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Sample records for ovarian steroid hormones

  1. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival12

    PubMed Central

    Jönsson, Jenny-Maria; Skovbjerg Arildsen, Nicolai; Malander, Susanne; Måsbäck, Anna; Hartman, Linda; Nilbert, Mef; Hedenfalk, Ingrid

    2015-01-01

    Background and Aims: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival in epithelial ovarian cancer. Methods: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer in an independent data set, hypothesizing that the expression levels and prognostic impact may differ between the subtypes. Results: Expression of PR or AR protein was associated with improved 5-year progression-free (P = .001 for both) and overall survival (P < .001 for both, log-rank test). ERα and ERβ did not provide prognostic information. Patients whose tumors coexpressed PR and AR had the most favorable prognosis, and this effect was retained in multivariable analyses. Analyses of the corresponding genes using an independent data set revealed differences among the molecular subtypes, but no clear relationship between high coexpression of PGR and AR and prognosis. Conclusions: A favorable outcome was seen for patients whose tumors coexpressed PR and AR. Gene expression data suggested variable effects in the different molecular subtypes. These findings demonstrate a prognostic role for PR and AR in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer. PMID:26500033

  2. 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. PMID:26873134

  3. Ovarian steroid hormone-regulated uterine remodeling occurs independently of macrophages in mice.

    PubMed

    Care, Alison S; Ingman, Wendy V; Moldenhauer, Lachlan M; Jasper, Melinda J; Robertson, Sarah A

    2014-09-01

    Macrophages are abundant in the uterine stroma and are intimately juxtaposed with other cell lineages comprising the uterine epithelial and stromal compartments. We postulated that macrophages may participate in mediating or amplifying the effects of ovarian steroid hormones to facilitate the uterine remodeling that is a characteristic feature of every estrus cycle and is essential for pregnancy. Using the Cd11b-Dtr transgenic mouse model with an ovariectomy and hormone replacement strategy, we depleted macrophages to determine their role in hormone-driven proliferation of uterine epithelial and stromal cells and uterine vascular development. Following diphtheria toxin (DT) administration, approximately 85% of EMR1-positive (EMR1⁺) macrophages, as well as 70% of CD11C⁺ dendritic cells, were depleted from Cd11b-Dtr mice. There was no change in bromodeoxyuridine incorporation into epithelial cells induced to proliferate by administration of 17beta-estradiol (E2) to ovariectomized mice or into stromal cells induced to proliferate in response to E2 and progesterone (P4), and the resulting sizes and structures of the luminal epithelial and stromal cell compartments were not altered compared with those of leukocyte replete controls. Depletion of CD11B⁺ myeloid cells failed to alter the density or pattern of distribution of uterine blood vessels, as identified by staining PECAM1-positive endothelial cells in the uterine stroma of E2- or E2 combined with P4 (E2P4)-treated ovariectomized mice. These experiments support the interpretation that macrophages are dispensable to regulation of proliferative events induced by steroid hormones in the cycling and early pregnant mouse uterus to establish the epithelial, stromal, and vascular architecture which is critical for normal reproductive competence. PMID:25061095

  4. 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. PMID:26819477

  5. Postnatal ovarian development and its relationship with steroid hormone receptors in JiNing Grey goats.

    PubMed

    Shi, YunZhi; Wang, ShuYing; Bai, Shu; Huang, LiBo; Hou, YanMeng

    2015-03-01

    In this work, we examined the ovarian development and its relationship with steroid hormone receptors levels and the precocious puberty in JiNing Gray goats by using optical microscopy, immunohistochemistry, quantitative real-time RT-PCR (qPCR) and Western blotting. We found that in the ovaries of neonatal kids, high level of receptors for estrogen (ERα and ERβ) and progesterone (PR) and their mRNA were observed along with growing follicles. From 0 to 30 days of age, the weight and volume of ovaries increased significantly and the boundary between the inner and outer cortex disappeared, while the expression of ERα, ERβ and PR and their mRNA decreased sharply. When 60 days old, the animals began to ovulate; the expression of ERα, ERβ and PR and their mRNA significantly increased, and the animals reached puberty. On day 90, the animals manifested sexual maturity with biggest mature follicles 6.18mm in diameter, the expression of ERβ and PR protein and their mRNA was maintained at a high level, with decreased expression of ERα and its mRNA. Before puberty, the expression of ovarian ERα (prepubertal dominant receptor) and it's mRNA was significantly higher than that of ERβ (dominant receptor after sexual maturity). The results showed that JiNing Grey goats' ovaries had fast development and early maturation, and ERα, ERβ and PR protein and mRNA expression in the ovary had distinct specificity for time and space, which may be closely related to the strain's progenitive characteristics. PMID:25616699

  6. 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.

  7. Influence of triiodothyronine (T(3)) on secretion of steroids and thyroid hormone receptor expression in chicken ovarian follicles.

    PubMed

    Sechman, A; Pawlowska, K; Rzasa, J

    2009-08-01

    The present study was designed to (1) assess the role of triiodothyronine (T(3)) with regard to in vitro steroid hormone secretion by chicken ovarian follicles; (2) determine whether T(3) influences the in vivo function of the pituitary-ovarian axis in the hen; and (3) detect expression of thyroid hormone receptor (TR) mRNA in chicken ovarian follicles. In the first experiment, laying hens were decapitated 22.5h before ovulation. White prehierarchical follicles (1-8mm) and fragments of theca and granulosa layers of the 3 largest yellow preovulatory follicles F3-F1 (22-35mm) were incubated in a medium supplemented with T(3) (0, 0.1, 1, 10, 100, or 1000ng/mL) or ovine luteinizing hormone (LH) (10ng/mL) in combination with doses of T(3) (1, 10, and 100ng/mL). Triiodothyronine decreased basal and LH-stimulated estradiol secretion by white follicles and the theca layer of all preovulatory follicles. On the other hand, it increased progesterone secretion by F2 and F1 follicles. In the second experiment, hens were injected 1h after ovulation with saline (control) or T(3) (10microg/100g body weight, intraperitoneally). Results indicated that exogenous T(3) decreased plasma concentrations of LH and estradiol and increased plasma concentrations of progesterone. In the third experiment, using reverse transcription polymerase chain reaction (RT-PCR) analysis, expression of thyroid hormone receptor (TRalpha and TRbeta0), mRNA was detected in all of the ovarian compartments. The expression of TRalpha mRNA was relatively greater in comparison with TRbeta0. There were no differences between white ovarian follicles in the expression of TRalpha and TRbeta0 mRNA. A considerably higher TRalpha and lower TRbeta0 expression was detected in the granulosa layer of preovulatory follicles in comparison with the theca layer. In conclusion, the data indicate that thyroid hormones acting via nuclear receptors are involved in regulation of the pituitary-ovarian axis and processes associated

  8. 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. PMID:8345070

  9. 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

  10. Reproductive steroid hormones and ovarian activity in felids of the Leopardus genus.

    PubMed

    Moreira, N.; Monteiro-Filho, E.L.A.; Moraes, W.; Swanson, W.F.; Graham, L.H.; Pasquali, O.L.; Gomes, M.L.F.; Morais, R.N.; Wildt, D.E.; Brown, J.L.

    2001-01-01

    Reproductive endocrine patterns were characterized in female ocelots (Leopardus pardalis; n = 3), tigrinas (Leopardus tigrinus; n = 2), and margays (Leopardus wiedii; n = 2) housed in captivity in southern Brazil. Females were maintained as singletons and exposed to natural fluctuations in photoperiod. Cyclic changes in ovarian steroids were monitored by analyzing estrogen and progestogen metabolites in fecal samples collected five times weekly for 14 to 18 months. Based on intervals between fecal estrogen peaks, mean (+/- SEM) duration of the estrous cycle was 18.4 +/- 1.6 days for the ocelots (range, 7-31 days; n = 75 cycles), 16.7 +/- 1.3 days for the tigrinas (range, 11-27 days; n = 23 cycles), and 17.6 +/- 1.5 days for the margays (range, 11-25 days; n = 32 cycles). Fecal progestogen analyses combined with two laparoscopic observations of the ovaries confirmed that ocelots and tigrinas did not ovulate spontaneously. In contrast, non-mating-induced luteal phases of 40.1 +/- 6.3 days in duration (range, 30-60 days) were observed frequently in both margays. There was no evidence of gonadal seasonality in margays in either follicular or luteal activity. In ocelots, cyclic changes in estrogen excretion were observed during each month of the year; however, only one female cycled continuously. In the other two ocelots, periods of acyclicity of several months' duration were observed. It was not possible to conclude whether tigrinas were aseasonal because estrous cyclicity was observed in only one of two individuals. In the female that cycled, a 3-month period of acyclicity was observed in the late fall/early winter. These data demonstrate similarities among three felid species of the genus Leopardus, including evidence they are polyestrous but experience unexplained periods of ovarian inactivity. Only the margays differed by exhibiting occasional spontaneous, non-mating-induced ovulations. Historically, these species have not bred well in captivity. However, it is

  11. Intrafollicular steroids and anti-mullerian hormone during normal and cystic ovarian follicular development in the cow.

    PubMed

    Monniaux, Danielle; Clemente, Nathalie di; Touzé, Jean-Luc; Belville, Corinne; Rico, Charlène; Bontoux, Martine; Picard, Jean-Yves; Fabre, Stéphane

    2008-08-01

    Development of follicular cysts is a frequent ovarian dysfunction in cattle. Functional changes that precede cyst formation are unknown, but a role for anti-Müllerian hormone (AMH) in the development of follicular cysts has been suggested in humans. This study aimed to characterize intrafollicular steroids and AMH during follicular growth in a strain of beef cows exhibiting a high incidence of occurrence of follicular cysts. Normal follicular growth and cyst development were assessed by ovarian ultrasonography scanning during the 8 days before slaughtering. Experimental regression of cysts was followed by rapid growth of follicles that reached the size of cysts within 3-5 days. These young cysts exhibited higher intrafollicular concentrations of testosterone, estradiol-17beta, and progesterone than large early dominant follicles did in normal ovaries, but they exhibited similar concentrations of AMH. Later-stage cysts were characterized by hypertrophy of theca interna cells, high intrafollicular progesterone concentration, and high steroidogenic acute regulatory protein mRNA expression in granulosa cells. Progesterone and AMH concentrations in the largest follicles (> or =10 mm) and cysts were negatively correlated (r = -0.45, P < 0.01). Smaller follicles (<10 mm) exhibited higher intrafollicular testosterone and estradiol-17beta concentrations in ovaries with cysts compared to normal ovaries. During follicular growth, AMH concentration dropped in follicles larger than 5 mm in diameter and in a similar way in ovaries with and without cysts. In conclusion, enhanced growth and steroidogenesis in antral follicles <10 mm preceded cyst formation in cow ovaries. Intrafollicular AMH was not a marker of cystic development in the cow, but low AMH concentrations in cysts were associated with luteinization. PMID:18448844

  12. The effect of ovariectomy and ovarian steroid treatment on growth hormone and insulin-like growth factor-I levels in the rat femur.

    PubMed

    Suliman, I A; El-Bakri, N K; Adem, A; Mustafa, A; Lindgren, J U

    2001-11-01

    Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF-I by ovarian steroids is well known, however, their effect on local GH and IGF-I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF-I levels as well as on bone density in the rat. Nine month-old rats were ovariectomized (OVX) or sham-operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17beta-estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF-I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF-I levels. Estradiol treatment increased femur GH and IGF-I levels compared to SHAM rats. Progesterone restored GH and increased IGF-I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF-I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone. PMID:11780998

  13. Alteration in localization of steroid hormone receptors and coregulatory proteins in follicles from cows with induced ovarian follicular cysts.

    PubMed

    Salvetti, Natalia R; Alfaro, Natalia S; Velázquez, Melisa M L; Amweg, Ayelen N; Matiller, Valentina; Díaz, Pablo U; Ortega, Hugo H

    2012-12-01

    Cystic ovarian disease (COD) is an important cause of infertility in cattle. The altered follicular dynamics and cellular differentiation observed in COD may be mediated through a disruption of the expression of steroid receptors and their associated transcriptional cofactors. The aim of this study was to determine the protein expression profiles of ESR1, ESR2, PGR, AR, NCOA3, NCOR2, and PHB2 (REA) in ovarian follicles in an experimental model of COD induced by the administration of ACTH. Ovaries were collected and follicles were dissected from heifers during the follicular phase (control) or from heifers treated with ACTH to induce the formation of ovarian follicular cysts. Ovaries were fixed, sectioned, and stained immunohistochemically for steroid receptors and the associated transcription factors. The relative expression of ESR1 was similar in follicular cysts and in tertiary follicles from both control and cystic cows and was significantly higher than in secondary follicles. The expression of ESR2 in the granulosa was higher in cystic follicles. No differences were seen for PGR. The expression of androgen receptor was significantly increased in tertiary follicles with lower immunostaining in cysts. The expression of NCOA3 was observed in the granulosa and theca with a significantly increased expression in the theca interna of cystic follicles. The highest levels of NCOR2 expression in granulosa, theca interna, and theca externa were observed in cysts. In granulosa cells, NCOR2 levels increase progressively as follicles mature and the treatment had no effect. In summary, ovaries from animals with induced COD exhibited altered steroid receptor expression compared with normal animals, as well as changes in the expression of their regulators. It is reasonable to suggest that in conditions characterized by altered ovulation and follicular persistence, such as COD, changes in the intra-ovarian expression of these proteins could play a role in their pathogenesis

  14. Cadmium exerts toxic effects on ovarian steroid hormone release in rats.

    PubMed

    Zhang, Wenchang; Pang, Fen; Huang, Yaqing; Yan, Ping; Lin, Wei

    2008-11-10

    This study examined the toxic effects of cadmium on the function of sexual hormone release in the ovaries of rats and the mechanism of this dysregulation. In vivo, adult female rats were randomly assigned to four groups based on weight. Cadmium was given ip 5 days/week for 6 weeks at doses of 1.0, 0.5, 0.25 and 0mg/kg. Following euthanasia, the ovaries were removed and placed into culture medium for 3h. The levels of progesterone (P) and estadiol (E) in the culture medium were then measured by radioimmunoassay. In vitro studies were done using the ovaries of adult rats in different stages of estrous (proestrus, estrus, metestrus and diestrus). Individual ovaries were collected, placed into culture medium and exposed to 0, 0.1, 1, or 2mM of CdCl(2) for 3h, at which time the levels of P and E in the ovary culture serum were determined by radioimmunoassay. The in vivo results showed that the levels of P and E in the ovary culture serum (5.3+/-1.4 ng/ml and 1.4+/-0.4 pg/ml, respectively) decreased significantly in the high dose group compared to the control (9.2+/-0.9 ng/ml and 3.9+/-0.7 pg/ml, respectively). In vitro, there were significant differences in P and E in between the different concentrations of cadmium and also between the different stages of the estrous cycle. These data suggest that cadmium can inhibit P and E release in ovaries. This may represent an important mechanism of endocrine disruption. PMID:18708132

  15. Steroid hormones, steroid receptors, and breast cancer stem cells.

    PubMed

    Finlay-Schultz, Jessica; Sartorius, Carol A

    2015-06-01

    The ovarian hormones progesterone and estrogen play important roles in breast cancer etiology, proliferation, and treatment. Androgens may also contribute to breast cancer risk and progression. In recent years, significant advances have been made in defining the roles of these steroid hormones in stem cell homeostasis in the breast. Stem cells are potential origins of breast cancer and may dictate tumor phenotype. At least a portion of breast cancers are proposed to be driven by cancer stem cells (CSCs), cells that mimic the self-renewing and repopulating properties of normal stem cells, and can confer drug resistance. Progesterone has been identified as the critical hormone regulating normal murine mammary stem cell (MaSC) populations and normal human breast stem cells. Synthetic progestins increase human breast cancer risk; one theory speculates that this occurs through increased stem cells. Progesterone treatment also increases breast CSCs in established breast cancer cell lines. This is mediated in part through progesterone regulation of transcription factors, signal transduction pathways, and microRNAs. There is also emerging evidence that estrogens and androgens can regulate breast CSC numbers. The evolving concept that a breast CSC phenotype is dynamic and can be influenced by cell signaling and external cues emphasizes that steroid hormones could be crucial players in controlling CSC number and function. Here we review recent studies on steroid hormone regulation of breast CSCs, and discuss mechanisms by which this occurs. PMID:26265122

  16. 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. PMID:26907940

  17. 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. PMID:18638025

  18. 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

  19. 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

  20. T-2 toxin regulates steroid hormone secretion of rat ovarian granulosa cells through cAMP-PKA pathway.

    PubMed

    Wu, Jing; Tu, Di; Yuan, Li-Yun; Yi, Jin-e; Tian, Yanan

    2015-02-01

    T-2 toxin is a secondary metabolite produced by Fusarium genus and is a common contaminant in food and feedstuffs of cereal origin. In porcine granulosa cells(GC), T-2 toxin has been shown to inhibit the steroidogenesis; however, the mechanism has not been well understood. Gonadotropin-stimulated steroidogenesis is regulated by the cAMP-PKA pathway. In this study, we investigated potential mechanisms for T-2 toxin-induced reproductive toxicity focusing on the critical steps of the cAMP-PKA pathway affected by T-2 toxin. We first analyzed the effects of T-2 toxin on progesterone and estrogen production in rat granulosa cells. For this purpose the granulosa cells were cultured for 48 h in 10% fetal bovine serum-containing medium followed by 24h in serum-free medium containing FSH (10 ng/ml) and androstenedione (3 ng/ml), both are required for normal steroidogenesis. Treatment of these cells with T-2 toxin dose-dependently inhibited the growth of cells and the steroid hormone production. Cellular cyclic AMP levels were dose-dependently inhibited by T-2 toxin (0, 1, 10 and 100 nM, 24 h). Furthermore, we found that although the induction of progesterone by 8-Br-cAMP (a FSH mimetic) and 22R-HC (substrate for progesterone) could both be inhibited by T-2 toxin treatment, the T-2-imposed inhibitory effects could be reversed by increasing doses of 22R-HC, while increasing 8-Br-cAMP had no effects, suggesting that T2 toxin targeted at distinct mechanisms. cAMP-stimulated steroidogenic acute regulatory protein (StAR) is a rate limiting protein in progesterone synthesis. Exposure to T2 toxin caused significant suppression of StAR expression as determined by Western blotting and semi-quantitative RT-PCR suggesting StAR is a sensitive target for T-2 toxin. Taken together, our results strongly suggest that T2 toxin inhibits steroidogenesis by suppressing cAMP-PKA pathway and StAR is a target for T-2-toxin. The antisteroidogenesis effects were observable at low T-2 dose (1 ng

  1. Effect of nutrition on plasma lipid profile and mRNA levels of ovarian genes involved in steroid hormone synthesis in Hu sheep during luteal phase.

    PubMed

    Ying, S J; Xiao, S H; Wang, C L; Zhong, B S; Zhang, G M; Wang, Z Y; He, D Y; Ding, X L; Xing, H J; Wang, F

    2013-11-01

    Ovarian steroid hormones regulate follicular growth and atresia. This study aims to determine whether key ovarian sterol-regulatory genes are differentially expressed in Hu sheep under different short-term nutritional regimens. Estrus was synchronized using intravaginal progestagen sponges. The ewes were assigned randomly to 3 groups. On d 6 to 12 of their estrous cycle, the control (CON) group received a maintenance diet (1.0×M), the supplemented (SUP) group received 1.5×M, and the restricted (R) group received 0.5×M. On d 7 to 12, blood samples were taken. The sheep were slaughtered at the end of the treatment, and their organs and ovaries were collected. The plasma concentrations of urea (P<0.01), total cholesterol (P<0.01), low-density lipoprotein cholesterol (P<0.01), NEFA (P<0.01), FSH (P<0.05), and estradiol (P<0.05) increased with decreasing dietary intake, whereas plasma triglyceride (P<0.01) and triiodothyronine (T3) concentrations decreased (P<0.05). The ewes in the R group had higher spleen weight and percentage of spleen to BW and lower liver and small intestine weights and percentage of liver/stomach to BW than the SUP group ewes (P<0.05). Nutritional restriction decreased the cytochrome p450 (CYP17A1) and estrogen receptor 1 (ESR1) mRNA expression (P<0.05) and increased the cytochrome p450 aromatase (CYP19A1) mRNA expression (P<0.05) in follicles>2.5 mm. Follicle size affected the mRNA expression of very low density lipoprotein receptor (VLDLR), estrogen receptor 2 (ESR2), FSH receptor (FSHR), CYP17A1, and CYP19A1 (P<0.05). In conclusion, we suggest that a potential mechanism by which short-term negative energy balance inhibits follicular growth may involve responses to disrupted reproductive hormone concentrations and influenced the intrafollicular expression of CYP17A1, CYP19A1, and ESR1. This result may be due to increased plasma urea and lipid concentrations. PMID:24045481

  2. Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.

    PubMed

    Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja; Jensen, Peter; Knudsen, Gitte M; Frokjaer, Vibe G; Siebner, Hartwig R

    2016-03-01

    Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women. PMID:26245498

  3. 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

  4. 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. PMID:27288742

  5. Neuroprotection against excitotoxic brain injury in mice after ovarian steroid depletion.

    PubMed

    Schauwecker, P Elyse; Wood, Ruth I; Lorenzana, Ariana

    2009-04-10

    Ovarian steroid hormones influence not only seizure phenomena, but also the neuronal cell death that follows. In the present study, we applied two models of ovarian steroid loss, ovariectomy and chemically-induced ovarian failure, to evaluate kainate-induced seizure activity and the susceptibility of hippocampal neurons to seizure-induced neurodegeneration. Young adult female FVB/NJ mice were ovariectomized with (OVX+E, n=6) or without (OVX, n=8) estrogen replacement. A separate group of females received the ovotoxin, 4-vinylcyclohexene diepoxide (VCD, n=8) to deplete ovarian follicles. Mice underwent kainate-induced status epilepticus and were evaluated for seizure activity (3 h) and delayed hippocampal neuronal injury (7 days). While there were no differences in latency or duration of severe seizures among control, OVX and VCD-treated mice, OVX+E mice exhibited seizures of a significantly longer duration. However, both VCD-induced ovarian failure and OVX led to a dramatic reduction in the extent of excitotoxic cell death, with slightly greater effects observed in VCD-treated mice. Estradiol administration to OVX mice also exerted a significant neuroprotective effect against kainate-induced cell death. These results support and extend earlier findings suggesting that the hormonal milieu may have differential effects on seizure susceptibility that are separate and distinct from those influencing hippocampal neuronal vulnerability. Collectively, these findings highlight the complex interactions among the loss of ovarian steroid hormones, estrogen replacement, seizures, and seizure-induced cell death. PMID:19236850

  6. 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. PMID:22951117

  7. 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.

  8. Cholesterol side-chain cleavage cytochrome P450 and 3beta-hydroxysteroid dehydrogenase expression and the concentrations of steroid hormones in the follicular fluids of different phenotypes of healthy and atretic bovine ovarian follicles.

    PubMed

    Irving-Rodgers, Helen F; Krupa, Malgorzata; Rodgers, Raymond J

    2003-12-01

    Bovine ovarian antral follicles exhibit either one or the other of two patterns of granulosa cell death in atresia. Death can commence either from the antrum and progress toward the basal lamina (antral atresia) or the converse (basal atresia). In basal atresia, the remaining live antrally situated cells appeared to continue maturing. Beyond that, little is known about these distinct patterns of atresia. Healthy (nonatretic) follicles also exhibit either one or the other of two patterns of granulosa cell shape, follicular basal lamina ultrastructure or location of younger cells within the membrana granulosa. To examine these different phenotypes, the expression of the steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (SCC) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in granulosa cells and concentrations of steroid hormones in follicular fluid were measured in individual histologically classified bovine antral follicles. Healthy follicles first expressed SCC and 3beta-HSD in granulosa cells only when the follicles reached an approximate threshold of 10 mm in diameter. The pattern of expression in antral atretic follicles was the same as healthy follicles. Basal atretic follicles were all <5 mm. In these, the surviving antral granulosa cells expressed SCC and 3beta-HSD. In examining follicles of 3-5 mm, basal atretic follicles were found to have substantially elevated progesterone (P < 0.001) and decreased androstenedione and testosterone compared to healthy and antral atretic follicles. Estradiol was highest in the large healthy follicles, lower in the small healthy follicles, lower still in the antral atretic follicles, and lowest in the basal atretic follicles. Our findings have two major implications. First, the traditional method of identifying atretic follicles by measurement of steroid hormone concentrations may be less valid with small bovine follicles. Second, features of the two forms of follicular atresia are so different as to

  9. 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

  10. EEG responses in regularly menstruating women and in amenorrheic women treated with ovarian hormones.

    PubMed

    Vogel, W; Broverman, D M; Klaiber, E L

    1971-04-23

    Electroencephalographic driving reponses to photic stimulation vary with the menstrual cycle and with manipulations of ovarian hormones thought to control the menstrual cycle. Estrogens reduce driving responses to photic stimulation, and estrogen plus progesterone enhance these responses. The electroencephalographic changes may reflect the effects of gonadal steroid hormones upon central adrenergic processes. PMID:4323796

  11. Effects of Ovarian Steroids on Immunoglobulin-Secreting Cell Function in Healthy Women

    PubMed Central

    Lü, Fabien X.; Ma, Zhongmin; Moser, Susie; Evans, Thomas G.; Miller, Christopher J.

    2003-01-01

    To determine the effect of the ovarian hormone cycle on immunity, immunoglobulin-secreting cell (ISC) frequency and lymphocyte subsets were examined in the blood of healthy women. We found that immunoglobulin A (IgA)-secreting cells (IgA-ISC) were fourfold more frequent than IgG-ISC in peripheral blood mononuclear cells (PBMC). Further, the ISC frequency in PBMC was highest (P < 0.05) during the periovulatory stage of the menstrual cycle. Thus, endogenous ovarian steroids regulate the ISC frequency and this may explain why women are more resistant to viral infections and tend to have more immune-mediated diseases than men do. PMID:12965931

  12. Steroid hormones in bovine oviductal fluid during the estrous cycle.

    PubMed

    Lamy, Julie; Liere, Philippe; Pianos, Antoine; Aprahamian, Fanny; Mermillod, Pascal; Saint-Dizier, Marie

    2016-10-01

    Ovarian steroid hormones are major regulators of the physiology of the oviduct and reproductive events occurring within the oviduct. To establish a whole steroid profiling of the bovine oviductal fluid (OF) during the estrous cycle, contralateral and ipsilateral (to the corpus luteum or preovulatory follicle) oviducts were classified into four stages of the estrous cycle (n = 18-27 cows per stage): postovulatory (Post-ov), mid-luteal (Mid-lut), late luteal (Late-lut), and preovulatory on the basis of the ovarian morphology and intrafollicular steroid concentrations. Steroids were extracted from pools of 150 to 200 μL OF (three to 10 cows per pool; three to four pools per "stage × side" group), purified, fractioned by high-performance liquid chromatography, and analyzed by gas chromatography coupled with tandem mass spectrometry. The concentrations of progesterone (P4) in ipsilateral OF increased from Post-ov (56.9 ± 13.4 ng/mL) to Mid-lut (120.3 ± 34.3 ng/mL), then decreased from Late-lut (76.7 ± 1.8 ng/mL) to Pre-ov (6.3 ± 1.7 ng/mL), and were four to 16 times higher than in contralateral OF. Most P4 metabolites followed similar patterns of variation. Concentrations of 17beta-estradiol (E2) were significantly higher at Pre-ov (290.5 ± 63.2 pg/mL) compared with all other stages (<118.3 pg/mL), with no difference regarding the side of ovulation. Concentrations of androstenedione displayed a pattern similar to that of E2, whereas other androgens, estrone, and corticoids did not vary between stages or sides. In conclusion, a highly concentrated and fluctuating hormonal environment was evidenced in the bovine OF. These results could be useful to improve media for IVF, embryo development, and culture of oviductal cells. PMID:27262884

  13. Ovarian Steroid Cell Tumour: Correlation of Histopathology with Clinicopathologic Features

    PubMed Central

    Mehdi, Ghazala; Ansari, Hena A.; Sherwani, Rana K.; Rahman, Khaliqur; Akhtar, Nishat

    2011-01-01

    Ovarian steroid cell tumours (not otherwise specified) are rare neoplasms of the ovary and are classified under lipid cell tumours. Their diagnosis can be considered as one of exclusion. Histopathologically, the tumour should carefully be evaluated for microscopic features of malignancy, but it is essential for the clinician and the pathologist to remember that in these tumours, pathologically benign histomorphology does not exclude the possibility of clinically malignant behaviour. Our case study focuses on the comparative findings in a postmenopausal female diagnosed with an ovarian steroid tumour (not otherwise specified). A careful correlation between clinical and surgical evaluation and microscopic analysis is necessary, as is a regular followup. PMID:21436872

  14. 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

  15. 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. PMID:25482110

  16. Noninvasive test for the diagnosis of ovarian hormone-secreting-neoplasm in postmenopausal women☆

    PubMed Central

    Cohen, Ilan; Nabriski, Dan; Fishman, Ami

    2015-01-01

    Context The diagnosis of ovarian hormone-secreting neoplasm in postmenopausal women is currently based on imaging modalities and selective venography. However, these diagnostic tests are not always accurate. In order to improve and simplify the diagnosis, we propose a noninvasive hormonal test. Objective To report our experience using noninvasive hormonal test for the diagnosis of ovarian hormone producing tumor in two postmenopausal women. Design and intervention Evaluation of androgen and estradiol serum levels following 1. Adrenal hormonal depression, 2. ovarian hormonal depression and 3. ovarian hormonal stimulation. Setting Tertiary care medical center. Main outcome measures Changes in androgen and estradiol levels. Results In the first case, total testosterone, free androgen index and estradiol serum levels decreased following ovarian depression by GnRH-antagonist (6.9 nmol/L, 67 nmol/L and < 70 pmol/L, respectively) and subsequently increased after ovarian stimulation with LH (11.5 nmol/L, 117 nmol/L and 176 pmol/L, respectively). Histological evaluation revealed steroid cell tumor in one ovary. In the second case, estradiol serum levels decreased following ovarian depression by GnRH-antagonist (73 pmol/L) and subsequently increased following ovarian stimulation with FSH (118 pmol/L). Histological evaluation revealed granulosa cell tumor in one ovary. Conclusions To our knowledge, these are the first cases of ovarian hormone-producing tumors in postmenopausal women diagnosed by noninvasive hormonal test. The proposed test can be considered in postmenopausal women suspected of having androgen and/or estrogen producing tumors. PMID:26937480

  17. 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. PMID:9835376

  18. Vitamin D, steroid hormones, and autoimmunity.

    PubMed

    Cutolo, Maurizio; Paolino, Sabrina; Sulli, Alberto; Smith, Vanessa; Pizzorni, Carmen; Seriolo, Bruno

    2014-05-01

    The endogenous serum metabolite of vitamin D (calcitriol, 1,25(OH)2 D3 ) is considered a true steroid hormone (D hormone), and like glucocorticoids (GCs) and gonadal hormones, may exert several immunomodulatory activities. Serum vitamin D deficiency (25(OH) D), and therefore reduced 1,25(OH)2 D3 availability, is considered a risk factor for several chronic/inflammatory or autoimmune conditions, including infectious diseases, type 1 diabetes, multiple sclerosis, and especially autoimmune rheumatic diseases (ARD). In ARD in particular, 1,25(OH)2 D3 regulates both innate and adaptive immunity, potentiating the innate response (antimicrobial activity) but reducing adaptive immunity (antigen presentation, T and B cell activities). Regarding a possible synergism between vitamin D and GCs, several studies show that 1,25(OH)2 D3 has significant additive effects on dexamethasone-mediated inhibition of human lymphocyte and monocyte proliferation. Conversely, vitamin D deficiency seems to play a role in increasing autoantibody production by B cells, and seasonal vitamin D declines may trigger flares in ARD, as recently shown. Finally, 1,25(OH)2 D3 seems to reduce aromatase activity and limit the negative effects related to increased peripheral estrogen metabolism (cell proliferation, B cell overactivity). PMID:24739090

  19. 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

  20. Virilizing Ovarian Steroid Cell Tumor: A Rare Case

    PubMed Central

    Rangaiah, Nagarathnamma; Prasad, Nagendra; Channaveeregowda, Savitha

    2015-01-01

    Ovarian steroid cell tumours are fewer than 5 percent of sex-cord stromal tumours and 0.1% of all ovarian tumours. The average age at diagnosis is the mid-20s, but patients can present at virtually any age. We present a case of 38-year-old multipara with history of secondary amenorrhea, clinical signs & symptoms of virilization developed over the past 5 years. With elevated (115ng/dL) serum testosterone level and radiological findings of a left adnexal solid mass; the patient was suspected to have a virilizing tumour of left ovary. Laparoscopic left salpingo-oophorectomy was performed. Histopathology revealed tumour cells in small nests with vacuolated to eosinophilic cytoplasm with nuclear atypia completely replacing the ovarian tissue suggestive of steroid cell tumour (NOS) of ovary. The patient was discharged and advised for follow up with serum testosterone levels after 3 weeks. PMID:26500963

  1. ROLE OF STEROID HORMONES AND DECIDUAL INDUCTION IN THE REGULATION OF ADENOSINE DIPHOSPHORIBOSYL TRANSFERASE ACTIVITY IN RAT ENDOMETRIUM

    EPA Science Inventory

    To assess the effect of ovarian steroid hormones on enzyme activity, adenosine diphosphoribosyl transferase (ADPRT) was measured in endometrial nuclei isolated on estrus and on d 4 from rats ovariectomized on estrus (d 0) and treated d 0-3 with (a) vehicle, (b) 1 ug estrone/d (E)...

  2. 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.

  3. Steroid receptor mRNA expression in the ovarian follicles of cows with cystic ovarian disease.

    PubMed

    Alfaro, Natalia S; Salvetti, Natalia R; Velazquez, Melisa M; Stangaferro, Matías L; Rey, Florencia; Ortega, Hugo H

    2012-06-01

    Steroid receptors have been demonstrated to be important intra-ovarian regulators of follicular development and ovulatory processes. The aim of the present study was to determine the expression of steroid receptor mRNA in ovarian follicular structures from cows with cystic ovarian disease (COD) compared with ovarian structures from regularly cycling cows using reverse transcription polymerase chain reaction (RT-PCR). The cystic follicles showed a higher estrogen receptor α (ESR1) mRNA expression in the theca and granulosa and a lower estrogen receptor β (ESR2) expression. The cystic follicles also showed a strong expression of androgen receptor mRNA in the granulosa. No changes were observed in total progesterone receptor mRNA, but a very significant increase in the B isoform was found in the granulosa of the cystic follicles. The findings of the current study provide evidence that an altered steroid signaling system may be present in bovine follicular cysts, and we suggest that in conditions characterized by altered ovulation, such as COD, changes in the expression of ovarian steroid receptors could play a fundamental role in the pathogeny of this disease. PMID:21536311

  4. A Computational Model to Predict Rat Ovarian Steroid Secretion from In Vitro Experiments with Endocrine Disruptors

    PubMed Central

    Quignot, Nadia; Bois, Frédéric Y.

    2013-01-01

    A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. Environmental toxicants are a serious health concern, and numerous studies have been devoted to studying the effects of endocrine disrupting chemicals (EDCs). The effects of EDCs on steroidogenic enzymes may influence steroid secretion and thus lead to reproductive toxicity. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model is able to predict ovarian sex steroid concentrations under normal estrous cycle in female rat, and ovarian estradiol concentrations in adult female rats exposed to atrazine, bisphenol A, metabolites of methoxychlor or vinclozolin, and letrozole. PMID:23326527

  5. Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques.

    PubMed

    Lu, N Z; Eshleman, A J; Janowsky, A; Bethea, C L

    2003-03-01

    The serotonin reuptake transporter (SERT) plays an important role in serotonin neurotransmission and in several psychopathological disorders such as depression and anxiety disorders. In this study, we investigated whether the ovarian steroids, estrogen (E) and progesterone (P) regulate SERT binding, intracellular distribution, and function using [(3)H]citalopram ligand binding with quantitative autoradiography, immunofluorescence histochemistry with confocal microscopy and [(3)H]serotonin uptake, respectively. Ovariectomized macaques received either placebo, E alone, P alone or E plus P for 28 days. In the raphe, E, P, and E+P treatments did not change SERT binding density. In several hypothalamic nuclei, [(3)H]citalopram binding was increased by E, P, and E+P. Immunofluorescent SERT in serotonin soma was intracellular and similar among treatments. In the hypothalamus, immunofluorescent SERT was located along the serotonergic axons and there was a significant proliferation of immunofluorescent fibers in hormone-treated animals. In addition, E and E+P treatment increased serotonin uptake in the basal ganglia. These findings suggest that ovarian hormones regulate SERT protein expression and distribution, perhaps via extracellular serotonin or mRNA stability, but not solely at the level of gene transcription. Further investigation on the possible action of ovarian steroids on the directionality of SERT transport is indicated. PMID:12660809

  6. 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. PMID:27217264

  7. 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. PMID:24957969

  8. 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

  9. The Endocannabinoid System and Sex Steroid Hormone-Dependent Cancers

    PubMed Central

    Taylor, Anthony H.; Marczylo, Timothy H.; Willets, Jonathon M.; Konje, Justin C.

    2013-01-01

    The “endocannabinoid system (ECS)” comprises the endocannabinoids, the enzymes that regulate their synthesis and degradation, the prototypical cannabinoid receptors (CB1 and CB2), some noncannabinoid receptors, and an, as yet, uncharacterised transport system. Recent evidence suggests that both cannabinoid receptors are present in sex steroid hormone-dependent cancer tissues and potentially play an important role in those malignancies. Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis. Here, the role of the endocannabinoid system in sex steroid hormone-dependent cancers is described and the potential for novel therapies assessed. PMID:24369462

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

    PubMed

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

    2016-06-28

    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

  11. 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

  12. The role of reproductive hormones in epithelial ovarian carcinogenesis.

    PubMed

    Gharwan, Helen; Bunch, Kristen P; Annunziata, Christina M

    2015-12-01

    Epithelial ovarian cancer comprises ∼85% of all ovarian cancer cases. Despite acceptance regarding the influence of reproductive hormones on ovarian cancer risk and considerable advances in the understanding of epithelial ovarian carcinogenesis on a molecular level, complete understanding of the biologic processes underlying malignant transformation of ovarian surface epithelium is lacking. Various hypotheses have been proposed over the past several decades to explain the etiology of the disease. The role of reproductive hormones in epithelial ovarian carcinogenesis remains a key topic of research. Primary questions in the field of ovarian cancer biology center on its developmental cell of origin, the positive and negative effects of each class of hormones on ovarian cancer initiation and progression, and the role of the immune system in the ovarian cancer microenvironment. The development of the female reproductive tract is dictated by the hormonal milieu during embryogenesis. Intensive research efforts have revealed that ovarian cancer is a heterogenous disease that may develop from multiple extra-ovarian tissues, including both Müllerian (fallopian tubes, endometrium) and non-Müllerian structures (gastrointestinal tissue), contributing to its heterogeneity and distinct histologic subtypes. The mechanism underlying ovarian localization, however, remains unclear. Here, we discuss the role of reproductive hormones in influencing the immune system and tipping the balance against or in favor of developing ovarian cancer. We comment on animal models that are critical for experimentally validating existing hypotheses in key areas of endocrine research and useful for preclinical drug development. Finally, we address emerging therapeutic trends directed against ovarian cancer. PMID:26373571

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

    PubMed

    Hammond, Geoffrey L

    2016-07-01

    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

  14. Convergence of Multiple Mechanisms of Steroid Hormone Action

    PubMed Central

    Mani, S. K.; Mermelstein, P. G.; Tetel, M. J.; Anesetti, G.

    2013-01-01

    Steroid hormones modulate a wide array of physiological processes including development, metabolism, and reproduction in various species. It is generally believed that these biological effects are predominantly mediated by their binding to specific intracellular receptors resulting in conformational change, dimerization, and recruitment of coregulators for transcription-dependent genomic actions (classical mechanism). In addition, to their cognate ligands, intracellular steroid receptors can also be activated in a “ligand-independent” manner by other factors including neurotransmitters. Recent studies indicate that rapid, nonclassical steroid effects involve extranuclear steroid receptors located at the membrane, which interact with cytoplasmic kinase signaling molecules and G-proteins. The current review deals with various mechanisms that function together in an integrated manner to promote hormone-dependent actions on the central and sympathetic nervous systems. PMID:22454239

  15. 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

  16. 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

  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. PMID:26775014

  18. 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

  19. [THE EFFECT OF HORMONAL STIMULATION OF STERLET (ACIPENSER RUTHENUS L.) ON STEROID LEVELS IN TISSUE INCUBATES].

    PubMed

    Bayunova, L V

    2016-01-01

    Sex steroids and corticol levels in Leibovitz's L-15 media samples after incubation of intact female and male sterlet (Acipenser rhutenus L.) tissue fragments and those if fishes treated with a superactive analogue of mammalian luteinising hormone-releasing hormone (LH-RH-A) were compared. 17,20β,21-trihydroxy-4-pregnen-3-one (20βS) levels were significantly higher in the media samples after incubation of ovarian follicles taken from females 5 h after treatment with LH-RH-A in comparison with 20βS levels in intact female samples. 20βS levels also increased after 1 μM progesterone (P4) adding to the media before incubation of ovarian follicles. Cortisol and testosterone levels in the media samples demonstrated the same tendency. Significant elevation of cortisol levels was observed in the blood serum samples of females 5 h after LH-RH-A treatment. The androgens (testosterone and 11-ketotestosterone) levels after incubation of testicular and liver fragments were high in the media samples in males who had high serum levels of these androgens before hormonal stimulation. Sex steroids and cortisol production was stimulated by P4 adding to the media before incubation of gonad fragments. 20βS media levels increased after P4 adding before incubation of liver fragments. PMID:27220236

  20. 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.

  1. Effect of tamoxifen on sex steroid concentrations in chicken ovarian follicles.

    PubMed

    Rzasa, Janusz; Sechman, Andrzej; Paczoska-Eliasiewicz, Helena; Hrabia, Anna

    2009-03-01

    The aim of the present investigation was to study the effect of tamoxifen (TAM), an oestrogen receptor antagonist, on the concentrations of sex hormones in chicken ovarian follicles. The experiment was carried out on Hy-line hens which were randomly divided into two groups (control and experimental). TAM was given at a dose of 4 mg/hen (per os) at first once a day for 7 consecutive days, and subsequently four times a day for the next 6 days. Control hens received placebo. Birds were killed on the day after the last TAM treatment. From the dissected ovaries the following compartments were isolated: stroma with follicles < 1 mm, white non-hierarchical (1-4 mm and 4-8 mm) and yellow hierarchical follicles (F6-F1; 18-35 mm). The concentrations of the sex steroids progesterone (P4), testosterone (T) and oestradiol (E2) in the ovarian follicles were determined by radioimmunoassay. In the TAM-treated group, a gradual decrease in egg-laying rate was observed from the 4th day of the experiment. Eventually, egg laying stopped entirely on the 12th day of the experiment. TAM significantly decreased the weight of the ovary and affected the sex hormone concentrations in the ovarian follicles. Following TAM treatment (1) a significant increase in E2 and T concentrations in the stroma, white follicles and the F4 and F1 follicles, (2) a significant decrease in E2 and T concentrations in the F2 follicle, and (3) a significant decline of P4 in the F4 to F1 follicles were observed. The results indicate that the blockade of oestrogen receptors by TAM significantly modulates the process of chicken ovarian steroidogenesis. PMID:19457777

  2. Regioselective hydroxylation of steroid hormones by human cytochromes P450.

    PubMed

    Niwa, Toshiro; Murayama, Norie; Imagawa, Yurie; Yamazaki, Hiroshi

    2015-05-01

    This article reviews in vitro metabolic activities [including Michaelis constants (Km), maximal velocities (Vmax) and Vmax/Km] and drug-steroid interactions [such as induction and cooperativity (activation)] of cytochromes P450 (P450 or CYP) in human tissues, including liver and adrenal gland, for 14 kinds of endogenous steroid compounds, including allopregnanolone, cholesterol, cortisol, cortisone, dehydroepiandrosterone, estradiol, estrone, pregnenolone, progesterone, testosterone and bile acids (cholic acid). First, we considered the drug-metabolizing P450s. 6β-Hydroxylation of many steroids, including cortisol, cortisone, progesterone and testosterone, was catalyzed primarily by CYP3A4. CYP1A2 and CYP3A4, respectively, are likely the major hepatic enzymes responsible for 2-/4-hydroxylation and 16α-hydroxylation of estradiol and estrone, steroids that can contribute to breast cancer risk. In contrast, CYP1A1 and CYP1B1 predominantly metabolized estrone and estradiol to 2- and 4-catechol estrogens, which are endogenous ultimate carcinogens if formed in the breast. Some metabolic activities of CYP3A4, including dehydroepiandrosterone 7β-/16α-hydroxylation, estrone 2-hydroxylation and testosterone 6β-hydroxylation, were higher than those for polymorphically expressed CYP3A5. Next, we considered typical steroidogenic P450s. CYP17A1, CYP19A1 and CYP27A1 catalyzed steroid synthesis, including hydroxylation at 17α, 19 and 27 positions, respectively. However, it was difficult to predict which hepatic drug-metabolizing P450 or steroidogenic P450 will be mainly responsible for metabolizing each steroid hormone in vivo based on these results. Further research is required on the metabolism of steroid hormones by various P450s and on prediction of their relative contributions to in vivo metabolism. The findings collected here provide fundamental and useful information on the metabolism of steroid compounds. PMID:25678418

  3. 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. PMID:606452

  4. 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

  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. PMID:26912936

  6. Hormone Therapy and Ovarian Cancer: Incidence and Survival

    PubMed Central

    Wernli, Karen J.; Newcomb, Polly A.; Hampton, John; Trentham-Dietz, Amy; Egan, Kathleen M.

    2009-01-01

    Objective We conducted a population-based case-control study to investigate the association between hormone therapy (HT) and ovarian cancer incidence, and followed all these cancer cases to determine the association of HT use with ovarian cancer mortality. Methods Seven hundred fifty-one incident cases of invasive epithelial ovarian cancer aged 40–79 years were diagnosed in Wisconsin and Massachusetts between 1993–1995 and 1998–2001 and matched to similarly-aged controls (n=5808). Study subjects were interviewed by telephone, which ascertained information on HT use and specific preparation, estrogen alone (E-alone) or estrogen plus progestin (EP). Ovarian cancer cases were followed-up for mortality through December 2005. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals (CI) for ovarian cancer incidence, and Cox proportional hazards modeling was used to estimate hazard ratios and corresponding confidence intervals for ovarian cancer mortality. Results Ever use of HT was significantly associated with an increased risk of ovarian cancer (odds ratio 1.57, 95% CI 1.31–1.87). The excess risk was confined to women who used E-alone preparations (OR 2.33, 95% CI 1.85–2.95). No significant associations were detected between pre-diagnosis HT use and ovarian cancer survival. Conclusions Hormone therapy increases risk of ovarian cancer among E-alone users, but there is no substantial impact on survival after diagnosis. PMID:18264784

  7. Identification of calcitonin expression in the chicken ovary: influence of follicular maturation and ovarian steroids.

    PubMed

    Krzysik-Walker, Susan M; Ocón-Grove, Olga M; Maddineni, Sreenivasa B; Hendricks, Gilbert L; Ramachandran, Ramesh

    2007-10-01

    Calcitonin (CALCA), a hormone primarily known for its role in calcium homeostasis, has recently been linked to reproduction, specifically as a marker for embryo implantation in the uterus. Although CALCA expression has been documented in several tissues, there has been no report of production of CALCA in the ovary of any vertebrate species. We hypothesized that the Calca gene is expressed in the chicken ovary, and its expression will be altered by follicular maturation or gonadal steroid administration. Using RT-PCR, we detected Calca mRNA and the calcitonin receptor (Calcr) mRNA in the granulosa and theca layers of preovulatory and prehierarchial follicles. Both CALCA and Calca mRNA were localized in granulosa and thecal cells by confocal microscopy. Using quantitative PCR analysis, F1 follicle granulosa layer was found to contain significantly greater Calca mRNA and Calcr mRNA levels compared with those of any other preovulatory or prehierarchial follicle. The granulosa layer contained relatively greater Calca and Calcr mRNA levels compared with the thecal layer in both prehierarchial and preovulatory follicles. Progesterone (P(4)) treatment of sexually immature chickens resulted in a significantly greater abundance of ovarian Calca mRNA, whereas estradiol (E(2)) or P(4) + E(2) treatment significantly reduced ovarian Calca mRNA quantity. Treatment of prehierarchial follicular granulosa cells in vitro with CALCA significantly decreased FSH-stimulated cellular viability. Collectively, our results indicate that follicular maturation and gonadal steroids influence Calca and Calcr gene expression in the chicken ovary. We conclude that ovarian CALCA is possibly involved in regulating follicular maturation in the chicken ovary. PMID:17582014

  8. Non-hormonal interruption of incessant ovulation as a potential approach for ovarian cancer prevention.

    PubMed

    Fathalla, Mahmoud F

    2016-03-01

    Ovarian cancer is a silent killer. There is a need to intensify research efforts on prevention strategies. The causative role of incessant ovulation has been supported by the protective effect of oral hormonal contraceptives. The released follicular fluid in the process of ovulation bathes not only the surface of the ovary but also the fimbrial end of the fallopian tube. Evidence has been accumulating about a fimbrial tubal origin for ovarian high-grade serous carcinoma, and for the potential of opportunistic or elective salpingectomy as an intervention strategy. Alternatively, periodic suppression of ovulation could be beneficial among women who have no need or are not using oral hormonal contraceptives. Rupture of the ovarian follicle releasing the ovum and follicular fluid is a prostaglandin-mediated inflammatory process. It can be stopped by nonsteroidal anti-inflammatory drugs, leading to pharmacologic production of a luteinized unruptured follicle, simulating a normal non-conception cycle with unaltered steroid patterns/levels and cycle length. Non-hormonal periodic interruption of incessant ovulation could be recommended for women who are at high risk of ovarian cancer, but further research is needed to validate the potential of this approach. PMID:26876699

  9. 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

  10. Steroid hormone synthetic pathways in prostate cancer.

    PubMed

    Mostaghel, Elahe A

    2013-09-01

    While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa) since the seminal recognition of the disease as androgen-dependent by Huggins and Hodges in 1941, therapy is uniformly marked by progression to castration-resistant prostate cancer (CRPC) over a period of about 18 months, with an ensuing median survival of 1 to 2 years. Importantly, castration does not eliminate androgens from the prostate tumor microenvironment. Castration resistant tumors are characterized by elevated tumor androgens that are well within the range capable of activating the AR and AR-mediated gene expression, and by steroid enzyme alterations which may potentiate de novo androgen synthesis or utilization of circulating adrenal androgens. The dependence of CRPC on intratumoral androgen metabolism has been modeled in vitro and in vivo, and residual intratumoral androgens are implicated in nearly every mechanism by which AR-mediated signaling promotes castration-resistant disease. These observations suggest that tissue based alterations in steroid metabolism contribute to the development of CRPC and underscore these metabolic pathways as critical targets of therapy. Herein, we review the accumulated body of evidence which strongly supports intracrine (tumoral) androgen synthesis as an important mechanism underlying PCa progression. We first discuss the presence and significance of residual prostate tumor androgens in the progression of CRPC. We review the classical and non-classical pathways of androgen metabolism, and how dysregulated expression of these enzymes is likely to potentiate tumor androgen production in the progression to CRPC. Next we review the in vitro and in vivo data in human tumors, xenografts, and cell line models which demonstrate the capacity of prostate tumors to utilize cholesterol and adrenal androgens in the production of testosterone (T) and dihydrotestosterone (DHT), and briefly review the potential role of exogenous

  11. Steroid hormone secretion in inflammatory breast cancer cell lines.

    PubMed

    Illera, Juan Carlos; Caceres, Sara; Peña, Laura; de Andres, Paloma J; Monsalve, Beatriz; Illera, Maria J; Woodward, Wendy A; Reuben, James M; Silvan, Gema

    2015-12-01

    Inflammatory breast carcinoma (IBC) is a special type of breast cancer with a poor survival rate. Though several IBC cell lines have been established, recently a first IMC cell line was established. The aims of this study were: (1) to validate a highly sensitive, reliable, accurate and direct amplified enzyme immunoassay (EIA) to measure several cell-secreted steroid hormones: progesterone (P4), androstenedione (A4), testosterone (T), 17β-estradiol (E2) and estrone sulfate (SO4E1) in the culture medium. (2) To assess whether hormone production profile by IPC-366 cells validates the IMC model for human IBC. We validated a non-competitive amplified EIA for inflammatory breast cancer cell lines based on the results of accuracy, precision, sensitivity and parallelism. The low detection limits of the technique were: P4=13.2 pg/well, A4=2.3 pg/well, T=11.4 pg/well, E2=1.9 pg/well and SO4E1=4.5 pg/well. Intra- and inter-assay coefficient of variation percentages were <10%. The mean recovery rate of hormone added to the culture medium was >90%. In all hormones studied SUM149 have higher levels (1.4 times, but not significant) than IPC-366, and the correlation index between SUM149 and IPC-366 concentrations were >97%. We can coclude that cells of both cell lines, IPC-366 and SUM149, are capable to produce steroid hormone in culture media. The presented EIA methodology is very valuable for the detection of steroid production in culture media and could be used in hormone regulation studies and therapeutic agents in cell lines of inflammatory and non-inflammatory mammary carcinoma or other cancer cell lines in preclinical studies. PMID:26495931

  12. Functional interactions between steroid hormones and neurotrophin BDNF.

    PubMed

    Numakawa, Tadahiro; Yokomaku, Daisaku; Richards, Misty; Hori, Hiroaki; Adachi, Naoki; Kunugi, Hiroshi

    2010-05-26

    Brain-derived neurotrophic factor (BDNF), a critical neurotrophin, regulates many neuronal aspects including cell differentiation, cell survival, neurotransmission, and synaptic plasticity in the central nervous system (CNS). Though BDNF has two types of receptors, high affinity tropomyosin-related kinase (Trk)B and low affinity p75 receptors, BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogen-activated protein kinase/extracellular signal-regulated protein kinase, phospholipase Cγ, and phosphoinositide 3-kinase pathways. Notably, it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke, Parkinson's disease, Alzheimer's disease, and mental disorders. On the other hand, glucocorticoids, stress-induced steroid hormones, also putatively contribute to the pathophysiology of depression. Interestingly, in addition to the reduction in BDNF levels due to increased glucocorticoid exposure, current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones, such as estrogen, are involved in not only sexual differentiation in the brain, but also numerous neuronal events including cell survival and synaptic plasticity. Furthermore, it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease, Alzheimer's disease, and mental illness, while serving to regulate BDNF expression and/or function. Here, we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones (glucocorticoids and estrogen). PMID:21540998

  13. Nuclear receptor coactivators: Essential players in steroid hormone action in brain and behavior

    PubMed Central

    Tetel, Marc J.

    2009-01-01

    Steroid hormones act in brain and throughout the body to influence behavior and physiology. Many of these effects of steroid hormones are elicited by transcriptional events mediated by their respective receptors. A variety of cell culture studies reveal that nuclear receptor coactivators are critical in modulating steroid receptor-dependent transcription. Thus, in addition to the availability of the hormone and the expression of its receptor, nuclear receptor coactivators are essential for steroid-dependent transactivation of genes. This review will discuss the mounting evidence that nuclear receptor coactivators are critical in modulating steroid hormone action in brain and the regulation of behavior. PMID:19207820

  14. [Anti-Müllerian hormone - a marker of ovarian function].

    PubMed

    Koskela, Sanna; Tapanainen, Juha

    2016-01-01

    Anti-Müllerian hormone (AMH), also known as Müllerian inhibitory substance, is a useful marker of ovarian function. Granulosa cells of growing follicles secrete AMH, and its serum levels reflect the remaining follicular pool and thus the remaining length of a woman's reproductive lifespan. Serum AMH measurement can be used as a marker of ovarian dysfunction such as primary ovarian insufficiency, polycystic ovarian syndrome and granulosa cell tumors. Furthermore, it helps to estimate ovarian damage due to chemotherapy or surgery and can be used as a tool in infertility treatment. The use of AMH in clinical practice will likely become more common in the future as the new automatic assay methods become available. PMID:26951026

  15. Assessment of ovarian activity in captive goral (Naemorhedus griseus) using noninvasive fecal steroid monitoring.

    PubMed

    Khonmee, Jaruwan; Brown, Janine L; Taya, Kazuyoshi; Rojanasthien, Suvichai; Punyapornwithaya, Veerasak; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Pongpiachan, Petai; Thitaram, Chatchote

    2014-10-15

    To date, there is no information on gonadal steroidogenic activity of female goral (Naemorhedus griseus), a threatened species of Thailand. Captive goral populations have been established to produce animals for ex situ conservation and reintroduction, but as yet none are self-sustaining. The objectives of the present study were to (1) determine the influence of season on ovarian steriodogenic function; and (2) examine the relationship between gonadal hormone excretion and sexual behaviors throughout the year. Fecal samples were collected 5 to 7 days/wk for 15 months from 8 adult females housed at Omkoi Wildlife Breeding Center in Thailand and analyzed for ovarian steroid metabolites using validated enzyme immunoassays. Observations of sexual behaviors and mating were conducted each morning for 30 min/session. Based on fecal estrogen and progestagen metabolite concentrations, the overall estrous cycle length was about 21 days, with a 2- to 3-day follicular phase and an 18- to 20-day luteal phase. Sexual behaviors, most notably tail-up, increased for 2 to 3 days during the time estrogens were elevated during mating. Fecal progestagens were elevated during luteal phases and increased further during gestation, which lasted approximately 7 months. The lactation period was 5 months, and females were anestrus for 2 to 5 of those months, with the exception of one that cycled continuously throughout. Two females conceived around 2 months postpartum and so were pregnant during lactation. Birth records over the past 21 years indicated young are born throughout the year. This combined with the hormonal data suggests that female gorals are not strongly seasonal, at least in captivity, although there was considerable variation among females in estrogen and progestagen patterns. In conclusion, fecal steroid metabolite monitoring is an effective means of assessing ovarian function in this species and will be a useful tool for breeding management and planned development of

  16. 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

  17. Analysis of Steroid Hormones in a Typical Dairy Waste Disposal System

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The environmental loading of steroid hormones contained in dairy wastes may cause a potential adversely affect on the aquatic species. This work was to investigate the profile of steroid hormones in a typical dairy waste operation system and assess the potential risk of hormone contaminations result...

  18. 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. PMID:25632672

  19. Tissue-steroid interactions in canine hormone-dependent tumours.

    PubMed

    Evans, C R; Pierrepoint, C G

    1975-12-13

    Mammary tumour tissue from two bitches and an anal adenoma from a dog were investigated for steroid receptor interaction. Both mammary tumours possessed cytoplasmic macromolecules sedimenting with coefficients of 4S and 8S that bound oestradiol-17beta. These receptors had molecular weights of approximately 60,000 and 180,000 respectively. Transfer of the oestrogen to the nucleus was shown and the presence of a 4-5S nuclear protein demonstrated. The anal adenoma had a cytoplasmic receptor, with a sedimentation value in a sucrose density gradient of 4-5S with respect to bovine serum albumin, that bound tritiated 5alpha-androstane-3alpha, 17alpha-diol. No affinity could be demonstrated for other C19-steroids examined. The significance of these findings in terms of the hormone dependence of the tumours investigated and the possible development of these studies to promote rational therapy in such cases is discussed. PMID:173072

  20. Independent elaboration of steroid hormone signaling pathways in metazoans.

    PubMed

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

    2009-07-21

    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

  1. 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

  2. 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. PMID:25172822

  3. Prediagnostic circulating follicle stimulating hormone concentrations and ovarian cancer risk.

    PubMed

    McSorley, Meghan A; Alberg, Anthony J; Allen, Diane S; Allen, Naomi E; Brinton, Louise A; Dorgan, Joanne F; Kaaks, Rudolf; Rinaldi, Sabina; Helzlsouer, Kathy J

    2009-08-01

    Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between prediagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, United Kingdom. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to 1 to 2 controls on age, menopausal status, time since last menstrual period, current hormone use and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend = 0.005). Compared with the lowest third of FSH concentrations, the OR among those in the middle and highest thirds were 0.45 [95% Confidence Interval (CI): 0.20-1.00] and 0.26 (95% CI: 0.10-0.70), respectively. Associations persisted after excluding cases diagnosed within 5 years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. PMID:19444906

  4. Ovarian hormones and the heterogeneous receptor mechanisms mediating the discriminative stimulus effects of ethanol in female rats.

    PubMed

    Helms, Christa M; McCracken, Aubrey D; Heichman, Sharon L; Moschak, Travis M

    2013-04-01

    Past studies have suggested that progesterone-derived ovarian hormones contribute to the discriminative stimulus effects of ethanol, particularly via progesterone metabolites that act at γ-aminobutyric acid type A (GABA(A)) receptors. It is unknown whether loss of ovarian hormones in women, for example, after menopause, may be associated with altered receptor mediation of the effects of ethanol. The current study measured the substitution of allopregnanolone, pregnanolone, pentobarbital, midazolam, dizocilpine, TFMPP, and RU 24969 in female sham and ovariectomized rats trained to discriminate 1.0 g/kg ethanol from water. The groups did not differ in the substitution of GABA(A)-positive modulators (barbiturates, benzodiazepines, neuroactive steroids) or the N-methyl-D-aspartate receptor antagonist dizocilpine. Similarly, blood-ethanol concentration did not differ between the groups, and plasma adrenocorticotropic hormone, progesterone, pregnenolone, and deoxycorticosterone were unchanged 30 min after administration of 1.0 g/kg ethanol or water. However, substitution of neuroactive steroids and RU 24969, a 5-hydroxytryptamine (5-HT)(1A/1B) receptor agonist, was lower than observed in previous studies of male rats, and TFMPP substitution was decreased in ovariectomized rats. Ovarian hormones appear to contribute to 5-HT receptor mediation of the discriminative stimulus effects of ethanol in rats. PMID:23399883

  5. Mimicking postmenopausal steroid metabolism in breast cancer cell culture: Differences in response to DHEA or other steroids as hormone sources.

    PubMed

    Xu, Dan; Lin, Sheng-Xiang

    2016-07-01

    Following menopause virtually 100% of estrogens are synthesized in peripheral target tissues from precursor steroids of adrenal origin. These steroids are the unique source of sex steroids in these women. This positions some steroid metabolizing enzymes as primary targets for novel therapies for estrogen receptor-positive (ER+) breast cancer. However, previous research on the steroid-converting enzymes has been performed using their direct substrate as a hormone source, depending on the facility where studied and the robust signal obtained. These experiments may not always provide an accurate reflection of physiological and post-menopausal conditions. We suggest providing dehydroepiandrosterone (DHEA) as an intracrinological hormone source, and comparing the role of steroid-converting enzymes using DHEA and their direct substrates when an extensive mechanistic understanding is required. Here, we present a comparative study of these enzymes with the provision of DHEA and the direct substrates, estrone (E1) or dihydrotestosterone (DHT), or additional steroids as hormone sources, in breast cancer cells. Enzyme knockdown by respective specific siRNAs and observations on the resulting differences in biological function were carried out. Cell biology studies showed no difference in biological function for 17β-HSD1 and 17β-HSD7 when cultured with different steroid hormones: cell proliferation and estradiol levels decreased, whereas DHT accumulated; cyclinD1, PCNA, and pS2 were down-regulated after knocking down these two enzymes, although the quantitative results varied. However, culture medium supplementation was found to have a marked impact on the study of 3α-HSD3. We demonstrated that provision of different steroids as a substrate or hormone sources may promote modified biological effects: provision of DHEA is the preferred choice to mimic postmenopausal steroid metabolism in cell culture. PMID:26200948

  6. 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.

  7. Inactivation of contraceptive steroid hormones by human intestinal clostridia.

    PubMed

    Bokkenheuser, V D; Winter, J; Cohen, B I; O'Rourke, S; Mosbach, E H

    1983-09-01

    Steroid hormones reduced in ring-A are devoid of hormonal activity. In metabolic experiments we found that human fecal flora reduced the delta 4-3-keto structure of natural progestins to 3 alpha-hydroxy, 5 beta-steroid metabolites (3 alpha,5 beta) and of synthetic progestins to a mixture of 3 alpha,5 beta and 3 beta,5 beta compounds. 3 alpha,5 beta-Reductase was synthesized by Clostridium paraputrificum and had a strong affinity for natural progestins such as progesterone. 3 beta,5 beta-Reductase was synthesized by Clostridium innoculin and had a stronger affinity for synthetic progestins. A third enzyme, 3 beta,5 alpha-reductase, was synthesized by St. Luke's strain 209 (Clostridium species "J-1") but was only observed when pure cultures were used. Ring-A reduction of synthetic progestins was 3 to 10 times slower than that of natural progestins, thus explaining the pharmacological superiority of synthetic progestins over naturally occurring analogs. PMID:6630441

  8. 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. PMID:26952754

  9. Protective actions of ovarian hormones in the serotonin system of macaques.

    PubMed

    Bethea, Cynthia L; Reddy, Arubala P; Tokuyama, Yukari; Henderson, Jessica A; Lima, Fernanda B

    2009-07-01

    The serotonin neurons of the dorsal and medial raphe nuclei project to all areas of the forebrain and play a key role in mood disorders. Hence, any loss or degeneration of serotonin neurons could have profound ramifications. In a monkey model of surgical menopause with hormone replacement and no neural injury, E and P decreased gene expression in the dorsal raphe nucleus of c-jun n-terminal kinase (JNK1) and kynurenine mono-oxygenase (KMO) that promote cell death. In concert, E and P increased gene expression of superoxide dismutase (SOD1), VEGF, and caspase inhibitory proteins that promote cellular resilience in the dorsal raphe nucleus. Subsequently, we showed that ovarian steroids inhibit pivotal genes in the caspase-dependent and caspase-independent pathways in laser-captured serotonin neurons including apoptosis activating factor (Apaf1), apoptosis-inducing factor (AIF) and second mitochondria-derived activator of caspases (Smac/Diablo). SOD1 was also increased specifically in laser-captured serotonin neurons. Examination of protein expression in the dorsal raphe block revealed that JNK1, phosphoJNK1, AIF and the translocation of AIF from the mitochondria to the nucleus decreased with hormone therapy, whereas pivotal execution proteins in the caspase pathway were unchanged. In addition, cyclins A, B, D1 and E were inhibited, which would prevent re-entry into the cell cycle and catastrophic death. These data indicated that in the absence of gross injury to the midbrain, ovarian steroids inhibit the caspase-independent pathway and cell cycle initiation in serotonin neurons. To determine if these molecular actions prevented cellular vulnerability or death, we examined DNA fragmentation in the dorsal raphe nucleus with the TUNEL assay (terminal deoxynucleotidyl transferase nick end labeling). Ovarian steroids significantly decreased the number of TUNEL-positive cells in the dorsal raphe. Moreover, TUNEL staining prominently colocalized with TPH immunostaining, a

  10. 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.

  11. Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature

    PubMed Central

    Lee, Jessica; John, Veena S.; Liang, Sharon X.; D'Agostino, Catherine A.; Menzin, Andrew W.

    2016-01-01

    We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID:27375912

  12. Study of urinary steroid hormone disorders: difference between hepatocellular carcinoma in early stage and cirrhosis.

    PubMed

    Dai, Weidong; Yin, Peiyuan; Chen, Ping; Kong, Hongwei; Luo, Ping; Xu, Zhiliang; Lu, Xin; Xu, Guowang

    2014-07-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Discovery of novel biomarkers for early HCC from other liver diseases such as cirrhosis is of great clinical benefit. In this study, a novel steroid hormone metabolomic method based on liquid chromatography-mass spectrometry combined with logistic regression analysis was applied to study the steroid hormone disorders and to screen potential urinary steroid hormone biomarkers of early HCC. Thirty-six urinary steroid hormones were detected and quantified in healthy controls, cirrhotic patients, and early HCC patients. Heat map analysis and multivariate statistical analysis suggested severe disorders of steroid hormone network and holistically decreased urinary steroid hormone pattern in cirrhotic and early HCC patients. Logistic regression analysis reveals that a panel of two urinary steroid hormones (epitestosterone and allotetrahydrocortisol) displayed excellent diagnostic capability for distinguishing early HCC from cirrhosis with area under the curve (AUC) = 0.938 of receiver operating characteristic (ROC) analysis. These results help to overcome the disadvantage of lower sensitivity and specificity of alpha-fetoprotein for distinguishing early HCC from cirrhosis. Our work shows that steroid hormone metabolomics is a promising biomarker tool for biomarker study of early HCC. PMID:24817358

  13. 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. PMID:27320926

  14. Sex differences and ovarian hormones in animal models of drug dependence.

    PubMed

    Carroll, Marilyn E; Anker, Justin J

    2010-06-01

    Increasing evidence indicates the presence of sex differences in many aspects of drug abuse. Most studies reveal that females exceed males during the initiation, escalation, extinction, and reinstatement (relapse) of drug-seeking behavior, but males are more sensitive than females to the aversive effects of drugs such as drug withdrawal. Findings from human and animal research indicate that circulating levels of ovarian steroid hormones account for these sex differences. Estrogen (E) facilitates drug-seeking behavior, while progesterone (P) and its metabolite, allopregnanalone (ALLO), counteract the effects of E and reduce drug seeking. Estrogen and P influence other behaviors that are affiliated with drug abuse such as drug-induced locomotor sensitization and conditioned place preference. The enhanced vulnerability to drug seeking in females vs. males is also additive with the other risk factors for drug abuse (e.g., adolescence, sweet preference, novelty reactivity, and impulsivity). Finally, treatment studies using behavioral or pharmacological interventions, including P and ALLO, also indicate that females show greater treatment effectiveness during several phases of the addiction process. The neurobiological basis of sex differences in drug abuse appears to be genetic and involves the influence of ovarian hormones and their metabolites, the hypothalamic pituitary adrenal (HPA) axis, dopamine (DA), and gamma-hydroxy-butyric acid (GABA). Overall, sex and hormonal status along with other biological risk factors account for a continuum of addiction-prone and -resistant animal models that are valuable for studying drug abuse prevention and treatment strategies. PMID:19818789

  15. 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.

  16. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, Robert J; Weiser, Michael J

    2014-04-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, prior to generating an appropriate response is the animal's reproductive status. Thus, PVN neurons express androgen and estrogen receptors and receive input from sites that also express these receptors. Consequently, changes in reproduction and gonadal steroid levels modulate the stress response and this underlies sex differences in HPA axis function. This review examines the make up of the HPA axis and hypothalamo-pituitary-gonadal (HPG) axis and the interactions between the two that should be considered when exploring normal and pathological responses to environmental stressors. PMID:24246855

  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. [Vitamin D as an important steroid hormone in breast cancer].

    PubMed

    Obermannova, R; Demlová, R; Drábová, K; Melichárková, K; Greplová, K; Mrkvicová, M; Zdražilová-Dubská, L; Vyzula, R; Valík, D

    2014-01-01

    Vitamin D is the third steroid hormone playing important bio-logical roles in the development of breast cancer. Decreased plasma levels of its 25- hydroxyderivative, 25OHD, display robust associations with higher incidence of breast cancer and shorter overall survival. Although no consensus exists, most authors agree that optimal plasma levels shall be within 75- 150 nmol/ l whereas levels higher than 375 nmol/ l can be potentially toxic with higher risk of hypercalcemia. To date, no data are available on the optimal levels of vitamin D related to the risk of breast cancer development, its phenotype features and the course of the disease. Published studies mostly describe associations among higher levels of 25OHD and lower bio-logically aggressiveness of the tumor. The polymorphism of VDR gene coding for the steroid receptor for vitamin Dmay be associated with higher disease incidence and also be of negative prognostic significance in breast cancer. This review presents an overall summary of the current knowledge and publications on vitamin D and breast cancer. PMID:24945552

  19. 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. PMID:25623143

  20. Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles

    PubMed Central

    Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.

    2009-01-01

    While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity. PMID:19649243

  1. Characterization of cyclicity and hormonal profile with impending ovarian failure in a novel chemical-induced mouse model of perimenopause.

    PubMed

    Lohff, Jessica C; Christian, Patricia J; Marion, Samuel L; Arrandale, Anthony; Hoyer, Patricia B

    2005-12-01

    4-Vinylcyclohexene diepoxide (VCD) causes early, gradual ovarian failure in mice because it specifically targets small pre-antral ovarian follicles. The period between loss of these follicles and ovarian failure is analogous to perimenopause in women. We sought to characterize the period of onset of ovarian failure in VCD-treated mice in regard to estrous cycle length and hormonal changes. Female C57Bl/6 mice (age, 28 days) were dosed daily for 15 days with VCD (160 mg/kg intraperitoneally) to cause early ovarian failure or with vehicle only (control animals). Cycle length was monitored by vaginal cytology. Plasma levels of 17beta-estradiol (E2), progesterone (P4), and follicle-stimulating hormone (FSH) in control and VCD-treated animals were measured during proestrus of cycles 1 through 12. Cycle length (mean, 5.8 days) did not differ between groups for cycles 1 through 4. In contrast, cycle length during cycles 5 through 12 was increased (mean length, 10.9 days; P < 0.05 versus control) in VCD-treated animals, which also showed an apparent increase in plasma FSH levels. Plasma E2 and P4 at proestrus did not differ between groups during any cycle. Ovarian failure in VCD-treated mice was confirmed by histological evaluation on day 156 after onset of dosing, whereas control animals were still cycling. Therefore, despite compromised cycle length in VCD-treated mice, peak ovarian steroid production in preovulatory follicles at proestrus is adequate. These results demonstrate that the VCD-treated mouse can serve as an appropriate model to mimic hormonal changes during the perimenopausal transition in women. PMID:16422148

  2. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    PubMed

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  3. 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

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

    PubMed

    Shultz, T D; Howie, B J

    1986-01-01

    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. 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, each bound the following percentage of unconjugated hormones: lignin, 87%; wheat and oat brans, 45% each; corn bran 44%; and oat hulls, 32%. 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 nature of adsorption and suggest that the components of fiber in diet should be considered separately when evaluating in vivo metabolic effects. PMID:3010251

  5. 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

  6. [Comparison of chemical and radiochemical methods in determination of steroid hormones].

    PubMed

    Menini, E

    1975-06-01

    While in some cases steroids can be measured directly in serum or plasma by radioimmunoassay (RIA), in other cases, especially when analyses are carried out in urine, the samples must be processed before RIA can be performed. The operations involved in the preparation of urinary or blood extracts suitable for the RIA of steroid hormones are examined and compared in terms of practicability with the analytical procedures currently used for the chemical determination of the same steroids or their metabolites. PMID:1223934

  7. 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

  8. Steroid signalling in human ovarian surface epithelial cells: the response to interleukin-1alpha determined by microarray analysis.

    PubMed

    Rae, M T; Niven, D; Ross, A; Forster, T; Lathe, R; Critchley, H O D; Ghazal, P; Hillier, S G

    2004-10-01

    The human ovarian surface epithelium (HOSE) is a common site of gynaecological disease including endometriosis and ovarian cancer, probably due to serial injury-repair events associated with successive ovulations. To comprehend the importance of steroid signalling in the regulation of the HOSE, we used a custom microarray to catalogue the expression of over 250 genes involved in the synthesis and reception of steroid hormones, sterols and retinoids. The array included a subset of non-steroidogenic genes commonly involved in pro-/anti-inflammatory signalling. HOSE cells donated by five patients undergoing surgery for non-malignant gynaecological conditions were cultured for 48 h in the presence and absence of 500 pg/ml interleukin-1alpha (IL-1alpha). Total RNA was reverse-transcribed into biotin-labelled cDNA, which was hybridised to the array and visualised by gold-particle resonance light scattering and charge-coupled device (CCD) camera detection. Results for selected genes were verified by quantitative reverse-transcription PCR. In five out of five cases, untreated HOSE cells expressed genes encoding enzymes required for de novo biosynthesis of cholesterol from acetate and subsequent formation of C21-pregnane and C19-androstane steroids. Consistent with the inability of HOSE cells to synthesise glucocorticoids, oestrogens or 5alpha-reduced androgens de novo, CYP21, CYP19 and 5alpha-reductase were not detected. The only steroidogenic gene significantly up-regulated by IL-1alpha was 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1). Other cytokine-induced genes were IL-6, IL-8, nuclear factor kappaB (NFkappaB) inhibitor alpha, metallothionein-IIA and lysyl oxidase: inflammation-associated genes that respond to glucocorticoids. The only steroidogenic gene significantly suppressed by IL-1alpha was 3betaHSD1. Other genes suppressed by IL-1alpha were aldehyde dehydrogenase (ALDH) 1, ALDH 10, gonadotrophin hormone-releasing hormone receptor, peroxisome

  9. 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

  10. 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

  11. Proteoglycans in Leiomyoma and Normal Myometrium: Abundance, Steroid Hormone Control, and Implications for Pathophysiology.

    PubMed

    Barker, Nichole M; Carrino, David A; Caplan, Arnold I; Hurd, William W; Liu, James H; Tan, Huiqing; Mesiano, Sam

    2016-03-01

    Uterine leiomyoma are a common benign pelvic tumors composed of modified smooth muscle cells and a large amount of extracellular matrix (ECM). The proteoglycan composition of the leiomyoma ECM is thought to affect pathophysiology of the disease. To test this hypothesis, we examined the abundance (by immunoblotting) and expression (by quantitative real-time polymerase chain reaction) of the proteoglycans biglycan, decorin, and versican in leiomyoma and normal myometrium and determined whether expression is affected by steroid hormones and menstrual phase. Leiomyoma and normal myometrium were collected from women (n = 17) undergoing hysterectomy or myomectomy. In vitro studies were performed on immortalized leiomyoma (UtLM) and normal myometrial (hTERT-HM) cells with and without exposure to estradiol and progesterone. In leiomyoma tissue, abundance of decorin messenger RNA (mRNA) and protein were 2.6-fold and 1.4-fold lower, respectively, compared with normal myometrium. Abundance of versican mRNA was not different between matched samples, whereas versican protein was increased 1.8-fold in leiomyoma compared with myometrium. Decorin mRNA was 2.4-fold lower in secretory phase leiomyoma compared with proliferative phase tissue. In UtLM cells, progesterone decreased the abundance of decorin mRNA by 1.3-fold. Lower decorin expression in leiomyoma compared with myometrium may contribute to disease growth and progression. As decorin inhibits the activity of specific growth factors, its reduced level in the leiomyoma cell microenvironment may promote cell proliferation and ECM deposition. Our data suggest that decorin expression in leiomyoma is inhibited by progesterone, which may be a mechanism by which the ovarian steroids affect leiomyoma growth and disease progression. PMID:26423601

  12. Evidence of steroid hormone activity in the chorioallantoic membrane of a Turtle (Pseudemys nelsoni).

    PubMed

    Cruze, Lori; Hamlin, Heather J; Kohno, Satomi; McCoy, Michael W; Guillette, Louis J

    2013-06-01

    Endocrine properties of extraembryonic membranes have traditionally been viewed as a characteristic of placental amniotes. However, our laboratory recently demonstrated that this ability extends to the extraembryonic membranes of two oviparous amniotes (chicken and alligator) indicating that endocrine extraembryonic membranes are not an innovation of placental amniotes and suggesting that this could be a shared amniote characteristic. In this study, we test our hypothesis that the chorioallantoic membrane (CAM) obtained from non-archosaurian obligate oviparous amniotes such as turtles, have the potential for steroid hormone activity. To investigate synthesis of a major placental hormone, we performed explant culture and found that the turtle CAM synthesizes progesterone in vitro in the presence of a steroid precursor. In addition, to examine whether the CAM has the ability to respond to steroid signaling, we quantified mRNA expression of the progesterone, androgen, and two estrogen receptors. Finally, to determine if steroid receptor mRNA is translated to protein, we performed immunolocalization of the progesterone receptor. Our data demonstrate that the turtle CAM exhibits steroid synthesis and has steroid hormone signaling capabilities. To that end, steroid hormone activity has now been demonstrated in the CAMs of three oviparous species that represent three independent lineages within oviparous Reptilia that have never exhibited viviparity; thus these data support our hypothesis that endocrine activity of extraembryonic membranes is a conserved trait of Amniota. PMID:23458289

  13. Analysis of steroid hormones in a typical dairy waste disposal system.

    PubMed

    Zheng, Wei; Yates, Scott R; Bradford, Scott A

    2008-01-15

    The environmental loading of steroid hormones contained in dairy wastes may cause an adverse effect on aquatic species. To better assess the potential risks of hormone contamination resulting from land application of dairy wastes, various steroid hormones were determined in a typical dairy waste disposal system. Quantitative methods using gas chromatography/mass spectrometry (GC/MS) were developed to monitor low levels of steroid hormones in complex solid and liquid samples contaminated with dairy manure. The preparation method for wastewater analysis consisted of solid-phase extraction and purification steps, which minimized interference from the sample matrices and achieved low detection limits for the studied hormones. In the dairy wastewater and lagoon water, three endogenous hormones-17alpha-estradiol, 17beta-estradiol, and estrone-were detected. The concentration of 17alpha-estradiol in fresh milk parlor effluent rapidly decreased along the wastewater disposal route, whereas the concentration of estrone increased along this same pathway. This suggests that 17alpha-estradiol was readily oxidized to the metabolite estrone. Levels of total steroid hormones in the sequencing lagoon water were approximately 1-3 orders of magnitude lower than those in the fresh dairy wastewaters, indicating significant removal of these hormones during the transport of dairy wastewater from source to field. In solid dairy waste samples, four steroid hormones were identified and quantified. Increasing the piling time of solid wastes and increasing the residence time of wastewater in sequencing lagoons are suggested to be economical and efficient agriculture practices to extend the degradation time of hormone contaminants and thereby reduce the hormone load to the environment. PMID:18284158

  14. 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...

  15. Anaerobic transformation kinetics and mechanism of steroid estrogenic hormones in dairy lagoon water

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wastewater from concentrated animal feeding operations (CAFOs) frequently contains high concentrations of steroid estrogenic hormones. Release of these hormones into the environment may occur when CAFO wastewater is applied to agricultural lands as a nutrient and/or water source for crop production....

  16. 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 ...

  17. 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

  18. 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

  19. 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

  20. REGULATION OF GENE EXPRESSION IN THE BOVINE MAMMARY GLAND BY OVARIAN STEROIDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent upon progesterone. Effects of these steroid hormones on gene expression in the mammary gland are ...

  1. 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

  2. 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. PMID:25866757

  3. 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.

  4. Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord.

    PubMed

    Zubeldia-Brenner, L; Roselli, C E; Recabarren, S E; Gonzalez Deniselle, M C; Lara, H E

    2016-07-01

    This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas. PMID:27262161

  5. 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. PMID:26639430

  6. The Metabolism, Analysis, and Targeting of Steroid Hormones in Breast and Prostate Cancer.

    PubMed

    Capper, Cameron P; Rae, James M; Auchus, Richard J

    2016-06-01

    Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research. PMID:26969590

  7. Anti-mullerian hormon level and polycystic ovarian syndrome diagnosis

    PubMed Central

    Zadehmodarres, Shahrzad; Heidar, Zahra; Razzaghi, Zahra; Ebrahimi, Leili; Soltanzadeh, Kaveh; Abed, Farhang

    2015-01-01

    Background: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy that accompanied with long term complications. The early diagnosis of this syndrome can prevent it. Objective: The aim was to determine the role of anti-mullerian hormon (AMH) in PCOS diagnosis and to find cut off level of it. Materials and Methods: In this cross sectional study, 117 women between 20-40 years old were participated in two groups: 60 PCOS women (based on Rotterdam criteria consensus) as the case group and 57 normal ovulatory women as the control group. In day 2-4 of cycle, transvaginal sonography was performed and serum hormonal level of AMH, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, fasting blood sugar (FBS), thyroid stimulating hormone (TSH), and prolactin (PRL) were measured in all of participants. For all of them score of hirsutism (base on Freeman-Galloway scoring) was determined. Results: There were statistically significant in irregular pattern of menstruation, AMH and FSH level, and presence of hirsutism between two groups. But regarding mean of age, body mass index, plasma level of PRL, TSH, LH, Testosterone, FBS, and E2 differences were not significant. Construction by ROC curve present 3.15 ng/ml as AMH cut off with 70.37% sensitivity and 77.36% specificity in order to PCOS diagnosis. Conclusion: AMH with cut off level of 3.15 ng/ml with sensitivity 70.37% and specificity 77.36% could use for early diagnosis of PCOS patients. PMID:26131012

  8. 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.

  9. Hormone Receptors in Serous Ovarian Carcinoma: Prognosis, Pathogenesis, and Treatment Considerations

    PubMed Central

    Voutsadakis, Ioannis A.

    2016-01-01

    A few breakthroughs have been accomplished for the treatment of ovarian cancer, the most deadly gynecologic carcinoma, in the current era of targeted oncologic treatment. The estrogen receptor was the first target of such treatments with the introduction of tamoxifen four decades ago in breast cancer therapeutics. Attempts to duplicate the success of hormonal therapies in ovarian cancer met with mixed results, which may be due to an inferior degree of hormone dependency in this cancer. Alternatively, this may be due to the failure to clearly identify the subsets of ovarian cancer with hormone sensitivity. This article reviews the expression of hormone receptors by ovarian cancer cells, the prognostic value of these expressions, and their predictive capacity for response to hormonal agents. The possible ways ahead are briefly discussed. PMID:27053923

  10. 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. PMID:8372477

  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. Steroids

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Steroids KidsHealth > For Kids > Steroids Print A A A ... a good idea to avoid them. What Are Steroids? "Steroids" has more than one meaning. Your body ...

  13. 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-...

  14. Serotonergic neurons respond to nutrients and regulate the timing of steroid hormone biosynthesis in Drosophila

    PubMed Central

    Shimada-Niwa, Yuko; Niwa, Ryusuke

    2014-01-01

    The temporal transition of development is flexibly coordinated in the context of the nutrient environment, and this coordination is essential for organisms to increase their survival fitness and reproductive success. Steroid hormone, a key player of the juvenile-to-adult transition, is biosynthesized in a nutrient-dependent manner; however, the underlying genetic mechanism remains unclear. Here we report that the biosynthesis of insect steroid hormone, ecdysteroid, is regulated by a subset of serotonergic neurons in Drosophila melanogaster. These neurons directly innervate the prothoracic gland (PG), an ecdysteroid-producing organ and share tracts with the stomatogastric nervous system. Interestingly, the projecting neurites morphologically respond to nutrient conditions. Moreover, reduced activity of the PG-innervating neurons or of serotonin signalling in the PG strongly correlates with a delayed developmental transition. Our results suggest that serotonergic neurons form a link between the external environment and the internal endocrine system by adaptively tuning the timing of steroid hormone biosynthesis. PMID:25502946

  15. Sex steroids level in blood plasma and ovarian follicles of the chimeric chicken.

    PubMed

    Sechman, A; Lakota, P; Wojtysiak, D; Hrabia, A; Mika, M; Lisowski, M; Czekalski, P; Rzasa, J; Kapkowska, E; Bednarczyk, M

    2006-12-01

    The study was performed to determine the hormonal status of mature germline chimeras obtained by blastodermal cell transfer from chicken embryos of a donor breed [Green-legged Partridgelike breed (GP) x Araucana (AR)] to those of a recipient breed [White Leghorn (WL)] being at the same stage of embryonic development. The egg-laying chimeras and WL hens (control) of the same age were used in the experiment. At first, blood samples were taken from each bird at 0.5, 5, 12.5 and 18.5 h following oviposition. Subsequently, the chimeras and the WL hens were decapitated 1-2 h after ovulation. A stroma and the following follicles were isolated from the ovary: white normal (1-4, 4-6 and 6-8 mm), white atretic and yellow preovulatory follicles (F4-F1). Sex hormones, progesterone (P4), testosterone (T) and oestradiol (E2) in blood plasma and ovarian follicles were determined radioimmunologically. The activity of the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the granulosa and theca layers of the follicles was analysed histochemically. In chimeric chickens, a higher level of T in blood plasma during the ovulatory cycle was noticed. However, in the stroma, white prehierarchical and medium-size preovulatory ovarian follicles the level of T was significantly lower. With respect to E2, its elevated levels were found both in blood and in the ovarian follicles. There were no significant differences in P4 concentrations in blood plasma while in ovarian follicles a higher level was observed only in white 6-8 mm follicles. 3beta-HSD activity in granulosa and theca layers of the ovarian follicles in chimeras was not different from that in the WL hens. In conclusion, the results obtained indicate that germline chimeras exhibit significant alterations in sex hormone levels in the ovary and blood plasma, which in turn may affect their reproductive abilities. PMID:17105570

  16. 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

  17. LC-MS based analysis of endogenous steroid hormones in human hair.

    PubMed

    Gao, Wei; Kirschbaum, Clemens; Grass, Juliane; Stalder, Tobias

    2016-09-01

    The quantification of endogenous steroid hormone concentrations in hair is increasingly used as a method for obtaining retrospective information on long-term integrated hormone exposure. Several different analytical procedures have been employed for hair steroid analysis, with liquid chromatography-mass spectrometry (LC-MS) being recognized as a particularly powerful analytical tool. Several methodological aspects affect the performance of LC-MS systems for hair steroid analysis, including sample preparation and pretreatment, steroid extraction, post-incubation purification, LC methodology, ionization techniques and MS specifications. Here, we critically review the differential value of such protocol variants for hair steroid hormones analysis, focusing on both analytical quality and practical feasibility issues. Our results show that, when methodological challenges are adequately addressed, LC-MS protocols can not only yield excellent sensitivity and specificity but are also characterized by relatively simple sample processing and short run times. This makes LC-MS based hair steroid protocols particularly suitable as a high-quality option for routine application in research contexts requiring the processing of larger numbers of samples. PMID:26718873

  18. Responses of sex steroid hormones to different intensities of exercise in endurance athletes.

    PubMed

    Sato, Koji; Iemitsu, Motoyuki; Katayama, Keisho; Ishida, Koji; Kanao, Yoji; Saito, Mitsuru

    2016-01-01

    Previous studies have shown that acute exercise elevates sex steroid hormone concentrations in rodents and that sprint exercise increases circulating testosterone in healthy young men. However, the effect of different exercise intensities on sex steroid hormone responses at different levels of physical fitness is still unclear. In this study, we compared circulating sex steroid hormone responses at different exercise intensities in athletes and non-athletes. Eight male endurance athletes and 11 non-athletes performed two 15 min sessions of submaximal exercise at 40 and 70% peak oxygen uptake (V̇(O2peak)), respectively, and exercised at 90% V̇(O2peak) until exhaustion. Venous blood samples were collected during the last minute of each submaximal exercise session and immediately after exhaustion. Acute exercise at 40, 70 and 90% V̇(O2peak) induced significant increases in serum dehydroepiandrosterone (DHEA) and free testosterone concentrations in non-athletes. On the contrary, only 90% V̇O2 peak exercise led to an increase in serum DHEA and free testosterone concentrations in athletes. Serum 5α-dihydrotestosterone concentrations increased with 90% V̇(O2peak) exercise in both athletes and non-athletes. Additionally, serum estradiol concentrations were significantly increased at moderate and high exercise intensities in both athletes and non-athletes. These results indicate that in endurance athletes, serum sex steroid hormone concentrations, especially serum DHEA and 5α-dihydrotestosterone concentrations, increased only with high-intensity exercise, suggesting that different responses of sex steroid hormone secretion are induced by different exercise intensities in individuals with low and high levels of physical fitness. In athletes, therefore, high-intensity exercise may be required to increase circulating sex steroid hormone concentrations. PMID:26518151

  19. Serum and Tissue Steroid Hormone Levels in Canine Mammary Tumours: Clinical and Prognostic Implications.

    PubMed

    Queiroga, F L; Pérez-Alenza, D; González-Gil, A; Silván, G; Peña, L; Illera, J C

    2015-10-01

    Hormonal dependency of canine mammary tumours (CMT) has been studied over the last few decades. However, studies assessing the prognostic and predictive potential of serum and/or tissue steroid hormone levels are still scarce in CMT. To the best of our knowledge, this is the first report relating serum and tissue levels of steroid hormones and prognosis in dogs. Serum and tumour tissue from 45 female dogs with spontaneous CMT were included in the study. Moreover, serum and normal mammary tissue from 13 healthy female dogs were also included as controls. Steroid hormones were determined by competitive enzyme immunoassay. Overall, levels of steroid hormones in serum and tissue homogenates were significantly different between malignant and benign mammary tumours (p < 0.01), except for progesterone (P4) serum levels that revealed no statistical differences between groups. In malignant tumours, oestrone sulphate (SO4E1), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T) and P4 elevated tissue concentrations were significantly associated with tumour relapse and/or distant metastasis during follow-up. A significant association was found between elevated tissue SO4E1 (p = 0.003), 17β-oestradiol (E2) (p = 0.036), DHEA (p = 0.022), A4 (p = 0.001) and P4 (p = 0.013) concentrations and shorter disease-free survival and overall survival in female dogs with malignant mammary tumours. The high levels of tissue steroids found in cases of poor prognosis open the possibility of additional new therapeutic approaches. Future clinical trials will be needed to clarify the usefulness of targeting steroid hormones in the treatment of this neoplastic disease. PMID:26332137

  20. 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. PMID:24685768

  1. Postpartum blues: relationship between not-protein bound steroid hormones in plasma and postpartum mood changes.

    PubMed

    Heidrich, A; Schleyer, M; Spingler, H; Albert, P; Knoche, M; Fritze, J; Lanczik, M

    1994-02-01

    The relationship between non-bound steroid hormone levels in plasma and the occurrence of postpartum mood changes was investigated in 26 newly delivered mothers throughout the first 5 days postpartum. Studies with saliva samples had reported higher concentrations of 17 beta-estradiol and progesterone on the days of symptoms in women experiencing postpartum blues. As there had been a controversy as to how far saliva concentrations reflect free hormone levels in plasma, free hormone levels of 17 beta-estradiol and progesterone were determined in plasma using ultrafiltration. No significant difference concerning free hormone levels could be found between women with and without postpartum blues. PMID:8201129

  2. 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

  3. Hormone Treatment Restores Bone Density for Young Women with Menopause-Like Condition (Primary Ovarian Insufficiency)

    MedlinePlus

    ... determine the effects of hormone treatment on bone mineral density of women with primary ovarian insufficiency. Researchers ... insufficiency (POI) led to increases in their bone mineral density, restoring levels to normal. The study was ...

  4. The Role of Steroid Receptor Coactivators in Hormone Dependent Cancers and Their Potential as Therapeutic Targets.

    PubMed

    Wang, Lei; Lonard, David M; O'Malley, Bert W

    2016-08-01

    Steroid receptor coactivator (SRC) family members (SRC-1, SRC-2, SRC-3) interact with nuclear receptors (NRs) and many transcription factors to enhance target gene transcription. Deregulation of SRCs is widely implicated in NR mediated diseases, especially hormone dependent cancers. By integrating steroid hormone signaling and growth factor pathways, SRC proteins exert multiple modes of oncogenic regulation in cancers and represent emerging targets for cancer therapeutics. Recent work has identified SRC-targeting agents that show promise in blocking tumor growth in vitro and in vivo, and have the potential to function as powerful and broadly encompassing treatments for different cancers. PMID:27125199

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

    PubMed

    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

  6. 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. PMID:25955311

  7. 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

  8. 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. PMID:26723541

  9. Different follicle stimulating hormone/luteinizing hormone ratios for ovarian stimulation.

    PubMed

    Duijkers, I J; Vemer, H M; Hollanders, J M; Willemsen, W N; Bastiaans, L A; Hamilton, C J; Thomas, C M; Borm, G F

    1993-09-01

    The aim of the present study was to investigate whether reducing the amount of luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth in in-vitro fertilization (IVF) cycles during suppression of endogenous LH levels. A selected group of 20 IVF patients was randomly divided into two groups. One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1], the other group with Metrodin (purified FSH), both during pituitary down-regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum concentrations of FSH, LH, oestradiol and progesterone were determined frequently and serial ultrasound examinations were performed. Multiple follicular growth with concomitant rise of oestradiol levels was observed in all cycles. The duration of the stimulation phase was shorter in the group treated with Org 31338 than in the group treated with Metrodin. The number of follicles and oocytes and the fertilization rate was larger and the mean embryo quality was higher in the Org 31338 group, but the differences did not reach statistical significance. No significant differences were found in hormonal values. In women with normal endocrine profiles, lowering of the LH activity in gonadotrophic preparations during gonadotrophin-releasing hormone agonist treatment results in adequate ovarian stimulation. However, a preparation with some LH needed a shorter stimulation than a purified FSH preparation. Whether the other beneficial effects of Org 31338 also occur in a larger population needs further investigation. PMID:8253923

  10. 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,...

  11. 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

    2013-01-01

    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. PMID:24135941

  12. 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

    2015-09-01

    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. PMID:25963796

  13. 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'. PMID:23196064

  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. Epigenetic regulation of the expression of genes involved in steroid hormone biosynthesis and action

    PubMed Central

    Martinez-Arguelles, Daniel B.; Papadopoulos, Vassilios

    2010-01-01

    Steroid hormones participate in organ development, reproduction, body homeostasis, and stress responses. The steroid machinery is expressed in a development- and tissue-specific manner, with the expression of these factors being tightly regulated by an array of transcription factors (TFs). Epigenetics provides an additional layer of gene regulation through DNA methylation and histone tail modifications. Evidence of epigenetic regulation of key steroidogenic enzymes is increasing, though this does not seem to be a predominant regulatory pathway. Steroid hormones exert their action in target tissues through steroid nuclear receptors belonging to the NR3A and NR3C families. Nuclear receptor expression levels and post-translational modifications regulate their function and dictate their sensitivity to steroid ligands. Nuclear receptors and TFs are more likely to be epigenetically regulated than proteins involved in steroidogenesis and have secondary impact on the expression of these steroidogenic enzymes. Here we review evidence for epigenetic regulation of enzymes, transcription factors, and nuclear receptors related to steroid biogenesis and action. PMID:20156469

  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. 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. PMID:24241072

  18. The role of metabolic state and obestatin in control of chicken ovarian hormone release.

    PubMed

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

    2016-08-01

    The aim of the present study was to examine the role and interrelationships between calorie restriction and obestatin in the control of hormone release by chicken ovarian tissue. For this purpose, we compared the release of progesterone (P), testosteron (T), estradiol (E), and arginine-vasotocin (AVT) by ovarian fragments isolated from chicken subjected and not subjested to food restriction, as well as the response of these ovarian fragments to obestatin additions.It was observed that food restriction promoted release of P, reduced output of T, but did not affect basal E and AVT release. Obestatin addition reduced E, promoted AVT, and did not alter P and T release by ovarian tissue isolated from ad libitum fed chicken. In ovarian fragments of fasted hens it reduced E, promoted T, and did not influence P and AVT release.The present observations demonstrate (1) that obestatin can directly control the release of avian ovarian hormones - regulators of reproduction, (2) that metabolic state can control the release of these hormones, and (3) metabolic state can alter the response of ovarian hormones to obestatin. PMID:27030691

  19. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Positive correlation of steroid hormones and EGF in canine mammary cancer.

    PubMed

    Queiroga, Felisbina L; Pérez-Alenza, Dolores; Silvan, Gema; Peña, Laura; Illera, Juan C

    2009-05-01

    There are no published studies focused on the potential crosstalk between steroid hormones and EGF in canine mammary tumourigenesis. The objective was to investigate the role of EGF in canine mammary tumours (CMT) and the relationship with steroid hormones. Sixty-three CMT (39 malignant including 10 inflammatory mammary carcinomas (IMC); 19 benign and 5 dysplasias), and 13 normal mammary glands from dogs without history of neoplastic disease were analysed. Levels of EGF and steroid hormones [progesterone (P4); 17beta-estradiol (E2); androstenedione (A4) and dehydroepiandrosterone (DHEA)], were analysed by EIA in CMT homogenates. Levels of EGF were significantly higher in malignant compared with benign tumours, dysplasias and normal mammary glands (p<0.001). IMC presented the highest EGF levels, with statistical significant difference between IMC and non-IMC cases (p<0.05). Steroid hormone levels were also significantly higher in malignant tumours compared with benign tumours, dysplasias and normal mammary glands (p<0.001). In malignant tumours (non-IMC and IMC), a strong correlation was observed between EGF and: P4 (r=0.452; p=0.003); E2 (r=0.624; p=0.023); A4 (r=0.496; p=0.038); DHEA (r=0.431; p=0.005). These results suggest that EGF is implicated in canine mammary tumourigenesis. The positive correlation observed, opens an interesting perspective of interaction that should be further investigated. PMID:19429455

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  4. Histological and sex steroid hormone receptor changes in testes of immature, mature, and aged chickens.

    PubMed

    González-Morán, María Genoveva; Guerra-Araiza, Christian; Campos, María G; Camacho-Arroyo, Ignacio

    2008-11-01

    Sex steroid hormone receptors play a central role in the regulation of reproduction in male chickens. In this work, we evaluated by histomorphometric methods and Western blot analysis changes in the number of the different cell populations and in the content of sex steroid hormone receptors in testes from immature (1.5-month-old), mature (12-month-old), and aged (48-month-old) chickens. The number of Sertoli cells, germ cells, and Leydig cells per area of testicular tissue markedly changed according to chicken age. The highest number of Sertoli and Leydig cells was found in testes of immature chickens, with a dramatic decrease in those of mature chickens; however, the number of germ cells was the highest in mature chickens in comparison with other ages. The content of androgen receptor diminished in testes of mature and aged animals in comparison with that of immature chickens. In contrast, the content of estrogen receptor alpha and progesterone receptor was higher in testes of mature animals than in other ages. Both progesterone receptor isoforms were expressed in a similar proportion in testes of immature and mature animals. Interestingly, progesterone receptor isoform A was the predominant isoform in aged animals. These results suggest that there are marked age-dependent changes in chicken testes histology and in sex steroid hormone receptors content that should contribute to sex steroid hormone actions, in this tissue throughout the lifespan of chickens. PMID:18815005

  5. Determination of steroid hormones in biological and environmental samples using green microextraction techniques: an overview.

    PubMed

    Aufartová, Jana; Mahugo-Santana, Cristina; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan; Nováková, Lucie; Solich, Petr

    2011-10-17

    Residues of steroid hormones have become a cause for concern because they can affect the biological activity of non-target organisms. Steroid hormones are a potential risk for wildlife and humans through the consumption of contaminated food or water. Their determination requires extraction and clean-up steps, prior to detection, to reach low concentration levels. In recent years, a great effort has been made to develop new analytical methodologies, such as microextraction techniques, that reduce environmental pollution. Researchers have modified old methods to incorporate procedures that use less-hazardous chemicals or that use smaller amounts of them. They are able to do direct analysis using miniaturised equipment and reduced amounts of solvents and wastes. These accomplishments are the main objectives of green analytical chemistry. In this overview, we focus on microextraction techniques for the determination of steroid hormones in biological (e.g., human urine, human serum, fish, shrimp and prawn tissue and milk) and environmental (e.g., wastewaters, surface waters, tap waters, river waters, sewage sludges, marine sediments and river sediments) samples. We comment on the most recent applications in sorptive-microextraction modes, such as solid phase microextraction (SPME) with molecularly imprinted polymers (MIPs), in-tube solid-phase microextraction (IT-SPME), stir-bar sorptive extraction (SBSE) and microextraction in packed sorbent (MEPS). We also describe liquid-phase microextraction (LPME) approaches reported in the literature that are applied to the determination of steroid hormones. PMID:21907019

  6. 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

  7. 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

  8. 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

    2014-10-01

    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. PMID:25148584

  9. 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. PMID:26869995

  10. Anaerobic transformation kinetics and mechanism of steroid estrogenic hormones in dairy lagoon water.

    PubMed

    Zheng, Wei; Li, Xiaolin; Yates, Scott R; Bradford, Scott A

    2012-05-15

    Wastewater from concentrated animal feeding operations (CAFOs) frequently contains high concentrations of steroid estrogenic hormones. Release of these hormones into the environment may occur when CAFO wastewater is applied to agricultural lands as a nutrient and water source for crop production. To assess the potential risk of hormone contaminants derived from animal wastewater, we investigated the transformation kinetics and mechanisms of three natural estrogenic hormones (17α-estradiol, 17β-estradiol, and estrone) in aqueous solutions blended with dairy lagoon water under anaerobic conditions. Initial transformations of the three hormones in the dairy lagoon water were dominated by biodegradation and the degradation rates were temperature-dependent. The total amounts of hormones (initial concentration at 5 mg L(-1)) remaining in the solution after 52 days at 35 °C accounted for approximately 85%, 78%, and 77% of the initial amounts of 17α-estradiol, 17β-estradiol, and estrone, respectively. This observation suggests that these hormones are relatively stable over time and may accumulate in anaerobic or anoxic environments and anaerobic CAFO lagoons. A racemization reaction between 17α-estradiol and 17β-estradiol via estrone was observed in aqueous solutions in the presence of CAFO wastewater under anaerobic conditions. The initial hormone concentrations did not affect this degradation mechanism. A reversible reaction kinetic model was applied to fit the observed transformation dynamics. The degradation and regeneration of the parent hormone and its metabolites were successfully simulated by this model. The information in this study is useful for assessing the environmental risk of steroid hormones released from CAFO wastewater and to better understand why these hormone contaminants persist in many aquatic environments. PMID:22519517

  11. Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.

    PubMed Central

    Grosso, D S; Boyden, T W; Pamenter, R W; Johnson, D G; Stevens, D A; Galgiani, J N

    1983-01-01

    In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients. PMID:6301363

  12. 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.

  13. 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

  14. 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. PMID:26311247

  15. 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

  16. 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. PMID:25001661

  17. Steroid hormone receptors in prostatic hyperplasia and prostatic carcinoma.

    PubMed

    Khalid, B A; Nurshireen, A; Rashidah, M; Zainal, B Y; Roslan, B A; Mahamooth, Z

    1990-06-01

    One hundred and six prostatic tissue samples obtained from transurethral resection were analysed for androgen and estrogen receptors. In 62 of these, progesterone and glucocorticoid receptors were also assayed. Steroid receptors were assayed using single saturation dose 3H-labelled ligand assays. Ninety percent of the 97 prostatic hyperplasia tissues and six of the nine prostatic carcinoma tissues were positive for androgen receptors. Estrogen receptors were only present in 19% and 33% respectively. Progesterone receptors were present in 70% of the tissues, but glucocorticoid receptors were present in only 16% of prostatic hyperplasia and none in prostatic carcinoma. PMID:1725553

  18. Sexual maturation, serum steroid concentrations, and mRNA expression of IGF-1, luteinizing and progesterone hormone receptors and survivin gene in Japanese quail hens.

    PubMed

    Shit, N; Sastry, K V H; Singh, R P; Pandey, N K; Mohan, J

    2014-03-15

    In avian species, sexual maturation represents the evidence of start laying, which is a consequence of the development of ovarian follicles. These follicles are the functional reproductive unit whose maturation and viability critically depends on endocrine, paracrine, and autocrine factors beyond the signals from the central nervous system. The present study was undertaken to investigate the correlation of sexual maturity with tissue growth, mRNA expression of certain genes, and serum steroid concentrations in Japanese quail hens. To carry out the present study, a total of forty Japanese quail hens (5 weeks) were housed individually under uniform husbandry condition with ad libitum quail layer ration and water at 14-hour photo schedule. On sixth week onwards, four birds were sacrificed at each time on 1, 3, 7, 10, 13, 16, 19, 22, 25, and 28 days. Serum was extracted aseptically to analyze the gonadal steroid hormones (estrogen and progesterone) and corticosterone to investigate the liaison with sexual maturation of the species. Expression analyses of four genes i.e., insulin-like growth factor-1, luteinizing hormone receptor, progesterone receptor, and survivin were carried out in the three largest ovarian yellow follicles. A significant (P < 0.05) increase in body weight gain and oviduct weight was recorded during the phase of sexual maturation. Smaller follicles revealed higher insulin-like growth factor-1 and survivin gene expression, whereas the reverse result was manifested in both the luteinizing and progesterone hormone receptors. In biochemical study, the gonadal steroids (estrogen and progesterone) were recorded higher at the first half of the experiment when a gradual decrease in corticosterone concentration was confirmed from the very beginning of this study. This result substantiated that sexual maturation in Japanese quail may be completed by the time of 8 weeks after its birth in support of the analyzed information studied in the current investigation

  19. Sorption, fate, and transport of endogenous steroid hormones in soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The natural hormones 17 beta-estradiol (E2) and testosterone (T) are present in animal manures that are applied to agricultural land as fertilizer and, potentially, may act as endocrine disruptors. Laboratory incubation, batch, and column experiments have been conducted on a series of soils and wer...

  20. 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

  1. 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.

  2. Regulation of the hyaluronan system in ovine endometrium by ovarian steroids.

    PubMed

    Raheem, Kabir A; Marei, Waleed F; Mifsud, Karen; Khalid, Muhammad; Wathes, D Claire; Fouladi-Nashta, Ali A

    2013-05-01

    In this study, we investigated steroid regulation of the hyaluronan (HA) system in ovine endometrium including HA synthases (HAS), hyaluronidases, and HA receptor-CD44 using 30 adult Welsh Mountain ewes. Eight ewes were kept intact and synchronized to estrous (day 0). Intact ewes were killed on day 9 (luteal phase; LUT; n=5) and day 16 (follicular phase; FOL; n=3). The remaining ewes (n=22) were ovariectomized and then treated (i.m.) with vehicle (n=6) or progesterone (n=8) for 10 days, or estrogen and progesterone for 3 days followed by 7 days of progesterone alone (n=8). Estradiol and progesterone concentrations in plasma correlated with the stage of estrous or steroid treatment. Our results showed trends (P<0.1) and statistically significant effects (P<0.05, by t-test) indicating that LUT had lower HAS1 and HAS2 and higher HAS3 and CD44 mRNA expression compared with FOL. This was reflected in immunostaining of the corresponding HAS proteins. Similarly, in ovariectomized ewes, progesterone decreased HAS1 and HAS2 and increased HAS3 and CD44, whereas estradiol tended to increase HAS2 and decrease CD44. Sometimes, HAS mRNA expression did not follow the same trend observed in the intact animals or the protein expression. HA and its associated genes and receptors were regulated by the steroids. In conclusion, these results show that the level of HA production and the molecular weight of HA in the endometrium are regulated by ovarian steroids through differential expression of different HAS both at the gene and at the protein levels. PMID:23630333

  3. Molecularly imprinted polymer applied to the selective isolation of urinary steroid hormones: an efficient tool in the control of natural steroid hormones abuse in cattle.

    PubMed

    Doué, Mickael; Bichon, Emmanuelle; Dervilly-Pinel, Gaud; Pichon, Valérie; Chapuis-Hugon, Florence; Lesellier, Eric; West, Caroline; Monteau, Fabrice; Le Bizec, Bruno

    2012-12-28

    The use of anabolic substances to promote growth in livestock is prohibited within the European Union as laid down in Directive 96/22/EC. Nowadays, efficient methods such as steroid profiling or isotopic deviation measurements allow to control natural steroid hormones abuse. In both cases, urine is often selected as the most relevant matrix and, due to its relatively high content of potential interferents, its preparation before analysis is considered as a key step. In this context, the use of a selective sorbent such as molecularly imprinted polymer (MIP) was investigated. A MIP was synthesized based on 17β-estradiol, methacrylic acid and acetonitrile as template, monomer and porogen, respectively. Two approaches were then tested for non-conjugated (aglycons and glucuronides deconjugated) steroid purification: (i) molecularly imprinted solid phase extraction (MISPE) and (ii) semi-preparative supercritical fluid chromatography with a commercial MIP as stationary phase (SFC-MIP). Parameters for both approaches were optimized based on the main bovine metabolites of testosterone, estradiol, nandrolone and boldenone. The MISPE protocol developed for screening purposes allowed satisfactory recoveries (upper 65% for the 12 target steroids) with sufficient purification for gas chromatography-mass spectrometry (GC-MS) analysis. For confirmatory purposes, the use of isotopic ratio mass spectrometry (IRMS) requires a higher degree of purity of the target compounds, which can be reached by the SFC-MIP protocol with three steps less compared to the official and current method. Purity, concentration and absence of isotopic fractionation of target steroids extracted from urine of treated cattle (treated with testosterone, estradiol, androstenedione, and boldenone) allowed the measurement of (13)C/(12)C isotopic ratios of corresponding metabolites and endogenous reference compounds (ERC) and proved the relevance of the strategy. PMID:23195708

  4. 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

  5. Sex steroids, growth hormone, leptin and the pubertal growth spurt.

    PubMed

    Rogol, Alan D

    2010-01-01

    A normal rate for the linear growth of a child or adolescent is a strong statement for the good general health of that child. Normal growth during childhood is primarily dependent on adequate nutrition, an adequate psychosocial environment, the absence of disease and adequate amounts thyroid hormone and growth hormone (and its downstream product, IGF-1). At adolescence there is the reawakening of the hypothalamic-pituitary-gonadal axis and its interaction with the GH/IGF-1 axis to subserve the pubertal growth spurt. The fat tissue-derived hormone, leptin and its receptor are likely involved in at least two aspects of pubertal development - sexual development itself and the alterations in body composition including the regional distribution of fat and bone mineralization. During the prepubertal years the male female differences in body composition are quite modest, but change remarkably during pubertal development with boys showing a relative decrement in fat percentage and girls a marked increase in concert with rising levels of circulating leptin. The boys show a much greater increase in lean body tissue and the relative proportions of water, muscle and bone. These may be observed as the differential growth of the shoulders and hips. The net effect of these pubertal changes is that the young adult woman has approximately 25% body fat in the 'gynoid' distribution while the male has much more muscle, especially in the shoulders and upper body but only approximately 13% body fat. PMID:19955758

  6. Intramuscular sex steroid hormones are associated with skeletal muscle strength and power in women with different hormonal status

    PubMed Central

    Pöllänen, Eija; Kangas, Reeta; Horttanainen, Mia; Niskala, Paula; Kaprio, Jaakko; Butler-Browne, Gillian; Mouly, Vincent; Sipilä, Sarianna; Kovanen, Vuokko

    2015-01-01

    Estrogen (E2)-responsive peripheral tissues, such as skeletal muscle, may suffer from hormone deficiency after menopause potentially contributing to the aging of muscle. However, recently E2 was shown to be synthesized by muscle and its systemic and intramuscular hormone levels are unequal. The objective of the study was to examine the association between intramuscular steroid hormones and muscle characteristics in premenopausal women (n = 8) and in postmenopausal monozygotic twin sister pairs (n = 16 co-twins from eight pairs) discordant for the use of E2-based hormone replacement. Isometric skeletal muscle strength was assessed by measuring knee extension strength. Explosive lower body muscle power was assessed as vertical jump height. Due to sequential nature of enzymatic conversion of biologically inactive dehydroepiandrosterone (DHEA) to testosterone (T) and subsequently to E2 or dihydrotestosterone (DHT), separate linear regression models were used to estimate the association of each hormone with muscle characteristics. Intramuscular E2, T, DHT, and DHEA proved to be significant, independent predictors of strength and power explaining 59–64% of the variation in knee extension strength and 80–83% of the variation of vertical jumping height in women (P < 0.005 for all models). The models were adjusted for age, systemic E2, and total body fat mass. The statistics used took into account the lack of statistical independence of twin sisters. Furthermore, muscle cells were shown to take up and actively synthesize hormones. Present study suggests intramuscular sex steroids to associate with strength and power regulation in female muscle providing novel insight to the field of muscle aging. PMID:25645687

  7. 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

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

    PubMed Central

    Pinto, Francisco M; Pintado, C Oscar; Pennefather, Jocelyn N; Patak, Eva; Candenas, Luz

    2009-01-01

    Background In the mouse uterus, pregnancy is accompanied by changes in tachykinin and tachykinin receptor gene expression and in the uterotonic effects of endogenous tachykinins. In this study we have investigated whether changes in tachykinin expression and responses are a result of changes in ovarian steroid levels. Methods We quantified the mRNAs of tachykinins and tachykinin receptors in uteri from ovariectomized mice and studied their regulation in response to estrogen and progesterone using real-time quantitative RT-PCR. Early (3 h) and late (24 h) responses to estrogen were evaluated and the participation of the estrogen receptors (ER), ERalpha and ERbeta, was analyzed by treating mice with propylpyrazole triol, a selective ERalpha agonist, or diarylpropionitrile, a selective agonist of ERbeta. Results All genes encoding tachykinins (Tac1, Tac2 and Tac4) and tachykinin receptors (Tacr1, Tacr2 and Tacr3) were expressed in uteri from ovariectomized mice. Estrogen increased Tac1 and Tacr1 mRNA after 3 h and decreased Tac1 and Tac4 expression after 24 h. Tac2 and Tacr3 mRNA levels were decreased by estrogen at both 3 and 24 h. Most effects of estrogen were also observed in animals treated with propylpyrazole triol. Progesterone treatment increased the levels of Tac2. Conclusion These results show that the expression of tachykinins and their receptors in the mouse uterus is tightly and differentially regulated by ovarian steroids. Estrogen effects are mainly mediated by ERalpha supporting an essential role for this estrogen receptor in the regulation of the tachykinergic system in the mouse uterus. PMID:19627578

  9. Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity

    PubMed Central

    Brenowitz, Eliot A.

    2014-01-01

    The avian song control system provides an excellent model for studying transsynaptic trophic effects of steroid sex hormones. Seasonal changes in systemic testosterone (T) and its metabolites regulate plasticity of this system. Steroids interact with the neurotrophin brain-derived neurotrophic factor (BDNF) to influence cellular processes of plasticity in nucleus HVC of adult birds, including the addition of newborn neurons. This interaction may also occur transsynpatically; T increases the synthesis of BDNF in HVC, and BDNF protein is then released by HVC neurons on to postsynaptic cells in nucleus RA where it has trophic effects on activity and morphology. Androgen action on RA neurons increases their activity and this has a retrograde trophic effect on the addition of new neurons to HVC. The functional linkage of sex steroids to BDNF may be of adaptive value in regulating the trophic effects of the neurotrophin and coordinating circuit function in reproductively relevant contexts. PMID:25285401

  10. Immunolocalization of steroid hormone receptors in normal and tumour cells: mechanisms of their cellular traffic.

    PubMed

    Perrot-Applanat, M; Guiochon-Mantel, A; Milgrom, E

    1992-01-01

    Experimental conditions are described for the detection of steroid receptors in tissue sections or cells at the light microscope level. Current knowledge about the ultrastructural distribution of these receptors is summarized; the mechanisms of their nuclear localization are described. Karyophilic signals involved in nuclear translocation are characterized by means of in vitro mutagenesis of steroid receptor cDNAs. Studies analysing the subcellular distribution of various transfected receptor mutants in energy depleted cells together with fusion experiments provide evidence for nucleoplasmic shuttling of progesterone receptors. We conclude that the "nuclear" location of the wild type progesterone receptor reflects a dynamic equilibrium between active nuclear import and outward diffusion. We also describe the use of immunocytochemistry in pathology, especially for the detection of steroid receptors in hormone dependent tumours. PMID:1423330

  11. 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.

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

    PubMed

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

    2008-02-27

    Steroid hormones effect 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

  13. 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. PMID:26050561

  14. Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis.

    PubMed

    Handa, R J; Burgess, L H; Kerr, J E; O'Keefe, J A

    1994-12-01

    The rapid activation of stress-responsive neuroendocrine systems is a basic reaction of animals to perturbations in their environment. One well-established response is that of the hypothalamo-pituitary-adrenal (HPA) axis. In rats, corticosterone is the major adrenal steroid secreted and is released in direct response to adrenocorticotropin (ACTH) secreted from the anterior pituitary gland. ACTH in turn is regulated by the hypothalamic factor, corticotropin-releasing hormone. A sex difference exists in the response of the HPA axis to stress, with females reacting more robustly than males. It has been demonstrated that in both sexes, products of the HPA axis inhibit reproductive function. Conversely, the sex differences in HPA function are in part due to differences in the circulating gonadal steroid hormone milieu. It appears that testosterone can act to inhibit HPA function, whereas estrogen can enhance HPA function. One mechanism by which androgens and estrogens modulate stress responses is through the binding to their cognate receptors in the central nervous system. The distribution and regulation of androgen and estrogen receptors within the CNS suggest possible sites and mechanisms by which gonadal steroid hormones can influence stress responses. In the case of androgens, data suggest that the control of the hypothalamic paraventricular nucleus is mediated trans-synaptically. For estrogen, modulation of the HPA axis may be due to changes in glucocorticoid receptor-mediated negative feedback mechanisms. The results of a variety of studies suggest that gonadal steroid hormones, particularly testosterone, modulate HPA activity in an attempt to prevent the deleterious effects of HPA activation on reproductive function. PMID:7729815

  15. 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. PMID:21145504

  16. 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

  17. 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

  18. Inhibition of catechol estrogen formation in rat liver microsomes by hormonal steroids and related compounds.

    PubMed

    Quail, J A; Newcombe, A M; Jellinck, P H

    1988-10-01

    The inhibitory action of a number of different hormonal steroids and related compounds on the 2-hydroxylation of estradiol by male rat liver microsomes was examined by a radiometric assay. Progesterone, Diethylstilbestrol, testosterone and 4-androstenedione were found to be the most potent of the compounds tested but inhibition was also observed with other steroids and a group of androgen analogs which are aromatization inhibitors. The kinetic constant Ki for those steroids which gave linear double reciprocal plots when added to [2-3H]estradiol was determined and the products from [14C]estradiol in the presence of the inhibitors were examined by TLC and autoradiography. The addition of steroids with a 17-hydroxyl group such as testosterone or dihydroequilin resulted in the formation of mainly 2-hydroxyestradiol with smaller amounts of other metabolites while those with a reducible ketonic group such as progesterone, 4-androstenedione, equilin or equilenin gave rise to considerable amounts of estrone in addition to the catechol estrogens. Further purification of the liver microsomes did not alter this effect. The possible role of progesterone and the catechol estrogens in the control of estrogen hydroxylation in liver as well as other aspects of steroid interaction are discussed. PMID:2845195

  19. Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone.

    PubMed

    Anderson, E; Lee, M T; Lee, G Y

    1992-11-01

    Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha-dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a

  20. CYP18A1 regulates tissue-specific steroid hormone inactivation in Bombyx mori.

    PubMed

    Li, Zhiqian; Ge, Xie; Ling, Lin; Zeng, Baosheng; Xu, Jun; Aslam, Abu F M; You, Lang; Palli, Subba Reddy; Huang, Yongping; Tan, Anjiang

    2014-11-01

    Insect development and metamorphosis are regulated by two major hormones, juvenile hormone and ecdysteroids. Despite being the key regulator of insect developmental transitions, the metabolic pathway of the primary steroid hormone, 20-hydroxyecdysone (20E), especially its inactivation pathway, is still not completely elucidated. A cytochrome P450 enzyme, CYP18A1, has been shown to play key roles in insect steroid hormone inactivation through 26-hydroxylation. Here, we identified two CYP18 (BmCYP18A1 and BmCYP18B1) orthologs in the lepidopteran model insect, Bombyx mori. Interestingly, BmCYP18A1 gene is predominantly expressed in the middle silk gland (MSG) while BmCYP18B1 expresses ubiquitously in B. mori. BmCYP18A1 is induced by 20E in vitro, suggesting its role in 20E metabolism. Using the binary Gal4/UAS transgenic system, we ectopically overexpressed BmCYP18A1 in a MSG-specific manner with a Sericin1-Gal4 (Ser-Gal4) driver or in a ubiquitous manner with an Actin3-Gal4 (A3-Gal4) driver. Ectopic overexpression of BmCYP18A1 in MSG or in all tissues resulted in developmental arrestment of transgenic animals during the final instar larval stage. The 20E titers in the transgenic animals expressing BmCYP18A1 were lower compared to the levels in the control animals. Although the biological significance of MSG-specific expression of BmCYP18A1 is unclear, our results provide the first evidence that BmCYP18A1, which is conserved in most arthropods, is involved in a tissue-specific steroid hormone inactivation in B. mori. PMID:25173591

  1. CYP18A1 regulates tissue-specific steroid hormone inactivation in Bombyx mori

    PubMed Central

    Li, Zhiqian; Ge, Xie; Ling, Lin; Zeng, Baosheng; Xu, Jun; Aslam, Abu F.M.; You, Lang; Palli, Subba Reddy; Huang, Yongping; Tan, Anjiang

    2015-01-01

    Insect development and metamorphosis are regulated by two major hormones, juvenile hormone and ecdysteroids. Despite being the key regulator of insect developmental transitions, the metabolic pathway of the primary steroid hormone, 20-hydroxyecdysone (20E), especially its inactivation pathway, is still not completely elucidated. A cytochrome P450 enzyme, CYP18A1, has been shown to play key roles in insect steroid hormone inactivation through 26-hydroxylation. Here, we identified two CYP18 (BmCYP18A1 and BmCYP18B1) orthologs in the lepidopteran model insect, Bombyx mori. Interestingly, BmCYP18A1 gene is predominantly expressed in the middle silk gland (MSG) while BmCYP18B1 expresses ubiquitously in B. mori. BmCYP18A1 is induced by 20E in vitro, suggesting its role in 20E metabolism. Using the binary Gal4/UAS transgenic system, we ectopically overexpressed BmCYP18A1 in a MSG-specific manner with a Sericin1-Gal4 (Ser-Gal4) driver or in a ubiquitous manner with an Actin3-Gal4 (A3-Gal4) driver. Ectopic overexpression of BmCYP18A1 in MSG or in all tissues resulted in developmental arrestment of transgenic animals during the final instar larval stage. The 20E titers in the transgenic animals expressing BmCYP18A1 were lower compared to the levels in the control animals. Although the biological significance of MSG-specific expression of BmCYP18A1 is unclear, our results provide the first evidence that BmCYP18A1, which is conserved in most arthropods, is involved in a tissue-specific steroid hormone inactivation in B. mori. PMID:25173591

  2. Peripheral vs. Central Sex Steroid Hormones in Experimental Parkinson’s Disease

    PubMed Central

    McArthur, Simon; Gillies, Glenda E.

    2011-01-01

    The nigrostriatal dopaminergic (NSDA) pathway degenerates in Parkinson’s disease (PD), which occurs with approximately twice the incidence in men than women. Studies of the influence of systemic estrogens in females suggest sex hormones contribute to these differences. In this review we analyze the evidence revealing great complexity in the response of the healthy and injured NSDA system to hormonal influences, and emphasize the importance of centrally generated estrogens. At physiological levels, circulating estrogen (in females) or estrogen precursors (testosterone in males, aromatized to estrogen centrally) have negligible effects on dopaminergic neuron survival in experimental PD, but can modify striatal dopamine levels via actions on the activity or adaptive responses of surviving cells. However, these effects are sexually dimorphic. In females, estradiol promotes adaptive responses in the partially injured NSDA pathway, preserving striatal dopamine, whereas in males gonadal steroids and exogenous estradiol have a negligible or even suppressive effect, effectively exacerbating dopamine loss. On balance, the different effects of gonadal factors in males and females contribute to sex differences in experimental PD. Fundamental sex differences in brain organization, including the sexually dimorphic networks regulating NSDA activity are likely to underpin these responses. In contrast, estrogen generated locally appears to preserve striatal dopamine in both sexes. The available data therefore highlight the need to understand the biological basis of sex-specific responses of the NSDA system to peripheral hormones, so as to realize the potential for sex-specific, hormone-based therapies in PD. Furthermore, they suggest that targeting central steroid generation could be equally effective in preserving striatal dopamine in both sexes. Clarification of the relative roles of peripheral and central sex steroid hormones is thus an important challenge for future studies

  3. 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.

  4. 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.

  5. Impact of ovarian hormones on the modulation of the serotonin transporter by fluvoxamine.

    PubMed

    Benmansour, Saloua; Piotrowski, Jonathan P; Altamirano, Alfonso V; Frazer, Alan

    2009-02-01

    Most preclinical studies examining the mechanism(s) of action of antidepressants are carried out using male animals. Blockade of serotonin transporter (SERT) function by selective serotonin reuptake inhibitors (SSRIs) is the initial event that triggers a not completely understood process that results in clinical improvement in depression. To investigate whether there are differences in the ability of SSRIs to inhibit the SERT between male and female rats at different phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was measured by in vivo chronoamperometry. Local application of the SSRI, fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5-HT clearance time parameters in male rats and female rats in estrus or diestrus, but not in proestrus. The contribution of ovarian steroids to this result was investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB) and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance time parameters, whereas EB and/or P treatment blocked this effect, consistent with what was seen in female rats in proestrus. This effect was gender-specific, since treatment of castrated rats with EB/P had no effect on the ability of fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed that 1-60 min after local application of 17-beta-estradiol (E(2)) into the CA3 region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E(2)-BSA mimicked E(2)'s effects at 10 min but not at 60 min. Pretreatment with estrogen receptor antagonists blocked the effects of E(2). The finding that acutely both estradiol and progesterone can inhibit the ability of an SSRI to slow the clearance of 5-HT, may have important implications for the use of SSRIs in women. PMID:18322468

  6. Hormonally-mediated Epigenetic Changes to Steroid Receptors in the Developing Brain: Implications for Sexual Differentiation

    PubMed Central

    Nugent, Bridget M.; Schwarz, Jaclyn M.; McCarthy, Margaret M.

    2010-01-01

    The establishment of sex-specific neural morphology, which underlies sex-specific behaviors, occurs during a perinatal sensitive window in which brief exposure to gonadal steroid hormones produces permanent masculinization of the brain. In the rodent, estradiol derived from testicular androgens is a principle organizational hormone. The mechanism by which transient estradiol exposure induces permanent differences in neuronal anatomy has been widely investigated, but remains elusive. Epigenetic changes, such as DNA methylation, allow environmental influences to alter long-term gene expression patterns and therefore may be a potential mediator of estradiol-induced organization of the neonatal brain. Here we review data that demonstrate sex and estradiol-induced differences in DNA methylation on the estrogen receptor α (ERα), estrogen receptor β (ERβ), and progesterone receptor (PR) promoters in sexually dimorphic brain regions across development. Contrary to the overarching view of DNA methylation as a permanent modification directly tied to gene expression, these data demonstrate that methylation patterns on steroid hormone receptors change across the life span and do not necessarily predict expression. Although further exploration into the mechanism and significance of estradiol-induced alterations in DNA methylation patterns in the neonatal brain is necessary, these results provide preliminary evidence that epigenetic alterations can occur in response to early hormone exposure and may mediate estradiol-induced organization of sex differences in the neonatal brain. PMID:20800064

  7. [Electron paramagnetic resonance study of the interactions between steroid hormones and binding proteins].

    PubMed

    Basset, M; Chambaz, E M; Defaye, G; Metz, B

    1978-01-01

    Interaction of a spin labeled corticosteroid (desoxycorticosterone nitroxyde: DOC -NO) with three purified proteins (albumin, transcortin, progesterone binding protein: PBG) was studied by electron spin resonance (ESR) spectroscopy. DOC-NO was competitive with natural corticosteroids and therefore bound at the same site to specific binding proteins. ESR spectra in the presence of each of the proteins showed an immobilized (bound) form of the spin labeled steroid and allowed the calculation of the corresponding association constant (Ka) at equilibrium. The three binding proteins could be characterized by the ESR parameters of the DOC-NO bound form. The thermodynamic parameters (deltaH, deltaS) of the steroid-protein interactions were calculated from the ESR data obtained within a wide temperature range (3--40 degrees C). The ESR spectra width (2T) was used to evaluate the polarity of the spin label environment within the steroid binding site: a hydrophobic character was observed for transcortin whereas PBG exhibited a more hydrophilic steroid binding sits. The rotational correlation time of the three protein DOC-NO complexes at equilibrium were calculated from ESR data; the results were correlated with the protein molecular size and suggested a non spherical shape for the binding macromolecule in solution. Spin labelling of biologically active steroids thus provides a novel approach for the study of the interaction of these hormones with their binding protein. Providing a suitable spin label, the ESR parameters may allow the characterization of several types of binding sites of different biological significance for the same hormone, in biological fluids as well as in target tissues. PMID:83166

  8. Accumulation of steroid hormones in soil and its adjacent aquatic environment from a typical intensive vegetable cultivation of North China.

    PubMed

    Zhang, Feng-Song; Xie, Yun-Feng; Li, Xue-Wen; Wang, Dai-Yi; Yang, Lin-Sheng; Nie, Zhi-Qiang

    2015-12-15

    Steroid hormones released from manure agricultural application are a matter of global concern. The residual levels of steroid hormones were studied in a typical intensive vegetable cultivation area in northeast China, with a long history of heavy manure application. Seven steroids (estrone, 17α-estradiol, 17β-estradiol, estriol, testosterone, androstendione and progesterone) were analyzed from soil sampled from vegetable greenhouses, from sediments and water from the adjacent drainage ditch and from the groundwater. The results showed that target steroids were detected in the soil samples, with detection frequencies varying from 3.13 to 100%. The steroid concentrations varied substantially in soils, ranging from below the detection limit to 109.7μg·kg(-1). Three steroids-progesterone, androstendione and estrone-were found to have relatively high residue concentrations in soil, with maximum concentrations of 109.7, 9.83 and 13.30μg·kg(-1), respectively. In adjacent groundwater, all the steroids, with the exception of estrone, were detected in one or more of the 13 groundwater samples. The concentrations of steroids in groundwater ranged from below the method detection limit to 2.38ng·L(-1). Six of the seven (excluding androstendione) were detected in drainage ditch water samples, with concentrations ranging from below the detection limit to 14ng·L(-1). Progesterone, androstendione and estrone accumulated relatively easily in soils; their concentrations in groundwater were lower than those of other steroids. The concentrations of testosterone and estriol were relatively low in soil, while in groundwater were higher than those of other steroids. The residual levels of steroids in soil and groundwater showed a clear spatial variation in the study area. The residual levels of steroid hormones in soil varied substantially between differently planted greenhouses. PMID:26318226

  9. Modulating Intrafollicular Hormonal Milieu in Controlled Ovarian Stimulation: Insights From PPAR Expression in Human Granulosa Cells.

    PubMed

    Tatone, Carla; Benedetti, Elisabetta; Vitti, Maurizio; Di Emidio, Giovanna; Ciriminna, Rosanna; Vento, Maria Elena; Cela, Vito; Borzì, Placido; Carta, Gaspare; Lispi, Monica; Cimini, Anna Maria; Artini, Paolo Giovanni

    2016-04-01

    Controlled ovarian stimulation (COS) leading to ovulation of multiple follicles is a crucial aspect of biomedical infertility care. Nevertheless, biomarkers useful for COS management are still lacking. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors relevant to steroid metabolism in granulosa cells (GCs). We investigated whether PPARs and their steroidogenic targets were differentially expressed in GCs differentiated under different recombinant or urinary gonadotropin preparations. GCs from women subjected to COS with r-hFSH, r-hFSH/r-hLH, or hMG-HP were processed to assess expression of PPARα, PPARβ/δ, PPARγ, and steroidogenic enzymes under PPAR modulation. As an evidence of their activation, all PPAR isotypes with their coactivators, the retinoic-X-receptors (RXRs), localized in the nucleus. When GCs from r-hFSH/r-hLH group were compared with r-hFSH, a significant reduction of PPARα protein was observed. By contrast, an increase of PPARβ/δ at both protein and mRNA levels along with that of PPARγ protein were detected. The steroidogenic enzymes 17βHSD IV, 3βHSD II, and HMG-CoA red were downregulated in the r-hFSH/r-hLH group in comparison to r-hFSH unlike CYP19A1 that remained unchanged. In GCs from urinary FSH-LH stimulation (hMG-HP), PPARα was more expressed in comparison with r-hFSH/r-hLH group. Likewise, 3βHSD II and 17βHSD IV were increased suggesting that hMG-HP partially mimicked r-hFSH/r-hLH effects. In summary, transcript analysis associated to protein investigation revealed differential effects of COS protocols on PPARs and their steroidogenic targets in relation to LH and gonadotropin source. These observations candidate PPARs as new biomarkers of follicle competence opening new hypotheses on COS effects on ovarian physiology. J. Cell. Physiol. 231: 908-914, 2016. © 2015 Wiley Periodicals, Inc. PMID:26332656

  10. Interaction between use of non-steroidal anti-inflammatory drugs and selected genetic polymorphisms in ovarian cancer risk

    PubMed Central

    Pinheiro, Simone P; Gates, Margaret A; DeVivo, Immaculata; Rosner, Bernard A; Tworoger, Shelley S; Titus-Ernstoff, Linda; Hankinson, Susan E; Cramer, Daniel W

    2010-01-01

    Inflammation and non-steroidal anti-inflammatory agents (NSAIDs) may play important role in ovarian cancer. However, epidemiologic data are inconsistent, possibly reflecting inter-individual genetic differences affecting the metabolism of NSAIDs. We examined whether common polymorphisms affecting the metabolism of NSAIDs modify the association between NSAIDs and ovarian cancer risk. We genotyped 1,353 DNA samples from women who developed ovarian cancer and 1,823 samples from matched controls participating in the New England Case-Control study and the Nurses' Health Studies. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) associated with regular use of NSAIDs and with relevant polymorphisms on ovarian cancer risk. Multivariable unconditional logistic regression estimated the association of NSAID use across stratum of each genotype. Regular use of NSAIDs was not associated with ovarian cancer risk. Multivariable OR (95% CI) associated with use NSAIDs was 0.85 (95% CI: 0.71-1.02). Associations between NSAID use and ovarian cancer risk did not differ significantly across strata of genotypes. None of the studied polymorphisms was associated with ovarian cancer risk. The multivariable ORs (95% CI) associated with CYP2C9 and UGT1A6 variant genotypes were 0.99 (0.90-1.08) and 0.93 (0.82-1.05), respectively. The multivariable ORs (95% CI) associated with PPAR-γ, COX-2 -765G>C, and COX-2 Ex10+837T>C polymorphisms were 1.02 (0.87-1.20), 0.87 (0.75-1.00), and 0.97 (0.87-1.09), respectively. In this relatively large study, we found no convincing evidence supporting an association between NSAIDs use and ovarian cancer risk. Furthermore, data did not suggest interaction between selected polymorphisms and use of NSAIDs in relation to ovarian cancer risk. PMID:21532843

  11. Steroid induction of a peptide hormone gene leads to orchestration of a defined behavioral sequence.

    PubMed

    Zitnan, D; Ross, L S; Zitnanova, I; Hermesman, J L; Gill, S S; Adams, M E

    1999-07-01

    At the end of each molt, insects shed the old cuticle by performing preecdysis and ecdysis behaviors. Regulation of these centrally patterned movements involves peptide signaling between endocrine Inka cells and the CNS. In Inka cells, we have identified the cDNA and gene encoding preecdysis-triggering hormone (PETH) and ecdysis-triggering hormone (ETH), which activate these behaviors. Prior to behavioral onset, rising ecdysteroid levels induce expression of the ecdysone receptor (EcR) and ETH gene in Inka cells and evoke CNS sensitivity to PETH and ETH. Subsequent ecdysteroid decline is required for peptide release, which initiates three motor patterns in specific order: PETH triggers preecdysis I, while ETH activates preecdysis II and ecdysis. The Inka cell provides a model for linking steroid regulation of peptide hormone expression and release with activation of a defined behavioral sequence. PMID:10433264

  12. Ovarian hormones influence odor cues emitted by female meadow voles, Microtus pennsylvanicus.

    PubMed

    Ferkin, M H; Gorman, M R; Zucker, I

    1991-12-01

    During the spring-summer breeding season female meadow voles emit odors that are preferred by males, whereas in the autumn-winter season of reproductive quiescence females emit odors that are not preferred by males, but are attractive to females. The effects of daylength and ovarian hormones on salience of female odors were determined by assaying male responses to odors. Females housed in long and short photoperiods transmitted odors that elicited responses similar to those of spring and autumn female voles, respectively. The odor cues emitted by ovariectomized (OVX) females, irrespective of photoperiodic history, were similar to those generated by females during the nonbreeding season. In the absence of ovarian hormones, long daylengths were not sufficient to induce females to broadcast the spring odors preferred by males. Spring-type odor cues were, however, emitted by OVX voles housed in either photoperiod and treated with estradiol. Ovarian hormones appear necessary and sufficient to generate breeding season odor cues and sufficient to induce production of such cues during the nonbreeding season. We conclude that daylength affects odor cues emitted by females by altering ovarian hormone activity. PMID:1813382

  13. 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…

  14. 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. PMID:26059287

  15. Serum Anti-Müllerian Hormone Levels before Surgery in Patients with Ovarian Endometriomas Compared to Other Benign Ovarian Cysts

    PubMed Central

    Jeon, Ji Hyun; Park, So Yun; Lee, Sa Ra; Chung, Hye Won

    2015-01-01

    Objectives To evaluate preoperative anti-Müllerian hormone (AMH) levels in women with endometrioma or other benign ovarian cysts and differences of AMH changes according to various characteristics. Methods Ninety-seven patients aged 20 to 39 years who underwent surgery for benign ovarian cyst were enrolled retrospectively. Of these, 65 patients were diagnosed as endometriomas, and 32 had other benign cysts. Serum AMH, mean, maximum, and total diameter of ovarian cysts were measured. The AMH levels were compared according to pathology (endometrioma vs. other benign cyst), size of ovarian cyst, age-matched AMH quartile percentile and characteristics of endometrioma. Results Preoperative serum AMH level was significantly lower in endometrioma group than other benign cyst group (4.12 ± 2.42 ng/mL vs. 6.02 ± 2.29 ng/mL, P < 0.001). Serum AMH level was significantly lower in endometrioma group, especially in patients aged 30 to 39 years. Dividing to age-matched AMH quartile percentile, there were significantly fewer patients with AMH level ≥ 75 percentile in endometrioma group (24.6% vs. 50.0%, P = 0.035). Among 4 subgroups of endometrioma, patients with AMH level ≥ 75 percentile were significantly decreased in multiple bilateral endometrioma group. Mean and total diameter of cysts were negatively correlated with preoperative serum AMH level in other benign cyst group. Conclusion We suggest that preoperative AMH level measurement might be considered in women with endometrioma, especially in 30 to 39 years old, multiple bilateral type, or big-sized other benign ovarian cyst to assess the diminished ovarian reserve. PMID:26793679

  16. Lipopolysaccharide in ovarian follicular fluid influences the steroid production in large follicles of dairy cows.

    PubMed

    Magata, Fumie; Horiuchi, Maya; Echizenya, Riku; Miura, Ryotaro; Chiba, Shiori; Matsui, Motozumi; Miyamoto, Akio; Kobayashi, Yoshiyasu; Shimizu, Takashi

    2014-01-10

    In postpartum dairy cows, various inflammatory diseases depress reproductive performance. Lipopolysaccharide (LPS) derived from infections of the uterus or mammary gland with Gram-negative bacteria was shown to suppress steroid production in the granulosa cells of follicles in vitro. The aim of the study was to investigate the relationship between LPS in ovarian follicular fluid and steroidogenesis by the theca and granulosa cells of the large follicles in vivo. Bovine ovaries were collected from a slaughterhouse, and the largest (F1) and the second largest (F2) follicles were used (>8 mm in diameter, n=38). LPS concentration in the follicular fluid was measured using quantitative kinetic assay. Follicular steroidogenesis was evaluated by measuring the estradiol (E2) and progesterone (P4) concentration in follicular fluid and by analysing transcription levels of steroidogenesis-related genes in theca and granulosa cells. LPS concentration detected in follicular fluid ranged from 0.2 to 2.0 EU/mL. In follicles with a high level of LPS (>0.5 EU/mL, n=15), the concentration of E2 was lower and that of P4 was higher when compared to those in follicles with a low level of LPS (<0.5 EU/mL, n=23), which was observed both in F1 and F2 follicles. Furthermore, in follicles with a high level of LPS, transcripts of steroidogenic enzymes such as CYP17 and P450arom were lower. In those follicles, the expression of caspase-3 was high, suggesting an association with follicular atresia. These findings indicate that LPS present in follicular fluid may cause ovarian dysfunction by inhibiting follicular activity. PMID:24321186

  17. Association of follicle stimulating hormone receptor promoter with ovarian response in IVF-ET patients

    PubMed Central

    Dan, Wang; Jing, Gao; Liangbin, Xia; Ting, Zhang; Ying, Zeng

    2015-01-01

    Background: Poor ovarian response phenomenon has been observed in some of the in vitro fertilization-embryo transfer patients. Some investigations found that follicle stimulating hormone receptor (FSHR) gene plays a role in the process, but no direct evidence shows the correlation between genotypes of FSHR and ovarian response. Objective: Exploring the molecular mechanism behind the mutation of FSHR promoter association with ovarian granulosa cells and poor ovarian response. Materials and Methods: This cross sectional study was performed using 158 women undergoing the controlled short program ovarian stimulation for IVF treatment. The 263 bp DNA fragments before the follicle stimulating hormone (FSH) receptor 5' initiation site were sequenced in the patients under IVF cycle, 70 of which had poor ovarian response and 88 showed normal ovarian responses. Results: With a mutation rate of 40%, 63 in 158 cases showed a 29th site G→A point mutation; among the mutated cases, the mutation rate of the poor ovarian responders was significantly higher than the normal group (60% versus 23.9%; χ2=21.450, p<0.001). Besides, the variability was also obvious in antral follicle count, and ovum pick-ups. The estradiol peak values and the number of mature eggs between the two groups had significant difference. However, there was no obvious variability (t=0.457, p=0.324) in the basic FSH values between the two groups (normal group, 7.2±2.3 U/L; mutation group, 7.1±2.0 U/L). Conclusion: The activity of FSHR promoter is significantly affected by the 29th site G→A mutation that will weaken promoter activity and result in poor response to FSH. PMID:26730247

  18. 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

  19. A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing.

    PubMed

    Danielsen, E Thomas; Moeller, Morten E; Yamanaka, Naoki; Ou, Qiuxiang; Laursen, Janne M; Soenderholm, Caecilie; Zhuo, Ran; Phelps, Brian; Tang, Kevin; Zeng, Jie; Kondo, Shu; Nielsen, Christian H; Harvald, Eva B; Faergeman, Nils J; Haley, Macy J; O'Connor, Kyle A; King-Jones, Kirst; O'Connor, Michael B; Rewitz, Kim F

    2016-06-20

    Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. In addition, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann-Pick type C1 deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol-trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensures proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. PMID:27326933

  20. Causes and consequences of age-related steroid hormone changes: insights gained from nonhuman primates.

    PubMed

    Sorwell, K G; Urbanski, H F

    2013-11-01

    Similar to 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 the real-time polymerase chain reaction, we have shown that the genes for the enzymes associated with the conversion of DHEA to oestradiol and testosterone (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and aromatase) are highly expressed in brain areas associated with cognition and behaviour, including the hippocampus, prefrontal cortex and amygdala. Taken together, these findings suggest that the administration of supplementary DHEA in the elderly may have therapeutic potential for cognitive and behavioural disorders, although 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 the 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 with respect to reversing age-associated disorders, including perturbed sleep-wake cycles and cognitive decline, as well as an impaired immune response. PMID:23796387

  1. Occurrence and distribution of steroids, hormones and selected pharmaceuticals in South Florida coastal environments.

    PubMed

    Singh, Simrat P; Azua, Arlette; Chaudhary, Amit; Khan, Shabana; Willett, Kristine L; Gardinali, Piero R

    2010-02-01

    The common occurrence of human derived contaminants like pharmaceuticals, steroids and hormones in surface waters has raised the awareness of the role played by the release of treated or untreated sewage in the water quality along sensitive coastal ecosystems. South Florida is home of many important protected environments ranging from wetlands to coral reefs which are in close proximity to large metropolitan cities. Because, large portions of South Florida and most of the Florida Keys population are not served by modern sewage treatment plants and rely heavily on the use of septic systems, a comprehensive survey of selected human waste contamination markers was conducted in three areas to assess water quality with respect to non-traditional micro-constituents. This study documents the occurrence and distribution of fifteen hormones and steroids and five commonly detected pharmaceuticals in surface water samples collected from different near shore environments along South Florida between 2004 and 2006. The compounds most frequently detected were: cholesterol, caffeine, estrone, DEET, coprostanol, biphenol-A, beta-estradiol, and triclosan. The concentration detected for estrone and beta-estradiol were up to 5.2 and 1.8 ng/L, respectively. Concentrations of caffeine (5.5-68 ng/L) and DEET (4.8-49 ng/L) were generally higher and more prevalent than were the steroids. Distribution of microconstituents was site specific likely reflecting a diversity of sources. In addition to chemical analysis, the yeast estrogen screen assay was used to screen the samples for estrogen equivalency. Overall, the results show that water collected from inland canals and restricted circulation water bodies adjacent to heavily populated areas had high concentrations of multiple steroids, pharmaceuticals, and personal care products while open bay waters were largely devoid of the target analytes. PMID:19779818

  2. 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. PMID:26464260

  3. Role of biofilms in sorptive removal of steroidal hormones and 4-nonylphenol compounds from streams.

    PubMed

    Writer, Jeffrey H; Ryan, Joseph N; Barber, Larry B

    2011-09-01

    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 17β-estradiol (10(2.5-2.8) L kg(-1)), 17α-ethynylestradiol (10(2.5-2.9) L kg(-1)), 4-nonylphenol (10(3.4-4.6) L kg(-1)), 4-nonylphenolmonoethoxylate (10(3.5-4.0) L kg(-1)), and 4-nonylphenoldiethoxylate (10(3.9-4.3) 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 17β-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

  4. 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

  5. Role of biofilms in sorptive removal of steroidal hormones and 4-nonylphenol compounds from streams

    USGS Publications Warehouse

    Writer, Jeffrey H.; Ryan, Joseph N.; Barber, Larry 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 (Kom, L kg-1) for 17β-estradiol (102.5-2.8 L kg-1), 17α-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 17β-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

  6. 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

  7. 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. PMID:27006974

  8. Data for stable formulation of steroid hormone receptor-targeted liposomes for cancer therapeutics

    PubMed Central

    Sharma, Priyanka; Banerjee, Rajkumar; Narayan, Kumar Pranav

    2016-01-01

    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. PMID:27006974

  9. Transitional versus surgical menopause in a rodent model: etiology of ovarian hormone loss impacts memory and the acetylcholine system.

    PubMed

    Acosta, Jazmin I; Mayer, Loretta; Talboom, Joshua S; Tsang, Candy Wing S; Smith, Constance J; Enders, Craig K; Bimonte-Nelson, Heather A

    2009-09-01

    Clinical research suggests that type of ovarian hormone loss at menopause influences cognition. Until recently ovariectomy (OVX) has been the primary rodent model to examine effects of ovarian hormone loss on cognition. This model limits evaluations to abrupt and complete ovarian hormone loss, modeling less than 13% of women who receive surgical menopause. The majority of women do not have their ovaries surgically removed and undergo transitional hormone loss via ovarian follicular depletion. 4-Vinylcyclohexene-diepoxide (VCD) produces gradual ovarian follicular depletion in the rodent, with hormone profiles more similar to naturally menopausal women vs. OVX. We directly compared VCD and OVX models to examine whether type of hormone loss (transitional vs. surgical) impacted cognition as assessed on a maze battery as well as the cholinergic system tested via scopolamine mnemonic challenge and brain acetylcholinesterase activity. Middle-aged rats received either sham surgery, OVX surgery, VCD, or VCD then OVX to assess effects of removal of residual ovarian output after transitional menopause and follicular depletion. VCD-induced transitional menopause impaired learning of a spatial recent memory task; surgical removal of residual ovarian hormones by OVX abolished this negative effect of transitional menopause. Furthermore, transitional menopause before OVX was better for memory than an abrupt loss of hormones via OVX only. Surgical ovarian hormone loss, regardless of menopause history, increased hippocampal acetylcholinesterase activity. Circulating gonadotropin and androstenedione levels were related to cognitive competence. Collectively, findings suggest that in the rat, initiation of transitional menopause before surgical ovary removal can benefit mnemonic function and could obviate some negative cognitive consequences of surgical menopause alone. PMID:19470706

  10. 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

  11. 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. PMID:24167314

  12. 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, delayed ... some diseases. Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. Using ...

  13. Steroid secretion following exposure of ovarian follicular cells to single congeners and defined mixture of polybrominateddibenzoethers (PBDEs), p,p'-DDT and its metabolite p,p'-DDE.

    PubMed

    Gregoraszczuk, Ewa Ł; Rak, Agnieszka; Kawalec, K; Ropstad, Erik

    2008-05-01

    The main objective of the present study was to describe in vitro effects of individual congeners of polybrominateddibenzoethers (PBDEs) (PBDE-47, 99, 100, 209), p,p'-dichlorodiphenyltrichloroethane (DDT) and p,p'-dichlorodiphenyldichloroethylene (DDE) present at the highest amount in real-life mixtures of POPs extracted from liver oil of burbot from Lake Mjøsa in Norway, and defined combinations of these compounds on steroidogenesis in porcine ovarian follicular cells. Co-culture of theca and granulosa cells (Gc) was exposed by individual congeners of PBDEs or mixture. Media samples were collected and used for cell viability and steroid determination, while cells were used for the measurement of caspase-3 activity. All investigated PBDEs congeners increased both testosterone (T) and estradiol (E2) secretion. We noted additive stimulatory action of BDE-47 and BDE-100 on both T and E2 secretion, and then inhibitory action on both of these hormones production when additionally BDE-99 and then BDE-209 were included in this mixture. The situation was different when DDT and DDE were added to the defined mixture. Stimulatory action on E2 secretion with parallel decrease of T secretion was noted. In conclusion, the data indicated: (1) stimulatory action of individual congeners of PBDEs on both E2 and T secretion by ovarian follicular cells points to stimulatory action on enzymes responsible for testosterone secretion; (2) the overall effect of a real-life mixture on the steroidogenic response in ovarian follicular cells could be dependent on the concentration of DDTs in the mixture; (3) the predicted effect of mixture, calculated based on a sum of independent action of individual congeners, was higher than that noted under the influence of defined mixture. PMID:18406082

  14. Presence of a putative steroidal allosteric site on glycoprotein hormone receptors.

    PubMed

    Rossi, Mario; Dimida, Antonio; Ferrarini, Eleonora; Silvano, Elena; De Marco, Giuseppina; Agretti, Patrizia; Aloisi, Gabriella; Simoncini, Tommaso; Di Bari, Lorenzo; Tonacchera, Massimo; Giorgi, Franco; Maggio, Roberto

    2009-11-25

    In a previous work we found that the insecticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), inhibits the accumulation of cAMP as induced by the bovine thyroid stimulating hormone (bTSH) in cells transfected with the TSH receptor. In this work, we demonstrate that the DDT molecular analogues, diethylstilbestrol and quercetine, are more potent inhibitors of the TSH receptor activity than DDT itself. The notion that all these compounds interfere with nuclear estrogen receptors, as either agonists (DDT and diethylstilbestrol) or antagonists (quercetin), prompted us to test the ability of the steroid hormone 17-beta-estradiol to inhibit the TSH receptor activity. We found that estrogen exposure causes a modest but significant inhibition of the bTSH induced cAMP accumulation both in transfected CHO-TSH receptor and Fischer Rat Thyroid Low Serum 5% (FRTL-5) cells. When applied to CHO cells transfected with the luteinizing hormone receptor, 17-beta-estradiol proved capable of inhibiting the hCG induced cAMP accumulation at a concentration as low as 10nM, though the effect was not greater than 35%. The effect of 17-beta-estradiol was not estrogen receptors mediated, as co-transfection of the estrogen receptor alpha and beta subunits with LH receptor caused cAMP to increase above the level attained by the sole hCG stimulation, and not to decrease it as expected. These data suggest the presence of a steroidal-like allosteric binding site on glycoprotein hormone receptors. PMID:19766106

  15. 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.

  16. 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. PMID:25765474

  17. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on secretion of steroids and STAR, HSD3B and CYP19A1 mRNA expression in chicken ovarian follicles.

    PubMed

    Sechman, Andrzej; Antos, Piotr; Katarzyńska, Dorota; Grzegorzewska, Agnieszka; Wojtysiak, Dorota; Hrabia, Anna

    2014-03-01

    The aim of the study was to investigate the in vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on steroid hormone secretion by chicken ovarian follicles and mRNA expression of genes involved in steroids synthesis. In the first in vitro experiment, white (WF) and yellowish (YF) follicles and fragments of the theca (TL) and granulosa (GL) layers of the 3 largest yellow preovulatory follicles (F3-F1) were incubated in a medium supplemented with TCDD (0.01-100nM). In the second experiment, they were incubated in a medium with TCDD (10nM), ovine LH (10ng/mL; oLH) or a combination of oLH (10ng/mL) and TCDD (10nM). It was found that TCDD decreased estradiol (E2) secretion by WF and the TL of all preovulatory follicles, testosterone (T) secretion by WF, YF, and the TL of F2 and F1 follicles, and progesterone (P4) secretion by the GL of the preovulatory follicles. It also reduced oLH-stimulated E2 and P4 secretion by all examined follicles and T by WF. Real-time qPCR revealed that TCDD affected basal and oLH-stimulated expression of STAR, HSD3B and CYP19A1 mRNAs in all investigated ovarian follicles. In conclusion, the data obtained indicate that TCDD inhibits sex steroids secretion from chicken ovarian follicles. The effects of TCDD depend on its concentration and the stage of follicle maturation, and are associated with modulation of STAR, HSD3B and CYP19A1 mRNAs expression. These results indicate that the exposure of the laying hen to TCDD by influence of ovarian steroidogenesis may impair the selection of white follicles to preovulatory hierarchy and disturb their growth and preovulatory maturation. PMID:24398026

  18. Modelling the binding affinity of steroids to zebrafish sex hormone-binding globulin.

    PubMed

    Saxena, A K; Devillers, J; Pery, A R R; Beaudouin, R; Balaramnavar, V M; Ahmed, S

    2014-01-01

    The circulating endogenous steroids are transported in the bloodstream. These are bound to a highly specific sex hormone-binding globulin (SHBG) and in lower affinity to proteins such as the corticosteroid-binding protein and albumin in vertebrates, including fish. It is generally believed that the glycoprotein SHBG protects these steroids from rapid metabolic degradation and thus intervenes in its availability at the target tissues. Endocrine disrupters binding to SHBG affect the normal activity of natural steroids. Since xenobiotics are primarily released in the aquatic environment, there is a need to evaluate the binding affinity of xenosteroid mimics on fish SHBG, especially in zebrafish (Danio rerio), a small freshwater fish originating in India and widely employed in ecotoxicology, toxicology, and genetics. In this context, a zebrafish SHBG (zfSHBG) homology model was developed using the human SHBG (hSHBG) receptor structure as template. It was shown that interactions with amino acids Ser-36, Asp-59 and Thr-54 were important for binding affinity. A ligand-based pharmacophore model was also developed for both zfSHBG and hSHBG inhibitors that differentiated binders from non-binders, but also demonstrated structural requirements for zfSHBG and hSHBG ligands. The study provides insights into the mechanism of action of endocrine disruptors in zebrafish as well as providing a useful tool for identifying anthropogenic compounds inhibiting zfSHBG. PMID:24874994

  19. Metabolic profiling of cholesterol and sex steroid hormones to monitor urological diseases.

    PubMed

    Moon, Ju-Yeun; Choi, Man Ho; Kim, Jayoung

    2016-10-01

    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

  20. A Fluorescence Polarization Assay To Detect Steroid Hormone Traces in Milk.

    PubMed

    Varriale, Antonio; Pennacchio, Anna; Pinto, Gabriella; Oliviero, Giorgia; D'Errico, Stefano; Majoli, Adelia; Scala, Andrea; Capo, Alessandro; Pennacchio, Angela; Di Giovanni, Stefano; Staiano, Maria; D'Auria, Sabato

    2015-10-21

    Steroids are a class of hormones improperly used in livestock as growth-promoting agents. Due to their high risk for human health, the European Union (EU) has strictly forbidden the administration of all natural and synthetic steroid hormones to food-producing animals, and the development of new rapid detection methods are greatly encouraged. This work reports a novel fluorescence polarization assay, ready to use, capable of detecting 17β-estradiol directly in milk samples with a low limit of detection of <10 pmol. It is based on the coupling of monospecific antibodies against 17β-estradiol and fluorophores, capable of modulating the fluorescence polarization emission on the basis of the specific binding of antibodies to fluorescence-labeled 17β-estradiol derivative. The successful detection of 17β-estradiol has disclosed the development of an efficient method, easily extensible to any food matrix and having the potential to become a milestone in food quality and safety. PMID:26434254

  1. 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

  2. Expression of steroid hormone receptors in the genital structures of a true hermaphrodite pug dog.

    PubMed

    Bartel, C; Meyer, F; Schäfer-Somi, S; Walter, I

    2015-02-01

    Hermaphroditism is a rare and a not well-understood disordered sexual development (DSD) in dogs. The objective of the study was to analyse the sex steroid hormone receptor (STHR) expression patterns in the internal genital structures, because the responsiveness of the different tissue types to the steroid hormones may have a key role in pathological alterations based on DSDs. Furthermore, the adhesion molecule β-catenin was investigated by means of immunohistochemistry because of its important role in development, tissue integrity and disease. Molecular sexing was performed via PCR targeting DBX/DBY genes to identify the pug dog as a true XX hermaphrodite. The portions of uterine tissue revealed comparable expression patterns for STHRs as investigated in normal female reproductive tissue. In the male parts, β-catenin showed strong expression in the Sertoli cells of the seminiferous tubules; this was in contrast to normal testicular tissue. Likewise, the layers of smooth muscle actin-positive cells surrounding the seminiferous tubules were reduced in the hermaphrodite. The results of this study deepen the knowledge of tissue characteristics in a hermaphrodite dog and highlight the importance of early diagnosis because the STH responsiveness in maldeveloped reproductive tissue might lead to serious problems for the dog. PMID:25472589

  3. 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. PMID:20213838

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

    PubMed Central

    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

    2014-01-01

    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. DOI: http://dx.doi.org/10.7554/eLife.03558.001 PMID:25313867

  5. Unique responses of midbrain CART neurons in macaques to ovarian steroids.

    PubMed

    Lima, F B; Henderson, J A; Reddy, A P; Tokuyama, Y; Hubert, G W; Kuhar, M J; Bethea, C L

    2008-08-28

    CART (cocaine and amphetamine regulated transcript) is a neuropeptide involved in the control of several physiological processes, such as response to psychostimulants, food intake, depressive diseases and neuroprotection. It is robustly expressed in the brain, mainly in regions that control emotional and stress responses and it is regulated by estrogen in the hypothalamus. There is a distinct population of CART neurons located in the vicinity of the Edinger-Westphal nucleus of the midbrain that also colocalize urocortin-1. The aims of this study were 1) to determine the distribution of CART immunoreactive neurons in the monkey midbrain, 2) to examine the effects of estrogen (E) and progesterone (P) on midbrain CART mRNA and peptide expression and 3) to determine whether midbrain CART neurons contain steroid receptors. Adult female rhesus monkeys (Macaca mulatta) were spayed and either treated with placebo (OVX), estrogen alone (E), progesterone alone (P) or E+P. Animals were prepared (a) for RNA extraction followed by microarray analysis and quantitative (q) RT-PCR (n=3/group); (b) for immunohistochemical analysis of CART and CART+tryptophan hydroxylase (TPH), CART+estrogen receptors (ER) or CART+progesterone receptors (n=5/group) and (c) for Western blots (n=3/group). Both E- and E+P-administration decreased CART gene expression on the microarray and with qRT-PCR. Stereological analysis of CART immunostaining at five levels of the Edinger-Westphal nucleus indicated little effect of E or E+P administration on the area of CART immunostaining. However, P administration increased CART-immunopositive area in comparison to the OVX control group with Student's t-test, but not with ANOVA. CART 55-102 detection on Western blot was unchanged by hormone administration. ERbeta and PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe. In summary, E decreased CART mRNA, but this effect did not translate to the

  6. Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics.

    PubMed

    Kärkkäinen, Olli; Häkkinen, Merja R; Auriola, Seppo; Kautiainen, Hannu; Tiihonen, Jari; Storvik, Markus

    2016-05-01

    Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of alcoholics (N = 14) and non-alcoholic controls (N = 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior cingulate cortex (ACC), and anterior insula (AINS). DHEA levels were increased in most alcoholic subjects compared to controls. However, only a subgroup of alcoholics showed increased PREGN levels. Negative Spearman correlations between tissue levels of PREGN and previous reports of [(3)H]naloxone binding to μ-opioid receptors were observed in the AINS, ACC, NAC, and frontal cortex (R values between -0.6 and -0.8; p values ≤ 0.002), suggesting an association between the opioid system and brain PREGN levels. Although preliminary, and from relatively small diagnostic groups, these results show significantly increased levels of DHEA and PREGN in the brains of alcoholics, and could be associated with the pathology of alcoholism. PMID:27139239

  7. Dehydroepiandrosterone Sulfate (DHEAS) Stimulates the First Step in the Biosynthesis of Steroid Hormones

    PubMed Central

    Neunzig, Jens; Bernhardt, Rita

    2014-01-01

    Dehydroepiandrosterone sulfate (DHEAS) is the most abundant circulating steroid in human, with the highest concentrations between age 20 and 30, but displaying a significant decrease with age. Many beneficial functions are ascribed to DHEAS. Nevertheless, long-term studies are very scarce concerning the intake of DHEAS over several years, and molecular investigations on DHEAS action are missing so far. In this study, the role of DHEAS on the first and rate-limiting step of steroid hormone biosynthesis was analyzed in a reconstituted in vitro system, consisting of purified CYP11A1, adrenodoxin and adrenodoxin reductase. DHEAS enhances the conversion of cholesterol by 26%. Detailed analyses of the mechanism of DHEAS action revealed increased binding affinity of cholesterol to CYP11A1 and enforced interaction with the electron transfer partner, adrenodoxin. Difference spectroscopy showed Kd-values of 40±2.7 µM and 24.8±0.5 µM for CYP11A1 and cholesterol without and with addition of DHEAS, respectively. To determine the Kd-value for CYP11A1 and adrenodoxin, surface plasmon resonance measurements were performed, demonstrating a Kd-value of 3.0±0.35 nM (with cholesterol) and of 2.4±0.05 nM when cholesterol and DHEAS were added. Kinetic experiments showed a lower Km and a higher kcat value for CYP11A1 in the presence of DHEAS leading to an increase of the catalytic efficiency by 75%. These findings indicate that DHEAS affects steroid hormone biosynthesis on a molecular level resulting in an increased formation of pregnenolone. PMID:24586990

  8. 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.

  9. Pre-diagnostic circulating follicle stimulating hormone (FSH) concentrations and ovarian cancer risk

    PubMed Central

    McSorley, MA; Alberg, AJ; Allen, DS; Allen, NE; Brinton, LA; Dorgan, JF; Kaaks, R; Rinaldi, S; Helzlsouer, KJ

    2009-01-01

    Gonadotropins have been indicted in ovarian carcinogenesis but direct evidence has been limited and inconsistent. The aim of this study was to determine the association between pre-diagnostic levels of follicle stimulating hormone (FSH) and subsequent development of invasive epithelial ovarian cancer. A nested case-control study was conducted using cases and controls drawn from three cohorts: CLUE I and CLUE II of Washington County, MD, and the Island of Guernsey Study, UK. In total, 67 incident invasive epithelial ovarian cancer cases were each matched to one to two controls on age, menopausal status, time since last menstrual period, current hormone use, and other relevant factors. FSH concentrations were classified into ranked thirds of low, medium, or high based on the distribution among controls. Conditional logistic regression was used to estimate the odds ratio (OR) across increasing thirds of FSH concentrations. Results of the analysis showed that ovarian cancer risk decreased with higher FSH concentrations (p-trend =0.005). Compared to the lowest third of FSH concentrations, the odds ratio among those in the middle and highest thirds were 0.45 (95% Confidence Interval (CI) 0.20– 1.00) and 0.26 (95% CI 0.10–0.70), respectively. Associations persisted after excluding cases diagnosed within five years of follow-up. In conclusion, a reduction in subsequent risk of invasive epithelial ovarian cancer was observed among women with higher circulating FSH concentrations. These findings contradict the hypothesized role of FSH as a risk factor in ovarian carcinogenesis. PMID:19444906

  10. Caloric Restriction Effect on Proinflammatory Cytokines, Growth Hormone, and Steroid Hormone Concentrations during Exercise in Judokas.

    PubMed

    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