  1. Assessing reproductive status in elasmobranch fishes using steroid hormones extracted from skeletal muscle tissue

    PubMed Central

    Prohaska, Bianca K.; Tsang, Paul C. W.; Driggers, William B.; Hoffmayer, Eric R.; Wheeler, Carolyn R.; Brown, A. Christine; Sulikowski, James A.

    2013-01-01

    Elasmobranch fishes (sharks, skates, and rays) are particularly susceptible to anthropogenic threats, making a thorough understanding of their life history characteristics essential for proper management. Historically, elasmobranch reproductive data have been collected by lethal sampling, an approach that is problematic for threatened and endangered species. However, recent studies have demonstrated that non-lethal approaches can be as effective as lethal ones for assessment of the reproductive status of an animal. For example, plasma has been used to examine concentrations of steroid hormones. Additionally, skeletal muscle tissue, which can be obtained non-lethally and with minimal stress, can also be used to quantify concentrations of steroid hormones. Skeletal muscle progesterone, testosterone, and estradiol concentrations were determined to be statistically significant indicators of reproductive status in the oviparous Leucoraja erinacea, the yolk-dependent viviparous Squalus acanthias, and the yolk-sac placental viviparous Rhizoprionodon terraenovae. The results of the present study demonstrate that steroid hormones present in non-lethally harvested skeletal muscle tissue can be used as reliable indicators of reproductive status in elasmobranchs. PMID:27293612

  2. The effects of prenatal sex steroid hormones on sexual differentiation of the brain.

    PubMed

    Karaismailoğlu, Serkan; Erdem, Ayşen

    2013-01-01

    Most of the anatomical, physiological and neurochemical gender-related differences in the brain occur prenatally. The sexual differences in the brain are affected by sex steroid hormones, which play important roles in the differentiation of neuroendocrine system and behavior. Testosterone, estrogen and dihydrotestosterone are the main steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The structural and behavioral differences in the female and male brains are observed in many animal species; however, these differences are variable between species. Animal and human (in vivo imaging and postmortem) studies on sex differences in the brain have shown many differences in the local distribution of the cortex, the gray-white matter ratio, corpus callosum, anterior commissure, hypothalamus, bed nucleus of the stria terminalis, limbic system and neurotransmitter systems. This review aims to evaluate the anatomical, physiological and neurochemical differences in the female and male brains and to assess the effect of prenatal exposure to sex steroid hormones on the developing brain.

  3. Skin permeation of different steroid hormones from polymeric coated liposomal formulations.

    PubMed

    Biruss, Babette; Valenta, Claudia

    2006-02-01

    In this study, the effect of various polymers (polycarbophil, chitosan-EDTA, polymeric emulsifier and carrageenan) on the permeation, the chemical and microbial stability of 17-beta-estradiol, progesterone, cyproterone acetate (cpa) and finasteride incorporated in DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) liposomes has been investigated. The liposomes contained 1% (w/w) of the steroid hormones. Standard diffusion experiments were performed. Drug stability was monitored by analysing the steroid hormone content in the different formulations over a time period of 8 weeks and visually inspecting for microbial contamination. In addition, viscosity measurements were performed. The permeation rate could be improved by addition of polymeric agents depending on their type and drug. In all tested formulations, finasteride exhibited the highest diffusion. Both the chemical and the microbial stability of the hormones were significantly improved by the polymers in comparison to the pure liposomes after an observation period of 8 weeks. After that time microbial stability was still evident for all semisolid formulations. In contrast to this in the pure liposomes already after 2 weeks the steroid drugs showed complete insufficient chemical stability and microbial contamination. Additional rheological measurements indicated an influence of the polymers and drugs on the viscosity in all formulations. The elasticity predominated in nearly all polymeric formulations.

  4. G-protein-coupled receptor controls steroid hormone signaling in cell membrane

    PubMed Central

    Wang, Di; Zhao, Wen-Li; Cai, Mei-Juan; Wang, Jin-Xing; Zhao, Xiao-Fan

    2015-01-01

    G-protein-coupled receptors (GPCRs) are involved in animal steroid hormone signaling, but their mechanism is unclear. In this research, we report that a GPCR called ErGPCR-2 controls steroid hormone 20-hydroxyecdysone (20E) signaling in the cell membrane of the lepidopteran insect Helicoverpa armigera. ErGPCR-2 was highly expressed during molting and metamorphosis. 20E, via ErGPCR-2, regulated rapid intracellular calcium increase, protein phosphorylation, gene transcription, and insect metamorphosis. ErGPCR-2 was located in the cell surface and was internalized by 20E induction. GPCR kinase 2 participated in 20E-induced ErGPCR-2 phosphorylation and internalization. The internalized ErGPCR-2 was degraded by proteases to desensitize 20E signaling. ErGPCR-2 knockdown suppressed the entrance of 20E analog [3H] ponasterone A ([3H]Pon A) into the cells. ErGPCR-2 overexpression or blocking of ErGPCR-2 internalization increased the entrance of [3H]Pon A into the cells. However, ErGPCR-2 did not bind to [3H]Pon A. Results suggest that ErGPCR-2 transmits steroid hormone 20E signaling and controls 20E entrance into cells in the cell membrane. PMID:25728569

  5. Expression of sex steroid hormone receptors in C cell hyperplasia and medullary thyroid carcinoma.

    PubMed

    Bléchet, Claire; Lecomte, Pierre; De Calan, Loïc; Beutter, Patrice; Guyétant, Serge

    2007-04-01

    Previous studies have shown that C cells are twice as numerous in male than in female thyroids and that C cell hyperplasia (CCH) is much more frequent in men. These findings suggest regulation involving sex steroid hormones through the expression of sex steroid hormone receptors on C cells. To investigate this hypothesis, we performed an immunohistochemical study of estrogen receptors alpha (ER alpha) and beta (ER beta), progesterone receptors (PR), and androgen receptors (AR) on specimens from a series of 40 patients operated on for a medullary thyroid carcinoma (MTC; n=28; female 18, male 10) and/or CCH (n=19; female 6, male 13). ER beta was the only receptor to be consistently expressed in CCH (100%) and MTC (96.5%), whereas ER alpha was never expressed. PR and AR were rarely expressed in MTC (7 and 14%, respectively). AR was expressed in half the CCH cases (53%), with a trend to male predominance (61% in men vs 33% in women). Our study is the first to describe ER beta expression in CCH. In addition, our findings suggest that CCH, and possibly MTC, might be influenced by sex steroid hormones, namely, estrogens and androgens, through the expression of ER beta and AR on C cells.

  6. Gender Differences in Subjective and Physiological Responses to Caffeine and the Role of Steroid Hormones

    PubMed Central

    Ziegler, Amanda M.

    2011-01-01

    Background We have shown previously that male and female adolescents differ in their responses to caffeine, but to date, the mechanisms underlying these gender differences are unknown. Objective The purpose of this study was to test the hypothesis that differences in circulating steroid hormones mediate gender differences in response to caffeine. Methods Subjective and physiological responses to caffeine were tested in adolescents using a double-blind, placebo controlled, crossover design. Participants were tested every 2 weeks for 8 weeks and received placebo and caffeine (2 mg/kg) twice each. Females were tested with placebo and caffeine in each phase of their menstrual cycle. Salivary concentrations of testosterone, estradiol, and progesterone were also measured. Results Males showed greater positive subjective effects than females. In females, higher levels of estradiol were associated with little or no subjective responses to caffeine, but lower levels of estradiol were associated with negative subjective responses to caffeine relative to placebo. There were gender differences in cardiovascular responses to caffeine, with males showing greater decreases in heart rate after caffeine administration than females, but females showing greater increases in diastolic blood pressure than males after caffeine administration. These gender differences may be related to steroid hormone concentrations. Blood pressure responses to caffeine were lower in males when estradiol was high, but higher in females when estradiol was high. Conclusions When taken together, these findings suggest that males and females differ in their responses to caffeine and that these differences may be mediated by changes in circulating steroid hormones. PMID:24761262

  7. Steroid hormone inactivation is required during the juvenile-adult transition in Drosophila.

    PubMed

    Rewitz, Kim F; Yamanaka, Naoki; O'Connor, Michael B

    2010-12-14

    Steroid hormones are systemic signaling molecules that regulate juvenile-adult transitions in both insects and mammals. In insects, pulses of the steroid hormone 20-hydroxyecdysone (20E) are generated by increased biosynthesis followed by inactivation/clearance. Although mechanisms that control 20E synthesis have received considerable recent attention, the physiological significance of 20E inactivation remains largely unknown. We show that the cytochrome P450 Cyp18a1 lowers 20E titer during the Drosophila prepupal to pupal transition. Furthermore, this reduction of 20E levels is a prerequisite to induce βFTZ-F1, a key factor in the genetic hierarchy that controls early metamorphosis. Resupplying βFTZ-F1 rescues Cyp18a1-deficient prepupae. Because Cyp18a1 is 20E-inducible, it appears that the increased production of steroid is responsible for its eventual decline, thereby generating the regulatory pulse required for proper temporal progression of metamorphosis. The coupling of hormone clearance to βFTZ-F1 expression suggests a general mechanism by which transient signaling drives unidirectional progression through a multistep process.

  8. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy.

    PubMed

    Pařízek, A; Dušková, M; Vítek, L; Šrámková, M; Hill, M; Adamcová, K; Šimják, P; Černý, A; Kordová, Z; Vráblíková, H; Boudová, B; Koucký, M; Malíčková, K; Stárka, L

    2015-01-01

    Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women.

  9. Effect of short-term fasting on hepatic steroid hormone metabolism in cows.

    PubMed

    Ono, Mamiko; Ohtaki, Tadatoshi; Tanemura, Kouichi; Ishii, Mitsuo; Watanabe, Gen; Taya, Kazuyoshi; Tsumagari, Shigehisa

    2011-09-01

    In the present study, the effect of 4-day fasting on steroid hormone metabolism in the liver and secretion of LH was examined in cows. Six non pregnant, dry Holstein cows were used. The estrous cycle was synchronized in all cows using CIDR-Ovsynch. Cows were allocated to a control group (n=3) and a fasting group (n=3). In the fasting group, cows were fasted for four days from day -4 to day -1 (day 0=day of 2nd GnRH injection) but otherwise were fed ad libitum. The experiment was repeated in a crossover design after an interval of about one month. The peripheral progesterone (P(4)) concentration in the fasting group was significantly higher than in the control group on day -1 and 0. The peripheral estradiol-17β concentration in the fasting group was also significantly higher than in the control group on day -1 and 0. The portal vein P(4) concentration in the fasting group was significantly higher than in the control group. On day 0, there was no difference in LH secretion between groups. The mean percentages of lipid droplets in liver cells in the fasting group were significantly higher than in the control group on day 0. These results suggest that short-term fasting leads to reduced hepatic steroid hormone metabolism by accumulation of fat in the liver, which causes high peripheral steroid hormone concentrations.

  10. The effects of prenatal sex steroid hormones on sexual differentiation of the brain

    PubMed Central

    Karaismailoğlu, Serkan; Erdem, Ayşen

    2013-01-01

    Most of the anatomical, physiological and neurochemical gender-related differences in the brain occur prenatally. The sexual differences in the brain are affected by sex steroid hormones, which play important roles in the differentiation of neuroendocrine system and behavior. Testosterone, estrogen and dihydrotestosterone are the main steroid hormones responsible for the organization and sexual differentiation of brain structures during early development. The structural and behavioral differences in the female and male brains are observed in many animal species; however, these differences are variable between species. Animal and human (in vivo imaging and postmortem) studies on sex differences in the brain have shown many differences in the local distribution of the cortex, the gray-white matter ratio, corpus callosum, anterior commissure, hypothalamus, bed nucleus of the stria terminalis, limbic system and neurotransmitter systems. This review aims to evaluate the anatomical, physiological and neurochemical differences in the female and male brains and to assess the effect of prenatal exposure to sex steroid hormones on the developing brain. PMID:24592097

  11. Effects of thermal regime on ovarian maturation and plasma sex steroids in farmed white sturgeon, Acipenser transmontanus

    USGS Publications Warehouse

    Webb, M.A.H.; Van Eenennaam, J. P.; Feist, G.W.; Linares-Casenave, J.; Fitzpatrick, M.S.; Schreck, C.B.; Doroshov, S.I.

    2001-01-01

    Recently, commercial aquaculture farms in Northern California have exposed gravid, cultured white sturgeon females to cold water (12 ?? 1??C) throughout the late phase of vitellogenesis and ovarian follicle maturation resulting in improved ovulation rates and egg quality. However, the optimum timing for transfer of broodfish to the cold water and the capacity of transferred broodfish to maintain reproductive competence over an extended time in cold water had not been evaluated. Gravid white sturgeon females that have been raised at water temperatures of 16-20??C were transported to either cold water (12 ?? 1??C; Group 1) in November 1997 or maintained in ambient water temperatures (10-19??C; Group 2) until early spring. In March 1998, half of the fish in Group 2 had regressed ovaries, but the remaining females had intact ovarian follicles and were transported to the cold water. Ovarian follicles and blood were collected from females until they reached the stage of spawning readiness (determined by germinal vesicle position and an oocyte maturation assay) or underwent ovarian regression. Exposure of gravid sturgeon females to ambient water temperatures (14.5 ?? 2.3??C, mean ?? S.D.) from October to March led to a decrease in plasma sex steroids and a high incidence of ovarian regression in fish with a more advanced stage of oocyte development. Transfer of females with intact ovarian follicles to cold water (12 ?? 1??C) in the fall or early spring resulted in normal ovarian development in the majority of females. Holding females in cold water does not seem to override their endogenous reproductive rhythms but extends their capacity to maintain oocyte maturational competence over a longer period of time. A temperature-sensitive phase in ovarian development may occur during the transition from vitellogenic growth to oocyte maturation, and the degree and timing of sensitivity to environmental temperature are dependent on the female's endogenous reproductive rhythm

  12. Evaluation of Ovarian Reserve with Anti-Müllerian Hormone in Familial Mediterranean Fever.

    PubMed

    Şahin, Ali; Karakuş, Savaş; Durmaz, Yunus; Yıldız, Çağlar; Aydın, Hüseyin; Cengiz, Ahmet Kıvanç; Güler, Duygu

    2015-01-01

    Objective. To investigate ovarian reserves in attack-free familial Mediterranean fever (AF-FMF) patients at the reproductive age by anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, and hormonal parameters. Methods. Thirty-three AF-FMF patients aging 18-45 years and 34 healthy women were enrolled and FSH, LH, E2, PRL, and AMH levels were measured in the morning blood samples at 2nd-4th days of menstruation by ELISA. Concomitant pelvic ultrasonography was performed to calculate AFC and ovarian volumes. Results. In FMF patient group, median AMH levels were statistically significantly lower in the M69V mutation positive group than in the negative ones (P = 0.018). There was no statistically significant difference in median AMH levels between E148Q mutation positive patients and the negative ones (P = 0.920). There was also no statistically significant difference in median AMH levels between M680I mutation positive patients and the negative ones (P = 0.868). No statistically significant difference was observed in median AMH levels between patients who had at least one mutation and those with no mutations (P = 0.868). We realized that there was no difference in comparisons between ovarian volumes, number of follicles, and AMH levels ovarian reserves when compared with FMF patients and healthy individuals. Conclusions. Ovarian reserves of FMF pateints were similar to those of healthy subjects according to AMH. However, AMH levels were lower in FMF patients with M694V mutation.

  13. Influence of Ovarian Hormones on Strength Loss in Healthy and Dystrophic Female Mice

    PubMed Central

    Kosir, Allison M.; Mader, Tara L.; Greising, Angela G.; Novotny, Susan A.; Baltgalvis, Kristen A.; Lowe, Dawn A.

    2014-01-01

    Purpose The primary objective of this study was to determine if strength loss and recovery following eccentric contractions is impaired in healthy and dystrophic female mice with low levels of ovarian hormones. Methods Female C57BL/6 (wildtype) or mdx mice were randomly assigned to ovarian-intact (Sham) and ovariectomized (Ovx) groups. Anterior crural muscles were tested for susceptibility to injury from 150 or 50 eccentric contractions in wildtype and mdx mice, respectively. An additional experiment challenged mdx mice with a 2-wk treadmill running protocol followed by an eccentric contraction injury to posterior crural muscles. Functional recovery from injury was evaluated in wildtype mice by measuring isometric torque 3, 7, 14, or 21 days following injury. Results Ovarian hormone deficiency in wildtype mice did not impact susceptibility to injury as the ~50% isometric torque loss following eccentric contractions did not differ between Sham and Ovx mice (p=0.121). Similarly in mdx mice, hormone deficiency did not affect percent of pre injury isometric torque lost by anterior crural muscles following eccentric contractions (p=0.952), but the percent of pre injury torque in posterior crural muscles was lower in Ovx compared to Sham mice (p=0.014). Recovery from injury in wildtype mice was affected by hormone deficiency. Sham mice recovered pre injury isometric strength by 14 days (96 ± 2%) while Ovx mice maintained deficits at 14 and 21 days post injury (80 ± 3% and 84 ± 2%; p<0.001) Conclusion Ovarian hormone status did not impact the vulnerability of skeletal muscle to strength loss following eccentric contractions. However, ovarian hormone deficiency did impair the recovery of muscle strength in female mice. PMID:25255128

  14. The Impact of Genetics and Hormonal Contraceptives on the Steroid Profile in Female Athletes

    PubMed Central

    Schulze, Jenny J.; Mullen, Jenny E.; Berglund Lindgren, Emma; Ericsson, Magnus; Ekström, Lena; Hirschberg, Angelica Lindén

    2014-01-01

    The steroid module of the Athlete Biological Passport, the newest innovation in doping testing, is currently being finalized for implementation. Several factors, other than doping, can affect the longitudinal steroid profile. In this study, we investigated the effect of hormonal contraceptives (HC) as well as the effect of three polymorphisms on female steroid profiles in relation to doping controls. The study population consisted of 79 female elite athletes between the ages of 18 and 45. HC were used by 32% of the subjects. A full urinary steroid profile was obtained using World Anti-Doping Agency accredited methods. In addition all subjects were genotyped for copy number variation of UGT2B17 and SNPs in UGT2B7 and CYP17. Subjects using HC excreted 40% less epitestosterone as compared to non-users (p = 0.005) but showed no difference in testosterone excretion. When removing individuals homozygous for the deletion in UGT2B17, the testosterone to epitestosterone (T/E) ratio was 29% higher in the HC group (p = 0.016). In agreement with previous findings in men, copy number variation of UGT2B17 had significant effect on female urinary testosterone excretion and therefore also the T/E ratio. Subjects homozygous for the T allele of CYP17 showed a lower urinary epitestosterone concentration than the other CYP17 genotypes. It is of great importance that the athlete’s steroidal passport can compensate for all possible normal variability in steroid profiles from women. Therefore, considering the large impact of HC on female steroid profiles, we suggest that the use of HC should be a mandatory question on the doping control form. PMID:24782830

  15. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction.

    PubMed

    Lu, L J; Anderson, K E; Grady, J J; Nagamani, M

    1996-01-01

    Soybean consumption is associated with reduced rates of breast, prostate, and colon cancer, which is possibly related to the presence of isoflavones that are weakly estrogenic and anticarcinogenic. We examined the effects of soya consumption on circulating steroid hormones in six healthy females 22-29 years of age. Starting within 6 days after the onset of menses, the subjects ingested a 12-oz portion of soymilk with each of three meals daily for 1 month on a metabolic unit. Daily isoflavone intakes were approximately 100 mg of daidzein (mostly as daidzin) and approximately 100 mg of genistein (mostly as genistin). Serum 17 beta-estradiol levels on cycle days 5-7, 12-14, and 20-22 decreased by 31% (P = 0.09), 81% (P = 0.03), and 49% (P = 0.02), respectively, during soya feeding. Decreases persisted for two or three menstrual cycles after withdrawal from soya feeding. The luteal phase progesterone levels decreased by 35% during soya feeding (P = 0.002). Dehydroepiandrosterone sulfate levels decreased progressively during soya feeding by 14-30% (P = 0.03). Menstrual cycle length was 28.3 +/- 1.9 days before soymilk feeding, increased to 31.8 +/- 5.1 days during the month of soymilk feeding (P = 0.06), remained increased at 32.7 +/- 8.4 days (P = 0.11) at one cycle after termination of soymilk feeding, and returned to pre-soya diet levels five to six cycles later. These results suggest that consumption of soya diets containing phytoestrogens may reduce circulating ovarian steroids and adrenal androgens and increase menstrual cycle length. Such effects may account at least in part for the decreased risk of breast cancer that has been associated with legume consumption.

  16. Do mollusks use vertebrate sex steroids as reproductive hormones? Part I: Critical appraisal of the evidence for the presence, biosynthesis and uptake of steroids.

    PubMed

    Scott, Alexander P

    2012-11-01

    The consensus view is that vertebrate-type steroids are present in mollusks and perform hormonal roles which are similar to those that they play in vertebrates. Although vertebrate steroids can be measured in molluscan tissues, a key question is 'Are they formed endogenously or they are picked up from their environment?'. The present review concludes that there is no convincing evidence for biosynthesis of vertebrate steroids by mollusks. Furthermore, the 'mollusk' genome does not contain the genes for key enzymes that are necessary to transform cholesterol in progressive steps into vertebrate-type steroids; nor does the mollusk genome contain genes for functioning classical nuclear steroid receptors. On the other hand, there is very strong evidence that mollusks are able to absorb vertebrate steroids from the environment; and are able to store some of them (by conjugating them to fatty acids) for weeks to months. It is notable that the three steroids that have been proposed as functional hormones in mollusks (i.e. progesterone, testosterone and 17β-estradiol) are the same as those of humans. Since humans (and indeed all vertebrates) continuously excrete steroids not just via urine and feces, but via their body surface (and, in fish, via the gills), it is impossible to rule out contamination as the sole reason for the presence of vertebrate steroids in mollusks (even in animals kept under supposedly 'clean laboratory conditions'). Essentially, the presence of vertebrate steroids in mollusks cannot be taken as reliable evidence of either endogenous biosynthesis or of an endocrine role. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  17. Steroid hormone excretion is enhanced by sucrose feeding to rats

    SciTech Connect

    Kruger, T.C.; Hsu, H.; Saunders, J.P.; Kim, S.S.; Given-Proctor, J.; Ahrens, R.A.

    1986-03-01

    The hypothesis tested was that feeding rats sucrose rather than invert sugar (50:50 mixture of glucose and fructose) or cornstarch would result in a more rapid excretion of intravenously injected 1,2-/sup 3/H aldosterone or 1,2,6,7-/sup 3/H cortisol. The three carbohydrate sources provided 45% of dietary energy when fed, respectively, to one of three groups of 10 male, Sprague Dawley rats. After 4 or 8 weeks of ad lib feeding of the three diets 5 ..mu..CI of /sup 3/H-labeled hormones were injected intravenously and % recovery in urine and feces was measured for 4 days by liquid scintillation counting. Nearly 90% of the /sup 3/H injected as 1,2-/sup 3/H aldosterone was recovered over 4 days in the excreta of the sucrose fed rats. This recovery of /sup 3/H from aldosterone was significantly greater (P < 0.01) than when invert sugar (65%) or cornstarch (60%) were fed. The recovery of /sup 3/H from intravenously injected 1,2,6,7-/sup 3/H cortisol followed a similar pattern. The authors anticipate that the excretion of all metabolic end products and xenobiotics excreted as glucuronides would be enhanced by sucrose feeding. Oxocarbonium ions from the glucose portion of sucrose digestion in the mammalian small intestine are thought to compete with oxocarbonium ions from the glucuronic acid portion of glucuronide hydrolysis. Such competition may slow glucuronide hydrolysis and promote glucuronide excretion, including the glucuronides derived from aldosterone and cortisol.

  18. Sex Hormone Binding Globulin and Sex Steroids Among Premenopausal Women in the Diabetes Prevention Program

    PubMed Central

    Pi-Sunyer, Xavier; Barrett-Connor, Elizabeth; Stentz, Frankie B.; Murphy, Mary Beth; Kong, Shengchun; Nan, Bin; Kitabchi, Abbas E.

    2013-01-01

    Context: It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS). Objectives: We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity. Participants: A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301). Interventions: Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo. Results: Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (∼11%) compared to decreases of 1.1 nmol/L in the placebo arm (P < .05). This comparison remained significant after adjustment for changes in covariates including waist circumference. However, associations with glucose were not significant. Median baseline A4 was lower in Hispanics compared to NHWs (5.7 nmol/L vs 6.5 nmol/L, P < .05) and increases in A4 were greater in Hispanics compared to NHWs (3.0 nmol/ vs 1.2 nmol/L, P < .05), and these differences did not differ significantly by intervention arm. No other racial/ethnic differences were significant. Conclusions: Among premenopausal glucose-intolerant women, no intervention changed sex steroids. ILS increased SHBG, although associations with glucose were not significant. SHBG and sex steroids were similar by race/ethnicity, with the possible exception of lower baseline A4 levels in Hispanics compared to NHWs. PMID:23709655

  19. Is immune system-related hypertension associated with ovarian hormone deficiency?

    PubMed

    Sandberg, Kathryn; Ji, Hong; Einstein, Gillian; Au, April; Hay, Meredith

    2016-03-01

    What is the topic of this review? This review summarizes recent data on the role of ovarian hormones and sex in inflammation-related hypertension. What advances does it highlight? The adaptive immune system has recently been implicated in the development of hypertension in males but not in females. The role of the immune system in the development of hypertension in women and its relationship to ovarian hormone production are highlighted. The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

  20. Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic agents

    SciTech Connect

    McEwen, B.S.

    1987-10-01

    Gonadal, adrenal, and thyroid hormones affect the brain directly, and the sensitivity to hormones begins in embryonic life with the appearance of hormone receptor sites in discrete populations of neurons. Because the secretion of hormones is also under control by its neural and pituitary targets, the brain-endocrine axis during development is in a delicately balanced state that can be upset in various ways, and any agent that disrupts normal hormone secretion can upset normal brain development. Moreover, exogenous substances that mimic the actions of natural hormones can also play havoc with CNS development and differentiation. This paper addresses these issues in the following order: First, actions of glucocorticoids on the developing nervous system related to cell division dendritic growth and neurotransmitter phenotype will be presented followed by a discussion of the developmental effects of synthetic steroids. Second, actions of estrogens related to brain sexual differentiation will be described, followed by a discussion of the actions of the nonsteroidal estrogen, diethylstilbestrol, as an example of exogenous estrogenic substances. The most important aspect of the potency of exogenous estrogens appears to be the degree to which they either bypass protective mechanisms or are subject to transformations to more active metabolites. Third, agents that influence hormone levels or otherwise modify the neuroendocrine system, such as nicotine, barbiturates, alcohol, opiates, and tetrahydrocannabinol, will be noted briefly to demonstrate the diversity of toxic agents that can influence neural development and affect personality, cognitive ability, and other aspects of behavior. 53 references.

  1. Steroid hormone runoff from agricultural test plots applied with municipal biosolids

    USGS Publications Warehouse

    Yang, Yun-Ya; Gray, James L.; Furlong, Edward T.; Davis, Jessica G.; ReVollo, Rhiannon C.; Borch, Thomas

    2012-01-01

    The potential presence of steroid hormones in runoff from sites where biosolids have been used as agricultural fertilizers is an environmental concern. A study was conducted to assess the potential for runoff of seventeen different hormones and two sterols, including androgens, estrogens, and progestogens from agricultural test plots. The field containing the test plots had been applied with biosolids for the first time immediately prior to this study. Target compounds were isolated by solid-phase extraction (water samples) and pressurized solvent extraction (solid samples), derivatized, and analyzed by gas chromatography–tandem mass spectrometry. Runoff samples collected prior to biosolids application had low concentrations of two hormones (estrone -1 and androstenedione -1) and cholesterol (22.5 ± 3.8 μg L-1). In contrast, significantly higher concentrations of multiple estrogens (-1), androgens (-1), and progesterone (-1) were observed in runoff samples taken 1, 8, and 35 days after biosolids application. A significant positive correlation was observed between antecedent rainfall amount and hormone mass loads (runoff). Hormones in runoff were primarily present in the dissolved phase (<0.7-μm GF filter), and, to a lesser extent bound to the suspended-particle phase. Overall, these results indicate that rainfall can mobilize hormones from biosolids-amended agricultural fields, directly to surface waters or redistributed to terrestrial sites away from the point of application via runoff. Although concentrations decrease over time, 35 days is insufficient for complete degradation of hormones in soil at this site.

  2. Model approach for stress induced steroidal hormone cascade changes in severe mental diseases.

    PubMed

    Volko, Claus D; Regidor, Pedro A; Rohr, Uwe D

    2016-03-01

    Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1

  3. Postmenopausal hormone use and incident ovarian cancer: Associations differ by regimen.

    PubMed

    Hildebrand, Janet S; Gapstur, Susan M; Feigelson, Heather Spencer; Teras, Lauren R; Thun, Michael J; Patel, Alpa V

    2010-12-15

    Ovarian cancer has been associated in epidemiologic studies with postmenopausal hormone use. Whether associations differ by hormone regimen, current status or duration of use is unclear. We examined epithelial ovarian cancer incidence in relation to unopposed estrogen (E-only) and estrogen plus progestin (E + P) among 54,436 postmenopausal women of the Cancer Prevention Study II Nutrition Cohort, a US cohort prospectively followed for cancer incidence since 1992. Demographic, medical, reproductive and lifestyle information was collected at enrollment and updated throughout follow-up via self-administered questionnaire. Extended Cox models were used to estimate age- and multivariate-adjusted relative risk (RR) of ovarian cancer according to hormone regimen, current status and duration of use. During 15 years of follow-up, 297 incident cases were identified. Relative to "never" use of hormones, current E-only use was associated with a twofold higher risk [RR 2.07, 95% confidence interval (CI) 1.50-2.85]; each 5-year increment of use was associated with a 25% higher risk (RR 1.25, 95% CI 1.15-1.36); ≥ 20 years of use was associated with a near threefold higher risk (RR 2.89; 95% CI 1.71-4.87; trend p = 0.01). Past E-only use was not significantly associated with ovarian cancer, although a modest increase in risk per each 5-year increment of use was suggested (RR 1.14, 95% CI 0.92-1.41). Neither current nor former E + P use was associated with ovarian cancer risk (RR 1.08, 95% CI 0.86-1.35; RR 1.08, 95% CI 0.68-1.71, respectively, per 5-year increment). These findings suggest that progestins may mitigate some of the detrimental effects of estrogen on the ovarian epithelium.

  4. Effects of long-term cortisol treatments on gonadal development, sex steroids levels and ovarian cortisol content in cultured great sturgeon Huso huso.

    PubMed

    Poursaeid, Samaneh; Falahatkar, Bahram; Mojazi Amiri, Bagher; Van Der Kraak, Glen

    2012-09-01

    The objective of this study was to examine the effect of cortisol implantations on gonadal development, sex steroid levels, and ovarian cortisol content in cultured great sturgeon Huso huso. Three groups of 5 fish for each treatment were considered. The experimental groups included: control (capsules containing cocoa butter alone), low cortisol (C(5); 5mg cortisol/kg body mass+cocoa butter) and, high cortisol (C(50); 50mg cortisol/kg body mass+cocoa butter). The capsules containing hormones and cocoa butter were intraperitoneally implanted into 3-year-old female fish at pre-vitellogenic stage (mean initial body mass 6809.7 ± 73 g) every 6 weeks over a 6-month period from January to June. The serum levels of cortisol, glucose, cholesterol and sex steroids (testosterone and 17β-estradiol) were determined at the initial time and three weeks after each implantation. Oocyte histological characteristics (the diameter and area of the oocyte, the diameter and area of the nucleus and the ratio of the nucleus area to the oocyte area) were measured at the end of the experiment and compared to those at the initial time. Ovarian cortisol content was measured at the end of the experiment. The results showed that serum cortisol levels varied in a dose-independent manner, so that the highest cortisol concentrations were observed in C(5)-treated fish throughout the experiment. Serum glucose levels were significantly higher in cortisol-treated groups than those in the control group. The high dose of cortisol elicited a significant constant increase in serum cholesterol concentrations. Fish implanted with the high cortisol dose showed significant declines in serum testosterone and 17β-estradiol concentrations throughout the experiment. No significant differences were found in oocyte histological characteristics among experimental groups. The cortisol implants elicited a dose-dependent increase in ovarian cortisol content. At the end of trial, body-growth indices were the lowest in

  5. Relationships between steroid hormones in hair and social behaviour in ring-tailed lemurs (Lemur catta).

    PubMed

    Tennenhouse, Erica M; Putman, Sarah; Boisseau, Nicole P; Brown, Janine L

    2017-01-01

    Relationships between the hypothalamic-pituitary adrenal and hypothalamic-pituitary gonadal axes and social behaviour in primates are complex. By using hair to quantify steroid hormones, one can obtain retrospective estimates of long-term free hormone levels from a single sample. In this study, hair was used to quantify long-term levels of cortisol, testosterone, and estradiol among members of a colony of ring-tailed lemurs (Lemur catta) to explore associations between intra- and intersexual levels of these hormones and social behaviour between the breeding and birthing seasons. Positive trends between hair cortisol and rates of receiving aggression approached significance for males and females after controlling for age. While there was no relationship between sex steroid concentrations and intrasexual social interactions, high rates of aggression in females over the study period coincided with females exhibiting the same average concentrations of testosterone as males. We, therefore, conclude that being the recipient of aggression might be more stressful than being aggressive in ring-tailed lemurs, and that testosterone potentially mediates female dominance in this species. We suggest that further investigation of hair hormones and behaviour in additional primate species could provide a useful comparative framework to guide interpretation of these novel findings.

  6. Long-term suppression of ovarian function by a luteinizing-hormone releasing hormone agonist implant in patients with endometriosis.

    PubMed

    Fraser, H M; Sandow, J; Cowen, G M; Lumsden, M A; Haining, R; Smith, S K

    1990-01-01

    Ten endometriosis patients received luteinizing hormone releasing hormone (LH-RH) agonist (buserelin) implant injections (6.6 mg subcutaneously) at days 0, 42, 84 and 126. Serum LH and follicle-stimulating hormone (FSH) were lowered by day 14. Luteinizing hormone remained at basal concentrations while FSH returned to values in the low-normal range of the menstrual cycle by day 35. At the end of the luteal phase during which treatment commenced, estrone and pregnanediol declined and remained at postmenopausal or early follicular phase values until days 305 to 460. Time to first ovulation ranged from 321 to 481 days after starting treatment. After the initial menstruation, only three instances of bleeding occurred during treatment. Pelvic pain was relieved or markedly reduced by day 42 and remained absent throughout the period of ovarian suppression. These results indicate the potential of a long-acting LH-RH agonist implant to form the basis for the treatment of symptomatic endometriosis.

  7. Primary Ovarian Insufficiency

    MedlinePlus

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Learn About Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ...

  8. Why we may abandon basal follicle-stimulating hormone testing: a sea change in determining ovarian reserve using antimüllerian hormone.

    PubMed

    Toner, James P; Seifer, David B

    2013-06-01

    Antimüllerian hormone is the most informative serum marker of ovarian reserve currently available and should be considered an important part of any contemporary reproductive medicine practice. It is both more convenient and informative than basal FSH and can be assessed at any point in the cycle. It is the most useful serum method of determining ovarian reserve, which guides pretreatment counseling, choice of infertility treatment, and avoidance of ovarian hyperstimulation. The future role of basal FSH testing is in doubt.

  9. Toxicological impact of technical imidacloprid on ovarian morphology, hormones and antioxidant enzymes in female rats.

    PubMed

    Kapoor, Upasana; Srivastava, M K; Srivastava, L P

    2011-12-01

    Technical imidacloprid was evaluated for its effect on ovarian morphology, hormones and antioxidant enzymes in female rats after 90 days oral exposure. Luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone levels were estimated in serum of rats and activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced glutathione (GSH) and lipid peroxidation (LPO) were estimated in ovary after oral administration of imidacloprid (5, 10, and 20mg/kg/day) for 90 days. Decreased ovarian weight together with significant patho-morphological changes in follicles, antral follicles and atretic follicles were observed at 20mg/kg/day. Imidacloprid at 5 and 10mg/kg/day has not produced any significant changes in ovarian morphology, hormones and antioxidant status of ovary. However 20mg/kg/day dose has produced significant alterations in the levels of LH, FSH and progesterone. Similarly significant changes in SOD, CAT, GPx, GSH, and LPO were observed at 20mg/kg/day dose level. Therefore, it is concluded that imidacloprid at 20mg/kg/day dose level has produced significant toxicological impact on ovary of female rats as evident by pathomorphological changes, hormonal imbalance and generating oxidative stress and can be considered primarily as Lowest Observed Effect Level (LOEL) for chronic study.

  10. The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats.

    PubMed

    Grönbladh, Alfhild; Johansson, Jenny; Kushnir, Mark M; Bergquist, Jonas; Hallberg, Mathias

    2013-12-11

    Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0I U/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC-MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17-hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. control, AAS, rhGH and the combination of AAS and rhGH treatment.

  11. Association Between Sex Steroid Hormones and Hematocrit in a Nationally Representative Sample of Men

    PubMed Central

    Paller, Channing J.; Shiels, Meredith S.; Rohrmann, Sabine; Menke, Andy; Rifai, Nader; Nelson, William G.; Platz, Elizabeth A.; Dobs, Adrian S.

    2013-01-01

    Low or high hematocrit levels are associated with increased morbidity and mortality, mediated via anemia or thromboembolic events, respectively. It is therefore important to identify factors that influence hematocrit. Although androgens are known to stimulate hematopoietic cells, it is unknown whether circulating sex steroid hormones affect hematocrit. The association between serum sex steroid hormone concentrations and hematocrit in men aged ≥20 years was evaluated in a cross-sectional study of 1273 men in the Third National Health and Nutrition Examination Survey (1988–1991). Outcomes were low (<10th percentile), high (>90th percentile), and mean hematocrit. Men with low free testosterone levels had a lower hematocrit than men with normal free testosterone levels (P = .03), although no relationship was found between total testosterone level and hematocrit. The relationship between sex hormone–binding globulin (SHBG) and hematocrit was complex, with both low (P < .001) and high (P = .01) SHBG levels associated with lower hematocrit in men aged ≥20 years and only high (P = .01) SHBG levels in men aged ≥50 years. The odds ratio (OR) of high vs normal hematocrit increased as total estradiol (OR, 2.84; P trend = .04) and free estradiol (OR, 2.23; P trend = .09) levels increased. In this nationally representative study of men, sex steroid hormone levels, particularly low free testosterone and high SHBG levels, were associated with lower hematocrit, and high total and free estradiol levels were associated with high hematocrit. Thus, changes in sex hormone levels with aging may contribute to the increased prevalence of anemia and thromboembolic stroke in men as they age. PMID:22604627

  12. Fate of steroid hormones and endocrine activities in swine manure disposal and treatment facilities.

    PubMed

    Combalbert, Sarah; Bellet, Virginie; Dabert, Patrick; Bernet, Nicolas; Balaguer, Patrick; Hernandez-Raquet, Guillermina

    2012-03-01

    Manure may contain high concern endocrine-disrupting compounds (EDCs) such as steroid hormones, naturally produced by pigs, which are present at μgL(-1) levels. Manure may also contain other EDCs such as nonylphenols (NP), polycyclic aromatic hydrocarbons (PAHs) and dioxins. Thus, once manure is applied to the land as soil fertilizer these compounds may reach aquifers and consequently living organisms, inducing abnormal endocrine responses. In France, manure is generally stored in anaerobic tanks prior spreading on land; when nitrogen removal is requested, manure is treated by aerobic processes before spreading. However, little is known about the fate of hormones and multiple endocrine-disrupting activities in such manure disposal and treatment systems. Here, we determined the fate of hormones and diverse endocrine activities during manure storage and treatment by combining chemical analysis and in vitro quantification of estrogen (ER), aryl hydrocarbon (AhR), androgen (AR), pregnane-X (PXR) and peroxysome proliferator-activated γ (PPARγ) receptor-mediated activities. Our results show that manure contains large quantities of hormones and activates ER and AhR, two of the nuclear receptors studied. Most of these endocrine activities were found in the solid fraction of manure and appeared to be induced mainly by hormones and other unidentified pollutants. Hormones, ER and AhR activities found in manure were poorly removed during manure storage but were efficiently removed by aerobic treatment of manure. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. HPLC-MS/MS analysis of steroid hormones in environmental water samples.

    PubMed

    Avar, P; Maasz, G; Takács, P; Lovas, S; Zrinyi, Z; Svigruha, R; Takátsy, A; Tóth, L G; Pirger, Z

    2016-01-01

    Today, freshwaters, such as lakes and rivers, are subject to controlled pollution. Steroid hormones are chemically very stable highly lipophilic molecules. Their biological properties have a strong impact on the endocrine regulation of species. Steroids have estrogenic, androgenic, thyroidogenic or progestogenic effects and based on them, they could disturb the physiological mechanisms of freshwater species. We focused on progestins as they are the main active ingredients of contraceptive pharmaceuticals. Progestins have been shown to impair reproduction in fish, amphibians, and mollusks at low ng/L concentrations. Certain progestins, such as levonorgestrel (LNG) have androgenic properties also. We selected the most used active substances drospirenone (DRO), LNG, and progesterone (PRG) and then developed and optimized a liquid chromatographic-mass spectrometric method with solid-phase extraction to measure them. Using our sensitive method (LOQ 0.03-0.11 ng/L) we could measure steroids even between 0.1 and 1 ng/L. Analyzing freshwater samples from the Lake Balaton catchment area, we found influents where the concentration of these hormones was 0.26-4.30 (DRO), 0.85-3.40 (LNG), and 0.23-13.67 (PRG) ng/L. Out of 53 collecting places, 21 contained measurable progestin levels, which clearly demonstrates the applicability of our method, legitimates toxicology experiments with effected species, and indicates monitoring efforts. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers

    PubMed Central

    Jamil, Zehra; Fatima, Syeda Sadia; Ahmed, Khalid; Malik, Rabia

    2016-01-01

    Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR). Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR. Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles. PMID:26977116

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  17. Effects of ovarian hormones on manifestation of purulent endometritis in rat uteruses infected with Escherichia coli.

    PubMed

    Nishikawa, Y; Baba, T

    1985-01-01

    To assess the influence of hormones on uterine infections, Escherichia coli was infused into uterine lumens of ovariectomized or adrenoovariectomized rats receiving exogenous administration of various doses of ovarian hormones. Large numbers of E. coli were recovered from the rat uterine lumens, irrespective of hormonal influences. The number of leukocytes in the uterine flushings, representing the magnitude of purulent inflammation, differed significantly depending upon the hormonal regimen given to each host. Purulent endometritis was induced by E. coli in ovariectomized rats receiving progesterone or corn oil (hormone vehicle). Infections were asymptomatic in rats receiving estradiol, but promethazine-treated uterine horns were susceptible to infection. When progesterone was administered along with estradiol, purulent inflammation was caused by E. coli, but the number of leukocytes in the uterine lumens was significantly less than that obtained from the rats treated with progesterone or corn oil. These effects of ovarian hormones on uterine infections were observed in adrenoovariectomized rats as well as in ovariectomized rats. It is suggested that estradiol alters the nature of endometrial epithelium and prevent manifestation of purulent endometritis; progesterone antagonizes estradiol. Adrenal hormones appear not to participate in the pathogenesis of endometritis induced by E. coli.

  18. Reproductive and hormonal factors in association with ovarian cancer in the Netherlands cohort study.

    PubMed

    Braem, M G M; Onland-Moret, N C; van den Brandt, P A; Goldbohm, R A; Peeters, P H M; Kruitwagen, R F P M; Schouten, L J

    2010-11-15

    Parity, oral contraceptive use, and hysterectomy are known to protect against ovarian cancer, whereas the effect of other reproductive factors remains unclear. The authors investigated the association between several reproductive and hormonal factors and the risk of epithelial invasive ovarian cancer among postmenopausal women participating in the Netherlands Cohort Study on Diet and Cancer. Information on reproductive history and exogenous hormone use was obtained through a self-administered questionnaire at baseline in 1986. After 16.3 years of follow-up, 375 cases and 2,331 subcohort members were available for case-cohort analysis. Ovarian cancer risk was reduced for parous women, with increasing parity, and for hysterectomized women. Moreover, the authors found evidence that oral contraceptive use is protective against ovarian cancer, even when initiated at an older age. In addition, a reduced risk was observed for each year reduction in age at natural menopause and per year reduction in total menstrual life span. A small increased risk was observed with prolonged time to pregnancy, but no difference was found between ever-married nulliparous women and never-married nulliparous women. Moreover, no associations were observed for age at first birth, age at menarche, age at first and last use of oral contraceptives, and use of hormone replacement therapy.

  19. Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women.

    PubMed

    Zhao, Ming Xu; Zhou, Guo Yu; Zhu, Jing Yuan; Gong, Biao; Hou, Jia Xiang; Zhou, Tong; Duan, Li Ju; Ding, Zhong; Cui, Liu Xin; Ba, Yue

    2015-09-01

    The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women.

  20. Hormonal Regulation and Distinct Functions of Semaphorin-3B and Semaphorin-3F in Ovarian Cancer

    PubMed Central

    Joseph, Doina; Ho, Shuk-Mei; Syed, Viqar

    2009-01-01

    Semaphorins comprise a family of molecules that influence neuronal growth and guidance. Class-3 semaphorins, semaphorin-3B (SEMA3B) and semaphorin-3F (SEMA3F) illustrate their effects by forming a complex with neuropilins (NP-1 or NP-2) and plexins. We examined the status and regulation of semaphorins and their receptors in human ovarian cancer cells. A significantly reduced expression of SEMA3B (83 kD), SEMA3F (90 kD), and plexin-A3 was observed in ovarian cancer (OVCA) cell lines when compared to normal human ovarian surface epithelial (HOSE) cells. The expression of NP-1, NP-2 and plexin-A1 was not altered in HOSE and OVCA cells. The decreased expression of SEMA3B, SEMA3F, and plexin-A3 was confirmed in stage 3 ovarian tumors. Treatment of OVCA cells with luteinizing hormone, follicle-stimulating hormone, and estrogen induced a significant upregulation of SEMA3B, whereas SEMA3F was upregulated only by estrogen. Co-treatment of cell lines with a hormone and its specific antagonist blocked the effect of the hormone. Ectopic expression of SEMA3B or SEMA3F reduced soft-agar colony formation, adhesion, and cell invasion of OVCA cell cultures. Forced expression of SEMA3B, but not SEMA3F, inhibited viability of OVCA cells. Overexpression of SEMA3B and SEMA3F reduced focal adhesion kinase (FAK) phosphorylation and matrix metalloproteinase (MMP)-2 and -9 expression in OVCA cells. Forced expression of SEMA3F, but not SEMA3B in OVCA cells, significantly inhibited endothelial cell tube formation. Collectively, our results suggest loss of SEMA3 expression could be a hallmark of cancer progression. Furthermore, gonadotropin- and/or estrogen-mediated maintenance of SEMA3 expression could control ovarian cancer angiogenesis and metastasis. PMID:20124444

  1. Reproductive and hormonal factors in relation to survival and platinum resistance among ovarian cancer cases.

    PubMed

    Shafrir, Amy L; Babic, Ana; Tamimi, Rulla M; Rosner, Bernard A; Tworoger, Shelley S; Terry, Kathryn L

    2016-11-22

    Ovarian cancer survival is poor, particularly for platinum-resistant cases. The previous literature on pre-diagnostic reproductive factors and ovarian cancer survival has been mixed. Therefore, we evaluated pre-diagnostic reproductive and hormonal factors with overall survival and, additionally, platinum-chemotherapy resistance. We followed 1649 invasive epithelial ovarian cancer cases who were enrolled between 1992 and 2008 for overall mortality within the New England Case-Control Study and abstracted chemotherapy data on a subset (n=449). We assessed pre-diagnostic reproductive and hormonal factors during in-person interviews. We calculated hazard ratios (HRs) using Cox-proportional hazards models. We observed 911 all-cause deaths among 1649 ovarian cancer cases. Self-reported endometriosis and longer duration of hormone therapy use were associated with improved survival (HR: 0.72; 95% confidence interval (CI): 0.54-0.94 and HR, ⩾5 years vs never: 0.70; 95% CI: 0.55-0.90, respectively). Older age at menopause and menarche were associated with worse survival (HR, ⩽50 vs >50 years: 1.23; 95% CI: 1.03-1.46 and HR, 13 vs <13 years: 1.24; 95% CI: 1.06-1.44, respectively). We observed no association between oral contraceptive use, parity and tubal ligation, and overall survival. No significant associations were observed for any of the reproductive and hormonal factors and platinum resistance. These results suggest that pre-diagnostic exposures such as endometriosis and HT use may influence overall survival among ovarian cancer patients.

  2. The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response

    PubMed Central

    Park, Hyun Jong; Lee, Geun Ho; Gong, Du Sik; Yoon, Tae Ki

    2016-01-01

    Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response. PMID:27689035

  3. The meaning of anti-Müllerian hormone levels in patients at a high risk of poor ovarian response.

    PubMed

    Park, Hyun Jong; Lee, Geun Ho; Gong, Du Sik; Yoon, Tae Ki; Lee, Woo Sik

    2016-09-01

    Measurements of ovarian reserve play an important role in predicting the clinical results of assisted reproductive technology (ART). The ideal markers of ovarian reserve for clinical applications should have high specificity in order to determine genuine poor responders. Basal follicle-stimulating hormone levels, antral follicle count, and serum anti-Müllerian hormone (AMH) levels have been suggested as ovarian reserve tests that may fulfill this requirement, with serum AMH levels being the most promising parameter. Serum AMH levels have been suggested to be a predictor of clinical pregnancy in ART for older women, who are at a high risk for decreased ovarian response. We reviewed the prognostic significance of ovarian reserve tests for patients undergoing ART treatment, with a particular focus on the significance of serum AMH levels in patients at a high risk of poor ovarian response.

  4. A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure.

    PubMed

    Pankhurst, Michael W

    2017-04-01

    The mammalian ovary has a finite supply of oocytes, which are contained within primordial follicles where they are arrested in a dormant state. The number of primordial follicles in the ovary at puberty is highly variable between females of the same species. Females that enter puberty with a small ovarian reserve are at risk of a shorter reproductive lifespan, as their ovarian reserve is expected to be depleted faster. One of the roles of anti-Müllerian hormone (AMH) is to inhibit primordial follicle activation, which slows the rate at which the ovarian reserve is depleted. A simple interpretation is that the function of AMH is to conserve ovarian reserve. However, the females with the lowest ovarian reserve and the greatest risk of early reserve depletion have the lowest levels of AMH. In contrast, AMH apparently strongly inhibits primordial follicle activation in females with ample ovarian reserve, for reasons that remain unexplained. The rate of primordial follicle activation determines the size of the developing follicle pool, which in turn, determines how many oocytes are available to be selected for ovulation. This review discusses the evidence that AMH regulates the size of the developing follicle pool by altering the rate of primordial follicle activation in a context-dependent manner. The expression patterns of AMH across life are also consistent with changing requirements for primordial follicle activation in the ageing ovary. A potential role of AMH in the fertility of ageing females is proposed herein. © 2017 Society for Endocrinology.

  5. Anti-Müllerian hormone and risk of ovarian cancer in nine cohorts.

    PubMed

    Jung, Seungyoun; Allen, Naomi; Arslan, Alan A; Baglietto, Laura; Barricarte, Aurelio; Brinton, Louise A; Egleston, Brian L; Falk, Roni T; Fortner, Renée T; Helzlsouer, Kathy J; Gao, Yutang; Idahl, Annika; Kaaks, Rudolph; Krogh, Vittorio; Merritt, Melissa A; Lundin, Eva; Onland-Moret, N Charlotte; Rinaldi, Sabina; Schock, Helena; Shu, Xiao-Ou; Sluss, Patrick M; Staats, Paul N; Sacerdote, Carlotta; Travis, Ruth C; Tjønneland, Anne; Trichopoulou, Antonia; Tworoger, Shelley S; Visvanathan, Kala; Weiderpass, Elisabete; Zeleniuch-Jacquotte, Anne; Dorgan, Joanne F

    2017-09-18

    Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer. © 2017 UICC.

  6. Steroid hormone signaling during development has a latent effect on adult male sexual behavior in the butterfly Bicyclus anynana.

    PubMed

    Bear, Ashley; Prudic, Kathleen L; Monteiro, Antónia

    2017-01-01

    It is well established that steroid hormones regulate sexual behavior in vertebrates via organizational and activational effects. However, whether the organizational/activational paradigm applies more broadly to the sexual behavior of other animals such as insects is not well established. Here we describe the hormonal regulation of a sexual behavior in the seasonally polyphenic butterfly Bicyclus anynana is consistent with the characteristics of an organizational effect. By measuring hormone titer levels, quantifying hormone receptor gene expression in the brain, and performing hormone manipulations, we demonstrate steroid hormone signaling early in pupal development has a latent effect on adult male sexual behavior in B. anynana. These findings suggest the organizational/activational paradigm may be more highly conserved across animal taxa than previously thought.

  7. Steroid hormone signaling during development has a latent effect on adult male sexual behavior in the butterfly Bicyclus anynana

    PubMed Central

    Bear, Ashley; Prudic, Kathleen L.

    2017-01-01

    It is well established that steroid hormones regulate sexual behavior in vertebrates via organizational and activational effects. However, whether the organizational/activational paradigm applies more broadly to the sexual behavior of other animals such as insects is not well established. Here we describe the hormonal regulation of a sexual behavior in the seasonally polyphenic butterfly Bicyclus anynana is consistent with the characteristics of an organizational effect. By measuring hormone titer levels, quantifying hormone receptor gene expression in the brain, and performing hormone manipulations, we demonstrate steroid hormone signaling early in pupal development has a latent effect on adult male sexual behavior in B. anynana. These findings suggest the organizational/activational paradigm may be more highly conserved across animal taxa than previously thought. PMID:28328961

  8. Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry

    PubMed Central

    Soldin, Offie P.; Guo, Tiedong; Weiderpass, Elisabete; Tractenberg, Rochelle E.; Hilakivi-Clarke, Leena; Soldin, Steven J.

    2013-01-01

    Objective To establish normal, trimester-specific reference intervals for serum 17β-estradiol, progesterone (P), 17α-hydroxyprogesterone, cortisol, 11-deoxycortisol, androstenedione, DHEA, and DHEAS, measured simultaneously using isotope dilution tandem mass spectrometry. Design Sequential cohort study. Patient(s) Healthy women undergoing a normal pregnancy (age, 25–38 years; mean, 30 years) attending a prenatal well clinic at gestation weeks 12, 22, and 32 and approximately 1 year postpartum. Main Outcome Measure(s) Trimester-specific reference intervals of endogenous steroid hormones analyzed using an isotope dilution tandem mass spectrometer equipped with an atmospheric pressure photoionization source with deuterium-labeled internal standards. Result(s) Serum estradiol, P, 17α-hydroxyprogesterone, and 11-deoxycortisol increased throughout pregnancy; cortisol increased up to the second trimester and then remained steady, while androstenedione increased by 80 percent by gestation week 12, then remained constant. Serum DHEA-S decreased by 50% by the third trimester. Conclusion(s) Trimester-specific reference intervals are reported for eight serum steroids. The ratios of individual serum hormone concentrations during pregnancy relative to their 1-year postpartum concentrations illustrate the expected normal trends of changes in hormone concentrations during pregnancy. PMID:16169406

  9. Follicular steroid hormones as markers of oocyte quality and oocyte development potential.

    PubMed

    Carpintero, Nayara López; Suárez, Onica Armijo; Mangas, Carmen Cuadrado; Varea, Carolina González; Rioja, Rubén Gómez

    2014-07-01

    Various components of follicular fluid are suggested as biochemical predictors of oocyte quality. Previous studies of follicular steroid hormone levels have shown disparate results when related with fertilization outcomes. The objective of the study was to relate the levels of steroid hormones of each individual follicle with oocyte maturation, fertilization results, embryo quality, and pregnancy rates. Prospective cohort study in a university hospital. In 31 patients, who underwent intracytoplasmic sperm injection, it was performed an ultrasound guided aspiration of follicular fluid of the first two mature follicles from each ovary. Follicular levels of estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate were measured by chemiluminescent immunoassay. Generalized estimating equation model. In follicular fluids with mature oocyte presence, in normal as well as in failed fertilization, there was a positive correlation between follicular testosterone and progesterone (r = 0.794, P = 0.0001 and r = 0.829, P = 0.0001). Progesterone levels were higher in cases of normal fertilization compared to failed fertilization (P = 0.003). B quality embryos came from oocytes immersed in follicular fluids with higher estradiol values and higher estradiol/progesterone and estradiol/testosterone ratios than those of C quality (P = 0.01; P = 0.0009; P = 0.001). Estradiol levels were higher in patients who achieved pregnancy (P = 0.02). The analysis of follicular hormone composition could be considered as an additional tool in oocyte selection.

  10. Follicular steroid hormones as markers of oocyte quality and oocyte development potential

    PubMed Central

    Carpintero, Nayara López; Suárez, Onica Armijo; Mangas, Carmen Cuadrado; Varea, Carolina González; Rioja, Rubén Gómez

    2014-01-01

    CONTEXT: Various components of follicular fluid are suggested as biochemical predictors of oocyte quality. Previous studies of follicular steroid hormone levels have shown disparate results when related with fertilization outcomes. AIM: The objective of the study was to relate the levels of steroid hormones of each individual follicle with oocyte maturation, fertilization results, embryo quality, and pregnancy rates. SETTINGS AND DESIGN: Prospective cohort study in a university hospital. METHODS: In 31 patients, who underwent intracytoplasmic sperm injection, it was performed an ultrasound guided aspiration of follicular fluid of the first two mature follicles from each ovary. Follicular levels of estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate were measured by chemiluminescent immunoassay. STATISTICAL ANALYSIS: Generalized estimating equation model. RESULTS: In follicular fluids with mature oocyte presence, in normal as well as in failed fertilization, there was a positive correlation between follicular testosterone and progesterone (r = 0.794, P = 0.0001 and r = 0.829, P = 0.0001). Progesterone levels were higher in cases of normal fertilization compared to failed fertilization (P = 0.003). B quality embryos came from oocytes immersed in follicular fluids with higher estradiol values and higher estradiol/progesterone and estradiol/testosterone ratios than those of C quality (P = 0.01; P = 0.0009; P = 0.001). Estradiol levels were higher in patients who achieved pregnancy (P = 0.02). CONCLUSION: The analysis of follicular hormone composition could be considered as an additional tool in oocyte selection. PMID:25395744

  11. Steroid hormones in biosolids and poultry litter: a comparison of potential environmental inputs.

    PubMed

    Bevacqua, Christine E; Rice, Clifford P; Torrents, Alba; Ramirez, Mark

    2011-05-01

    Steroid hormones can act as potent endocrine disruptors when released into the environment. The main sources of these chemicals are thought to be wastewater treatment plant discharges and waste from animal feeding operations. While these compounds have frequently been found in wastewater effluents, few studies have investigated biosolids or manure, which are routinely land applied, as potential sources. This study assessed the potential environmental contribution of steroid hormones from biosolids and chicken litter. Hormone concentrations in samples of limed biosolids collected at a waste treatment plant over a four year period ranged from <2.5 to 21.7ng/g dry weight for estrone (E1) and <2.5 to 470ng/g dry weight for progesterone. Chicken litter from 12 mid-Atlantic farms had averages of 41.4ng/g dry weight E1, 63.4ng/g dry weight progesterone, and 19.2ng/g dry weight E1-sulfate (E1-S). Other analytes studied were 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), testosterone, E2-3-sulfate (E2-3-S), and E2-17-sulfate (E2-17-3). Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

    PubMed

    Singh, Gurmeet K S; Balzer, Ben W R; Desai, Reena; Jimenez, Mark; Steinbeck, Katharine S; Handelsman, David J

    2015-11-01

    Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable. © The Author(s) 2015.

  13. Effect of microwave hydrolysis on transformation of steroidal hormones during anaerobic digestion of municipal sludge cake.

    PubMed

    Hamid, Hanna; Eskicioglu, Cigdem

    2013-09-15

    Fate and removal of 16 steroidal (estrogenic, androgenic and progestogenic) hormones were studied during advanced anaerobic digestion of sludge cake using microwave (MW) pretreatment. Effect of pretreatment temperature (80, 120, 160 °C), operating temperature (mesophilic at 35 ± 2 °C, thermophilic at 55 ± 2 °C) and sludge retention time (SRT: 20, 10, 5 days) were studied employing eight lab-scale semi-continuously fed digesters. To determine the potential effect of MW hydrolysis, hormones were quantified in total (sorbed + soluble) and supernatant (soluble) phases of the digester influent and effluent streams. Seven of 16 hormones were above the method reporting limit (RL) in one or more of the samples. Hormone concentrations in total phase of un-pretreated (control) and pretreated digester feeds ranged in <157-2491 ng/L and <157-749 ng/L, respectively. The three studied factors were found to be statistically significant (95% confidence level) in removal of one or more hormones from soluble and/or total phase. MW hydrolysis of the influent resulted in both release (from sludge matrix) and attenuation of hormones in the soluble phase. Accumulation of estrone (E1) as well as progesterone (Pr) and androstenedione (Ad) in most of the digesters indicated possible microbial transformations among the hormones. Compared to controls, all pretreated digesters had lower total hormone concentrations in their influent streams. At 20 days SRT, highest total removal (E1+E2+Ad +Pr) was observed for the thermophilic control digester (56%), followed by pretreated mesophilic digesters at 120 °C and 160 °C with around 48% efficiency. In terms of conventional performance parameters, relative (to control) improvements of MW pretreated digesters at a 5-d SRT ranged in 98-163% and 57-121%, for volatile solids removal and methane production, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Desensitization of brain opiate receptor mechanisms by gonadal steroid treatments that stimulate luteinizing hormone secretion.

    PubMed

    Berglund, L A; Derendorf, H; Simpkins, J W

    1988-06-01

    We studied the effects of two ovarian steroid treatments that induce proestrous-like surges in LH secretion on responsiveness to morphine sulfate (MS), as measured by induced hypothermic, antinociceptive, behavioral, and LH secretory changes. Ovariectomized rats received no steroids (OVX), 7.5 micrograms estradiol benzoate 2 days before the experiment (EB), or EB and then 5 mg progesterone 48 h later (EBP). MS administration coincided with the steroid-induced LH hypersecretion that occurs in the EB and EBP rats at 1530-1630 h. Serum LH concentrations were determined 30 min after administration of MS. In OVX and EB rats, MS caused a dose-dependent decrease in serum LH, but even 20 mg/kg MS did not alter serum LH during the EBP-induced LH surge. Brain-mediated morphine-induced analgesia was evaluated in the three steroid treatment groups from measurement of latency to pawlick on a hot plate. EB and EBP rats were less responsive than OVX rats to MS-induced antinociception. EB and EBP rats were also less responsive than OVX animals to the spinal cord-mediated analgesia due to MS, as calculated by tail-flick latency. MS-induced hypothermia revealed a responsiveness order of OVX greater than EB greater than EBP. Whereas MS caused a dose-dependent reduction in locomotor activity in OVX and EB rats, EBP rats showed marked hyperactivity at low MS doses and were less responsive to the suppression of locomotor activity at higher doses. These marked steroid-induced changes in MS responsiveness could not be explained by altered pharmacokinetic disposition of morphine. These data indicate that treatment with EBP, which stimulates a preovulatory-like LH surge, decreases the ability of MS to induce hypothermic, antinociceptive, and behavioral responses and abolishes its capacity to suppress LH release. These effects of gonadal steroids were not observed before the LH surge, which suggests that this surge is linked to the decline in MS sensitivity. Further, the diminished response

  15. Doping with growth hormone/IGF-1, anabolic steroids or erythropoietin: is there a cancer risk?

    PubMed

    Tentori, Lucio; Graziani, Grazia

    2007-05-01

    Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

  16. Towards an understanding of the evolution of the chorioallantoic placenta: steroid biosynthesis and steroid hormone signaling in the chorioallantoic membrane of an oviparous reptile.

    PubMed

    Cruze, Lori; Kohno, Satomi; McCoy, Michael W; Guillette, Louis J

    2012-09-01

    Amniotes, mammals, reptiles, and birds form common extraembryonic membranes during development to perform essential functions, such as protection, nutrient transfer, gas exchange, and waste removal. Together with the maternal uterus, extraembryonic membranes of viviparous (live-bearing) amniotes develop as an endocrine placenta that synthesizes and responds to steroid hormones critical for development. The ability of these membranes to synthesize and respond to steroid hormone signaling has traditionally been considered an innovation of placental amniotes. However, our laboratory recently demonstrated that this ability extends to the chorioallantoic membrane (CAM) of an oviparous (egg-laying) amniote, the domestic chicken, and we hypothesized that steroidogenic extraembryonic membranes could be an evolutionarily conserved characteristic of all amniotes because of similarities in basic structure, function, and shared evolutionary ancestry. In this study, we examined steroid hormone synthesis and signaling in the CAM of another oviparous amniote, the American alligator (Alligator mississippiensis). We quantified mRNA expression of a steroidogenic factor involved in the regulation of steroidogenesis (NR5A1), the key steroidogenic enzymes involved in the synthesis of progestins (HSD3B1), androgens (CYP17A1), and estrogens (CYP19A1), and the receptors involved in the signaling of progestins (PR), androgens (AR), estrogens (ESR1 and ESR2), and glucocorticoids (GR). Furthermore, we performed protein immunolocalization for PR and ESR1. Collectively, our findings indicate that the alligator CAM has the capability to regulate, synthesize, and respond to steroid hormone signaling, thus, supporting our hypothesis that the extraembryonic membranes of Amniota share a unifying characteristic, that is, the ability to synthesize and respond to steroid hormones.

  17. [Concentrations of adrenal steroids and sex hormones in postmenopausal women suffering from coronary artery disease].

    PubMed

    Sablik, Zbigniew; Samborska-Sablik, Anna; Goch, Jan Henryk

    2008-10-01

    The lack of the benefits in the prevention of coronary artery disease (CAD) from the hormonal substitution with preparations of estradiol (E2) suggests that higher frequency of CAD in postmenopausal women (PMW) may be influenced by a hormonal mechanism different from the postmenopausal hypoestrogenism. Due to the fact adrenal glands are the important source of steroids in PMW the aim of our research was the assessment of the concentrations of the adrenal hormones and their possible relations with CAD. W-CAD group--31 PMW at the age of 66 +/- 9 years with angiographically proven CAD; 3/4 of them suffered from myocardial infarction. W-H group--17 healthy women at the age of 59 +/- 7 years. Common clinical and biochemical risk factors were searched for in each and every of the PMW. In the venous blood samples taken from them by means of immunological methods the concentrations of the hormones were assessed: starving insulin, adrenocorticotropic hormone (ACTH), E2, progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS), cortisol, aldosterone, androstenedione, folliculotropic hormone and luteinising hormone. The levels of the hormones were compared between the groups. Logistic regression analysis was used to discover possible relations among the clinical and hormonal parameters and CAD. In W-CAD mean concentration of DHEAS was lower than in W-H, close to the significant value (75 +/- 76 vs 102 +/- 79 microg/dl, p<0,08). In PMW with CAD mean concentration of cortisol (18 +/- 5 vs 15 +/- 6 microg/dl, p<0,07) and ACTH was higher, but mean concentration of aldosterone was more than twice as small as in the healthy ones. The levels of the rest aforementioned hormones were similar in the groups. In the univariate model created by logistic regression analysis DHEAS was the only hormone that revealed the significant relation between its level and the occurrence of CAD. In PMW diminished concentration of DHEAS is correlated with occurrence of CAD. The differences of

  18. Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones.

    PubMed

    Nunez, Nomeli P; Perkins, Susan N; Smith, Nicole C P; Berrigan, David; Berendes, David M; Varticovski, Lyuba; Barrett, J Carl; Hursting, Stephen D

    2008-01-01

    Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.

  19. Identification of a Dynamic Mitochondrial Protein Complex Driving Cholesterol Import, Trafficking, and Metabolism to Steroid Hormones

    PubMed Central

    Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Ye, Xiaoying; Blonder, Josip; Veenstra, Timothy

    2012-01-01

    Steroid hormones are critical for organismal development and health. The rate-limiting step in steroidogenesis is the transport of cholesterol from the outer mitochondrial membrane (OMM) to the cytochrome P450 enzyme CYP11A1 in the inner mitochondrial membrane (IMM). Cholesterol transfer occurs through a complex termed the “transduceosome,” in which cytosolic steroidogenic acute regulatory protein interacts with OMM proteins translocator protein and voltage-dependent anion channel (VDAC) to assist with the transfer of cholesterol to OMM. It has been proposed that cholesterol transfer from OMM to IMM occurs at specialized contact sites bridging the two membranes composed of VDAC and IMM adenine nucleotide translocase (ANT). Blue native PAGE of Leydig cell mitochondria identified two protein complexes that were able to bind cholesterol at 66- and 800-kDa. Immunoblot and mass spectrometry analyses revealed that the 800-kDa complex contained the OMM translocator protein (18-kDa) and VDAC along with IMM CYP11A1, ATPase family AAA domain-containing protein 3A (ATAD3A), and optic atrophy type 1 proteins, but not ANT. Knockdown of ATAD3A, but not ANT or optic atrophy type 1, in Leydig cells resulted in a significant decrease in hormone-induced, but not 22R-hydroxycholesterol-supported, steroid production. Using a 22-phenoxazonoxy-5-cholene-3-beta-ol CYP11A1-specific probe, we further demonstrated that the 800-kDa complex offers the microenvironment needed for CYP11A1 activity. Addition of steroidogenic acute regulatory protein to the complex mobilized the cholesterol bound at the 800-kDa complex, leading to increased steroid formation. These results identify a bioactive, multimeric protein complex spanning the OMM and IMM unit that is responsible for the hormone-induced import, segregation, targeting, and metabolism of cholesterol. PMID:22973050

  20. Role of biofilms in sorptive removal of steroidal hormones and 4-nonylphenol compounds from streams

    USGS Publications Warehouse

    Writer, J.H.; Ryan, J.N.; Barber, L.B.

    2011-01-01

    Stream biofilms play an important role in geochemical processing of organic matter and nutrients, however, the significance of this matrix in sorbing trace organic contaminants is less understood. This study focused on the role of stream biofilms in sorbing steroidal hormones and 4-nonylphenol compounds from surface waters using biofilms colonized in situ on artificial substrata and subsequently transferred to the laboratory for controlled batch sorption experiments. Steroidal hormones and 4-nonylphenol compounds readily sorb to stream biofilms as indicated by organic matter partition coefficients (K om, L kg-1) for 17??-estradiol (102.5-2.8 L kg-1), 17??-ethynylestradiol (102.5-2.9 L kg -1), 4-nonylphenol (103.4-4.6 L kg-1), 4-nonylphenolmonoethoxylate (103.5-4.0 L kg-1), and 4-nonylphenoldiethoxylate (103.9-4.3 L kg-1). Experiments using water quality differences to induce changes in the relative composition of periphyton and heterotrophic bacteria in the stream biofilm did not significantly affect the sorptive properties of the stream biofilm, providing additional evidence that stream biofilms will sorb trace organic compounds under of variety of environmental conditions. Because sorption of the target compounds to stream biofilms was linearly correlated with organic matter content, hydrophobic partition into organic matter appears to be the dominant mechanism. An analysis of 17??-estradiol and 4-nonylphenol hydrophobic partition into water, biofilm, sediment, and dissolved organic matter matrices at mass/volume ratios typical of smaller rivers showed that the relative importance of the stream biofilm as a sorptive matrix was comparable to bed sediments. Therefore, stream biofilms play a primary role in attenuating these compounds in surface waters. Because the stream biofilm represents the base of the stream ecosystem, accumulation of steroidal hormones and 4-nonylphenol compounds in the stream biofilm may be an exposure pathway for organisms in higher trophic

  1. The role of ovarian hormones in sexual reward states of the female rat.

    PubMed

    Parada, Mayte; Vargas, Erica Barbosa; Kyres, Maria; Burnside, Kimberly; Pfaus, James G

    2012-09-01

    To what extent does the reward value of sexual stimulation in females depend on ovarian hormones? The effects of estradiol benzoate (EB) and progesterone (P) were examined on the acquisition and expression of sexual reward induced by paced copulation and clitoral stimulation (CLS) in ovariectomized (OVX) rats. In experiment 1 we examined the expression of a pacing-induced conditioned place preference (CPP). Ovariectomized, hormone-primed rats were given experience with paced copulation associated with one side of a CPP apparatus. Changing hormonal status prior to the final CPP test did not alter pacing-induced CPP. However, subsequent partial extinction of CPP was observed only in rats primed with EB+P, a treatment previously shown to induce sexual desire and receptivity. In Experiment 2, significant CLS-induced CPP developed in ovariectomized rats regardless of hormone priming. Our results show that the expression of the sexual reward state induced by paced copulation, and CLS in particular, is independent of hormone priming. We propose that ovarian hormones sensitize sensory and motor pathways necessary for sexual behavior and stimulation to induce reward. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Interrelationship between feeding level and the metabolic hormones leptin, ghrelin and obestatin in control of chicken egg laying and release of ovarian hormones.

    PubMed

    Sirotkin, Alexander V; Grossmann, Roland

    2015-06-01

    The aim of the present experiment is to examine the role of nutritional status, metabolic hormones and their interrelationships in the control of chicken ovarian ovulatory and secretory activity. For this purpose, we identified the effect of food restriction, administration of leptin, ghrelin 1-18, obestatin and combinations of food restriction with these hormones for 3days on chicken ovulation (egg laying) rate and ovarian hormone release. The release of progesterone (P), testosterone (T), estradiol (E) and arginine-vasotocin (AVT) by isolated and cultured ovarian fragments was determined by EIA. It was observed that food restriction significantly reduced the egg-laying rate, T, E and AVT release and promoted P output by ovarian fragments. Leptin, administrated to ad libitum-fed chickens, did not change these parameters besides promoting E release. Nevertheless, administration of leptin was able to prevent the effect of food restriction on ovulation, T and E (but not P or AVT) release. Ghrelin 1-18 administration to ad libitum-fed birds did not affect the measured parameters besides a reduction in P release. Ghrelin 1-18 administration prevented the food restriction-induced decrease in ovarian T, E and AVT, but it did not change P output or egg laying. Obestatin administrated to control chicken promoted their ovarian P, E and inhibited ovarian AVT release but did not affect egg laying. It was able to promote the effect of food restriction on P, T and AVT, but not E release or egg laying. Our results (1) confirm an inhibitory effect of food restriction on chicken ovulation rate; (2) shows that food restriction-induced reduction in egg laying is associated with a decrease in ovarian T, E and AVT and an increase in ovarian P release; (3) confirm the involvement of metabolic hormones leptin, ghrelin and obestatin in the control of chicken ovarian hormones output; and (4) the ability of metabolic hormones to mimic/antagonize or prevent/promote the effects of food

  3. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    SciTech Connect

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-03-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E{sub 2}) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E{sub 2} dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E{sub 2} increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab.

  4. The microRNA biogenesis machinery: regulation by steroid hormones and alterations in cancer.

    PubMed

    González-Duarte, Ramiro José; Cázares-Ordoñez, Verna; Ávila-Chávez, Euclides

    2014-01-01

    MicroRNAs are a class of non-coding RNAs that regulate gene expression at the post-transcriptional level. The major proteins of the canonical microRNA biogenesis pathway in human are: Drosha, DGCR8, DDX5, DDX17, Exportin 5, Dicer and Argonaute 2. Recent studies suggest that gene expression of some canonical microRNA biogenesis components could be regulated by steroid hormones. Furthermore, various alterations in microRNA biogenesis have been associated with diseases like cancer. Due to the importance of microRNAs in cell physiology, the study of the factors that regulate or affect their biogenesis is critical.

  5. Data for stable formulation of steroid hormone receptor-targeted liposomes for cancer therapeutics.

    PubMed

    Sharma, Priyanka; Banerjee, Rajkumar; Narayan, Kumar Pranav

    2016-06-01

    A detailed description of steroid hormone ligand containing liposomes and their stability has been given. Liposomes were complexed with β-gal DNA and used to transfect cancer and non-cancer cells. The stability of the liposomes and lipoplexes were analysed using dynamic light scattering and DNA-binding gel images. The formulations were used to assess the delivery of anticancer gene, p53 in cancer cells. The dataset consists of DNA-binding gel images, transfection, cytotoxicity and reverse transcriptase PCR images.

  6. Steroid hormones promote bovine oocyte growth and connection with granulosa cells.

    PubMed

    Makita, Miho; Miyano, Takashi

    2014-09-01

    Many approaches have been investigated for growing oocytes in vitro in mammals. To support oocyte growth in vitro, the culture systems must meet certain conditions for maintaining connections between oocytes and surrounding granulosa cells. The aims of this study were to determine the effects of combinations of 17β-estradiol (E2) and androstenedione (A4) on in vitro growth of bovine oocytes and to determine the number of connections between the oocyte and granulosa cells. Oocyte-granulosa cell complexes (OGCs) collected from early antral follicles (0.4-0.7 mm in diameter) were cultured for 14 days in a medium with different concentrations of E2 and A4, either alone or in combinations. We then assessed the number of transzonal projections (TZPs), which extend from granulosa cells through the zona pellucida to the oolemma. During in vitro growth culture, OGC structures were maintained in the medium with steroid hormones. The mean diameter of oocytes grown in the medium with both E2 and A4 was increased from 95.8 μm to around 120 μm, larger than oocytes grown without steroid hormones (109.9 μm) and similar in size to in vivo fully grown oocytes (119.4 μm) from 4- to 6-mm antral follicles. In subsequent in vitro maturation culture (22 hours), 30% (12 of 40) and 34% (14 of 41) of oocytes grown with E2 or A4 alone, respectively, matured to metaphase II; meanwhile, oocytes grown with a combination of E2 and A4 matured to metaphase II at a high rate (58%, 23 of 40). Growing oocytes isolated from early antral follicles had many uniformly distributed TZPs throughout the zona pellucida. After 14 days of culture, there was a significant decrease in the number of TZPs in oocytes grown without steroid hormones, whereas the number of TZPs was maintained in oocytes grown with steroid hormones. In particular, oocytes grown with E2 alone or with a combination of E2 and A4 had numbers of TZPs similar to oocytes before growth culture. In conclusion, a combination of

  7. Exposure assessment of prepubertal children to steroid endocrine disruptors. 2. Determination of steroid hormones in milk, egg, and meat samples.

    PubMed

    Courant, Frédérique; Antignac, Jean-Philippe; Laille, Julie; Monteau, Fabrice; Andre, François; Le Bizec, Bruno

    2008-05-14

    In the present study, the occurrence of the main sex steroid hormones in milk, egg, and meat was evaluated on the basis of a highly specific gas chromatography-tandem mass spectrometry measurement method. Globally, the results indicated that targeted estrogens and androgens occurred at similar levels (concentration levels in the 10-100 ng kg (-1) range) in the analyzed muscle and milk samples. The same compounds occurred at about 10-fold higher concentrations (i.e., in the 100-1000 ng kg (-1) range) in eggs and kidney samples. More precisely, egg and milk appeared as a non-negligible sources of estradiol (i.e., 2.2 +/- 0.8 and 3.1 +/- 2.0 ng day (-1), respectively), whereas testosterone exposure is caused by ingestion of meat and/or egg (i.e., 12.2 +/- 48.2 and 5.2 +/- 2.3 ng day (-1), respectively). The provided exposure data will be further exploited in the scope of a risk assessment study regarding endocrine disruption associated with these molecules.

  8. Are the phenotypic traits of hatchling lizards affected by maternal allocation of steroid hormones to the egg?

    PubMed

    Radder, Rajkumar S; Shine, Richard

    2007-01-01

    In lizards as in many other kinds of animals, strong maternal effects on the phenotypic traits of hatchlings are frequently reported. One plausible non-genetic mechanism that might produce such differences among clutches involves maternal allocation of steroid hormones. Lizard eggs often display considerable inter-clutch variation in the quantities of maternally allocated steroids, and exogenous application of such steroids has been reported to influence the phenotypic traits (especially, sex) of hatchlings. We examined correlations between naturally occurring yolk steroid levels and offspring traits in the scincid lizard Bassiana duperreyi, and also conducted experimental trials (exogenous application of testosterone or 17beta-oestradiol to eggs) to test for causal effects of hormones. Although exogenous hormones readily reversed sex of the hatchling lizards, no other phenotypic traits of the hatchlings (morphology, locomotor performance) were significantly correlated with naturally occurring levels of testosterone, dihydrotestosterone or estrogen, nor were these phenotypic traits significantly affected by exogenous application of hormones. Hence, our results do not support the hypothesis that reproducing female lizards manipulate the phenotypic traits of their offspring by differential allocation of steroid hormones.

  9. Enrichment of steroid hormones in water with porous and hydrophobic polymer-based SPE followed by HPLC-UV determination.

    PubMed

    Hu, Yinfen; Zhang, Man; Tong, Changlun; Wu, Jianmin; Liu, Weiping

    2013-10-01

    There have been great concerns about the persistence of steroid hormones in surface water. Since the concentrations of these compounds in water samples are usually at a trace level, the efficient enrichment of steroid hormones is vital for further analysis. In this work, a porous and hydrophobic polymer was synthesized and characterized. The composition of solvent used as porogen in the synthetic process was shown to have an effect on the morphology of the polymer, which was successfully used as an SPE sorbent for simultaneously enriching steroid hormones in surface water samples. The recoveries of the steroid hormones on the custom-made polymer ranged from 93.4 to 106.2%, whereas those on commercialized ENVI-18, LC-18, and Oasis HLB ranged from 54.8 to 104.9, 66 to 93.6, and 77.2 to 106%, respectively. Five types of steroid hormones were simultaneously measured using HPLC-UV after they were enriched by the custom-made sorbent. Based on these findings, the SPE-HPLC method was developed. The LODs of this method for estriol, estradiol, estrone, androstenedione, progesterone were 0.07, 0.43, 0.61, 0.27, and 0.42 μg/L, respectively, while precision and reproducibility RSDs were <6.40 and 7.49%, respectively. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Brain stem auditory evoked potentials: effects of ovarian steroids correlated with increased incidence of Bell's palsy in pregnancy.

    PubMed

    Ben David, Y; Tal, J; Podoshin, L; Fradis, M; Sharf, M; Pratt, H; Faraggi, D

    1995-07-01

    To investigate the effect of ovarian steroids on the brain stem during changes of estrogen and progesterone blood levels, we recorded brain stem auditory evoked potentials with increased stimulus rates from 26 women treated for sterility by menotropins (Pergonal and Metrodin). These women were divided into three groups according to their estrogen and progesterone blood levels. The brain stem auditory evoked potential results revealed a significant delay of peak III only, with an increased stimulus rate in the group with the highest estrogen level. Estrogen may cause a brain stem synaptic impairment, presumably because of ischemic changes, and thus also may be responsible for a higher incidence of Bell's palsy during pregnancy.

  11. The influence of androgenic steroid hormones on female aggression in ‘atypical’ mammals

    PubMed Central

    French, Jeffrey A.; Mustoe, Aaryn C.; Cavanaugh, Jon; Birnie, Andrew K.

    2013-01-01

    Dimorphism on dominance and agonistic behaviour in mammals tends to be strongly biased toward males. In this review, we focus on a select few species of mammals in which females are as or more aggressive than males, and/or are dominant to males, and explore the role of androgenic hormones in mediating this important difference. While the data are not as clear-cut as those published on traditional laboratory mammals, our review highlights important endocrine substrates for both organizational and activational influences of steroids on female aggressive behaviour. We highlight areas in which further observations and experiments are crucial, especially the potential facilitative effects of androgens on female aggression. Finally, new and innovative techniques, including molecular genetics and receptor pharmacology, portend important insights into the ways in which androgenic hormones regulate aggressive behaviour in ‘atypical’ female mammals. PMID:24167314

  12. The influence of androgenic steroid hormones on female aggression in 'atypical' mammals.

    PubMed

    French, Jeffrey A; Mustoe, Aaryn C; Cavanaugh, Jon; Birnie, Andrew K

    2013-01-01

    Dimorphism on dominance and agonistic behaviour in mammals tends to be strongly biased toward males. In this review, we focus on a select few species of mammals in which females are as or more aggressive than males, and/or are dominant to males, and explore the role of androgenic hormones in mediating this important difference. While the data are not as clear-cut as those published on traditional laboratory mammals, our review highlights important endocrine substrates for both organizational and activational influences of steroids on female aggressive behaviour. We highlight areas in which further observations and experiments are crucial, especially the potential facilitative effects of androgens on female aggression. Finally, new and innovative techniques, including molecular genetics and receptor pharmacology, portend important insights into the ways in which androgenic hormones regulate aggressive behaviour in 'atypical' female mammals.

  13. Evaluation of Ovarian Reserve with Anti-Müllerian Hormone in Familial Mediterranean Fever

    PubMed Central

    Şahin, Ali; Karakuş, Savaş; Durmaz, Yunus; Yıldız, Çağlar; Aydın, Hüseyin; Cengiz, Ahmet Kıvanç; Güler, Duygu

    2015-01-01

    Objective. To investigate ovarian reserves in attack-free familial Mediterranean fever (AF-FMF) patients at the reproductive age by anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, and hormonal parameters. Methods. Thirty-three AF-FMF patients aging 18–45 years and 34 healthy women were enrolled and FSH, LH, E2, PRL, and AMH levels were measured in the morning blood samples at 2nd–4th days of menstruation by ELISA. Concomitant pelvic ultrasonography was performed to calculate AFC and ovarian volumes. Results. In FMF patient group, median AMH levels were statistically significantly lower in the M69V mutation positive group than in the negative ones (P = 0.018). There was no statistically significant difference in median AMH levels between E148Q mutation positive patients and the negative ones (P = 0.920). There was also no statistically significant difference in median AMH levels between M680I mutation positive patients and the negative ones (P = 0.868). No statistically significant difference was observed in median AMH levels between patients who had at least one mutation and those with no mutations (P = 0.868). We realized that there was no difference in comparisons between ovarian volumes, number of follicles, and AMH levels ovarian reserves when compared with FMF patients and healthy individuals. Conclusions. Ovarian reserves of FMF pateints were similar to those of healthy subjects according to AMH. However, AMH levels were lower in FMF patients with M694V mutation. PMID:26064124

  14. Pre-diabetes and serum sex steroid hormones among US men.

    PubMed

    Arthur, R; Rohrmann, S; Møller, H; Selvin, E; Dobs, A S; Kanarek, N; Nelson, W; Platz, E A; Van Hemelrijck, M

    2017-01-01

    Several studies demonstrate a link between diabetes and sex steroid hormones, but the link with pre-diabetes remains elusive. In this study, we hypothesize that pre-diabetes, which is characterised by having impaired fasting glucose and/or impaired glucose tolerance and/or impaired HbA1C, may influence circulating sex steroid hormone concentrations in men. Thus, we investigated whether serum sex steroid hormone concentrations differ between men with and without pre-diabetes. We analyzed data for 1139 men who were aged 20+ years when they participated in the Third National Health and Nutrition Examination Survey. We calculated adjusted geometric mean serum concentrations of total and estimated free testosterone, androstanediol glucuronide, total and estimated free estradiol, and sex hormone-binding globulin (SHBG) in men with and without pre-diabetes. Logistic regression was used to calculate adjusted odds ratios (OR) of lower concentrations of androgens and SHBG, and higher concentrations of estradiol by prediabetes status. Adjusting for age and race/ethnicity, total testosterone concentration was lower among men with (geometric mean: 4.68 ng/mL) than without (5.36 ng/mL, p = 0.01) pre-diabetes. SHBG concentration was also lower in men with (31.67 nmol/L) than without (36.16 nmol/L; p = 0.01) pre-diabetes. Concentrations of the other hormones did not differ between men with and without pre-diabetes. After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58; 95% CI: 1.54-4.29), higher free estradiol level (OR: 1.59; 95% CI: 1.14-2.22), and lower SHBG level (OR: 2.27; 95% CI: 1.32-3.92) compared to men without pre-diabetes. These associations were attenuated after adjusting for adiposity (testosterone OR: 1.76; 95% CI 0.95-3.27, free estradiol OR: 1.29, 95% CI: 0.88-1.88, SHBG OR: 1.71; 95% CI 0.88-3.30). Our findings suggest that men with pre-diabetes have lower circulating total testosterone

  15. Association between endogenous sex steroid hormones and inflammatory biomarkers in US men

    PubMed Central

    Tsilidis, Konstantinos K.; Rohrmann, Sabine; McGlynn, Katherine A.; Nyante, Sarah J.; Lopez, David S.; Bradwin, Gary; Feinleib, Manning; Joshu, Corinne E.; Kanarek, Norma; Nelson, William G.; Selvin, Elizabeth; Platz, Elizabeth A.

    2013-01-01

    Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone binding globulin (SHBG) with biomarkers of inflammation, C-reactive protein (CRP) and white blood cell (WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999–2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per 1 quintile in concentration, −0.18; P-trend, 0.001) and calculated free (slope, −0.13; P-trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (≤3.3 ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (≥ 3 mg/L) compared to men in the top four quintiles (OR, 1.61; 95% CI, 1.00 – 2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; P-trend, <0.001; Free E2: slope, 0.15; P-trend, <0.001) and WBC (Total E2: slope, 0.02; P-trend, 0.08; Free E2: slope, 0.02; P-trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, −0.03; P-trend, 0.04), but not with CRP. These cross-sectional findings are consistent with the hypothesis that higher androgen and lower estrogen concentrations may have an anti-inflammatory effect in men. PMID:24124163

  16. Lgr4 is required for endometrial receptivity acquired through ovarian hormone signaling.

    PubMed

    Kida, Tomoyo; Oyama, Kazunori; Sone, Mizuki; Koizumi, Masae; Hidema, Shizu; Nishimori, Katsuhiko

    2014-01-01

    Previously, using the Keratin5-Cre transgenic mouse model we reported that female Lgr4-conditional KO mice (Lgr4(K5 KO)) showed subfertility with defective stromal decidualization due to abnormal development of the uterine gland. However, the impact of the LGR4 defect on luminal epithelial cells was not investigated in the previous report. Here, we focused on the receptive state of the luminal epithelium in Lgr4(K5 KO) mice that received ovarian hormone treatment. In Lgr4(K5 KO) mice, progesterone failed to inhibit the luminal epithelial cell proliferation. Immunohistochemical and qRT-PCR analyses revealed down-regulated progesterone signaling in the uterus of Lgr4(K5 KO) mice. These results demonstrated that LGR4 is essential for the acquisition of endometrial receptivity through ovarian hormone signaling.

  17. Is immune system-related hypertension associated with ovarian hormone deficiency?

    PubMed Central

    Sandberg, Kathryn; Ji, Hong; Einstein, Gillian; Au, April; Hay, Meredith

    2017-01-01

    The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women. PMID:26419911

  18. Influence of metabolic hormones and nutrition on ovarian follicle development in cattle: practical implications.

    PubMed

    Gong, J G

    2002-07-01

    Nutrition has long been known to have a profound influence on reproductive performance of female cattle, but the underlying mechanism remains poorly understood. Whilst early investigations focused on the modulation of nutrition on hypothalamic-pituitary axis, more recent studies have tested the hypothesis that metabolic hormones as nutritional signals exert a direct effect at the ovarian level. In cattle, treatment with recombinant bovine somatotrophin (rGH) significantly increases the population of small ovarian follicles. This is associated with increases in circulating concentrations of insulin and insulin-like growth factor-I (IGF-I). Subsequent studies, both in vitro and in vivo, have highlighted the importance of IGF-I and/or insulin acting in synergy with FSH and LH. More recently, we demonstrated that feeding heifers with 200% maintenance requirements for a short period significantly increases circulating insulin concentrations and population of small ovarian follicles. Based on these findings, our recent work has aimed at addressing some practical problems in cattle production. Firstly, we showed that both rGH pretreatment and increased dietary intake significantly enhance the response to standard superovulatory regimes. Secondly, we have demonstrated that feeding a diet to increase circulating insulin concentrations during the early lactation can advance the first ovulation postpartum and increase conception rate to the first service in dairy cows. In summary, nutrition influences ovarian follicle development in cattle possibly through changes in metabolic hormones. These interactions can be manipulated to improve reproductive performance.

  19. Effect of reproductive hormones on ovarian epithelial tumors: II. Effect on angiogenic activity.

    PubMed

    Chen, Chen; Petitclerc, Eric; Zhou, Hong; Brooks, Peter C; Sun, Tong; Yu, Mimi C; Zheng, Wenxin; Dubeau, Louis

    2002-01-01

    Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.

  20. Inhibitory Actions of Anti-Müllerian Hormone (AMH) on Ovarian Primordial Follicle Assembly

    PubMed Central

    Nilsson, Eric E.; Schindler, Ryan; Savenkova, Marina I.; Skinner, Michael K.

    2011-01-01

    The current study was designed to investigate the actions of Anti-Müllerian Hormone (AMH) on primordial follicle assembly. Ovarian primordial follicles develop from the breakdown of oocyte nests during fetal development for the human and immediately after birth in rodents. AMH was found to inhibit primordial follicle assembly and decrease the initial primordial follicle pool size in a rat ovarian organ culture. The AMH expression was found to be primarily in the stromal tissue of the ovaries at this period of development, suggesting a stromal-epithelial cell interaction for primordial follicle assembly. AMH was found to promote alterations in the ovarian transcriptome during primordial follicle assembly with over 200 genes with altered expression. A gene network was identified suggesting a potential central role for the Fgf2/Nudt6 antisense transcript in the follicle assembly process. A number of signal transduction pathways are regulated by AMH actions on the ovarian transcriptome, in particular the transforming growth factor – beta (TGFß) signaling process. AMH is the first hormone/protein shown to have an inhibitory action on primordial follicle assembly. Due to the critical role of the primordial follicle pool size for female reproduction, elucidation of factors, such as AMH, that regulate the assembly process will provide insights into potential therapeutics to manipulate the pool size and female reproduction. PMID:21637711

  1. Inhibitory actions of Anti-Müllerian Hormone (AMH) on ovarian primordial follicle assembly.

    PubMed

    Nilsson, Eric E; Schindler, Ryan; Savenkova, Marina I; Skinner, Michael K

    2011-01-01

    The current study was designed to investigate the actions of Anti-Müllerian Hormone (AMH) on primordial follicle assembly. Ovarian primordial follicles develop from the breakdown of oocyte nests during fetal development for the human and immediately after birth in rodents. AMH was found to inhibit primordial follicle assembly and decrease the initial primordial follicle pool size in a rat ovarian organ culture. The AMH expression was found to be primarily in the stromal tissue of the ovaries at this period of development, suggesting a stromal-epithelial cell interaction for primordial follicle assembly. AMH was found to promote alterations in the ovarian transcriptome during primordial follicle assembly with over 200 genes with altered expression. A gene network was identified suggesting a potential central role for the Fgf2/Nudt6 antisense transcript in the follicle assembly process. A number of signal transduction pathways are regulated by AMH actions on the ovarian transcriptome, in particular the transforming growth factor-beta (TGFß) signaling process. AMH is the first hormone/protein shown to have an inhibitory action on primordial follicle assembly. Due to the critical role of the primordial follicle pool size for female reproduction, elucidation of factors, such as AMH, that regulate the assembly process will provide insights into potential therapeutics to manipulate the pool size and female reproduction.

  2. Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells.

    PubMed

    van den Dungen, Myrthe W; Rijk, Jeroen C W; Kampman, Ellen; Steegenga, Wilma T; Murk, Albertinka J

    2015-06-01

    Persistent organic pollutants (POPs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorobiphenyl (PCB) 126 and 153, perfluorooctanesulfonic acid (PFOS), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), tributyltin (TBT), and methylmercury (MeHg) can be accumulated in seafood and then form a main source for human exposure. Some POPs have been associated with changes in steroid hormone levels in both humans and animals. This study describes the in vitro effects of these POPs and mixtures thereof in H295R adrenocortical carcinoma cells. Relative responses for 13 steroid hormones and 7 genes involved in the steroidogenic pathway, and CYP1A1, were analyzed. PFOS induced the most pronounced effects on steroid hormone levels by significantly affecting 9 out of 13 hormone levels measured, with the largest increases found for 17β-estradiol, corticosterone, and cortisol. Furthermore, TCDD, both PCBs, and TBT significantly altered steroidogenesis. Increased steroid hormone levels were accompanied by related increased gene expression levels. The differently expressed genes were MC2R, CYP11B1, CYP11B2, and CYP19A1 and changes in gene expression levels were more sensitive than changes in hormone levels. The POP mixtures tested showed mostly additive effects, especially for DHEA and 17β-estradiol levels. This study shows that some seafood POPs are capable of altering steroidogenesis in H295R cells at concentrations that mixtures might reach in human blood, suggesting that adverse health effects cannot be excluded.

  3. Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats.

    PubMed

    Aagaard, Niels Kristian; Grøfte, Thorbjørn; Greisen, Jacob; Malmlöf, Kjell; Johansen, Peter B; Grønbaek, Henning; Ørskov, Hans; Tygstrup, Niels; Vilstrup, Hendrik

    2009-10-01

    Growth hormone (GH) reduces the catabolic side effects of steroid treatment via effects on the amino-nitrogen metabolism. Ipamorelin is a synthetic peptide with GH releasing properties. We wished to study the metabolic effects of Ipamorelin and GH on selected hepatic measures of alpha-amino-nitrogen conversion during steroid-induced catabolism. Five groups of rats were included: (1) free-fed controls (2) pair-fed controls (3) prednisolone (delcortol, 4 mg x kg(-1) x day(-1)) (4) prednisolone and GH (1 mg x kg(-1) x day(-1)) (5) prednisolone and Ipamorelin (0.5 mg x kg(-1) x day(-1)). After seven days the hepatic capacity of urea-N synthesis (CUNS) was determined in parallel with measurements of liver mRNA levels of urea cycle enzymes, whole-body N-balance, and N-contents of various organs. Compared to pair-fed controls, prednisolone increased CUNS (p<0.01) as well as the expression of urea cycle genes (p<0.01), and decreased N-balance (p<0.01) as well as organ N-contents (p<0.05). Compared to prednisolone treated animals, co-administration of GH reduced CUNS by 33% (p<0.01), normalized urea cycle gene expression, improved N-balance 2.5-fold, and normalized or improved organ N-contents. In prednisolone treated rats Ipamorelin reduced CUNS by 20% (p<0.05), decreased the expression of urea cycle enzymes, neutralised N-balance, and normalized or improved organ N-contents. Accelerated nitrogen wasting in the liver and other organs caused by prednisolone treatment was counteracted by treatment with either GH or its secretagogue Ipamorelin, though at the doses given less efficiently by the latter. This functional study of animals confirms that the GH secretagogue exerts GH related metabolic effects and may be useful in the treatment of steroid-induced catabolism.

  4. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    PubMed

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  5. Metabolic profiling of cholesterol and sex steroid hormones to monitor urological diseases

    PubMed Central

    Moon, Ju-Yeon

    2016-01-01

    Cholesterol and sex steroid hormones including androgens and estrogens play a critical role in the development and progression of urological diseases such as prostate cancer. This disease remains the most commonly diagnosed malignant tumor in men and is the leading cause of death from different cancers. Attempts to understand the role of cholesterol and steroid metabolism in urological diseases have been ongoing for many years, but despite this, our mechanistic and translational understanding remains elusive. In order to further evaluate the problem, we have taken an interest in metabolomics; a discipline dedicated to the systematic study of biologically active metabolites in cells, tissues, hair and biofluids. Recently, we provided evidence that a quantitative measurement of cholesterol and sex steroid metabolites can be successfully achieved using hair of human and mouse models. The overall goal of this short review article is to introduce current metabolomic technologies for the quantitative biomarker assay development and also to provide new insight into understanding the underlying mechanisms that trigger the pathological condition. Furthermore, this review will place a particular emphasis on how to prepare biospecimens (e.g., hair fiber), quantify molecular profiles and assess their clinical significance in various urological diseases. PMID:27580660

  6. Steroid hormones for contraception in men: systematic review of randomized controlled trials.

    PubMed

    Grimes, David A; Gallo, Maria F; Grigorieva, Vera; Nanda, Kavita; Schulz, Kenneth F

    2005-02-01

    Male hormonal contraception has been an elusive goal. Administration of sex steroids to men can shut off sperm production through effects on the pituitary and hypothalamus. However, this approach also decreases production of testosterone, so an "add-back" therapy is needed. We conducted a systematic review of all randomized controlled trials of male hormonal contraception and azoospermia. Few significant differences emerged from these trials. Levonorgestrel implants combined with injectable testosterone enanthate (100 mg im) were significantly more effective than was levonorgestrel 125 microg po daily combined with testosterone patches [10 mg/d; odds ratio (OR) for azoospermia with the oral levonorgestrel regimen, 0.03; 95% CI, 0.00-0.29]. The addition of levonorgestrel 500 microg po daily improved the effectiveness of testosterone enanthate 100 mg im weekly by itself (OR for azoospermia with the combined regimen, 4.0; 95% CI, 1.00-15.99). Several regimens, including testosterone alone and gonadotropin-releasing hormone agonists and antagonists, had disappointing results. In conclusion, no male hormonal contraceptive is ready for clinical use. All trials published to date have been small exploratory studies. As a result, their power to detect important differences has been limited and their results have been imprecise. In addition, the definition of oligospermia has been imprecise or inconsistent in many reports. To avoid bias, future trials need to pay more attention on the methodological requirements for randomized controlled trials. Trials with adequate power would also be helpful.

  7. Dwarfism and cytochrome P450-mediated C-6 oxidation of plant steroid hormones.

    PubMed

    Bishop, G; Nomura, T; Yokota, T; Montoya, T; Castle, J; Harrison, K; Kushiro, T; Kamiya, Y; Yamaguchi, S; Bancos, S; Szatmári, A-M; Szekeres, M

    2006-12-01

    BRs (brassinosteroids) are plant steroid hormones that are essential for normal plant development. The dramatic dwarfism exhibited by mutants in the CYP (cytochrome P450) enzymes involved in BR biosynthesis indicates a role for these hormones in plant growth and development. Since the mid-1990s, collaborative research has been geared towards developing a better understanding of the CYP85 class of CYPs involved in BR biosynthesis in both Arabidopsis and tomato. Some of the most recent observations include the fact that certain CYP85 CYPs catalyse the synthesis of the most bioactive BR, BL (brassinolide). Current evidence suggests that evolution of this function may have occurred independently in different dicotyledonous species. Interestingly, BL accumulates in tomato fruits, highlighting a key role for this hormone in fruit development. At the same time as developing a better understanding of the enzymatic function of these CYPs, we have also carried out experiments towards characterizing where and when these genes are expressed and mechanisms of their regulation. As expected for a hormone involved in growth and development, biosynthetic gene promoter activity is associated with young rapidly growing cells and with fruit development.

  8. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies

    PubMed Central

    Collaborative Group on Epidemiological Studies of Ovarian Cancer

    2015-01-01

    Summary Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. Funding

  9. DAF as a therapeutic target for steroid hormones: implications for host-pathogen interactions.

    PubMed

    Nowicki, Bogdan; Nowicki, Stella

    2013-01-01

    In this chapter, we present a concise historic prospective and a summary of accumulated knowledge on steroid hormones, DAF expression, and therapeutic implication of steroid hormone treatment on multiple pathologies, including infection and the host-pathogen interactions. DAF/CD55 plays multiple physiologic functions including tissue protection from the cytotoxic complement injury, an anti-inflammatory function due to its anti-adherence properties which enhance transmigration of monocytes and macrophages and reduce tissue injury. DAF physiologic functions are essential in many organ systems including pregnancy for protection of the semiallogeneic fetus or for preventing uncontrolled infiltration by white cells in their pro- and/or anti-inflammatory functions. DAF expression appears to have multiple regulatory tissue-specific and/or menstrual cycle-specific mechanisms, which involve complex signaling mechanisms. Regulation of DAF expression may involve a direct or an indirect effect of at least the estrogen, progesterone, and corticosteroid regulatory pathways. DAF is exploited in multiple pathologic conditions by pathogens and viruses in chronic tissue infection processes. The binding of Escherichia coli bearing Dr adhesins to the DAF/CD55 receptor is DAF density dependent and triggers internalization of E. coli via an endocytic pathway involving CD55, lipid rafts, and microtubules. Dr+ E. coli or Dr antigen may persist in vivo in the interstitium for several months. Further understanding of such processes should be instrumental in designing therapeutic strategies for multiple conditions involving DAF's protective or pathologic functions and tailoring host expression of DAF.

  10. Metabolism of steroid hormones by Taenia solium and Taenia crassiceps cysticerci.

    PubMed

    Jiménez, P; Valdez, R A; Romano, M C

    2006-06-01

    Previous in vitro experiments showed that both, Taenia crassiceps and Taenia solium cysticerci have the ability to metabolize exogenous androstenedione to testosterone. Here we evaluate on the capacity of both cysticerci to synthesize several sex steroid hormones, using different hormonal precursors. Experiments using thin layer chromatography (TLC) showed that both cysticerci were able to produce (3)H-hydroxyprogesterone, (3)H-androstenedione and (3)H-testosterone when (3)H-progesterone was used as the precursor. They also synthesized (3)H-androstenediol and (3)H-testosterone when (3)H-dehydroepiandrosterone was the precursor. In addition, both cysticerci interconverted (3)H-estradiol and (3)H-estrone. These results, strongly suggest the presence and activity of the Delta4 and Delta5 steroid pathway enzymes, 3beta-hydroxysteroid dehydrogenase/Delta(5-4) isomerase-like enzyme (3beta-HSD), that converts androstenediol into testosterone; and the 17beta-hydroxysteroid dehydrogenase that interconverts estradiol and estrone, in both types of cysticerci.

  11. In vivo absorption of steroidal hormones from smart polymer based delivery systems.

    PubMed

    Chen, Sibao; Pederson, Daniel; Oak, Mayura; Singh, Jagdish

    2010-08-01

    The purpose of this study was to develop smart polymer based controlled delivery systems to deliver steroidal hormones after single subcutaneous (s.c.) injection at predetermined rates over extended period of time. In vivo absorption and pharmacokinetics of levonorgestrel (LNG) and testosterone (TSN) were investigated from the thermosensitive and phase sensitive polymeric controlled delivery systems. A selective, reliable, and rapid method for determination of serum LNG concentration was developed using high-performance liquid chromatography-tandom mass spectrometry with atmospheric pressure chemical ionization interface (HPLC-MS-MS with APCI), while TSN in serum samples was detected and quantified by a competitive immunoassay. The delivery systems controlled the absorption of LNG in rabbits up to 6 weeks from thermosensitive and approximately 4 weeks from phase sensitive polymeric delivery systems. In vivo study of TSN delivery systems in castrated rabbits controlled the release of TSN for at least 2 months from both thermosensitive and phase sensitive polymers. Thermosensitive and phase sensitive polymer formulations significantly (p < 0.05) increased relative bioavailability of steroidal hormones compared to control. In conclusion, thermosensitive and phase sensitive polymer based delivery systems controlled the release in vivo in rabbits for longer duration after single s.c. injection. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  12. Intrinsic epigenetic factors cooperate with the steroid hormone ecdysone to govern dendrite pruning in Drosophila.

    PubMed

    Kirilly, Daniel; Wong, Jack Jing Lin; Lim, Edwin Kok Hao; Wang, Yan; Zhang, Heng; Wang, Cheng; Liao, Qiuming; Wang, Haifeng; Liou, Yih-Cherng; Wang, Hongyan; Yu, Fengwei

    2011-10-06

    Pruning that selectively removes unnecessary axons/dendrites is crucial for sculpting neural circuits during development. During Drosophila metamorphosis, dendritic arborization sensory neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone. However, it is unknown whether epigenetic factors are involved in dendrite pruning. Here, we analyzed 81 epigenetic factors, from which a Brahma (Brm)-containing chromatin remodeler and a histone acetyltransferase CREB-binding protein (CBP) were identified for their critical roles in initiating dendrite pruning. Brm and CBP specifically activate a key ecdysone response gene, sox14, but not EcR-B1. Furthermore, the HAT activity of CBP is important for sox14 expression and dendrite pruning. EcR-B1 associates with CBP in the presence of ecdysone, which is facilitated by Brm, resulting in local enrichment of an active chromatin mark H3K27Ac at the sox14 locus. Thus, specific intrinsic epigenetic factors cooperate with steroid hormones to activate selective transcriptional programs, thereby initiating neuronal remodeling.

  13. Pigments, Parasites and Personalitiy: Towards a Unifying Role for Steroid Hormones?

    PubMed Central

    Kittilsen, Silje; Johansen, Ida Beitnes; Braastad, Bjarne Olai; Øverli, Øyvind

    2012-01-01

    A surging interest in the evolution of consistent trait correlations has inspired research on pigment patterns as a correlate of behavioural syndromes, or “animal personalities”. Associations between pigmentation, physiology and health status are less investigated as potentially conserved trait clusters. In the current study, lice counts performed on farmed Atlantic salmon Salmo salar naturally infected with ectoparasitic sea lice Lepeophtheirus salmonis showed that individual fish with high incidence of black melanin-based skin spots harboured fewer female sea lice carrying egg sacs, compared to less pigmented fish. There was no significant association between pigmentation and lice at other developmental stages, suggesting that host factors associated with melanin-based pigmentation may modify ectoparasite development to a larger degree than settlement. In a subsequent laboratory experiment a strong negative correlation between skin spots and post-stress cortisol levels was revealed, with less pigmented individuals showing a more pronounced cortisol response to acute stress. The observation that lice prevalence was strongly increased on a fraction of sexually mature male salmon which occurred among the farmed fish further supports a role for steroid hormones as mediators of reduced parasite resistance. The data presented here propose steroid hormones as a proximate cause for the association between melanin-based pigmentation and parasites. Possible fundamental and applied implications are discussed. PMID:22493685

  14. Steroid hormone may modulate hepatic somatomedin C production in newborn calves.

    PubMed

    Coxam, V; Davicco, M J; Durand, D; Bauchart, D; Opmeer, F; Barlet, J P

    1990-01-01

    We have studied the possible influence of steroid hormones and a beta-agonist (clembuterol) on hepatic insulin-like growth factor 1 (IGF1) production in young calves. For this purpose nine 20- to 40-day-old Holstein X Friesian male calves were fitted with chronically indwelling catheters in hepatic and portal veins and hepatic artery. Estradiol induced a simultaneous increase in plasma growth hormone (GH nmol/l) and IGF1 (nmol/l) levels (0.35 +/- 0.05 vs. 0.10 +/- 0.01 in control calves; 9.5 +/- 1.0 vs. 5.9 +/- 0.5 in controls, respectively). In the same way, 90 min after starting testosterone treatment, plasma GH levels increased from 0.21 +/- 0.08 to 1.30 +/- 0.40 while plasma IGF1 concentrations began to rise only 240 min after starting infusion (8.4 +/- 1.0) to reach maximal values at 300 min (10.7 +/- 1.1). Cortisol and clembuterol did not significantly modify either plasma GH levels or plasma IGF1 concentrations. Our results indicate that in young calves gonadal steroids exert their anabolic action through GH and IGF1.

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

    PubMed Central

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

    2008-01-01

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

  16. Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer.

    PubMed

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

    2008-03-01

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

  17. Physiological and analytical validations of fecal steroid hormone measures in black howler monkeys.

    PubMed

    Rangel-Negrín, Ariadna; Flores-Escobar, Elizabeth; Chavira, Roberto; Canales-Espinosa, Domingo; Dias, Pedro Américo D

    2014-10-01

    The measurement of hormones in fecal samples allows for the noninvasive assessment of the endocrine status of free-ranging primates. However, procedures and techniques for hormone analysis in feces must be validated, both analytically and physiologically. Few studies have addressed the endocrinology of black howler monkeys (Alouatta pigra). Due to its conservation status, direct handling of individuals from this species and invasive sample collection are highly regulated, and therefore traditional methods for the validation of hormone assays, such as pharmacological challenges, are not allowed. As a consequence, sometimes studies of the fecal hormones of free-ranging black howler monkeys do not report physiological validations and therefore the biological reliability of such measurements cannot be assessed. In order to stimulate future research with this species, the present study aimed at providing methodological bases for fecal endocrine monitoring. Specifically, we compared the validity of two immunoassays (radioimmunoassays, RIA; solid-phase chemiluminescent enzyme immunoassay, SPCEI) performed with commercial kits to measure cortisol, testosterone, estradiol, and progesterone; and demonstrate how the physiological functions of these steroid hormones can be determined through non-pharmacological validations. We found no differences between the analytical validity of RIA and SPCEI assays to measure cortisol and testosterone, whereas for estradiol and progesterone RIA showed better results. Concerning the physiological validation of our assays, we demonstrated that: (1) comparisons between pre- and post-stress situations may be used to assess cortisol response, (2) comparisons between females and males may be used to assess variation in testosterone levels, and (3) comparisons between pregnant and non-pregnant females may be used to determine variation in estradiol and progesterone activity. The analytical and physiological validations that we performed

  18. Opioid modulation of prolactin secretion induced by stress during late pregnancy. Role of ovarian steroids.

    PubMed

    Valdez, Susana R; Pennacchio, Gisela E; Gamboa, Dante F; de Di Nasso, Elina G; Bregonzio, Claudia; Soaje, Marta

    2014-06-01

    The opioid system modulates prolactin release during late pregnancy. Its role and the participation of ovarian hormones in this modulation are explored in ether stress-induced prolactin release. Estrous, 3-day and 19-day pregnant rats were used. We administered the antagonist mifepristone (Mp) and tamoxifen to evaluate progesterone and estradiol action in naloxone (NAL, opioid antagonist) or saline treated rats. Ether stress had no effect on serum prolactin levels in controls but increased prolactin release in NAL-treated rats. Prolactin response to stress in NAL-treated rats was blocked by l-DOPA administration. Mp treatment on day 18 of pregnancy increased prolactin levels after stress without alterations by NAL. Tamoxifen on days 14 and 15 of pregnancy completely blocked Mp and NAL effects on prolactin release at late pregnancy. In contrast, stress significantly increased prolactin levels in estrous rats and pretreatment with NAL prevented this. On day 3 of pregnancy, at 6.00 p.m., stress and NAL treatment inhibited prolactin levels in saline-treated rat. No effect of stress or NAL administration was detected on day 3 of pregnancy at 9.00 a.m. icv administration of specific opioids antagonist, B-Funaltrexamine but not Nor-Binaltorphimine or Naltrindole, caused a significant increase in stress-induced prolactin release. Opioid system suppression of prolactin stress response during late pregnancy was observed only after progesterone withdrawal, involving a different opioid mechanism from its well-established stimulatory role. This mechanism acts through a mu opioid receptor and requires estrogen participation. The opioid system and progesterone may modulate stress-induced prolactin release, probably involving a putative prolactin-releasing factor. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  19. Quantitative analysis of steroid hormones in human hair using a column-switching LC-APCI-MS/MS assay.

    PubMed

    Gao, Wei; Stalder, Tobias; Foley, Paul; Rauh, Manfred; Deng, Huihua; Kirschbaum, Clemens

    2013-06-01

    The analysis of steroid hormones in hair is increasingly used in the field of stress-related research to obtain a retrospective index of integrated long-term hormone secretion. Here, most laboratories have so far relied on immunochemical assays originally developed for salivary analyses. Although these assays are fast and easy to perform, they have a reduced reliability and specificity due to cross-reactivity with other substances and are limited to the detection of one hormone at a time. Here, we report the development of a LC-MS/MS-based method for simultaneous identification of endogenous concentrations of seven steroid hormones (cortisol, cortisone, testosterone, progesterone, corticosterone, dehydroepiandrosterone (DHEA) and androstenedione) in human hair. Hair samples were washed with isopropanol and steroid hormones were extracted from 10mg whole, nonpulverized hair by methanol incubation. A column switching strategy for on-line solid phase extraction (SPE) was applied, followed by analyte detection on an AB Sciex API 5000 QTrap mass spectrometer. Results indicated linearity of the method for all steroids over ranges of 0.09-90pg/mg (0.9-900pg/mg for DHEA) with correlation coefficients ranging between 0.9995 and 0.9999. Intra- and inter-assay coefficients of variation were between 3.7 and 9.1%. The limits of quantification (LOQ) were below (or equal to) 0.1pg/mg for all steroids, except of DHEA for which the LOQ was 0.9pg/mg. An analysis of 30 natural hair samples (15 men/15 women) using this method confirmed that all steroid hormones could be quantified at endogenous levels in each individual. In addition, the use of whole hair samples and on-line SPE resulted in a significant reduction in sample throughput times, increasing the applicability of this method for research questions where a larger number of samples needs to be processed. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Endometrial prostaglandin synthases, ovarian steroids, and oxytocin receptors in mares with oxytocin-induced luteal maintenance.

    PubMed

    Rebordão, Maria R; Galvão, António; Pinto-Bravo, Pedro; Pinheiro, Joana; Gamboa, Sandra; Silva, Elisabete; Mateus, Luísa; Ferreira-Dias, Graça

    2017-01-01

    epithelium. Also, ESR2 may attenuate the transcriptional activity of ESR1 in mare endometrium. This study offers new knowledge on the endometrial expression of ovarian steroids and OXT receptors in OXT pharmacologically induced luteal maintenance in the mare. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Steroid hormone profiles in women treated with aminoglutethimide for metastatic carcinoma of the breast.

    PubMed

    Samojlik, E; Santen, R J; Kirschner, M A; Ertel, N H

    1982-08-01

    Recent evidence suggests that aminoglutethimide (AG), a known inhibitor of adrenal steroidogenesis, is a potent blocker of aromatase and thus of estrogen production. These properties of AG have been exploited clinically to reduce the biosynthesis of adrenal estrogen precursors and extraglandular estrogen production in postmenopausal women with metastatic breast carcinoma. In this study, we have explored the effects of AG on a variety of steroids, including delta 5-C19 and -C21 compounds and delta 4-C19 and -C21 steroids as well as plasma and urinary estrogens in a series of postmenopausal women with breast cancer treated for 2 to 26 weeks. Plasma concentrations of delta 5-C21 and -C19 compounds were reduced 3- to 5-fold during AG therapy and remained suppressed over the duration of the study. By contrast, the delta 4-steroids such as progesterone, androstenedione, and 17 alpha- hydroxyprogesterone rose 2- to 10-fold during the initial 2 weeks of AG treatment and then fell back to starting levels or were suppressed. Plasma levels of the potent androgens testosterone and dihydrotestosterone were relatively preserved during AG therapy. The possible contribution of the postmenopausal ovary to the above hormone levels during AG therapy was examined by comparing steroid values from surgically castrated and spontaneously menopausal women. No statistically significant differences between the two groups were observed. In response to AG therapy, plasma levels of estrone and estrone sulfate were decreased 61 to 72%, and urinary estrone similarly fell 85% over the 12-week period. Estradiol concentrations in urine and plasma were similarly reduced 40 to 66% from basal values over this same period.

  2. Mitochondria and the insect steroid hormone receptor (EcR): A complex relationship.

    PubMed

    Vafopoulou, Xanthe; Steel, Colin G H

    2016-10-01

    The actions of the insect steroid molting hormones, ecdysteroids, on the genome of target cells has been well studied, but little is known of their extranuclear actions. We previously showed in Rhodnius prolixus that much of the ecdysteroid receptor (EcR) resides in the cytoplasm of various cell types and undergoes shuttling between nucleus and cytoplasm with circadian periodicity, possibly using microtubules as tracks for translocation to the nucleus. Here we report that cytoplasmic EcR appears to be also involved in extranuclear actions of ecdysteroids by association with the mitochondria. Western blots of subcellular fractions of brain lysates revealed that EcR is localized in the mitochondrial fraction, indicating an intimate association of EcR with mitochondria. Confocal laser microscopy and immunohistochemistry using anti-EcR revealed abundant co-localization of EcR with mitochondria in brain neurons and their axons, especially intense in the subplasmalemmal region, raising the possibility of EcR involvement in mitochondrial functions in subplasmalemmal microdomains. When mitochondria are dispersed by disruption of microtubules with colchicine, EcR remains associated with mitochondria showing strong receptor association with mitochondria. Treatment in vitro with ecdysteroids of brains of developmentally arrested R. prolixus (containing neither ecdysteroids nor EcR) induces EcR and abundant co-localization with mitochondria in neurons, concurrently with a sharp increase of the mitochondrial protein COX 1, suggesting involvement of EcR in mitochondrial function. These findings align EcR with various vertebrate steroid receptors, where actions of steroid receptors on mitochondria are widely known and suggest that steroid receptors across distant phyla share similar functional attributes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo

    SciTech Connect

    Chaudhuri, G.; Steingold, K.A.; Pardridge, W.M.; Judd, H.L. )

    1988-01-01

    The metabolic clearance rate (MCR) of gonadal or adrenal steroid hormones in rabbits often does not bear the expected inverse relationship with hormone binding to testosterone-binding globulin (TeBG) or corticosteroid-binding globulin (CBG). This suggests TeBG or CBG may not impede steroid hormone delivery to tissues. The effects of rabbit plasma proteins on the influxes of {sup 3}H-labeled steroids from the circulation into the rabbit uterus were measured in vivo using a tissue sampling single-injection technique. In the absence of plasma proteins, estradiol (E{sub 2}) and testosterone (T) were freely diffusible through the uterine microvasculature (i.e., extraction >80%). The extractions of dihydrostestosterone (DHT) and corticosterone (B) ranged from 60 to 72%, while that of cortisol (F) was reduced at 40%. Rabbit serum exerted no inhibition of the influxes of the steroids tested. The influxes of T and B greatly exceeded the rates that would be expected if only the free and albumin-bound fractions estimated in vitro were diffusible in vivo. However, the extraction of ({sup 3}H)corticosteroid-binding globulin or bovine ({sup 3}H)albumin were low, consistent with little, if any, extravascular uptake of the plasma proteins. The results indicate both albumin-bound and globulin-bound steroid hormone are available for transport into the uterus in the rabbit in vivo without significant exodus of the plasma protein, per se.

  4. Consequences of elevated luteinizing hormone on diverse physiological systems: use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology.

    PubMed

    Mann, Rachel J; Keri, Ruth A; Nilson, John H

    2003-01-01

    Chronically elevated luteinizing hormone (LH) induces significant pathology in the LHbetaCTP transgenic mouse model, which uses the bovine gonadotropin alpha (alpha)-subunit promoter to direct transgene expression specifically to gonadotropes in the anterior pituitary. Previously, it was shown that female LHbetaCTP mice are infertile due to anovulation, develop granulosa cell tumors, and undergo precocious puberty from elevated LH and steroid hormones that fail to completely repress the alpha-subunit promoter. This chapter will discuss recent studies that further elucidate the impact of chronically elevated LH on diverse physiological systems. Granulosa cell tumors induced by elevated LH are strain dependent and prevented when transgenics are treated with human chorionic gonadotropin (hCG) surges. A granulosa cell tumor-associated transcriptome is generated, revealing several possible gene candidates for ovarian granulosa cell tumorigenesis. Primordial follicles in LHbetaCTP transgenics become depleted and oocytes exhibit increased rates of meiotic segregation defects, although meiotic competency is acquired normally. Anovulation can be rescued in transgenics by superovulation, though pregnancy fails at midgestation due to maternal factors. Uterine receptivity defects prevent implantation of normal embryos following induction of pseuodpregnancy. Transgenics develop Cushing-like adrenocortical hyperfunction with increased corticosterone production following induction of adrenal LH receptor expression. Elevated LH acts as a tumor promoter in the gonads and the adrenal gland, when expressed in conjunction with the inhibin-alpha SV40 transgene. Finally, chronic elevated LH promotes mammary tumorigenesis. The understanding of multiple clinical pathologies--including ovarian cancer, perimenopausal reproductive aging, premature ovarian failure, polycystic ovarian syndrome, Cushing's syndrome, and breast cancer--may be enhanced through further study of this useful

  5. Cardioprotective effects of ovarian hormones and the HERS in perspective.

    PubMed

    Rosano, G M; Graziottin, A; Fini, M

    2000-04-01

    The increased population of women in menopause living in the industrialized countries is associated with an increase of diseases which are dependent or facilitated by a state of estrogen deficiency such as cardiovascular and cerebrovascular diseases. Several studies have shown that estrogen replacement therapy reduces the occurrence of coronary and may be of cerebrovascular disease by nearly 50% in treated women compared to non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls as well as a direct effect on the vessel wall. Progestins may, in some cases, counteract the beneficial effect of estrogens upon cardiovascular functions. More androgenic progestins may have a detrimental effect upon vascular reactivity while less androgenic progestins seem not to reduce the beneficial effect of estrogens. Of interest, continuous combined administration of hormone replacement therapy seem to be preferable for women with coronary artery disease or for those with increased cardiovascular risk. Case-control and cohort studies have shown that estrogen progestin therapy is associated with a significant reduction of cardiovascular mortality and morbidity. The HERS study has added critical data regarding the cardioprotective effect of hormone replacement therapy in elderly women with proven coronary artery disease. Because of the several methodological and statistical flaws of the HERS study, further studies are warranted to evaluate the effect of hormone replacement therapy on cardiovascular prognosis. Large scale randomized studies will evaluate the effect of estrogen and estrogen-progestin replacement therapy upon cardiovascular events in menopausal women. Until completion of these studies hormone replacement therapy in women with increased cardiovascular risk should be seen with no enthusiasm but also with no

  6. Simultaneous profiling of 17 steroid hormones for the evaluation of endocrine-disrupting chemicals in H295R cells.

    PubMed

    Jumhawan, Udi; Yamashita, Toshiyuki; Ishida, Kazuya; Fukusaki, Eiichiro; Bamba, Takeshi

    2017-01-01

    There is urgent need to develop a new protocol for the evaluation of chemical substances to potentially interact with the endocrine system and induce numerous pathological issues. The recently validated in vitro screening assay is limited on monitoring two steroid hormones. Methodology & results: The H295R model cell was exposed to seven endocrine disrupting chemicals (EDCs). The levels of 17 steroid hormones in cell extracts were subsequently determined by a quantitative targeted GC/MS/MS method. Through wide coverage, this system managed to capture the effects of exposure to increasing EDCs concentrations in the entire steroidogenic pathways. The developed approach could be beneficial for the mechanistic investigation of EDCs.

  7. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas

    PubMed Central

    Abedelmalek, Salma; Chtourou, Hamdi; Souissi, Nizar; Tabka, Zouhair

    2015-01-01

    The aim of this study was to evaluate the effect of caloric restriction on the immune and hormonal responses during exercise in judo athletes. In a randomised order, 11 male judokas (age: 20.45 ± 0.51; height: 1.71 ± 0.3 m; and body weight: 75.9 ± 3.1 kg) participate in this study during a period of weight maintenance (baseline) and after 7 days of caloric restriction (CR). All subjects performed the Special Judo Fitness Test (SJFT) during the two conditions. Values for nutrient intakes were obtained from a 7 d food record kept during a period of weight maintenance and after a 7-day food restriction (−5~6 MJ/day). Our results showed that CR resulted in significant decreases in body weight (P < 0.05) and performance (P < 0.05). However, heart rate and SJFT index (P < 0.05) increase significantly during CR in comparison to baseline. Moreover, exercise leads to a significant increase in testosterone, cortisol, growth hormone (GH), leukocytes, neutrophils, TNF-α, and IL-6, in both CR and baseline conditions. Compared to baseline, TNF-α and IL-6 were significantly higher during CR condition (P < 0.05). Additionally, CR leads to an increase in cortisol and GH (P < 0.05) and a decrease in testosterone concentrations (P < 0.05). PMID:26075039

  8. Markers of Ovarian Cancer Using a Glycoprotein/Antibody Array

    DTIC Science & Technology

    2014-05-01

    ovarian cancer are desperately needed. In addition, a number of benign conditions, including pregnancy , endometriosis, normal menstruation, and pelvic...CBG is a plasma glycoprotein that binds steroid hormones such as progesterone and cortisol, which have been implicated in the progression of ovarian...Welander, C. E. The effects of estrogen, progesterone , and tamoxifen alone and in combination with cytotoxic agents against human ovarian carcinoma in

  9. FLASH interacts with p160 coactivator subtypes and differentially suppresses transcriptional activity of steroid hormone receptors.

    PubMed

    Kino, Tomoshige; Ichijo, Takamasa; Chrousos, George P

    2004-12-01

    We previously reported that tumor necrosis factor alpha receptor- and Fas-associated FLASH interacts with one of the p160 nuclear receptor coactivators, glucocorticoid receptor-interacting protein (GRIP) 1, at its nuclear receptor-binding (NRB) domain, and that inhibits the transcriptional activity of the glucocorticoid receptor (GR) by interfering with association of GR and GRIP1. Here, we further examined the specificity of FLASH suppressive effect and the physical/functional interactions between this protein and two other p160 family subtypes. The suppressive effect of FLASH on GR transactivation was observed in several cell lines and on the chromatin-integrated mouse mammary tumor virus (MMTV) promoter. FLASH strongly interacted with the NRB domain of the thyroid hormone receptor activator molecule (TRAM) 1, a member of the steroid hormone receptor coactivator (SRC) 3/nuclear receptor coactivator (N-CoA) 3 subtypes, as well as with SRC2/N-CoA2 p160 coactivator GRIP1, while its interaction with SRC1a, one of the SRC1/N-CoA1 proteins, was faint in yeast two-hybrid assays. Accordingly, FLASH strongly suppressed TRAM1- and GRIP1-induced enhancement of GR-stimulated transactivation of the MMTV promoter in HCT116 cells, while it did not affect SRC1a-induced potentiation of transcription. Furthermore, FL