Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.

PubMed

Cook, Michael B; Stanczyk, Frank Z; Wood, Shannon N; Pfeiffer, Ruth M; Hafi, Muhannad; Veneroso, Carmela C; Lynch, Barlow; Falk, Roni T; Zhou, Cindy Ke; Niwa, Shelley; Emanuel, Eric; Gao, Yu-Tang; Hemstreet, George P; Zolfghari, Ladan; Carroll, Peter R; Manyak, Michael J; Sesterhann, Isabell A; Levine, Paul H; Hsing, Ann W

2017-11-01

Background: Sex hormones have been implicated in prostate carcinogenesis, yet epidemiologic studies have not provided substantiating evidence. We tested the hypothesis that circulating concentrations of sex steroid hormones reflect intraprostatic concentrations using serum and adjacent microscopically verified benign prostate tissue from prostate cancer cases. Methods: Incident localized prostate cancer cases scheduled for surgery were invited to participate. Consented participants completed surveys, and provided resected tissues and blood. Histologic assessment of the ends of fresh frozen tissue confirmed adjacent microscopically verified benign pathology. Sex steroid hormones in sera and tissues were extracted, chromatographically separated, and then quantitated by radioimmunoassays. Linear regression was used to account for variations in intraprostatic hormone concentrations by age, body mass index, race, and study site, and subsequently to assess relationships with serum hormone concentrations. Gleason score (from adjacent tumor tissue), race, and age were assessed as potential effect modifiers. Results: Circulating sex steroid hormone concentrations had low-to-moderate correlations with, and explained small proportions of variations in, intraprostatic sex steroid hormone concentrations. Androstane-3α,17β-diol glucuronide (3α-diol G) explained the highest variance of tissue concentrations of 3α-diol G (linear regression r 2 = 0.21), followed by serum testosterone and tissue dihydrotestosterone ( r 2 = 0.10), and then serum estrone and tissue estrone ( r 2 = 0.09). There was no effect modification by Gleason score, race, or age. Conclusions: Circulating concentrations of sex steroid hormones are poor surrogate measures of the intraprostatic hormonal milieu. Impact: The high exposure misclassification provided by circulating sex steroid hormone concentrations for intraprostatic levels may partly explain the lack of any consistent association of circulating

Effects of Sex Steroids on Fish Leukocytes

PubMed Central

Cabas, Isabel

2018-01-01

In vertebrates, in addition to their classically reproductive functions, steroids regulate the immune system. This action is possible mainly due to the presence of steroid receptors in the different immune cell types. Much evidence suggests that the immune system of fish is vulnerable to xenosteroids, which are ubiquitous in the aquatic environment. In vivo and in vitro assays have amply demonstrated that oestrogens interfere with both the innate and the adaptive immune system of fish by regulating the main leukocyte activities and transcriptional genes. They activate nuclear oestrogen receptors and/or G-protein coupled oestrogen receptor. Less understood is the role of androgens in the immune system, mainly due to the complexity of the transcriptional regulation of androgen receptors in fish. The aim of this manuscript is to review our present knowledge concerning the effect of sex steroid hormones and the presence of their receptors on fish leukocytes, taking into consideration that the studies performed vary as regard the fish species, doses, exposure protocols and hormones used. Moreover, we also include evidence of the probable role of progestins in the regulation of the immune system of fish. PMID:29315244

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

PubMed Central

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

2016-01-01

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

Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones.

PubMed

Schöning, S; Engelien, A; Kugel, H; Schäfer, S; Schiffbauer, H; Zwitserlood, P; Pletziger, E; Beizai, P; Kersting, A; Ohrmann, P; Greb, R R; Lehmann, W; Heindel, W; Arolt, V; Konrad, C

2007-11-05

Recent observations indicate that sex and level of steroid hormones may influence cortical networks associated with specific cognitive functions, in particular visuo-spatial abilities. The present study probed the influence of sex, menstrual cycle, and sex steroid hormones on 3D mental rotation and brain function using 3-T fMRI. Twelve healthy women and 12 men were investigated. Menstrual cycle and hormone levels were assessed. The early follicular and midluteal phase of the menstrual cycle were chosen to examine short-term cyclical changes. Parietal and frontal areas were activated during mental rotation in both sexes. Significant differences between men and women were revealed in both phases of menstrual cycle. In men we observed a significant correlation of activation levels with testosterone levels in the left parietal lobe (BA 40). In women, a cycle-dependent correlation pattern was observed for testosterone: brain activation correlated with this male hormone only during the early follicular phase. In both cycle phases females' brain activation was significantly correlated with estradiol in frontal and parietal areas. Our study provides evidence that fMRI-related activity during performance of cognitive tasks varies across sex and phases of the menstrual cycle. The variation might be partly explained by better task performance in men, but our results indicate that further explanations like basic neuronal or neurovascular effects modulated by steroid hormones must be considered. Both estradiol and testosterone levels may influence fMRI signals of cognitive tasks, which should affect selection of subjects for future fMRI studies.

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors

PubMed Central

Natale, Christopher A; Duperret, Elizabeth K; Zhang, Junqian; Sadeghi, Rochelle; Dahal, Ankit; O'Brien, Kevin Tyler; Cookson, Rosa; Winkler, Jeffrey D; Ridky, Todd W

2016-01-01

The association between pregnancy and altered cutaneous pigmentation has been documented for over two millennia, suggesting that sex hormones play a role in regulating epidermal melanocyte (MC) homeostasis. Here we show that physiologic estrogen (17β-estradiol) and progesterone reciprocally regulate melanin synthesis. This is intriguing given that we also show that normal primary human MCs lack classical estrogen or progesterone receptors (ER or PR). Utilizing both genetic and pharmacologic approaches, we establish that sex steroid effects on human pigment synthesis are mediated by the membrane-bound, steroid hormone receptors G protein-coupled estrogen receptor (GPER), and progestin and adipoQ receptor 7 (PAQR7). Activity of these receptors was activated or inhibited by synthetic estrogen or progesterone analogs that do not bind to ER or PR. As safe and effective treatment options for skin pigmentation disorders are limited, these specific GPER and PAQR7 ligands may represent a novel class of therapeutics. DOI: http://dx.doi.org/10.7554/eLife.15104.001 PMID:27115344

Sex steroids regulate skin pigmentation through nonclassical membrane-bound receptors.

PubMed

Natale, Christopher A; Duperret, Elizabeth K; Zhang, Junqian; Sadeghi, Rochelle; Dahal, Ankit; O'Brien, Kevin Tyler; Cookson, Rosa; Winkler, Jeffrey D; Ridky, Todd W

2016-04-26

The association between pregnancy and altered cutaneous pigmentation has been documented for over two millennia, suggesting that sex hormones play a role in regulating epidermal melanocyte (MC) homeostasis. Here we show that physiologic estrogen (17β-estradiol) and progesterone reciprocally regulate melanin synthesis. This is intriguing given that we also show that normal primary human MCs lack classical estrogen or progesterone receptors (ER or PR). Utilizing both genetic and pharmacologic approaches, we establish that sex steroid effects on human pigment synthesis are mediated by the membrane-bound, steroid hormone receptors G protein-coupled estrogen receptor (GPER), and progestin and adipoQ receptor 7 (PAQR7). Activity of these receptors was activated or inhibited by synthetic estrogen or progesterone analogs that do not bind to ER or PR. As safe and effective treatment options for skin pigmentation disorders are limited, these specific GPER and PAQR7 ligands may represent a novel class of therapeutics.

Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

PubMed

Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

2011-11-01

Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-10-01

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

Regucalcin Expression in Bovine Tissues and Its Regulation by Sex Steroid Hormones in Accessory Sex Glands

PubMed Central

Starvaggi Cucuzza, Laura; Divari, Sara; Mulasso, Chiara; Biolatti, Bartolomeo; Cannizzo, Francesca T.

2014-01-01

Regucalcin (RGN) is a mammalian Ca2+-binding protein that plays an important role in intracellular Ca2+ homeostasis. Recently, RGN has been identified as a target gene for sex steroid hormones in the prostate glands and testis of rats and humans, but no studies have focused on RGN expression in bovine tissues. Thus, in the present study, we examined RGN mRNA and protein expression in the different tissues and organs of veal calves and beef cattle. Moreover, we investigated whether RGN expression is controlled through sex steroid hormones in bovine target tissues, namely the bulbo-urethral and prostate glands and the testis. Sex steroid hormones are still illegally used in bovine husbandry to increase muscle mass. The screening of the regulation and function of anabolic sex steroids via modified gene expression levels in various tissues represents a new approach for the detection of illicit drug treatments. Herein, we used quantitative PCR, western blot and immunohistochemistry analyses to demonstrate RGN mRNA and protein expression in bovine tissues. In addition, estrogen administration down-regulated RGN gene expression in the accessory sex glands of veal calves and beef cattle, while androgen treatment reduced RGN gene expression only in the testis. The confirmation of the regulation of RGN gene expression through sex steroid hormones might facilitate the potential detection of hormone abuse in bovine husbandry. Particularly, the specific response in the testis suggests that this tissue is ideal for the detection of illicit androgen administration in veal calves and beef cattle. PMID:25415588

Sex hormone binding globulin and sex steroids among premenopausal women in the diabetes prevention program.

PubMed

Kim, Catherine; Pi-Sunyer, Xavier; Barrett-Connor, Elizabeth; Stentz, Frankie B; Murphy, Mary Beth; Kong, Shengchun; Nan, Bin; Kitabchi, Abbas E

2013-07-01

It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS). We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity. A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301). Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo. Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (~11%) compared to decreases of 1.1 nmol/L in the placebo arm (P < .05). This comparison remained significant after adjustment for changes in covariates including waist circumference. However, associations with glucose were not significant. Median baseline A4 was lower in Hispanics compared to NHWs (5.7 nmol/L vs 6.5 nmol/L, P < .05) and increases in A4 were greater in Hispanics compared to NHWs (3.0 nmol/ vs 1.2 nmol/L, P < .05), and these differences did not differ significantly by intervention arm. No other racial/ethnic differences were significant. Among premenopausal glucose-intolerant women, no intervention changed sex steroids. ILS increased SHBG, although associations with glucose were not significant. SHBG and sex steroids were similar by race/ethnicity, with the possible exception of lower baseline A4 levels in Hispanics compared to NHWs.

Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

PubMed Central

Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

2016-01-01

The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

Sex steroids, immune system, and parasitic infections: facts and hypotheses.

PubMed

Nava-Castro, Karen; Hernández-Bello, Romel; Muñiz-Hernández, Saé; Camacho-Arroyo, Ignacio; Morales-Montor, Jorge

2012-07-01

It has been widely reported that the incidence and the severity of natural parasitic infections are different between males and females of several species, including humans. This sexual dimorphism involves a distinct exposure of males and females to various parasite infective stages, differential effects of sex steroids on immune cells, and direct effects of these steroids on parasites, among others. Typically, for a large number of parasitic diseases, the prevalence and intensity is higher in males than females; however, in several parasitic infections, males are more resistant than females. In the present work, we review the effects of sex hormones on immunity to protozoa and helminth parasites, which are the causal agents of several diseases in humans, and discuss the most recent research related to the role of sex steroids in the complex host-parasite relationship. © 2012 New York Academy of Sciences.

Sex steroid hormone metabolism takes place in human ocular cells.

PubMed

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

2003-08-01

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

Plasma levels of immune factors and sex steroids in the male seahorse Hippocampus erectus during a breeding cycle.

PubMed

Lin, Tingting; Liu, Xin; Xiao, Dongxue; Zhang, Dong

2017-06-01

To better understand the endocrine- and immune-response pattern during reproduction in a fish species having parental care behaviors and also to accumulate the endocrine- and immune-related data for future explanations of the low reproductive efficiency in seahorse species, the variations of immune factors and sex steroids in the plasma of the male lined seahorse Hippocampus erectus at different breeding stages, i.e., pre-pregnancy, pregnancy (early, middle, and late periods), and post-pregnancy, were investigated in the present study. The immune factors included monocytes/leucocytes (M/L), leucocyte phagocytic rate (LPR), immunoglobulin M (Ig M), interleukin-2 (IL-2), interferon-α (IFN-α), and lysozyme (LZM). The sex steroids included testosterone (T), 11-ketotestosterone (11-KT), 11β-hydroxytestosterone (11β-OHT), 17α-methyltestosterone (17α-MT), 17β-estradiol (E2), and 17α-hydroxy-20β-dihydroprogesterone (17α-20β-P). Moreover, the immune metabolic activity of epithelium cells in the brood pouch at different breeding stages was also analyzed through ultrastructural observations of the abundance of cytoplasmic granules, mitochondria, endoplasmic reticulum, lysosomes, and exocytosis. The results show that a higher immune level was observed during pregnancy, particularly in the early and middle periods, and a lower immune level was noted during pre-pregnancy. Correspondingly, the epithelium cells in the brood pouch also showed a stronger immune metabolic activity during pregnancy and weaker activity during pre-pregnancy. Four sex steroids of T, 11β-OHT, 17α-MT, and E2 were higher during pre-pregnancy and lower during post-pregnancy, whereas 11-KT and 17α-20β-P, which were positively correlated with part immune factors, were higher during pregnancy. No negative correlations between sex steroids and immune factors were observed. In conclusion, the higher immune competence during pregnancy may indicate that parental care could improve immunity, which may

The influence of steroid sex hormones on the cognitive and emotional processing of visual stimuli in humans.

PubMed

Little, Anthony C

2013-10-01

Steroid sex hormones are responsible for some of the differences between men and women. In this article, I review evidence that steroid sex hormones impact on visual processing. Given prominent sex-differences, I focus on three topics for sex hormone effects for which there is most research available: 1. Preference and mate choice, 2. Emotion and recognition, and 3. Cerebral/perceptual asymmetries and visual-spatial abilities. For each topic, researchers have examined sex hormones and visual processing using various methods. I review indirect evidence addressing variation according to: menstrual cycle phase, pregnancy, puberty, and menopause. I further address studies of variation in testosterone and a measure of prenatal testosterone, 2D:4D, on visual processing. The most conclusive evidence, however, comes from experiments. Studies in which hormones are administrated are discussed. Overall, many studies demonstrate that sex steroids are associated with visual processing. However, findings are sometimes inconsistent, differences in methodology make strong comparisons between studies difficult, and we generally know more about activational than organizational effects. Copyright © 2013 Elsevier Inc. All rights reserved.

Chronic Hypoxia Inhibits Sex Steroid Hormone-Mediated Attenuation of Ovine Uterine Arterial Myogenic Tone in Pregnancy

PubMed Central

Chang, Katherine; Xiao, DaLiao; Huang, Xiaohui; Xue, Zhice; Yang, Shumei; Longo, Lawrence D.; Zhang, Lubo

2010-01-01

Previous studies in ovine uterine arteries have demonstrated that sex steroid hormones upregulate ERK1/2 expression and downregulate PKC signaling pathway, resulting in the attenuated myogenic tone in pregnancy. The present study tested the hypothesis that chronic hypoxia during gesttation inhibits the sex steroid-mediated adaptation of ERK1/2 and PKC signaling pathways and increases the myogenic tone of uterine arteries. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) hypoxia for 110 days. In contrast to the previous findings in normoxic animals, 17β-estradiol and progesterone failed to suppress PKC-induced contractions and the pressure-induced myogenic tone in uterine arteries from hypoxic animals. Western analyses showed that the sex steroids lost their effects on ERK1/2 expression and phospho-ERK1/2 levels, as well as the activation of PKC isozymes in uterine arteries of hypoxic ewes. In normoxic animals, pregnancy and the sex steroid treatments significantly increased uterine artery estrogen receptor α and progesterone receptor B expression. Chronic hypoxia selectively downregulated estrogen receptor α expression in uterine arteries of pregnant animals, and eliminated the upregulation of estrogen receptor α in pregnancy or by the steroid treatments observed in normoxic animals. The results demonstrate that in the ovine uterine artery chronic hypoxia in pregnancy inhibits the sex steroid hormone-mediated adaptation of decreased myogenic tone by downregulating estrogen receptor α expression, providing a mechanism linking hypoxia and maladaptation of uteroplacental circulation, and an increased risk of preeclampsia in pregnancy. PMID:20660818

Plasma sex steroid binding in Chiroptera.

PubMed

Kwiecinski, G G; Damassa, D A; Gustafson, A W; Armao, M E

1987-04-01

Plasma steroid binding was examined in samples obtained from seven species of bats representing four different families. A specific sex steroid-binding protein (SBP) was identified by steady-state polyacrylamide gel electrophoresis in representatives of two families, the phyllostomids and the vespertilionids. In these species, as in primates, SBP not only exhibited high affinity for the androgens testosterone and dihydrotestosterone (DHT), but also for estradiol. A specific SBP was not identified in the tropical American vampire bat or in the two species of pteropodids examined. In all species examined, except for the vampire bat, a specific corticosteroid-binding globulin (CBG) was also identified. In addition to binding glucocorticoids, CBG in these species appeared to bind androgens as well.

Sex and sex steroids: impact on the kinetics of fatty acids underlying body shape.

PubMed

Santosa, Sylvia; Jensen, Michael D

2014-10-01

Adult humans have a remarkable sexual dimorphism in body shape. Men tend to store relatively more fat in the upper body whereas women store more fat in the lower body. We do not have a complete understanding of the mechanisms underlying these differences, but we know that people who preferentially store abdominal fat are at greater risk of metabolic disease. It is also known that the changes in sex steroid concentrations during puberty and again with advancing age are accompanied by changes in body fat distribution. The objective of this review is to describe what has been learned regarding the mechanisms underlying changes in regional body fat distribution that occur as a result of changes in sex hormones and to delineate effects of sex steroids in modulating body composition.

Sex steroid modulation of cortisol secretion in sheep.

PubMed

van Lier, E; Carriquiry, M; Meikle, A

2014-06-01

There is strong evidence that the gonads modulate the hypothalamic-pituitary-adrenal axis. To investigate these sex differences at the adrenal glands of sheep we compared the cortisol response to ACTH (experiment 1) and measured the relative expression of oestrogen receptor alpha (ERS1), androgen receptor (AR), melanocortin 2 receptor (MC2R) and steroid acute regulatory protein (STAR) mRNA in adrenal glands (experiment 2) of gonadectomised rams and ewes either with or without sex steroid replacement. In experiment 1 six castrated adult rams and four ovariectomised adult ewes were used in two ACTH trials. On each trial blood samples were taken every 15 min for 4 h through an indwelling jugular catheter and each animal received 0.5 mg of an ACTH analogue i.v., immediately after the sample at 1 h from the beginning of the trial. Four days after the first trial the males received 100 mg of Testosterone Cyclopentilpropionate (TC) i.m. and the females received 2.5 mg of Oestradiol Benzoate (EB) i.m. At 72 h after TC or EB administration the second trial was performed. In experiment 2 the adrenal glands were obtained from gonadectomised adult rams (n=8) and adult ewes (n=8). Four rams received 100 mg of TC i.m. and four females received 0.5 mg of EB i.m. Blood samples were taken at 0, 12, 24, 48 and 72 h relative to steroid replacement and the animals were thereafter slaughtered. Cortisol, testosterone and 17β-oestradiol were determined by radioimmunoanalysis. The transcripts of ERS1, AR, MC2R and STAR were determined by real-time reverse transcription PCR in adrenal tissue. Cortisol secretion was higher in female sheep than in male sheep, and higher in EB-treated than non-treated ewes. No difference in cortisol secretion was observed between TC-treated and non-treated rams. Gonadectomised rams treated with TC presented greater AR mRNA and MC2R mRNA expression than males without the steroid replacement. Gonadectomised ewes treated with EB tended to present lower AR m

Impact of sex steroids and reproductive stage on sleep-dependent memory consolidation in women.

PubMed

Baker, Fiona C; Sattari, Negin; de Zambotti, Massimiliano; Goldstone, Aimee; Alaynick, William A; Mednick, Sara C

2018-03-21

Age and sex are two of the three major risk factors for Alzheimer's disease (ApoE-e4 allele is the third), with women having a twofold greater risk for Alzheimer's disease after the age of 75 years. Sex differences have been shown across a wide range of cognitive skills in young and older adults, and evidence supports a role for sex steroids, especially estradiol, in protecting against the development of cognitive decline in women. Sleep may also be a protective factor against age-related cognitive decline, since specific electrophysiological sleep events (e.g. sleep spindle/slow oscillation coupling) are critical for offline memory consolidation. Furthermore, studies in young women have shown fluctuations in sleep events and sleep-dependent memory consolidation during different phases of the menstrual cycle that are associated with the levels of sex steroids. An under-appreciated possibility is that there may be an important interaction between these two protective factors (sex steroids and sleep) that may play a role in daily fluctuations in cognitive processing, in particular memory, across a woman's lifespan. Here, we summarize the current knowledge of sex steroid-dependent influences on sleep and cognition across the lifespan in women, with special emphasis on sleep-dependent memory processing. We further indicate gaps in knowledge that require further experimental examination in order to fully appreciate the complex and changing landscape of sex steroids and cognition. Lastly, we propose a series of testable predictions for how sex steroids impact sleep events and sleep-dependent cognition across the three major reproductive stages in women (reproductive years, menopause transition, and post-menopause). Copyright © 2018 Elsevier Inc. All rights reserved.

SEASONAL VARIATION IN PLASMA SEX STEROID CONCENTRATION IN JUVENILE ALLIGATORS

EPA Science Inventory

Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make...

Interactions between inflammation, sex steroids, and Alzheimer’s disease risk factors

PubMed Central

Uchoa, Mariana F.; Moser, V. Alexandra; Pike, Christian J.

2016-01-01

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder for which there are no effective strategies to prevent or slow its progression. Because AD is multifactorial, recent research has focused on understanding interactions among the numerous risk factors and mechanisms underlying the disease. One mechanism through which several risk factors may be acting is inflammation. AD is characterized by chronic inflammation that is observed before clinical onset of dementia. Several genetic and environmental risk factors for AD increase inflammation, including apolipoprotein E4, obesity, and air pollution. Additionally, sex steroid hormones appear to contribute to AD risk, with age-related losses of estrogens in women and androgens in men associated with increased risk. Importantly, sex steroid hormones have anti-inflammatory actions and can interact with several other AD risk factors. This review examines the individual and interactive roles of inflammation and sex steroid hormones in AD, as well as their relationships with the AD risk factors apolipoprotein E4, obesity, and air pollution. PMID:27651175

Sex steroid hormones and brain function: PET imaging as a tool for research.

PubMed

Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

2018-02-01

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for

Sex differences in β-amyloid accumulation in 3xTg-AD mice: role of neonatal sex steroid hormone exposure.

PubMed

Carroll, Jenna C; Rosario, Emily R; Kreimer, Sara; Villamagna, Angela; Gentzschein, Elisabet; Stanczyk, Frank Z; Pike, Christian J

2010-12-17

The risk of Alzheimer's disease (AD) is higher in women than in men, a sex difference that likely results from the effects of sex steroid hormones. To investigate this relationship, we first compared progression of β-amyloid (Aβ) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly greater Aβ burden and larger behavioral deficits than age-matched males. Next, we evaluated how the organizational effects of sex steroid hormones during postnatal development may affect adult vulnerability to Aβ pathology. We observed that male 3xTg-AD mice demasculinized during early development exhibit significantly increased Aβ accumulation in adulthood. In contrast, female mice defeminized during early development exhibit a more male-like pattern of Aβ pathology in adulthood. Taken together, these results demonstrate significant sex differences in pathology in 3xTg-AD mice and suggest that these differences may be mediated by organizational actions of sex steroid hormones during development. Copyright © 2010 Elsevier B.V. All rights reserved.

Association between endogenous sex steroid hormones and insulin-like growth factor proteins in US men.

PubMed

Papatheodorou, Stefania I; Rohrmann, Sabine; Lopez, David S; Bradwin, Gary; Joshu, Corinne E; Kanarek, Norma; Nelson, William G; Rifai, Nader; Platz, Elizabeth A; Tsilidis, Konstantinos K

2014-03-01

Sex steroid hormone concentrations and insulin-like growth factor (IGF) proteins have been independently associated with risk of cancer, chronic diseases, and mortality. However, studies that evaluated the inter-relation between the sex hormones and IGF pathways have provided mixed results. We examined the association between endogenous sex hormones and sex hormone-binding globulin (SHBG) with IGF-1 and IGF-binding protein 3 (IGFBP-3) in a population-based sample of US men. Data from 1,135 men aged 20 years or older participating in the third National Health and Nutrition Examination Survey (NHANES III) were analyzed. Weighted linear regression was used to estimate geometric means and 95 % confidence intervals for IGF-1 and IGFBP-3 concentrations by sex steroid hormones and SHBG after adjusting for age, race/ethnicity, body mass index, waist circumference, alcohol consumption, cigarette smoking, physical activity, diabetes, and mutually adjusting for other sex hormones and SHBG. No significant association was observed between sex steroid hormones, SHBG, and IGF-1 concentrations. Total estradiol (% difference in Q5 - Q1 geometric means -9.7 %; P-trend 0.05) and SHBG (% difference -7.3 %; P-trend 0.02) were modestly inversely associated with IGFBP-3. Total testosterone was modestly inversely associated with IGFBP-3 (% difference -6.2 %; P-trend 0.01), but this association disappeared after adjustment for total estradiol and SHBG (% difference 2.6 %; P-trend 0.23). Androstanediol glucuronide was not associated with IGFBP-3. These findings suggest that there may be inter-relationships between circulating total estradiol, SHBG, and IGFBP-3 concentrations. Future research may consider these inter-relationships when evaluating potential joint effects of the sex hormones and IGF pathways.

A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers

PubMed Central

Abderrahman, Balkees; Curpan, Ramona F; Hawsawi, Yousef M; Fan, Ping; Jordan, V Craig

2018-01-01

Prostate and breast cancer are the two cancers with the highest incidence in men and women, respectively. Here, we focus on the known biology of acquired resistance to antihormone therapy of prostate and breast cancer and compare laboratory and clinical similarities in the evolution of the disease. Laboratory studies and clinical observations in prostate and breast cancer demonstrate that cell selection pathways occur during acquired resistance to antihormonal therapy. Following sex steroid deprivation, both prostate and breast cancer models show an initial increased acquired sensitivity to the growth potential of sex steroids. Subsequently, prostate and breast cancer cells either become dependent upon the antihormone treatment or grow spontaneously in the absence of hormones. Paradoxically, the physiologic sex steroids now kill a proportion of selected, but vulnerable, resistant tumor cells. The sex steroid receptor complex triggers apoptosis. We draw parallels between acquired resistance in prostate and breast cancer to sex steroid deprivation. Clinical observations and patient trials confirm the veracity of the laboratory studies. We consider therapeutic strategies to increase response rates in clinical trials of metastatic disease that can subsequently be applied as a preemptive salvage adjuvant therapy. The goal of future advances is to enhance response rates and deploy a safe strategy earlier in the treatment plan to save lives. The introduction of a simple evidence-based enhanced adjuvant therapy as a global healthcare strategy has the potential to control recurrence, reduce hospitalization, reduce healthcare costs and maintain a healthier population that contributes to society. PMID:29162647

The influence of sex steroids on structural brain maturation in adolescence.

PubMed

Koolschijn, P Cédric M P; Peper, Jiska S; Crone, Eveline A

2014-01-01

Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used high-resolution structural MRI scans from 215 typically developing individuals between ages 8-25, to examine the association between cortical thickness, surface area and (sub)cortical brain volumes with luteinizing hormone, testosterone and estradiol, and pubertal stage based on self-reports. Our results indicate sex-specific differences in testosterone related influences on gray matter volumes of the anterior cingulate cortex after controlling for age effects. No significant associations between subcortical structures and sex hormones were found. Pubertal stage was not a stronger predictor than chronological age for brain anatomical differences. Our findings indicate that sex steroids are associated with cerebral gray matter morphology in a sex specific manner. These hormonal and morphological differences may explain in part differences in brain development between boys and girls.

Taenia solium tapeworms synthesize corticosteroids and sex steroids in vitro.

PubMed

Valdez, R A; Jiménez, P; Fernández Presas, A M; Aguilar, L; Willms, K; Romano, M C

2014-09-01

Cysticercosis is a disease caused by the larval stage of Taenia solium cestodes that belongs to the family Taeniidae that affects a number of hosts including humans. Taeniids tapeworms are hermaphroditic organisms that have reproductive units called proglottids that gradually mature to develop testis and ovaries. Cysticerci, the larval stage of these parasites synthesize steroids. To our knowledge there is no information about the capacity of T. solium tapeworms to metabolize progesterone or other precursors to steroid hormones. Therefore, the aim of this paper was to investigate if T. solium tapeworms were able to transform steroid precursors to corticosteroids and sex steroids. T. solium tapeworms were recovered from the intestine of golden hamsters that had been orally infected with cysticerci. The worms were cultured in the presence of tritiated progesterone or androstenedione. At the end of the experiments the culture media were analyzed by thin layer chromatography. The experiments described here showed that small amounts of testosterone were synthesized from (3)H-progesterone by complete or segmented tapeworms whereas the incubation of segmented tapeworms with (3)H-androstenedione, instead of (3)H-progesterone, improved their capacity to synthesize testosterone. In addition, the incubation of the parasites with (3)H-progesterone yielded corticosteroids, mainly deoxicorticosterone (DOC) and 11-deoxicortisol. In summary, the results described here, demonstrate that T. solium tapeworms synthesize corticosteroid and sex steroid like metabolites. The capacity of T. solium tapeworms to synthesize steroid hormones may contribute to the physiological functions of the parasite and also to their interaction with the host. Copyright © 2014 Elsevier Inc. All rights reserved.

Major cardiac surgery induces an increase in sex steroids in prepubertal children.

PubMed

Heckmann, Matthias; d'Uscio, Claudia H; de Laffolie, Jan; Neuhaeuser, Christoph; Bödeker, Rolf-Hasso; Thul, Josef; Schranz, Dietmar; Frey, Brigitte M

2014-03-01

While the neuroprotective benefits of estrogen and progesterone in critical illness are well established, the data regarding the effects of androgens are conflicting. Surgical repair of congenital heart disease is associated with significant morbidity and mortality, but there are scant data regarding the postoperative metabolism of sex steroids in this setting. The objective of this prospective observational study was to compare the postoperative sex steroid patterns in pediatric patients undergoing major cardiac surgery (MCS) versus those undergoing less intensive non-cardiac surgery. Urinary excretion rates of estrogen, progesterone, and androgen metabolites (μg/mmol creatinine/m(2) body surface area) were determined in 24-h urine samples before and after surgery using gas chromatography-mass spectrometry in 29 children undergoing scheduled MCS and in 17 control children undergoing conventional non-cardiac surgery. Eight of the MCS patients had Down's syndrome. There were no significant differences in age, weight, or sex between the groups. Seven patients from the MCS group showed multi-organ dysfunction after surgery. Before surgery, the median concentrations of 17β-estradiol, pregnanediol, 5α-dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) were (control/MCS) 0.1/0.1 (NS), 12.4/11.3 (NS), 4.7/4.4 (NS), and 2.9/1.1 (p=0.02). Postoperatively, the median delta 17β-estradiol, delta pregnanediol, delta DHT, and delta DHEA were (control/MCS) 0.2/6.4 (p=0.0002), -3.2/23.4 (p=0.013), -0.6/3.7 (p=0.0004), and 0.5/4.2 (p=0.004). Postoperative changes did not differ according to sex. We conclude that MCS, but not less intensive non-cardiac surgery, induced a distinct postoperative increase in sex steroid levels. These findings suggest that sex steroids have a role in postoperative metabolism following MCS in prepubertal children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bidirectional sex change induced by sex steroid implantation in the hermaphrodite fish, Pseudolabrus sieboldi.

PubMed

Ohta, Kohei; Sakai, Mami; Sundaray, Jittendra Kumar; Kitano, Takeshi; Takeda, Tatsusuke; Yamaguchi, Akihiko; Matsuyama, Michiya

2012-11-01

Sex steroids have been suggested to be involved in gonadal sex change in hermaphrodite fish. Aromatase, the enzyme that catalyzes the conversion of androgens into estrogens, is a principal enzyme regulating gonadal sex. However, the detailed functions of each steroid hormone remain to be evaluated. Recent studies have demonstrated that estradiol-17β (E2) is synthesized via estrone (E1) in some hermaphrodite species. On the other hand, 11-ketotestosterone (11KT) is produced in the testis via testosterone (T). In this study, we hypothesized that E1 and T are also involved in the sex change as precursors for E2 and 11KT, respectively. We implanted females of the wrasse, Pseudolabrus sieboldi, with T and 11KT, and males with E1 and E2, by use of sustained-release capsules. In females, testicular tissues and body color change were observed after androgen administration, in which 11KT was more effective than T. In contrast, after estrogen administration, the gonads of males contained oocytes. In females, the administration of T and 11KT resulted in reduced serum E2 levels. Conversely, serum 11KT levels decreased in the E1- and E2-treated males. Thus, we successfully induced bidirectional sex change in the gonad by estrogen and androgen administration in vivo. Moreover, this study raises the possibility that E1 and T are involved in the sex change as precursors for E2 and 11KT, respectively. Copyright © 2012 Wiley Periodicals, Inc.

Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.

PubMed

Vanderschueren, Dirk; Vandenput, Liesbeth; Boonen, Steven

2005-01-01

During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.

Sex Steroid Modulation of Fatty Acid Utilization and Fatty Acid Binding Protein Concentration in Rat Liver

PubMed Central

Ockner, Robert K.; Lysenko, Nina; Manning, Joan A.; Monroe, Scott E.; Burnett, David A.

1980-01-01

The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated. In previous studies we showed that [14C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males. The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females. These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis. In the present studies, sex steroid effects on hepatocyte [14C]oleate utilization and FABP concentration were investigated directly. Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [14C]oleate utilization. With maturation, total [14C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d. Fatty acid oxidation was little affected. Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [14C]oleate utilization was studied. Castration virtually eliminated maturational changes and blunted the sex differences in adults. Estradiol or testosterone largely reproduced the appropriate adult pattern of [14C]oleate utilization regardless of the genotypic sex of the treated animal. In immature females and males, total cytosolic FABP concentrations were similar. In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [14C]oleate utilization (r = 0.91) and incorporation into triglycerides (r = 0.94) on the other. In 30-d-old animals rates of [14C

Sex differences and the roles of sex steroids in apoptosis of sexually dimorphic nuclei of the preoptic area in postnatal rats.

PubMed

Tsukahara, S

2009-03-01

The brain contains several sexually dimorphic nuclei that exhibit sex differences with respect to cell number. It is likely that the control of cell number by apoptotic cell death in the developing brain contributes to creating sex differences in cell number in sexually dimorphic nuclei, although the mechanisms responsible for this have not been determined completely. The milieu of sex steroids in the developing brain affects sexual differentiation in the brain. The preoptic region of rats has two sexually dimorphic nuclei. The sexually dimorphic nucleus of the preoptic area (SDN-POA) has more neurones in males, whereas the anteroventral periventricular nucleus (AVPV) has a higher cell density in females. Sex differences in apoptotic cell number arise in the SDN-POA and AVPV of rats in the early postnatal period, and an inverse correlation exists between sex differences in apoptotic cell number and the number of living cells in the mature period. The SDN-POA of postnatal male rats exhibits a higher expression of anti-apoptotic Bcl-2 and lower expression of pro-apoptotic Bax compared to that in females and, as a potential result, apoptotic cell death via caspase-3 activation more frequently occurs in the SDN-POA of females. The patterns of expression of Bcl-2 and Bax in the SDN-POA of postnatal female rats are changed to male-typical ones by treatment with oestrogen, which is normally synthesised from testicular androgen and affects the developing brain in males. In the AVPV of postnatal rats, apoptotic regulation also differs between the sexes, although Bcl-2 expression is increased and Bax expression and caspase-3 activity are decreased in females. The mechanisms of apoptosis possibly contributing to the creation of sex differences in cell number and the roles of sex steroids in apoptosis are discussed.

Prenatal and postnatal energetic conditions and sex steroids levels across the first year of life.

PubMed

Thompson, Amanda L; Lampl, Michelle

2013-01-01

Human biologists have documented variability in reproductive maturation, fertility, and cancer risk related to developmental conditions. Yet no previous studies have directly examined the impact of prenatal and postnatal energetic environments on sex steroids in infancy, a critical period for hypothalamic-pituitary-gonadal axis development. Thus, we examined the impact of maternal characteristics, birth size, and feeding practices on fecal sex steroid production in a longitudinal sample of 31 American infants followed from 2 weeks to 12 months of age. Maternal characteristics and birth size were collected at study enrollment, infant diet was assessed through weekly 24-h food diaries, and anthropometrics were measured weekly. Fecal estradiol and testosterone levels were assessed weekly using validated microassay RIA techniques. Mixed models were used to test for associations between maternal and birth characteristics, feeding practices, and sex steroids across the first year of life. Formal mediation analysis examined whether the relationship between infant feeding and hormone levels was mediated by infant size. Maternal and birth characteristics had persistent effects on fecal sex steroid levels, with taller maternal height and larger birth size associated with lower estradiol levels in girls and higher testosterone levels in boys. Infant diet was also associated with sex steroid levels independently of infant size. Formula feeding was associated with higher estradiol levels in boys and girls and with higher testosterone in girls. These results suggest that markers of early energy availability influence sex hormone levels with potential long-term consequences for reproductive development and function. Copyright © 2013 Wiley Periodicals, Inc.

Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp

PubMed Central

Erickson, Dana; Miles, John M.; Bowers, Cyril Y.

2011-01-01

To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E2; women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu (P = 0.019) and dual-peptide stimulation (P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E2/T exposure elevated nadir GH concentrations during saline infusion (P = 0.003), whereas dual-peptide infusion did so independently of T/E2 and sex difference (P = 0.001). All three of sex difference (P = 0.001), sex steroid treatment (P = 0.005), and double-peptide stimulation (P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men (P = 0.016). E2/T augmented peak GH recovery during saline infusion (P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment (P = 0.012) and peptide infusion (P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain. PMID:21467302

Effect of sex steroid hormones on the number of serotonergic neurons in rat dorsal raphe nucleus.

PubMed

Kunimura, Yuyu; Iwata, Kinuyo; Iijima, Norio; Kobayashi, Makito; Ozawa, Hitoshi

2015-05-06

Disorders caused by the malfunction of the serotonergic system in the central nervous system show sex-specific prevalence. Many studies have reported a relationship between sex steroid hormones and the brain serotonergic system; however, the interaction between sex steroid hormones and the number of brain neurons expressing serotonin has not yet been elucidated. In the present study, we determined whether sex steroid hormones altered the number of serotonergic neurons in the dorsal raphe nucleus (DR) of adult rat brains. Animals were divided into five groups: ovariectomized (OVX), OVX+low estradiol (E2), OVX+high E2, castrated males, and intact males. Antibodies against 5-hydroxytryptamine (5-HT, serotonin) and tryptophan hydroxylase (Tph), an enzyme for 5-HT synthesis, were used as markers of 5-HT neurons, and the number of 5-HT-immunoreactive (ir) or Tph-ir cells was counted. We detected no significant differences in the number of 5-HT-ir or Tph-ir cells in the DR among the five groups. By contrast, the intensity of 5-HT-ir showed significant sex differences in specific subregions of the DR independent of sex steroid levels, suggesting that the manipulation of sex steroid hormones after maturation does not affect the number and intensive immunostaining of serotonergic neurons in rat brain. Our results suggest that, the sexual dimorphism observed in the serotonergic system is due to factors such as 5-HT synthesis, transportation, and degradation but not to the number of serotonergic neurons. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sex steroids effects in normal endocrine pancreatic function and diabetes.

PubMed

Morimoto, Sumiko; Jiménez-Trejo, Francisco; Cerbón, Marco

2011-01-01

Traditionally the role of sexual steroid hormones was focused primarily on reproductive organs: the breast, female reproductive tract (uterus, mammary gland, and ovary), and male reproductive tract (testes, epididymis and prostate), however our current understanding of tissue-specific effects of sex steroids has elucidated new aspects in its functionality. Recent data have shown that many other tissues are targets of those hormones in addition to classical reproductive organs. The pancreas (which performs both endocrine and exocrine functions), has proven to be an extragonadal target of sexual steroid hormone action. The endocrine pancreas has a pivotal role on carbohydrate homeostasis and deterioration in function produces diabetes. Diabetes is a metabolic disorder that has high prevalence worldwide, particularly in developing countries. It has been shown that steroid hormones have an important role in susceptibility and development of diabetes in animal models, in humans its role is less clear, however the most evident effect is on the perimenopausal women, in this stage the decrease in gonadal steroids produces an increase on susceptibility to develop diabetes mellitus; in men, hypoandrogenism is associated with an increased prevalence of insulin resistance. This review focused on the effects of sexual steroids on pancreatic function and diabetes.

Sex steroid imbalances in the muricid Stramonita haemastoma from TBT contaminated sites.

PubMed

Rossato, M; Castro, I B; Paganini, C L; Colares, E P; Fillmann, G; Pinho, G L L

2016-04-01

Imposex incidence, organotin tissue levels, and sex steroid (free and esterified testosterone and estradiol) levels were assessed in Stramonita haemastoma from Babitonga Bay (Santa Catarina State, Southern Brazil). The imposex levels showed a reduction when compared to a previous evaluation performed in the same area. In spite of that, the detected imposex incidence indicated the occurrence of tributyltin (TBT) inputs that were still able to produce endocrine disruption in local gastropods. In addition, a high level of organotins was observed in tissues of imposexed females. These females also showed a hormonal imbalance, especially in the total testosterone/total estradiol ratio. These findings obtained under realistic field conditions suggest that the steroid pathway could be responsible by the imposex induction after exposure to TBT. In this case, measurements of sex steroid levels can be an additional evidence for monitoring sites and impose affected gastropod populations.

Inhibition of Aromatase Induces Partial Sex Change in a Cichlid Fish: Distinct Functions for Sex Steroids in Brains and Gonads.

PubMed

Göppert, Carolin; Harris, Rayna M; Theis, Anya; Boila, Anna; Hohl, Simon; Rüegg, Attila; Hofmann, Hans A; Salzburger, Walter; Böhne, Astrid

2016-01-01

Sex steroids are major drivers of sexual development and also responsible for the maintenance of the established gender. Especially fishes exhibit great plasticity and less conservation in sex determination and sexual development compared to other vertebrate groups. In addition, fishes have a constant sex steroid production throughout their entire lifespan, which makes them particularly susceptible to interferences with the endogenous sex steroid system. This susceptibility has recently been used to show that inhibition of the key enzyme of estrogen synthesis, aromatase Cyp19a1, can induce functional sex reversal even in adult fish. Here, we investigated the impact of the aromatase inhibitor (AI) fadrozole in adult females of the East African cichlid fish Astatotilapia burtoni. Using gene expression, phenotypic measurements, behavioral experiments, and hormone measurements, we assessed if females treated with fadrozole develop a male-like phenotype. We found that AI treatment has a different effect on gene expression in the gonad compared to the brain, the 2 tissues mostly implicated in sexual development. In contrast to observations in other gonochoristic species, A. burtoni ovaries cannot be transformed into functional testis by AI. However, rapid changes towards a male-like phenotype can be induced with AI in coloration, hormone levels, and behavior. © 2016 S. Karger AG, Basel.

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

PubMed

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

2017-03-01

Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol OR continuous per ½ IQR   = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone OR continuous per ½ IQR   = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis. © 2017 American Society of Andrology and European Academy of Andrology.

Endogenous sex steroids and cardio- and cerebro-vascular disease in the postmenopausal period.

PubMed

Pappa, Theodora; Alevizaki, Maria

2012-08-01

Cardio- and cerebro-vascular diseases are two leading causes of death and long-term disability in postmenopausal women. The acute fall of estrogen in menopause is associated with increased cardiovascular risk. The relative contribution of androgen to this risk is also being recognized. The use of more sensitive assays for estradiol measurement and the study of receptor and carrier protein gene polymorphisms have provided some new information on the clinical relevance of endogenous sex steroids. We provide an update on the role of endogenous sex steroids on cardio- and cerebro-vascular disease in the postmenopausal period. We performed a PubMed search using the terms 'endogenous estrogen', 'androgen', 'cardiovascular disease', 'cerebro-vascular disease', 'stroke', 'carotid artery disease', and 'subclinical atherosclerosis'. The majority of studies show a beneficial effect of endogenous estrogen on the vasculature; however, there are a few studies reporting the contrary. A significant body of literature has reported associations of endogenous estrogen and androgen with early markers of atherosclerosis and metabolic parameters. Data on the relevance of endogenous sex steroids in heart disease and stroke are inconclusive. Most studies support a beneficial role of endogenous estrogens and, probably, an adverse effect of androgens in the vasculature in postmenopausal women. However, the described associations may not always be considered as causal. It is possible that circulating estrogen might represent a marker of general health status or alternatively reflect the sum of endogenous androgens aromatized in the periphery. Elucidating the role of sex steroids in cardio- and cerebro-vascular disease remains an interesting field of future research.

Body Image Dissatisfaction and Distortion, Steroid Use, and Sex Differences in College Age Bodybuilders.

ERIC Educational Resources Information Center

Peters, Mark Anthony; Phelps, LeAddelle

2001-01-01

Compares college age bodybuilders by sex and steroid intake on two variables: body image dissatisfaction and body image distortion. Results reveal only a significant effect for gender on body distortion. No steroid-use differences were apparent for either body image dissatisfaction or body image distortion. Analyses indicate that female…

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

PubMed

Scott, Alexander P

2013-02-01

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

Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men.

PubMed

Shiels, Meredith S; Rohrmann, Sabine; Menke, Andy; Selvin, Elizabeth; Crespo, Carlos J; Rifai, Nader; Dobs, Adrian; Feinleib, Manning; Guallar, Eliseo; Platz, Elizabeth A

2009-08-01

We evaluated the associations of smoking, alcohol consumption, and physical activity with sex steroid hormone concentrations among 1,275 men > or =20 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Serum concentrations of testosterone, estradiol, and sex hormone-binding globulin (SHBG) were measured. We compared geometric mean concentrations across levels of smoking, alcohol, and physical activity using multiple linear regression. Current smokers had higher total testosterone (5.42, 5.10, and 5.26 ng/ml in current, former, and never smokers), free testosterone (0.110, 0.102, and 0.104 ng/ml), total estradiol (40.0, 34.5, and 33.5 pg/ml), and free estradiol (1.05, 0.88, and 0.84 pg/ml) compared with former and never smokers (all p < or = 0.05). Men who consumed > or =1 drink/day had lower SHBG than men who drank less frequently (31.5 vs. 34.8 nmol/l, p = 0.01); total (p-trend = 0.08) and free testosterone (p-trend = 0.06) increased with number of drinks per day. Physical activity was positively associated with total (p-trend = 0.01) and free testosterone (p-trend = 0.05). In this nationally representative sample of men, smoking, alcohol, and physical activity were associated with hormones and SHBG, thus these factors should be considered as possible confounders or upstream variables in studies of hormones and men's health, including prostate cancer.

Sex hormones, their receptors and bone health.

PubMed

Venken, K; Callewaert, F; Boonen, S; Vanderschueren, D

2008-11-01

Sex steroids regulate skeletal maturation and preservation in both men and women, as already recognized in the 1940s by Albright and Reifenstein. The impact of gonadal insufficiency on skeletal integrity has been widely recognized in adult men and women ever since. In the context of their skeletal actions, androgens and estrogens are no longer considered as just male and female hormones, respectively. Androgens can be converted into estrogens within the gonads and peripheral tissues and both are present in men and women, albeit in different concentrations. In the late 1980s, sex steroid receptors were discovered in bone cells. However, the understanding of sex steroid receptor activation and translation into biological skeletal actions is still incomplete. Due to the complex metabolism, sex steroids may have not only endocrine but also paracrine and/or autocrine actions. Also, circulating sex steroid concentrations do not necessarily reflect their biological activity due to strong binding to sex hormone binding globulin (SHBG). Finally, sex steroid signaling may include genomic and non-genomic effects in bone and non-bone cells. This review will focus on our current understanding of gonadal steroid metabolism, receptor activation, and their most relevant cellular and biological actions on bone.

Serum levels of sex steroid hormones and matrix metalloproteinases after intra-articular glucocorticoid treatment in female patients with rheumatoid arthritis.

PubMed

Weitoft, T; Larsson, A; Rönnblom, L

2008-03-01

To study metalloproteinase activity and sex steroid hormone production in serum after intra-articular glucocorticoid treatment for knee synovitis. 18 female patients with rheumatoid arthritis and synovitis of the knee with need for intra-articular glucocorticoid treatment were included in this study. Serum samples of matrix metalloproteinases (MMP-1/TIMP complex and MMP-3), dehydroepiandrosterone sulphate, testosterone, oestradiol, steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone were collected before injection with 20 mg triamcinolone hexacetonide, and 24 h, 48 h, 1 week and 2 weeks after injection, respectively. Serum levels of MMP-3 were significantly decreased, but MMP-1/TIMP complex was unaffected. Dehydroepiandrosterone sulphate, testosterone and oestradiol levels all decreased and tended to return to baseline levels during the observation period. Steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone levels were unchanged. Intra-articular glucocorticoid treatment causes a temporary, but considerable suppression of sex steroid hormone secretion. The reduction of MMP-3 indicates an inhibition of the inflammatory, but probably also the cartilage destructive processes within the treated joint.

Selection and use of crystallization inhibitors for matrix-type transdermal drug-delivery systems containing sex steroids.

PubMed

Lipp, R

1998-12-01

The purpose of this study was to stabilize transdermal drug-delivery systems (TDDS) highly loaded with sex steroids against recrystallization of drugs during storage. To facilitate the selection of potential crystallization inhibitors a drug-excipient interaction test was also established. Analysis of the thermal behaviour of 1:1 steroid-excipient mixtures by differential scanning calorimetry (DSC) revealed that oestradiol and gestodene interact strongly with silicone dioxide and povidones, e.g. povidone K12. The addition of povidone K12 to polyacrylate-based matrix TDDS containing either 3% oestradiol or 2% gestodene resulted in stable systems which did not recrystallize during storage at 25 degrees C for more than 5 years. Significant recrystallization was, on the other hand, observed in non-stabilized reference patches even after 1 to 2 months storage. The DSC screening model proved very effective for selection of inhibitors of the crystallization of sex steroids in matrix TDDS. The crystallization inhibitor approach is a highly versatile stabilization tool for matrix patches containing high concentrations of sex steroids.

Multiples of Median-Transformed, Normalized Reference Ranges of Steroid Profiling Data Independent of Age, Sex, and Units.

PubMed

Zalas, Dominika; Reinehr, Thomas; Niedziela, Marek; Borzikowsky, Christoph; Flader, Maciej; Simic-Schleicher, Gunter; Akkurt, Halit Ilker; Heger, Sabine; Hornig, Nadine; Holterhus, Paul-Martin; Kulle, Alexandra E

2018-01-01

The high complexity of pediatric reference ranges across age, sex, and units impairs clinical application and comparability of steroid hormone data, e.g., in congenital adrenal hyperplasia (CAH). We developed a multiples-of-median (MoM) normalization tool to overcome this major drawback in pediatric endocrinology. Liquid chromatography tandem mass spectrometry data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to > 16 years) from 2 previous datasets were MoM transformed across age and sex. Twenty-three genetically proven CAH patients were included (21-hydroxylase deficiency [21OHD], n = 19; 11β-hydroxylase deficiency [11OHD], n = 4). MoM cutoffs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, n = 8; adrenal cortical carcinoma, n = 6; obesity, n = 40). 21OHD and 11OHD patients showed disease-typical, easily recognizable MoM patterns independent of age, sex, and concentration units. Two single-steroid cutoffs indicated 21OHD: 3.87 MoM for 17-hydroxyprogesterone (100% sensitivity and 98.83% specificity) and 12.28 MoM for 21-deoxycortisol (94.74% sensitivity and 100% specificity). A cutoff of 13.18 MoM for 11-deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity). Age- and sex-independent MoMs are straightforward for a clinically relevant display of multi-steroid patterns. In addition, defined single-steroid MoMs can serve alone as predictors of 21OHD and 11OHD. Finally, MoM transformation offers substantial enhancement of routine and scientific steroid hormone data exchange due to improved comparability. © 2018 S. Karger AG, Basel.

Offspring sex in a TSD gecko correlates with an interaction between incubation temperature and yolk steroid hormones

NASA Astrophysics Data System (ADS)

Ding, Guo-Hua; Yang, Jing; Wang, Jin; Ji, Xiang

2012-12-01

We incubated eggs of the Japanese gecko Gekko japonicus at three temperatures, and measured yolk testosterone (T) and 17β-estradiol (E2) levels at three time points in embryonic development (oviposition, 1/3 of incubation, and 2/3 of incubation), to examine whether maternal influence on offspring sex via yolk steroid hormone deposition is significant in the species. Eggs incubated at 24 °C and 32 °C produced mostly females, and eggs incubated at 28 °C almost a 50:50 sex ratio of hatchlings. Female-producing eggs were larger than male-producing eggs. Clutches in which eggs were incubated at the same temperature produced mostly same-sex siblings. Yolk T level at laying was negatively related to eggs mass, and yolk E2/T ratio was positively related to egg mass. Results of two-way ANOVA with incubation temperature and stage as the factors show that: yolk E2 level was higher at 32 °C than at 24 °C; yolk T level was higher, whereas yolk E2/T ratio was smaller, at 28 °C than at 24 °C; yolk E2 and T levels were higher at 2/3 than at 1/3 of incubation. Our data in G. japonucus show that: (1) maternal influence on offspring sex via yolk steroid hormone deposition is significant; (2) incubation temperature affects the dynamics of developmental changes in yolk steroid hormones; (3) influences of yolk steroid hormones on offspring sex are secondary relative to incubation temperature effects; and (4) offspring sex correlates with an interaction between incubation temperature and yolk steroid hormones.

Offspring sex in a TSD gecko correlates with an interaction between incubation temperature and yolk steroid hormones.

PubMed

Ding, Guo-Hua; Yang, Jing; Wang, Jin; Ji, Xiang

2012-12-01

We incubated eggs of the Japanese gecko Gekko japonicus at three temperatures, and measured yolk testosterone (T) and 17β-estradiol (E2) levels at three time points in embryonic development (oviposition, 1/3 of incubation, and 2/3 of incubation), to examine whether maternal influence on offspring sex via yolk steroid hormone deposition is significant in the species. Eggs incubated at 24 °C and 32 °C produced mostly females, and eggs incubated at 28 °C almost a 50:50 sex ratio of hatchlings. Female-producing eggs were larger than male-producing eggs. Clutches in which eggs were incubated at the same temperature produced mostly same-sex siblings. Yolk T level at laying was negatively related to eggs mass, and yolk E2/T ratio was positively related to egg mass. Results of two-way ANOVA with incubation temperature and stage as the factors show that: yolk E2 level was higher at 32 °C than at 24 °C; yolk T level was higher, whereas yolk E2/T ratio was smaller, at 28 °C than at 24 °C; yolk E2 and T levels were higher at 2/3 than at 1/3 of incubation. Our data in G. japonucus show that: (1) maternal influence on offspring sex via yolk steroid hormone deposition is significant; (2) incubation temperature affects the dynamics of developmental changes in yolk steroid hormones; (3) influences of yolk steroid hormones on offspring sex are secondary relative to incubation temperature effects; and (4) offspring sex correlates with an interaction between incubation temperature and yolk steroid hormones.

Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study.

PubMed

Petrick, Jessica L; Falk, Roni T; Hyland, Paula L; Caron, Patrick; Pfeiffer, Ruth M; Wood, Shannon N; Dawsey, Sanford M; Abnet, Christian C; Taylor, Philip R; Guillemette, Chantal; Murray, Liam J; Anderson, Lesley A; Cook, Michael B

2018-01-01

Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered. This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

Sex steroid levels and AD-like pathology in 3xTgAD mice

PubMed Central

Ma, Chunqi; Taves, Matthew D.; Soma, Kiran K.; Mufson, Elliott J.

2014-01-01

Decreases in testosterone (T) and 17β-oestradiol (E2) are associated with an increased risk for Alzheimer's disease (AD), which has been attributed to an increase in beta amyloid (Aβ) and tau pathologic lesions. While recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD-like pathology, virtually none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age-related changes in T and E2 concentrations, as well as androgen receptor (AR) and oestrogen receptor (ER) α and β expression, in brain regions displaying AD pathology in intact male and female 3xTgAD and non-transgenic (ntg) mice. We report for the first time that circulating and brain T levels significantly increase in male 3xTgAD mice with age, but without changes in AR-immunoreactive (ir) cell number in either the hippocampal CA1 or medial amygdala. The age-related increase in hippocampal T levels correlated positively with increases in the conformational tau isoform, Alz50. These data suggest that the over-expression of human tau may up regulate the hypothalamic-pituitary-gonadal axis in these mice. Although circulating and brain E2 levels remained stable with age in both male and female 3xTgAD and ntg mice, ER-ir cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Further, E2 levels were significantly higher in the hippocampus than in serum, suggesting local production of E2. Although triple transgenic mice mimic AD-like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions. PMID:22889357

Neurosteroids in Adult Hippocampus of Male and Female Rodents: Biosynthesis and Actions of Sex Steroids.

PubMed

Hojo, Yasushi; Kawato, Suguru

2018-01-01

The brain is not only the target of steroid hormones but also is able to locally synthesize steroids de novo . Evidence of the local production of steroids in the brain has been accumulating in various vertebrates, including teleost fish, amphibia, birds, rodents, non-human primates, and humans. In this review, we mainly focus on the local production of sex steroids in the hippocampal neurons of adult rodents (rats and mice), a center for learning and memory. From the data of the hippocampus of adult male rats, hippocampal principal neurons [pyramidal cells in CA1-CA3 and granule cells in dentate gyrus (DG)] have a complete system for biosynthesis of sex steroids. Liquid chromatography with tandem-mass-spectrometry (LC-MS/MS) enabled us to accurately determine the levels of hippocampal sex steroids including 17β-estradiol (17β-E2), testosterone (T), and dihydrotestosterone (DHT), which are much higher than those in blood. Next, we review the steroid synthesis in the hippocampus of female rats, since previous knowledge had been biased toward the data from males. Recently, we clarified that the levels of hippocampal steroids fluctuate in adult female rats across the estrous cycle. Accurate determination of hippocampal steroids at each stage of the estrous cycle is of importance for providing the account for the fluctuation of female hippocampal functions, including spine density, long-term potentiation (LTP) and long-term depression (LTD), and learning and memory. These functional fluctuations in female had been attributed to the level of circulation-derived steroids. LC-MS/MS analysis revealed that the dendritic spine density in CA1 of adult female hippocampus correlates with the levels of hippocampal progesterone and 17β-E2. Finally, we introduce the direct evidence of the role of hippocampus-synthesized steroids in hippocampal function including neurogenesis, LTP, and memory consolidation. Mild exercise (2 week of treadmill running) elevated synthesis of DHT

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Esophageal/Gastric Cardia Adenocarcinoma Among Men.

PubMed

Petrick, Jessica L; Hyland, Paula L; Caron, Patrick; Falk, Roni T; Pfeiffer, Ruth M; Dawsey, Sanford M; Abnet, Christian C; Taylor, Philip R; Weinstein, Stephanie J; Albanes, Demetrius; Freedman, Neal D; Gapstur, Susan M; Bradwin, Gary; Guillemette, Chantal; Campbell, Peter T; Cook, Michael B

2018-05-17

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case-control study drawn from participants in three prospective cohort studies. Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.

The role of sex steroids in forming anxiety states in female mice.

PubMed

Galeeva, A Yu; Tuohimaa, P; Shalyapina, V G

2003-05-01

Natural fluctuations in sex hormones during the ovarian cycle have enormous influences on ongoing psychological status in the female body. We report here studies of the effects of exogenous sex steroids on anxiety levels in female mice, as evaluated in the elevated cross maze test. Female NMRI mice were subjected to bilateral oophorectomy and one week later received s.c. injections of solvent (sesame oil, controls) or estradiol benzoate for 7 days, either alone or with an additional dose of progesterone on day 7. Elevated maze tests performed 6 h later showed that animals given progesterone had the highest levels of anxiety and the highest levels of grooming reactions as compared with the other groups. Immunohistochemical analysis of the distribution of progesterone receptors in different parts of the brain demonstrated significant increases in the numbers of immunopositive cells after injections of estradiol benzoate alone, with further increases after progesterone injections. Thus, the data obtained here suggest that the genomic effects of sex steroids are important, as they appear to be involved in non-sexual forms of behavior, particularly the level of anxiety.

Association of serum calcium with serum sex steroid hormones in men in NHANES III.

PubMed

Van Hemelrijck, Mieke; Michaelsson, Karl; Nelson, William G; Kanarek, Norma; Dobs, Adrian; Platz, Elizabeth A; Rohrmann, Sabine

2013-12-01

Bone is a positive regulator of male fertility, which indicates a link between regulation of bone remodeling and reproduction or more specifically a link between calcium and androgens. This possibly suggests how calcium is linked to prostate cancer development through its link with the reproductive system. We studied serum calcium and sex steroid hormones in the Third National Health and Nutrition Examination Survey (NHANES III). Serum calcium and sex steroid hormones were measured for 1262 men in NHANES III. We calculated multivariable-adjusted geometric means of serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide (AAG), and sex hormone binding globulin (SHBG) by categories of calcium (lowest 5% [<1.16 mmol/L], mid 90%, top 5% [≥1.30 mmol/L]). Levels of total and free testosterone, total estradiol or AAG did not differ across categories of serum calcium. Adjusted SHBG concentrations were 36.4 for the bottom 5%, 34.2 for the mid 90% and 38.9 nmol/L for the top 5% of serum calcium (Ptrend = 0.006), free estradiol levels were 0.88, 0.92 and 0.80 pg/ml (Ptrend = 0.048). This link between calcium and sex steroid hormones, in particular the U-shaped pattern with SHBG, may, in part, explain why observational studies have found a link between serum calcium and risk of prostate cancer.

Pre-diabetes and serum sex steroid hormones among US men.

PubMed

Arthur, R; Rohrmann, S; Møller, H; Selvin, E; Dobs, A S; Kanarek, N; Nelson, W; Platz, E A; Van Hemelrijck, M

2017-01-01

Several studies demonstrate a link between diabetes and sex steroid hormones, but the link with pre-diabetes remains elusive. In this study, we hypothesize that pre-diabetes, which is characterised by having impaired fasting glucose and/or impaired glucose tolerance and/or impaired HbA1C, may influence circulating sex steroid hormone concentrations in men. Thus, we investigated whether serum sex steroid hormone concentrations differ between men with and without pre-diabetes. We analyzed data for 1139 men who were aged 20+ years when they participated in the Third National Health and Nutrition Examination Survey. We calculated adjusted geometric mean serum concentrations of total and estimated free testosterone, androstanediol glucuronide, total and estimated free estradiol, and sex hormone-binding globulin (SHBG) in men with and without pre-diabetes. Logistic regression was used to calculate adjusted odds ratios (OR) of lower concentrations of androgens and SHBG, and higher concentrations of estradiol by prediabetes status. Adjusting for age and race/ethnicity, total testosterone concentration was lower among men with (geometric mean: 4.68 ng/mL) than without (5.36 ng/mL, p = 0.01) pre-diabetes. SHBG concentration was also lower in men with (31.67 nmol/L) than without (36.16 nmol/L; p = 0.01) pre-diabetes. Concentrations of the other hormones did not differ between men with and without pre-diabetes. After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58; 95% CI: 1.54-4.29), higher free estradiol level (OR: 1.59; 95% CI: 1.14-2.22), and lower SHBG level (OR: 2.27; 95% CI: 1.32-3.92) compared to men without pre-diabetes. These associations were attenuated after adjusting for adiposity (testosterone OR: 1.76; 95% CI 0.95-3.27, free estradiol OR: 1.29, 95% CI: 0.88-1.88, SHBG OR: 1.71; 95% CI 0.88-3.30). Our findings suggest that men with pre-diabetes have lower circulating total testosterone

Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Vikas; Sharma, Vikas; Singh, Vishal

The predominant estrogen-receptor (ER)-β signaling in normal prostate is countered by increased ER-α signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(α/β) and/or AR, viz. 3,3′diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H-indol-3-yl)methyl) aniline (DIMA) was identified as themore » most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-β, p21 and p27 protein levels in LNCaP cells and exhibited ∼ 5 times more selective binding for ER-β than ER-α, in comparison to raloxifene. DIMA exhibited a dose-dependent ER-β agonism and ER-α antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 μM (P < 0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi-steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-β mediated telomerase inhibition, by countering actions of ER-α and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP.« less

A possible relationship between Takotsubo cardiomyopathy and female sex steroid-related modulation of functional cerebral asymmetry.

PubMed

Drača, S

2015-03-01

Takotsubo cardiomyopathy (Tc) is a transient left ventricular apical ballooning syndrome, with symptoms and signs of acute myocardial infarction. Tc syndrome, which occurs predominantly in postmenopausal women, is characterized by increase of sympathetic activity. Studies on the gender-specific differences in sympatho-vagal regulation and functional cerebral asymmetry (FCA) imply that female pattern of dominance is characterized by the left hemisphere, which is believed to have parasympathetic predominance, whereas male pattern indicates dominance of the right hemisphere, which is believed to have sympathetic predominance. Fluctuating levels of female sex steroids are supposed to change FCA, modulating transcallosal inter-hemispheric inhibition across the menstrual cycle. The findings suggest that FCA is enhanced during the low steroid phase (menstrual phase), whereas, during high estrogen and/or progesterone phases (follicular and luteal phase) FCA is reduced. This theory is in line with concept of decreased magnitude of inter-hemispheric cortical lateralization in premenopausal women compared to men and postmenopausal women. Therefore, if postmenopausal women are more lateralized for a variety of cerebral functions, they have less balanced equilibrium between the right-sided sympathetic and left-sided parasympathetic predominance. Decrease of endogenous female sex steroid levels in postmenopausal women leads to reduced influence of estrogens to the left hemisphere, which is believed to have parasympathetic predominance. If both of these mechanisms result in sympatho-vagal imbalance, increasing sympathetic system activity in postmenopausal women, it seems reasonable why postmenopausal women became more susceptible to sympathetically-mediated syndromes such as Takotsubo cardiomyopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of sex steroids on expression of genes regulating growth-related mechanisms in rainbow trout (Oncorhynchus mykiss).

PubMed

Cleveland, Beth M; Weber, Gregory M

2015-05-15

Effects of a single injection of 17β-estradiol (E2), testosterone (T), or 5β-dihydrotestosterone (DHT) on expression of genes central to the growth hormone (GH)/insulin-like growth factor (IGF) axis, muscle-regulatory factors, transforming growth factor-beta (TGFβ) superfamily signaling cascade, and estrogen receptors were determined in rainbow trout (Oncorhynchus mykiss) liver and white muscle tissue. In liver in addition to regulating GH sensitivity and IGF production, sex steroids also affected expression of IGF binding proteins, as E2, T, and DHT increased expression of igfbp2b and E2 also increased expression of igfbp2 and igfbp4. Regulation of this system also occurred in white muscle in which E2 increased expression of igf1, igf2, and igfbp5b1, suggesting anabolic capacity may be maintained in white muscle in the presence of E2. In contrast, DHT decreased expression of igfbp5b1. DHT and T decreased expression of myogenin, while other muscle regulatory factors were either not affected or responded similarly for all steroid treatments. Genes within the TGFβ superfamily signaling cascade responded to steroid treatment in both liver and muscle, suggesting a regulatory role for sex steroids in the ability to transmit signals initiated by TGFβ superfamily ligands, with a greater number of genes responding in liver than in muscle. Estrogen receptors were also regulated by sex steroids, with era1 expression increasing for all treatments in muscle, but only E2- and T-treatment in liver. E2 reduced expression of erb2 in liver. Collectively, these data identify how physiological mechanisms are regulated by sex steroids in a manner that promotes the disparate effects of androgens and estrogens on growth in salmonids. Published by Elsevier Inc.

No relationship between circulating levels of sex steroids and mammographic breast density: the Prospect-EPIC cohort

PubMed Central

Verheus, Martijn; Peeters, Petra HM; van Noord, Paulus AH; van der Schouw, Yvonne T; Grobbee, Diederick E; van Gils, Carla H

2007-01-01

Background High breast density is associated with increased breast cancer risk. Epidemiologic studies have shown an increase in breast cancer risk in postmenopausal women with high levels of sex steroids. Hence, sex steroids may increase postmenopausal breast cancer risk via an increase of breast density. The objective of the present study was to study the relation between circulating oestrogens and androgens as well as sex hormone binding globulin (SHBG) in relation to breast density. Methods We conducted a cross-sectional study among 775 postmenopausal women, using baseline data of a random sample of the Prospect-EPIC study. Prospect-EPIC is one of two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition, and women were recruited via a breast cancer screening programme. At enrolment a nonfasting blood sample was taken and a mammogram was made. Oestrone, oestradiol, dehydroepiandrosterone sulfate, androstenedione, testosterone and SHBG levels were measured, using double-antibody radioimmunoassays. Concentrations of free oestradiol and free testosterone were calculated from the measured oestradiol, testosterone and SHBG levels Mammographic dense and nondense areas were measured using a semiquantitative computerized method and the percentage breast density was calculated. Mean breast measures for quintiles of hormone or SHBG levels were estimated using linear regression analyses. Results Both oestrogens and testosterone were inversely related with percent breast density, but these relationships disappeared after adjustment for BMI. None of the sex steroids or SHBG was associated with the absolute measure of breast density, the dense area. Conclusion The results of our study do not support the hypothesis that sex steroids increase postmenopausal breast cancer risk via an increase in breast density. PMID:17692133

Sex Reversal and Analyses of Possible Involvement of Sex Steroids in Scallop Gonadal Development in Newly Established Organ-Culture Systems.

PubMed

Otani, Ayano; Nakajima, Tadaaki; Okumura, Tomomi; Fujii, Shiro; Tomooka, Yasuhiro

2017-04-01

Many molluscs perform sex reversal, and sex hormones may be involved in the process. In adult scallops, Patinopecten yessoensis, gonadotropin releasing hormone and 17β-estradiol (E 2 ) are involved in male sexual maturation, however, little is known about the effects of E 2 and testosterone (T) on the gonadal differentiation in young scallops. In the present study, scallop gonadal development was analyzed to determine the sex reversal stage in Funka bay, and effects of E 2 and T were examined. In Funka bay, almost all scallops were male at month 12. Scallops equipped with ambiguous gonads were 61.1% at month 16 and disappeared at month 18. Therefore, sex reversal in Funka bay occurs at around month 16. For establishment of organ culture systems for bivalves, Manila clam gonads were cultured in 15% L-15 medium diluted with HBSS containing 10% KSR on agarose gel at 10°C, and the gonads survived for 14 days. Scallop gonads were also able to be cultured in 30% L15 medium diluted with ASW containing 10% KSR on agarose gel for seven days. At mature stage, Foxl2 and Tesk were predominantly expressed in ovary and testis, respectively. When scallop gonads at sex reversal stage were organ-cultured, sex steroid treatment decreased Tesk expression in the majority of scallop gonads at sex reversal stage. However, no obvious change in Foxl2 and Tesk expression was detected in mature gonads in response to either E 2 or T in culture, suggesting sex steroid treatment might affect gonadal development at sex reversal stage.

New steroid derivative with hypoglycemic activity

PubMed Central

Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

2014-01-01

Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative. PMID:25550906

Factors That Contribute to Assay Variation in Quantitative Analysis of Sex Steroid Hormones Using Liquid and Gas Chromatography-Mass Spectrometry

ERIC Educational Resources Information Center

Xu, Xia; Veenstra, Timothy D.

2012-01-01

The list of physiological events in which sex steroids play a role continues to increase. To decipher the roles that sex steroids play in any condition requires high quality cohorts of samples and assays that provide highly accurate quantitative measures. Liquid and gas chromatography coupled with mass spectrometry (LC-MS and GC-MS) have…

Metabolite profiling of sex developmental steroid conjugates reveals an association between decreased levels of steroid sulfates and adiposity in obese girls.

PubMed

Lee, Su Hyeon; Kim, Shin Hye; Lee, Won-Yong; Chung, Bong Chul; Park, Mi Jung; Choi, Man Ho

2016-09-01

Free and conjugated steroids coexist in a dynamic equilibrium due to complex biosynthetic and metabolic processes. This may have clinical significance related to various physiological conditions, including sex development involving the reproductive system. Therefore, we performed quantitative profiling of 16 serum steroids conjugated with glucuronic and sulfuric acids using liquid chromatography-mass spectrometry (LC-MS). All steroid conjugates were purified by solid-phase extraction and then separated through a 3-μm particle size C18 column (150mm×2.1mm) at a flow rate of 0.3 mL/min in the negative ionization mode. The LC-MS-based analysis was found to be linear (r(2)>0.99), and all steroid conjugates had a limit-of-quantification (LOQ) of 10ng/mL, except for cholesterol sulfate and 17β-estradiol-3,17-disulfate (20ng/mL). The extraction recoveries of all steroid conjugates ranged from 97.9% to 110.7%, while the overall precision (% CV) and accuracy (% bias) ranged from 4.8% to 10.9% and from 94.4% to 112.9% at four different concentrations, respectively. Profiling of steroid conjugates corrected by adiposity revealed decreased levels of steroid sulfates (P<0.01) in overweight and obese girls compared to normal girls. The suggested technique can be used for evaluating metabolic changes in steroid conjugates and for understanding the pathophysiology and relative contributions of adiposity in childhood obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Changes in steroid profiles of the blue mussel Mytilus trossulus as a function of season, stage of gametogenesis, sex, tissue and mussel bed depth.

PubMed

Smolarz, Katarzyna; Zabrzańska, Sandra; Konieczna, Lucyna; Hallmann, Anna

2018-04-01

This paper describes changes in the content of free steroid hormones e.g. testosterone (T), estradiol-17β (E2), estrone (E1) and estriol (E3) of Mytilus trossulus from the southern Baltic Sea as a function of season, stage of gametogenesis, sex, tissue (gonadal and somatic) and depth. The highest levels of T, E2, E1 and E3 were found in mussels sampled in spring and summer while the lowest levels were found in winter. This pattern was stable and was seen in both sexes and tissues in mussels from both mussel beds. The spring and summer peaks in steroid levels (SL) coincided with advanced levels of gametogenesis (the highest gonadal index, GI) of our model species. But, the lowest GI (autumn) and the lowest steroids content (winter) did not overlap. Instead, water temperature increase was followed by increase of SL and vice versa. This suggests that steroids may not be actively involved in the early stages of gamete development and does not preclude them from potentially being involved as endogenous modulators in the final stages of reproduction (e.g. spawning). Hence, observed fluctuations in SL in our model species are unlikely to be caused by reproductive cycle but are rather of unknown nature, likely linked with environmental conditions. Sex-related differences in steroid content included estrogen domination in females and androgen domination in males. A trend towards higher level of steroids in gills than in gonads was found, supporting the hypothesis about an exogenous origin of steroids in bivalves. However, based on the present results, we cannot exclude the possibility that these steroids have both an endogenous and exogenous origin. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural sensitivity to sex steroids predicts individual differences in aggression: implications for behavioural evolution.

PubMed

Rosvall, K A; Bergeon Burns, C M; Barske, J; Goodson, J L; Schlinger, B A; Sengelaub, D R; Ketterson, E D

2012-09-07

Testosterone (T) regulates many traits related to fitness, including aggression. However, individual variation in aggressiveness does not always relate to circulating T, suggesting that behavioural variation may be more closely related to neural sensitivity to steroids, though this issue remains unresolved. To assess the relative importance of circulating T and neural steroid sensitivity in predicting behaviour, we measured aggressiveness during staged intrusions in free-living male and female dark-eyed juncos (Junco hyemalis). We compared aggressiveness to plasma T levels and to the abundance of androgen receptor (AR), aromatase (AROM) and oestrogen receptor alpha (ORα) mRNA in behaviourally relevant brain areas (avian medial amygdala, hypothalamus and song control regions). We also asked whether patterns of covariation among behaviour and endocrine parameters differed in males and females, anticipating that circulating T may be a better predictor of behaviour in males than in females. We found that circulating T related to aggressiveness only in males, but that gene expression for ORα, AR and AROM covaried with individual differences in aggressiveness in both sexes. These findings are among the first to show that individual variation in neural gene expression for three major sex steroid-processing molecules predicts individual variation in aggressiveness in both sexes in nature. The results have broad implications for our understanding of the mechanisms by which aggressive behaviour may evolve.

Differential Responses of Brain, Gonad and Muscle Steroid Levels to Changes in Social Status and Sex in a Sequential and Bidirectional Hermaphroditic Fish

PubMed Central

Lorenzi, Varenka; Earley, Ryan L.; Grober, Matthew S.

2012-01-01

Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli) is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E2), testosterone (T) and 11-ketotestosterone (KT). Females had more T than males in the gonads, and more E2 in all tissues but there was no sex difference in KT. For both sexes, E2 was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E2 levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change. PMID:23251444

Effect of sex steroid hormones on replication and transmission of major HIV subtypes.

PubMed

Ragupathy, Viswanath; Devadas, Krishnakumar; Tang, Shixing; Wood, Owen; Lee, Sherwin; Dastyer, Armeta; Wang, Xue; Dayton, Andrew; Hewlett, Indira

2013-11-01

The HIV epidemic is expanding worldwide with an increasing number of distinct viral subtypes and circulating recombinant forms (CRFs). Out of 34 million adults living with HIV and AIDS, women account for one half of all HIV-1 infections worldwide. These gender differences in HIV pathogenesis may be attributed to sex hormones. Little is known about the role of sex hormone effects on HIV Subtypes pathogenesis. The aim of our study was to determine sex hormone effects on replication and transmissibility of HIV subtypes. Peripheral blood mononuclear cells (PBMC) and monocyte derived dendritic cells (MDDC) from male and female donors were infected with HIV subtypes A-D and CRF02_AG, CRF01_AE, MN (lab adapted), Group-O, Group-N and HIV-2 at a concentration of 5ng/ml of p24 or p27. Virus production was evaluated by measuring p24 and p27 levels in culture supernatants. Similar experiments were carried out in the presence of physiological concentrations of sex steroid hormones. R5/X4 expressions measured by flow cytometry and transmissibility was evaluated by transfer of HIV from primary dendritic cells (DC) to autologous donor PBMC. Our results from primary PBMC and MDDC from male and female donors indicate in the absence of physiological concentrations of hormone treatment virus production was observed in three clusters; high replicating virus (subtype B and C), moderate replicative virus (subtype A, D, CRF01_AE, Group_N) and least replicative virus (strain MN). However, dose of sex steroid hormone treatment influenced HIV replication and transmission kinetics in PBMC, DCs and cell lines. Such effects were inconsistent between donors and HIV subtypes. Sex hormone effects on HIV entry receptors (CCR5/CXCR4) did not correlate with virus production. Subtypes B and C showed higher replication in PBMC from males and females and were transmitted more efficiently through DC to male and female PBMC compared with other HIV-1 subtypes, HIV-1 Group O and HIV-2. These findings are

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

PubMed Central

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

2017-01-01

Bisphenol A (BPA) is an industrial chemical found in thermal receipts and food and beverage containers. Previous studies have shown that BPA can affect the numbers and health of ovarian follicles and the production of sex steroid hormones, but they often did not include a wide range of doses of BPA, used a small sample size, focused on relatively short-term exposures to BPA, and/or did not examine the consequences of chronic BPA exposure on the ovaries or steroid levels. Thus, this study was designed to examine the effects of a wide range of doses of BPA on ovarian morphology and sex steroid hormone production. Specifically, this study tested the hypothesis that prenatal and continuous BPA exposure reduces ovarian follicle numbers and sex steroid hormone levels. To test this hypothesis, rats were dosed with vehicle, ethinyl estradiol (0.05 and 0.5 μg/kg body weight/d), or BPA (2.5, 25, 250, 2500, and 25,000 μg/kg body weight/d) from gestation day 6 until 1 year as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). Ovaries and sera were collected on postnatal days 1, 21, and 90, and at 6 months and 1 year. The ovaries were subjected to histological evaluation of follicle numbers and the sera were subjected to measurements of estradiol and progesterone. Collectively, these data indicate that BPA exposure at some doses and time points affects ovarian follicle numbers and sex steroid levels, but these effects are different than those observed with ethinyl estradiol exposure and some previous studies on BPA. PMID:28324068

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

PubMed

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

2017-06-01

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

Regulation of Kiss1 Expression by Sex Steroids in the Amygdala of the Rat and Mouse

PubMed Central

Kim, Joshua; Semaan, Sheila J.; Clifton, Donald K.; Steiner, Robert A.; Dhamija, Sangeeta

2011-01-01

Kisspeptin (encoded by the Kiss1 gene) is an important regulator of reproduction. In rodents, Kiss1 is expressed in two hypothalamic regions, the arcuate nucleus and anteroventral periventricular/ periventricular continuum, where it is regulated by sex steroids. However, the distribution, regulation, and functional significance of neural kisspeptin outside of the hypothalamus have not been studied and are poorly understood. Here, we report the expression of Kiss1 in the amygdala, predominantly in the medial nucleus of the amygdala (MeA), a region implicated in social and emotional behaviors as well as various aspects of reproduction. In gonadally intact rats and mice, Kiss1-expressing neurons were identified in the MeA of both sexes, with higher Kiss1 expression levels in adult males than females in diestrus. In rats, Kiss1 expression in the MeA changed as a function of the estrous cycle, with highest levels at proestrus. Next, we tested whether Kiss1 in the MeA is regulated by the circulating sex steroid milieu. Kiss1 levels in the MeA were low in gonadectomized mice and rats of both sexes, and treatment with either testosterone or estradiol amplified Kiss1 expression in this region. Testosterone's inductive effect on Kiss1 expression in the MeA likely occurs via estrogen receptor-dependent pathways, not through the androgen receptor, because dihydrotestosterone (a nonaromatizable androgen) did not affect MeA Kiss1 levels. Thus, in rodents, Kiss1 is expressed and regulated by sex steroids in the MeA of both sexes and may play a role in modulating reproduction or brain functions that extend beyond reproduction. PMID:21363930

Depot differences in steroid receptor expression in adipose tissue: possible role of the local steroid milieu.

PubMed

Rodriguez-Cuenca, S; Monjo, M; Proenza, A M; Roca, P

2005-01-01

Sex hormones play an important role in adipose tissue metabolism by activating specific receptors that alter several steps of the lipolytic and lipogenic signal cascade in depot- and sex-dependent manners. However, studies focusing on steroid receptor status in adipose tissue are scarce. In the present study, we analyzed steroid content [testosterone (T), 17beta-estradiol (17beta-E2), and progesterone (P4)] and steroid receptor mRNA levels in different rat adipose tissue depots. As expected, T levels were higher in males than in females (P = 0.031), whereas the reverse trend was observed for P4 (P < 0.001). It is noteworthy that 17beta-E2 adipose tissue levels were higher in inguinal than in the rest of adipose tissues for both sexes, where no sex differences in 17beta-E2 tissue levels were noted (P = 0.010 for retroperitoneal, P = 0.005 for gonadal, P = 0.018 for mesenteric). Regarding steroid receptor levels, androgen (AR) and estrogen receptor (ER)alpha and ERbeta densities were more clearly dependent on adipose depot location than on sex, with visceral depots showing overall higher mRNA densities than their subcutaneous counterparts. Besides, expression of ERalpha predominated over ERbeta expression, and progesterone receptor (PR-B form and PR-A+B form) mRNAs were identically expressed regardless of anatomic depot and sex. In vitro studies in 3T3-L1 cells showed that 17beta-E2 increased ERalpha (P = 0.001) and AR expression (P = 0.001), indicating that estrogen can alter estrogenic and androgenic signaling in adipose tissue. The results highlighted in this study demonstrate important depot-dependent differences in the sensitivity of adipose tissues to sex hormones between visceral and subcutaneous depots that could be related to metabolic situations observed in response to sex hormones.

P-Glycoprotein Activity in Steroid-Responsive vs. Steroid-Resistant Nephrotic Syndrome.

PubMed

Badr, Hassan S; El-Hawy, Mahmoud A; Helwa, Mohammed A

2016-11-01

To explore the expression of P-glycoprotein (P-gp) in the peripheral blood nucleated cells (PBNCs) of children with nephrotic syndrome in relation to their clinical response to glucocorticoid treatment. Thirty-six children with nephrotic syndrome (20 cases of steroid-responsive and 16 cases of steroid-resistant) were examined. All the participants were subjected to complete history taking, thorough clinical examination, laboratory investigations (24-h urinary protein, serum albumin, complete blood count with differential white blood cell count, serum cholesterol, serum urea, serum creatinine) and functional assay of P-gp using FACS Calibur flowcytometry. P-gp assay was done in both groups during remission. P-gp activity was significantly higher in steroid-resistant than steroid-sensitive cases. P-gp can be used as a predictor of outcome, as a part of laboratory evaluation of the cases before starting steroid therapy, so as to determine whether to use alternative line of therapy or use one of the P-gp inhibitors with steroid therapy.

The role of sex hormone-binding globulin (SHBG), testosterone, and other sex steroids, on the development of type 2 diabetes in a cohort of community-dwelling middle-aged to elderly men.

PubMed

Gyawali, Prabin; Martin, Sean A; Heilbronn, Leonie K; Vincent, Andrew D; Taylor, Anne W; Adams, Robert J T; O'Loughlin, Peter D; Wittert, Gary A

2018-05-29

Contrasting findings exist regarding the association between circulating sex hormone-binding globulin (SHBG) and testosterone levels and type 2 diabetes (T2D) in men. We examined prospective associations of SHBG and sex steroids with incident T2D in a cohort of community-dwelling men. Participants were from a cohort study of community-dwelling (n = 2563), middle-aged to elderly men (35-80 years) from Adelaide, Australia (the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study). The current study included men who were followed for 5 years and with complete SHBG and sex steroid levels (total testosterone (TT), dihydrotestosterone (DHT) and oestradiol (E2)), but without T2D at baseline (n = 1597). T2D was identified by either self-report, fasting glucose (≥ 7.0 mmol/L), HbA1c (≥ 6.5%/48.0 mmol/mol), and/or prescriptions for diabetes medications. Logistic binomial regression was used to assess associations between SHBG, sex steroids and incident T2D, adjusting for confounders including age, smoking status, physical activity, adiposity, glucose, triglycerides, symptomatic depression, SHBG and sex steroid levels. During an average follow-up of 4.95 years, 14.5% (n = 232) of men developed new T2D. Multi-adjusted models revealed an inverse association between baseline SHBG, TT, and DHT levels, and incident T2D (odds ratio (OR) = 0.77, 95% CI [0.62, 0.95], p = 0.02; OR 0.70 [0.57, 0.85], p < 0.001 and OR 0.78 [0.63, 0.96], p = 0.02), respectively. However, SHBG was no longer associated with incident T2D after additional adjustment for TT (OR 0.92 [0.71, 1.17], p = 0.48; TT in incident T2D: OR 0.73 [0.57, 0.92], p = 0.01) and after separate adjustment for DHT (OR 0.83 [0.64, 1.08], p = 0.16; DHT in incident T2D: OR 0.83 [0.65, 1.05], p = 0.13). There was no observed effect of E2 in all models of incident T2D. In men, low TT, but not SHBG and other sex steroids, best predicts the development of T2D

Molecular characterization of kiss2 and differential regulation of reproduction-related genes by sex steroids in the hypothalamus of half-smooth tongue sole (Cynoglossus semilaevis).

PubMed

Wang, Bin; Liu, Quan; Liu, Xuezhou; Xu, Yongjiang; Song, Xuesong; Shi, Bao

2017-11-01

Kisspeptin (Kiss) plays a critical role in mediating gonadal steroid feedback to the gonadotropin-releasing hormone (GnRH) neurons in mammals. However, little information regarding the regulation of kisspeptin gene by sex steroids is available in teleosts. In this study, we examined the direct actions of estradiol (E2) and testosterone (T) on hypothalamic expression of kisspeptin and other key factors involved in reproductive function of half-smooth tongue sole. As a first step, a partial-length cDNA of kiss2 was identified from the brain of tongue sole and kiss2 transcript levels were shown to be widely expressed in various tissues, notably in the ovary. Then, the actions of sex steroids on kiss2 and other reproduction-related genes were evaluated using a primary hypothalamus culture system. Our results showed that neither kiss2 nor its receptor kiss2r mRNA levels were significantly altered by sex steroids. Moreover, sex steroids did not modify hypothalamic expression of gonadotropin-inhibitory hormone (gnih) and its receptor gnihr mRNAs, either. However, E2 markedly stimulated both gnrh2 and gnrh3 mRNAs levels. Overall, this study provides insights into the role of sex steroids in the reproductive function of Pleuronectiform teleosts. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of male and female sex steroids on the development of normal and the transient Froriep's dorsal root ganglia of the chick embryo.

PubMed

Liu, Jiali; Chen, Dawei; Goldstein, Ronald S; Cui, Sheng

2005-03-22

Sex steroids can influence developmental processes and support the survival of neurons in the embryonic central nervous system. Recent studies have shown that estrogen receptors are also expressed in the peripheral nervous system, in the dorsal root ganglia (DRG) of chick embryos. However, no studies have examined the effects of sex steroids on development of embryonic DRG. In the present study, 0.2 microg, 1.0 microg, 5.0 microg 10 microg, 20 microg, 25 microg, and 40 microg doses of testosterone or estradiol were delivered to chick embryos at Hamburger and Hamilton stage 18 (E3). The actions of these doses of sex steroids on the development of the C5DRG (fifth cervical ganglion, a "normal" DRG) and C2DRG (a transient ganglion known as a "Froriep's DRG") were then evaluated by quantifying ganglionic volumes, cell number, proliferation, and apoptosis after 1 day of growth to stage 23. We found that both testosterone and estradiol promoted proliferation of cells in both normal DRG and the Froriep's ganglia. By contrast, estradiol significantly increased the number of apoptotic cells, while testosterone strongly inhibited apoptosis. These actions of sex steroids on DRG development were dose-dependent, and C5DRG and C2DRG showed different sensitivities to the applied sex steroids. In addition, the present results demonstrated that specific ER and AR inhibitors (tamoxifen and flutamide) did not influence the effects of 5 microg E2 and 5 microg T on C2 and C5DRG significantly. These results demonstrate that male and female sex steroids can modulate DRG development through an epigenetic mechanism, as had been shown for the central nervous system.

Sex steroids in relation to sexual and skeletal maturation in obese male adolescents.

PubMed

Vandewalle, S; Taes, Y; Fiers, T; Van Helvoirt, M; Debode, P; Herregods, N; Ernst, C; Van Caenegem, E; Roggen, I; Verhelle, F; De Schepper, J; Kaufman, J M

2014-08-01

Childhood obesity is associated with an accelerated skeletal maturation. However, data concerning pubertal development and sex steroid levels in obese adolescents are scarce and contrasting. To study sex steroids in relation to sexual and skeletal maturation and to serum prostate specific antigen (PSA), as a marker of androgen activity, in obese boys from early to late adolescence. Ninety obese boys (aged 10-19 y) at the start of a residential obesity treatment program and 90 age-matched controls were studied cross-sectionally. Pubertal status was assessed according to the Tanner method. Skeletal age was determined by an x-ray of the left hand. Morning concentrations of total testosterone (TT) and estradiol (E2) were measured by liquid chromatography-tandem mass spectrometry, free T (FT) was measured by equilibrium dialysis, and LH, FSH, SHBG, and PSA were measured by immunoassays. Genital staging was comparable between the obese and nonobese groups, whereas skeletal bone advancement (mean, 1 y) was present in early and midadolescence in the obese males. Although both median SHBG and TT concentrations were significantly (P < .001) lower in obese subjects during mid and late puberty, median FT, LH, FSH, and PSA levels were comparable to those of controls. In contrast, serum E2 concentrations were significantly (P < .001) higher in the obese group at all pubertal stages. Obese boys have lower circulating SHBG and TT, but similar FT concentrations during mid and late puberty in parallel with a normal pubertal progression and serum PSA levels. Our data indicate that in obese boys, serum FT concentration is a better marker of androgen activity than TT. On the other hand, skeletal maturation and E2 were increased from the beginning of puberty, suggesting a significant contribution of hyperestrogenemia in the advancement of skeletal maturation in obese boys.

Assessment of spermatogenesis and plasma sex steroids in a seasonal breeding teleost: a comparative study in an area of influence of a tributary, downstream from a hydroelectric power dam, Brazil.

PubMed

Domingos, Fabricio F T; Thomé, Ralph G; Arantes, Fabio P; Castro, Antonio Carlos S; Sato, Yoshimi; Bazzoli, Nilo; Rizzo, Elizete

2012-12-01

River damming and building of hydroelectric power plants interrupt the reproductive migration routes and change the major physicochemical parameters of water quality, with drastic consequences for populations of migratory fishes. The goal of this study was to evaluate proliferation and cell death during spermatogenesis and serum profiles of sex steroids in Prochilodus argenteus, from the São Francisco River, downstream from the Três Marias Dam. A total of 257 adult males were caught quarterly during a reproductive cycle in two sites: the first 34 km of the river after the dam (site 1) and the second 34-54 km after the dam (site 2), after the confluence with a tributary, the Abaeté River. Seasonal changes in the testicular activity associated with morphometric analyses of germ cells as well as proliferation and testicular apoptosis support a more active spermatogenesis in fish from site 2, where higher levels of sex steroids and gonadosomatic index (GSI) were also found. In site 1, fish presented low serum levels of testosterone, 17β-estradiol and 17α-hydroxyprogesterone and a low GSI during gonadal maturation. Spermatogonial proliferation (PCNA) and apoptosis (TUNEL) were more elevated in fish from site 1, but spermatocytes were mainly labelled in fish from site 2. Overall, these data demonstrate changes in testicular activity and plasma sex steroids in a neotropical teleost fish living downstream from a hydroelectric dam, supplying new data on fish reproduction in regulated rivers. Moreover, morphometric analyses associated with sex steroids profiles provide reliable tools to assess fish spermatogenesis under environmental stress conditions.

Sex-Dependent Expression of Caveolin 1 in Response to Sex Steroid Hormones Is Closely Associated with Development of Obesity in Rats

PubMed Central

Mukherjee, Rajib; Kim, Sang Woo; Choi, Myung Sook; Yun, Jong Won

2014-01-01

Caveolin-1 (CAV1) is a conserved group of structural membrane proteins that form special cholesterol and sphingolipid-rich compartments, especially in adipocytes. Recently, it has been reported that CAV1 is an important target protein in sex hormone-dependent regulation of various metabolic pathways, particularly in cancer and diabetes. To clarify distinct roles of CAV1 in sex-dependent obesity development, we investigated the effects of high fat diet (HFD) and sex steroid hormones on CAV1 expression in adipose tissues of male and female rats. Results of animal experiments revealed that estrogen (17-β-estradiol, E2) and androgen (dihydrotestosterone, DHT) had opposite effects on body weight gain as well as on the regulation of CAV1, hormone sensitive lipase (HSL) and uncoupling protein 1 (UCP1) in adipose tissues. Furthermore, sex hormone receptors and aromatase were differentially expressed in a sex-dependent manner in response to E2 and DHT treatments. In vivo data were confirmed using 3T3-L1 and HIB1B cell lines, where Cav1 knock down stimulated lipogenesis but suppressed sex hormone receptor signaling proteins. Most importantly, co-immunoprecipitation enabled the identification of previously unrecognized CAV1-interacting mitochondrial or lipid oxidative pathway proteins in adipose tissues. Taken together, current data showed that CAV1 may play important preventive role in the development of obesity, with more prominent effects in females, and proved to be an important target protein for the hormonal regulation of adipose tissue metabolism by manipulating sex hormone receptors and mitochondrial oxidative pathways. Therefore, we can report, for the first time, the molecular mechanism underlying the effects of sex steroid hormones in the sex-dimorphic regulation of CAV1. PMID:24608114

Influence of female and male sex steroids on body composition in the rabbit model.

PubMed

Alexandersen, P; Hassager, C; Christiansen, C

2001-09-01

To study the influence on body composition of estrogen replacement therapy (ERT) in female rabbits and of replacement therapy with testosterone (TRT) in male rabbits using dual-energy X-ray absorptiometry (DEXA). Cholesterol-fed female and male rabbits receiving a weight-restricted diet (100 g/day) were used. Total lean tissue mass (LTM), total body fat tissue mass (FTM) and total tissue mass (TTM) were determined by DEXA at baseline, after which the animals were gonadectomized and treated with sex steroids. Soft body composition was then determined again after 30-31 weeks of treatment. Relative to controls, ERT with estradiol (E2) doses of 2 and 4 mg/day significantly increased LTM (p < 0.001), whereas E2 0.5 and 1 mg/day had a neutral effect on LTM. The change in fat mass, however, was not statistically significant between groups. In male rabbits, compared with castrated control rabbits, LTM decreased in testosterone-treated animals (by 7-12%; p < 0.001) but FTM decreased relatively more (by 66-79%; p < 0.0001). In both genders, body weight correlated with TTM as determined by DEXA (r = 0.89-0.91, p < 0.0001). In this in vivo model of growing rabbits, estrogen replacement significantly increased LTM in female animals, whereas testosterone replacement significantly decreased FTM in males, suggesting that soft body composition of both genders is significantly affected by replacement with sex steroids. Until comparable human data are available, it is speculated that similar changes in soft body composition may occur in humans treated with sex steroids.

Sex steroid levels in XY males and sex-reversed XX males, of rainbow trout (Oncorhynchus mykiss), during the reproductive cycle.

PubMed

Espinosa, E; Josa, A; Gil, L; González, N

2011-02-01

In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-oestradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared, for XY males (n=35) and sex-reversed XX males (n=27) rainbow trout, to establish possible endocrinology differences. Both in XY males and sex-reversed XX males, significant correlation was shown between body weight and T (r=0.5046 and 0.34078, respectively; p<0.0001) or KT (r=0.52494 and 0.43545, respectively; p<0.0001) concentrations. Plasma androgen levels in XY and sex-reversed XX males were similar and showed an intense seasonal variation. The highest levels for T and 11-KT were detected from December to April with a peak in January (51.67 ± 5.11 and 61.95 ± 4.25 ng/ml, for XY males and 57.1 ± 5.82 and 59.27 ± 4.84 ng/ml, respectively, for XX males). In addition, there was a positive correlation (p<0.0001) between T and 11-KT levels for XY males (r=0.7533) and sex-reversed XX males (r=0.6019). Concentrations of DHP in XY males also showed seasonal variation with a peak in February (25.18 ± 12.99 ng/ml). However, DHP levels in sex-reversed XX males were undetectable (<0.1 ng/ml) over the year. Levels of E2 were undetectable through the year in both groups of trout. In conclusion, the androgenic and oestrogenic profiles of sex-reversed XX males were similar to those observed in XY males. The only difference in the annual gonadal steroid cycle between XY and sex-reversed XX males was in the DHP profile. © 2009 Blackwell Verlag GmbH.

Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women.

PubMed

Slemenda, C; Longcope, C; Peacock, M; Hui, S; Johnston, C C

1996-01-01

Although bone loss around the time of menopause is driven by estrogen deficiency, the roles of estrogens and androgens in the preservation of skeletal mass at other stages of life are less well understood. To address this issue we studied 231 women between the ages of 32 and 77 with multiple measurements of sex steroids and bone mass over a period of 2-8 yr. In all women bone mass was negatively associated with concentrations of sex-hormone binding globulin, and positively associated with weight. Bone loss occurred from all skeletal sites in peri- and postmenopausal women, but premenopausal women lost bone only from the hip (-0.3%/yr) and had positive rates of change in the radius and spine. Bone loss was significantly associated with lower androgen concentrations in premenopausal women, and with lower estrogens and androgens in peri- and postmenopausal women. Sex steroids are important for the maintenance of skeletal integrity before menopause, and for as long as 20-25 yr afterwards.

Androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway: Insights into enzyme activities and steroid fluxes in healthy infants during the first year of life from the urinary steroid metabolome.

PubMed

Dhayat, Nasser A; Dick, Bernhard; Frey, Brigitte M; d'Uscio, Claudia H; Vogt, Bruno; Flück, Christa E

2017-01-01

The steroid profile changes dramatically from prenatal to postnatal life. Recently, a novel backdoor pathway for androgen biosynthesis has been discovered. However, its role remains elusive. Therefore, we investigated androgen production from birth to one year of life with a focus on minipuberty and on production of androgens through the backdoor pathway. Additionally, we assessed the development of the specific steroid enzyme activities in early life. To do so, we collected urine specimens from diapers in 43 healthy newborns (22 females) at 13 time points from birth to one year of age in an ambulatory setting, and performed in house GC-MS steroid profiling for 67 steroid metabolites. Data were analyzed for androgen production through the classic and backdoor pathway and calculations of diagnostic ratios for steroid enzyme activities were performed. Analysis revealed that during minipuberty androgen production is much higher in boys than in girls (e.g. androsterone (An)), originates largely from the testis (An boys -An girls ), and uses predominantly the alternative backdoor pathway (An/Et; Δ5<Δ4 lyase activity). Modelling of steroid enzyme activities showed age-related effects for 21-, 11-, 17-hydroxylase and P450 oxidoreductase activities as well as 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase type 1/2 and 5α-reductase activities. Sex-related characteristics were found for 21-hydroxylase and 5α-reductase activities. Overall, our study shows that androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway. Calculations of specific diagnostic ratios for enzyme activities seem to allow the diagnosis of specific steroid disorders from the urinary steroid metabolome. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex steroids do not affect muscle weight, oxidative metabolism or cytosolic androgen reception binding of functionally overloaded rat Plantaris muscles

NASA Technical Reports Server (NTRS)

Max, S. R.; Rance, N.

1983-01-01

The effects of sex steroids on muscle weight and oxidative capacity of rat planaris muscles subjected to functional overload by removal of synergistic muscles were investigated. Ten weeks after bilateral synergist removal, plantaris muscles were significantly hypertrophic compared with unoperated controls. After this period, the ability of the muscles to oxide three substrates of oxidative metabolism was assessed. Experimental procedures are discussed and results are presented herein. Results suggest a lack of beneficial effect of sex hormone status on the process of hypertrophy and on biochemical changes in overloaded muscle. Such findings are not consistent with the idea of synergistic effects of sex steroids and muscle usage.

Mad men, women and steroid cocktails: A review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors

PubMed Central

Henderson, Leslie P.

2016-01-01

Rationale For several decades, elite athletes and a growing number of recreational consumers have used anabolic androgenic steroids (AAS) as performance enhancing drugs. Despite mounting evidence that illicit use of these synthetic steroids has detrimental effects on affective states, information available on sex-specific actions of these drugs is lacking. Objectives The focus of this review is to assess information to date on the importance of sex and its interaction with other environmental factors on affective behaviors, with an emphasis on data derived from non-human studies. Methods The PubMed database was searched for relevant studies in both sexes. Results Studies examining AAS use in females are limited, reflecting the lower prevalence of use in this sex. Data, however, indicate significant sex-specific differences in AAS effects on anxiety-like and aggressive behaviors, interactions with other drugs of abuse, and the interplay of AAS with other environmental factors such as diet and exercise. Conclusions Current methods for assessing AAS use have limitations that suggest biases of both under- and over-reporting, which may be amplified for females who are poorly represented in self-report studies of human subjects and are rarely used in animal studies. Data from animal literature suggest that there are significant sex-specific differences in the impact of AAS on aggression, anxiety, and concomitant use of other abused substances. These results have relevance for human females who take these drugs as performance enhancing substances and for transgender XX individuals who may illicitly self-administer AAS as they transition to a male gender identity. PMID:26758282

Mad men, women and steroid cocktails: a review of the impact of sex and other factors on anabolic androgenic steroids effects on affective behaviors.

PubMed

Onakomaiya, Marie M; Henderson, Leslie P

2016-02-01

For several decades, elite athletes and a growing number of recreational consumers have used anabolic androgenic steroids (AAS) as performance enhancing drugs. Despite mounting evidence that illicit use of these synthetic steroids has detrimental effects on affective states, information available on sex-specific actions of these drugs is lacking. The focus of this review is to assess information to date on the importance of sex and its interaction with other environmental factors on affective behaviors, with an emphasis on data derived from non-human studies. The PubMed database was searched for relevant studies in both sexes. Studies examining AAS use in females are limited, reflecting the lower prevalence of use in this sex. Data, however, indicate significant sex-specific differences in AAS effects on anxiety-like and aggressive behaviors, interactions with other drugs of abuse, and the interplay of AAS with other environmental factors such as diet and exercise. Current methods for assessing AAS use have limitations that suggest biases of both under- and over-reporting, which may be amplified for females who are poorly represented in self-report studies of human subjects and are rarely used in animal studies. Data from animal literature suggest that there are significant sex-specific differences in the impact of AAS on aggression, anxiety, and concomitant use of other abused substances. These results have relevance for human females who take these drugs as performance-enhancing substances and for transgender XX individuals who may illicitly self-administer AAS as they transition to a male gender identity.

Vitamin D deficiency and low ionized calcium are linked with semen quality and sex steroid levels in infertile men.

PubMed

Blomberg Jensen, Martin; Gerner Lawaetz, Jacob; Andersson, Anna-Maria; Petersen, Jørgen Holm; Nordkap, Loa; Bang, Anne Kirstine; Ekbom, Pia; Joensen, Ulla Nordström; Prætorius, Lisbeth; Lundstrøm, Peter; Boujida, Vibeke Hartvig; Lanske, Beate; Juul, Anders; Jørgensen, Niels

2016-08-01

Are low vitamin D levels linked with semen quality and sex steroids in infertile men? Infertile men with vitamin D deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B, sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher levels of free sex steroids, than infertile men with normal vitamin D levels. Low vitamin D levels have been associated with decreased sperm motility in healthy men, but a relationship between vitamin D and calcium with semen quality and especially sex steroids has not been sufficiently described in infertile men. This study comprises baseline characteristics of 1427 infertile men screened from 2011 to 2014 for inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study. In total 1427 infertile men, consecutively referred to our tertiary andrological centre for fertility workup, underwent a physical examination and had semen quality assessed based on two samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B, luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25-OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to serious comorbidities or anabolic steroid usage, leaving 1248 patients for analyses. Men with 25-OHD >75 nmol/l had higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P < 0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower, respectively, while free testosterone and estradiol ratios were 6 and 13% higher, respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+) levels had higher progressive sperm motility and inhibin B/FSH ratio but lower testosterone/estradiol ratio (all P < 0.05). All outcomes presented are predefined end-points but inferral of causality is compromised by the descriptive study design. It remains to be shown whether the links

Sex steroid receptors in male human bladder: expression and biological function.

PubMed

Chavalmane, Aravinda K; Comeglio, Paolo; Morelli, Annamaria; Filippi, Sandra; Fibbi, Benedetta; Vignozzi, Linda; Sarchielli, Erica; Marchetta, Matilde; Failli, Paola; Sandner, Peter; Saad, Farid; Gacci, Mauro; Vannelli, Gabriella B; Maggi, Mario

2010-08-01

In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens. Within the bladder, LUTS are linked to RhoA/Rho-kinase (ROCK) pathway overactivity. To investigate the effects of changing sex steroids on bladder smooth muscle. ER α, ER β, GPR30/GPER1 and aromatase mRNA expression was analyzed in male genitourinary tract tissues, and cells isolated from bladder, prostate, and urethra. Estrogen and G1 effect on RhoA/ROCK signaling output like cell migration, gene expression, and cytoskeletal remodeling, and [Ca(2+) ](i) was also studied in hB cells. Contractile studies on bladder strips from castrated male rats supplemented with estradiol and testosterone was also performed. The effects of classical (ER α, ER β) and nonclassical (GPR30/GPER1) estrogen receptor ligands (17 β-estradiol and G1, respectively) and androgens on RhoA/ROCK-.mediated cell functions were studied in hB cells. Contractility studies were also performed in bladder strips from castrated male rats supplemented with testosterone or estradiol. Aromatase and sex steroid receptors, including GPR30, were expressed in human bladder and mediates several biological functions. Both 17 β-estradiol and G1 activated calcium transients and induced RhoA/ROCK signaling (cell migration, cytoskeleton remodeling and smooth muscle gene expression). RhoA/ROCK inhibitors blunted these effects. Estrogen-, but not androgen-supplementation to castrated rats increased sensitivity to the ROCK inhibitor, Y-27632 in isolated bladder strips. In hB cells, testosterone elicited effects similar to estrogen, which were abrogated by blocking its aromatization through letrozole. Our data indicate for the first time that estrogen-more than androgen-receptors up-regulate RhoA/ROCK signaling. Since an altered estrogen

The role of sex steroids in catamenial epilepsy and premenstrual dysphoric disorder: Implications for diagnosis and treatment

PubMed Central

Guille, Constance; Spencer, Susan; Cavus, Idil; Epperson, C. Neill

2014-01-01

Despite our understanding of hormonal influences on central nervous system (CNS) function, there is still much to learn about the pathogenesis of menstrual cycle-linked disorders. A growing literature suggests that the influence of sex steroids on neurological and psychiatric disorders is in part mediated by an aberrant CNS response to neuroactive steroids. Although sex steroids such as estradiol, progesterone, and the progesterone derivative allopregnanolone (ALLO) influence numerous neurotransmitter systems, it is their potent effect on the brain's primary inhibitory and excitatory neurotransmitters γ aminobutyric acid (GABA) and glutamate that links the study of premenstrual dysphoric disorder (PMDD) and catamenial epilepsy (CE). After providing an overview of these menstrual cycle-linked disorders, this article focuses on the preclinical and clinical research investigating the role of estradiol and progesterone (via ALLO) in the etiology of PMDD and CE. Through exploration of the phenomenological and neurobiological overlap between CE and PMDD, we aim to highlight areas for future research and development of treatments for menstrual cycle-linked neuropsychiatric disorders. PMID:18346939

Decreased glutathione S-transferase expression and activity and altered sex steroids in Lake Apopka brown bullheads (Ameriurus nebulosus)

USGS Publications Warehouse

Gallagher, E.P.; Gross, T.S.; Sheehy, K.M.

2001-01-01

A number of freshwater lakes and reclaimed agricultural sites in Central Florida have been the receiving waters for agrochemical and municipal runoff. One of these sites, Lake Apopka, is also a eutrophic system that has been the focus of several case studies reporting altered reproductive activity linked to bioaccumulation of persistent organochlorine chemicals in aquatic species. The present study was initiated to determine if brown bullheads (Ameriurus nebulosus) from the north marsh of Lake Apopka (Lake Apopka Marsh) exhibit an altered capacity to detoxify environmental chemicals through hepatic glutathione S-transferase (GST)-mediated conjugation as compared with bullheads from a nearby reference site (Lake Woodruff). We also compared plasma sex hormone concentrations (testosterone, 17-?? estradiol, and 11 keto-testosterone) in bullheads from the two sites. Female bullheads from Lake Apopka had 40% lower initial rate GST conjugative activity toward 1-chloro-2,4-dinitrobenzene (CDNB), 50% lower activity towards p-nitrobutyl chloride (NBC), 33% lower activity toward ethacrynic acid (ECA), and 43% lower activity toward ??5-androstene-3,17-dione (??5-ADI), as compared with female bullheads from Lake Woodruff. Enzyme kinetic analyses demonstrated that female bullheads from Lake Apopka had lower GST-catalyzed CDNB clearance than did female Lake Woodruff bullheads. Western blotting studies of bullhead liver cytosolic proteins demonstrated that the reduced GST catalytic activities in female Lake Apopka bullheads were accompanied by lower expression of hepatic GST protein. No site differences were observed with respect to GST activities or GST protein expression in male bullheads. Female Lake Apopka bullheads also had elevated concentrations of plasma androgens (testosterone and 11-ketotestosterone) as compared with females from Lake Woodruff. In contrast, male Lake Apopka bullheads had elevated levels of plasma estrogen but similar levels of androgens as compared with

Sex differences and the impact of steroid hormones on the developing human brain.

PubMed

Neufang, Susanne; Specht, Karsten; Hausmann, Markus; Güntürkün, Onur; Herpertz-Dahlmann, Beate; Fink, Gereon R; Konrad, Kerstin

2009-02-01

Little is known about the hormonal effects of puberty on the anatomy of the developing human brain. In a voxel-based morphometry study, sex-related differences in gray matter (GM) volume were examined in 46 subjects aged 8-15 years. Males had larger GM volumes in the left amygdala, whereas females had larger right striatal and bilateral hippocampal GM volumes than males. Sexually dimorphic areas were related to Tanner stages (TS) of pubertal development and to circulating level of steroid hormones in a subsample of 30 subjects. Regardless of sex, amygdala and hippocampal volumes varied as a function of TS and were associated with circulating testosterone (TEST) levels. By contrast, striatal GM volumes were unrelated to pubertal development and circulating steroid hormones. Whole-brain regression analyses revealed positive associations between circulating estrogen levels and parahippocampal GM volumes as well as between TEST levels and diencephalic brain structures. In addition, a negative association was found between circulating TEST and left parietal GM volumes. These data suggest that GM development in certain brain regions is associated with sexual maturation and that pubertal hormones might have organizational effects on the developing human brain.

Validation of murine and human placental explant cultures for use in sex steroid and phase II conjugation toxicology studies

PubMed Central

Sato, Brittany L.; Ward, Monika A.; Astern, Joshua M.; Kendal-Wright, Claire E.; Collier, Abby C.

2014-01-01

Human primary placental explant culture is well established for cytokine signaling and toxicity, but has not been validated for steroidogenic or metabolic toxicology. The technique has never been investigated in the mouse. We characterized human and mouse placental explants for up to 96hr in culture. Explant viability (Lactate dehydrogenase) and sex steroid levels were measured in media using spectrophotometry and ELISA, respectively. Expression and activities of the steroidogenic (3β-hydroxysteroid dehydrogenase, Cytochrome P45017A1, Cytochrome P45019), conjugation (UDP-glucuronosyltransferase, sulfotransferase (SULT)), and regeneration (β-glucuronidase, arylsulfatase C (ASC)) enzymes were determined biochemically in tissues with fluorimetric and spectrophotometric assays, and western blot. Explants were viable up to 96hr, but progesterone, estrone, and 17β-estradiol secretion decreased. Steroidogenic enzyme expression and activities were stable in mouse explants and similar to levels in freshly isolated tissues, but were lower in human explants than in fresh tissue (P<0.01). Human and mouse explants exhibited significantly less conjugation after 96hr, SULT was not detected in the mouse, and neither explants had active ASC, although proteins were expressed. Mouse explants may be useful for steroid biochemistry and endocrine disruption studies, but not metabolic conjugation. In contrast, human explants may be useful for studying conjugation for <48hr, but not for steroid/endocrine studies. PMID:25283089

Sex-hormone-binding globulin.

PubMed

Anderson, D C

1974-01-01

A review was made to understand how plasma binding protein might influence sex-hormone action in target tissues. Steroids are predominately bound to plasma proteins and only unbound steroids enter the cells. Sex-hormone-binding globulin (SHBG) binds to both the main circulating steroid T and E2 but changes in SHBG concentrations exert significant results. Increased SHBG levels increase estrogen production and decreases T activity; whereas, increased androgens increase T action and inhibit SHBG production. These disturbances in hormone maintenance may lead to abnormal adult sex differentiation such as hirsutism and forms of hynaecomastia. By developing SHBG concentration measurement methods-responses of hirsutism to glucocorticoid or estrogem may be assessed. In addition, the effect of thyroid hormones on SHBG may also have therapeutic implications in endocrine disease.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Craig, Zelieann R., E-mail: zelieann@illinois.edu

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 culturemore » 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.« less

Gender and gonadal maturity stage identification of captive Chinese sturgeon, Acipenser sinensis, using ultrasound imagery and sex steroids.

PubMed

Du, Hao; Zhang, Xiaoyan; Leng, Xiaoqian; Zhang, Shuhuan; Luo, Jiang; Liu, Zhigang; Qiao, Xingmei; Kynard, Boyd; Wei, Qiwei

2017-05-01

Long lifespan and late maturation make it difficult to establish gamete maturity and breeding age of captive endangered Chinese sturgeon, Acipenser sinensis. This greatly handicaps timely breeding and future conservation stocking efforts. We used ultrasound imagery and sex steroids to determine the gender and gonadal maturity stage of captive Chinese sturgeon (age, 10-17years old). The echogenicity of the reproductive organs and the respective morphology of the gonads were described and two quantitative parameters p o (proportion of the ovary to the entire reproductive organs) and d (thickness of the reproductive organs) were measured to characterize sex and maturity stage of Chinese sturgeon. Females were accordingly placed fish into several categories: F II (F II - , F II , F II + ), F III (F III , F III + ) and F IV (F IV , F IV + ) and F VI and males as M II , M III , M IV , M V and M VI . The accuracy of gender and maturity stage determination provided by ultrasonographic methods was 72.7% for F II - ovary (n=11) and 76.2% for M II testis (n=42). Accuracy of sex and maturity determination using only serum sex steroid of testosterone (T) and estradiol-17β (E 2 ) was low (58-73%, depending on maturity stage). However, when the two methods were used together, accuracy increased sharply, especially for immature (II stage) females. In summary, of 151 Chinese sturgeon, whose sex and maturity stage were independently confirmed, 88.1% (n=133), 62.9% (n=95), and 96.7% (n=146) were successfully sexed and staged using ultrasound, sex steroids, or both methods, respectively. The results provide reliable non-invasive techniques for determining sex and gonadal maturation of captive Chinese sturgeon. These methods can track individual gonad characteristics over multi-year reproductive cycles, which will assist captive broodstock management, artificial reproduction, and future conservation stocking. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of 17 α-methyltestosterone on transcriptome, gonadal histology and sex steroid hormones in rare minnow Gobiocypris rarus.

PubMed

Gao, Jiancao; Liu, Shaozhen; Zhang, Yingying; Yang, Yanping; Yuan, Cong; Chen, Shu; Wang, Zaizhao

2015-09-01

The 17α-methyltestosterone (MT), a synthetic androgen, is known for its interference effects on the endocrine system. Aiming to investigate the transcriptome profiling of gonads induced by MT and to understand the molecular mechanism by which MT causes adverse effects in fish, transcriptome profiling of gonads, gonadal histology and the sex steroid hormones in response to MT were analyzed in Gobiocypris rarus. Eight libraries, 4 from the ovary and 4 from the testis, were constructed and sequenced and then a total number of clean reads per sample ranging from 7.03 to 9.99 million were obtained. In females, a total of 191 transcripts were differentially regulated by MT, consisting of 102 up-regulated transcripts and 89 down-regulated transcripts. In males, 268 differentially expressed genes with 108 up-regulated and 160 down-regulated were detected upon MT exposure. Testosterone serves as the major sex steroid hormone content in G. rarus of both sexes. The concentrations of 17β-estradiol, testosterone and 11-ketotestosterone were significantly increased in females and decreased in males after MT exposure. Interestingly, MT caused a decreased number of vitellogenic oocytes in the ovary and spermatozoa in the testis. After MT exposure, four differentially expressed genes (ndufa4, slc1a3a, caskin-2 and rpt3) were found in G. rarus of both sexes. Overall, we suggest that MT seemed to affect genes involved in pathways related to physiological processes in the gonads of G. rarus. These processes include the electron transfer of Complex IV, endothelial cell activation, axon growth and guidance, and proteasome assembly and glutamate transport metabolic. Copyright © 2015 Elsevier Inc. All rights reserved.

Age-related changes in dorsal root ganglia, circulating and vascular calcitonin gene-related peptide (CGRP) concentrations in female rats: Effect of female sex steroid hormones

PubMed Central

Gangula, Pandu R.R.; Chauhan, Madhu; Reed, Luckey; Yallampalli, Chandra

2009-01-01

The aim of the present study is to investigate whether immunoreactive (I) calcitonin gene-related peptide (CGRP) content is decreased in plasma and mesenteric arteries (resistance arteries) in middle-aged rats and if so, whether sex steroid hormones enhance I-CGRP in middle-aged female rats. We also examined whether vascular CGRP receptor components, calcitonin receptor like receptor (CRLR) and receptor activity modifying protein 1 (RAMP1) are elevated by sex steroid hormones treatment in middle-aged female rats. Young adult (3 months old) and middle-aged (10–12 months old) ovariectomized rats were treated subcutaneously with estradiol-17β (E2; 2 mg), progesterone (P4; 5 mg), E2 +P4 (2 mg + 20 mg) or placebo (control). Radioimmunoassay and Western blot analysis were performed to measure I-CGRP content and CGRP receptor components in dorsal root ganglia (DRG), in resistance arteries and in plasma. Immunofluorescent staining methods were employed to determine cellular localization of CRLR, RAMP1 in resistance arteries. Our data demonstrated that I-CGRP content was significantly (p < 0.05) lower in the plasma and resistance arteries of middle-aged female rats compared to young controls. Both RAMP1 and CRLR were concentrated in vascular endothelium and the underlying smooth muscle cells. RAMP1 but not CRLR appeared to be decreased in middle-aged rat vasculature. Chronic perfusion of sex steroid hormones to ovariectomized rats: (1) significantly (p < 0.05) elevated I-CGRP in the DRG and in the plasma, and (2) significantly elevated RAMP1 (p < 0.05) but did not alter CRLR in resistance arteries. These data suggest that female sex steroid treatment enhances I-CGRP and its receptors, and thus regulate the blood pressure in aged female rats. PMID:19429067

The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are Independent and Mechanistically Distinct

PubMed Central

Ucer, Serra; Iyer, Srividhya; Kim, Ha-Neui; Han, Li; Rutlen, Christine; Allison, Kelly; Thostenson, Jeff D; de Cabo, Rafael; Jilka, Robert L; O’Brien, Charles; Almeida, Maria; Manolagas, Stavros C

2017-01-01

Old age and sex steroid deficiency are the two most critical factors for the development of osteoporosis. It remains unknown, however, whether the molecular culprits of the two conditions are similar or distinct. We show herein that at 19.5 months of age —a time by which the age-dependent decline of cortical and cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice—these animals remained functionally estrogen sufficient. Transgenic mice with conditional expression of mitochondria-targeted catalase—a potent H2O2 inactivating enzyme—in cells of the myeloid lineage (mitoCAT;LysM-Cre mice) were protected from the loss of cortical, but not cancellous, bone caused by gonadectomy in either sex. Consistent with these findings, in vitro studies with ERα-deficient Prx1+ cells and gonadectomized young adult mice showed that in both sexes decreased ERα signaling in Prx1+ cells leads to an increase in SDF1, a.k.a. CXCL12, an osteoclastogenic cytokine whose effects were abrogated in macrophages from mitoCAT;LysM-Cre mice. In contrast to sex steroid deficiency, the adverse effects of aging on either cortical or cancellous bone were unaffected in mitoCAT;LysM-Cre mice. On the other hand, attenuation of H2O2 generation in cells of the mesenchymal lineage targeted by Prx1-Cre partially prevented the loss of cortical bone caused by old age. Our results suggest the effects of sex steroid deficiency and aging on the murine skeleton are independent and result from distinct mechanisms. In the former, the prevailing mechanism of the cortical bone loss in both sexes is increased osteoclastogenesis caused by estrogen deficiency; this is likely driven, at least in part, by mesenchymal/stromal cell–derived SDF1. Decreased osteoblastogenesis, owing in part to increased H2O2, combined with increased osteoclastogenesis caused by aging mechanisms independent of estrogen deficiency, are the prevailing mechanisms of the loss of cortical bone with old age

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians.

PubMed

Kim, Catherine; Kong, Shengchun; Krauss, Ronald M; Stanczyk, Frank Z; Reddy, Srinivasa T; Needham, Belinda L; Kanaya, Alka M

2015-12-01

Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians. We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity. Among women, lower logSHBG levels were associated with smaller logLDL particle size and higher logtriglycerides, logVLDL, and logIDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower logSHBG levels was significantly associated with lower logmedium LDL and logsmall LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower logSHBG was also associated with smaller logLDL peak diameter size and higher logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR. Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.

Sex Differences in Brain-Derived Neurotrophic Factor Signaling and Functions

PubMed Central

Chan, Chi Bun; Ye, Keqiang

2016-01-01

Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies report that some functions or action mechanisms of BDNF vary in a sex-dependent manner. In particular, BDNF content in some brain parts and the tendency of developing BDNF-deficient-related diseases like depression is higher in female animals. With the support of other relevant studies, it is suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross-talk between BDNF and sex steroids has been detected for decades and some sex steroids like estrogen have a positive regulatory effect to BDNF expression and signaling. Thus, the sex of animal models used is critical when studying the functions of BDNF in vivo. In this review, we will summarize our current findings on the difference in expression, signaling, and functions of BDNF between sexes. We will also discuss the potential mechanisms in mediating these differential responses with a specific emphasis on sex steroids. By presenting and discussing these findings, we encourage taking sex influences into consideration when designing experiments, interpreting results and drawing conclusions. PMID:27870419

Expression of Sex Steroid Hormone Receptors in Vagal Motor Neurons Innervating the Trachea and Esophagus in Mouse

PubMed Central

Mukudai, Shigeyuki; Ichi Matsuda, Ken; Bando, Hideki; Takanami, Keiko; Nishio, Takeshi; Sugiyama, Yoichiro; Hisa, Yasuo; Kawata, Mitsuhiro

2016-01-01

The medullary vagal motor nuclei, the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV), innervate the respiratory and gastrointestinal tracts. We conducted immunohistochemical analysis of expression of the androgen receptor (AR) and estrogen receptor α (ERα), in relation to innervation of the trachea and esophagus via vagal motor nuclei in mice. AR and ERα were expressed in the rostral NA and in part of the DMV. Tracing experiments using cholera toxin B subunit demonstrated that neurons of vagal motor nuclei that innervate the trachea and esophagus express AR and ERα. There was no difference in expression of sex steroid hormone receptors between trachea- and esophagus-innervating neurons. These results suggest that sex steroid hormones may act on vagal motor nuclei via their receptors, thereby regulating functions of the trachea and esophagus. PMID:27006520

Modulation of the cytosolic androgen receptor in striated muscle by sex steroids

NASA Technical Reports Server (NTRS)

Rance, N. E.; Max, S. E.

1982-01-01

The influence of orchiectomy (GDX) and steroid administration on the level of the cytosolic androgen receptor in the rat levator ani muscle and in rat skeletal muscles (tibialis anterior and extensor digitorum longus) was studied. Androgen receptor binding to muscle cytosol was measured using H-3 methyltrienolone (R1881) as ligand, 100 fold molar excess unlabeled R1881 to assess nonspecific binding, and 500 fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Results demonstrate that modification of the levels of sex steroids can alter the content of androgen receptors of rat striated muscle. Data suggest that: (1) cytosolic androgen receptor levels increase after orchiectomy in both levator ani muscle and skeletal muscle; (2) the acute increase in receptor levels is blocked by an inhibitor of protein synthesis; and (3) administration of estradiol-17 beta to castrated animals increases receptor binding in levator ani muscle but not in skeletal muscle.

Effects of oral contraceptive agents and sex steroids on carbohydrate metabolism.

PubMed

Kalkhoff, R K

1972-01-01

The article offers a general interpretation of the influence of oral contraceptive agents on glucose tolerance, emphasizing comparisons of synthetic sex hormones. Although there are conflicting reports on steroid-induced diabetes in normal women, their glucose curves are often higher when under oral contraceptive treatment, suggesting that oral contraceptives may induce a form of subclinical diabetes melitus that is reversible. Evidence from diabetic women suggests definite deliterious effects from contraceptive administration. Estradiol, estriol, and estrone may improve glucose tolerance in nondiabetic women and reduce insulin requirements in diabetics. Progesterone has little effect on carbohydrate tolerance, as did synthetic progestin. Conjugated equine estrogens (equilenine or Premarin) may provoke mild to moderate deterioration of carbohydrate tolerance. Parenterally administered natural estrogens and orally administered synthetic derivatives appear to differ sharply in their effects. Sex hormones' effects on carbohydrate metabolism likely involve interactions with insulin and endogenous glucocorticoids.

Regulation of Estrogen Receptor α Expression in the Hypothalamus by Sex Steroids: Implication in the Regulation of Energy Homeostasis.

PubMed

Liu, Xian; Shi, Haifei

2015-01-01

Sex differences exist in the complex regulation of energy homeostasis that utilizes central and peripheral systems. It is widely accepted that sex steroids, especially estrogens, are important physiological and pathological components in this sex-specific regulation. Estrogens exert their biological functions via estrogen receptors (ERs). ERα, a classic nuclear receptor, contributes to metabolic regulation and sexual behavior more than other ER subtypes. Physiological and molecular studies have identified multiple ERα-rich nuclei in the hypothalamus of the central nervous system (CNS) as sites of actions that mediate effects of estrogens. Much of our understanding of ERα regulation has been obtained using transgenic models such as ERα global or nuclei-specific knockout mice. A fundamental question concerning how ERα is regulated in wild-type animals, including humans, in response to alterations in steroid hormone levels, due to experimental manipulation (i.e., castration and hormone replacement) or physiological stages (i.e., puberty, pregnancy, and menopause), lacks consistent answers. This review discusses how different sex hormones affect ERα expression in the hypothalamus. This information will contribute to the knowledge of estrogen action in the CNS, further our understanding of discrepancies in correlation of altered sex hormone levels with metabolic disturbances when comparing both sexes, and improve health issues in postmenopausal women.

Sex steroid hormone metabolism in relation to risk of aggressive prostate cancer

PubMed Central

Black, Amanda; Pinsky, Paul F.; Grubb, Robert L.; Falk, Roni T.; Hsing, Ann W.; Chu, Lisa; Meyer, Tamra; Veenstra, Timothy D.; Xu, Xia; Yu, Kai; Ziegler, Regina G.; Brinton, Louise A.; Hoover, Robert N.; Cook, Michael B.

2014-01-01

Background The combined action of androgens and estrogens—specifically their balance—may play a role in prostate carcinogenesis but existing evidence is sparse and inconsistent. We investigated associations between serum sex steroid hormones, including estrogen metabolites, and risk of aggressive prostate cancer. Methods In a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort we measured serum estrone, estradiol and 13 estrogen metabolites, in the 2-, 4, or 16-hydroxylation pathways, using a liquid chromatography-tandem mass spectrometry assay. Cases (n=195) were non-Hispanic white men aged 55–70 years when diagnosed with aggressive prostate cancer (stage III or IV and/or Gleason ≥7). Controls (n=195) were non-Hispanic white men without prostate cancer who were frequency-matched to cases by age and year at blood draw, time since baseline screen. Only men with serum testosterone and sex hormone-binding globulin measured previously were eligible. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI). Results Risk of aggressive prostate cancer was strongly inversely associated with estradiol:testosterone ratio (OR4th quartile vs. 1st =0.27, 95% CI 0.12–0.59, p trend=0.003) and positively associated with 2:16α-hydroxyestrone ratio (OR4th quartile vs. 1st =2.44, 95% CI 1.34–4.45, p trend=0.001). Estradiol, estrone and estrogen metabolites were unrelated to risk. Conclusions Our findings suggest that sex steroid hormones, specifically the estrogen-androgen balance, may be important in the development of aggressive prostate cancer. Impact Improved understanding of the hormonal etiology of prostate cancer is critical for prevention and therapeutic interventions. PMID:25178985

Altered expression of epithelial mesenchymal transition and pluripotent associated markers by sex steroid hormones in human embryonic stem cells.

PubMed

Jeon, So-Ye; Hwang, Kyung-A; Kim, Cho-Won; Jeung, Eui-Bae; Choi, Kyung-Chul

2017-07-01

Embryonic stem (ES) cells are pluripotent stem cells derived from a developmental stage of pre‑implanted embryos. The present study investigated the effect of female sex steroid hormones on the characteristics of human ES cells by using a feeder‑free culture protocol. In a feeder‑free condition without sex hormones, human ES cells assumed the form of tightly packed cells that grow in a monolayer. The cells had clean and defined edges with no evidence of differentiation and expressed several markers specific for undifferentiated ES cells including POU class 5 homeobox 1 (POU5F1), sex determining region Y‑box 2 (SOX2) and NANOG homeobox (NANOG). It was then investigated if female sex steroid hormones including 17β‑estradiol (E2) and progesterone (P4) altered the protein expression of epithelial-mesenchymal transition (EMT) associated markers in addition to pluripotency markers including POU5F1, SOX2 and NANOG in human ES cells. The protein expression levels of N‑cadherin, Snail and Slug were increased while E‑cadherin expression was decreased by treatment of E2 or P4, and the expression levels of POU5F1, SOX2 and NANOG were decreased by the treatment of E2 or P4. When E2 and P4 were treated in combination with an estrogen receptor inhibitor (ICI 182,780) and progesterone receptor inhibitor (RU486) respectively, their effects on EMT and pluripotency of ES cells were restored to control levels. The results suggested that E2 and P4 may regulate EMT and pluripotency of human ES cells by mediating their receptors. The present study may aid in the understanding of the role of sex steroid hormones in the cellular biology of human ES cells.

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

PubMed Central

Payne, Asha S.; Freishtat, Robert J.

2012-01-01

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

Sex steroid-related genes and male-to-female transsexualism.

PubMed

Henningsson, Susanne; Westberg, Lars; Nilsson, Staffan; Lundström, Bengt; Ekselius, Lisa; Bodlund, Owe; Lindström, Eva; Hellstrand, Monika; Rosmond, Roland; Eriksson, Elias; Landén, Mikael

2005-08-01

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and--after aromatase-catalyzed conversion to estradiol--via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERbeta repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

Sexual steroids in serum and prostatic tissue of human non-cancerous prostate (STERPROSER trial).

PubMed

Neuzillet, Yann; Raynaud, Jean-Pierre; Radulescu, Camélia; Fiet, Jean; Giton, Franck; Dreyfus, Jean-François; Ghoneim, Tarek P; Lebret, Thierry; Botto, Henry

2017-11-01

The specific involvement of the sex steroids in the growth of the prostatic tissue remains unclear. Sex steroid concentrations in plasma and in fresh surgical samples of benign central prostate were correlated to prostate volume. Monocentric prospective study performed between September 2014 and January 2017. Age, obesity parameters, and both serum and intraprostatic concentrations of sex steroids were collected complying with the latest Endocrine Society guidelines and the steroids assessed by GC/MS. Statistical calculations were adjusted for age and body mass index (BMI). Thirty-two patients, equally divided between normal- and high-volume prostate groups, were included in the analysis. High-volume prostate patients were older, heavier and had higher BMI. Comparison adjusted for age and BMI showed higher DHT concentrations in high-volume prostate. Both normal- and high-volume prostate tissues concentrate sex steroids in a similar way. Comparison of enzymatic activity surrogate marker ratios within tissue highlighted similar TT/E1 and TT/E2 ratios, and higher DHT/E1 ratio and lower DHT/PSA ratio in the high-volume prostates. STERPROSER trial provides evidence for higher DHT concentration in highvolume prostates, that could reflect either higher 5-alpha reductase expression or lower expression of downstream metabolizing enzymes such as 3a-hydoxysteroid dehydrogenase. © 2017 Wiley Periodicals, Inc.

Discrepancy between Exercise Performance, Body Composition, and Sex Steroid Response after a Six-Week Detraining Period in Professional Soccer Players

PubMed Central

Koundourakis, Nikolaos E.; Androulakis, Nikolaos E.; Malliaraki, Niki; Tsatsanis, Christos; Venihaki, Maria; Margioris, Andrew N.

2014-01-01

Purpose The aim of this study was to examine the effects of a six-week off-season detraining period on exercise performance, body composition, and on circulating sex steroid levels in soccer players. Methods Fifty-five professional male soccer players, members of two Greek Superleague Teams (Team A, n = 23; Team B, n = 22), participated in the study. The first two weeks of the detraining period the players abstained from any physical activity. The following four weeks, players performed low-intensity (50%–60% of VO2max) aerobic running of 20 to 30 minutes duration three times per week. Exercise performance testing, anthropometry, and blood sampling were performed before and after the six-week experimental period. Results Our data showed that in both teams A and B the six-week detraining period resulted in significant reductions in maximal oxygen consumption (60,31±2,52 vs 57,67±2,54; p<0.001, and 60,47±4,13 vs 58,30±3,88; p<0.001 respectively), squat-jump (39,70±3,32 vs 37,30±3,08; p<0.001, and 41,05±3,34 vs 38,18±3,03; p<0.001 respectively), and countermovement-jump (41,04±3,99 vs 39,13±3,26; p<0.001 and 42,82±3,60 vs 40,09±2,79; p<0.001 respectively), and significant increases in 10-meters sprint (1,74±0,063 vs 1,79±0,064; p<0.001, and 1,73±0,065 vs 1,78±0,072; p<0.001 respectively), 20-meters sprint (3,02±0,05 vs 3,06±0,06; p<0.001, and 3,01±0,066 vs 3,06±0,063; p<0.001 respectively), body fat percentage (Team A; p<0.001, Team B; p<0.001), and body weight (Team A; p<0.001, Team B; p<0.001). Neither team displayed any significant changes in the resting concentrations of total-testosterone, free-testosterone, dehydroepiandrosterone-sulfate, Δ4-androstenedione, estradiol, luteinizing hormone, follicle-stimulating hormone, and prolactin. Furthermore, sex steroids levels did not correlate with exercise performance parameters. Conclusion Our results suggest that the six-week detraining period resulted in a rapid loss of exercise

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-...

Sex steroids and personality traits in the middle luteal phase of healthy normally menstruating young professional women.

PubMed

Avgoustinaki, Pavlina D; Mitsopoulou, Effrosyni; Chlouverakis, Gregorios; Triantafillou, Theoni; Venihaki, Maria; Koukouli, Sofia; Margioris, Andrew N

2012-01-01

Sex steroids affect human behavior. The aim of the present study was to determine the associations, if any, between the circulating levels of gonadal and adrenal sex steroids in the mid luteal phase (21st day of a normal menstrual cycle, MC) of young professional women and psychometric parameters as assessed by the Minnesota Multiphasic Personality Inventory (MMPI). Our results are as follows: (a) The metabolic product of activated adrenal and gonadal androgens, 3alpha-diolG, was modestly but significantly associated with the social introversion scale (10-SI) (r=0.36, p<0.05), independently accounting for 13% of its variation across participants (R²=0.13, F(1,45)=6.58, p=0.014). (b) Total testosterone was significantly associated with the paranoia scale (6-Pa) (r=0.27, p<0.05). Multiple regression analyses indicated that 10% of the variability in paranoia scores could be independently explained by total testosterone levels (R²=0.10, F(1,57)=6.23, p=0.016). We were unable to find any association between the circulating androgens and scores on the masculinity-femininity scale (Mf). We were also unable to document any association between the weak adrenal androgens DHEA and DHEA-S and depression in contrast to several published reports. (c) Our data suggest a marginally significant association between progesterone and scores on the 7-Pt (obsessive/compulsive/psychasthenia) scale (r=0.27, p<0.05). However, only 7% of the 7-Pt variance was explained by progesterone (R²=0.071, F(1,50)=3.81, p=0.057). We have found that total testosterone was associated with the paranoia score, the metabolic product of activated androgens, 3alpha-diolG, to social introversion and, finally, progesterone to obsessive-compulsive behavior.

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

PubMed

Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

2016-12-01

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

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…

Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training.

PubMed

He, Zihong; Rankinen, Tuomo; Leon, Arthur S; Skinner, James S; Tchernof, André; Bouchard, Claude

2018-03-05

Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program. In the sedentary state, 270 men (29% Blacks) and 304 women (34% Blacks) from the HERITAGE Family Study were available. Among them, 242 men and 238 women completed a 20-week fully standardized exercise program. Fourteen steroid hormones and SHBG concentrations were assayed in a fasted state and were compared for their associations with adiposity in men and women and in response to the exercise program. Covariates adjusted for in partial correlation analysis were age, ancestry, menopause status (women), and oral contraceptives/hormone replacement treatment status (women) at baseline, as well as baseline value of the trait for the training response. Differences among normal weight, overweight, and obese subjects were also considered. Statistical significance was set at P < 0.0001. Baseline levels of dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone-binding globulin (SHBG), and testosterone (TESTO) were negatively associated with fat mass and abdominal fat (P < 0.0001) in men and for SHBG in women (P < 0.0001). TESTO was not correlated with fat-free mass in men or women, but was significantly associated with % fat-free mass in men. No association was detected between baseline steroid hormone levels and changes in adiposity traits in response to 20 weeks of exercise. In men, low DHT, OHPROG, SHBG, and TESTO were associated with higher adiposity and abdominal and visceral fat. A similar adiposity profile was observed in women with low SHBG.

Sex and the development of Alzheimer’s disease

PubMed Central

Pike, Christian J.

2016-01-01

Men and women exhibit differences in the development and progression of Alzheimer’s disease (AD). The factors underlying the sex differences in AD are not well understood. This review emphasizes the contributions of sex steroid hormones to the relationship between sex and AD. In women, events that decrease lifetime exposure to estrogens are generally associated with increased AD risk, whereas estrogen-based hormone therapy administered near the time of menopause may reduce AD risk. In men, estrogens do not exhibit age-related reduction and are not significantly associated with AD risk. Rather, normal age-related depletions of testosterone in plasma and brain predict enhanced vulnerability to AD. Both estrogens and androgens exert numerous protective actions in the adult brain that increase neural functioning and resilience as well as specifically attenuate multiple aspects of AD-related neuropathology. Aging diminishes the activational effects of sex hormones in sex-specific manners, which is hypothesized to contribute to the relationship between aging and AD. Sex steroid hormones may also drive sex differences in AD through their organizational effects during developmental sexual differentiation of the brain. Specifically, sex hormone actions during early development may confer inherent vulnerability of the female brain to development of AD in advanced age. The combined effects of organizational and activational effects of sex steroids yield distinct sex differences in AD pathogenesis, a significant variable that must be more rigorously considered in future research. PMID:27870425

Sexual Fate Reprogramming in the Steroid-Induced Bi-Directional Sex Change in the Protogynous Orange-Spotted Grouper, Epinephelus coioides.

PubMed

Wu, Guan-Chung; Tey, Wei-Guan; Li, Hau-Wen; Chang, Ching-Fong

2015-01-01

Androgen administration has been widely used for masculinization in fish. The mechanism of the sex change in sexual fate regulation is not clear. Oral administration or pellet implantation was applied. We orally applied an aromatase inhibitor (AI, to decrease estrogen levels) and 17α-methyltestosterone (MT, to increase androgen levels) to induce masculinization to clarify the mechanism of the sex change in the protogynous orange-spotted grouper. After 3 mo of AI/MT administration, male characteristics were observed in the female-to-male sex change fish. These male characteristics included increased plasma 11-ketotestosterone (11-KT), decreased estradiol (E2) levels, increased male-related gene (dmrt1, sox9, and cyp11b2) expression, and decreased female-related gene (figla, foxl2, and cyp19a1a) expression. However, the reduced male characteristics and male-to-female sex change occurred after AI/MT-termination in the AI- and MT-induced maleness. Furthermore, the MT-induced oocyte-depleted follicle cells (from MT-implantation) had increased proliferating activity, and the sexual fate in a portion of female gonadal soma cells was altered to male function during the female-to-male sex change. In contrast, the gonadal soma cells were not proliferative during the early process of the male-to-female sex change. Additionally, the male gonadal soma cells did not alter to female function during the male-to-female sex change in the AI/MT-terminated fish. After MT termination in the male-to-female sex-changed fish, the differentiated male germ cells showed increased proliferating activities together with dormancy and did not show characteristics of both sexes in the early germ cells. In conclusion, these findings indicate for the first time in a single species that the mechanism involved in the replacement of soma cells is different between the female-to-male and male-to-female sex change processes in grouper. These results also demonstrate that sexual fate determination

Sexual Fate Reprogramming in the Steroid-Induced Bi-Directional Sex Change in the Protogynous Orange-Spotted Grouper, Epinephelus coioides

PubMed Central

Wu, Guan-Chung; Tey, Wei-Guan; Li, Hau-Wen; Chang, Ching-Fong

2015-01-01

Androgen administration has been widely used for masculinization in fish. The mechanism of the sex change in sexual fate regulation is not clear. Oral administration or pellet implantation was applied. We orally applied an aromatase inhibitor (AI, to decrease estrogen levels) and 17α-methyltestosterone (MT, to increase androgen levels) to induce masculinization to clarify the mechanism of the sex change in the protogynous orange-spotted grouper. After 3 mo of AI/MT administration, male characteristics were observed in the female-to-male sex change fish. These male characteristics included increased plasma 11-ketotestosterone (11-KT), decreased estradiol (E2) levels, increased male-related gene (dmrt1, sox9, and cyp11b2) expression, and decreased female-related gene (figla, foxl2, and cyp19a1a) expression. However, the reduced male characteristics and male-to-female sex change occurred after AI/MT-termination in the AI- and MT-induced maleness. Furthermore, the MT-induced oocyte-depleted follicle cells (from MT-implantation) had increased proliferating activity, and the sexual fate in a portion of female gonadal soma cells was altered to male function during the female-to-male sex change. In contrast, the gonadal soma cells were not proliferative during the early process of the male-to-female sex change. Additionally, the male gonadal soma cells did not alter to female function during the male-to-female sex change in the AI/MT-terminated fish. After MT termination in the male-to-female sex-changed fish, the differentiated male germ cells showed increased proliferating activities together with dormancy and did not show characteristics of both sexes in the early germ cells. In conclusion, these findings indicate for the first time in a single species that the mechanism involved in the replacement of soma cells is different between the female-to-male and male-to-female sex change processes in grouper. These results also demonstrate that sexual fate determination

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

PubMed Central

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

2013-01-01

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

Activational effects of sex hormones on cognition in men.

PubMed

Ulubaev, A; Lee, D M; Purandare, N; Pendleton, N; Wu, F C W

2009-11-01

Changing world demographic patterns, such as the increasing number of older people and the growing prevalence of cognitive impairment, present serious obstacles to preserving the quality of life and productivity of individuals. The severity of dementia varies from subclinical, mild cognitive impairment to neurodegenerative diseases such as Alzheimer's. In normally ageing men, these age-related cognitive declines are accompanied by gradual but marked decreases in androgen levels and changes in other hormone profiles. While developmental effects of sex hormones on cognition in the pre- and early postnatal period have been demonstrated, their activational effects in later life are still a focus of contemporary research. Although there is a plethora of published research on the topic, results have been inconsistent with different studies reporting positive, negative or no effects of sex hormones on various aspects of mental agility. This review summarizes the evidence supporting the biological plausibility of the activational effects of sex hormones upon cognition and describes the mechanisms of their actions. It offers a comprehensive summary of the studies of the effects of sex hormones on fluid intelligence in men utilizing elements from the Cochrane Collaboration Guidelines for Reviews. The results of both observational (cross-sectional and longitudinal) and interventional studies published to date are collated in table form and further discussed in the text. Factors contributing to the difficulties in understanding the effects of sex hormones on cognition are also examined. Although there is convincing evidence that steroid sex hormones play an organizational role in brain development in men, the evidence for activational effects of sex hormones affecting cognition in healthy men throughout adult life remains inconsistent. To address this issue, a new multifactorial approach is proposed which takes into account the status of other elements of the sex hormones axis

Quantification of three steroid hormone receptors of the leopard gecko (Eublepharis macularius), a lizard with temperature-dependent sex determination: their tissue distributions and the effect of environmental change on their expressions.

PubMed

Endo, Daisuke; Park, Min Kyun

2003-12-01

Sex steroid hormones play a central role in the reproduction of all vertebrates. These hormones function through their specific receptors, so the expression levels of the receptors may reflect the responsibility of target organs. However, there was no effective method to quantify the expression levels of these receptors in reptilian species. In this study, we established the competitive-PCR assay systems for the quantification of the mRNA expression levels of three sex steroid hormone receptors in the leopard gecko. These assay systems were successfully able to detect the mRNA expression level of each receptor in various organs of male adult leopard geckoes. The expression levels of mRNA of these receptors were highly various depending on the organs assayed. This is the first report regarding the tissue distributions of sex steroid hormone receptor expressions in reptile. The effects of environmental conditions on these hormone receptor expressions were also examined. After the low temperature and short photoperiod treatment for 6 weeks, only the androgen receptor expression was significantly increased in the testes. The competitive-PCR assay systems established in this report should be applicable for various studies of the molecular mechanism underlying the reproductive activity of the leopard gecko.

Identification and properties of steroid-binding proteins in nesting Chelonia mydas plasma.

PubMed

Ikonomopoulou, M P; Bradley, A J; Whittier, J M; Ibrahim, K

2006-11-01

We report for the first time the presence of a sex steroid-binding protein in the plasma of green sea turtles Chelonia mydas, which provides an insight into reproductive status. A high affinity, low capacity sex hormone steroid-binding protein was identified in nesting C. mydas and its thermal profile was established. In nesting C. mydas testosterone and oestradiol bind at 4 degrees C with high affinity (K (a) = 1.49 +/- 0.09 x 10(9) M(-1); 0.17 +/- 0.02 x 10(7) M(-1)) and low binding capacity (B (max) = 3.24 +/- 0.84 x 10(-5) M; 0.33 +/- 0.06 x 10(-4) M). The binding affinity and capacity of testosterone at 23 and 36 degrees C, respectively were similar to those determined at 4 degrees C. However, oestradiol showed no binding activity at 36 degrees C. With competition studies we showed that oestradiol and oestrone do not compete for binding sites. Furthermore, in nesting C. mydas plasma no high-affinity binding was observed for adrenocortical steroids (cortisol and corticosterone) and progesterone. Our results indicate that in nesting C. mydas plasma temperature has a minimal effect on the high-affinity binding of testosterone to sex steroid-binding protein, however, the high affinity binding of oestradiol to sex steroid-binding protein is abolished at a hypothetically high (36 degrees C) sea/ambient/body temperature. This suggests that at high core body temperatures most of the oestradiol becomes biologically available to the tissues rather than remaining bound to a high-affinity carrier.

Learning and memory: Steroids and epigenetics.

PubMed

Colciago, Alessandra; Casati, Lavinia; Negri-Cesi, Paola; Celotti, Fabio

2015-06-01

Memory formation and utilization is a complex process involving several brain structures in conjunction as the hippocampus, the amygdala and the adjacent cortical areas, usually defined as medial temporal lobe structures (MTL). The memory processes depend on the formation and modulation of synaptic connectivity affecting synaptic strength, synaptic plasticity and synaptic consolidation. The basic neurocognitive mechanisms of learning and memory are shortly recalled in the initial section of this paper. The effect of sex hormones (estrogens, androgens and progesterone) and of adrenocortical steroids on several aspects of memory processes are then analyzed on the basis of animal and human studies. A specific attention has been devoted to the different types of steroid receptors (membrane or nuclear) involved and on local metabolic transformations when required. The review is concluded by a short excursus on the steroid activated epigenetic mechanisms involved in memory formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mammalian sex chromosomes. III. Activity of pseudoautosomal steroid sulfatase enzyme during spermatogenesis in Mus musculus.

PubMed

Raman, R; Das, P

1991-09-01

Parallel to the inactivation of the X chromosome in somatic cells of female, the male X in mammals is rendered inactive during spermatogenesis. Pseudoautosomal genes, those present on the X-Y meiotically pairable region of male, escape inactivation in female soma. It is suggested, but not demonstrated, that they may also be refractory to the inactivation signal in male germ cells. We have assayed activity of the enzyme steroid sulfatase, product of a pseudoautosomal gene, in testicular cells of the mouse and shown its presence in premeiotic, meiotic (pachytene), and postmeiotic (spermatid) cell types. It appears that, as in females, pseudoautosomal genes may escape inactivation in male germ cells also.

Obesity during pregnancy affects sex steroid concentrations depending on fetal gender.

PubMed

Maliqueo, M; Cruz, G; Espina, C; Contreras, I; García, M; Echiburú, B; Crisosto, N

2017-11-01

It is not clear whether maternal obesity along with fetal gender affect sex steroid metabolism during pregnancy. Therefore, we compared sex steroid concentrations and placental expression of steroidogenic enzymes between non-obese and obese pregnant women with non-pathological pregnancies, and investigated the influence of fetal gender on these parameters. In 35 normal weight (body mass index (BMI) 20-24.9 kg m - 2 ) (controls) and 36 obese women (BMI 30-36 kg m - 2 ) (obese), a fasting blood sample was obtained at first and at third trimester of gestation to measure progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione, testosterone and estradiol by liquid chromatography-tandem mass spectrometry and estrone by radioimmunoassay. In a subset of women, placental mRNA and protein expression of steroidogenic enzymes was measured by quantitative PCR and western blot, respectively. The comparisons were primarily made between controls and obese, and then separately according to fetal gender. At first and third trimesters of gestation serum progesterone was lower whereas testosterone was higher in obese women (P<0.05, respectively). Upon analyzing according to fetal gender, lower progesterone levels were present in obese pregnant women with male fetuses at first trimester and with female fetuses at third trimester (P<0.05, respectively). Testosterone was higher in obese women with male fetuses compared to control women with male fetuses (P<0.05). The placental protein expression of P450scc was higher in obese women compared to controls (P<0.05). P450 aromatase was higher in obese women with female fetuses (P=0.009), whereas in obese women with male fetuses P450 aromatase was lower compared to control women (P=0.026). Obesity in non-pathological pregnancies alters the maternal serum progesterone and testosterone concentrations depending on fetal gender. These changes can be attributed to gender-related placental adaptations, as the expression of

Does the mechanism of sex determination constrain the potential for sex manipulation? A test in geckos with contrasting sex-determining systems

NASA Astrophysics Data System (ADS)

Kratochvíl, Lukáš; Kubička, Lukáš; Landová, Eva

2008-03-01

The concentration of yolk steroids was suggested to influence offspring gender in oviparous animals subject to both temperature-dependent sex determination (TSD) and genotypic sex determination (GSD). However, the proposed mechanisms of steroid effects are thought to differ between TSD and GSD: a direct effect of oestrogens on gonad feminisation in TSD species vs a differential induction of male-producing or female-producing gametes in GSD species. Geckos offer an ideal opportunity for testing these suggested mechanisms. Closely related gecko species differ in their modes of sex determination. They lay clutches of two synchronously formed eggs; both eggs share equal steroid levels. If identical hormonal composition and environment during vitellogenesis, gravidity and incubation determine the sex of the progeny, siblings should share the same gender in both TSD and GSD geckos. We found strong support for this prediction in a TSD gecko species. Among clutches that were incubated at the temperature that produced both sexes, there were no clutches with siblings of the opposite sex. On the other hand, about half of the clutches yielded siblings of the opposite sex in four GSD species. These results suggest that sex-determining systems constrain the ability of the female to produce single-sex siblings and, hence, it seems that the GSD mechanism constrains the opportunities for sex ratio manipulation in geckos via yolk steroid manipulation.

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

Synthesis and acetylcholinesterase inhibitory activity of polyhydroxylated sulfated steroids: structure/activity studies.

PubMed

Richmond, Victoria; Murray, Ana P; Maier, Marta S

2013-11-01

Disulfated and trisulfated steroids have been synthesized from cholesterol and their acetylcholinesterase inhibitory activity has been evaluated. In our studies we have found that the activity was not only dependent on the location of the sulfate groups but on their configurations. 2β,3α,6α-trihydroxy-5α-cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of 15.48 μM comparable to that of 2β,3α-dihydroxy-5α-cholestan-6-one disulfate (1). Both compounds were found to be less active than the reference compound eserine. The butyrylcholinesterase activity of 1 and 18 was one magnitude lower than that against acetylcholinesterase revealing a selective inhibitor profile. Copyright © 2013 Elsevier Inc. All rights reserved.

Steroid ligands bind human sex hormone-binding globulin in specific orientations and produce distinct changes in protein conformation.

PubMed

Grishkovskaya, Irina; Avvakumov, George V; Hammond, Geoffrey L; Catalano, Maria G; Muller, Yves A

2002-08-30

The amino-terminal laminin G-like domain of human sex hormone-binding globulin (SHBG) contains a single high affinity steroid-binding site. Crystal structures of this domain in complex with several different steroid ligands have revealed that estradiol occupies the SHBG steroid-binding site in an opposite orientation when compared with 5 alpha-dihydrotestosterone or C19 androgen metabolites (5 alpha-androstan-3 beta,17 beta-diol and 5 alpha-androstan-3 beta,17 alpha-diol) or the synthetic progestin levonorgestrel. Substitution of specific residues within the SHBG steroid-binding site confirmed that Ser(42) plays a key role in determining high affinity interactions by hydrogen bonding to functional groups at C3 of the androstanediols and levonorgestrel and the hydroxyl at C17 of estradiol. Among residues participating in the hydrogen bond network with hydroxy groups at C17 of C19 steroids or C3 of estradiol, Asp(65) appears to be the most important. The different binding mode of estradiol is associated with a difference in the position/orientation of residues (Leu(131) and Lys(134)) in the loop segment (Leu(131)-His(136)) that covers the steroid-binding site as well as others (Leu(171)-Lys(173) and Trp(84)) on the surface of human SHBG and may provide a basis for ligand-dependent interactions between SHBG and other macromolecules. These new crystal structures have also enabled us to construct a simple space-filling model that can be used to predict the characteristics of novel SHBG ligands.

Linking physiological approaches to marine vertebrate conservation: using sex steroid hormone determinations in demographic assessments

PubMed Central

Labrada-Martagón, Vanessa; Zenteno-Savín, Tania; Mangel, Marc

2014-01-01

Sex, age and sexual maturation are key biological parameters for aspects of life history and are fundamental information for assessing demographic changes and the reproductive viability and performance of natural populations under exploitation pressures or in response to environmental influences. Much of the information available on the reproductive condition, length at sexual maturity and sex determinations of endangered species has been derived from direct examination of the gonads in dead animals, either intentionally or incidentally caught, or from stranded individuals. However, morphological data, when used alone, do not provide accurate demographic information in sexually monomorphic marine vertebrate species (e.g. sharks, sea turtles, seabirds and cetaceans). Hormone determination is an accurate and non-destructive method that provides indirect information about sex, reproductive condition and sexual maturity of free-ranging individuals. Correlations between sex steroid concentrations and biochemical parameters, gonadal development and state, reproductive behaviour and secondary external features have been already demonstrated in many species. Different non-lethal approaches (e.g. surgical and mark–recapture procedures), with intrinsic advantages and disadvantages when applied on free-ranging organisms, have been proposed to asses sex, growth and reproductive condition. Hormone determination from blood samples will generate valuable additional demographic information needed for stock assessment and biological conservation. PMID:27293619

Effect of steroids on the activation status of platelets in patients with Immune thrombocytopenia (ITP).

PubMed

Bhoria, Preeti; Sharma, Saniya; Varma, Neelam; Malhotra, Pankaj; Varma, Subhash; Luthra-Guptasarma, Manni

2015-01-01

The activation status of platelets in Immune Thrombocytopenia (ITP) patients--which is still somewhat controversial--is of potential interest, because activated platelets tend to aggregate (leading to excessive clotting or thromboembolic events) but cannot do so when platelet numbers are low, as in ITP. Although corticosteroids are the first line of therapy in ITP, the effect of steroids on activation of platelets has not been evaluated so far. We examined the status of platelet activation (with and without stimulation with ADP) in ITP patients, at the start of therapy (pre-steroid treatment, naive) and post-steroid treatment (classified on the basis of steroid responsiveness). We used flow cytometry to evaluate the levels of expression of P-selectin, and PAC-1 binding to platelets of 55 ITP patients and a similar number of healthy controls, treated with and without ADP. We found that platelets in ITP patients exist in an activated state. In patients who are responsive to steroids, the treatment reverses this situation. Also, the fold activation of platelets upon treatment with ADP is more in healthy controls than in ITP patients; treatment with steroids causes platelets in steroid-responsive patients to become more responsive to ADP-activation, similar to healthy controls. Thus steroids may cause changes in the ability of platelets to get activated with an agonist like ADP. Our results provide new insights into how, and why, steroid therapy helps in the treatment of ITP.

Sex steroids, sexual behavior, and selection attention for erotic stimuli in women using oral contraceptives.

PubMed

Alexander, G M; Sherwin, B B

1993-01-01

The relationship between sex steroids and sexual behavior was examined in 19 oral contraceptive users. Retrospective assessment of sexual attitudes were obtained and women completed daily ratings of sexual behavior and well-being for 28 days. Plasma levels of free testosterone (T), estradiol, and progesterone were measured at weekly intervals. In addition, women performed a novel selective attention task designed to measure the strength of the tendency to be distracted by sexual stimuli. Multiple regression analyses using average sexual behavior variables as dependent variables, and hormone levels sexual attitudes and well-being as predictor variables, showed that free T was strongly and positively associated with sexual desire, sexual thoughts, and anticipation of sexual activity. A role for T in attention to sexual stimuli was also supported by the positive correlation between free T and the bias for sexual stimuli in a subgroup of women. These results are consistent with the hypothesis that T may enhance cognitive aspects of women's sexual behavior.

Steroids and endocrine disruptors--History, recent state of art and open questions.

PubMed

Hampl, Richard; Kubátová, Jana; Stárka, Luboslav

2016-01-01

This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3β-, 11β- and 17β-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in

Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia.

PubMed

Mieritz, Mikkel G; Sorensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Hagen, Casper P; Hilsted, Linda; Andersson, Anna-Maria; Juul, Anders

2014-05-01

Pubertal gynaecomastia is a very common condition. Although the underlying aetiology is poorly understood, it is generally accepted that excess of oestrogens and deficit of androgens are involved in the pathogenesis. Furthermore, adiposity as well as the GH/IGF-I axis may play a role. In this study, we elucidate the association of adiposity and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), testosterone, oestrogen, IGF-I and IGFBP-3 with the presence of pubertal gynaecomastia in a large cohort of healthy boys. A total of 501 healthy Danish school boys (aged 6·1-19·8 year) from the COPENHAGEN Puberty Study. Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Body fat percentage was calculated by means of four skin folds and impedance. Nonfasting blood samples were analysed for FSH, LH, testosterone, SHBG, oestradiol, IGF-I, IGFBP-3 and prolactin. We found that 23% (31/133) of all pubertal boys had gynaecomastia. More specifically, 63% (10/16) of boys in genital stage 4 had gynaecomastia. Boys with gynaecomastia had significantly higher IGF-I levels compared with controls (IGF-I SD-score 0·72 vs -0·037, P < 0·001). This difference was maintained after adjusting for confounders (age and pubertal stage). Sex steroid levels, oestradiol/testosterone ratio or free testosterone were not associated with the presence of gynaecomastia with or without adjustment for confounders. IGF-I levels were elevated in healthy boys with pubertal gynaecomastia compared with boys without gynaecomastia, whereas sex steroid levels did not differ. We speculate that the GH-IGF-I axis may be involved in the pathogenesis of pubertal gynaecomastia. © 2013 John Wiley & Sons Ltd.

Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers.

PubMed

Zhou, Cindy Ke; Stanczyk, Frank Z; Hafi, Muhannad; Veneroso, Carmela C; Lynch, Barlow; Falk, Roni T; Niwa, Shelley; Emanuel, Eric; Gao, Yu-Tang; Hemstreet, George P; Zolfghari, Ladan; Carroll, Peter R; Manyak, Michael J; Sesterhenn, Isabell A; Levine, Paul H; Hsing, Ann W; Cook, Michael B

2017-12-01

Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (<7 vs ≥7) and race (European American vs. African American). We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak

Actions of sex steroids on kisspeptin expression and other reproduction-related genes in the brain of the teleost fish European sea bass.

PubMed

Alvarado, M V; Servili, A; Molés, G; Gueguen, M M; Carrillo, M; Kah, O; Felip, A

2016-11-01

Kisspeptins are well known as mediators of the coordinated communication between the brain-pituitary axis and the gonads in many vertebrates. To test the hypothesis that gonadal steroids regulate kiss1 and kiss2 mRNA expression in European sea bass (a teleost fish), we examined the brains of gonad-intact (control) and castrated animals, as well as castrated males (GDX) and ovariectomized females (OVX) that received testosterone (T) and estradiol (E 2 ) replacement, respectively, during recrudescence. In GDX males, low expression of kiss1 mRNA is observed by in situ hybridization in the caudal hypothalamus (CH) and the mediobasal hypothalamus (MBH), although hypothalamic changes in kiss1 mRNA levels were not statistically different among the groups, as revealed by real-time PCR. However, T strongly decreased kiss2 expression levels in the hypothalamus, which was documented in the MBH and the nucleus of the lateral recess (NRLd) in GDX T-treated sea bass males. Conversely, it appears that E 2 evokes low kiss1 mRNA in the CH, while there were cells expressing kiss2 in the MBH and NRLd in these OVX females. These results demonstrate that kisspeptin neurons are presumably sensitive to the feedback actions of sex steroids in the sea bass, suggesting that the MBH represents a major site for sex steroid actions on kisspeptins in this species. Also, recent data provide evidence that both positive and negative actions occur in key factors involved in sea bass reproductive function, including changes in the expression of gnrh-1/gonadotropin, cyp19b, er and ar genes and sex steroid and gonadotropin plasma levels in this teleost fish. © 2016. Published by The Company of Biologists Ltd.

Steroid signaling system responds differently to temperature and hormone manipulation in the red-eared slider turtle (Trachemys scripta elegans), a reptile with temperature-dependent sex determination.

PubMed

Ramsey, M; Crews, D

2007-01-01

Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor alpha (Esr1, hereafter referred to as ERalpha), estrogen receptor beta (Esr2, hereafter referred to as ERbeta), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERalpha and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERalpha and AR expression while ERbeta is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E(2)) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERalpha and ERbeta redirected to the cortex in E(2)-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization. 2007 S. Karger AG, Basel

Changes in sex steroid hormone levels reflect the reproductive status of captive female zebra sharks (Stegostoma fasciatum).

PubMed

Nozu, Ryo; Murakumo, Kiyomi; Yano, Nagisa; Furuyama, Rina; Matsumoto, Rui; Yanagisawa, Makio; Sato, Keiichi

2018-03-03

Captive breeding in aquaria is a useful means for ex situ preservation of threatened elasmobranch species. To promote captive breeding, it is important to determine the female reproductive status. However, information regarding reproductive status in female elasmobranchs is limited. Here, we used zebra sharks, Stegostoma fasciatum, as a model for elasmobranch reproduction in captivity. We investigated the relationships among changes in the sex steroid hormone levels, follicle size, and egg-laying period to develop indicators for the female reproductive status. We confirmed that mature female zebra sharks undergo an annual reproductive cycle. Additionally, we showed that the variations in sex steroid hormone levels correlated with reproductive status in mature female zebra sharks. Plasma estradiol-17ß (E2) concentrations increased two months before ovarian follicle development and decreased along with follicle regression. Interestingly, E2 levels were inversely correlated with water temperature (R = -0.901). Moreover, high levels of testosterone (T) correlated well with the laying period. These results strongly suggest that E2 is an indicator for ovarian follicle development, and that T is a useful indicator for both the onset and end of the egg-laying period in captive zebra sharks. Copyright © 2018 Elsevier Inc. All rights reserved.

Steroidal Saponins

NASA Astrophysics Data System (ADS)

Sahu, N. P.; Banerjee, S.; Mondal, N. B.; Mandal, D.

The medicinal activities of plants are generally due to the secondary metabolites (1) which often occur as glycosides of steroids, terpenoids, phenols etc. Saponins are a group of naturally occurring plant glycosides, characterized by their strong foam-forming properties in aqueous solution. The cardiac glycosides also possess this, property but are classified separately because of their specific biological activity. Unlike the cardiac glycosides, saponins generally do not affect the heart. These are classified as steroid or triterpenoid saponins depending on the nature of the aglycone. Steroidal glycosides are naturally occurring sugar conjugates of C27 steroidal compounds. The aglycone of a steroid saponin is usually a spirostanol or a furostanol. The glycone parts of these compounds are mostly oligosaccharides, arranged either in a linear or branched fashion, attached to hydroxyl groups through an acetal linkage (2, 3). Another class of saponins, the basic steroid saponins, contain nitrogen analogues of steroid sapogenins as aglycones.

Selected variants of the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2 and the sex steroid hormone receptors ESR1, ESR2 and PGR: no association with female pattern hair loss identified.

PubMed

Redler, Silke; Tazi-Ahnini, Rachid; Drichel, Dmitriy; Birch, Mary P; Brockschmidt, Felix F; Dobson, Kathy; Giehl, Kathrin A; Refke, Melanie; Kluck, Nadine; Kruse, Roland; Lutz, Gerhard; Wolff, Hans; Böhm, Markus; Becker, Tim; Nöthen, Markus M; Betz, Regina C; Messenger, Andrew

2012-05-01

Female pattern hair loss (FPHL) is a common disorder with a complex mode of inheritance. Although understanding of its etiopathogenesis is incomplete, an interaction between genetic and hormonal factors is assumed to be important. The involvement of an androgen-dependent pathway and sex steroid hormones is the most likely hypothesis. We therefore selected a total of 21 variants from the steroid-5-alpha-reductase isoforms SRD5A1 and SRD5A2, the sex steroid hormone receptors ESR1, ESR2 (oestrogen receptor) and PGR (progesterone receptor) and genotyped these in a case-control sample of 198 patients (145 UK; 53 German patients) and 329 controls (179 UK; 150 German). None of these variants showed any significant association, either in the overall UK and German samples or in the subgroup analyses. In summary, the present results, while based on a limited selection of gene variants, do not point to the involvement of SRD5A1, SRD5A2, ESR1, ESR2 or PGR in FPHL. © 2012 John Wiley & Sons A/S.

Sex steroids and the GH axis: Implications for the management of hypopituitarism.

PubMed

Birzniece, Vita; Ho, Ken K Y

2017-02-01

Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Steroid osteopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conway, J.J.; Weiss, S.C.

1984-01-01

Patients receiving steroids or having disease processes which increase natural steroid production often demonstrate ''the classic x-ray changes'' of avascular necrosis of bone. Bone scintigraphy in these patients most frequently demonstrates an increased radionuclide localization. The literature suggests that the increased activity is related to healing of the avascular process. In a recent study of Legg-Calve-Perthes Disease (LCPD), 37 of the children had multiple studies and increased activity within the epiphysis during revascularization was extremely rare. Not only are the scintigraphic findings in steroid osteopathy dissimilar to that in healing LCPD, but the time interval for healing is much tomore » short for that of a vascular necrosis and no patients demonstrated an avascular phase on bone scintigraphy. Of 15 children with renal transplants on steroid therapy, 9 demonstrated x-ray and clinical findings of osteopathy. In 8 of 9 instances, bone scintigraphy showed increased localization of radionuclide in the affected bone. Improvement or a return to normal occurred in those patients in whom steroids were discontinued. The following is a proposed mechanism for steroid osteopathy. Steroids affect the osteoblastic and osteoclastic activity of bone and weaken its internal structure. Ordinary stress produces microtrabecular fractures. Fractures characteristically stimulate reactive hyperemia and increase bone metabolism. The result is increased bone radiopharmaceutical localization. The importance of recognizing this concept is that steroid osteopathy is preventable by reducing the administered steroid dose. As opposed to avascular necrosis, bone changes are reversible.« less

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

PubMed

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

2016-09-20

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

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

PubMed Central

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

2016-01-01

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

Determination of 17OHPreg and DHEAS by LC-MS/MS: Impact of Age, Sex, Pubertal Stage, and BMI on the Δ5 Steroid Pathway.

PubMed

Kulle, Alexandra E; Reinehr, Thomas; Simic-Schleicher, Gunter; Hornig, Nadine C; Holterhus, Paul-Martin

2017-01-01

Dehydroepiandrosterone sulfate (DHEAS) and 17-hydroxypregnenolone (17OHPreg) are important for understanding the Δ5 pathway (e.g., in adrenarche and obesity). Although mass spectrometry has become the state-of-the-art method for quantifying steroids, there are few comprehensive age-, sex-, and pubertal stage-specific reference ranges for children. To develop a sensitive and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of DHEAS and 17OHPreg and to establish entire age-, sex- and pubertal stage-specific reference ranges in children. A total of 684 children, 453 (243 female, 210 male) with normal body mass index (BMI; <90th) and 231 (132 female, 99 male) obese subjects (>97th), were categorized into 11 age groups, and age- and Tanner stage (PH)-specific reference ranges were determined. The limit of detection was 0.05 nmol/L for 17OHPreg and 0.5 nmol/L for DHEAS. Levels of both steroids declined after the neonatal period. Comparisons with RIA assays (Siemens, Munich, Germany) (DHEAS) and an in-house kit (17OHPreg) revealed 0.95 and 0.93, respectively, as coefficients of determination. Although DHEAS-generally higher in boys-increased continuously starting at 3 to 6 years, 17OHPreg remained largely constant. In obese patients, both were significantly elevated, also in part after alignment to Tanner stages (PH). UPLC-MS/MS is sensitive and reliable for quantifying DHEAS and 17OHPreg. Our data support differential maturation of CYP17 during adrenarche with successively increasing 17,20-lyase activity but largely constant 17α-hydroxylation activity. Endocrine interpretation of 17OHPreg and DHEAS must consider differential patterns for age, sex, pubertal stage, and BMI. Copyright © 2017 by the Endocrine Society

Behavioral evidence for sex steroids hypersensitivity in castrated male canaries.

PubMed

Shevchouk, Olesya; Ghorbanpoor, Samar; Smith, Ed; Liere, Philippe; Schumacher, Michael; Ball, Gregory F; Cornil, Charlotte A; Balthazart, Jacques

2018-06-14

In seasonally breeding songbirds such as canaries, singing behavior is predominantly under the control of testosterone and its metabolites. Short daylenths in the fall that break photorefractoriness are followed by increasing daylengths in spring that activate singing via both photoperiodic and hormonal mechanisms. However, we observed in a group of castrated male Fife fancy canaries maintained for a long duration under a short day photoperiod a large proportion of subjects that sang at high rates. This singing rate was not correlated with variation in the low circulating concentrations of testosterone. Treatment of these actively singing castrated male canaries with a combination of an aromatase inhibitor (ATD) and an androgen receptor blocker (flutamide) only marginally decreased this singing activity as compared to control untreated birds and did not affect various measures of song quality. The volumes of HVC and of the medial preoptic nucleus (POM) were also unaffected by these treatments but were relatively large and similar to volumes in testosterone-treated males. In contrast, peripheral androgen-sensitive structures such as the cloacal protuberance and syrinx mass were small, similar to what is observed in castrates. Together these data suggest that after a long-term steroid deprivation singing behavior can be activated by very low concentrations of testosterone. Singing normally depends on the activation by testosterone and its metabolites of multiple downstream neurochemical systems such as catecholamines, nonapeptides or opioids. These transmitter systems might become hypersensitive to steroid action after long term castration as they probably are at the end of winter during the annual cycle in seasonally breeding temperate zone species. Copyright © 2017. Published by Elsevier Inc.

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

PubMed

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

2015-09-05

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

Comparing sex steroid levels during the annual cycles of rainbow trout (Oncorhynchus mykiss) diploid female (XX) and triploid female (XXX) genotypic sex.

PubMed

Espinosa, E; Josa, A; Gil, L; Malo, C; Mitjana, O

2013-02-01

In this study, the annual cycle of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), 17β-estradiol (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) was determined using radioimmunoassay and then compared for two populations of rainbow trout, XX diploid females (n = 40) and XXX triploid females (n = 15). In females, E2 and DHP levels were found to be significantly related to body weight (r = 0.22513; p < 0.0001 and r = 0.15831; p > 0.001, respectively). In this group, E2 concentrations peaked in November (25.05 ng/ml), while maximum DHP levels, only measurable from October to April, were attained in February (64.14 ng/ml). No significant differences in hormone ranges related to egg output ability were observed. Finally, sex steroid concentrations were low in the triploid female XXX fish compared to the female XX population. Nevertheless, maximum T (33.85 ng/ml) and 11-KT (32.35 ng/ml) levels were recorded in January, for XXX. The levels for these two hormones are relatively high and are also significantly associated (r = 0.8430; p < 0.0001). Diploid females showed significantly higher levels of E2 than triploids over the 12-month study period. The female triploid fish produced the lowest steroid hormone levels, such that these would be the most suitable for human consumption. © 2012 Blackwell Verlag GmbH.

Sex steroids and human behavior: prenatal androgen exposure and sex-typical play behavior in children.

PubMed

Hines, Melissa

2003-12-01

Gonadal hormones, particularly androgens, direct certain aspects of brain development and exert permanent influences on sex-typical behavior in nonhuman mammals. Androgens also influence human behavioral development, with the most convincing evidence coming from studies of sex-typical play. Girls exposed to unusually high levels of androgens prenatally, because they have the genetic disorder, congenital adrenal hyperplasia (CAH), show increased preferences for toys and activities usually preferred by boys, and for male playmates, and decreased preferences for toys and activities usually preferred by girls. Normal variability in androgen prenatally also has been related to subsequent sex-typed play behavior in girls, and nonhuman primates have been observed to show sex-typed preferences for human toys. These findings suggest that androgen during early development influences childhood play behavior in humans at least in part by altering brain development.

Association of serum inorganic phosphate with sex steroid hormones and vitamin D in a nationally representative sample of men.

PubMed

Wulaningsih, W; Van Hemelrijck, M; Michaelsson, K; Kanarek, N; Nelson, W G; Ix, J H; Platz, E A; Rohrmann, S

2014-11-01

Defects in bone regulatory pathways have been linked to chronic diseases including cardiovascular disease and cancer. In men, a link between bone metabolism and gonadal hormones has been suggested. However, to date, there is lack of evidence on the association between serum inorganic phosphate (Pi) and sex steroid hormones. The objective of this study was to investigate the association between Pi, sex steroid hormones and a known Pi metabolic regulator, vitamin D, in men in the National Health and Nutrition Examination Survey III (NHANES III). From NHANES III, we selected 1412 men aged 20+ who participated in the morning session of Phase I (1988-1991) with serum measurements of Pi, sex hormones, and vitamin D. Multivariable linear regression was used to calculate crude and geometric mean Pi by total and estimated free testosterone and estradiol, sex hormone-binding globulin, androstanediol glucuronide (AAG), and vitamin D. Similar analyses were performed while stratifying by race/ethnicity and vitamin D levels. We found a lack of statistically significant difference in geometric means of Pi across quintiles of concentrations of sex hormones, indicating a tight regulation of Pi. However, Pi levels were inversely associated with calculated free testosterone in non-Hispanic black men, with geometric mean levels of Pi of 1.16 and 1.02 ng/mL for those in the lowest and highest quintiles of free testosterone, respectively (p-trend < 0.05). A similar but weaker pattern was seen between total testosterone and Pi. An inverse association was also seen between AAG and Pi in men with vitamin D concentration below the median (<24.2 ng/mL). No associations were observed among men with vitamin D levels at or above the median. Our findings suggest a weak link among sex hormones, vitamin D, and Pi in men. The observed effects of race/ethnicity and vitamin D indicate a complex association involving various regulators of Pi homeostasis. © 2014 American Society of Andrology and

Sleep, rhythms, and the endocrine brain: influence of sex and gonadal hormones.

PubMed

Mong, Jessica A; Baker, Fiona C; Mahoney, Megan M; Paul, Ketema N; Schwartz, Michael D; Semba, Kazue; Silver, Rae

2011-11-09

While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master "circadian clock" within the suprachiasmatic nucleus, modulate photic effects on activity in males point to novel mechanisms of circadian control. Work in aromatase-deficient mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a Mini-Symposium at the 2011 annual meeting of the Society for Neuroscience.

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.

Effect of contraceptive steroids on monoamine oxidase activity

PubMed Central

Southgate, Jennifer; Collins, G. G. S.; Pryse-Davies, J.; Sandler, M.

1969-01-01

Cyclical variations in monoamine oxidase activity during the human menstrual cycle, specific to the endometrium and modified in women undergoing contraceptive steroid treatment, may reflect changes in hormonal environment. Treatment of rats with individual constituents of the contraceptive pill causes analogous changes: oestrogens inhibit and progestogens potentiate uterine monoamine oxidase activity. ImagesFig. 2Fig. 3

A high-throughput UPC2-MS/MS method for the separation and quantification of C19 and C21 steroids and their C11-oxy steroid metabolites in the classical, alternative, backdoor and 11OHA4 steroid pathways.

PubMed

du Toit, Therina; Stander, Maria A; Swart, Amanda C

2018-03-30

In the present study an ultra-performance convergence chromatography tandem mass spectrometry (UPC 2 -MS/MS) analytical method was developed and validated for the determination of 17 C 19 and 14 C 21 steroids, including C11-oxy C 19 and C11-oxy C 21 steroids. The limit of detection and limit of quantification ranged from 0.01 to 10 ng/mL and from 0.01 to 20 ng/mL, respectively, and the method shows the recovery, matrix effect and process efficiency of steroids isolated from a serum matrix to be within acceptable limits. Good accuracy, repeatability and reproducibility were also shown and the method provided excellent sensitivity and selectivity as stereoisomers and regioisomers were also resolved and quantified accurately. Clinical conditions such as congenital adrenal hyperplasia, polycystic ovary syndrome in females and disorders of sex development in neonates and in children, amongst others, are characterized by abnormal steroid levels. Steroid profiling is essential to accurately diagnose steroid levels in the above settings as well as in androgen excess or deficiency in adrenal-linked endocrine diseases. Our method, separating C 19 and C 21 steroids in a single chromatographic step, offers a reduced sample turnover rate in the clinical setting, while providing comprehensive steroid profiles of in vivo steroids in the nmol/L range. This is, to our knowledge, the first method reported to simultaneously separate C 19 and C 21 steroids, together with their C11-hydroxy and C11-keto metabolites -one which may hold promise in the identification of new steroid markers in steroid-linked endocrine diseases, in addition to profiling steroid metabolism and abnormal enzyme activity in patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Steroids and Autoimmunity.

PubMed

Trombetta, Amelia Chiara; Meroni, Marianna; Cutolo, Maurizio

2017-01-01

From the middle of the 19th century, it is known that endocrine and immune systems interact bi-directionally in different processes that ensure organism homeostasis. Endocrine and nervous systems have a pivotal role in the balancing of pro- and anti-inflammatory functions of immune system, and constitute a complex circadian neuroendocrine network. Autoimmune diseases have in fact a complex pathogenic origin in which the importance of endocrine system was demonstrated. In this chapter, we will mention the structure and function of steroidal hormones involved in the neuroendocrine immune network and we will address the ways in which endocrine and immune systems influence each other, in a bi-directional fashion. Adrenal hormones, sex hormones, vitamin D, and melatonin and prolactin importantly all contribute to the homeostasis of the immune system. Indeed, some of the steroidal hormone activities determine inhibition or stimulation of immune system components, in both physiological (i.e. suppression of an unwanted response in pregnancy, or stimulation of a protective response in infections) and pathological conditions. We will finally mention the rationale for optimization of exogenous administration of glucocorticoids in chronic autoimmune diseases, and the latest developments concerning these drugs. © 2017 S. Karger AG, Basel.

Association Between Circulating Levels of Sex Steroid Hormones and Barrett's Esophagus in Men: a Case–Control Analysis

PubMed Central

Cook, Michael B.; Wood, Shannon N.; Cash, Brooks D.; Young, Patrick; Acosta, Ruben D.; Falk, Roni T.; Pfeiffer, Ruth M.; Hu, Nan; Su, Hua; Wang, Lemin; Wang, Chaoyu; Gherman, Barbara; Giffen, Carol; Dykes, Cathy; Turcotte, Veronique; Caron, Patrick; Guillemette, Chantal; Dawsey, Sanford M.; Abnet, Christian C.; Hyland, Paula L.; Taylor, Philip R.

2014-01-01

Background & Aims Esophageal adenocarcinoma is believed to result from the progression of gastroesophageal reflux disease to erosive esophagitis and re-epithelialization of the esophagus with a columnar cell population termed Barrett's esophagus (BE). Men develop BE and esophageal adenocarcinoma more frequently than women, and the ratio is increasing; approximately 7 men are diagnosed with malignancy for every woman, yet little is known about the mechanisms of this difference. We assessed whether sex steroid hormones were associated with BE in a male population. Methods We analyzed data from the Barrett's Esophagus Early Detection Case Control Study, based at the Walter Reed National Military Medical Center. Blood samples were collected from 173 men with BE and 213 men without BE (controls, based on endoscopic analysis); 13 sex steroid hormones were measured by mass spectrometry and sex hormone binding globulin was measured by ELISA. We also calculated free estradiol, free testosterone and free dihydrotestosterone (DHT). We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, race, smoking status, alcohol consumption, body mass index (BMI; kg/m2), heartburn, regurgitation, and gastroesophageal symptom score (excluding heartburn and regurgitation). Results Levels of free testosterone and free DHT were positively associated with BE risk; patients in the highest quartile for these hormones were most likely to have BE (for free testosterone, OR=5.36; 95% CI, 2.21–13.03; P=0.0002 and for free DHT, OR=4.25, 95% CI, 1.87–9.66; P=.001). Level of estrone sulfate was inversely associated with BE risk (P for trend=.02). No other hormone was associated with BE risk. Relationships were not modified by age or BMI. Conclusions In an analysis of men, levels of free testosterone and free DHT were significantly associated with risk of BE. PMID:25158929

Effect of Sex Differences on Brain Mitochondrial Function and Its Suppression by Ovariectomy and in Aged Mice.

PubMed

Gaignard, Pauline; Savouroux, Stéphane; Liere, Philippe; Pianos, Antoine; Thérond, Patrice; Schumacher, Michael; Slama, Abdelhamid; Guennoun, Rachida

2015-08-01

Sex steroids regulate brain function in both normal and pathological states. Mitochondria are an essential target of steroids, as demonstrated by the experimental administration of 17β-estradiol or progesterone (PROG) to ovariectomized female rodents, but the influence of endogenous sex steroids remains understudied. To address this issue, mitochondrial oxidative stress, the oxidative phosphorylation system, and brain steroid levels were analyzed under 3 different experimental sets of endocrine conditions. The first set was designed to study steroid-mediated sex differences in young male and female mice, intact and after gonadectomy. The second set concerned young female mice at 3 time points of the estrous cycle in order to analyze the influence of transient variations in steroid levels. The third set involved the evaluation of the effects of a permanent decrease in gonadal steroids in aged male and female mice. Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.

Sex steroids, the insulin-like growth factor regulatory system, and aging: implications for the management of older postmenopausal women.

PubMed

Rosen, C J; Glowacki, J; Craig, W

1998-01-01

Aging is associated with profound changes in the growth hormone/insulin-like growth factor (IGF) regulatory system. These include reductions in growth hormone, IGF-I, IGFBP3, and IGFBP-5 and an increase in IGFBP-4. These changes, coupled with rather marked declines in sex steroid production from both the ovary and adrenals may combine to have very deleterious effects on several organ systems in the postmenopausal woman. In particular, the prevalence of two very common diseases, osteoporosis and coronary artery disease, increase dramatically after the cessation of gonadal steroid production. The complex interrelationship between the IGF regulatory system and estrogens/androgens in the postmenopausal period may provide important clues as to the pathophysiology of both these disorders. In this paper, we begin to define the role of IGF-I (and its constituent IGF binding proteins) in skeletal and vascular tissue. Recent experimental data show the effects of estrogen on circulating and tissue IGFs in older individuals. Finally, estrogen replacement therapy affects the IGF regulatory system in postmenopausal women. Although conclusions from early studies remain somewhat preliminary, it is likely that the IGF regulatory system will be a prime target for future studies into the pathogenesis of several age and sex hormone related degenerative disorders.

Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome.

PubMed

Chakrabarti, B; Dudbridge, F; Kent, L; Wheelwright, S; Hill-Cawthorne, G; Allison, C; Banerjee-Basu, S; Baron-Cohen, S

2009-06-01

Genetic studies of autism spectrum conditions (ASC) have mostly focused on the "low functioning" severe clinical subgroup, treating it as a rare disorder. However, ASC is now thought to be relatively common ( approximately 1%), and representing one end of a quasi-normal distribution of autistic traits in the general population. Here we report a study of common genetic variation in candidate genes associated with autistic traits and Asperger syndrome (AS). We tested single nucleotide polymorphisms in 68 candidate genes in three functional groups (sex steroid synthesis/transport, neural connectivity, and social-emotional responsivity) in two experiments. These were (a) an association study of relevant behavioral traits (the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ)) in a population sample (n=349); and (b) a case-control association study on a sample of people with AS, a "high-functioning" subgroup of ASC (n=174). 27 genes showed a nominally significant association with autistic traits and/or ASC diagnosis. Of these, 19 genes showed nominally significant association with AQ/EQ. In the sex steroid group, this included ESR2 and CYP11B1. In the neural connectivity group, this included HOXA1, NTRK1, and NLGN4X. In the socio-responsivity behavior group, this included MAOB, AVPR1B, and WFS1. Fourteen genes showed nominally significant association with AS. In the sex steroid group, this included CYP17A1 and CYP19A1. In the socio-emotional behavior group, this included OXT. Six genes were nominally associated in both experiments, providing a partial replication. Eleven genes survived family wise error rate (FWER) correction using permutations across both experiments, which is greater than would be expected by chance. CYP11B1 and NTRK1 emerged as significantly associated genes in both experiments, after FWER correction (P<0.05). This is the first candidate-gene association study of AS and of autistic traits. The most promising candidate genes require independent

Sex steroid receptors and apoptosis-related proteins are differentially expressed in polycystic ovaries of adult dogs.

PubMed

Chuffa, Luiz Gustavo de Almeida; Lupi Júnior, Luiz Antonio; da Maia Lima, Alfredo Feio

2016-02-01

In Polycystic Ovaries (PCOs), the dynamics of sex hormone receptors and follicle-related apoptotic signaling remain unknown. In this study, we investigated the expression of androgen receptors (AR), estrogen receptors (ERα and ERβ), and apoptosis-related molecules (BAX, active caspase-3, Bcl-2 and Survivin) on different follicular stages of PCOs in adult dogs. Clinical evidences of high estradiol and testosterone levels, persistent estrus and vaginal discharge were observed. Inhibin B immunolabeling was increased in primary and 2 to 5-mm follicles, and a marked epithelial hyperplasia was common in the ovarian surface. Ovarian epithelia and primary follicles showed low expression of AR, ERα, and ERβ, whereas a moderate immunoexpression of AR was found in theca cells of secondary follicles and cysts. In PCOs, growing follicles displayed ERα expression, and secondary follicles exhibited higher ERβ expression. In addition, while few ERα-positive cells were found in the cysts, ERβ was moderately expressed in growing follicles and cysts. BAX was upregulated in the ovarian epithelium, primary follicles, and in the wall of follicular cysts. Active caspase-3 was significantly downregulated in the epithelium, primary follicles, and follicular cysts, whereas growing follicles had a strong immunoexpression in the granulosa cells. Bcl-2 and survivin were increased in the epithelium and primary follicles, and only survivin was upregulated in secondary and growing follicles. While Bcl-2 had a diffuse immunexpression in the follicular cysts, survivin was overexpressed by these cells. We concluded that sex steroid receptors and apoptotic proteins are differentially expressed in the follicles of adult dogs with PCOs. Copyright © 2015 Elsevier Ltd. All rights reserved.

The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development

PubMed Central

Schulz, Kalynn M.; Sisk, Cheryl L.

2016-01-01

Adolescence is a developmental period characterized by dramatic changes in cognition, risk-taking and social behavior. Although gonadal steroid hormones are well-known mediators of these behaviors in adulthood, the role gonadal steroid hormones play in shaping the adolescent brain and behavioral development has only come to light in recent years. Here we discuss the sex-specific impact of gonadal steroid hormones on the developing adolescent brain. Indeed, the effects of gonadal steroid hormones during adolescence on brain structure and behavioral outcomes differs markedly between the sexes. Research findings suggest that adolescence, like the perinatal period, is a sensitive period for the sex-specific effects of gonadal steroid hormones on brain and behavioral development. Furthermore, evidence from studies on male sexual behavior suggests that adolescence is part of a protracted postnatal sensitive period that begins perinatally and ends following adolescence. As such, the perinatal and peripubertal periods of brain and behavioral organization likely do not represent two discrete sensitive periods, but instead are the consequence of normative developmental timing of gonadal hormone secretions in males and females. PMID:27497718

Sleep, Rhythms, and the Endocrine Brain: Influence of Sex and Gonadal Hormones

PubMed Central

Mong, Jessica A.; Baker, Fiona C.; Mahoney, Megan M.; Paul, Ketema N.; Schwartz, Michael D.; Semba, Kazue; Silver, Rae

2011-01-01

While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master “circadian clock” within the suprachiasmatic nucleus (SCN), modulate photic effects on activity in males points to novel mechanisms of circadian control. Work in aromatase deficient (ArKO) mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a mini-symposium at the 2011 annual meeting of the Society for Neuroscience. PMID:22072663

Symmetry adapted cluster-configuration interaction calculation of the photoelectron spectra of famous biological active steroids

NASA Astrophysics Data System (ADS)

Abyar, Fatemeh; Farrokhpour, Hossein

2014-11-01

The photoelectron spectra of some famous steroids, important in biology, were calculated in the gas phase. The selected steroids were 5α-androstane-3,11,17-trione, 4-androstane-3,11,17-trione, cortisol, cortisone, corticosterone, dexamethasone, estradiol and cholesterol. The calculations were performed employing symmetry-adapted cluster/configuration interaction (SAC-CI) method using the 6-311++G(2df,pd) basis set. The population ratios of conformers of each steroid were calculated and used for simulating the photoelectron spectrum of steroid. It was found that more than one conformer contribute to the photoelectron spectra of some steroids. To confirm the calculated photoelectron spectra, they compared with their corresponding experimental spectra. There were no experimental gas phase Hesbnd I photoelectron spectra for some of the steroids of this work in the literature and their calculated spectra can show a part of intrinsic characteristics of this molecules in the gas phase. The canonical molecular orbitals involved in the ionization of each steroid were calculated at the HF/6-311++g(d,p) level of theory. The spectral bands of each steroid were assigned by natural bonding orbital (NBO) calculations. Knowing the electronic structures of steroids helps us to understand their biological activities and find which sites of steroid become active when a modification is performing under a biological pathway.

The relationship between pubertal gynecomastia, prostate specific antigen, free androgen index, SHBG and sex steroids.

PubMed

Kilic, Mustafa; Kanbur, Nuray; Derman, Orhan; Akgül, Sinem; Kutluk, Tezer

2011-01-01

To investigate the relationships between pubertal gynecomastia, prostate-specific antigen (PSA), free androgen index (FAI), sex hormone-binding globulin (SHBG) and sex steroids. A total of 61 male adolescents (10-17 years old; mean: 13.67 +/- 1.08) with gynecomastia were enrolled into the study group. A total of 65 healthy age-matched adolescents were included in the control group. Body mass index (BMI), Tanner staging, testis volume, stretched penis length (SPL) and bone age were evaluated. Serum follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), testosterone, free testosterone, SHBG, PSA levels were determined and FAI was calculated. In the study group, free testosterone (p = 0.012) and FAI (p = 0.05) were significantly lower than the control group. In the control group, SHBG levels decreased (p < 0.05) and FAI increased (p < 0.05) significantly with increasing Tanner stages; however, no such difference was observed in the study group (p > 0.05). High FAI was found to decrease the risk of gynecomastia (odds ratio: 0.211, 95% confidence interval: 0.064-0.694, p = 0.01). PSA showed a positive correlation with FAI, free testosterone, Tanner staging, testosterone, E2 and LH levels. PSA is a good indicator of androgen activity during puberty. However, owing to FAI remaining as the single significant variable for pubertal gynecomastia, we suggest that it is still the best parameter to elucidate the etiopathogenesis of gynecomastia as well as other pubertal developmental abnormalities in male adolescents, and further longitudinal studies are needed to investigate the relationships between PSA and FAI in puberty.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons.

PubMed

Nodari, Francesco; Hsu, Fong-Fu; Fu, Xiaoyan; Holekamp, Terrence F; Kao, Lung-Fa; Turk, John; Holy, Timothy E

2008-06-18

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is essentially unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost >80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly sized stimulus set containing the majority of all previously reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knock-outs for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons

PubMed Central

Nodari, Francesco; Hsu, Fong-Fu; Fu, Xiaoyan; Holekamp, Terrence F.; Kao, Lung-Fa; Turk, John; Holy, Timothy E.

2009-01-01

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is largely unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost more than 80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly-sized stimulus set containing the majority of all previously-reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knockouts for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many-fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice. PMID:18562612

Are sex steroids involved in the sexual growth dimorphism in Eurasian perch juveniles?

PubMed

Mandiki, S N M; Houbart, M; Babiak, I; Vandeloise, E; Gardeur, J N; Kestemont, P

2004-02-01

Individual growth and food intake were monitored in Eurasian perch (Perca fluviatilis L.) juveniles (13.5+/-3.4 g initial body weight) to determine whether androgens and estrogens may mediate sex-related growth differences. Fish were individually tagged with chips and implanted with cocoa butter containing 20 microg of either 17alpha-methyltestosterone (MT) or 17beta-estradiol (E(2)) per gram of fish body; controls were implanted with cocoa butter without hormones. All fish were bled at the end of the experiment for measurement of E(2) in females and testosterone (T) in males (MT was not measured) and triiodothyronine (T3) in both genders. Survival, gonadosomatic index and hepatosomatic index were not affected by steroid treatments. Relative food intake (RFI), feed efficiency (FE) and specific growth rate (SGR) were higher in females than in males in all treatments. MT treatment significantly lowered RIF, FE and SGR in both sexes, while E(2) treatment showed no significant effect on growth and feeding parameters. In contrast to E(2) and T concentrations, T3 levels were significantly and positively correlated with SGR and RFI. The results provide evidence that MT may affect sexually related growth dimorphism by decreasing food intake and FE in Eurasian perch.

Steroid Assays in Paediatric Endocrinology

PubMed Central

2010-01-01

Most steroid disorders of the adrenal cortex come to clinical attention in childhood and in order to investigate these problems, there are many challenges to the laboratory which need to be appreciated to a certain extent by clinicians. The analysis of sex steroids in biological fluids from neonates, over adrenarche and puberty present challenges of specificities and concentrations often in small sample sizes. Different reference ranges are also needed for interpretations. For around 40 years, quantitative assays for the steroids and their regulatory peptide hormones have been possible using immunoassay techniques. Problems are recognised and this review aims to summarise the benefits and failings of immunoassays and introduce where tandem mass spectrometry is anticipated to meet the clinical needs for steroid analysis in paediatric endocrine investigations. It is important to keep a dialogue between clinicians and the laboratory, especially when any laboratory result does not make sense in the clinical investigation. Conflict of interest:None declared. PMID:21274330

Structure-activity relationship (SAR) analysis of a family of steroids acutely controlling steroidogenesis.

PubMed

Midzak, Andrew; Rammouz, Georges; Papadopoulos, Vassilios

2012-11-01

Steroids metabolically derive from lipid cholesterol, and vertebrate steroids additionally derive from the steroid pregnenolone. Pregnenolone is derived from cholesterol by hydrolytic cleavage of the aliphatic tail by mitochondrial cytochrome P450 enzyme CYP11A1, located in the inner mitochondrial membrane. Delivery of cholesterol to CYP11A1 comprises the principal control step of steroidogenesis, and requires a series of proteins spanning the mitochondrial double membranes. A critical member of this cholesterol translocation machinery is the integral outer mitochondrial membrane translocator protein (18kDa, TSPO), a high-affinity drug- and cholesterol-binding protein. The cholesterol-binding site of TSPO consists of a phylogenetically conserved cholesterol recognition/interaction amino acid consensus (CRAC). Previous studies from our group identified 5-androsten-3β,17,19-triol (19-Atriol) as drug ligand for the TSPO CRAC motif inhibiting cholesterol binding to CRAC domain and steroidogenesis. To further understand 19-Atriol's mechanism of action as well as the molecular recognition by the TSPO CRAC motif, we undertook structure-activity relationship (SAR) analysis of the 19-Atriol molecule with a variety of substituted steroids oxygenated at positions around the steroid backbone. We found that in addition to steroids hydroxylated at carbon C19, hydroxylations at C4, C7, and C11 contributed to inhibition of cAMP-mediated steroidogenesis in a minimal steroidogenic cell model. However, only substituted steroids with C19 hydroxylations exhibited specificity to TSPO, its CRAC motif, and mitochondrial cholesterol transport, as the C4, C7, and C11 hydroxylated steroids inhibited the metabolic transformation of cholesterol by CYP11A1. We thus provide new insights into structure-activity relationships of steroids inhibiting mitochondrial cholesterol transport and steroidogenic cholesterol metabolic enzymes. Copyright © 2012 Elsevier Inc. All rights reserved.

Seasonal and sex-related variations in serum steroid hormone levels in wild and farmed brown trout Salmo trutta L. in the north-west of Spain.

PubMed

Fregeneda-Grandes, Juan M; Hernández-Navarro, Salvador; Fernandez-Coppel, Ignacio A; Correa-Guimaraes, Adriana; Ruíz-Potosme, Norlan; Navas-Gracia, Luis M; Aller-Gancedo, J Miguel; Martín-Gil, Francisco J; Martín-Gil, Jesús

2013-12-01

Serum steroid profiles were investigated in order to evaluate the potential use of circulating sex steroid levels as a tool for sex identification in brown trout. Changes in the serum concentrations of testosterone (T), progesterone (P), 17-β-estradiol (E2), and cortisol (F) in wild and farmed mature female and male brown trout, Salmo trutta L., were measured in each season (January, May, July, and October) in six rivers and four hatcheries located in the north-west of Spain. Serum cortisol levels in farmed brown trout were significantly higher and showed a seasonal pattern opposite to that found in wild trout. Because levels of the hormones under study can be affected by disruptive factors such as exposure to phytoestrogens (which alters the hypothalamic-pituitary-gonadal axis) and infection with Saprolegnia parasitica (which alters the hypothalamic-pituitary-adrenal axis), both factors are taken into account.

The effect of glucocorticoids on sex steroid synthesis in cultured Taenia crassiceps Wake Forest University (WFU) cysticerci.

PubMed

Hinojosa, L; Valdez, R A; Salvador, V; Rodríguez, A G; Willms, K; Romano, M C

2012-12-01

We have shown previously that cultured Taenia crassiceps Wake Forest University (WFU) and Taenia solium cysticerci, as well as the adult worms, synthesize sex steroid hormones from [3H]steroid precursors and that androgens and oestrogens influence the in vitro development of the parasites. Glucocorticoids (GCs) are used to control the inflammation caused by T. solium cysticerci in the brain. These steroids stimulate oestrogen synthesis in several tissues. Since there is no information on the effect of GC on the endocrine function of cysticerci, we investigated the effect of natural and synthetic GCs on the synthesis of oestrogens in cultured T. crassiceps WFU cysticerci. The cysticerci were obtained from the peritoneal cavity of infected female BALB/c mice; the cysts were washed extensively and pre-cultured in Dulbecco's Modified Eagle's Medium (DMEM) plus antibiotics for 5 days. The parasites were further cultured with different doses of corticosterone, dexamethasone or the vehicle for 5 days. [3H]Dehydroepiandrosterone (3H-DHEA) was added to the media and the cysticerci were further incubated for 6 or 24 h. Media were then removed and the steroids ether-extracted. Aliquots of the media were seeded on silica gel plates and developed in solvent systems. Parasites incubated in the presence of 3H-DHEA synthesized [3H]androstenediol, [3H]testosterone and [3H]17β-oestradiol ([3H]17β-E2). The addition of 100 nm or higher corticosterone doses to the media increased [3H]17β-E2 synthesis fourfold after 24 h. Dexamethasone also increased [3H]17β-E2 synthesis. The experiments presented here show for the first time that corticosterone and the synthetic GC dexamethasone modulate the synthesis of oestrogens by cysticerci.

The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development.

PubMed

Schulz, Kalynn M; Sisk, Cheryl L

2016-11-01

Adolescence is a developmental period characterized by dramatic changes in cognition, risk-taking and social behavior. Although gonadal steroid hormones are well-known mediators of these behaviors in adulthood, the role gonadal steroid hormones play in shaping the adolescent brain and behavioral development has only come to light in recent years. Here we discuss the sex-specific impact of gonadal steroid hormones on the developing adolescent brain. Indeed, the effects of gonadal steroid hormones during adolescence on brain structure and behavioral outcomes differs markedly between the sexes. Research findings suggest that adolescence, like the perinatal period, is a sensitive period for the sex-specific effects of gonadal steroid hormones on brain and behavioral development. Furthermore, evidence from studies on male sexual behavior suggests that adolescence is part of a protracted postnatal sensitive period that begins perinatally and ends following adolescence. As such, the perinatal and peripubertal periods of brain and behavioral organization likely do not represent two discrete sensitive periods, but instead are the consequence of normative developmental timing of gonadal hormone secretions in males and females. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative structure activity relationships from optimised ab initio bond lengths: steroid binding affinity and antibacterial activity of nitrofuran derivatives

NASA Astrophysics Data System (ADS)

Smith, P. J.; Popelier, P. L. A.

2004-02-01

The present day abundance of cheap computing power enables the use of quantum chemical ab initio data in Quantitative Structure-Activity Relationships (QSARs). Optimised bond lengths are a new such class of descriptors, which we have successfully used previously in representing electronic effects in medicinal and ecological QSARs (enzyme inhibitory activity, hydrolysis rate constants and pKas). Here we use AM1 and HF/3-21G* bond lengths in conjunction with Partial Least Squares (PLS) and a Genetic Algorithm (GA) to predict the Corticosteroid-Binding Globulin (CBG) binding activity of the classic steroid data set, and the antibacterial activity of nitrofuran derivatives. The current procedure, which does not require molecular alignment, produces good r2 and q2 values. Moreover, it highlights regions in the common steroid skeleton deemed relevant to the active regions of the steroids and nitrofuran derivatives.

The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens.

PubMed

Salerni, Sara; Di Francescomarino, Samanta; Cadeddu, Christian; Acquistapace, Flavio; Maffei, Silvia; Gallina, Sabina

2015-06-01

Human response to different physiologic stimuli and cardiovascular (CV) adaptation to various pathologies seem to be gender specific. Sex-steroid hormones have been postulated as the major contributors towards these sex-related differences. This review will discuss current evidence on gender differences in CV function and remodelling, and will present the different role of the principal sex-steroid hormones on female heart. Starting from a review of sex hormones synthesis, receptors and CV signalling, we will summarize the current knowledge concerning the role of sex hormones on the regulation of our daily activities throughout the life, via the modulation of autonomic nervous system, excitation-contraction coupling pathway and ion channels activity. Many unresolved questions remain even if oestrogen effects on myocardial remodelling and function have been extensively studied. So this work will focus attention also on the controversial and complex relationship existing between androgens, progesterone and female heart. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus.

PubMed

Kimoto, Tetsuya; Ishii, Hirotaka; Higo, Shimpei; Hojo, Yasushi; Kawato, Suguru

2010-12-01

Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.

Plasma sex-steroid binding protein in a seasonally breeding reptile, Alligator mississippiensis.

PubMed

Ho, S M; Lance, V; Megaloudis, M

1987-01-01

The properties of a sex-steroid binding protein (SSBP) in the plasma of the American alligator, Alligator mississippiensis, were partially characterized. Alligator SSBP has a sedimentation coefficient of 4S in a 5-20% sucrose gradient. It binds to estradiol-17 beta (E2) and testosterone (T) with limited capacities and moderate affinities (association constant for [3H]E2 is 4.70 +/- 0.09 X 10(8) M-1 and for [3H]T is 1.05 +/- 0.07 X 10(8) M-1, mean +/- SEM of six determinations). Plasma SSBP level, as measured by plasma [3H]E2 binding capacity, varies from 30 to 140 nmol per liter plasma (nM) and was found to be dependent on the gender, sexual maturity, and reproductive state of the animal. Distinct annual fluctuations in plasma SSBP level were observed in female alligators. In adult females, plasma SSBP levels were high (122 +/- 6 nM) in the fall during the nonbreeding season and low (30-60 nM) in spring and early summer during the breeding season. A minimum (33 +/- 6 nM) was reached in mid-June coinciding with the time of oviposition and rapid decline in circulating estrogen levels. This decline in adult female plasma SSBP levels during the breeding season was not observed in immature females. On the contrary, plasma SSBP levels in immature females increased from 81 +/- 14 nM in April to 134 +/- 9 nM in June. Plasma SSBP levels in male alligators showed little changes throughout the entire breeding season; they remained within the range of 80-100 nM from March to June. We believe that seasonal fluctuations in plasma SSBP levels constitute part of the mechanism involved in the regulation of free steroid delivered to target organs in female alligators and that such a mechanism does not exist in male animals.

Neuroendocrine correlates of sex-role reversal in barred buttonquails

PubMed Central

2016-01-01

Sex differences in brain structure and behaviour are well documented among vertebrates. An excellent model exploring the neural mechanisms of sex differences in behaviour is represented by sex-role-reversed species. In the majority of bird species, males compete over access to mates and resources more strongly than do females. It is thought that the responsible brain regions are therefore more developed in males than in females. Because these behaviours and brain regions are activated by androgens, males usually have increased testosterone levels during breeding. Therefore, in species with sex-role reversal, certain areas of the female brain should be more developed or steroid hormone profiles should be sexually reversed. Here, I studied circulating hormone levels and gene expression of steroid hormone receptors and aromatase in a captive population of barred buttonquails (Turnix suscitator). While females performed courtship and agonistic behaviours, there was no evidence for sexually reversed hormone profiles. However, I found female-biased sex differences in gene expression of androgen receptors in several hypothalamic and limbic brain regions that were already in place at hatching. Such sex differences are not known from non-sex-role-reversed species. These data suggest that increased neural sensitivity to androgens could be involved in the mechanisms mediating sex-role-reversed behaviours. PMID:27881754

Brain nonapeptide and gonadal steroid responses to deprivation of heterosexual contact in the black molly

PubMed Central

Kulczykowska, Ewa; Kalamarz-Kubiak, Hanna; Nietrzeba, Marta; Gozdowska, Magdalena

2015-01-01

ABSTRACT Fish may respond to different social situations with changes in both physiology and behaviour. A unique feature of fish is that social interactions between males and females strongly affect the sexual characteristics of individuals. Here we provide the first insight into the endocrine background of two phenomena that occur in mono-sex groups of the black molly (Poecilia sphenops): masculinization in females and same-sex sexual behaviour, manifested by gonopodial displays towards same-sex tank mates and copulation attempts in males. In socially controlled situations, brain neurohormones impact phenotypic sex determination and sexual behaviour. Among these hormones are the nonapeptides arginine vasotocin (AVT) and isotocin (IT), counterparts of the well-known mammalian arginine vasopressin and oxytocin, respectively. To reveal potential hormone interactions, we measured the concentrations of bioactive AVT and IT in the brain, along with those of the sex steroids 17β-estradiol and 11-ketotestosterone in the gonads, of females, masculinized females, males displaying same-sex sexual behaviour and those who did not. These data were supplemented by morphological and histological analyses of the gonads. Correlations between brain nonapeptides and gonadal steroids strongly suggest a cross talk between hormonal systems. In the black molly, the masculinization process was associated with the production of brain AVT and gonadal steroids, whereas same-sex sexual behaviour involves both brain nonapeptides, but neither of the sex steroids. This study extends current knowledge of endocrine control of phenotypic sex and sexual behaviour in fish and for the first time links brain nonapeptides with the occurrence of male-male sexual behaviour in lower vertebrates. PMID:25527645

Structural characterization of sulfated steroids that activate mouse pheromone-sensing neurons.

PubMed

Hsu, Fong-Fu; Nodari, Francesco; Kao, Lung-Fa; Fu, Xiaoyan; Holekamp, Terrence F; Turk, John; Holy, Timothy E

2008-12-30

In many species, social behavior is organized via chemical signaling. While many of these signals have been identified for insects, the chemical identity of these social cues (often called pheromones) for mammals is largely unknown. We recently isolated these chemical cues that caused firing in the pheromone-sensing neurons of the vomeronasal organ from female mouse urine [Nodari, F., et al. (2008) J. Neurosci. 28, 6407-6418]. Here, we report their structural characterization. Mass spectrometric approaches, including tandem quadrupole, multiple-stage linear ion trap, high-resolution mass spectrometry, and H-D exchange followed by ESI mass spectrometry, along with (1)H and (13)C nuclear magnetic resonance spectroscopy, including two-dimensional correlation spectroscopy, total correlation spectroscopy, heteronuclear multiple-quantum coherence, and NOE, were used to identify two sulfated steroids, 4-pregnene-11beta,20,21-triol-3-one 21-sulfate (I) (the configuration at C20 was not deduced) and 4-pregnene-11beta,21-diol-3,20-dione 21-sulfate (II), whose presence is sex-specific. The identification of this novel class of mammalian social signaling compounds suggests that steroid hormones, upon conjugation, assume a new biological role, conveying information about the organism's identity and physiological state.

Role of sex steroids in progesterone and corticosterone response to acute restraint stress in rats: sex differences.

PubMed

Kalil, B; Leite, C M; Carvalho-Lima, M; Anselmo-Franci, J A

2013-07-01

Adrenal progesterone secretion increases along with corticosterone in response to stress in male and female rats to modulate some stress responses. Here we investigated the role of sex steroids in sex differences in the progesterone response to 60 min of restraint stress in adult male and female rats. Comparisons between males and females in the progesterone response were evaluated in parallel with corticosterone responses. From day 5 to 7 after gonadectomy, female and male rats were treated with estradiol or testosterone, respectively (OVX-E and ORCH-T groups), or oil (OVX and ORCH groups). Female rats in proestrus, intact and 7 d adrenalectomized (ADX) male rats were also studied. At 10:00 h, blood samples were withdrawn via an implanted jugular cannula before (-5 min), during (15, 30, 45, 60 min) and after (90 and 120 min) restraint stress to measure plasma progesterone and corticosterone concentrations by radioimmunoassay. Intact male and proestrus female rats exhibited similar progesterone responses to stress. Gonadectomy did not alter the amount of progesterone secreted during stress in female rats but decreased secretion in male rats. Unlike corticosterone, the progesterone response to stress in females was not influenced by estradiol. In males, testosterone replacement attenuated the progesterone and corticosterone responses to stress. Basal secretion of progesterone among intact, ORCH and ADX males was similar, but ADX-stressed rats secreted little progesterone. Hence, the gonads differently modulate adrenal progesterone and corticosterone responses to stress in female and male rats. The ovaries enhance corticosterone but not progesterone secretion, while the testes stimulate progesterone but not corticosterone secretion.

The moderating impact of lifestyle factors on sex steroids, sexual activities and aging in Asian men.

PubMed

Goh, Victor H H; Tong, Terry Y Y

2011-07-01

The present study sought to evaluate the relative associations of exercise, sleep and other lifestyle habits with aging, sex hormones, percent body fat (%BF) and sexual activities in men living in the community. A better understanding of this complex interrelationship is important in helping the formulation of modalities for a holistic approach to the management of aging men. The results showed that age is a major determinant for many physiological parameters, including sleep, hormonal and metabolic parameters, some lifestyle factors and sexual activities. Testosterone (T), bioavailable testosterone (BioT) and dehydroepiandrosterone sulphate (DHEAS) concentrations decreased with age, while estradiol (E2), sex hormone-binding globulin (SHBG) and %BF increased with age. In addition, there exist intricate associations among hormonal and lifestyle factors, %BF and age. High-intensity exercise and longer duration of sleep were associated with higher concentrations of T and BioT. T was shown to be associated positively with men who were engaged in masturbation. DHEAS was associated with men wanting more sex and with good morning penile rigidity. Older Singaporean men tended to sleep for shorter duration, but exercised more intensely than younger men. Coital and masturbation frequencies decreased with age, and a significantly greater number of younger men were engaged in masturbation. Relationship between the partners is a key determinant of sexuality in men. It appears that T may have a limited, while dehydroepiandrosterone (DHEA) have a greater role than previously suggest, as a motivational signal for sexual function in men. Both biological and psychosocial factors interact with each other to influence sexual functions in men. Hence, a biopsychosocial approach may be more appropriate for a more lasting resolution to sexual dysfunctions in men.

Morphology, sex steroid level and gene expression analysis in gonadal sex reversal of triploid female (XXX) rainbow trout (Oncorhynchus mykiss).

PubMed

Xu, Gefeng; Huang, Tianqing; Jin, Xian; Cui, Cunhe; Li, Depeng; Sun, Cong; Han, Ying; Mu, Zhenbo

2016-02-01

In non-mammalian vertebrates, estrogens and expressions of cyp19a1 and foxl2 play critical roles in maintaining ovary differentiation and development, while dmrt1 and sox9 are male-specific genes in testicular differentiation and are highly conserved. In order to deeply understand the morphological change, sex steroids level and molecular mechanism of triploid female gonadal reversal in rainbow trout, we studied the ovary morphology, tendency of estradiol-17β (E2) and testosterone (T) levels and the relative expressions of dmrt1, cyp19a1, sox9 and foxl2 in juvenile and adult fish. Our results demonstrated that the development of triploid female gonads in rainbow trout went through arrested development, oocytes dedifferentiation, ovary reconstruction and sex reversal finally. During early gonadal development (154-334 days post-fertilization), the expressions of foxl2 and cyp19a1 increased linearly, while expressions of dmrt1 and sox9 were extremely suppressed, and E2 level was higher, while T level was lower. During the mid-to-late period of triploid female gonadal development (574-964 days post-fertilization), the expressions of dmrt1 and sox9 remained high and were very close to the quantity of diploid male genes, and T levels were even reaching diploid male plasma concentrations, while expressions of cyp19a1 and foxl2 were decreased, leading to decrease in E2 level. We realized that the development model of rainbow trout triploid female gonads was extremely rare, and the regulatory mechanism was very special. Genes involved in gonadal development and endogenous estrogens are pivotal factors in fish natural sex reversal.

Do changes in sex steroid hormones precede or follow increases in body weight during the menopause transition? Results from the Study of Women's Health Across the Nation.

PubMed

Wildman, Rachel P; Tepper, Ping G; Crawford, Sybil; Finkelstein, Joel S; Sutton-Tyrrell, Kim; Thurston, Rebecca C; Santoro, Nanette; Sternfeld, Barbara; Greendale, Gail A

2012-09-01

Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. The objective of the study was to characterize the potential reciprocal nature of the associations between sex hormones and their binding protein with waist circumference in midlife women. The study included 1528 women (mean age 46 yr) with 9 yr of follow-up across the menopause transition from the observational Study of Women's Health Across the Nation. Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. Current waist circumference predicted future SHBG, testosterone, and FSH but not vice versa. For each SD higher current waist circumference, at the subsequent visit SHBG was lower by 0.04-0.15 SD, testosterone was higher by 0.08-0.13 SD, and log(2) FSH was lower by 0.15-0.26 SD. Estradiol results were distinct from those above, changing direction across the menopause transition. Estradiol and waist circumference were negatively associated in early menopausal transition stages and positively associated in later transition stages (for each SD higher current waist circumference, future estradiol was lower by 0.15 SD in pre- and early perimenopause and higher by 0.38 SD in late peri- and postmenopause; P for interaction <0.001). In addition, they appeared to be reciprocal, with current waist circumference associated with future estradiol and current estradiol associated with future waist circumference. However, associations in the direction of current waist circumference predicting future estradiol levels were of considerably larger magnitude than the reverse. These Study of Women's Health Across the Nation data suggest that the predominant temporal sequence is that weight gain leads to changes in sex steroids rather than vice versa.

Neuroactive steroids and PTSD treatment.

PubMed

Rasmusson, Ann M; Marx, Christine E; Pineles, Suzanne L; Locci, Andrea; Scioli-Salter, Erica R; Nillni, Yael I; Liang, Jennifer J; Pinna, Graziano

2017-05-10

This review highlights early efforts to translate pre-clinical and clinical findings regarding the role of neuroactive steroids in stress adaptation and PTSD into new therapeutics for PTSD. Numerous studies have demonstrated PTSD-related alterations in resting levels or the reactivity of neuroactive steroids and their targets. These studies also have demonstrated substantial variability in the dysfunction of specific neuroactive steroid systems among PTSD subpopulations. These variabilities have been related to the developmental timing of trauma, severity and type of trauma, genetic background, sex, reproductive state, lifestyle influences such as substance use and exercise, and the presence of comorbid conditions such as depression and chronic pain. Nevertheless, large naturalistic studies and a small placebo-controlled interventional study have revealed generally positive effects of glucocorticoid administration in preventing PTSD after trauma, possibly mediated by glucocorticoid receptor-mediated effects on other targets that impact PTSD risk, including other neuroactive steroid systems. In addition, clinical and preclinical studies show that administration of glucocorticoids, 17β-estradiol, and GABAergic neuroactive steroids or agents that enhance their synthesis can facilitate extinction and extinction retention, depending on dose and timing of dose in relation to these complex PTSD-relevant recovery processes. This suggests that clinical trials designed to test neuroactive steroid therapeutics in PTSD may benefit from such considerations; typical continuous dosing regimens may not be optimal. In addition, validated and clinically accessible methods for identifying specific neuroactive steroid system abnormalities at the individual level are needed to optimize both clinical trial design and precision medicine based treatment targeting. Copyright © 2017. Published by Elsevier B.V.

Do mollusks use vertebrate sex steroids as reproductive hormones? Part I: Critical appraisal of the evidence for the presence, biosynthesis and uptake of steroids.

PubMed

Scott, Alexander P

2012-11-01

The consensus view is that vertebrate-type steroids are present in mollusks and perform hormonal roles which are similar to those that they play in vertebrates. Although vertebrate steroids can be measured in molluscan tissues, a key question is 'Are they formed endogenously or they are picked up from their environment?'. The present review concludes that there is no convincing evidence for biosynthesis of vertebrate steroids by mollusks. Furthermore, the 'mollusk' genome does not contain the genes for key enzymes that are necessary to transform cholesterol in progressive steps into vertebrate-type steroids; nor does the mollusk genome contain genes for functioning classical nuclear steroid receptors. On the other hand, there is very strong evidence that mollusks are able to absorb vertebrate steroids from the environment; and are able to store some of them (by conjugating them to fatty acids) for weeks to months. It is notable that the three steroids that have been proposed as functional hormones in mollusks (i.e. progesterone, testosterone and 17β-estradiol) are the same as those of humans. Since humans (and indeed all vertebrates) continuously excrete steroids not just via urine and feces, but via their body surface (and, in fish, via the gills), it is impossible to rule out contamination as the sole reason for the presence of vertebrate steroids in mollusks (even in animals kept under supposedly 'clean laboratory conditions'). Essentially, the presence of vertebrate steroids in mollusks cannot be taken as reliable evidence of either endogenous biosynthesis or of an endocrine role. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

The Dynamics of Neurosteroids and Sex-Related Hormones in the Pathogenesis of Alzheimer's Disease.

PubMed

Hasanpour, Milad; Nourazarian, Alireza; Geranmayeh, Mohammad Hossein; Nikanfar, Masoud; Khaki-Khatibi, Fatemeh; Rahbarghazi, Reza

2018-05-04

Alzheimer's disease (AD) is commonly diagnosed by vast extracellular amyloid deposits and existence of intracellular neurofibrillary tangles. In accordance with the literature, age-related loss of sex steroid hormones in either males or females was found in relation to AD subjects. The dynamics of these hormones have been previously described in both physiological and pathological conditions with the evidence of changes in various intracellular signalings regarding the neurodegenerative disease. The potent protective effects of sex steroid hormones and their synthetic analogs are indicative of the decrease in the accumulated levels of intercellular beta-amyloid (Aβ) protein and an increase of specific proteases activity, resulting in the improvement of pathological features. In the current review, we focused on the dynamic of signaling pathway related to sex steroid hormones. It is logical to hypothesize that androgen hormones have regulatory actions on the kinetics of Aβ which make them as a promising preventive approach for neurodegenerative diseases in the near future.

A cross-sectional study of the association of age, race and ethnicity, and body mass index with sex steroid hormone marker profiles among men in the National Health and Nutrition Examination Survey (NHANES III)

PubMed Central

Ritchey, Jamie; Karmaus, Wilfried; Sabo-Attwood, Tara; Steck, Susan E; Zhang, Hongmei

2012-01-01

Objectives Since sex hormone markers are metabolically linked, examining sex steroid hormones singly may account for inconsistent findings by age, race/ethnicity and body mass index (BMI) across studies. First, these markers were statistically combined into profiles to account for the metabolic relationship between markers. Then, the relationships between sex steroid hormone profiles and age, race/ethnicity and BMI were explored in multinomial logistic regression models. Design Cross-sectional survey. Setting The US Third National Health and Nutrition Examination Survey (NHANES III). Participants 1538 Men, >17 years. Primary outcome measure Sex hormone profiles. Results Cluster analysis was used to identify four statistically determined profiles with Blom-transformed T, E, sex hormone binding globulin (SHBG), and 3-α diol G. We used these four profiles with multinomial logistic regression models to examine differences by race/ethnicity, age and BMI. Mexican American men >50 years were associated with the profile that had lowest T, E and 3-α diol G levels compared to other profiles (p<0.05). Non-Hispanic Black, overweight (25–29.9 kg/m2) and obese (>30 kg/m2) men were most likely to be associated with the cluster with the lowest SHBG (p<0.05). Conclusion The associations of sex steroid hormone profiles by race/ethnicity are novel, while the findings by age and BMI groups are largely consistent with observations from single hormone studies. Future studies should validate these hormone profile groups and investigate these profiles in relation to chronic diseases and certain cancers. PMID:23043125

Obesity-induced down-regulation of the mitochondrial translocator protein (TSPO) impairs placental steroid production.

PubMed

Lassance, Luciana; Haghiac, Maricela; Minium, Judi; Catalano, Patrick; Hauguel-de Mouzon, Sylvie

2015-01-01

Low concentrations of estradiol and progesterone are hallmarks of adverse pregnancy outcomes as is maternal obesity. During pregnancy, placental cholesterol is the sole source of sex steroids. Cholesterol trafficking is the limiting step in sex steroid biosynthesis and is mainly mediated by the translocator protein (TSPO), present in the mitochondrial outer membrane. The objective of the study was to investigate the effects of maternal obesity in placental sex steroid biosynthesis and TSPO regulation. One hundred forty-four obese (body mass index 30-35 kg/m(2)) and 90 lean (body mass index 19-25 kg/m(2)) pregnant women (OP and LP, respectively) recruited at scheduled term cesarean delivery. Placenta and maternal blood were collected. This study was conducted at MetroHealth Medical Center (Cleveland, Ohio). Maternal metabolic components (fasting glucose, insulin, leptin, estradiol, progesterone, and total cholesterol) and placental weight were measured. Placenta (mitochondria and membranes separated) and cord blood cholesterol values were verified. The expression and regulation of TSPO and mitochondrial function were analyzed. Plasma estradiol and progesterone concentrations were significantly lower (P < .04) in OP as compared with LP women. Maternal and cord plasma cholesterol were not different between groups. Placental citrate synthase activity and mitochondrial DNA, markers of mitochondrial density, were unchanged, but the mitochondrial cholesterol concentrations were 40% lower in the placenta of OP. TSPO gene and protein expressions were decreased 2-fold in the placenta of OP. In vitro trophoblast activation of the innate immune pathways with lipopolysaccharide and long-chain saturated fatty acids reduced TSPO expression by 2- to 3-fold (P < .05). These data indicate that obesity in pregnancy impairs mitochondrial steroidogenic function through the negative regulation of mitochondrial TSPO.

Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives.

PubMed

Khan, Salman Ahmad; Kumar, Praveen; Joshi, Rajkumar; Iqbal, Prince F; Saleem, Kishwar

2008-09-01

We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 degrees C in high yield. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR and mass spectroscopic data, to find an effective antibacterial agent. The antibacterial activity was first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds was determined. The results showed that the steroidal thiosemicarbazones derivatives inhibit growth of both types of the bacteria (Gram-positive and Gram-negative). The acetoxy and chloro derivatives of cyclopentyl and cyclohexyl amine thiosemicarbazones were found to have more antibacterial activity than the other derivatives.

Sex differences in the brain-an interplay of sex steroid hormones and sex chromosomes.

PubMed

Grgurevic, Neza; Majdic, Gregor

2016-09-01

Although considerable progress has been made in our understanding of brain function, many questions remain unanswered. The ultimate goal of studying the brain is to understand the connection between brain structure and function and behavioural outcomes. Since sex differences in brain morphology were first observed, subsequent studies suggest different functional organization of the male and female brains in humans. Sex and gender have been identified as being a significant factor in understanding human physiology, health and disease, and the biological differences between the sexes is not limited to the gonads and secondary sexual characteristics, but also affects the structure and, more crucially, the function of the brain and other organs. Significant variability in brain structures between individuals, in addition to between the sexes, is factor that complicates the study of sex differences in the brain. In this review, we explore the current understanding of sex differences in the brain, mostly focusing on preclinical animal studies. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

``Sex Hormones'' in Secondary School Biology Textbooks

NASA Astrophysics Data System (ADS)

Nehm, Ross H.; Young, Rebecca

2008-11-01

This study explores the extent to which the term “sex hormone” is used in science textbooks, and whether the use of the term “sex hormone” is associated with pre-empirical concepts of sex dualism, in particular the misconceptions that these so-called “sex hormones” are sex specific and restricted to sex-related physiological functioning. We found that: (1) all the texts employed the term “sex hormone”; (2) in all texts estrogen is characterized as restricted to females and testosterone is characterized as restricted to males; and (3) in all texts testosterone and estrogen are discussed as exclusively involved in sex-related physiological roles. We conclude that (1) contemporary science textbooks preserve sex-dualistic models of steroid hormones (one sex, one “sex hormone”) that were rejected by medical science in the early 20th century and (2) use of the term “sex hormone” is associated with misconceptions regarding the presence and functions of steroid hormones in male and female bodies.

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

PubMed

Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A

2017-08-01

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

The moderating impact of lifestyle factors on sex steroids, sexual activities and aging in Asian men

PubMed Central

Goh, Victor HH; Tong, Terry YY

2011-01-01

The present study sought to evaluate the relative associations of exercise, sleep and other lifestyle habits with aging, sex hormones, percent body fat (%BF) and sexual activities in men living in the community. A better understanding of this complex interrelationship is important in helping the formulation of modalities for a holistic approach to the management of aging men. The results showed that age is a major determinant for many physiological parameters, including sleep, hormonal and metabolic parameters, some lifestyle factors and sexual activities. Testosterone (T), bioavailable testosterone (BioT) and dehydroepiandrosterone sulphate (DHEAS) concentrations decreased with age, while estradiol (E2), sex hormone-binding globulin (SHBG) and %BF increased with age. In addition, there exist intricate associations among hormonal and lifestyle factors, %BF and age. High-intensity exercise and longer duration of sleep were associated with higher concentrations of T and BioT. T was shown to be associated positively with men who were engaged in masturbation. DHEAS was associated with men wanting more sex and with good morning penile rigidity. Older Singaporean men tended to sleep for shorter duration, but exercised more intensely than younger men. Coital and masturbation frequencies decreased with age, and a significantly greater number of younger men were engaged in masturbation. Relationship between the partners is a key determinant of sexuality in men. It appears that T may have a limited, while dehydroepiandrosterone (DHEA) have a greater role than previously suggest, as a motivational signal for sexual function in men. Both biological and psychosocial factors interact with each other to influence sexual functions in men. Hence, a biopsychosocial approach may be more appropriate for a more lasting resolution to sexual dysfunctions in men. PMID:21532602

C-reactive protein in the hemolymph of Achatina fulica: interrelationship with sex steroids and metallothionein.

PubMed

Bose, R; Bhattacharya, S

2000-04-01

C-reactive protein in Achatina fulica (ACRP) is a normal component of the hemolymph. Its concentration varied from 1mg/ml in the newly hatched male, 3-5 mg/ml in the most active hermaphrodite and 1.5-2.8 mg/ml in the sedentary female showing a direct relationship of the protein with the active phase of the animal. ACRP has a molecular mass of 400 kDa and showed high absorbance in the region of 200-230 nm. It has four subunits with relative molecular masses of 110, 90, 62 and 60 kDa, respectively. Interestingly, rat platelet aggregation in vitro was significantly enhanced by ACRP in presence of 10 microM ADP and 2 mM Ca(2+) suggesting a probable role of ACRP in the aggregation of amoebocytes during the formation of plug in injured tissue. Like other vertebrate CRPs, ACRP also acts as a scavenger of chromatin fragments as evidenced by its binding to poly-L-arginine. Among the sex steroids, 4-androstenedione induces ACRP synthesis in the newly hatched male reaching the level found in the most active hermaphrodite phase (4 mg/ml). A very high molar ratio (5) of mercury binding to ACRP confirmed its sequestration property of heavy metals as observed in vertebrates. The level of metallothionein (MT) in the hemolymph gradually increased from the male to the hermaphrodite to the female, a pattern distinctly different from that of the ACRP titer. Since both MT and ACRP can sequester inorganic mercury, the high level of MT compensates functionally for the low titer of ACRP in the sedentary female.

Cyclodextrins sequester neuroactive steroids and differentiate mechanisms that rate limit steroid actions

PubMed Central

Shu, H-J; Zeng, C-M; Wang, C; Covey, D F; Zorumski, C F; Mennerick, S

2006-01-01

Background and purpose: Neuroactive steroids are potent modulators of GABAA receptors and are thus of interest for their sedative, anxiolytic, anticonvulsant and anaesthetic properties. Cyclodextrins may be useful tools to manipulate neuroactive effects of steroids on GABAA receptors because cyclodextrins form inclusion complexes with at least some steroids that are active at the GABAA receptor, such as (3α,5α)-3-hydroxypregnan-20-one (3α5αP, allopregnanolone). Experimental approach: To assess the versatility of cyclodextrins as steroid modulators, we investigated interactions between γ-cyclodextrin and neuroactive steroids of different structural classes. Key results: Both a bioassay based on electrophysiological assessment of GABAA receptor function and optical measurements of cellular accumulation of a fluorescent steroid analogue suggest that γ-cyclodextrin sequesters steroids rather than directly influencing GABAA receptor function. Neither a 5β-reduced A/B ring fusion nor a sulphate group at carbon 3 affected the presumed inclusion complex formation between steroid and γ-cyclodextrin. Apparent dissociation constants for interactions between natural steroids and γ-cyclodexrin ranged from 10-60 μM. Although γ-cyclodextrin accommodates a range of natural and synthetic steroids, C11 substitutions reduced inclusion complex formation. Using γ-cyclodextrin to remove steroid not directly bound to GABAA receptors, we found that cellular retention of receptor-unbound steroid rate limits potentiation by 3α- hydroxysteroids but not inhibition by sulphated steroids. Conclusions and implications: We conclude that γ-cyclodextrins can be useful, albeit non-specific, tools for terminating the actions of multiple classes of naturally occurring neuroactive steroids. PMID:17160009

Steroid hormone levels associated with passive and active smoking

PubMed Central

Soldin, Offie P.; Makambi, Kepher H.; Soldin, Steven J.; O’Mara, Daniel M.

2013-01-01

Context Cigarette tobacco smoke is a potent environmental contaminant known to adversely affect health including fertility and pregnancy. Objective To examine the associations between second-hand cigarette tobacco-smoke exposure, or active smoking and serum concentrations of steroid hormones using tandem mass spectrometry. Design Healthy women (18–45 y) from the general community in the Metropolitan Washington, DC were recruited at the follicular stage of their menstrual cycle. Participants were assigned to one of three study groups: active smokers (N= 107), passive smokers (N= 86), or non-smokers (N= 100). Classifications were based on a combination of self-reporting and serum cotinine concentrations. Methods Serum androgens, estrogens, progestins, androstenedione, aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 11-deoxycortisol and 25-hydroxy-vitamin D3 (25-OHVitD3) and cotinine were measured by isotope dilution tandem mass spectrometry (LC/MS/MS) (API-5000). Kruskal–Wallis tests were used to assess median differences among the three groups, with Dunn’s multiple comparison test for post hoc analysis. Results Serum estrone, estradiol, and estriol concentrations were lower in active and passive smokers than in non-smokers. The three study groups differed significantly in serum concentrations of 16-OHE1, aldosterone and 25-OHVitD3, as well as in the ratios of many of the steroids. Pair-wise comparison of the groups demonstrated significant differences in hormone concentrations between (i) smokers and nonsmokers for aldosterone: (ii) passive smokers and non-smokers for aldosterone, progesterone and estriol. Moreover, for smokers and passive smokers, there were no significant differences in these hormone concentrations. Conclusions Smoke exposure was associated with lower than normal median steroid hormone concentrations. These processes may be instrumental in explaining some adverse effects of

Obesity and Sex Steroid Changes Across Puberty: Evidence for Marked Hyperandrogenemia in Pre- and Early Pubertal Obese Girls*

PubMed Central

McCartney, Christopher R.; Blank, Susan K.; Prendergast, Kathleen A.; Chhabra, Sandhya; Eagleson, Christine A.; Helm, Kristin D.; Yoo, Richard; Chang, R. Jeffrey; Foster, Carol M.; Caprio, Sonia; Marshall, John C.

2008-01-01

Context Peripubertal obesity is associated with abnormal sex steroid concentrations, but the timing of onset and degree of these abnormalities remain unclear. Objective To assess the degree of hyperandrogenemia across puberty in obese girls, and to assess overnight sex steroid changes in Tanner 1–3 girls. Design Cross-sectional analysis. Setting General Clinical Research Centers. Subjects Thirty normal weight (BMI-for-age < 85%) and 74 obese (BMI-for-age ≥ 95%) peripubertal girls. Intervention Blood samples (circa 0500–0700 h) while fasting. Samples from the preceding evening (circa 2300 h) were obtained in 23 Tanner 1–3 girls. Main outcome measures Hormone concentrations stratified by Tanner stage. Results Compared to normal weight girls, mean free testosterone (T) was elevated 2- to 9-fold across puberty in obese girls, while fasting insulin was 3-fold elevated in obese Tanner 1–3 girls (P < 0.05). Mean LH was lower in obese Tanner 1 and 2 girls (P < 0.05), but not in more mature girls. In a subgroup of normal weight Tanner 1–3 girls (n = 17), mean progesterone (P) and T increased overnight 2.3- and 2.4-fold, respectively (P ≤ 0.001). In obese Tanner 1–3 girls (n = 6), evening P and T were elevated, and both tended to increase overnight (mean 1.4- and 1.6-fold, respectively [P = 0.06]). Conclusions Peripubertal obesity is associated with hyperandrogenemia and hyperinsulinemia throughout puberty, being especially marked shortly before and during early puberty. Progesterone and testosterone concentrations in normal weight Tanner 1–3 girls increase overnight, with similar but less evident changes in obese girls. PMID:17118995

Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease

PubMed Central

Yacyshyn, B R; Chey, W Y; Goff, J; Salzberg, B; Baerg, R; Buchman, A L; Tami, J; Yu, R; Gibiansky, E; Shanahan, W R

2002-01-01

Background and aims: To evaluate the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) in Crohn's disease. Methods: Active (Crohn's disease activity index (CDAI) 200–350), steroid dependent (prednisone 10–40 mg) Crohn's patients were randomised into three treatment groups: placebo versus ISIS 2302 (2 mg/kg intravenously three times a week) for two or four weeks. Patients were treated in months 1 and 3, with steroid withdrawal attempted by week 10. The primary end point (steroid free remission) was a CDAI <150 off steroids at the end of week 14. Results: A total of 299 patients were enrolled, with a mean baseline CDAI of 276 and steroid dose of 23 mg/day. Rates of steroid free remission were equivalent for the two and four week ISIS 2302 groups (20.2% and 21.2%) and the placebo group (18.8%). At week 14, steroid withdrawal was successful in more ISIS 2302 patients compared with placebo treated patients (78% v 64%; p=0.032). Steroid free remission was highly correlated with exposure (p=0.0064). Other clinical responses were correlated with exposure, with significant results versus placebo being observed in the highest area under the curve subgroup. CDAI scores decreased by 136 (112) at week 14 versus 52 (107) for placebo (p=0.027) and inflammatory bowel disease score questionnaire improved by 43 (31) versus 15 (36) for placebo (p=0.027). Conclusions: Although the primary outcomes failed to demonstrate efficacy, pharmacodynamic modelling suggests that alicaforsen (ISIS 2302) may be an effective therapy for steroid dependent Crohn's disease. PMID:12077088

Metabolism of sex steroids is influenced by acquired adiposity-A study of young adult male monozygotic twin pairs.

PubMed

Vihma, Veera; Naukkarinen, Jussi; Turpeinen, Ursula; Hämäläinen, Esa; Kaprio, Jaakko; Rissanen, Aila; Heinonen, Sini; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Mikkola, Tomi S; Tikkanen, Matti J; Pietiläinen, Kirsi H

2017-09-01

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22-36kg/m 2 ] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m 2 ]. Sex steroid concentrations were determined by liquid chromatography-tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI=5.9kg/m 2 ), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs. 2.4 (1.0) nmol/l, P=0.040] and mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) higher in the heavier compared to the leaner co-twins. Serum free 17β-estradiol (E2) was higher [2.3 (0.5) vs. 1.9 (0.5) pmol/l, P=0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs. 90 (22) pmol/l, P=0.006; and 123 (43) vs. 105 (27) pmol/l, P=0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations (P<0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG (P<0.05), and 3) liver fat with SHBG (P=0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2, HSD11B1, and aromatase in adipose tissue (P<0.05). In conclusion, acquired adiposity was

Associations of sex steroid hormones with mortality in women with breast cancer.

PubMed

Duggan, Catherine; Stanczyk, Frank; Campbell, Kristin; Neuhouser, Marian L; Baumgartner, Richard N; Baumgartner, Kathy B; Bernstein, Leslie; Ballard, Rachel; McTiernan, Anne

2016-02-01

Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log-transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26-0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43-0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05-0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer-specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts.

WHY WE SHOULD CONSIDER SEX (AND STUDY SEX DIFFERENCES) IN ADDICTION RESEARCH

PubMed Central

Sanchis-Segura, Carla; Becker, Jill

2017-01-01

Among mammals, every cell has a biological sex, and the sex of an individual pervades its body and brain. In this review we describe the processes through which mammals become phenotypically male or female by organizational and activational influences of genes and hormones throughout development. We emphasized that the molecular and cellular changes triggered by sex chromosomes and steroid hormones may generate sex differences in overt physiological functions and behavior, but they may alternatively promote end-point convergences between males and females. Clinical and preclinical evidence suggest that sex and gender differences modulate drug consumption as well as of the transition towards drug-promoted pathological states such as dependence and addiction. Additionally, sex differences in drug pharmacokinetics and pharmacodynamics will also influence dependence and addiction as well as side effects of drugs. These effects will further interact with socially gendered factors to result in sex differences in the access to, engagement in, and efficacy of any therapeutic attempt. Finally, we maintain that “sex-sameness” is as important as “sex differences” when building a complete understanding of biology for both males and females and provide a framework with which to classify and guide investigation into the mechanisms mediating sex differences and sex-sameness. PMID:27029841

Role of sex steroids and their receptors in human preterm infants: Impacts on future treatment strategies for cerebral development.

PubMed

Hübner, Stephanie; Reich, Bettina; Heckmann, Matthias

2015-12-15

Preterm birth is a major risk factor for cerebral complications, such as hemorrhage or periventricular leukomalacia, which lead to lifelong neurodevelopmental deficits. Hypoxia/ischemia, inflammation, hyperoxia, and prematurity itself contribute to the extent of impaired neurodevelopment. Preterm birth leads to disruption of the placental supply of estrogens and progesterone. Postnatally, the plasma levels of estrogens and progesterone drop 100-fold. Preterm infants are deprived of the placental supply of these hormones for up to sixteen weeks. Thus, supplementation of estradiol and progesterone to mimic intrauterine conditions may potentially improve a premature infant́s extrauterine development and help protect the brain against neurological complications. However, preliminary clinical studies did not find improved outcomes except for a trend towards less cerebral palsy. The decrease in estrogen and progesterone concentrations is accompanied by persistent, high postnatal production of fetal zone steroids, mainly dehydroepiandrosterone, which serve as precursors for maternal estrogen synthesis during pregnancy. This commentary will combine knowledge from endocrinology, pharmacology, and neonatology to explain the discrepancies between promising animal models and clinical findings. Most important targets will be classical and non-classical estrogen receptors, which interact differently-not only with estrogens but also with fetal zone steroids. The fetal zone is unique among humans and higher primates. Therefore, a clearly defined model is required to study the role of sex steroids and their receptors before further clinical studies begin. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed Central

Frick, Karyn M.

2012-01-01

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

Sex differences in effective fronto-limbic connectivity during negative emotion processing.

PubMed

Lungu, Ovidiu; Potvin, Stéphane; Tikàsz, Andràs; Mendrek, Adrianna

2015-12-01

In view of the greater prevalence of depression and anxiety disorders in women than in men, functional magnetic resonance imaging (fMRI) studies have examined sex-differences in brain activations during emotion processing. Comparatively, sex-differences in brain connectivity received little attention, despite evidence for important fronto-limbic connections during emotion processing across sexes. Here, we investigated sex-differences in fronto-limbic connectivity during negative emotion processing. Forty-six healthy individuals (25 women, 21 men) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Sex steroid hormones and feminine-masculine traits were also measured. Subjective ratings of negative emotional images were higher in women than in men. Across sexes, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the right amygdala. Granger connectivity from right amygdala was significantly greater than that from dmPFC during the 'high negative' condition, an effect driven by men. Magnitude of this effect correlated negatively with highly negative image ratings and feminine traits and positively with testosterone levels. These results highlight critical sex differences in brain connectivity during negative emotion processing and point to the fact that both biological (sex steroid hormones) and psychosocial (gender role and identity) variables contribute to them. As the dmPFC is involved in social cognition and action planning, and the amygdala-in threat detection, the connectivity results suggest that compared to women, men have a more evaluative, rather than purely affective, brain response during negative emotion processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Steroid Hormones in NF1 Tumorigenesis

DTIC Science & Technology

2005-08-01

Schwannomatosis , in Aspen in June this year. Table 3. Summary of current xenograft proliferation/TUNEL (apoptosis) data. Culture I sex I Outlier? I PI/Al I...Biology of NF1, NF2, and schwannomatosis . Aspen, CO, June 2005, poster. CONCLUSIONS: In vitro data indicate that steroid hormone receptor levels in normal

Steroid therapy in children with fulminant hepatitis A.

PubMed

Zakaria, H M; Salem, T A; El-Araby, H A; Salama, R M; Elbadry, D Y; Sira, A M; Ali, M A; Salem, M E; Abd-Alaaty, B M; Goda, S S; Eltaras, S M; Khalil, F O; Abou-Zeinah, S S; Sira, M M

2018-02-03

Fulminant hepatic failure is a life-threatening disease. Hepatitis A virus (HAV) can cause fulminant hepatic failure and death in about 0.2% of cases. Extensive destruction of infected hepatocytes by immune-mediated lysis is thought to be the cause. We aimed to evaluate the use of steroid therapy in children with fulminant HAV. This study included 33 children with fulminant HAV in two groups. Steroid group: comprised of 18 children who received prednisolone (1 mg/kg/d) or its equivalent dose of methylprednisolone, and the nonsteroid group: comprised another 15 children who did not receive steroid therapy. Age and sex were matched for both groups (P > .05), and they were comparable regarding baseline clinical and laboratory characteristics. Of the steroid group, 15 patients survived and 3 died, while in the nonsteroid group, 4 patients survived and 11 died (P = .001). Of the living patients, 15 of 19 (78.9%) received steroids while only 3 of 14 (21.4%) of the dead patients received steroids (P = .001). Stepwise regression analysis showed that steroid therapy was the only independent variable associated with recovery (P = .001). Steroid therapy in children with fulminant HAV associated significantly with improved outcome and survival. Future studies on a larger population size are strongly recommended. © 2018 John Wiley & Sons Ltd.

Sexual Dimorphism in the Regulation of Estrogen, Progesterone, and Androgen Receptors by Sex Steroids in the Rat Airway Smooth Muscle Cells

PubMed Central

Zarazúa, Abraham; González-Arenas, Aliesha; Ramírez-Vélez, Gabriela; Bazán-Perkins, Blanca; Guerra-Araiza, Christian; Campos-Lara, María G.

2016-01-01

The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC), and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17β-estradiol, progesterone, 17β-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-α-actin smooth muscle and antibodies to each hormone receptor). ERα, ERβ, tPR, and AR were detected in females or males. ERα was upregulated by E2 and T and downregulated by P4 in females; in males, ERα was downregulated by P4, E + P, and T. ERβ was downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats. PMID:27110242

Sex steroid hormones and sex hormone binding globulin levels, CYP17 MSP AI (-34T:C) and CYP19 codon 39 (Trp:Arg) variants in children with developmental stuttering.

PubMed

Mohammadi, Hiwa; Joghataei, Mohammad Taghi; Rahimi, Zohreh; Faghihi, Faezeh; Khazaie, Habibolah; Farhangdoost, Hashem; Mehrpour, Masoud

2017-12-01

Developmental stuttering is known to be a sexually dimorphic and male-biased speech motor control disorder. In the present case-control study, we investigated the relationship between developmental stuttering and steroid hormones. Serum levels of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), oestradiol, progesterone, cortisol, and sex hormone binding globulin (SHBG), as well as the 2nd/4th digit ratio (2D:4D), an indicator of prenatal testosterone level, were compared between children who stutter (CWS) and children who do not stutter (CWNS). Moreover, two SNPs (CYP17 -34 T:C (MSP AI) and CYP19 T:C (Trp:Arg)) of cytochrome P450, which is involved in steroid metabolism pathways, were analysed between the groups. Our results showed significantly higher levels of testosterone, DHT, and oestradiol in CWS in comparison with CWNS. The severity of stuttering was positively correlated with the serum levels of testosterone, DHEA, and cortisol, whereas no association was seen between the stuttering and digit ratio, progesterone, or SHBG. The CYP17CC genotype was significantly associated with the disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Steroids in teleost fishes: A functional point of view.

PubMed

Tokarz, Janina; Möller, Gabriele; Hrabě de Angelis, Martin; Adamski, Jerzy

2015-11-01

Steroid hormones are involved in the regulation of a variety of processes like embryonic development, sex differentiation, metabolism, immune responses, circadian rhythms, stress response, and reproduction in vertebrates. Teleost fishes and humans show a remarkable conservation in many developmental and physiological aspects, including the endocrine system in general and the steroid hormone related processes in particular. This review provides an overview of the current knowledge about steroid hormone biosynthesis and the steroid hormone receptors in teleost fishes and compares the findings to the human system. The impact of the duplicated genome in teleost fishes on steroid hormone biosynthesis and perception is addressed. Additionally, important processes in fish physiology regulated by steroid hormones, which are most dissimilar to humans, are described. We also give a short overview on the influence of anthropogenic endocrine disrupting compounds on steroid hormone signaling and the resulting adverse physiological effects for teleost fishes. By this approach, we show that the steroidogenesis, hormone receptors, and function of the steroid hormones are reasonably well understood when summarizing the available data of all teleost species analyzed to date. However, on the level of a single species or a certain fish-specific aspect of physiology, further research is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum steroid concentrations remain within normal postmenopausal values in women receiving daily 6.5mg intravaginal prasterone for 12 weeks.

PubMed

Martel, Céline; Labrie, Fernand; Archer, David F; Ke, Yuyong; Gonthier, Renaud; Simard, Jean-Nicolas; Lavoie, Lyne; Vaillancourt, Mario; Montesino, Marlene; Balser, John; Moyneur, Érick

2016-05-01

This study integrates all data obtained in women aged 40-80years enrolled with moderate to severe symptoms of vulvovaginal atrophy (VVA) who received daily intravaginal administration of 0.50% (6.5mg) dehydroepiandrosterone (DHEA; prasterone) for 12weeks (n=723; ITT-S population) as compared with placebo (n=266; ITT-S population). To this end, serum steroid levels (DHEA, DHEA-sulfate (DHEA-S), androst-5-ene-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1), estradiol (E2), estrone sulfate (E1-S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G)) were measured at Day 1 and Week 12 by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following validation performed according to the FDA guidelines [1-6]. In agreement with the mechanisms of intracrinology where DHEA is exclusively transformed intracellularly into active sex steroids which act and are inactivated locally before being released as glucuronided or sulfated metabolites for elimination by the kidneys and liver, all sex steroids remained well within normal postmenopausal values following administration of intravaginal DHEA. Serum estradiol, the most relevant sex steroid, was measured after 12weeks of treatment at 3.36pg/ml (cITT-S population) or 19% below the normal postmenopausal value of 4.17pg/ml. On the other hand, serum E1-S, the best recognized marker of global estrogenic activity, shows an average value of 209pg/ml at 12 weeks compared to 220pg/ml in normal postmenopausal women. Moreover, serum ADT-G, the main metabolite of androgens, also remains well within normal postmenopausal values. The present data shows that a low daily intravaginal dose (6.5mg) of DHEA (prasterone) which is efficacious on the symptoms and signs of VVA, permits to achieve the desired local efficacy without systemic exposure, in agreement with the stringent mechanisms of menopause established after 500 million years of

Microbial biotransformation of bioactive and clinically useful steroids and some salient features of steroids and biotransformation.

PubMed

Sultana, Nighat

2018-01-31

Steroids are perhaps one of the most widely used group of drugs in present day. Beside the established utilization as immunosuppressive, anti-inflammatory, anti-rheumatic, progestational, diuretic, sedative, anabolic and contraceptive agents, recent applications of steroid compounds include the treatment of some forms of cancer, osteoporosis, HIV infections and treatment of declared AIDS. Steroids isolated are often available in minute amounts. So biotransformation of natural products provides a powerful means in solving supply problems in clinical trials and marketing of the drug for obtaining natural products in bulk amounts. If the structure is complex, it is often an impossible task to isolate enough of the natural products for clinical trials. The microbial biotransformation of steroids yielded several novel metabolites, exhibiting different activities. The metabolites produced from pregnenolone acetate by Cunning hamella elegans and Rhizopus stolonifer were screened against tyrosinase and cholinesterase showed significant inhibitory activities than the parent compound. Diosgenin and its transformed sarsasapogenin were screened for their acetyl cholinesterase and butyryl cholinesterase inhibitory activities. Sarsasapogenin was screened for phytotoxicity, and was found to be more active than the parent compound. Diosgenin, prednisone and their derivatives were screened for their anti-leishmanial activity. All derivatives were found to be more active than the parent compound. The biotransformation of steroids have been reviewed to a little extent. This review focuses on the biotransformation and functions of selected steroids, the classification, advantages and agents of enzymatic biotransformation and examines the potential role of new enzymatically transformed steroids and their derivatives in the chemoprevention and treatment of other diseases. tyrosinase and cholinesterase inhibitory activities, severe asthma, rheumatic disorders, renal disorders and

No effect of sex steroids on compensatory muscle hypertrophy

NASA Technical Reports Server (NTRS)

Max, S. R.; Rance, N. E.

1984-01-01

The effects of orchiectomy and/or subcutaneously implanted testosterone propionate (TP) on the hypertrophic response of rat plantaris muscles to functional overload (induced by bilateral removal of gastrocnemius and soleus muscles) are investigated experimentally. Muscle wet weight, metabolic substrate oxidation, and cytosolic androgen-receptor binding are measured, and the results are presented in tables. Eight weeks after surgery, the plantaris muscle weight as a percentage of body weight is found to be about twice that in rats without muscle overload, regardless of the sex-hormone status. Overloading causes decreased ability to oxidize glucose and pyruvate, decreased succinate dehydrogenase specific activity, and no change in the ability to oxidize beta-hydroxybutyrate or in androgen-receptor binding. The oxidative response is unaffected by orchiectomy or TP or both. It is argued that the actions of sex hormones and functional overload are not synergistic.

Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis

PubMed Central

Laurent, Michaël R.; Hammond, Geoffrey L.; Blokland, Marco; Jardí, Ferran; Antonio, Leen; Dubois, Vanessa; Khalil, Rougin; Sterk, Saskia S.; Gielen, Evelien; Decallonne, Brigitte; Carmeliet, Geert; Kaufman, Jean-Marc; Fiers, Tom; Huhtaniemi, Ilpo T.; Vanderschueren, Dirk; Claessens, Frank

2016-01-01

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens. According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues. Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally. To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene. SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life. Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated. This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures. These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology. PMID:27748448

Determinants of Maternal Sex Steroids During the First Half of Pregnancy

PubMed Central

Toriola, Adetunji T; Vääräsmäki, Marja; Lehtinen, Matti; Zeleniuch-Jacquotte, Anne; Lundin, Eva; Rodgers, Kenneth-Gary; Lakso, Hans-Ake; Chen, Tianhui; Schock, Helena; Hallmans, Goran; Pukkala, Eero; Toniolo, Paolo; Grankvist, Kjell; Surcel, Helja-Marja; Lukanova, Annekatrin

2011-01-01

Objective To examine the associations of maternal and child characteristics with early pregnancy maternal concentrations of testosterone, androstenedione, progesterone, 17-hydroxyprogesterone and estradiol. Methods We analyzed these hormones among 1,343 women with singleton pregnancies who donated serum samples to the Finnish Maternity Cohort from 1986 to 2006 during the first half of pregnancy (median, 11 weeks). The associations of maternal and child characteristics with hormone concentrations were investigated by correlation and multivariable regression. Results Women above age 30 had lower androgen and estradiol but higher progesterone concentrations than women below that age. Multiparous women had 14% lower testosterone, 11% lower androstenedione and 17-hydroxyprogesterone, 9% lower progesterone, and 16% lower estradiol concentrations compared to nulliparous women (all P<.05). Smoking mothers had 11%, 18%, and 8% higher testosterone, androstenedione, and 17-hydroxyprogesterone levels, respectively, but 10% lower progesterone compared to non-smoking women (all P<.05). Estradiol concentrations were 9% higher (P<0.05) among women with a female fetus compared to those with a male fetus. Conclusions Parity, smoking, and to a lesser extent maternal age and child gender are associated with sex steroid levels during the first half of a singleton pregnancy. The effects of smoking on the maternal hormonal environment and the possible long-term deleterious consequences on the fetus deserve further evaluation. PMID:22015870

Synthesis and cytotoxic activity of two steroids: icogenin aglycone analogs.

PubMed

Guan, Yu-Yao; Li, Shu-Zhen; Lei, Ping-Sheng

2017-05-01

During the process of icogenin analog research, we obtained two cytotoxic steroids: compound 4 and compound 6 casually. Their in vitro antitumor activities were tested by the standard MTT assay. The results disclosed that compound 4 (IC 50  = 3.65-6.90 μM) showed potential antitumor activities against HELA, KB cell lines and compound 6 (IC 50  = 2.40-9.05 μM) showed potential antitumor activities against HELA, BGC-823, KB, A549, HCT-8 cell lines.

Framework for sex differences in adolescent neurobiology: A focus on cannabinoids

PubMed Central

Viveros, Maria-Paz; Marco-López, Eva María; López-Gallardo, Meritxell; Garcia-Segura, Luis Miguel; Wagner, Edward J.

2017-01-01

This review highlights the salient findings that have furthered our understanding of how sex differences are initiated during development and maintained throughout life. First we discuss how gonadal steroid hormones organize the framework for sex differences within critical periods of development—namely, during those exposures which occur in utero and post-partum, as well as those which occur during puberty. Given the extensive precedence of sex differences in cannabinoid-regulated biology, we then focus on the disparities within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB1 receptors is regulated throughout development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse, followed by the organizational and activational roles of gonadal steroids in establishing and maintaining the sex dependence in the biological actions of cannabinoids. Finally, we discuss ways to utilize this knowledge to strategically target critical developmental windows of vulnerability/susceptibility and thereby implement more effective therapeutic interventions for afflictions that may be more prevalent in one sex vs. the other. PMID:20869396

Sex differences in the neural substrates of spatial working memory during adolescence are not mediated by endogenous testosterone

PubMed Central

Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A.; Nagel, Bonnie J.

2014-01-01

Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. PMID:25312831

Androgenic/estrogenic balance in the male rat cerebral circulation: metabolic enzymes and sex steroid receptors

PubMed Central

Gonzales, Rayna J; Ansar, Saema; Duckles, Sue P; Krause, Diana N

2008-01-01

Tissues from males can be regulated by a balance of androgenic and estrogenic effects because of local metabolism of testosterone and expression of relevant steroid hormone receptors. As a critical first step to understanding sex hormone influences in the cerebral circulation of males, we investigated the presence of enzymes that metabolize testosterone to active products and their respective receptors. We found that cerebral blood vessels from male rats express 5α-reductase type 2 and aromatase, enzymes responsible for conversion of testosterone into dihydrotestosterone (DHT) and 17β-estradiol, respectively. Protein levels of these enzymes, however, were not modulated by long-term in vivo hormone treatment. We also showed the presence of receptors for both androgens (AR) and estrogens (ER) from male cerebral vessels. Western blot analysis showed bands corresponding to the full-length AR (110 kDa) and ERα (66 kDa). Long-term in vivo treatment of orchiectomized rats with testosterone or DHT, but not estrogen, increased AR levels in cerebral vessels. In contrast, ERα protein levels were increased after in vivo treatment with estrogen but not testosterone. Fluorescent immunostaining revealed ERα, AR, and 5α-reductase type 2 in both the endothelial and smooth muscle layers of cerebral arteries, whereas aromatase staining was solely localized to the endothelium. Thus, cerebral vessels from males are target tissues for both androgens and estrogen. Furthermore, local metabolism of testosterone might balance opposing androgenic and estrogenic influences on cerebrovascular as well as brain function in males. PMID:17406656

Endogenous sex steroids and risk of cervical carcinoma: results from the EPIC study.

PubMed

Rinaldi, Sabina; Plummer, Martyn; Biessy, Carine; Castellsagué, Xavier; Overvad, Kim; Krüger Kjær, Susanne; Tjønneland, Anne; Clavel-Chapelon, Françoise; Chabbert-Buffet, Nathalie; Mesrine, Sylvie; Lukanova, Annekatrin; Kaaks, Rudolf; Weikert, Cornelia; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, Bas; van Kranen, Henk J; Peeters, Petra Hm; Bakken, Kjersti; Lund, Eiliv; Gram, Inger Torhild; Rodríguez, Laudina; Bosch, F Xavier; Sánchez, Maria-José; Dorronsoro, Miren; Navarro, Carmen; Gurrea, Aurelio Barricarte; Kjellberg, Lennart; Dillner, Joakim; Manjer, Jonas; Butt, Salma; Khaw, Kay-Tee; Wareham, Nicholas; Allen, Naomi E; Travis, Ruth; Romieu, Isabelle; Ferrari, Pietro; Riboli, Elio; Franceschi, Silvia

2011-12-01

Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC). Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E(2)); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E(2) were calculated from absolute concentrations of T, E(2), and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression. Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile = 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E(2), fE(2), and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR = 3.14; 95% CI, 1.21-9.37), whereas E(2) and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre- or postmenopausal women. Our findings suggest for the first time that T and possibly E(2) may be involved in the etiology of ICC. The responsiveness of cervical tumors to hormone modulators is worth exploring.

Effects of one's sex and sex hormones on sympathetic responses to chemoreflex activation.

PubMed

Usselman, Charlotte W; Steinback, Craig D; Shoemaker, J Kevin

2016-03-01

What is the topic of this review? This review summarizes sex-dependent differences in the sympathetic responses to chemoreflex activation, with a focus on the role of circulating sex hormones on the sympathetic outcomes. What advances does it highlight? The importance of circulating sex hormones for the regulation of sympathetic nerve activity in humans has only recently begun to be elucidated, and few studies have examined this effect during chemoreflex regulation. We review recent studies indicating that changes in circulating sex hormones are associated with alterations to chemoreflex-driven increases in sympathetic activity and highlight those areas which require further study. Sex-dependent differences in baseline sympathetic nerve activity are established, but little information exists on the influence of sex on sympathetic activation during chemoreflex stimulation. In this article, we review the evidence for the effect of sex on chemoreflex-driven increases in sympathetic nerve activity. We also review recent studies which indicate that changes in circulating sex hormones, as initiated by the menstrual cycle and hormonal contraceptive use, elicit notable changes in the muscle sympathetic activation during chemoreflex stimulation. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

PubMed

Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne

2015-06-30

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Steroids

MedlinePlus

... Staying Safe Videos for Educators Search English Español Steroids KidsHealth / For Kids / Steroids What's in this article? ... a good idea to avoid them. What Are Steroids? "Steroids" has more than one meaning. Your body ...

Ethanol acts as an enhancer of steroid anesthetic activity in mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bukusoglu, C.; Mok, W.M.; Krieger, N.R.

1992-02-26

Ethanol and the steroid 3{alpha}-hydroxy-5{alpha}-pregnan-20-one (3{alpha}) are each potent general anesthetics that bring about the rapid loss of the righting response (LRR) in mice. Ethanol is known to enhance the actions of a range of sedative and anesthetic agents. However the effects of ethanol on steroid anesthesia have not previously been described. When ethanol was co-injected with 3{alpha} as compared to 3{alpha} injected alone, the percentage of mice that lost the righting response was substantially increased; the time to LRR was shortened; and 3{alpha} brain levels were increased. The interactions between the two agents were analyzed with the aid ofmore » an isobologram and they were found to be consistent with a hypothesis of additivity. The authors speculate that the role of ethanol as an enhancer of administered 3{alpha} activity described here may extend to the enhancement of endogenous 3{alpha} activity.« less

Impact of X/Y genes and sex hormones on mouse neuroanatomy.

PubMed

Vousden, Dulcie A; Corre, Christina; Spring, Shoshana; Qiu, Lily R; Metcalf, Ariane; Cox, Elizabeth; Lerch, Jason P; Palmert, Mark R

2018-06-01

Biological sex influences brain anatomy across many species. Sex differences in brain anatomy have classically been attributed to differences in sex chromosome complement (XX versus XY) and/or in levels of gonadal sex steroids released from ovaries and testes. Using the four core genotype (4CG) mouse model in which gonadal sex and sex chromosome complement are decoupled, we previously found that sex hormones and chromosomes influence the volume of distinct brain regions. However, recent studies suggest there may be more complex interactions between hormones and chromosomes, and that circulating steroids can compensate for and/or mask underlying chromosomal effects. Moreover, the impact of pre vs post-pubertal sex hormone exposure on this sex hormone/sex chromosome interplay is not well understood. Thus, we used whole brain high-resolution ex-vivo MRI of intact and pre-pubertally gonadectomized 4CG mice to investigate two questions: 1) Do circulating steroids mask sex differences in brain anatomy driven by sex chromosome complement? And 2) What is the contribution of pre- versus post-pubertal hormones to sex-hormone-dependent differences in brain anatomy? We found evidence of both cooperative and compensatory interactions between sex chromosomes and sex hormones in several brain regions, but the interaction effects were of low magnitude. Additionally, most brain regions affected by sex hormones were sensitive to both pre- and post-pubertal hormones. This data provides further insight into the biological origins of sex differences in brain anatomy. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Sex-Typed Activities: Cause or Effect?

ERIC Educational Resources Information Center

Carpenter, C. Jan; Huston-Stein, Aletha

Sex differences in activity selection or choice appear by age 12 or 18 months. These choices are one of the earliest indicators of sex differences in the behavior of young children. Differences in activity participation or toy choices are evident long before the emergence of sex differences in personality characteristics like passivity or…

Mechanism of Action of Bolandiol (19-Nortestosterone-3β,17β-Diol), a Unique Anabolic Steroid with Androgenic, Estrogenic, and Progestational Activities*

PubMed Central

Attardi, Barbara J.; Page, Stephanie T.; Hild, Sheri A.; Coss, Christopher C.; Matsumoto, Alvin M.

2009-01-01

Bolandiol is a synthetic anabolic steroid that increases lean body mass and bone mineral density without significant stimulation of sex accessory glands in castrate adult male rats. Since bolandiol suppresses gonadotropins and endogenous testosterone (T) production, we investigated its mechanism of action. We compared the potency of bolandiol in vitro and in vivo with T, 5α-dihydrotestosterone (DHT), 19-nortestosterone (19-NT) and estradiol (E2). Bolandiol bound with lower affinity to the recombinant rat androgen receptor (AR) than the other androgens and had low, but measurable, affinity for recombinant human progestin receptors (PR-A, PR-B), and estrogen receptors (ERα and β-1). Functional agonist activity was assessed in transcription assays mediated by AR, PR, or ER. Bolandiol was stimulatory in all these assays, but only 4–9% as potent as T, DHT, and 19-NT via AR, 1% as potent as progesterone via PR, and 3% and 1% as potent as E2 acting through ERα or ERβ, respectively. In immature castrate rats, bolandiol was equipotent to T in stimulating growth of the levator ani muscle but less potent than T in stimulating growth of the sex accessory glands. Bolandiol also stimulated uterine weight increases in immature female rats, which were partly blocked by ICI 182,780, but it was not aromatized in vitro by recombinant human aromatase. In contrast to T, stimulation of sex accessory gland weights by bolandiol was not inhibited by concomitant treatment with the dual 5α-reductase inhibitor dutasteride. As bolandiol exhibits tissue selectivity in vivo, it may act via AR, PR, and/or ER, utilize alternative signaling pathway(s) or transcriptional coregulators, and/or be metabolized to a more potent selective steroid. PMID:19941958

Sex-steroid and thyroid hormone concentrations in juvenile alligators (Alligator mississippiensis) from contaminated and reference lakes in Florida, USA

USGS Publications Warehouse

Grain, D.A.; Guillette, L.J.; Pickford, D.B.; Percival, H.F.; Woodward, A.R.

1998-01-01

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-171?? (E2), testosterone (T), triiodothyronine (T3), and thyroxine (T4) in juvenile alligators (60-140 cm total length) from two contaminated lakes and one reference lake in Florida. First, the data were analyzed by comparing hormone concentrations among males and females from the different lakes. Whereas there were no differences in plasma E2 concentrations among animals of the three lakes, male alligators from the contaminated lakes (Lake Apopka and Lake Okeechobee) had significantly lower plasma T concentrations compared 10 males from the reference take (Lake Woodruff). Concentrations of thyroid hormones also differed in animals of the three lakes, with T4 concentrations being elevated in Lake Okeechobee males compared to Lake Woodruff males. Second, the relationship between body size and hormone concentration was examined using regression analysis. Most notably for steroid hormones, no clear relationship was detected between E2 and total length in Apopka females (r2 0.09, p = 0.54) or between T and total length in Apopka males (r2 = 0.007, p = 0.75). Females from Apopka (r2 = 0.318, p = 0.09) and Okeechobee (r2 = 0.222, p = 0.09) exhibited weak correlations between T3 and total length. Males from Apopka (r2 = 0.015, p = 0.66) and Okeechobee (r2 = 0.128, p = 0.19) showed no correlation between T4 and total length. These results indicate: some of the previously reported abnormalities in steroid hormones of hatchling alligators persist, at least, through the juvenile years; steroid and thyroid hormones are related to body size in juvenile alligators from the reference lake, whereas alligators living in lakes Apopka and Okeechobee experience alterations in circulating thyroid and steroid

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

PubMed

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

2010-01-27

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

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

Beyond T and DHT - Novel Steroid Derivatives Capable of Wild Type Androgen Receptor Activation

PubMed Central

Mostaghel, Elahe A

2014-01-01

While androgen deprivation therapy (ADT) remains the primary treatment for metastatic prostate cancer (PCa), castration does not eliminate androgens from the prostate tumor microenvironment, and residual intratumoral androgens are implicated in nearly every mechanism by which androgen receptor (AR)-mediated signaling promotes castration-resistant disease. The uptake and intratumoral (intracrine) conversion of circulating adrenal androgens such as dehydroepiandrosterone sulfate (DHEA-S) to steroids capable of activating the wild type AR is a recognized driver of castration resistant prostate cancer (CRPC). However, less well-characterized adrenal steroids, including 11-deoxcorticosterone (DOC) and 11beta-hydroxyandrostenedione (11OH-AED) may also play a previously unrecognized role in promoting AR activation. In particular, recent data demonstrate that the 5α-reduced metabolites of DOC and 11OH-AED are activators of the wild type AR. Given the well-recognized presence of SRD5A activity in CRPC tissue, these observations suggest that in the low androgen environment of CRPC, alternative sources of 5α-reduced ligands may supplement AR activation normally mediated by the canonical 5α-reduced agonist, 5α-DHT. Herein we review the emerging data that suggests a role for these alternative steroids of adrenal origin in activating the AR, and discuss the enzymatic pathways and novel downstream metabolites mediating these effects. We conclude by discussing the potential implications of these findings for CRPC progression, particularly in context of new agents such as abiraterone and enzalutamide which target the AR-axis for prostate cancer therapy. PMID:24948873

Race differences in obesity and its relationship to the sex hormone milieu.

PubMed

Perry, Arlette C; Martin, Lorena

2014-09-01

A sexual dimorphism exists in which increased abdominal and visceral adipose tissue (VAT) - found in women and marked by low sex hormone binding globulin (SHBG) and high bioavailable testosterone (BT) - is related to the metabolic risk profile. In men, increased BT is related to decreased abdominal obesity and a decrease in the metabolic risk profile. In women, race differences have been found in androgenic sex steroids including SHBG and BT as well as central fat distribution, creating inherently greater metabolic risk for certain populations. Estrogen and estrogen receptor isoforms play a role in fat deposition and distribution and may influence the changes that occur during the menopausal transition. Androgenic sex steroids serve a mediating role, influencing VAT accumulation and its associated metabolic risk factors while VAT also serves a mediating role influencing the androgenic sex steroid-metabolic risk relationship in women. Furthermore, androgenic sex steroids and VAT may independently contribute to the variance in several metabolic variables associated with cardiovascular disease, type 2 diabetes, and their antecedent conditions such as the metabolic syndrome. Race has been shown to modify the relationship between androgenic sex steroids and metabolic variables associated with risk for diabetes in Black and White women. Further research is warranted to examine the mechanisms involved in race differences. Total adiposity and central fat distribution in accordance with changes in the hormone and metabolic milieu influence breast cancer risk, which varies by race and menopausal status. These findings have broader implications for the study of health promotion/disease prevention in women.

Sex differences in the neural substrates of spatial working memory during adolescence are not mediated by endogenous testosterone.

PubMed

Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A; Nagel, Bonnie J

2014-12-17

Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 years completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. Copyright © 2014 Elsevier B.V. All rights reserved.

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men.

PubMed

Sato, K; Samocha-Bonet, D; Handelsman, D J; Fujita, S; Wittert, G A; Heilbronn, L K

2014-12-01

Low-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH-) a family history of type 2 diabetes. Following a 3-day lead in energy balanced diet, FH+ (n = 9) and FH- men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11). Body weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P<0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04). Overfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Structural architecture of the human long non-coding RNA, steroid receptor RNA activator

PubMed Central

Novikova, Irina V.; Hennelly, Scott P.; Sanbonmatsu, Karissa Y.

2012-01-01

While functional roles of several long non-coding RNAs (lncRNAs) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human lncRNA, the steroid receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a non-coding RNA that coactivates several human sex hormone receptors and is strongly associated with breast cancer. Coding isoforms of SRA are also expressed to produce proteins, making the SRA gene a unique bifunctional system. Our experimental findings (SHAPE, in-line, DMS and RNase V1 probing) reveal that this lncRNA has a complex structural organization, consisting of four domains, with a variety of secondary structure elements. We examine the coevolution of the SRA gene at the RNA structure and protein structure levels using comparative sequence analysis across vertebrates. Rapid evolutionary stabilization of RNA structure, combined with frame-disrupting mutations in conserved regions, suggests that evolutionary pressure preserves the RNA structural core rather than its translational product. We perform similar experiments on alternatively spliced SRA isoforms to assess their structural features. PMID:22362738

Steroids and osteoporosis: the quest for mechanisms

PubMed Central

Manolagas, Stavros C.

2013-01-01

Advances made during the last 35 years have improved our understanding of the mechanisms of steroid hormone action on bone and how physiologic, pathologic, or iatrogenic changes in hormone levels can lead to increased fracture risk. Estrogens, androgens, and glucocorticoids alter the cellular composition of bone by regulating the supply and lifespan of osteoclasts and osteoblasts. Additionally, they influence the survival of osteocytes, long-lived cells that are entombed within the mineralized matrix and mediate the homeostatic adaptation of bone to mechanical forces. Altered redox balance is a proximal underlying mechanism of some of these effects, and sex steroid deficiency or glucocorticoid excess contributes to the aging of the skeleton. PMID:23635790

Sex steroids and variants of gender identity.

PubMed

Meyer-Bahlburg, Heino F L

2013-09-01

This article summarizes for the practicing endocrinologist the current literature on the psychobiology of the development of gender identity and its variants in individuals with disorders of sex development (DSD) or with non-DSD transgenderism. Gender reassignment remains the treatment of choice for strong and persistent gender dysphoria in both categories, but more research is needed on the short-term and long-term effects of puberty-suppressing medications and cross-sex hormones on brain and behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Sex and Exercise Interact to Alter the Expression of Anabolic Androgenic Steroid-Induced Anxiety-Like Behaviors in the Mouse

PubMed Central

Onakomaiya, Marie M.; Porter, Donna M.; Oberlander, Joseph G.; Henderson, Leslie P.

2014-01-01

Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711

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

PubMed

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

2014-10-07

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

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

PubMed Central

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

2017-01-01

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

Altered levels of sex and stress steroid hormones assessed daily over a 28-day cycle in early abstinent cocaine-dependent females

PubMed Central

Hong, Kwangik A.; Paliwal, Prashni; Morgan, Peter T.; Sinha, Rajita

2009-01-01

Rationale There is growing evidence of alterations in brain stress and reward circuits associated with cocaine dependence. Sex differences are also documented and sex steroid hormones have been linked to cocaine reinforcement. Objectives The current study therefore assessed daily fluctuations in stress and sex hormones in cocaine-dependent females compared with healthy females. Method Daily salivary samples of cortisol, progesterone, and estradiol were collected at waking across 28 days from 12 cocaine-dependent females receiving inpatient treatment and 10 healthy females. Participants also completed mood-rating scales each week corresponding to four phases of the menstrual cycle and cocaine craving was monitored in cocaine patients at each phase. Results Cocaine-dependent females in their first month of abstinence demonstrated significantly higher levels of both cortisol and progesterone across the menstrual cycle and significantly lower estradiol/progesterone (E2/P) ratios compared to healthy controls. They also showed significantly increased negative mood compared with controls, but no variation in cocaine craving across the menstrual cycle. Conclusions Findings indicate altered stress and sex hormones suggestive of an overactive stress system during the first month of cocaine abstinence after chronic cocaine abuse. These increased levels of cortisol and progesterone could impact both abstinence-related symptoms such as negative mood and susceptibility to drug-seeking behavior in cocaine-dependent females. PMID:17891383

Steroid toxicity and detoxification in ascomycetous fungi.

PubMed

Cvelbar, Damjana; Zist, Vanja; Kobal, Katja; Zigon, Dušan; Zakelj-Mavrič, Marija

2013-02-25

In the last couple of decades fungal infections have become a significant clinical problem. A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship. Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae. Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone. For their protection, fungi use several mechanisms to lower the toxic effects of steroids. The efficiency of biotransformation in detoxification depended on the microorganism and steroid substrate used. Biotransformation was a relatively slow process as it also depended on the growth phase of the fungus. In addition to biotransformation, steroid extrusion out of the cells contributed to the lowering of the active intracellular steroid concentration. Plasma membrane Pdr5 transporter was found to be the most effective, followed by Snq2 transporter and vacuolar transporters Ybt1 and Ycf1. Proteins Aus1 and Dan1 were not found to be involved in steroid import. The research of possible targets of steroid hormone action in fungi suggests that steroid hormones inhibit ergosterol biosynthesis in S. cerevisiae and H. werneckii. Results of this inhibition caused changes in the sterol content of the cellular membrane. The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Sex differences in cognitive impairment and Alzheimer's disease.

PubMed

Li, Rena; Singh, Meharvan

2014-08-01

Studies have shown differences in specific cognitive ability domains and risk of Alzheimer's disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer's disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer's disease in men and women. Copyright © 2014 Elsevier Inc. All rights reserved.

Oestradiol and prostaglandin F2α regulate sexual displays in females of a sex-role reversed fish

PubMed Central

Gonçalves, David; Costa, Silvia Santos; Teles, Magda C.; Silva, Helena; Inglês, Mafalda; Oliveira, Rui F.

2014-01-01

The mechanisms regulating sexual behaviours in female vertebrates are still poorly understood, mainly because in most species sexual displays in females are more subtle and less frequent than displays in males. In a sex-role reversed population of a teleost fish, the peacock blenny Salaria pavo, an external fertilizer, females are the courting sex and their sexual displays are conspicuous and unambiguous. We took advantage of this to investigate the role of ovarian-synthesized hormones in the induction of sexual displays in females. In particular, the effects of the sex steroids oestradiol (E2) and testosterone (T) and of the prostaglandin F2α (PGF2α) were tested. Females were ovariectomized and their sexual behaviour tested 7 days (sex steroids and PGF2α) and 14 days (sex steroids) after ovariectomy by presenting females to an established nesting male. Ovariectomy reduced the expression of sexual behaviours, although a significant proportion of females still courted the male 14 days after the ovary removal. Administration of PGF2α to ovariectomized females recovered the frequency of approaches to the male's nest and of courtship displays towards the nesting male. However, E2 also had a positive effect on sexual behaviour, particularly on the frequency of approaches to the male's nest. T administration failed to recover sexual behaviours in ovariectomized females. These results suggest that the increase in E2 levels postulated to occur during the breeding season facilitates female mate-searching and assessment behaviours, whereas PGF2α acts as a short-latency endogenous signal informing the brain that oocytes are mature and ready to be spawned. In the light of these results, the classical view for female fishes, that sex steroids maintain sexual behaviour in internal fertilizers and that prostaglandins activate spawning behaviours in external fertilizers, needs to be reviewed. PMID:24452030

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

PubMed

Parker, M Rockwell; Mason, Robert T

2012-03-01

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

Steroids

MedlinePlus

... or sometimes with chemotherapy. Steroids are used for short-term symptom control although they may occasionally be continued ... even in lymphoma steroids are not typically a long-term cure for this tumor. HOW ARE STEROIDS TAKEN? ...

Annual changes in plasma levels of cortisol and sex steroid hormones in male rainbow trout, Oncorhynchus mykiss

NASA Astrophysics Data System (ADS)

Hou, Ya-Yi; Han, Xiao-Dong; Suzuki, Yuzuru

2001-09-01

The profiles of cortisol, testosterone, 11-ketotestosterone and 17α, 20β-dihydroxy-4-pregnene-3-one in male rainbow trout reared under constant water temperature and natural photoperiod were determined by radioimmunoassay. Gonads of male rainbow trout reached maturity when the fish were two years old. Changes in the plasma levels of both sex steroid hormones and cortisol were closely related to the GSI. Plasma levels of testosterone, 11-ketotestosterone and 17α; 20β-dihydroxy 4-pregnene-3-one showed a clear peak in the annual breeding season, when the GSI reached their maxima. Plasma cortisol levels also showed clearly seasonal changes in both two- and three-year-old fish. The results suggest that the elevated plasma levels of cortisol may not just be due to stresses during the breeding season but have certain physiological functions in the reproduction of rainbow trout.

Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats

PubMed Central

Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L.; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L.

2013-01-01

The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT-7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. PMID:23792034

Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

PubMed

Oyola, Mario G; Handa, Robert J

2017-09-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity

PubMed Central

Oyola, Mario G.; Handa, Robert J.

2018-01-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism’s response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life. PMID:28859530

Modulation of follistatin and myostatin propeptide by anabolic steroids and gender.

PubMed

Mosler, S; Geisler, S; Hengevoss, J; Schiffer, T; Piechotta, M; Adler, M; Diel, P

2013-07-01

The purpose of this pilot study was to investigate the impact of training, anabolic steroids and endogenous hormones on myostatin-interacting proteins in order to identify manipulations of myostatin signalling. To identify whether analysis of the myostatin interacting proteins follistatin and myostatin propeptide is suitable to detect the abuse of anabolic steroids, their serum concentrations were monitored in untrained males, bodybuilders using anabolic steroids and natural bodybuilders. In addition, we analysed follistatin and myostatin propeptide serum proteins in females during menstrual cycle. Our results showed increased follistatin concentrations in response to anabolic steroids. Furthermore, variations of sex steroid levels during the menstrual cycle had no impact on the expression of follistatin and myostatin propetide. In addition, we identified gender differences in the basal expression of the investigated proteins. In general, follistatin and myostatin propeptide concentrations were relatively stable within the same individual both in males and females. In conclusion, the current findings provide an insight into gender differences in myostatin-interacting proteins and their regulation in response to anabolic steroids and endogenous hormones. Therefore our data provide new aspects for the development of doping prevention strategies. © Georg Thieme Verlag KG Stuttgart · New York.

Sex hormones alter sex ratios in the Indian skipper frog, Euphlyctis cyanophlyctis: Determining sensitive stages for gonadal sex reversal.

PubMed

Phuge, S K; Gramapurohit, N P

2015-09-01

In amphibians, although genetic factors are involved in sex determination, gonadal sex differentiation can be modified by exogenous steroid hormones suggesting a possible role of sex steroids in regulating the process. We studied the effect of testosterone propionate (TP) and estradiol-17β (E2) on gonadal differentiation and sex ratio at metamorphosis in the Indian skipper frog, Euphlyctis cyanophlyctis with undifferentiated type of gonadal differentiation. A series of experiments were carried out to determine the optimum dose and sensitive stages for gonadal sex reversal. Our results clearly indicate the importance of sex hormones in controlling gonadal differentiation of E. cyanophlyctis. Treatment of tadpoles with 10, 20, 40, and 80μg/L TP throughout larval period resulted in the development of 100% males at metamorphosis at all concentrations. Similarly, treatment of tadpoles with 40μg/L TP during ovarian and testicular differentiation resulted in the development of 90% males, 10% intersexes and 100% males respectively. Treatment of tadpoles with 10, 20, 40, and 80μg/L E2 throughout larval period likewise produced 100% females at all concentrations. Furthermore, exposure to 40μg/L E2 during ovarian and testicular differentiation produced 95% females, 5% intersexes and 91% females, 9% intersexes respectively. Both TP and E2 were also effective in advancing the stages of gonadal development. Present study shows the effectiveness of both T and E2 in inducing complete sex reversal in E. cyanophlyctis. Generally, exposure to E2 increased the larval period resulting in significantly larger females than control group while the larval period of control and TP treated groups was comparable. Copyright © 2014 Elsevier Inc. All rights reserved.

Hepatic overexpression of steroid sulfatase ameliorates mouse models of obesity and type 2 diabetes through sex-specific mechanisms.

PubMed

Jiang, Mengxi; He, Jinhan; Kucera, Heidi; Gaikwad, Nilesh W; Zhang, Bin; Xu, Meishu; O'Doherty, Robert M; Selcer, Kyle W; Xie, Wen

2014-03-21

The steroid sulfatase (STS)-mediated desulfation is a critical metabolic mechanism that regulates the chemical and functional homeostasis of endogenous and exogenous molecules. In this report, we first showed that the liver expression of Sts was induced in both the high fat diet (HFD) and ob/ob models of obesity and type 2 diabetes and during the fed to fasting transition. In defining the functional relevance of STS induction in metabolic disease, we showed that overexpression of STS in the liver of transgenic mice alleviated HFD and ob/ob models of obesity and type 2 diabetes, including reduced body weight, improved insulin sensitivity, and decreased hepatic steatosis and inflammation. Interestingly, STS exerted its metabolic benefit through sex-specific mechanisms. In female mice, STS may have increased hepatic estrogen activity by converting biologically inactive estrogen sulfates to active estrogens and consequently improved the metabolic functions, whereas ovariectomy abolished this protective effect. In contrast, the metabolic benefit of STS in males may have been accounted for by the male-specific decrease of inflammation in white adipose tissue and skeletal muscle as well as a pattern of skeletal muscle gene expression that favors energy expenditure. The metabolic benefit in male STS transgenic mice was retained after castration. Treatment with the STS substrate estrone sulfate also improved metabolic functions in both the HFD and ob/ob models. Our results have uncovered a novel function of STS in energy metabolism and type 2 diabetes. Liver-specific STS induction or estrogen/estrogen sulfate delivery may represent a novel approach to manage metabolic syndrome.

Ovine placental steroid synthesis and metabolism in late gestation.

PubMed

Reynolds, Lawrence P; Legacki, Erin L; Corbin, C Jo; Caton, Joel S; Vonnahme, Kimberly A; Stanley, Scott; Conley, Alan J

2018-04-14

Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude 1) that diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and 2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

The behavioural consequences of sex reversal in dragons

PubMed Central

Li, Hong; Holleley, Clare E.; Elphick, Melanie; Georges, Arthur

2016-01-01

Sex differences in morphology, physiology, and behaviour are caused by sex-linked genes, as well as by circulating sex-steroid levels. Thus, a shift from genotypic to environmental sex determination may create an organism that exhibits a mixture of male-like and female-like traits. We studied a lizard species (Central Bearded Dragon, Pogona vitticeps), in which the high-temperature incubation of eggs transforms genetically male individuals into functional females. Although they are reproductively female, sex-reversed dragons (individuals with ZZ genotype reversed to female phenotype) resemble genetic males rather than females in morphology (relative tail length), general behaviour (boldness and activity level), and thermoregulatory tactics. Indeed, sex-reversed ‘females’ are more male-like in some behavioural traits than are genetic males. This novel phenotype may impose strong selection on the frequency of sex reversal within natural populations, facilitating rapid shifts in sex-determining systems. A single period of high incubation temperatures (generating thermally induced sex reversal) can produce functionally female individuals with male-like (or novel) traits that enhance individual fitness, allowing the new temperature-dependent sex-determining system to rapidly replace the previous genetically based one.

Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8-, and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study.

PubMed

Wen, Hui-Ju; Sie, Lillian; Su, Pen-Hua; Chuang, Chia-Jui; Chen, Hsiao-Yen; Sun, Chien-Wen; Huang, Li-Hua; Hsiung, Chao Agnes; Julie Wang, Shu-Li

2017-11-01

Phthalate diesters are commonly used and have been well established as environmental endocrine disruptors. However, few studies have examined their effects on sex steroid hormones in children. We followed children over time to examine the association between pre- and post-natal phthalate exposure and sex steroid hormone levels at 2, 5, 8, and 11 years of age. We recruited 430 pregnant women from central Taiwan from 2000 to 2001 and assessed their children at birth, 2, 5, 8, and 11 years of age. We studies children with at least one measurement for both phthalate and hormone levels during each any of the follow-up time point (n = 193). Estradiol, free testosterone, testosterone, and progesterone were measured from venous blood. Three monoesters of di-2-ethylhexyl phthalate (DEHP), mono-benzyl phthalate, mono-n-butyl phthalate, mono-ethyl phthalate, and mono-methyl phthalate were measured in maternal urine collected during the 3rd trimester and child urine collected at each follow-up point. The sum of mono-2-ethylhexyl phthalate (∑MEHP) was calculated by summing the concentrations of the three DEHP monoesters. Generalized estimating equation regression analysis with repeated measures was used to estimate associations between phthalate metabolites and hormone levels. After adjustment for potential confounders, maternal ∑MEHP level was associated with decreased levels of progesterone in girls (β = -0.309 p = 0.001). The child ∑MEHP concentration was associated with decreased levels of progesterone for girls (β = -0.194, p = 0.003) and with decreased levels of free testosterone for boys (β = -0.124, p = 0.004). Early-life DEHP exposure may alter sex steroid hormones of children over time, which may pose potential reproductive health risks. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Sex Differences in Cognitive Impairment and Alzheimer’s Disease

PubMed Central

Li, Rena; Singh, Meharvan

2014-01-01

Studies have shown differences in specific cognitive ability domains and risk of Alzheimer’s disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer’s disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer’s disease in men and women. PMID:24434111

Steroid plant hormones: effects outside plant kingdom.

PubMed

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

2015-05-01

Brassinosteroids (BS) are the first group of steroid-hormonal compounds isolated from and acting in plants. Among numerous physiological effects of BS growth stimulation and adaptogenic activities are especially remarkable. In this review, we provide evidence that BS possess similar types of activity also beyond plant kingdom at concentrations comparable with those for plants. This finding allows looking at steroids from a new point of view: how common are the mechanisms of steroid bioregulation in different types of organisms from protozoa to higher animals. Copyright © 2014 Elsevier Inc. All rights reserved.

Non-steroidal anti-inflammatory drugs and benign oesophageal stricture.

PubMed Central

Heller, S R; Fellows, I W; Ogilvie, A L; Atkinson, M

1982-01-01

Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution. PMID:6807392

Sex change strategy and the aromatase genes.

PubMed

Gardner, L; Anderson, T; Place, A R; Dixon, B; Elizur, A

2005-04-01

Sequential hermaphroditism is a common reproductive strategy in many teleosts. Steroid production is known to mediate both the natural and induced sex change, yet beyond this the physiology directing this process has received little attention. Cytochrome P450 aromatase is a key enzyme in the hormonal pathway catalysing the conversion of sex steroids, androgens to oestrogens, and thus is highly relevant to the process of sex change. This study reports the isolation of cDNA sequences for aromatase isoforms CYP19A1 and CYP19A2 from teleost species representing three forms of sexual hermaphroditism: Lates calcarifer (protandry), Cromileptes altivelis (protogyny), and Gobiodon histrio (bi-directional). Deduced amino acid analysis of these isoforms with other reported isoforms from gonochoristic (single sex) teleosts revealed 56-95% identity within the same isoform while only 48-65% identity between isoforms irrespective of species and sexual strategy. Phylogenetic analysis supported this result separating sequences into isoform exclusive clades in spite of species apparent evolutionary distance. Furthermore, this study isolates 5' flanking regions of all above genes and describes putative cis-acting elements therein. Elements identified include steroidogenic factor 1 binding site (SF-1), oestrogen response element (ERE), progesterone response element (PRE), androgen response element (ARE), glucocorticoid response elements (GRE), peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha heterodimer responsive element (PPARalpha/RXRalpha), nuclear factor kappabeta (NF-kappabeta), SOX 5, SOX 9, and Wilms tumor suppressor (WTI). A hypothetical in vivo model was constructed for both isoforms highlighting potential roles of these putative cis-acting elements with reference to normal function and sexual hermaphroditism.

Characterizing the distribution of steroid sulfatase during embryonic development: when and where might metabolites of maternal steroids be reactivated?

PubMed

Paitz, Ryan T; Duffield, Kristin R; Bowden, Rachel M

2017-12-15

All vertebrate embryos are exposed to maternally derived steroids during development. In placental vertebrates, metabolism of maternal steroids by the placenta modulates embryonic exposure, but how exposure is regulated in oviparous vertebrates is less clear. Recent work in oviparous vertebrates has demonstrated that steroids are not static molecules, as they can be converted to more polar steroid sulfates by sulfotransferase enzymes. Importantly, these steroid sulfates can be converted back to the parent compound by the enzyme steroid sulfatase (STS). We investigated when and where STS was present during embryonic development in the red-eared slider turtle, Trachemys scripta We report that STS is present during all stages of development and in all tissues we examined. We conclude that STS activity may be particularly important for regulating maternal steroid exposure in oviparous vertebrates. © 2017. Published by The Company of Biologists Ltd.

Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis.

PubMed

Zhao, R; Wang, H; Wang, X; Feng, F

2017-03-01

This meta-analysis synthesized current evidence from 10 trials to evaluate the association between steroid therapy and osteonecrosis incidence in patients with severe acute respiratory syndrome (SARS). Our results suggest that higher cumulative doses and longer treatment durations of steroids are more likely to lead to the development of osteonecrosis in SARS patients. The link between steroid treatment and the risk of osteonecrosis in SARS patients remains unknown. The present meta-analysis aimed to examine the dose-response association between steroid therapy and osteonecrosis incidence in SARS patients. The sex differences in the development of steroid-induced osteonecrosis were also examined. We searched PubMed, Web of Science, CNKI, and WANFANG for studies that involved steroid therapy and reported osteonecrosis data in SARS patients. Two authors independently extracted the data from the individual studies, and the rate ratio (RR) of osteonecrosis was calculated using random-effect models. Ten studies with 1137 recovered SARS patients met the inclusion criteria. Close relationships between osteonecrosis incidence and both the cumulative dose and treatment duration of steroids were observed. The summary RR of osteonecrosis was 1.57 (95% confidence interval (CI) 1.30-1.89, p < 0.001) per 5.0 g increase in the cumulative dose of steroids and was 1.29 (95% CI 1.09-1.53, p = 0.003) for each 10-day increment of increase in treatment duration. The relationship was non-linear (p non-linear  < 0.001 and p non-linear  = 0.022). There were no significant differences in the risk of developing osteonecrosis between the male and female patients (RR 0.01, 95% CI -0.03 to 0.06, p = 0.582). SARS patients who received higher cumulative doses and longer treatment durations of steroids were more likely to develop osteonecrosis, and there were no sex differences in this dose-dependent side effect. Our findings suggest that it is important to reduce osteonecrosis risk by

The Sturm und Drang of anabolic steroid use: angst, anxiety, and aggression

PubMed Central

Oberlander, Joseph G.; Henderson, Leslie P.

2014-01-01

Anabolic androgenic steroids (AAS) are illicitly administered to enhance athletic performance and body image. Although conferring positive actions on performance, steroid abuse is associated with changes in anxiety and aggression. AAS users are often keenly invested in understanding the biological actions of these drugs. Thus, mechanistic information on AAS actions is important not only for the biomedical community, but also for steroid users. Here we review findings from animal studies on the impact of AAS exposure on neural systems that are crucial for the production of anxiety and aggression, and compare the effects of the different classes of AAS and their potential signaling mechanisms, as well as context-, age- and sex-dependent aspects of their actions. PMID:22516619

Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats.

PubMed

Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L

2013-10-01

The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT--7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. Copyright © 2013 Elsevier B.V. All rights reserved.

Obesity and Sex Interact in the Regulation of Alzheimer’s Disease

PubMed Central

Moser, V. Alexandra; Pike, Christian J.

2015-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which a number of genetic, environmental, and lifestyle risk factors have been identified. A significant modifiable risk factor is obesity in mid-life. Interestingly, both obesity and AD exhibit sex differences and are regulated by sex steroid hormones. Accumulating evidence suggests interactions between obesity and sex in regulation of AD risk, although the pathways underlying this relationship are unclear. Inflammation and the E4 allele of apolipoprotein E have been identified as independent risk factors for AD and both interact with obesity and sex steroid hormones. We review the individual and cooperative effects of obesity and sex on development of AD and examine the potential contributions of apolipoprotein E, inflammation, and their interactions to this relationship. PMID:26708713

Steroid hormones specifically modify the activity of organic anion transporting polypeptides.

PubMed

Koenen, Anna; Köck, Kathleen; Keiser, Markus; Siegmund, Werner; Kroemer, Heyo K; Grube, Markus

2012-11-20

Previously, the steroid hormone progesterone has been demonstrated to stimulate OATP2B1-mediated transport of estrone-3-sulphate (E(1)S), dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PS), which may influence the uptake of precursor molecules for steroid hormone synthesis. However, it is unclear whether OATP2B1 drug substrates like atorvastatin or glibenclamide are also affected by this phenomenon. In addition, it has not been studied so far if this stimulatory effect is specific for OATP2B1. To address these questions, we examined the influence of progesterone on OATP2B1-mediated atorvastatin and glibenclamide uptake and studied the impact of steroid hormones on the transport activity of OATP1A2, OATP1B1 and OATP1B3. Comparison of the substrate spectrum of the investigated OATPs revealed that DHEAS and atorvastatin are substrates of all transporters, while E(1)S was only significantly transported by OATP1A2, OATP2B1 and OATP1B1. Glibenclamide uptake was limited to OATP1A2, OATP1B1 and OATP2'B1. Subsequent interaction studies indicated that progesterone only increases OATP2B1-mediated E(1)S and DHEAS transport, whereas uptake of BSP, atorvastatin and glibenclamide was either inhibited or not affected. Moreover, the steroid hormone effect was specific for OATP2B1; neither OATP1B1, OATP1B3 nor OATP1A2 function was stimulated in the presence of progesterone. Similar to progesterone, the glucocorticoide dexamethasone stimulated OATP2B1-mediated transport of E(1)S and DHEAS (EC(50) for E(1)S: 10.2 ± 5.6 μM and 17.9 ± 15.4 μM for DHEAS). In conclusion, our data demonstrate that among the tested compounds the stimulatory effect of progesterone is specific for OATP2B1 and restricted to sulphated steroids like E(1)S and DHEAS while the OATP-mediated drug transport is not enhanced. Copyright © 2012 Elsevier B.V. All rights reserved.

Sex and Stress Hormone Influences on the Expression and Activity of Brain-Derived Neurotrophic Factor

PubMed Central

Carbone, David L.; Handa, Robert J.

2012-01-01

The neurotrophin, brain-derived neurotrophic factor (BDNF), is recognized as a key component in the regulation of central nervous system ontogeny, homeostasis and adult neuroplasticity. The importance of BDNF in central nervous system development and function is well documented by numerous reports from animal studies linking abnormal BDNF signaling to metabolic disturbances and anxiety or depressive-like behavior. Despite the diverse roles for BDNF in nearly all aspects of central nervous system physiology, the regulation of BDNF expression, as well as our understanding of the signaling mechanisms associated with this neurotrophin, remains incomplete. However, links between sex hormones such as estradiol and testosterone, as well as endogenous and synthetic glucocorticoids, have emerged as important mediators of BDNF expression and function. Examples of such regulation include brain region-specific induction of Bdnf mRNA in response to estradiol. Additional studies have also documented regulation of the expression of the high-affinity BDNF receptor TrkB by estradiol, thus implicating sex steroids not only in the regulation of BDNF expression, but on mechanisms of signaling associated with it. In addition to gonadal steroids, further evidence also suggests functional interaction between BDNF and glucocorticoids, such as in the regulation of corticotrophin-releasing hormone and other important neuropeptides. In this review, we provide an overview of the roles played by selected sex or stress hormones in the regulation of BDNF expression and signaling in the central nervous system PMID:23211562

Pharmacology of anabolic steroids.

PubMed

Kicman, A T

2008-06-01

Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic-androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided.

Pharmacology of anabolic steroids

PubMed Central

Kicman, A T

2008-01-01

Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic–androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co-activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non-genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided. PMID:18500378

Seco-pregnane steroidal glycosides from the roots of Cynanchum atratum and their anti-TMV activity.

PubMed

Yan, Ying; Zhang, Jian-xin; Liu, Kai-xing; Huang, Tao; Yan, Chen; Huang, Lie-jun; Liu, Sheng; Mu, Shu-zhen; Hao, Xiao-jiang

2014-09-01

Fifteen new seco-pregnane steroidal glycosides cynanosides A-O (1-15) together with twenty-seven known ones were isolated from the roots of Cynanchum atratum. The structures of 1-15 were determined by extensive analysis of spectroscopic data. The anti-tobacco mosaic virus (TMV) activity of these steroidal glycosides was screened by the conventional half-leaf method, enzyme-linked immunosorbent assay, and Western blot methods, most of them showed potent anti-TMV activity. Among them, compounds 1, 7, 13, 28 and 31 showed significantly anti-TMV activity with an IC50 value of 20.5, 18.6, 22.0, 19.2 and 22.2 μg/mL, respectively, and were much more effective than the positive control, ningnanmycin (IC50=49.6 μg/mL). Copyright © 2014 Elsevier B.V. All rights reserved.

New steroids from Anemarrhena asphodeloides rhizome and their α-glucosidase inhibitory activity.

PubMed

Khang, Pham Van; Phuong, Dao Mai; Ma, Lei

2017-05-01

Two new steroids were isolated from acid hydrolysis residue of the rhizomes of Anemarrhena asphodeloides. Their structures were identified on the basis of several spectroscopic analysis approaches including 1D, 2D-NMR techniques, and MS data, and by the comparison of spectral data of the known compounds. The biological activities of these two isolated compounds were explored on α-glucosidase. Compound 1 displayed 4.7 folds inhibitory activity against α-glucosidase compared with the positive control acarbose.

Antifungal activity and fungal metabolism of steroidal glycosides of Easter lily (Lilium longiflorum Thunb.) by the plant pathogenic fungus, Botrytis cinerea.

PubMed

Munafo, John P; Gianfagna, Thomas J

2011-06-08

Botrytis cinerea Pers. Fr. is a plant pathogenic fungus and the causal organism of blossom blight of Easter lily (Lilium longiflorum Thunb.). Easter lily is a rich source of steroidal glycosides, compounds which may play a role in the plant-pathogen interaction of Easter lily. Five steroidal glycosides, including two steroidal glycoalkaloids and three furostanol saponins, were isolated from L. longiflorum and evaluated for fungal growth inhibition activity against B. cinerea, using an in vitro plate assay. All of the compounds showed fungal growth inhibition activity; however, the natural acetylation of C-6''' of the terminal glucose in the steroidal glycoalkaloid, (22R,25R)-spirosol-5-en-3β-yl O-α-L-rhamnopyranosyl-(1→2)-[6-O-acetyl-β-D-glucopyranosyl-(1→4)]-β-D-glucopyranoside (2), increased antifungal activity by inhibiting the rate of metabolism of the compound by B. cinerea. Acetylation of the glycoalkaloid may be a plant defense response to the evolution of detoxifying mechanisms by the pathogen. The biotransformation of the steroidal glycoalkaloids by B. cinerea led to the isolation and characterization of several fungal metabolites. The fungal metabolites that were generated in the model system were also identified in Easter lily tissues infected with the fungus by LC-MS. In addition, a steroidal glycoalkaloid, (22R,25R)-spirosol-5-en-3β-yl O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (6), was identified as both a fungal metabolite of the steroidal glycoalkaloids and as a natural product in L. longiflorum for the first time.

In vitro steroid-induced meiosis in Rhinella arenarum oocytes: role of pre-MPF activation.

PubMed

Arias Torres, Ana Josefina; Bühler, Marta Inés; Zelarayán, Liliana Isabel

2016-04-01

In this work we showed the relationship between seasonal periods and the response of R. arenarum follicles and oocytes to different steroids. Using in vitro germinal vesicle breakdown (GVBD) assays, we demonstrated that P4 is the main steroid capable of inducing maturation in R. arenarum oocytes and follicles. In the second part of this work we showed that androgens can activate pre-maturation promoting factors (pre-MPFs) such as P4, by cytoplasm microinjection experiments. The results indicated that the steroids assayed induced oocyte and follicle maturation in a dose- and time-dependent manner. In oocytes, P4 was the most efficient steroid as a maturation inducer (EC50 of the reproductive period, 6 nM, EC50 of the non-reproductive period ≅ 30 nM). Androgens (DHEA, dehydroepiandrosterone; T, testosterone; and AD, androstenedione) were less efficient maturation inducers than P4 (EC50 reproductive period ≅ 50, 120 and 600 nM respectively). Similar results were obtained with intact follicles in both seasonal periods. Although the response of follicles to the different androgens was variable, in no case was it above the above the response induced by P4. Independently of the season, oocytes and follicles incubated in P4, P5 and T underwent GVBD after 6-10 h while oocytes and follicles incubated in DHEA and AD matured more slowly. Furthermore, we demonstrated that microinjection of mature cytoplasm from androgen-treated oocytes is sufficient to promote GVBD in immature recipient oocytes (DHEA, 57 ± 12%; AD, 60 ± 8%; T, 56 ± 13%). Thus, androgens such as DHEA, T and AD are as competent as P4 to activate pre-MPF.

Birdsong and the neural production of steroids

PubMed Central

Remage-Healey, Luke; London, Sarah E.; Schinger, Barney A.

2009-01-01

The forebrain circuits involved in singing and audition (the ‘song system’) in songbirds exhibit a remarkable capacity to synthesize and respond to steroid hormones. This review considers how local brain steroid production impacts the development, sexual differentiation, and activity of song system circuitry. The songbird forebrain contains all of the enzymes necessary for the de novo synthesis of steroids - including neuroestrogens - from cholesterol. Steroid production enzymes are found in neuronal cell bodies, but they are also expressed in pre-synaptic terminals in the song system, indicating a novel mode of brain steroid delivery to local circuits. The song system expresses nuclear hormone receptors, consistent with local action of brain-derived steroids. Local steroid production also occurs in brain regions that do not express nuclear hormone receptors, suggesting a non-classical mode-of-action. Recent evidence indicates that local steroid levels can change rapidly within the forebrain, in a manner similar to traditional neuromodulators. Lastly, we consider growing evidence for modulatory interactions between brain-derived steroids and neurotransmitter/neuropeptide networks within the song system. Songbirds have therefore emerged as a rich and powerful model system to explore the neural and neurochemical regulation of social behavior. PMID:19589382

Into the world of steroids

PubMed Central

2010-01-01

Evolution of steroids such as sex hormones and ecdysteroids occurred independently in the animal and plant kingdoms. Plants use phytoecdysteroids (PEs) to control defense interactions with some predators; furthermore, PEs can exert beneficial influence on many aspects of mammalian metabolism. Endocrine disrupting compounds such as the estrogen agonist bisphenol A (BPA) are widespread in the environment, posing a potential hormonal risk to animals and plants. Adverse BPA effects on reproductive development and function are coupled with other toxic effects. BPA bioremediation techniques could be developed by exploiting some tolerant plant species. PMID:20671439

The Impact of Sex, Puberty, and Hormones on White Matter Microstructure in Adolescents

PubMed Central

Herting, Megan M.; Maxwell, Emily C.; Irvine, Christy

2012-01-01

Background: During adolescence, numerous factors influence the organization of the brain. It is unclear what influence sex and puberty have on white matter microstructure, as well as the role that rapidly increasing sex steroids play. Methods: White matter microstructure was examined in 77 adolescents (ages 10–16) using diffusion tensor imaging. Multiple regression analyses were performed to examine the relationships between fractional anisotropy (FA) and mean diffusivity (MD) and sex, puberty, and their interaction, controlling for age. Follow-up analyses determined if sex steroids predicted microstructural characteristics in sexually dimorphic and pubertal-related white matter regions, as well as in whole brain. Results: Boys had higher FA in white matter carrying corticospinal, long-range association, and cortico-subcortical fibers, and lower MD in frontal and temporal white matter compared with girls. Pubertal development was related to higher FA in the insula, while a significant sex-by-puberty interaction was seen in superior frontal white matter. In boys, testosterone predicted white matter integrity in sexually dimorphic regions as well as whole brain FA, whereas estradiol showed a negative relationship with FA in girls. Conclusions: Sex differences and puberty uniquely relate to white matter microstructure in adolescents, which can partially be explained by sex steroids. PMID:22002939

Joint Effects of Smoking and Gene Variants Involved in Sex Steroid Metabolism on Hot Flashes in Late Reproductive-Age Women

PubMed Central

Freeman, Ellen W.; Sammel, Mary D.; Queen, Kaila; Lin, Hui; Rebbeck, Timothy R.

2012-01-01

Background: Although smoking has a known association with hot flashes, the factors distinguishing smokers at greatest risk for menopausal symptoms have not been well delineated. Recent evidence supports a relationship between menopausal symptoms and variants in several genes encoding enzymes that metabolize substrates such as sex steriods, xenobiotics, and catechols. It is currently not known whether the impact of smoking on hot flashes is modified by the presence of such variants. Objective: The objective of the study was to investigate the relationship between smoking and hot flash occurrence as a function of genetic variation in sex steroid-metabolizing enzymes. Methods: A cross-sectional analysis of data from the Penn Ovarian Aging study, an ongoing population-based cohort of late reproductive-aged women, was performed. Smoking behavior was characterized. Single-nucleotide polymorphisms in five genes were investigated: COMT Val158Met (rs4680), CYP1A2*1F (rs762551), CYP1B1*4 (Asn452Ser, rs1800440), CYP1B1*3 (Leu432Val, rs1056836), and CYP3A4*1B (rs2740574). Results: Compared with nonsmokers, European-American COMT Val158Met double-variant carriers who smoked had increased odds of hot flashes [adjusted odds ratio (AOR) 6.15, 95% confidence interval (CI) 1.32–28.78)]; European-American COMT Val158Met double-variant carriers who smoked heavily had more frequent moderate or severe hot flashes than nonsmokers (AOR 13.7, 95% CI 1.2–154.9). European-American CYP 1B1*3 double-variant carriers who smoked described more frequent moderate or severe hot flashes than nonsmoking (AOR 20.6, 95% CI 1.64–257.93) and never-smoking (AOR 20.59, 95% CI 1.39–304.68) carriers, respectively. African-American single-variant CYP 1A2 carriers who smoked were more likely to report hot flashes than the nonsmoking carriers (AOR 6.16, 95% CI 1.11–33.91). Conclusion: This is the first report demonstrating the effects of smoking within the strata of gene variants involved in sex

Joint effects of smoking and gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women.

PubMed

Butts, Samantha F; Freeman, Ellen W; Sammel, Mary D; Queen, Kaila; Lin, Hui; Rebbeck, Timothy R

2012-06-01

Although smoking has a known association with hot flashes, the factors distinguishing smokers at greatest risk for menopausal symptoms have not been well delineated. Recent evidence supports a relationship between menopausal symptoms and variants in several genes encoding enzymes that metabolize substrates such as sex steriods, xenobiotics, and catechols. It is currently not known whether the impact of smoking on hot flashes is modified by the presence of such variants. The objective of the study was to investigate the relationship between smoking and hot flash occurrence as a function of genetic variation in sex steroid-metabolizing enzymes. A cross-sectional analysis of data from the Penn Ovarian Aging study, an ongoing population-based cohort of late reproductive-aged women, was performed. Smoking behavior was characterized. Single-nucleotide polymorphisms in five genes were investigated: COMT Val158Met (rs4680), CYP1A2*1F (rs762551), CYP1B1*4 (Asn452Ser, rs1800440), CYP1B1*3 (Leu432Val, rs1056836), and CYP3A4*1B (rs2740574). Compared with nonsmokers, European-American COMT Val158Met double-variant carriers who smoked had increased odds of hot flashes [adjusted odds ratio (AOR) 6.15, 95% confidence interval (CI) 1.32-28.78)]; European-American COMT Val158Met double-variant carriers who smoked heavily had more frequent moderate or severe hot flashes than nonsmokers (AOR 13.7, 95% CI 1.2-154.9). European-American CYP 1B1*3 double-variant carriers who smoked described more frequent moderate or severe hot flashes than nonsmoking (AOR 20.6, 95% CI 1.64-257.93) and never-smoking (AOR 20.59, 95% CI 1.39-304.68) carriers, respectively. African-American single-variant CYP 1A2 carriers who smoked were more likely to report hot flashes than the nonsmoking carriers (AOR 6.16, 95% CI 1.11-33.91). This is the first report demonstrating the effects of smoking within the strata of gene variants involved in sex steroid metabolism on hot flashes in late reproductive-age women

Mono-hydroxy methoxychlor alters levels of key sex steroids and steroidogenic enzymes in cultured mouse antral follicles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Craig, Zelieann R., E-mail: zelieann@gmail.co; Leslie, Traci C., E-mail: traci.leslie@gmail.co; Hatfield, Kimberly P., E-mail: kpm9786@yahoo.co

Methoxychlor (MXC) is an organochlorine pesticide that reduces fertility in female rodents by decreasing antral follicle numbers and increasing follicular death. MXC is metabolized in the body to mono-hydroxy MXC (mono-OH). Little is known about the effects of mono-OH on the ovary. Thus, this work tested the hypothesis that mono-OH exposure decreases production of 17{beta}-estradiol (E{sub 2}) by cultured mouse antral follicles. Antral follicles were isolated from CD-1 mice (age 35-39 days) and exposed to dimethylsulfoxide (DMSO), or mono-OH (0.1-10 {mu}g/mL) for 96 h. Media and follicles were collected for analysis of sex steroid levels and mRNA expression, respectively. Mono-OHmore » treatment (10 {mu}g/mL) decreased E{sub 2} (DMSO: 3009.72 {+-} 744.99 ng/mL; mono-OH 0.1 {mu}g/mL: 1679.66 {+-} 461.99 ng/mL; 1 {mu}g/mL: 1752.72 {+-} 532.41 ng/mL; 10 {mu}g/mL: 45.89 {+-} 33.83 ng/mL), testosterone (DMSO: 15.43 {+-} 2.86 ng/mL; mono-OH 0.1 {mu}g/mL: 17.17 {+-} 4.71 ng/mL; 1 {mu}g/mL: 13.64 {+-} 3.53 ng/mL; 10 {mu}g/mL: 1.29 {+-} 0.23 ng/mL), androstenedione (DMSO: 1.92 {+-} 0.34 ng/mL; mono-OH 0.1 {mu}g/mL: 1.49 {+-} 0.43 ng/mL; 1 {mu}g/mL: 0.64 {+-} 0.31 ng/mL; 10 {mu}g/mL: 0.12 {+-} 0.06 ng/mL) and progesterone (DMSO: 24.11 {+-} 4.21 ng/mL; mono-OH 0.1 {mu}g/mL: 26.77 {+-} 4.41 ng/mL; 1 {mu}g/mL: 20.90 {+-} 3.75 ng/mL; 10 {mu}g/mL: 9.44 {+-} 2.97 ng/mL) levels. Mono-OH did not alter expression of Star, Hsd3b1, Hsd17b1 and Cyp1b1, but it did reduce levels of Cyp11a1, Cyp17a1 and Cyp19a1 mRNA. Collectively, these data suggest that mono-OH significantly decreases levels of key sex steroid hormones and the expression of enzymes required for steroidogenesis.« less

1-Ene-steroid reductase of Mycobacterium sp. NRRL B-3805.

PubMed

Goren, T; Harnik, M; Rimon, S; Aharonowitz, Y

1983-12-01

The microbial enzymatic reduction of 1,4-androstadiene-3,17-dione (ADD) to 4-androstene-3,17-dione (AD), testosterone and 1-dehydrotestosterone (DHT) is described. Two reducing activities observed in washed cell suspensions and cell free extracts of Mycobacterium sp. NRRL B-3805 were found to account for these bioconversions. One was a 1-ene-steroid reductase and the other a 17-keto steroid reductase. The first reducing activity was found to appear in the soluble cell fraction whereas the latter could be precipitated by centrifugation. Maximum 1-ene-steroid reductase specific activity was achieved during the exponential growth phase of the organism and significantly increased upon induction with ADD. The 1-ene-steroid reductase was partially purified (30-fold) by ammonium sulfate fractionation, gel-filtration and ion-exchange chromatography, and was eluted from a Sephacryl S-300 column with an Mr = 115,000. The 1-ene-steroid reductase activity was NADPH-dependent and had specificity towards steroid compounds containing C-1,2 double bond with an apparent Km for ADD of 2.2 X 10(-5) M. The reverse reaction catalyzing C-1,2 dehydrogenation could not be detected in our preparations. The results suggest that in Mycobacterium sp NRRL B-3805 and B-3683 the steroid C-1,2 dehydrogenation and 1-ene reduction are two separable activities.

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

Thyroid hormone modulates offspring sex ratio in a turtle with temperature-dependent sex determination

PubMed Central

Li, Teng; Mu, Yi; McGlashan, Jessica K.; Georges, Arthur

2016-01-01

The adaptive significance of temperature-dependent sex determination (TSD) has attracted a great deal of research, but the underlying mechanisms by which temperature determines the sex of a developing embryo remain poorly understood. Here, we manipulated the level of a thyroid hormone (TH), triiodothyronine (T3), during embryonic development (by adding excess T3 to the eggs of the red-eared slider turtle Trachemys scripta, a reptile with TSD), to test two competing hypotheses on the proximate basis for TSD: the developmental rate hypothesis versus the hormone hypothesis. Exogenous TH accelerated embryonic heart rate (and hence metabolic rate), developmental rate, and rates of early post-hatching growth. More importantly, hyperthyroid conditions depressed expression of Cyp19a1 (the gene encoding for aromatase) and levels of oestradiol, and induced more male offspring. This result is contrary to the direction of sex-ratio shift predicted by the developmental rate hypothesis, but consistent with that predicted by the hormone hypothesis. Our results suggest an important role for THs in regulating sex steroid hormones, and therefore, in affecting gonadal sex differentiation in TSD reptiles. Our study has implications for the conservation of TSD reptiles in the context of global change because environmental contaminants may disrupt the activity of THs, and thereby affect offspring sex in TSD reptiles. PMID:27798296

Comparison of Oogenesis and Sex Steroid Profiles between Twice and Once Annually Spawning of Rainbow Trout Females (Oncorhynchus mykiss)

PubMed Central

Estay, Francisco; Colihueque, Nelson; Araneda, Cristian

2012-01-01

This study compares the gonadosomatic index (GSI), oocyte growth (OG), gonadal histology, and plasma level concentrations of sex hormones (estradiol-17β (E2) and vitellogenin (V)) of twice-spawning (T-SP) and once-spawning (O-SP) females of rainbow trout throughout the additional and the normal reproductive cycle, respectively. In T-SP, the GSI values rapidly increase from May to November, in contrast to O-SP, which showed low and constant GSI values (1.19 to 14.5 and 1.19 to 0.63, resp.). T-SP exhibited a marked increase of OG in the same period, reaching a maximum diameter of 4,900 ± 141.42 μm, in contrast to O-SP, which presented a slow OG. The gonadal histology of T-SP agreed with the general pattern of ovogenesis observed for O-SP (vitellogenesis, ovulation, and recrudescence); however, this process was nonsynchronous between the two breeder groups. Plasma steroid levels showed significant variation during oogenesis, which agreed with the GSI, OG, and gonadal histology patterns. The level of E2 increased to a maximum value of 26.2 ng/mL and 36.0 ng/mL in O-SP and T-SP, respectively, one or two months before the spawning event where vitellogenesis was fully active. The V concentrations followed a pattern similar to those of E2. PMID:23213308

Purification, characterization, and substrate specificity of a glucoamylase with steroidal saponin-rhamnosidase activity from Curvularia lunata.

PubMed

Feng, Bing; Hu, Wei; Ma, Bai-ping; Wang, Yong-ze; Huang, Hong-ze; Wang, Sheng-qi; Qian, Xiao-hong

2007-10-01

It has been previously reported that a glucoamylase from Curvularia lunata is able to hydrolyze the terminal 1,2-linked rhamnosyl residues of sugar chains at C-3 position of steroidal saponins. In this work, the enzyme was isolated and identified after isolation and purification by column chromatography including gel filtration and ion-exchange chromatography. Analysis of protein fragments by MALDI-TOF/TOF proteomics Analyzer indicated the enzyme to be 1,4-alpha-D-glucan glucohydrolase EC 3.2.1.3, GA and had considerable homology with the glucoamylase from Aspergillus oryzae. We first found that the glucoamylase was produced from C. lunata and was able to hydrolyze the terminal rhamnosyl of steroidal saponins. The enzyme had the general character of glucoamylase, which hydrolyze starch. It had a molecular mass of 66 kDa and was optimally active at 50 degrees C, pH 4, and specific activity of 12.34 U mg of total protein(-1) under the conditions, using diosgenin-3-O-alpha-L-rhamnopyranosyl(1-->4)-[alpha-L-rhamnopyranosyl (1-->2)]-beta-D-glucopyranoside (compound II) as the substrate. Furthermore, four kinds of commercial glucoamylases from Aspergillus niger were investigated in this work, and they had the similar activity in hydrolyzing terminal rhamnosyl residues of steroidal saponin.

Using sex differences in the developing brain to identify nodes of influence for seizure susceptibility and epileptogenesis.

PubMed

Kight, Katherine E; McCarthy, Margaret M

2014-12-01

Sexual differentiation of the developing brain organizes the neural architecture differently between males and females, and the main influence on this process is exposure to gonadal steroids during sensitive periods of prenatal and early postnatal development. Many molecular and cellular processes are influenced by steroid hormones in the developing brain, including gene expression, cell birth and death, neurite outgrowth and synaptogenesis, and synaptic activity. Perturbations in these processes can alter neuronal excitability and circuit activity, leading to increased seizure susceptibility and the promotion of pathological processes that constitute epileptogenesis. In this review, we will provide a general overview of sex differences in the early developing brain that may be relevant for altered seizure susceptibility in early life, focusing on limbic areas of the brain. Sex differences that have the potential to alter the progress of epileptogenesis are evident at molecular and cellular levels in the developing brain, and include differences in neuronal excitability, response to environmental insult, and epigenetic control of gene expression. Knowing how these processes differ between the sexes can help us understand fundamental mechanisms underlying gender differences in seizure susceptibility and epileptogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Age Disparities in the Use of Steroid-sparing Therapy for Inflammatory Bowel Disease.

PubMed

Govani, Shail M; Wiitala, Wyndy L; Stidham, Ryan W; Saini, Sameer D; Hou, Jason K; Feagins, Linda A; Sussman, Jeremy B; Higgins, Peter D R; Waljee, Akbar K

2016-08-01

Corticosteroids are effective rescue therapies for patients with inflammatory bowel disease (IBD), but have significant side effects, which may be amplified in the growing population of elderly patients with IBD. We aimed to compare the use of steroids and steroid-sparing therapies (immunomodulators and biologics) and rates of complications among elderly (≥65) and younger patients in a national cohort of veterans with IBD. We used national Veterans Health Administrative data to conduct a retrospective study of veterans with IBD between 2002 and 2010. Medications and the incidence of complications were obtained from the Veterans Health Administrative Decision Support Systems. Multivariate logistic regression accounting for facility-level clustering was used to identify predictors of use of steroid-sparing medications. We identified 30,456 veterans with IBD. Of these, 94% were men and 40% were more than 65, and 32% were given steroids. Elderly veterans were less likely to receive steroids (23.8% versus 38.3%, P < 0.001) and were less likely to be prescribed steroid-sparing medications (25.5% versus 46.9%, respectively, P < 0.001). In multivariate analysis controlling for sex, age <65 (odds ratio, 2.19; 95% CI, 1.54-3.11) and gastroenterology care (odds ratio, 8.42; 95% CI, 6.18-11.47) were associated with initiation of steroid-sparing medications. After starting steroids, fracture rates increased in the elderly patients with IBD, whereas increases in venous thromboembolism and infections after starting steroids affected both age groups. Elderly veterans are less likely to receive steroids and steroid-sparing medications than younger veterans; elderly patients exposed to steroids were more likely to have fractures than the younger population.

Benign stricture of the oesophagus: role of non-steroidal anti-inflammatory drugs.

PubMed Central

Wilkins, W E; Ridley, M G; Pozniak, A L

1984-01-01

The medication history of patients presenting with benign oesophageal stricture is compared with an age and sex matched control population selected from the community. Fifty five out of 151 consecutive admissions to a dysphagia clinic were found to have benign oesophageal stricture. Twenty six out of 53 (49%) had been prescribed non-steroidal anti-inflammatory drugs in the year preceding their clinic appointment. Ten patients (19%) had been prescribed other drugs implicated in oesophageal disease over the same period. In the control population, 20 out of 165 (12%) had been prescribed non-steroidal anti-inflammatory drugs, and 31 out of 165 had been prescribed 'other' drugs in the preceding year. The difference between numbers on non-steroidal anti-inflammatory drugs in the patient and control groups was highly significant (X2 = 23.87, p less than 0.1%). This study has shown an association between the prescribing of non-steroidal anti-inflammatory drugs and benign stricture of the oesophagus. PMID:6714790

Binding of alkylphenols and alkylated non-phenolics to the rainbow trout (Oncorhynchus mykiss) plasma sex steroid-binding protein.

PubMed

Tollefsen, K-E

2007-09-01

Alkylphenols are well-known endocrine disrupters, mediating effects through the estrogen receptor (ER). Although the estrogenic properties of the alkylphenols are well documented, alternative mechanisms of action are poorly described. In the present work, the interaction of a range of alkyl-substituted phenols and alkyl-substituted non-phenolics with the rainbow trout (Oncorhynchus mykiss) sex steroid-binding protein (rtSBP) were determined by competitive ligand-binding studies. The role of alkyl chain length and branching, substituent position, number of alkylated groups, and the requirement of a phenolic ring structure were assessed. The results showed that the rtSBP binds to most chemical structures tested, although the highest affinity was obtained for mono-substituted alkylphenols with a chain length of four to eight methyl groups. Interestingly, rtSBP binding was also observed for non-phenolic compounds such as 4-t-butylcyclohexanol and 4-t-butylnitrobenzene suggesting that the rtSBP has a broad binding specificity for alkylphenols and alkylated non-phenolics.

Electronic-topological study of the structure-activity relationships in a series of steroids with mineralocorticoid binding affinity.

PubMed

Kandemirli, Fatma; Tokay, Nesrin; Shvets, Nataly M; Dimoglo, Anatoly S

2003-01-01

Conformational analysis and quantum chemical calculations were carried out using molecular mechanics (MMP2) and semi-empirical quantum chemistry (CNDO/2) methods for 51 steroid homologues belonging to a series of 17-spirolactones. Matrices called Electronic-Topological Matrices of Conjunction (ETMCs) were formed using data obtained from quantum chemical calculations. A structural fragment of activity was identified in the series of steroids. As seen from the fragment's properties, active compounds are characterized by the presence of two atoms of oxygen, O1 and O3, which are situated at a distance of 13.5 A and possess high negative charges (-0.29 to -0.31 e).

Sex differences in visuospatial abilities persist during induced hypogonadism

PubMed Central

Guerrieri, Gioia M.; Wakim, Paul G.; Keenan, P.A.; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J.; Rubinow, David R.; Schmidt, Peter J.

2016-01-01

Background Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. Objective To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Methods Men (n = 16) and women (n = 15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 68 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. Results During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). Conclusion The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in

Sex differences in visuospatial abilities persist during induced hypogonadism.

PubMed

Guerrieri, Gioia M; Wakim, Paul G; Keenan, P A; Schenkel, Linda A; Berlin, Kate; Gibson, Carolyn J; Rubinow, David R; Schmidt, Peter J

2016-01-29

Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. Men (n=16) and women (n=15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 6-8 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus

Effects of sex steroids on bones and muscles: similarities, parallels, and putative interactions in health and disease

PubMed Central

Carson, James A.; Manolagas, Stavros C.

2015-01-01

Estrogens and androgens influence the growth and maintenance of bones and muscles and are responsible for their sexual dimorphism. A decline in their circulating levels leads to loss of mass and functional integrity in both tissues. In the article, we highlight the similarities of the molecular and cellular mechanisms of action of sex steroids in the two tissues; the commonality of a critical role of mechanical forces on tissue mass and function; emerging evidence for an interplay between mechanical forces and hormonal and growth factor signals in both bones and muscles; as well as the current state of evidence for or against a cross-talk between muscles and bone. In addition, we review evidence for the parallels in the development of osteoporosis and sarcopenia with advancing age and the potential common mechanisms responsible for the age-dependent involution of these two tissues. Lastly, we discuss the striking difference in the availability of several drug therapies for the prevention and treatment of osteoporosis, as compared to none for sarcopenia. PMID:26453497

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 ...

Mycobacterium smegmatis synthesizes in vitro androgens and estrogens from different steroid precursors.

PubMed

Dlugovitzky, Diana G; Fontela, María Sol; Martinel Lamas, Diego J; Valdez, Ricardo A; Romano, Marta C

2015-07-01

Fast-growing mycobacteria such as Mycobacterium sp. and Mycobacterium smegmatis degrade natural sterols. They are a model to study tuberculosis. Interestingly, M. smegmatis has been found in river effluents derived from paper production, and therefore, it would be important to gain further insight into its capacity to synthesize steroids that are potential endocrine disruptors affecting the development and reproduction of fishes. To our knowledge, the capacity of M. smegmatis to synthesize estrogens and even testosterone has not been previously reported. Therefore, the objective of this study was to investigate the capacity of M. smegmatis to synthesize in vitro testosterone and estrogens from tritiated precursors and to investigate the metabolic pathways involved. Results obtained by thin-layer chromatography showed that (3)H-progesterone was transformed to 17OH-progesterone, androstenedione, testosterone, estrone, and estradiol after 6, 12, or 24 h of incubation. (3)H-androstenedione was transformed into testosterone and estrogens, mainly estrone, and (3)H-testosterone was transformed to estrone and androstenedione. Incubation with (3)H-dehydroepiandrosterone rendered androstenediol, testosterone, and estrogens. This ability to transform less potent sex steroids like androstenedione and estrone into other more active steroids like testosterone and estradiol or vice versa suggests that M. smegmatis can influence the amount of self-synthesized strong androgens and estrogens and can transform those found in the environment.

Characterization of the oestrogenic activity of non-aromatic steroids: are there male-specific endogenous oestrogen receptor modulators?

PubMed Central

Wang, Pan; Wen, Yujing; Han, Gui-Zhen; Sidhu, Pritam Kaur; Zhu, Bao Ting

2009-01-01

Background and purpose: The endogenous oestrogens have important biological functions in men as well as in women. Because 17β-oestradiol and oestrone are also formed in the male body, these aromatic oestrogens are generally thought to be responsible for exerting the required oestrogenic functions in the male. In the present study, we tested the hypothesis that some of the non-aromatic steroids that are androgen precursors or metabolites with hydroxyl groups at C-3 and/or C-17 positions may also be able to serve as ligands for the oestrogen receptors (ER) in the male. Experimental approach: A total of sixty non-aromatic steroids (selected from families of androstens, androstans, androstadiens, oestrens and oestrans) were analysed for their ability to bind and activate the human ERα and ERβin vitro and in cultured cells. Key results: Six of the non-aromatic steroids, that is, 5-androsten-3β,17β-diol, 5α-androstan-3β,17β-diol, 5(10)-oestren-3α,17β-diol, 5(10)-oestren-3β,17β-diol, 4-oestren-3β,17β-diol and 5α-oestran-3β,17β-diol, were found to have physiologically relevant high binding affinity (∼50% of that of oestrone) for human ERα and ERβ. These non-aromatic steroids also activated the transcriptional activity of human ERs and elicited biological responses (such as growth stimulation) in two representative ER-positive human cancer cell lines (MCF-7 and LNCaP) with physiologically relevant potency and efficacy. Molecular docking analysis of these six active compounds showed that they could bind to ERα and ERβ in a manner similar to that of 17β-oestradiol. Conclusions and implications: These results provide evidence for the possibility that some of the endogenous androgen precursors or metabolites could serve as male-specific ER ligands. PMID:19888961

Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary

ClinicalTrials.gov

2018-03-20

Malignant Ovarian Epithelial Tumor; Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

Environmental sex determination mechanisms in reptiles.

PubMed

Merchant-Larios, H; Díaz-Hernández, V

2013-01-01

Temperature-dependent sex determination (TSD) was first discovered in reptiles. Since then, a great diversity of sex-determining responses to temperature has been reported. Higher temperatures can produce either males or females, and the temperature ranges and lengths of exposure that influence TSD are remarkably variable among species. In addition, transitory gene regulatory networks leading to gonadal TSD have evolved. Although most genes involved in gonadal development are conserved in vertebrates, including TSD species, temporal and spatial gene expression patterns vary among species. Despite variation in TSD pattern and gene expression heterochrony, the structural framework, the medullary cords, and cortex of the bipotential gonad have been strongly conserved. Aromatase (CYP19), which regulates gonadal estrogen levels, is proposed to be the main target of a putative thermosensitive factor for TSD. However, manipulation of estrogen levels rarely mimics the precise timing of temperature effects on expression of gonadal genes, as occurs with TSD. Estrogen levels may influence sex determination or gonad differentiation depending on the species. Furthermore, the process leading to sex determination under the influence of temperature poses problems that are not encountered by species with genetic sex determination. Yolk steroids of maternal origin and steroids produced by the embryonic nervous system should also be considered as sources of hormones that may play a role in TSD. Copyright © 2012 S. Karger AG, Basel.

Adolescent Steroid Use.

ERIC Educational Resources Information Center

Office of Inspector General (DHHS), Washington, DC.

The study focused on non-medical steroid use by adolescents according to data obtained from the National Institute on Drug Abuse, professional literature, 30 key informants knowledgeable in steroid issues, and 72 current or former steroid users. The findings indicated: (1) over 250,000 adolescents, primarily males, used or have used steroids, and…

Seasonal modulation of immunity by melatonin and gonadal steroids in a short day breeder goat Capra hircus.

PubMed

Ghosh, Somenath; Singh, Amaresh K; Haldar, Chandana

2014-11-01

Role of melatonin in regulation of immunity and reproduction has never been studied in detail in goats. The aim of the present study was to explore hormonal regulation of immunity in goats with special reference to melatonin. Plasma of male and female goats (n = 18 per sex per season) was processed for hormonal (estrogen, testostrone, and melatonin) and cytokine (interleukin [IL-2], IL-6, and tumor necrosis factor α) measurements during three seasons, i.e., summer, monsoon, and winter. To assess cell-mediated immune response, percent stimulation ratio of thymocytes was recorded during three seasons. To support and establish the modulation by hormones, Western blot analysis for expressions of melatonin receptors (MT1, MT2), androgen receptor, and estrogen receptor α and estimations of marker enzymes, arylalkylamine N-acetyltransferase for melatonin and 3β-hydroxysteroid dehydrogenase activities for steroidogenesis were performed in thymus. All the hormones and cytokines were estimated by commercial kits. Biochemical, immunologic, and Western blot analyses were done by standardized protocols. We noted a significant increase in estrogen and testosterone levels (P < 0.05) in circulation during monsoon along with melatonin (P < 0.05) presenting a parallel relationship. Expressions of melatonin receptors (MT1 and MT2) in thymus of both the sexes were significantly high (P < 0.01) during winter. Estrogen receptor α expression in female thymus was significantly high during monsoon (P < 0.05). However, androgen receptor showed almost static expression pattern in male thymus during three seasons. Further, both arylalkylamineN-acetyltransferase and 3β-hydroxysteroid dehydrogenase enzyme activities were significantly high (P < 0.05; P < 0.01, respectively) during monsoon. These results suggest that there may be a functional parallelism between gonadal steroids and melatonin as melatonin is progonadotrophic in goats. Cell-mediated immune parameters (percent stimulation

Optical activities of steroid ketones - Elucidation of the octant rule

NASA Astrophysics Data System (ADS)

Hatanaka, Masashi; Sayama, Daisuke; Miyasaka, Makoto

2018-07-01

Theoretical calculations of optical activities in steroid ketones are presented by using modern semi-empirical PM7 wavefunctions. Both circular dichroism (CD) and specific rotation, which is proportional to optical rotation dispersion (ORD), are well simulated, and signs of the Cotton effect at the most long-wavelength region are fully in accordance with the experimental results. The good accordance is related to the octant rule, which is deduced within the framework of the perturbation theory. Our treatment is promising to predict the signs of the Cotton effect of large molecules, and thus, the absolute configurations can also be grasped without demanding procedures.

Accurate and sensitive liquid chromatography/tandem mass spectrometry simultaneous assay of seven steroids in monkey brain.

PubMed

Bertin, Jonathan; Dury, Alain Y; Ke, Yuyong; Ouellet, Johanne; Labrie, Fernand

2015-06-01

Following its secretion mainly by the adrenal glands, dehydroepiandrosterone (DHEA) acts primarily in the cells/tissues which express the enzymes catalyzing its intracellular conversion into sex steroids by the mechanisms of intracrinology. Although reliable assays of endogenous serum steroids are now available using mass spectrometry (MS)-based technology, sample preparation from tissue matrices remains a challenge. This is especially the case with high lipid-containing tissues such as the brain. With the combination of a UPLC system with a sensitive tandem MS, it is now possible to measure endogenous unconjugated steroids in monkey brain tissue. A Shimadzu UPLC LC-30AD system coupled to a tandem MS AB Sciex Qtrap 6500 system was used. The lower limits of quantifications are achieved at 250 pg/mL for DHEA, 200 pg/mL for 5-androstenediol (5-diol), 12 pg/mL for androstenedione (4-dione), 50 pg/mL for testosterone (Testo), 10 pg/mL for dihydrotestosterone (DHT), 4 pg/mL for estrone (E1) and 1 pg/mL for estradiol (E2). The linearity and accuracy of quality controls (QCs) and endogenous quality controls (EndoQCs) are according to the guidelines of the regulatory agencies for all seven compounds. We describe a highly sensitive, specific and robust LC-MS/MS method for the simultaneous measurement of seven unconjugated steroids in monkey brain tissue. The single and small amount of sample required using a relatively simple preparation method should be useful for steroid assays in various peripheral tissues and thus help analysis of the role of locally-made sex steroids in the regulation of specific physiological functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex worker activism, feminist discourse and HIV in Bangladesh.

PubMed

Sultana, Habiba

2015-01-01

This paper explores the relationship between sex worker activism and HIV-related discourse in Bangladesh, relating recent developments in activism to the influence of feminist thought. Following their eviction in 1991 from brothels from red light areas, Bangladeshi sex workers started a social movement, at just about the same time that programmes started to work with sex workers to reduce the transmission of HIV. This paper argues that both sex worker activism and HIV-prevention initiatives find impetus in feminist pro-sex-work perspectives, which place emphasis on individual and collective agency. However, by participating in these programmes, sex workers failed to contest the imagery of themselves as 'vectors' of HIV. In this way, they were unwittingly complicit in reproducing their identity as 'polluting others'. Moreover, by focusing on individual behaviour and the agency of sex workers, HIV programmes ignored the fact that the 'choices' made by sex workers are influenced by a wide range of structural and discursive factors, including gender norms and notions of bodily purity, which in turn have implications for the construction of HIV-related risk.

Hormonal regulation of steroid receptor coactivator-1 mRNA in the male and female green anole brain.

PubMed

Kerver, H N; Wade, J

2015-03-01

Green anole lizards are seasonal breeders, with male sexual behaviour primarily regulated by an annual increase in testosterone. Morphological, biochemical and behavioural changes associated with reproduction are activated by testosterone, generally with a greater effect in the breeding season (BS) than in the nonbreeding season (NBS). The present study investigates the possibility that differences in a steroid receptor coactivator may regulate this seasonal difference in responsiveness to testosterone. In situ hybridisation was used to examine the expression of steroid receptor coactivator-1 (SRC-1) in the brains of gonadally intact male and female green anoles across breeding states. A second experiment examined gonadectomised animals with and without testosterone treatment. Gonadally intact males had more SRC-1 expressing cells in the preoptic area and larger volumes of this region as defined by these cells than females. Main effects of both sex and season (males > females and BS > NBS) were present in cell number and volume of the ventromedial hypothalamus. An interaction between sex and season suggested that high expression in BS males was driving these effects. In hormone-manipulated animals, testosterone treatment increased both the number of SRC-1 expressing cells in and volumes of the preoptic area and amygdala. These results suggest that testosterone selectively regulates SRC-1, and that this coactivator may play a role in facilitating reproductive behaviours across both sexes. However, changes in SRC-1 expression are not likely responsible for the seasonal change in responsiveness to testosterone. © 2014 British Society for Neuroendocrinology.

A missense mutation in the human cytochrome b5 gene causes 46,XY disorder of sex development due to true isolated 17,20 lyase deficiency.

PubMed

Idkowiak, Jan; Randell, Tabitha; Dhir, Vivek; Patel, Pushpa; Shackleton, Cedric H L; Taylor, Norman F; Krone, Nils; Arlt, Wiebke

2012-03-01

Isolated 17,20 lyase deficiency is commonly defined by apparently normal 17α-hydroxylase activity but severely reduced 17,20 lyase activity of the bifunctional enzyme cytochrome P450 (CYP) enzyme 17A1 (CYP17A1), resulting in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. Cytochrome b5 (CYB5A) is thought to selectively enhance 17,20 lyase activity by facilitating the allosteric interaction of CYP17A1 with its electron donor P450 oxidoreductase (POR). We investigated a large consanguineous family including three siblings with 46,XY disorder of sex development (DSD) presenting with isolated 17,20 lyase deficiency. We investigated the clinical and biochemical phenotype, conducted genetic analyses, and functionally characterized the identified CYB5A mutation in cell-based CYP17A1 coexpression assays. All three siblings presented with 46,XY DSD, sex steroid deficiency, normal mineralocorticoids and glucocorticoids, and a urine steroid metabolome suggestive of isolated 17,20 lyase deficiency. CYP17A1 and POR sequences were normal, but we detected a homozygous CYB5A missense mutation (g.28,400A→T; p.H44L). Functional in vitro analysis revealed normal CYP17A1 17α-hydroxylase activity but severely impaired 17,20 lyase activity. In silico analysis suggested the disruption of CYB5A heme binding by p.H44L. We have identified the first human CYB5A missense mutation as the cause of isolated 17,20 lyase deficiency in three individuals with 46,XY DSD. Detailed review of previously reported cases with apparently isolated 17,20 lyase deficiency due to mutant CYP17A1 and POR reveals impaired 17α-hydroxylase activity as assessed by steroid metabolome analysis and short cosyntropin testing. This suggests that truly isolated 17,20 lyase deficiency is observed only in individuals with inactivating CYB5A mutations.

Molecular properties of steroids involved in their effects on the biophysical state of membranes.

PubMed

Wenz, Jorge J

2015-10-01

The activity of steroids on membranes was studied in relation to their ordering, rigidifying, condensing and/or raft promoting ability. The structures of 82 steroids were modeled by a semi-empirical procedure (AM1) and 245 molecular descriptors were next computed on the optimized energy conformations. Principal component analysis, mean contrasting and logistic regression were used to correlate the molecular properties with 212 cases of documented activities. It was possible to group steroids based on their properties and activities, indicating that steroids having similar molecular properties have similar activities on membranes. Steroids having high values of area, partition coefficient, volume, number of rotatable bonds, molar refractivity, polarizability or mass displayed ordering, rigidifying, condensing and/or raft promoting activity on membranes higher than those steroids having low values in such molecular properties. After a variable selection procedure circumventing correlation problems among descriptors, area and log P were found as the most relevant properties in governing and predicting the activity of steroids on membranes. A logistic regression model as a function of the area and log P of the steroids is proposed, which is able to predict correctly 92.5% of the cases. A rationale of the findings is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Steroids

NASA Astrophysics Data System (ADS)

Frey, Felix J.; Frey, Brigitte M.; Benet, Leslie Z.

If a radioimmunoassay, a protein binding method, or a colorimetric assay for the assessment of a steroid level is replaced by high performance liquid chromatography (HPLC), the cost for the determination of a steroid level increases at least initially because one must acquire the new HPLC equipment. Therefore, if an older method provides the same results as the new, "advanced" HPLC method, the only advantage resulting from the introduction of a high performance chromatographic assay is that gained by the manufacturer in terms of greater sales. Thus, justification for the assessment of steroids by HPLC is only obtained if the quality and/or quantity of information gained is significantly increased as compared to that provided by the conventional methods. But this evidential relation, that more and better information justifies a higher price in any case, is no longer true in health care, with the birth some years ago of the categoric imperative for the reduction of costs in the medical sector. That is, each new technology introduced for health maintenance should demonstrate at least a stabilizing impact on total medical expenditures. Therefore, after reviewing the presently available HPLC methods for the clinically important steroids, we will consider whether HPLC analyses for these steroids can be recommended without violating this vox populi.

What goes on behind closed doors: physiological vs. pharmacological steroid hormone actions

PubMed Central

Simons, S. Stoney

2009-01-01

Summary Steroid hormone-activated receptor proteins are among the best understood class of factors for altering gene transcription in cells. Steroid receptors are of major importance in maintaining normal human physiology by responding to circulating concentrations of steroid in the nM range. Nonetheless, most studies of steroid receptor action have been conducted using the supra-physiological conditions of saturating concentrations (≥100 nM) of potent synthetic steroid agonists. Here we summarize the recent developments arising from experiments using two clinically relevant conditions: subsaturating concentrations of agonist (to mimic the circulating concentrations in mammals) and saturating concentrations of antagonists (which are employed in endocrine therapies to block the actions of endogenous steroids). These studies have revealed new facets of steroid hormone action that could not be uncovered by conventional experiments with saturating concentrations of agonist steroids, such as a plethora of factors/conditions for the differential control of gene expression by physiological levels of steroid, a rational approach for examining the gene-specific variations in partial agonist activity of antisteroids, and a dissociation of steroid potency and efficacy that implies the existence of separate, and possibly novel, mechanistic steps and cofactors. PMID:18623071

Sex dependent influence of a functional polymorphism in steroid 5-α-reductase type 2 (SRD5A2) on post-traumatic stress symptoms.

PubMed

Gillespie, Charles F; Almli, Lynn M; Smith, Alicia K; Bradley, Bekh; Kerley, Kimberly; Crain, Daniel F; Mercer, Kristina B; Weiss, Tamara; Phifer, Justine; Tang, Yilang; Cubells, Joseph F; Binder, Elisabeth B; Conneely, Karen N; Ressler, Kerry J

2013-04-01

A non-synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5-α-reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post-traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African-American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post-traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex-dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex-specific way, the severity of post-traumatic stress symptoms and risk for diagnosis of PTSD. Copyright © 2013 Wiley Periodicals, Inc.

Environmental hormones and their impacts on sex differentiation in fathead minnows

EPA Science Inventory

Runoff from lands fertilized with animal manure from concentrated animal feeding operations (CAFOs) is a source of hormones to surface water. To test the hypothesis that juvenile fathead minnows exposed to sex steroids singly and in a “typical” CAFO mixture while undergoing sex...

Total synthesis of steroids and heterosteroids from BISTRO.

PubMed

Ibrahim-Ouali, Malika

2015-06-01

Due to their high profile biological activity, the steroids are among the most important secondary metabolites. A review of literature on the total synthesis of steroids starting from BISTRO (1,8-bis(trimethylsilyl)-2,6-octadiene) is presented. Copyright © 2015 Elsevier Inc. All rights reserved.

New tricks by an old dogma: mechanisms of the Organizational/Activational Hypothesis of steroid-mediated sexual differentiation of brain and behavior.

PubMed

McCarthy, Margaret M; Wright, Christopher L; Schwarz, Jaclyn M

2009-05-01

The hormonal regulation of sexual behavior has been the topic of study for over 50 years and yet controversies persist regarding the importance of early versus late events and the identity of the critical neural and cellular substrates. We have taken a mechanistic approach toward the masculinizing actions of the gonadal steroid estradiol, as a means to understand how organization of the neuroarchitechture during a perinatal sensitive period exerts enduring influences on adult behavior. We have identified important roles for prostaglandins, FAK and paxillin, PI3 kinase and glutamate, and determined that cell-to-cell signaling is a critical component of the early organizational events. We have further determined that the mechanisms mediating different components of sexual behavior are distinct and regionally specific. The multitude of mechanisms by which the steroid estradiol, exerts divergent effects on the developing nervous system provides for a multitude of phenotypes which can vary significantly both within and between the sexes.

New tricks by an old dogma: Mechanisms of the Organizational/Activational Hypothesis of steroid-mediated sexual differentiation of brain and behavior

PubMed Central

McCarthy, Margaret M.; Wright, Christopher L.; Schwarz, Jaclyn M.

2009-01-01

The hormonal regulation of sexual behavior has been the topic of study for over 50 years and yet controversies persist regarding the importance of early versus late events and the identity of the critical neural and cellular substrates. We have taken a mechanistic approach toward the masculinizing actions of the gonadal steroid estradiol, as a means to understand how organization of the neuroarchitechture during a perinatal sensitive period exerts enduring influences on adult behavior. We have identified important roles for prostaglandins, FAK and paxillin, PI3 kinase and glutamate, and determined that cell-to-cell signaling is a critical component of the early organizational events. We have further determined that the mechanisms mediating different components of sexual behavior are distinct and regionally specific. The multitude of mechanisms by which the steroid estradiol, exerts divergent effects on the developing nervous system provides for a multitude of phenotypes which can vary significantly both within and between the sexes. PMID:19682425

The Regulation of Steroid Action by Sulfation and Desulfation

PubMed Central

Mueller, Jonathan W.; Gilligan, Lorna C.; Idkowiak, Jan; Arlt, Wiebke

2015-01-01

Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined. PMID:26213785

A bibliometric analysis of research updates and tendencies on steroid biotransformation

NASA Astrophysics Data System (ADS)

Song, Zhaoyu

2018-03-01

Steroid biotransformation, as a powerful tool for generation of steroid active pharmaceutical ingredients and key intermediates, has received widespread attention with increasing market demand for steroid-based drugs. In our study, a bibliometric analysis of steroid biotransformation was performed to trace the research updates and tendencies from 1993 to 2016, based on the Science Citation Index Expanded (SCIE) database. Results showed a notable growth trend in publication outputs. Although the USA was the most productive country between 1993 and 2016, developing nations, including China and India, contributed the prominent growth in recent years (2005–2016). Steroids was the leading journal in this field, and the research outputs had notably increased in the field of ‘Chemistry’, ‘Pharmacology and Pharmacy’ and ‘Biotechnology and Applied Microbiology’. Finally, research focused mainly on the efficient production of novel steroid active pharmaceutical ingredients and key intermediates through steroid biotransformation. Furthermore, cytochrome P450 involved in the side-chain oxidation of sterols has gradually become a hotspot issue in recent years.

Sex worker activism, feminist discourse and HIV in Bangladesh

PubMed Central

Sultana, Habiba

2015-01-01

This paper explores the relationship between sex worker activism and HIV-related discourse in Bangladesh, relating recent developments in activism to the influence of feminist thought. Following their eviction in 1991 from brothels from red light areas, Bangladeshi sex workers started a social movement, at just about the same time that programmes started to work with sex workers to reduce the transmission of HIV. This paper argues that both sex worker activism and HIV-prevention initiatives find impetus in feminist pro-sex-work perspectives, which place emphasis on individual and collective agency. However, by participating in these programmes, sex workers failed to contest the imagery of themselves as ‘vectors’ of HIV. In this way, they were unwittingly complicit in reproducing their identity as ‘polluting others’. Moreover, by focusing on individual behaviour and the agency of sex workers, HIV programmes ignored the fact that the ‘choices’ made by sex workers are influenced by a wide range of structural and discursive factors, including gender norms and notions of bodily purity, which in turn have implications for the construction of HIV-related risk. PMID:25588539

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...

Design of an Escherichia coli system for whole cell mediated steroid synthesis and molecular evolution of steroid hydroxylases.

PubMed

Hannemann, Frank; Virus, Cornelia; Bernhardt, Rita

2006-06-25

The 15beta-hydroxylase (CYP106A2) from Bacillus megaterium, one of the few bacterial steroid hydroxylases, which has been isolated and characterized so far, catalyses the 15beta-hydroxylation of a variety of steroids. The enzyme can be supported in its activity with adrenodoxin (Adx) and adrenodoxin reductase (AdR) from bovine adrenals, supplying this enzyme with the reducing equivalents necessary for steroid hydroxylation activity. This three-component electron transfer chain was implemented in Escherichia coli by coexpression of the corresponding coding sequences from two plasmids, containing different selection markers and compatible origins of replication. The cDNAs of AdR and Adx on the first plasmid were separated by a ribosome binding sequence, with the reductase preceding the ferredoxin. The second plasmid for CYP106A2 expression was constructed with all features necessary for a molecular evolution approach. The transformed bacteria show the inducible ability to efficiently convert 11-deoxycorticosterone (DOC) to 15beta-DOC at an average rate of 1 mM/d in culture volumes of 300 ml. The steroid conversion system was downscaled to the microtiter plate format and a robot set-up was developed for a fluorescence-based conversion assay as well as a CO difference spectroscopy assay, which enables the screening for enzyme variants with higher activity and stability.

Actions of Steroids: New Neurotransmitters

PubMed Central

Cornil, Charlotte A.; Mittelman-Smith, Melinda A.; Rainville, Jennifer R.; Remage-Healey, Luke; Sinchak, Kevin; Micevych, Paul E.

2016-01-01

Over the past two decades, the classical understanding of steroid action has been updated to include rapid, membrane-initiated, neurotransmitter-like functions. While steroids were known to function on very short time spans to induce physiological and behavioral changes, the mechanisms by which these changes occur are now becoming more clear. In avian systems, rapid estradiol effects can be mediated via local alterations in aromatase activity, which precisely regulates the temporal and spatial availability of estrogens. Acute regulation of brain-derived estrogens has been shown to rapidly affect sensorimotor function and sexual motivation in birds. In rodents, estrogens and progesterone are critical for reproduction, including preovulatory events and female sexual receptivity. Membrane progesterone receptor as well as classical progesterone receptor trafficked to the membrane mediate reproductive-related hypothalamic physiology, via second messenger systems with dopamine-induced cell signals. In addition to these relatively rapid actions, estrogen membrane-initiated signaling elicits changes in morphology. In the arcuate nucleus of the hypothalamus, these changes are needed for lordosis behavior. Recent evidence also demonstrates that membrane glucocorticoid receptor is present in numerous cell types and species, including mammals. Further, membrane glucocorticoid receptor influences glucocorticoid receptor translocation to the nucleus effecting transcriptional activity. The studies presented here underscore the evidence that steroids behave like neurotransmitters to regulate CNS functions. In the future, we hope to fully characterize steroid receptor-specific functions in the brain. PMID:27911748

Sex differences in activated CRF neurons within stress-related neurocircuitry and HPA axis hormones following restraint in rats

PubMed Central

Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

2013-01-01

Women may be more vulnerable to certain stress-related psychiatric illnesses than men due to differences in hypothalamic-pituitary-adrenocortical (HPA) axis function. To investigate potential sex differences in forebrain regions associated with HPA axis activation in rats, these experiments utilized acute exposure to a psychological stressor. Male and female rats in various stages of the estrous cycle were exposed to 30 min of restraint, producing a robust HPA axis hormonal response in all animals, the magnitude of which was significantly higher in female rats. Although both male and female animals displayed equivalent c-fos expression in many brain regions known to be involved in the detection of threatening stimuli, three regions had significantly higher expression in females: the paraventricular nucleus of the hypothalamus (PVN), the anteroventral division of the bed nucleus of the stria terminalis (BSTav), and the medial preoptic area (MPOA). Dual fluorescence in-situ hybridization analysis of neurons containing c-fos and corticotropin-releasing factor (CRF) mRNA in these regions revealed significantly more c-fos and CRF single-labeled neurons, as well as significantly more double-labeled neurons in females. Surprisingly, there was no effect of the estrous cycle on any measure analyzed, and an additional experiment revealed no demonstrable effect of estradiol replacement following ovariectomy on HPA axis hormone induction following stress. Taken together, these data suggest sex differences in HPA axis activation in response to perceived threat may be influenced by specific populations of CRF neurons in key stress-related brain regions, the BSTav, MPOA, and PVN, which may be independent of circulating sex steroids. PMID:23305762

Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis

PubMed Central

Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

2017-01-01

Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed “long-interval cytapheresis (LI-CAP)”, in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC. PMID:28924114

Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis.

PubMed

Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

2017-10-15

Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.

Quest for steroidomimetics: Amino acids derived steroidal and nonsteroidal architectures.

PubMed

Shagufta; Ahmad, Irshad; Panda, Gautam

2017-06-16

The chiral pool amino acids have been utilized for the construction of steroidal and non-steroidal architectures in the quest for steroidomimetics. Chirality derived from amino acid-based architectures provides new and easy to incorporate chiral chemical space, which is otherwise very difficult to introduce and comprised of several synthetic steps for asymmetric steroids. The different and exciting ligand-receptor interactions may arise from the use of each amino acid enantiomer that was introduced into the chiral steroidal backbone. The A and D rings of steroidal architectures can be mimicked by the phenyl group of the amino acid tyrosine. The Mitsunobu reaction, nucleophilic substitution and elimination, etc. were utilized for constructing diverse tri- and tetracyclic steroidal skeletons as well as benzofused seco-steroids from amino acids. These benzofused, amino acid-derived steroidal and nonsteroidal molecules had promising biological activity in hormonal related disorders. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Analysis of nonderivatized steroids by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using C70 fullerene as matrix.

PubMed

Montsko, Gergely; Vaczy, Alexandra; Maasz, Gabor; Mernyak, Erzsebet; Frank, Eva; Bay, Csaba; Kadar, Zalan; Ohmacht, Robert; Wolfling, Janos; Mark, Laszlo

2009-10-01

Neutral steroid hormones are currently analyzed by gas or liquid chromatography/mass spectrometry based methods. Most of the steroid compounds, however, lack volatility and do not contain polar groups, which results in inadequate chromatographic behavior and low ionization efficiency. Derivatization of the steroids to form more volatile, thermostable, and charged products solves this difficulty, but the derivatization of compounds with unknown chemical moieties is not an easy task. In this study, a rapid, high-throughput, sensitive matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method is described using C(70) fullerene as a matrix compound. The application of the method is demonstrated for five general sex steroids and for synthetic steroid compounds in both negative and positive ionization modes.

Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones.

PubMed

Fernández-Guasti, A; Fiedler, J L; Herrera, L; Handa, R J

2012-07-01

The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design. © Georg Thieme Verlag KG Stuttgart · New York.

Synthesis and Cytotoxic Evaluation of Steroidal Copper (Cu (II)) Complexes

PubMed Central

Huang, Yanmin; Kong, Erbin; Zhan, Junyan; Chen, Shuang; Gan, Chunfang; Liu, Zhiping; Pang, Liping

2017-01-01

Using estrone and pregnenolone as starting materials, some steroidal copper complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide or diazanyl pyridine and then complexation of steroidal thiosemicarbazones or steroidal diazanyl pyridines with Cu (II). The complexes were characterized by IR, NMR, and HRMS. The synthesized compounds were screened for their cytotoxicity against HeLa, Bel-7404, and 293T cell lines in vitro. The results show that all steroidal copper (II) complexes display obvious antiproliferative activity against the tested cancer cells. The IC50 values of complexes 5 and 12 against Bel-7404 (human liver carcinoma) are 5.0 and 7.0 μM. PMID:29180937

Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase.

PubMed

Pettersson, Par L; Johansson, Ann-Sofie; Mannervik, Bengt

2002-08-16

A major goal in protein engineering is the tailor-making of enzymes for specified chemical reactions. Successful attempts have frequently been based on directed molecular evolution involving libraries of random mutants in which variants with desired properties were identified. For the engineering of enzymes with novel functions, it would be of great value if the necessary changes of the active site could be predicted and implemented. Such attempts based on the comparison of similar structures with different substrate selectivities have previously met with limited success. However, the present work shows that the knowledge-based redesign restricted to substrate-binding residues in human glutathione transferase A2-2 can introduce high steroid double-bond isomerase activity into the enzyme originally characterized by glutathione peroxidase activity. Both the catalytic center activity (k(cat)) and catalytic efficiency (k(cat)/K(m)) match the values of the naturally evolved glutathione transferase A3-3, the most active steroid isomerase known in human tissues. The substrate selectivity of the mutated glutathione transferase was changed 7000-fold by five point mutations. This example demonstrates the functional plasticity of the glutathione transferase scaffold as well as the potential of rational active-site directed mutagenesis as a complement to DNA shuffling and other stochastic methods for the redesign of proteins with novel functions.

Sex Reversal in Birds.

PubMed

Major, Andrew T; Smith, Craig A

2016-01-01

Sexual differentiation in birds is controlled genetically as in mammals, although the sex chromosomes are different. Males have a ZZ sex chromosome constitution, while females are ZW. Gene(s) on the sex chromosomes must initiate gonadal sex differentiation during embryonic life, inducing paired testes in ZZ individuals and unilateral ovaries in ZW individuals. The traditional view of avian sexual differentiation aligns with that expounded for other vertebrates; upon sexual differentiation, the gonads secrete sex steroid hormones that masculinise or feminise the rest of the body. However, recent studies on naturally occurring or experimentally induced avian sex reversal suggest a significant role for direct genetic factors, in addition to sex hormones, in regulating sexual differentiation of the soma in birds. This review will provide an overview of sex determination in birds and both naturally and experimentally induced sex reversal, with emphasis on the key role of oestrogen. We then consider how recent studies on sex reversal and gynandromorphic birds (half male:half female) are shaping our understanding of sexual differentiation in avians and in vertebrates more broadly. Current evidence shows that sexual differentiation in birds is a mix of direct genetic and hormonal mechanisms. Perturbation of either of these components may lead to sex reversal. © 2016 S. Karger AG, Basel.

Sjögren's syndome and extragonadal sex steroid formation: a clue to a better disease control?

PubMed

Konttinen, Y T; Stegajev, V; Al-Samadi, A; Porola, P; Hietanen, J; Ainola, M

2015-01-01

Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphoplasmacytoid focal adenitis leading to mucosal dryness, with 9:1 female dominance and peak incidence at menopause. Due to autoimmune adenitis it can be speculated that the normal epithelial cell renewal has failed, possibly as a result of local intracrine failure to process dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). Local intracrine/-cellular DHT deficiency seems to predispose to SS if estrogens are low, in menopausal women and in men. This intracrine failure could be the initial noxious stimulus, factor X, initiating the development of SS. Abnormal release and presentation of exocrine gland-derived antigens (Ag-epitopes), in a complex with major histocompatibility complex class II (MHC II), by migratory dendritic cells (DC) activates T-cells in the regional lymph nodes. B-cells with the same specificity capture and present self-Ag to Th-cells which provide T-cell help. B-cells transform to plasma cells and start to produce autoantibodies (Ab) against these T-cell-dependent Ag. Ab against SS-A/Ro and SS-B/La ribonucleoproteins occur only in HLA-DQw2.1/DQw6 heterozygous individuals, but hY-RNA and RNA polymerase III transcripts in these Ag may in all SS patients stimulate toll-like receptors (TLR) 7 and 9 of the plasmacytoid DCs, because IFN-α and IFN-signature are produced. CD8+αEβ7+cytotoxic T-cells activated via cross-presentation recirculate to attack intracrine-deficient, apoptotic epithelial cells expressing self-Ag on their surface. Exocrine glands fall into the sphere of mucosal/gut-associated lymphatic tissue. This together with immune complexes spreads the immunological memory/aggression to extra-glandular sites explaining the systemic nature of the syndrome. Secondary SS could be explained by disturbed lymphocyte recirculation. There is no conclusive evidence that SS in those few men affected is more severe than in women, suggesting that sex steroid endo

Genetic Variations in the Androgen Receptor Are Associated with Steroid Concentrations and Anthropometrics but Not with Muscle Mass in Healthy Young Men

PubMed Central

De Naeyer, Hélène; Bogaert, Veerle; De Spaey, Annelies; Roef, Greet; Vandewalle, Sara; Derave, Wim; Taes, Youri; Kaufman, Jean-Marc

2014-01-01

Objective The relationship between serum testosterone (T) levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR) gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings. Design 677 men (25–45 years) were recruited in a cross-sectional, population-based sibling pair study. Methods Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs), sex steroid levels (by LC-MS/MS), body composition (by DXA), muscle cross-sectional area (CSA) (by pQCT), muscle force (isokinetic peak torque, grip strength) and anthropometrics were studied using linear mixed-effect modelling. Results Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT) and free T (FT) levels were positively related to muscle CSA, whereas estradiol (E2) and free E2 (FE2) concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats. Conclusions Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR gene also

Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men.

PubMed

De Naeyer, Hélène; Bogaert, Veerle; De Spaey, Annelies; Roef, Greet; Vandewalle, Sara; Derave, Wim; Taes, Youri; Kaufman, Jean-Marc

2014-01-01

The relationship between serum testosterone (T) levels, muscle mass and muscle force in eugonadal men is incompletely understood. As polymorphisms in the androgen receptor (AR) gene cause differences in androgen sensitivity, no straightforward correlation can be observed between the interindividual variation in T levels and different phenotypes. Therefore, we aim to investigate the relationship between genetic variations in the AR, circulating androgens and muscle mass and function in young healthy male siblings. 677 men (25-45 years) were recruited in a cross-sectional, population-based sibling pair study. Relations between genetic variation in the AR gene (CAGn, GGNn, SNPs), sex steroid levels (by LC-MS/MS), body composition (by DXA), muscle cross-sectional area (CSA) (by pQCT), muscle force (isokinetic peak torque, grip strength) and anthropometrics were studied using linear mixed-effect modelling. Muscle mass and force were highly heritable and related to age, physical activity, body composition and anthropometrics. Total T (TT) and free T (FT) levels were positively related to muscle CSA, whereas estradiol (E2) and free E2 (FE2) concentrations were negatively associated with muscle force. Subjects with longer CAG repeat length had higher circulating TT, FT, and higher E2 and FE2 concentrations. Weak associations with TT and FT were found for the rs5965433 and rs5919392 SNP in the AR, whereas no association between GGN repeat polymorphism and T concentrations were found. Arm span and 2D:4D finger length ratio were inversely associated, whereas muscle mass and force were not associated with the number of CAG repeats. Age, physical activity, body composition, sex steroid levels and anthropometrics are determinants of muscle mass and function in young men. Although the number of CAG repeats of the AR are related to sex steroid levels and anthropometrics, we have no evidence that these variations in the AR gene also affect muscle mass or function.

Anabolic Steroids...What's the Hype?...

ERIC Educational Resources Information Center

Landry, Gregory L.; Wagner, Lauris L.

This pamphlet uses a question-and-answer format to examine the use and abuse of anabolic steroids. It begins by explaining that all steroids are not anabolic steroids and that anabolic steroids are those used specifically to build muscles quickly. Medical uses of anabolic steroids are reviewed; how people get steroids, how they take them, and…

Mutations of glucocorticoid receptor differentially affect AF2 domain activity in a steroid-selective manner to alter the potency and efficacy of gene induction and repression†

PubMed Central

Tao, Yong-guang; Xu, Yong; Xu, H. Eric; Simons, S. Stoney

2009-01-01

The transcriptional activity of steroid hormones is intimately associated with their structure. Deacylcortivazol (DAC) contains several features that were predicted to make it an inactive glucocorticoid. Nevertheless, gene induction and repression by complexes of glucocorticoid receptor (GR) with DAC occurs with greater potency (lower EC50) than, and equal efficacy (maximal activity, or Amax) to, the very active and smaller synthetic glucocorticoid dexamethasone (Dex). Guided by a recent x-ray structure of DAC bound to the GR ligand binding domain (LBD), we now report that several point mutants in the LBD have little effect on the binding of either agonist steroid. However, these same mutations dramatically alter the Amax and/or EC50 of exogenous and endogenous genes in a manner that depends on steroid structure. In some cases, Dex is no longer a full agonist. These properties appear to result from a preferential inactivation of the AF2 activation domain in the GR LBD of Dex-, but not DAC-, bound receptors. The Dex-bound receptors display normal binding to, but greatly reduced response to, the coactivator TIF2, thus indicating a defect in the transmission efficiency of GR-steroid complex information to the coactivator TIF2. In addition, all GR mutants that are active in gene induction with either Dex or DAC have greatly reduced activity in gene repression. This contrasts with the reports of GR mutations preferentially suppressing GR-mediated induction. The properties of these GR mutants in gene induction support the hypothesis that the Amax and EC50 of GR-controlled gene expression can be independently modified, indicate that the receptor can be modified to favor activity with a specific agonist steroid, and suggest that new ligands with suitable substituents may be able to affect the same LBD conformational changes and thereby broaden the therapeutic applications of glucocorticoid steroids PMID:18578507

Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice

PubMed Central

Huddy, Timothy F.; Ogawa-Okada, Maya; Adkins, Jamie L.

2018-01-01

Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice. PMID:29385171

Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice.

PubMed

Aguayo, Antonio; Martin, Camille S; Huddy, Timothy F; Ogawa-Okada, Maya; Adkins, Jamie L; Steele, Andrew D

2018-01-01

Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice.

Synthesis and anti-cancer activity of chiral tetrahydropyrazolo[1,5-a]pyridine-fused steroids.

PubMed

Lopes, Susana M M; Sousa, Emanuel P; Barreira, Luísa; Marques, Cátia; Rodrigues, Maria João; Pinho E Melo, Teresa M V D

2017-06-01

Regio- and stereoselective synthesis of novel chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroids via [8π+2π] cycloaddition of diazafulvenium methides with steroidal scaffolds is reported. The biological evaluation of the new family of hexacyclic steroids as anti-cancer agents was also carried out. Hexacyclic steroids bearing a benzyl group at C-22, derived from 16-dehydropregnenolone and 16-dehydroprogesterone, show considerable cytotoxicity against EL4 (murine T-lymphoma) in contrast with the corresponding C-22-unsubstituted derivatives showing low cytotoxicity. Thus, results indicate that the presence of the benzyl group is important to ensure cytotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification and transcriptional modulation of the largemouth bass, Micropterus salmoides, vitellogenin receptor during oocyte development by insulin and sex steroids.

PubMed

Dominguez, Gustavo A; Quattro, Joseph M; Denslow, Nancy D; Kroll, Kevin J; Prucha, Melinda S; Porak, Wesley F; Grier, Harry J; Sabo-Attwood, Tara L

2012-09-01

Fish vitellogenin synthesized and released from the liver of oviparous animals is taken up into oocytes by the vitellogenin receptor. This is an essential process in providing nutrient yolk to developing embryos to ensure successful reproduction. Here we disclose the full length vtgr cDNA sequence for largemouth bass (LMB) that reveals greater than 90% sequence homology with other fish vtgr sequences. We classify LMB Vtgr as a member of the low density lipoprotein receptor superfamily based on conserved domains and categorize as the short variant that is devoid of the O-glycan segment. Phylogenetic analysis places LMB Vtgr sequence into a well-supported monophyletic group of fish Vtgr. Real-time PCR showed that the greatest levels of LMB vtgr mRNA expression occurred in previtellogenic ovarian tissues. In addition, we reveal the effects of insulin, 17beta-estradiol (E(2)), and 11-ketotestosterone (11-KT) in modulation of vtgr, esr, and ar mRNAs in previtellogenic oocytes. Insulin increased vtgr expression levels in follicles ex vivo while exposure to E(2) or 11-KT did not result in modulation of expression. However, both steroids were able to repress insulin-induced vtgr transcript levels. Coexposure with insulin and E(2) or of insulin and 11-KT increased ovarian esr2b and ar mRNA levels, respectively, which suggest a role for these nuclear receptors in insulin-mediated signaling pathways. These data provide the first evidence for the ordered stage-specific expression of LMB vtgr during the normal reproductive process and the hormonal influence of insulin and sex steroids on controlling vtgr transcript levels in ovarian tissues.

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

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.

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

PubMed

Brown, G R; Spencer, K A

2013-09-26

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

Multiple monolithic fiber solid-phase microextraction based on a polymeric ionic liquid with high-performance liquid chromatography for the determination of steroid sex hormones in water and urine.

PubMed

Liao, Keren; Mei, Meng; Li, Haonan; Huang, Xiaojia; Wu, Cuiqin

2016-02-01

The development of a simple and sensitive analytical approach that combines multiple monolithic fiber solid-phase microextraction with liquid desorption followed by high-performance liquid chromatography with diode array detection is proposed for the determination of trace levels of seven steroid sex hormones (estriol, 17β-estradiol, testosterone, ethinylestradiol, estrone, progesterone and mestranol) in water and urine matrices. To extract the target analytes effectively, multiple monolithic fiber solid-phase microextraction based on a polymeric ionic liquid was used to concentrate hormones. Several key extraction parameters including desorption solvent, extraction and desorption time, pH value and ionic strength in sample matrix were investigated in detail. Under the optimal experimental conditions, the limits of detection were found to be in the range of 0.027-0.12 μg/L. The linear range was 0.10-200 μg/L for 17β-estradiol, 0.25-200 μg/L estriol, ethinylestradiol and estrone, and 0.50-200 μg/L for the other hormones. Satisfactory linearities were achieved for analytes with the correlation coefficients above 0.99. Acceptable method reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations of both less than 8%. The enrichment factors ranged from 54- to 74-fold. Finally, the proposed method was successfully applied to the analysis of steroid sex hormones in environmental water samples and human urines with spiking recoveries ranged from 75.6 to 116%. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wired on steroids: sexual differentiation of the brain and its role in the expression of sexual partner preferences.

PubMed

Alexander, Brenda M; Skinner, Donal C; Roselli, Charles E

2011-01-01

The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rat, ferret, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods result in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity.

Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men.

PubMed

Lovejoy, J C; Smith, S R; Bray, G A; Veldhuis, J D; Rood, J C; Tulley, R

1997-12-01

Although triiodothyronine (T3) exerts major regulatory actions in both animals and humans, most clinical studies of T3 administration have been relatively short-term. The present study examined the effects of more than 2 months (63 days) of low-dose T3 treatment on overnight pulsatile growth hormone (GH) secretion, short-term insulin secretion, and of sex steroid levels in seven healthy, lean men studied at an inpatient metabolic unit. At baseline, there were strong correlations between sex hormone-binding globulin (SHBG) and several measures of GH production, including total GH production (r = .99), GH interburst interval (r = -.75), and GH mass (r = .82). SHBG was also inversely correlated with basal insulin secretion (r = -.74). There was a 42% increase in serum levels of total testosterone (18.5 +/- 1.3 to 26.3 +/- 1.8 nmol/L, P = .005) and a 150% increase in SHBG (18.0 +/- 2.2 to 44.9 +/- 7.0 nmol/L, P = .008) following T3 treatment. Estradiol and free testosterone levels were unchanged by treatment, although free testosterone decreased from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L. T3 treatment significantly reduced the GH interburst interval (P < .05) and produced slight increases in the measures of GH secretion. There were no statistically significant effects of T3 treatment on insulin secretion, although insulin peak amplitude, mass secreted per burst, and total production all decreased. We conclude that experimentally induced T3 excess in healthy men produces significant and sustained changes in sex hormone levels and GH secretion. Furthermore, there are strong associations between SHBG and both GH and insulin secretion independent of thyroid hormone excess that require additional study.

The implication of neuroactive steroids in Tourette syndrome pathogenesis: a role for 5α-reductase?

PubMed Central

Bortolato, Marco; Frau, Roberto; Godar, Sean C; Mosher, Laura J; Paba, Silvia; Marrosu, Francesco; Devoto, Paola

2013-01-01

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by recurring motor and phonic tics. The pathogenesis of TS is thought to reflect dysregulations in the signaling of dopamine (DA) and other neurotransmitters, which lead to excitation/inhibition imbalances in cortico-striato-thalamocortical circuits. The causes of these deficits may reflect complex gene × environment × sex (G×E×S) interactions; indeed, the disorder is markedly predominant in males, with a male-to-female prevalence ratio of ~4:1. Converging lines of evidence point to neuroactive steroids as likely molecular candidates to account for GxExS interactions in TS. Building on these premises, our group has begun examining the possibility that alterations in the steroid biosynthetic process may be directly implicated in TS pathophysiology; in particular, our research has focused on 5α-reductase (5αR), the enzyme catalyzing the key rate-limiting step in the synthesis of pregnane and androstane neurosteroids. In clinical and preclinical studies, we found that 5αR inhibitors exerted marked anti-DAergic and tic-suppressing properties, suggesting a central role for this enzyme in TS pathogenesis. Based on these data, we hypothesize that enhancements in 5αR activity in early developmental stages may lead to an inappropriate activation of the “backdoor” pathway for androgen synthesis from adrenarche until the end of puberty. We predict that the ensuing imbalances in steroid homeostasis may impair the signaling of DA and other neurotransmitters, ultimately resulting in the facilitation of tics and other behavioral abnormalities in TS. PMID:23795653

Steroid receptor RNA activator (SRA1): unusual bifaceted gene products with suspected relevance to breast cancer

PubMed Central

Leygue, Etienne

2007-01-01

The steroid receptor RNA activator (SRA) is a unique modulator of steroid receptor transcriptional activity, as it is able to mediate its coregulatory effects as a RNA molecule. Recent findings, however, have painted a more complex picture of the SRA gene (SRA1) products. Indeed, even though SRA was initially thought to be noncoding, several RNA isoforms have now been found to encode an endogenous protein (SRAP), which is well conserved among Chordata. Although the function of SRAP remains largely unknown, it has been proposed that, much like its corresponding RNA, the protein itself might regulate estrogen and androgen receptor signaling pathways. As such, data suggest that both SRA and SRAP might participate in the mechanisms underlying breast, as well as prostate tumorigenesis. This review summarizes the published literature dealing with these two faces of the SRA gene products and underscores the relevance of this bifaceted system to breast cancer development. PMID:17710122

Steroid Hormones and Uterine Vascular Adaptation to Pregnancy

PubMed Central

Chang, Katherine; Zhang, Lubo

2008-01-01

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

Constraints on temperature-dependent sex determination in the leopard gecko ( Eublepharis macularius): response to Kratochvil et al.

NASA Astrophysics Data System (ADS)

Huang, Victoria; Sakata, Jon T.; Rhen, Turk; Coomber, Patricia; Simmonds, Sarah; Crews, David

2008-12-01

Kratochvil et al. (Naturwissenschaften 95:209 215, 2008) reported recently that in the leopard gecko ( Eublepharis macularius) of the family Eublepharidae with temperature-dependent sex determination (TSD), clutches in which eggs were incubated at the same temperature produce only same-sex siblings. Interpreting this result in light of studies of sex steroid hormone involvement in sex determination, they suggested that maternally derived yolk steroid hormones could constrain sex-determining mechanisms in TSD reptiles. We have worked extensively with this species and have routinely incubated clutches at constant temperatures. To test the consistency of high frequency same-sex clutches across different incubation temperatures, we examined our records of clutches at the University of Texas at Austin from 1992 to 2001. We observed that clutches in which eggs were incubated at the same incubation temperature produced mixed-sex clutches as well as same-sex clutches. Furthermore, cases in which eggs within a clutch were separated and incubated at different temperatures produced the expected number of mixed-sex clutches. These results suggest that maternal influences on sex determination are secondary relative to incubation temperature effects.

Sex steroid metabolism polymorphisms and mammographic density in pre- and early perimenopausal women

PubMed Central

Crandall, Carolyn J; Sehl, Mary E; Crawford, Sybil L; Gold, Ellen B; Habel, Laurel A; Butler, Lesley M; Sowers, MaryFran R; Greendale, Gail A; Sinsheimer, Janet S

2009-01-01

Introduction We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17β-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women. Methods The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age, race/ethnicity, parity, cigarette smoking, and body mass index (BMI). Results After multivariate adjustment, the CYP1B1 rs162555 CC genotype was associated with a 9.4% higher mammographic density than the TC/TT genotype (P = 0.04). The CYP19A1 rs936306 TT genotype was associated with 6.2% lower mammographic density than the TC/CC genotype (P = 0.02). The positive association between CYP1A1 rs2606345 and mammographic density was significantly stronger among participants with BMI greater than 30 kg/m2 than among those with BMI less than 25 kg/m2 (Pinteraction = 0.05). Among white participants, the ESR1 rs2234693 CC genotype was associated with a 7.0% higher mammographic density than the CT/TT genotype (P = 0.01). Conclusions SNPs in certain genes encoding sex steroid metabolism enzymes and ESRs were associated with mammographic density. Because the encoded enzymes and ESR1 are expressed in breast tissue, these SNPs may influence breast cancer risk by altering mammographic density. PMID:19630952

Sex and gender in psychoneuroimmunology research: past, present and future.

PubMed

Darnall, Beth D; Suarez, Edward C

2009-07-01

To date, research suggests that sex and gender impact pathways central to the foci of psychoneuroimmunology (PNI). This review provides a historical perspective on the evolution of sex and gender in psychoneuroimmunology research. Gender and sexually dimorphic pathways may have synergistic effects on health differences in men and women. We provide an overview of the literature of sex and gender differences in brain structure and function, sex steroids, gender role identification, hypothalamic-pituitary-adrenal axis function, genetics, immunology and cytokine response. Specific examples shed light on the importance of attending to sex and gender methodology in PNI research and recommendations are provided.

Cross-Sectional Associations between Body Size, Circulating Sex-Steroid Hormones and IGF Components among Healthy Chinese Women.

PubMed

McCullough, Lauren E; Miller, Erline E; Wang, Qiong; Li, Jia-Yuan; Liu, Li; Li, Hui; Zhang, Jing; Smith, Jennifer S

2015-01-01

The incidence of breast cancer has increased in Asian countries and rates of hormone receptor (HR) negative breast cancer exceed those of Western countries. Epidemiologic data suggest that the association between body size and BC risk may vary by HR status, and could differ geographically. While body size may influence BC risk by moderating the synthesis and metabolism of circulating sex-steroid hormones, insulin-like growth factor (IGF)-1 and related binding proteins, there is a dearth of literature among Asian women. We aimed to examine these specific associations in a sample of Chinese women. In Sichuan Province 143 women aged ≥40 years were recruited through outpatient services (2011-2012). Questionnaires, anthropometric measurements, and blood samples were utilized for data collection and linear regression was applied in data analyses. Among women <50 years we observed a non-monotonic positive association between body mass index (BMI) and 17β-estradiol, and a reversed J-shaped association between BMI and IGF-1 (p ≤0.05). We observed similar associations between waist-to-hip ratio and these markers. Our finding of augmented IGF-1 among women with low body mass may have implications for understanding breast tumor heterogeneity in diverse populations and should be evaluated in larger prospective studies with cancer outcomes.

Effect of gender and sex hormones on immune responses following shock.

PubMed

Angele, M K; Schwacha, M G; Ayala, A; Chaudry, I H

2000-08-01

Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

Developmental Programming: Postnatal Steroids Complete Prenatal Steroid Actions to Differentially Organize the GnRH Surge Mechanism and Reproductive Behavior in Female Sheep

PubMed Central

Jackson, Leslie M.; Mytinger, Andrea; Roberts, Eila K.; Lee, Theresa M.; Foster, Douglas L.; Padmanabhan, Vasantha

2013-01-01

In female sheep, estradiol (E2) stimulates the preovulatory GnRH/LH surge and receptive behavior, whereas progesterone blocks these effects. Prenatal exposure to testosterone disrupts both the positive feedback action of E2 and sexual behavior although the mechanisms remain unknown. The current study tested the hypothesis that both prenatal and postnatal steroids are required to organize the surge and sex differences in reproductive behavior. Our approach was to characterize the LH surge and mating behavior in prenatally untreated (Control) and testosterone-treated (T) female sheep subsequently exposed to one of three postnatal steroid manipulations: endogenous E2, excess E2 from a chronic implant, or no E2 due to neonatal ovariectomy (OVX). All females were then perfused at the time of the expected surge and brains processed for estrogen receptor and Fos immunoreactivity. None of the T females exposed postnatally to E2 exhibited an E2-induced LH surge, but a surge was produced in five of six T/OVX and all Control females. No surges were produced when progesterone was administered concomitantly with E2. All Control females were mounted by males, but significantly fewer T females were mounted by a male, including the T/OVX females that exhibited LH surges. The percentage of estrogen receptor neurons containing Fos was significantly influenced in a brain region-, developmental stage-, and steroid-specific fashion by testosterone and E2 treatments. These findings support the hypothesis that the feedback controls of the GnRH surge are sensitive to programming by prenatal and postnatal steroids in a precocial species. PMID:23417422

Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424).

PubMed

Cheng, Ting-Yuan David; Darke, Amy K; Redman, Mary W; Zirpoli, Gary R; Davis, Warren; Payne Ondracek, Rochelle; Bshara, Wiam; Omilian, Angela R; Kratzke, Robert; Reid, Mary E; Molina, Julian R; Kolesar, Jill M; Chen, Yuhchyau; MacRae, Robert M; Moon, James; Mack, Philip; Gandara, David R; Kelly, Karen; Santella, Regina M; Albain, Kathy S; Ambrosone, Christine B

2018-01-13

To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Patients with primary non-small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)-α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = -15.8, P = .003) and nuclear ER-β (β = -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = -42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Adrenal steroid hormones and metaphyseal bone in children.

PubMed

Remer, Thomas; Boye, Kai R; Hartmann, Michaela F; Neu, Christina; Schoenau, Eckhard; Manz, Friedrich; Wudy, Stefan A

2004-01-01

The responses of metaphyseal bone tissue to physiological variations of endogenous adrenal steroid hormones during childhood are unclear. Therefore, we studied potential hormonal influences in children before the appearance of pubic hair (onset of pubarche). Excretions of major glucocorticoid metabolites (C21), cortisol, sum of adrenarchal dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M), and 5-androstene-3beta,17beta-diol (hermaphrodiol) were analyzed in a cross-sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6-13 years, using steroid profiling by gas chromatography-mass spectrometry. Total and trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone strength strain index were determined with peripheral quantitative computed tomography at the distal forearm. In multiple regression analyses significant associations with the metaphyseal radius were seen for grip force, age, or BMI depending on gender and bone variable analyzed. DHEA&M did not contribute to the explanation of the variance of any bone variable. However, hermaphrodiol positively explained a significant part of variation of bone mineral densities, and BMC (p < 0.01) in girls. Significantly negative associations with all bone variables were seen in boys for cortisol. The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges, but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone in a sex-dependent manner during childhood. Copyright (c) 2004 S. Karger AG, Basel.

The utility and dynamics of salivary sex hormone measurements in the National Social Life, Health, and Aging Project, Wave 2.

PubMed

Kozloski, Michael J; Schumm, L Philip; McClintock, Martha K

2014-11-01

Sex hormones affect physical, mental, and social health, yet their role in mediating social effects on aging is understudied. To facilitate such analyses with the National Social Life, Health & Aging Project Wave 2, we summarize the conceptual background, collection protocols, laboratory assays, and data analysis strategies for biologically active (free) levels of testosterone, estradiol, progesterone, and dehydroepiandrosterone (DHEA). Saliva from passive drool was collected from returning Wave 1 respondents and non-respondents as well as their partners during an in-home interview. Specimens were frozen and sent to Dresden LabService GmbH for duplicate assays of biologically active steroids using identical assay kits from National Social Life, Health, and Aging Project (NSHAP) Wave 1 (SaliCap, Catalog No. RE69995). Overall, 2,772 testosterone, 2,504 estradiol, 2,714 progesterone, and 2,800 DHEA measurements are publically available for Wave 2 analyses. Through a series of weighted linear regressions, all 4 steroids are compared by gender and age and to Wave 1 measurements. Men had higher levels of both free testosterone and progesterone than women; women and men had the same levels of estradiol and DHEA. Both free testosterone and DHEA decreased with age. We also found significant wave effects for all 4 sex hormones. NSHAP Waves 1 and 2 are the first U.S. probability sample studies to measure these 4 salivary sex hormones simultaneously, providing individual profiles 5 years apart. Wave 2 data demonstrate differences by gender and trends by age that are similar to those found in other saliva-based and serum-based studies of free steroid levels. The differences between waves arising from the change in assay laboratory need to be adjusted in future longitudinal analyses using NSHAP Wave 1 and Wave 2 steroid data. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e

Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.

PubMed

Vanacker, Charlotte; Moya, Manuel Ricu; DeFazio, R Anthony; Johnson, Michael L; Moenter, Suzanne M

2017-10-01

Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. Pulse frequency is modulated by gonadal steroids and likely arises subsequent to coordination of GnRH neuron firing activity. The source of rhythm generation and the site of steroid feedback remain critical unanswered questions. Arcuate neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be involved in both of these processes. We tested the hypotheses that action potential firing in KNDy neurons is episodic and that gonadal steroids regulate this pattern. Targeted extracellular recordings were made of green fluorescent protein-identified KNDy neurons in brain slices from adult male mice that were intact, castrated, or castrated and treated with estradiol or dihydrotestosterone (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster analysis, occurred more frequently in castrated than intact mice, and either estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored peak frequency to intact levels. The frequency of peaks in firing rate and estradiol regulation of this frequency is similar to that observed for GnRH neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further examined the patterning of action potentials to identify bursts that may be associated with increased neuromodulator release. Burst frequency and duration are increased in castrated compared with intact and steroid-treated mice. The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation. Copyright © 2017 Endocrine Society.

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

PubMed

Guo, Lei; Chen, Yi-Xi; Hu, Yu-Ting; Wu, Xue-Yan; He, Yang; Wu, Juan-Li; Huang, Man-Li; Mason, Matthew; Bao, Ai-Min

2018-05-21

Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification and Transcriptional Modulation of the Largemouth Bass, Micropterus salmoides, Vitellogenin Receptor During Oocyte Development by Insulin and Sex Steroids1

PubMed Central

Dominguez, Gustavo A.; Quattro, Joseph M.; Denslow, Nancy D.; Kroll, Kevin J.; Prucha, Melinda S.; Porak, Wesley F.; Grier, Harry J.; Sabo-Attwood, Tara L.

2012-01-01

ABSTRACT Fish vitellogenin synthesized and released from the liver of oviparous animals is taken up into oocytes by the vitellogenin receptor. This is an essential process in providing nutrient yolk to developing embryos to ensure successful reproduction. Here we disclose the full length vtgr cDNA sequence for largemouth bass (LMB) that reveals greater than 90% sequence homology with other fish vtgr sequences. We classify LMB Vtgr as a member of the low density lipoprotein receptor superfamily based on conserved domains and categorize as the short variant that is devoid of the O-glycan segment. Phylogenetic analysis places LMB Vtgr sequence into a well-supported monophyletic group of fish Vtgr. Real-time PCR showed that the greatest levels of LMB vtgr mRNA expression occurred in previtellogenic ovarian tissues. In addition, we reveal the effects of insulin, 17beta-estradiol (E2), and 11-ketotestosterone (11-KT) in modulation of vtgr, esr, and ar mRNAs in previtellogenic oocytes. Insulin increased vtgr expression levels in follicles ex vivo while exposure to E2 or 11-KT did not result in modulation of expression. However, both steroids were able to repress insulin-induced vtgr transcript levels. Coexposure with insulin and E2 or of insulin and 11-KT increased ovarian esr2b and ar mRNA levels, respectively, which suggest a role for these nuclear receptors in insulin-mediated signaling pathways. These data provide the first evidence for the ordered stage-specific expression of LMB vtgr during the normal reproductive process and the hormonal influence of insulin and sex steroids on controlling vtgr transcript levels in ovarian tissues. PMID:22786822

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids

PubMed Central

Mannowetz, Nadja; Miller, Melissa R.

2017-01-01

The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization. PMID:28507119

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids.

PubMed

Mannowetz, Nadja; Miller, Melissa R; Lishko, Polina V

2017-05-30

The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that ( i ) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and ( ii ) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.

Steroids. A Resource Guide.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of School Health Education and Services.

This guide provides information on steroid use as well as prevention and intervention strategies. It is intended to serve as a supplement to drug abuse education and prevention programs in elementary and secondary schools and as the basis for local curriculum development and instructional activities. The following topics are covered: (1) history…

Higher growth rate and gene expression in male zebra finch embryos are independent of manipulation of maternal steroids in the eggs.

PubMed

Lutyk, Dorota; Tagirov, Makhsud; Drobniak, Szymon; Rutkowska, Joanna

2017-12-01

Sexual dimorphism in prenatal development is widespread among vertebrates, including birds. Its mechanism remains unclear, although it has been attributed to the effect of maternal steroid hormones. The aim of this study was to investigate how increased levels of steroid hormones in the eggs influence early embryonic development of male and female offspring. We also asked whether maternal hormones take part in the control of sex-specific expression of the genes involved in prenatal development. We experimentally manipulated hormones' concentrations in the egg yolk by injecting zebra finch females prior to ovulation with testosterone or corticosterone. We assessed growth rate and expression levels of CDK7, FBP1 and GHR genes in 37h-old embryos. We found faster growth and higher expression of two studied genes in male compared to female embryos. Hormonal treatment, despite clearly differentiating egg steroid levels, had no effect on the sex-specific pattern of the embryonic gene expression, even though we confirmed expression of receptors of androgens and glucocorticoids at such an early stage of development. Thus, our study shows high stability of the early sex differences in the embryonic development before the onset of sexual differentiation and indicates their independence of maternal hormones in the egg. Copyright © 2017 Elsevier Inc. All rights reserved.

Plasma Steroid Metabolome Profiling for Diagnosis and Subtyping Patients with Cushing Syndrome.

PubMed

Eisenhofer, Graeme; Masjkur, Jimmy; Peitzsch, Mirko; Di Dalmazi, Guido; Bidlingmaier, Martin; Grüber, Matthias; Fazel, Julia; Osswald, Andrea; Beuschlein, Felix; Reincke, Martin

2018-03-01

Diagnosis of Cushing syndrome requires a multistep process that includes verification of hypercortisolism followed by identification of the cause of adrenocortical hyperfunction. This study assessed whether pituitary, ectopic, and adrenal subtypes of Cushing syndrome were characterized by distinct plasma steroid profiles that might assist diagnosis. In this retrospective cross-sectional study, mass spectrometric measurements of a panel of 15 plasma steroids were applied to 222 patient samples tested for Cushing syndrome. Disease was excluded in 138 and confirmed in 51 patients with pituitary Cushing syndrome, 12 with ectopic adrenocorticotropin secretion, and 21 with adrenal disease. Another 277 age- and sex-matched hypertensive and normotensive volunteers were included for comparison. Compared with patients without disease, the largest increases in plasma steroids among patients with Cushing syndrome were observed for 11-deoxycortisol (289%), 21-deoxycortisol (150%), 11-deoxycorticosterone (133%), corticosterone (124%), and cortisol (122%). Patients with ectopic disease showed the most prominent increases, but there was considerable variation for other steroids according to subtype. Patients with adrenal disease had the lowest concentrations of androgens, whereas those with ectopic and pituitary disease showed the lowest concentrations of aldosterone. Plasma 18-oxocortisol was particularly low in ectopic disease. With the use of 10 selected steroids, subjects with and without different Cushing syndrome subtypes could be discriminated nearly as closely as with the use of salivary and urinary free cortisol, dexamethasone-suppressed cortisol, and plasma adrenocorticotropin (9.5% vs 5.8% misclassification). Patients with different subtypes of Cushing syndrome show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes. © 2017 American Association for Clinical Chemistry.

Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.

PubMed

O'Leary, Kathleen A; Shea, Michael P; Salituro, Stephanie; Blohm, Courtney E; Schuler, Linda A

2017-10-10

Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61 + luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Steroid Sulfatase Inhibition by Aryl Sulfamates: Clinical Progress, Mechanism and Future Prospects.

PubMed

Potter, Barry V L

2018-04-04

Steroid sulfatase is an emerging drug target for the endocrine therapy of hormone-dependent diseases, catalyzing estrogen sulfate hydrolysis to estrogen. Drug discovery, developing the core aryl O-sulfamate pharmacophore, has led to steroidal and non-steroidal drugs entering numerous clinical trials, with promising results in oncology and women's health. Steroidal estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors and one was developed clinically as an oral estradiol pro-drug and for endometriosis applications. This review summarizes work leading to the therapeutic concept of sulfatase inhibition, clinical trials executed to date and new insights into the mechanism of inhibition of steroid sulfatase. To date the non-steroidal sulfatase inhibitor Irosustat has been evaluated clinically in breast cancer, alone and in combination, in endometrial cancer and in prostate cancer. The versatile core pharmacophore both imbues attractive pharmaceutical properties and functions via three distinct mechanisms of action, as a pro-drug, an enzyme active site-modifying motif, likely through direct sulfamoyl group transfer, and as a structural component augmenting activity, for example by enhancing interactions at the colchicine binding site of tubulin. Preliminary new structural data on the Pseudomonas aeruginosa arylsulfatase enzyme suggest two possible sulfamate-based adducts with active site hydrated formylglycine as candidates for the inhibition end product via sulfamoyl group transfer, and a speculative choice is suggested. The clinical status of sulfatase inhibition is surveyed and how it might develop in the future. Also discussed are dual-targeting approaches, development of 2-substituted steroidal sulfamates and nonsteroidal derivatives as multi-targeting agents for hormone-independent tumours with other emerging directions.

Sex Steroid Metabolism in Benign and Malignant Intact Prostate Biopsies: Individual Profiling of Prostate Intracrinology

PubMed Central

Gianfrilli, Daniele; Pierotti, Silvia; Leonardo, Costantino; Ciccariello, Mauro

2014-01-01

In vitro studies reveal that androgens, oestrogens, and their metabolites play a crucial role in prostate homeostasis. Most of the studies evaluated intraprostatic hormone metabolism using cell lines or preprocessed specimens. Using an ex vivo model of intact tissue cultures with preserved architecture, we characterized the enzymatic profile of biopsies from patients with benign prostatic hyperplasia (BPH) or cancer (PC), focusing on 17β-hydroxy-steroid-dehydrogenases (17β-HSDs) and aromatase activities. Samples from 26 men who underwent prostate needle core biopsies (BPH n = 14; PC n = 12) were incubated with radiolabeled 3H-testosterone or 3H-androstenedione. Conversion was evaluated by TLC separation and beta-scanning of extracted supernatants. We identified three major patterns of conversion. The majority of BPHs revealed no active testosterone/oestradiol conversion as opposed to prostate cancer. Conversion correlated with histology and PSA, but not circulating hormones. Highest Gleason scores had a higher androstenedion-to-testosterone conversion and expression of 17β-HSD-isoenzymes-3/5. Conclusions. We developed an easy tool to profile individual intraprostatic enzymatic activity by characterizing conversion pathways in an intact tissue environment. In fresh biopsies we found that 17β-HSD-isoenzymes and aromatase activities correlate with biological behaviour allowing for morphofunctional phenotyping of pathology specimens and clinical monitoring of novel enzyme-targeting drugs. PMID:25184140

Inhibition of macrophage activation and lipopolysaccaride-induced death by seco-steroids purified from Physalis angulata L.

PubMed

Soares, Milena B P; Bellintani, Moema C; Ribeiro, Ivone M; Tomassini, Therezinha C B; Ribeiro dos Santos, Ricardo

2003-01-10

Physalis angulata L. is an annual herb widely used in popular medicine for the treatment of a variety of pathologies. Here, we tested immunomodulatory activities of physalins, seco-steroids purified from P. angulata extracts. Addition of physalins B, F or G, but not D, caused a reduction in nitric oxide production by macrophages stimulated with lipopolysaccaride and interferon-gamma. In the presence of physalin B, macrophages stimulated with lipopolysaccaride, alone or in combination with interferon-gamma, produced lower levels of tumour necrosis factor (TNF)-alpha, interleukin-6 and interleukin-12. The inhibitory activity of physalin B, unlike that of dexamethasone, was not reversed by RU486 [(4-dimethylamino) phenyl-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one], an antiglucocorticoid. Physalin B-treated mice had lower levels of serum TNF-alpha than control mice after lipopolysaccaride challenge. More importantly, mice injected with physalins B, F or G survived after a lethal lipopolysaccaride challenge. These results demonstrate that seco-steroids from P. angulata are potent immunomodulatory substances and act through a mechanism distinct from that of dexamethasone.

Wired on Steroids: Sexual Differentiation of the Brain and Its Role in the Expression of Sexual Partner Preferences

PubMed Central

Alexander, Brenda M.; Skinner, Donal C.; Roselli, Charles E.

2011-01-01

The preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. Development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. In the absence of androgen exposure, a male-directed partner preference develops. The development and expression of sexual partner preference has been extensively studied in rat, ferret, and sheep model systems. From these models it is clear that gonadal testosterone, often through estrogenic metabolites, cause both masculinization and defeminization of behavior during critical periods of brain development. Changes in the steroid environment during these critical periods result in atypical sexual partner preference. In this manuscript, we review the major findings which support the hypothesis that the organizational actions of sex steroids are responsible for sexual differentiation of sexual partner preferences in select non-human species. We also explore how this information has helped to frame our understanding of the biological influences on human sexual orientation and gender identity. PMID:22654808

Sex and gender in psychoneuroimmunology research: Past, present and future

PubMed Central

Darnall, Beth D.; Suarez, Edward C.

2009-01-01