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Sample records for active sex steroids

  1. Sex Steroids and the Dentate Gyrus

    PubMed Central

    Hajszan, Tibor; Leranth, Csaba

    2006-01-01

    In the late 1980s, the finding that the dentate gyrus contains more granule cells in the male than in the female of certain mouse strains provided the first indication that the dentate gyrus is a significant target for the effects of sex steroids during development. Gonadal hormones also play a crucial role in shaping the function and morphology of the adult brain. Besides reproduction-related processes, sex steroids participate in higher brain operations such as cognition and mood, in which the hippocampus is a critical mediator. Being part of the hippocampal formation, the dentate gyrus is naturally involved in these mechanisms and as such, this structure is also a critical target for the activational effects of sex steroids. These activational effects are the results of three major types of steroid-mediated actions. Sex steroids modulate the function of dentate neurons under normal conditions. In addition, recent research suggests that hormone-induced cellular plasticity may play a larger role than previously thought, particularly in the dentate gyrus. Specifically, the regulation of dentate gyrus neurogenesis and synaptic remodeling by sex steroids received increasing attention lately. Finally, the dentate gyrus is influenced by gonadal hormones in the context of cellular injury, and the work in this area demonstrates that gonadal hormones have neuroprotective potential. The expression of estrogen, progestin and androgen receptors in the dentate gyrus suggests that sex steroids, which could be of gonadal origin and/or synthesized locally in the dentate gyrus, may act directly on dentate cells. In addition, gonadal hormones could also influence the dentate gyrus indirectly, by subcortical hormone-sensitive structures such as the cholinergic septohippocampal system. Importantly, these three sex steroid-related themes, functional effects in the normal dentate gyrus, mechanisms involving neurogenesis and synaptic remodeling, as well as neuroprotection, have

  2. Neurology of sex steroids and oral contraceptives.

    PubMed

    Schipper, H M

    1986-11-01

    Under normal circumstances, sex steroids interact with diverse neural substrates to modulate a host of activities essential to the preservation of the individual and the species. In addition, sex hormones play an important role in various human neurologic conditions including strokes, migraine, certain movement disorders and peripheral neuropathies, and possibly even the behavior of CNS neoplasms. PMID:3025581

  3. CNS: sex steroids and SERMs.

    PubMed

    Bernardi, F; Pluchino, N; Stomati, M; Pieri, M; Genazzani, A R

    2003-11-01

    The central nervous system (CNS) is one of the main target tissues for sex steroid hormones, which act both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through nongenomic mechanisms, influencing electrical excitability, synaptic function, and morphological features. The identification of the brain as a de novo source of neurosteroids modulating cerebral function, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women could also be related to a modification in the levels of neurosteroids, particularly allopregnanolone and DHEA, GABA-A agonist, and antagonist, respectively. The selective estrogen receptor modulators (SERMs) are compounds that activate the estrogen receptors with different estrogenic and antiestrogenic tissue-specific effects. In addition to the effects of the classic steroid hormones on the CNS, the study of selective estrogen receptor modulators impact on the neuroendocrine system has recently provided encouraging results, indicating that raloxifene analog LY 117018 and the new generation SERM EM-652 have an estrogen-like action on beta-endorphin and on allopregnanolone in ovariectomized rats, while they exert an anti-estrogenic effect in fertile rats and in ovariectomized rats treated with estrogens. In addition, raloxifene administration in postmenopausal women plays an estrogen-like effect on circulating beta-EP and allopregnanolone levels, and it restores the response of beta-EP and allopregnanolone to neuroendocrine tests. In conclusion, the positive effects of HRT on mood and cognition in postmenopausal women occur via the modulation of neuroendocrine pathways and probably also of neurosteroidogenesis. The effects of raloxifene on mood and cognition encourage the efforts in the research of an ideal estrogen replacement therapy, showing all the positive effects of estrogens and fewer side effects. PMID:14644845

  4. [Steroid receptors and mechanism of action of sex steroids].

    PubMed

    Guiochon-Mantel, A; Milgrom, E

    1999-01-01

    Steroid hormone receptors define a large family of proteins. Recently, a new estradiol receptor has been identified. This discovery suggests the existence of a previously unrecognized pathway of estrogen signalling. Moreover, it implies important pharmacological consequences. Receptors activation induces the modulation of transcription of specific genes. Proteins involved in this effect have been identified: coactivators, corepressors and cointegrators. Their mechanism of action have been characterized. They modify histone acetylation of the corresponding promotor. Sex steroid receptors are located in the nucleus. This nuclear localization is in fact a dynamic situation, resulting from a continuous shuttling of the receptor between the cytoplasm and the nucleus. Non genomic effects of steroids have also been described. PMID:10542957

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

    SciTech Connect

    Verma, Vikas; Sharma, Vikas; Singh, Vishal; Sharma, Siddharth; Bishnoi, Ajay Kumar; Chandra, Vishal; Maikhuri, J.P.; Dwivedi, Anila; Kumar, Atul; Gupta, Gopal

    2014-10-15

    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 the 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.

  6. Implantation: mutual activity of sex steroid hormones and the immune system guarantee the maternal-embryo interaction.

    PubMed

    Gnainsky, Yulia; Dekel, Nava; Granot, Irit

    2014-09-01

    Implantation is strictly dependent on the mutual interaction between a receptive endometrium and the blastocyst. Hence, synchronization between blastocyst development and the acquisition of endometrial receptivity is a prerequisite for the success of this process. This review depicts the cellular and molecular events that coordinate these complex activities. Specifically, the involvement of the sex steroid hormones, estrogen and progesterone, as well as components of the immune system, such as cytokines and specific blood cells, is elaborated. PMID:24959815

  7. Sex Steroid Signaling: Implications for Lung Diseases

    PubMed Central

    Sathish, Venkatachalem; Martin, Yvette N.; Prakash, Y.S.

    2015-01-01

    There is increasing recognition that the sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine. PMID:25595323

  8. Sex Differences and Sex Steroids in Lung Health and Disease

    PubMed Central

    Townsend, Elizabeth A.; Miller, Virginia M.

    2012-01-01

    Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span. PMID:22240244

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

    PubMed

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

    2016-03-01

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

  10. Influence of Triazine Herbicide Exposure on Guppies (Poecilia sphenops) Aromatase Activities, Altered Sex Steroid Concentration and Vitellogenin Induction

    PubMed Central

    Vasanth, S.; Arul, G.; Karthikeyeni, S.; Kumar, T. S. V.; Vignesh, V.; Manimegalai, M.; Bupesh, G.; Thirumurugan, R.; Subramanian, P.

    2015-01-01

    Atrazine, a herbicide is one the most toxic and sustaining pollutants in aquatic environment. It is detectable in surface water and in underground sources of drinking water. Many studies indicate that atrazine might be a potent endocrine disrupting xenobiotic. There are limited studies have revealed that the effects of atrazine on sex steroids hormones, vitellogenin and induction of aromatase, gonadosomatic index and hepatosomatic index. In this study, juvenile Poecilia sphenops fish was exposed to three different (0.83, 1.25 and 2.5 ppm) concentration of atrazine for 100 d. Changes in plasma and gonadal content and concentrations of sex steroids and vitellogenin protein in poecilia sphenops under laboratory conditions were assessed. The low level of the atrazine show estrogenic effect in males, as determined by a shortage of testosterone induction. Present study suggests that low induction of plasma vitellogenin and aromatase in male fish become suitable biomarkers of exposure to estrogenic chemicals. PMID:26009647

  11. Sex Steroid Actions in Male Bone

    PubMed Central

    Laurent, Michaël R.; Claessens, Frank; Gielen, Evelien; Lagerquist, Marie K.; Vandenput, Liesbeth; Börjesson, Anna E.; Ohlsson, Claes

    2014-01-01

    Sex steroids are chief regulators of gender differences in the skeleton, and male gender is one of the strongest protective factors against osteoporotic fractures. This advantage in bone strength relies mainly on greater cortical bone expansion during pubertal peak bone mass acquisition and superior skeletal maintenance during aging. During both these phases, estrogens acting via estrogen receptor-α in osteoblast lineage cells are crucial for male cortical and trabecular bone, as evident from conditional genetic mouse models, epidemiological studies, rare genetic conditions, genome-wide meta-analyses, and recent interventional trials. Genetic mouse models have also demonstrated a direct role for androgens independent of aromatization on trabecular bone via the androgen receptor in osteoblasts and osteocytes, although the target cell for their key effects on periosteal bone formation remains elusive. Low serum estradiol predicts incident fractures, but the highest risk occurs in men with additionally low T and high SHBG. Still, the possible clinical utility of serum sex steroids for fracture prediction is unknown. It is likely that sex steroid actions on male bone metabolism rely also on extraskeletal mechanisms and cross talk with other signaling pathways. We propose that estrogens influence fracture risk in aging men via direct effects on bone, whereas androgens exert an additional antifracture effect mainly via extraskeletal parameters such as muscle mass and propensity to fall. Given the demographic trends of increased longevity and consequent rise of osteoporosis, an increased understanding of how sex steroids influence male bone health remains a high research priority. PMID:25202834

  12. 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

  13. Roles of sex and gonadal steroids in mammalian pheromonal communication.

    PubMed

    Baum, Michael J; Bakker, Julie

    2013-10-01

    A brain circuit (the accessory olfactory system) that originates in the vomeronasal organ (VNO) and includes the accessory olfactory bulb (AOB) plus additional forebrain regions mediates many of the effects of pheromones, typically comprised of a variety of non-volatile and volatile compounds, on aspects of social behavior. A second, parallel circuit (the main olfactory system) that originates in the main olfactory epithelium (MOE) and includes the main olfactory bulb (MOB) has also been shown to detect volatile pheromones from conspecifics. Studies are reviewed that point to specific roles of several different steroids and their water-soluble metabolites as putative pheromones. Other studies are reviewed that establish an adult, 'activational' role of circulating sex hormones along with sex differences in the detection and/or processing of non-steroidal pheromones by these two olfactory circuits. Persisting questions about the role of sex steroids in pheromonal processing are posed for future investigation. PMID:23872334

  14. The Effects of Sex Steroids on Spatial Performance: A Review and an Experimental Clinical Investigation.

    ERIC Educational Resources Information Center

    Liben, Lynn S.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan; Schwab, Jacqueline; Dubas, Judith Semon; Demers, Laurence M.; Lookingbill, Georgia; D'Arcangelo, M. Rose; Krogh, Holleen R.; Kulin, Howard E.

    2002-01-01

    Investigated the relationship between sex hormones and spatial performance among adolescents treated with sex steroids for delayed puberty. Found that spatial performance varied according to gender but did not vary with levels of actively circulating sex steroids. Reviewed physiological mechanisms, developmental periods, and past empirical work…

  15. Relationship between lipoprotein lipase activity and plasma sex steroid level in obese women.

    PubMed Central

    Iverius, P H; Brunzell, J D

    1988-01-01

    In obese women (n = 16) at their weight, fasting adipose tissue lipoprotein lipase (LPL) activity, obtained by elution with serum and heparin at 4 degrees and 37 degrees C, was inversely correlated to plasma estradiol levels (r = -0.724; P = 0.002) and (r = -0.641; P = 0.010), respectively. Furthermore, fasting postheparin plasma LPL activity during a heparin infusion, showed an even stronger inverse correlation to plasma estradiol when measured at 60 min (r = -0.815; P less than 0.001). None of the above parameters was correlated to the body mass index. Postprandial LPL activity in postheparin plasma, measured 10 min after a heparin injection, showed a strong positive correlation with plasma free testosterone (r = 0.780; P = 0.001). Neither of these parameters was correlated with the body mass index. The origin of this LPL activity is presently unknown but could conceivably represent a pool of LPL from skeletal muscle. Since it has been shown convincingly that estrogen decreases adipose tissue LPL activity in the rat, the present studies strongly suggest that estradiol is a major negative regulator of fasting adipose tissue LPL activity in women. PMID:3417867

  16. Sex steroids and glucose metabolism.

    PubMed

    Allan, Carolyn A

    2014-01-01

    Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM) and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference) is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain. PMID:24457840

  17. Sex steroids and bone: current perspectives.

    PubMed

    Balasch, Juan

    2003-01-01

    Although the process of bone remodelling or its control has not yet been fully elucidated there is, at present, sufficient information available to conclude that ovarian steroids (estrogens, androgens, progesterone) play an essential role in skeletal homeostasis. The mechanism of action of sex steroids on the skeleton is still not entirely clear, but it has traditionally included indirect effects on systemic hormones that regulate calcium balance and a direct receptor-mediated action. More recently, changes in cytokine production within the bone marrow, as well as pro-apoptotic and anti-apoptotic effects in the osteoblastic cells, have been proposed as new perspectives on the cellular and molecular mechanisms by which sex steroids influence adult bone homeostasis. Mechanical loading, when combined with estrogens or androgens, results in a greater osteogenic response than either condition separately. Women are especially at risk for osteoporosis if they have had a premature or surgical menopause and have not received hormone replacement therapy (HRT). Other reproductive factors that can help to identify women with osteopenia and emphasize the role of sex steroids in preserving bone mass in premenopausal women include: age at menarche, menstrual history and irregularities (including those associated with excessive exercise), age at menopause, previous hysterectomy, hyperprolactinaemia, anorexia nervosa, scoliosis, ovarian dysgenesis, pregnancy and lactation, and pharmacological ovarian suppression. The prevention of osteoporosis starts with the onset of the menarche. A combination of exercise, appropriate nutrition and a healthy lifestyle all maximize bone mineral accrual and result in optimal peak bone mass; normal ovarian function is essential to this process. Unfortunately, many women actually become aware of the need for osteoporosis prevention much later in life, usually after they have already become menopausal. HRT, however, has important limitations for

  18. 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...

  19. Interactions of sex steroids with mechanisms of inflammation.

    PubMed

    Obendorf, Maik; Patchev, Vladimir K

    2004-12-01

    Differential sex-specific liability to inflammatory and autoimmune diseases, and changes in symptom severity in association with physiological fluctuations in gonadal secretions are indicative of significant contribution of sex hormones to the regulation of immune responsiveness. Apart from a postulated role in sex-specific organization of the immune system during ontogeny, gonadal steroids may influence the immune response in numerous ways. This review analyzes existing concepts, experimental and clinical data, aiming at the definition of cellular and molecular mechanisms which may serve as suitable targets for discovery of immunomodulatory drugs whose principal feature is specific interaction with sex hormone receptors. Separation of immunomodulatory effects of sex steroids from those which are exerted by glucocorticoids, and subsequent identification of sex-hormone-specific molecular targets appear to be crucial for the justification of drug discovery on the basis of sex steroid receptor ligands. PMID:15584890

  20. Acetylcholinesterase activity in the sexually dimorphic area of the gerbil brain: sex differences and influences of adult gonadal steroids.

    PubMed

    Commins, D; Yahr, P

    1984-03-20

    The morphology of the medial preoptic area-anterior hypothalamus (MPOA-AH) of gerbils is sexually dimorphic and influenced by adult gonadal hormones. This research shows that the distribution of (MPOA-AH) cells that synthesize acetylcholinesterase (AChE) and the activity of AChE within the MPOA-AH are also sexually dimorphic and hormone sensitive. Adult male and female gerbils were gonadectomized, gonadectomized and implanted subcutaneously with testosterone (T), or sham operated 4-8 weeks before sacrifice. Coronal sections through the sexually dimorphic area (SDA) of the MPOA-AH were stained for AChE. Planimeter measurements of camera lucida drawings showed that the total volume of the SDA is similar in the two sexes, but the proportion of the SDA that stains darkly and/or stands out clearly from the surround (dark volume) is larger in males. Optical density readings also indicated that AChE staining is darker in the male SDA. Gonadectomy decreases staining intensity in both sexes and reduces total SDA volume. Dark volume decreases more than 50%. Testosterone treatment reverses all effects of gonadectomy, although hormonal influences are smaller in females than in males. There were no sex differences or hormonal influences on AChE staining lateral to the SDA. The pars compacta of the male SDA was essentially devoid of AChE, indicating that this cell group is distinct from the rest of the SDA. It also shrinks after castration unless the males receive T. Histochemical changes in the SDA may be related to hormonal control of scent marking, a form of communication in this species. PMID:6715576

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

    PubMed Central

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

    2013-01-01

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

  2. 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

  3. Sex steroid blockade enhances thymopoiesis by modulating Notch signaling

    PubMed Central

    Tsai, Jennifer J.; Holland, Amanda M.; Wertheimer, Tobias; Yu, Vionnie W.C.; Zakrzewski, Johannes L.; Tuckett, Andrea Z.; Singer, Natalie V.; West, Mallory L.; Smith, Odette M.; Young, Lauren F.; Kreines, Fabiana M.; Levy, Emily R.; Boyd, Richard L.; Scadden, David T.

    2014-01-01

    Paradoxical to its importance for generating a diverse T cell repertoire, thymic function progressively declines throughout life. This process has been at least partially attributed to the effects of sex steroids, and their removal promotes enhanced thymopoiesis and recovery from immune injury. We show that one mechanism by which sex steroids influence thymopoiesis is through direct inhibition in cortical thymic epithelial cells (cTECs) of Delta-like 4 (Dll4), a Notch ligand crucial for the commitment and differentiation of T cell progenitors in a dose-dependent manner. Consistent with this, sex steroid ablation (SSA) led to increased expression of Dll4 and its downstream targets. Importantly, SSA induced by luteinizing hormone-releasing hormone (LHRH) receptor antagonism bypassed the surge in sex steroids caused by LHRH agonists, the gold standard for clinical ablation of sex steroids, thereby facilitating increased Dll4 expression and more rapid promotion of thymopoiesis. Collectively, these findings not only reveal a novel mechanism underlying improved thymic regeneration upon SSA but also offer an improved clinical strategy for successfully boosting immune function. PMID:25332287

  4. Sex steroid blockade enhances thymopoiesis by modulating Notch signaling.

    PubMed

    Velardi, Enrico; Tsai, Jennifer J; Holland, Amanda M; Wertheimer, Tobias; Yu, Vionnie W C; Zakrzewski, Johannes L; Tuckett, Andrea Z; Singer, Natalie V; West, Mallory L; Smith, Odette M; Young, Lauren F; Kreines, Fabiana M; Levy, Emily R; Boyd, Richard L; Scadden, David T; Dudakov, Jarrod A; van den Brink, Marcel R M

    2014-11-17

    Paradoxical to its importance for generating a diverse T cell repertoire, thymic function progressively declines throughout life. This process has been at least partially attributed to the effects of sex steroids, and their removal promotes enhanced thymopoiesis and recovery from immune injury. We show that one mechanism by which sex steroids influence thymopoiesis is through direct inhibition in cortical thymic epithelial cells (cTECs) of Delta-like 4 (Dll4), a Notch ligand crucial for the commitment and differentiation of T cell progenitors in a dose-dependent manner. Consistent with this, sex steroid ablation (SSA) led to increased expression of Dll4 and its downstream targets. Importantly, SSA induced by luteinizing hormone-releasing hormone (LHRH) receptor antagonism bypassed the surge in sex steroids caused by LHRH agonists, the gold standard for clinical ablation of sex steroids, thereby facilitating increased Dll4 expression and more rapid promotion of thymopoiesis. Collectively, these findings not only reveal a novel mechanism underlying improved thymic regeneration upon SSA but also offer an improved clinical strategy for successfully boosting immune function. PMID:25332287

  5. Sex steroids and growth hormone interactions.

    PubMed

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

    2016-04-01

    GH and sex hormones are critical regulators of body growth and composition, somatic development, intermediate metabolism, and sexual dimorphism. Deficiencies in GH- or sex hormone-dependent signaling and the influence of sex hormones on GH biology may have a dramatic impact on liver physiology during somatic development and in adulthood. Effects of sex hormones on the liver may be direct, through hepatic receptors, or indirect by modulating endocrine, metabolic, and gender-differentiated functions of GH. Sex hormones can modulate GH actions by acting centrally, regulating pituitary GH secretion, and peripherally, by modulating GH signaling pathways. The endocrine and/or metabolic consequences of long-term exposure to sex hormone-related compounds and their influence on the GH-liver axis are largely unknown. A better understanding of these interactions in physiological and pathological states will contribute to preserve health and to improve clinical management of patients with growth, developmental, and metabolic disorders. PMID:26775014

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

    PubMed Central

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

    2013-01-01

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

  7. Sex steroid hormones and circulating IgE levels.

    PubMed

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

    1977-12-01

    The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies. PMID:606452

  8. 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. PMID:24011879

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

    PubMed Central

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

    2015-01-01

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

  10. Survey of receiving-water environmental impacts associated with discharges from pulp mills; 2: Gonad size, liver size, hepatic erod activity and plasma sex steroid levels in white sucker

    SciTech Connect

    Munkittrick, K.R.; Servos, M.R. . Great Lakes Lab. for Fisheries and Aquatic Sciences); Van Der Kraak, G.J.; McMaster, M.E. . Dept. of Zoology); Portt, C.B. ); Heuvel, M.R. van den . Dept. of Biology)

    1994-07-01

    Fish collected from the receiving areas of 12 Canadian pulp mills were examined, including sites receiving effluent from kraft mills using chlorine as well as sulfite mills. Field collections included sampling of receiving water for chemistry and toxicity testing, and sampling of local fish for organ weights, hepatic MFO (ethoxyresorufin-O-deethylase, EROD) activity, plasma steroid levels, and levels of liver dioxins. The main objectives of this study were to determine whether the discharge of effluent from pulp mills to sites other than Jackfish Bay was associated with physiological or biochemical disruptions in wild fish, whether there was any correlation between waste treatment and the presence of biological responses in wild fish, and whether there was any association between the use of chlorine as a bleaching agent and these responses. Although white sucker collected near bleached-kraft mills exhibited the highest EROD induction and dioxin levels, elevated enzyme activity was observed in fish from sites that did not use chlorine, and depressions in plasma sex steroid levels was not correlated with the level of EROD activity. The absence of chlorine bleaching or the presence of secondary treatment did not eliminate responses in fish, including decreased circulating levels of sex steroids, decreased gonadal size, and increase liver size. This survey has shown that (a) induction of hepatic EROD enzymes and depressions of plasma sex steroid levels during gonadal growth are found downstream of several pulp mills; (b) these changes are seen at some mills without chlorine bleaching and at mills that have secondary treatment; (c) substantial dilutions of nontoxic effluent do not appear to remove these responses; (d) the dominant factor determining the presence or absence of responses appeared to be dilution level; and (e) lab toxicity tests on invertebrates, rainbow trout, and fat-head minnows could not predict the presence of these responses in wild fish.

  11. Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts.

    PubMed

    Pomari, Elena; Dalla Valle, Luisa; Pertile, Paolo; Colombo, Lorenzo; Thornton, M Julie

    2015-02-01

    Peripheral intracrine sex steroid synthesis from adrenal precursors dehydroepiandrosterone (DHEA) and DHEA-sulfate has evolved in humans. We sought to establish if there are differences in intracrine, paracrine, and endocrine regulation of sex steroids by primary cultures of human skin epidermal keratinocytes and dermal fibroblasts. Microarray analysis identified multifunctional genes modulated by steroids, quantitative RT-PCR (qRT-PCR) mRNA expression, enzymatic assay aromatase activity, scratch assay cell migration, immunocytochemistry α-smooth muscle actin (α-SMA), and collagen gel fibroblast contraction. All steroidogenic components were present, although only keratinocytes expressed the organic anion organic anion transporter protein (OATP) 2B1 transporter. Both expressed the G-protein-coupled estrogen receptor (GPER1). Steroids modulated multifunctional genes, up-regulating genes important in repair and aging [angiopoietin-like 4 (ANGPTL4), chemokine (C-X-C motif) ligand 1 (CXCL1), lamin B1 (LMNB1), and thioredoxin interacting protein (TXNIP)]. DHEA-sulfate (DHEA-S), DHEA, and 17β-estradiol stimulated keratinocyte and fibroblast migration at early (4 h) and late (24-48 h) time points, suggesting involvement of genomic and nongenomic signaling. Migration was blocked by aromatase and steroid sulfatase (STS) inhibitors confirming intracrine synthesis to estrogen. Testosterone had little effect, implying it is not an intermediate. Steroids stimulated fibroblast contraction but not α-SMA expression. Mechanical wounding reduced fibroblast aromatase activity but increased keratinocyte activity, amplifying the bioavailability of intracellular estrogen. Cultured fibroblasts and keratinocytes provide a biologically relevant model system to investigate the complex pathways of sex steroid intracrinology in human skin. PMID:25392269

  12. Probing the impact of sex steroids and menopause-related sex steroid deprivation on modulation of immune senescence.

    PubMed

    Vrachnis, Nikolaos; Zygouris, Dimitrios; Iliodromiti, Zoe; Daniilidis, Angelos; Valsamakis, Georgios; Kalantaridou, Sophia

    2014-07-01

    Immune senescence denotes the general decline in immune system function, characterized by a reduced immune response and an increased inflammatory state. Menopause is a natural change in a women's life, the menopause-related low estrogen levels affecting many body functions, among them the immune system. Numerous human studies with menopausal women and animal models with surgically induced menopause show a clear impact of sex steroids in immune responses. Female superiority in vaccination response and predisposition to infections are eliminated after menopause, while during menopause inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukins-1β, 6, 8 and 13 (IL-1β, IL-6, IL-8, IL-13) and Monocyte Chemoattractant Protein-1 (MCP-1) are increased, implying a molecular connection of sex steroid loss with immune senescence. Moreover, immune cells modify their number and function after the menopausal transition, this offering another explanation for immune senescence. Until now most of the existing studies have concluded that menopause plays an additional role to aging in immune senescence. While it is clear that we are as yet far from thoroughly understanding the molecular pathways connecting sex steroids and menopause with immune senescence, such knowledge is highly likely to enable future targeted interventions in treatment and prevention of age-related diseases in women. PMID:24852404

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    McArthur, Simon; Gillies, Glenda E.

    2011-01-01

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

  15. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    SciTech Connect

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

    2012-05-15

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

  16. 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

    2016-01-01

    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. PMID:27115344

  17. Sex steroid sensitivity of developing bursa of Fabricius.

    PubMed

    Ylikomi, T; Tuohimaa, P

    1989-03-01

    Sex steroid sensitivity of the bursa of Fabricius (BF) was studied from the early embryonic time until its regression. Expression of progesterone receptor (PR) served as a dual marker: first, as a marker for progesterone sensitivity and second, as a marker for estrogen action, since it is an estrogen-induced protein. The progesterone binding molecule in the bursa was characterized by different chromatography methods and by steroid binding studies. We showed that it fulfils the criteria of a progesterone receptor by binding, structural and immunological properties. With immunohistochemistry and with the combined techniques of immunohistochemistry and autoradiography we demonstrated two cell types which express the PR: smooth muscle cells surrounding the BF and stromal cells located under the bursal epithelium and between the lymphoid follicles. The epithelium and the cells inside the lymphoid follicles were negative. Using immunoelectron microscopy the PR-expressing stromal cells were shown to be fibroblasts. The cloacal mesenchyme, from which the BF develops, was shown to be sensitive to exogenous estrogen very early during the embryonic time. The mesenchyme around and inside the developing BF reached estrogen sensitivity a few days later. The estrogen-sensitive mesenchymal cells were first seen surrounding the bursal primordium and later in the center of the plicae. During a natural sexual maturation without exogenous estradiol an expression of the PR was detected much later, at the age of 10-12 weeks after hatching. This expression correlates with the onset of the bursal regression and with the increase of the sex steroid levels in the blood. In the oviduct stroma PR was undetectable before the onset of sexual maturation. In the oviduct stroma PR becomes detectable a few weeks earlier than in the bursa. PMID:2485693

  18. No sex difference in yolk steroid concentrations of avian eggs at laying

    PubMed Central

    Pilz, Kevin M; Adkins-Regan, Elizabeth; Schwabl, Hubert

    2005-01-01

    Yolk steroids of maternal origin have been proposed to influence genetic sex determination in birds, based on sex differences in yolk steroid concentrations of peafowl eggs incubated for 10 days. More recent reports dispute this proposal, as yolk steroids in eggs incubated for 3 days do not show such sex differences. To date, research examining this phenomenon has only analysed incubated eggs, although sex in avian species is determined before incubation begins. This may be a serious methodological flaw because incubation probably affects yolk steroid concentrations. Therefore, we investigated sex differences in yolk steroid concentrations of unincubated avian eggs. We withdrew yolk for steroid analysis from fresh, unincubated Japanese quail (Coturnix japonica) eggs by biopsy, and then incubated those eggs for 10 days, after which we harvested the embryonic material for genetic sexing and the incubated yolk for further steroid analysis. We found no sex differences in fresh Japanese quail eggs; however, sex differences were apparent in yolk steroids by day 10 of incubation, when female eggs had significantly more oestrogen in relation to androgen than male eggs. Concentrations of all yolk androgens decreased dramatically between laying and day 10 of incubation, whereas oestradiol (E2) concentrations increased marginally. Thus, yolk concentrations of androgens and E2 do not appear critical for avian sex determination. PMID:17148197

  19. No sex difference in yolk steroid concentrations of avian eggs at laying.

    PubMed

    Pilz, Kevin M; Adkins-Regan, Elizabeth; Schwabl, Hubert

    2005-09-22

    Yolk steroids of maternal origin have been proposed to influence genetic sex determination in birds, based on sex differences in yolk steroid concentrations of peafowl eggs incubated for 10 days. More recent reports dispute this proposal, as yolk steroids in eggs incubated for 3 days do not show such sex differences. To date, research examining this phenomenon has only analysed incubated eggs, although sex in avian species is determined before incubation begins. This may be a serious methodological flaw because incubation probably affects yolk steroid concentrations. Therefore, we investigated sex differences in yolk steroid concentrations of unincubated avian eggs. We withdrew yolk for steroid analysis from fresh, unincubated Japanese quail (Coturnix japonica) eggs by biopsy, and then incubated those eggs for 10 days, after which we harvested the embryonic material for genetic sexing and the incubated yolk for further steroid analysis. We found no sex differences in fresh Japanese quail eggs; however, sex differences were apparent in yolk steroids by day 10 of incubation, when female eggs had significantly more oestrogen in relation to androgen than male eggs. Concentrations of all yolk androgens decreased dramatically between laying and day 10 of incubation, whereas oestradiol (E2) concentrations increased marginally. Thus, yolk concentrations of androgens and E2 do not appear critical for avian sex determination. PMID:17148197

  20. All sex steroids are made intracellularly in peripheral tissues by the mechanisms of intracrinology after menopause.

    PubMed

    Labrie, Fernand

    2015-01-01

    Following the arrest of estradiol secretion by the ovaries at menopause, all estrogens and all androgens in postmenopausal women are made locally in peripheral target tissues according to the physiological mechanisms of intracrinology. The locally made sex steroids exert their action and are inactivated intracellularly without biologically significant release of the active sex steroids in the circulation. The level of expression of the steroid-forming and steroid-inactivating enzymes is specific to each cell type in each tissue, thus permitting to each cell/tissue to synthesize a small amount of androgens and/or estrogens in order to meet the local physiological needs without affecting the other tissues of the organism. Achieved after 500 million years of evolution, combination of the arrest of ovarian estrogen secretion, the availability of high circulating levels of DHEA and the expression of the peripheral sex steroid-forming enzymes have permitted the appearance of menopause with a continuing access to intratissular sex steroids for the individual cells/tissues without systemic exposure to circulating estradiol. In fact, one essential condition of menopause is to maintain serum estradiol at biologically inactive (substhreshold) concentrations, thus avoiding stimulation of the endometrium and risk of endometrial cancer. Measurement of the low levels of serum estrogens and androgens in postmenopausal women absolutely requires the use of MS/MS-based technology in order to obtain reliable accurate, specific and precise assays. While the activity of the series of steroidogenic enzymes can vary, the serum levels of DHEA show large individual variations going from barely detectable to practically normal "premenopausal" values, thus explaining the absence of menopausal symptoms in about 25% of women. It should be added that the intracrine system has no feedback elements to adjust the serum levels of DHEA, thus meaning that women with low DHEA activity will not be

  1. Antifungal Activity of C-27 Steroidal Saponins

    PubMed Central

    Yang, Chong-Ren; Zhang, Ying; Jacob, Melissa R.; Khan, Shabana I.; Zhang, Ying-Jun; Li, Xing-Cong

    2006-01-01

    As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study. PMID:16641439

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

    PubMed

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

    1994-12-01

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

  3. 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

  4. Steroids

    MedlinePlus

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

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

    PubMed

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

    2016-10-01

    Cholesterol and sex steroid hormones including androgens and estrogens play a critical role in the development and progression of urological diseases such as prostate cancer. This disease remains the most commonly diagnosed malignant tumor in men and is the leading cause of death from different cancers. Attempts to understand the role of cholesterol and steroid metabolism in urological diseases have been ongoing for many years, but despite this, our mechanistic and translational understanding remains elusive. In order to further evaluate the problem, we have taken an interest in metabolomics; a discipline dedicated to the systematic study of biologically active metabolites in cells, tissues, hair and biofluids. Recently, we provided evidence that a quantitative measurement of cholesterol and sex steroid metabolites can be successfully achieved using hair of human and mouse models. The overall goal of this short review article is to introduce current metabolomic technologies for the quantitative biomarker assay development and also to provide new insight into understanding the underlying mechanisms that trigger the pathological condition. Furthermore, this review will place a particular emphasis on how to prepare biospecimens (e.g., hair fiber), quantify molecular profiles and assess their clinical significance in various urological diseases. PMID:27580660

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

    PubMed Central

    Cheng, Jie; Gonzalez, Frank J.

    2013-01-01

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

  7. Prognostic role of sex steroid receptors in pancreatic adenocarcinoma.

    PubMed

    Georgiadou, Despoina; Sergentanis, Theodoros N; Sakellariou, Stratigoula; Vlachodimitropoulos, Dimitris; Psaltopoulou, Theodora; Lazaris, Andreas C; Gounaris, Antonia; Zografos, George C

    2016-01-01

    From the available literature, it is unclear what proportion of pancreatic adenocarcinomas express estrogen receptors (ERα, ERβ), progesterone receptors (PR), and androgen receptors (AR), and if any of these markers have prognostic significance. We aimed to assess (1) the expression and (2) the correlation of the aforementioned markers with clinicopathological parameters and prognosis in patients with pancreatic adenocarcinoma. During a five-year period, 60 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institution. Immunohistochemical stains of the studied markers were quantified by Image analysis system. ERα expression was positively associated with PR expression. Moreover, ERβ was inversely associated with the presence of metastases, whereas no significant associations implicated AR. As far as the prognostic significance of the studied receptors is concerned, higher ERα expression correlated with poorer survival at the univariate analysis, but the finding dissipated at the multivariate approach. No significant associations with overall survival were noted regarding the other receptors. The role of sex hormone receptors in the survival from pancreatic adenocarcinoma seems rather limited. Further prospective studies assessing those receptors should ideally be designed in order to confirm our results and possibly outline additional correlations between other steroid receptors and features of pancreatic adenocarcinoma. PMID:26652605

  8. 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…

  9. Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics.

    PubMed

    Li, Jau-Yi; Chassaing, Benoit; Tyagi, Abdul Malik; Vaccaro, Chiara; Luo, Tao; Adams, Jonathan; Darby, Trevor M; Weitzmann, M Neale; Mulle, Jennifer G; Gewirtz, Andrew T; Jones, Rheinallt M; Pacifici, Roberto

    2016-06-01

    A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis. PMID:27111232

  10. Regional and sex-related differences in modulating effects of female sex steroids on ecto-5'-nucleotidase expression in the rat cerebral cortex and hippocampus.

    PubMed

    Mitrović, Nataša; Guševac, Ivana; Drakulić, Dunja; Stanojlović, Miloš; Zlatković, Jelena; Sévigny, Jean; Horvat, Anica; Nedeljković, Nadežda; Grković, Ivana

    2016-09-01

    Ecto-5'-nucleotidase (eN), a membrane rate-limiting enzyme of the purine catabolic pathway, catalyzes the conversion of AMP to adenosine involved in the regulation of many brain physiological and pathological processes. Since gender fundamentally determines hormonal milieu in the body and brain, it is reasonable to assume that sex differences in the activity of various signaling systems, including adenosine, may be generated by gonadal steroids. Thus, we examined expression of eN as a component of adenosine signaling system in the basal state in cerebral cortex and hippocampus of male and female rats at gene, protein and functional level, as well as in the state of gonadal hormone deprivation, induced by ovariectomy (OVX), whereas impact of steroid hormones was explored after repeated administration of 17α-estradiol, 17β-estradiol and progesterone for seven consecutive days. Results showed regional and sex-related differences in basal eN activity level, with the highest AMP hydrolysis observed in the hippocampus of male rats. Furthermore, ovarian steroids do not contribute to basal gene eN expression or the activity in cortical and hippocampal region of female rats. However, protein eN expression was increased in OVX rats in both investigated region. Investigated exogenous steroids had no influence on eN expression in male brain, while in OVX females alterations in eN activity were induced. The observed effects in female rats were different between examined regions e.g. in cortex, applied treatments predominantly decreased whereas in hippocampus increased eN activity. Based on the presented results, eN exerts regional and sex-related response in basal state as well as after treatment with female gonadal hormones, however the exact mechanisms of sex steroids actions on eN remain unclear and should be fully explored. PMID:27296672

  11. 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. PMID:27433022

  12. Preventing Anabolic Steroid Use: Guidelines and Activities.

    ERIC Educational Resources Information Center

    Nutter, June; Rauhe, Betty

    1997-01-01

    Information about anabolic steroids should be included in the school health curriculum as early as possible. The paper presents suggestions for planning education programs and offers a variety of activities and strategies appropriate for many age groups, including case studies, story completion, posters, demonstrations, projects, creative writing,…

  13. Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival12

    PubMed Central

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

    2015-01-01

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

  14. 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

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

    PubMed

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

    2014-01-01

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

  16. 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.

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

    PubMed Central

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

    2011-01-01

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

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

    SciTech Connect

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

    1995-12-31

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

  19. Reproductive Status Regulates Expression of Sex Steroid and GnRH Receptors in the Olfactory Bulb

    PubMed Central

    Fernald, Russell D.

    2010-01-01

    Neuromodulators including gonadotropin-releasing hormone (GnRH) and sex steroids help integrate an animal's internal physiological state with incoming external cues, and can have profound effects on the processing of behaviorally-relevant information, particularly from the olfactory system. While GnRH and steroid receptors are present in olfactory processing regions across vertebrates, little is known about whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA levels of two GnRH receptors (GnRH-R1, GnRH-R2), five sex steroid receptors (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ), and aromatase in the olfactory bulb of the highly social African cichlid fish Astatotilapia burtoni. We asked whether these receptor levels changed with reproductive condition in females, or with social status, which regulates reproductive capacity in males. Our results reveal that mRNA levels of multiple sex steroid, GnRH receptor subtypes, and aromatase in the olfactory bulb vary with sex, social status in males, and reproductive condition in females, which highlights the potential importance of changing receptor levels in fine-tuning the olfactory system during the reproductive cycle. Further, steroid receptor mRNA levels were positively correlated with circulating steroid levels in males, but negatively correlated in females, suggesting different regulatory control between sexes. These results provide support for the hypothesis that the first-order olfactory relay station is a substrate for both GnRH and sex steroid modulation, and suggest that changes in receptor levels could be an important mechanism for regulating reproductive, social, and seasonal plasticity in olfactory perception observed across vertebrates. PMID:20466023

  20. Prostate diseases--role of sex steroids and their inhibitors.

    PubMed

    Welén, Karin; Damber, Jan-Erik

    2011-04-01

    The normal prostate as well as prostatic diseases are influenced by androgens. The exact reason for an altered and uncontrolled response to androgens, whether benign as in benign prostate hyperplasia (BPH) or malignant as in the case of prostate cancer (PC), is not known in detail. Nevertheless, restriction of androgen receptor activation by reduction of available androgens is of great clinical value in both diseases. In BPH the inhibition of the conversion of testosterone into 5α-dihydrotestosterone (DHT) by 5α-reductase (5AR) is highly efficient and used in general practice, while the situation in PC is more complex. Specific inhibition of 5AR does not provide as efficient relief of symptoms as general androgen deprivation therapy (ADT), and the use of 5ARI for PC prevention is still under debate. Further, the altered steroid metabolism in castration resistant prostate cancer (CRPC) together with the complex paracrine signalling between different androgen responsive cell types, make the development of more specific drugs targeting androgen receptor signalling both more relevant and challenging. PMID:21397203

  1. Sex Differences in Seoul Virus Infection Are Not Related to Adult Sex Steroid Concentrations in Norway Rats

    PubMed Central

    Klein, Sabra L.; Bird, Brian H.; Glass, Gregory E.

    2000-01-01

    Field studies of hantavirus infection in rodents report that a higher percentage of infected individuals are males than females. To determine whether males were more susceptible to hantavirus infection than females, adult male and female Long Evans rats (Rattus norvegicus) were inoculated with doses of Seoul virus ranging from 10−4 to 106 PFU. The 50% infective doses (ID50) were not significantly different for male and female rats (100.05 and 100.8 PFU, respectively). To determine whether sex differences in response to infection were related to circulating sex steroid hormones, sex steroid concentrations were manipulated and antibody responses and virus shedding were assessed following inoculation with the ID90. Regardless of hormone treatment, males had higher anti-Seoul virus immunoglobulin G (IgG) and IgG2a (i.e., Th1) responses than females and IgG1 (i.e., Th2) responses similar to those of females. Males also shed virus in saliva and feces longer than females. Manipulation of sex steroids in adulthood did not alter immune responses or virus shedding, suggesting that sex steroids may organize adult responses to hantavirus earlier during ontogeny. PMID:10933735

  2. Sex steroid deficiency–associated bone loss is microbiota dependent and prevented by probiotics

    PubMed Central

    Li, Jau-Yi; Chassaing, Benoit; Tyagi, Abdul Malik; Vaccaro, Chiara; Luo, Tao; Adams, Jonathan; Darby, Trevor M.; Weitzmann, M. Neale; Mulle, Jennifer G.; Gewirtz, Andrew T.; Jones, Rheinallt M.

    2016-01-01

    A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency–induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid–deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid–deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis. PMID:27111232

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

    PubMed

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

    2016-01-01

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

  4. Steroid receptor expression in the fish inner ear varies with sex, social status, and reproductive state

    PubMed Central

    2010-01-01

    Background Gonadal and stress-related steroid hormones are known to influence auditory function across vertebrates but the cellular and molecular mechanisms responsible for steroid-mediated auditory plasticity at the level of the inner ear remain unknown. The presence of steroid receptors in the ear suggests a direct pathway for hormones to act on the peripheral auditory system, but little is known about which receptors are expressed in the ear or whether their expression levels change with internal physiological state or external social cues. We used qRT-PCR to measure mRNA expression levels of multiple steroid receptor subtypes (estrogen receptors: ERα, ERβa, ERβb; androgen receptors: ARα, ARβ; corticosteroid receptors: GR2, GR1a/b, MR) and aromatase in the main hearing organ of the inner ear (saccule) in the highly social African cichlid fish Astatotilapia burtoni, and tested whether these receptor levels were correlated with circulating steroid concentrations. Results We show that multiple steroid receptor subtypes are expressed within the main hearing organ of a single vertebrate species, and that expression levels differ between the sexes. We also show that steroid receptor subtype-specific changes in mRNA expression are associated with reproductive phase in females and social status in males. Sex-steroid receptor mRNA levels were negatively correlated with circulating estradiol and androgens in both males and females, suggesting possible ligand down-regulation of receptors in the inner ear. In contrast, saccular changes in corticosteroid receptor mRNA levels were not related to serum cortisol levels. Circulating steroid levels and receptor subtype mRNA levels were not as tightly correlated in males as compared to females, suggesting different regulatory mechanisms between sexes. Conclusions This is the most comprehensive study of sex-, social-, and reproductive-related steroid receptor mRNA expression in the peripheral auditory system of any single

  5. Annual changes in serum sex steroids in male and female black (Ursus americanus) and polar (Ursus maritimus) bears.

    PubMed

    Palmer, S S; Nelson, R A; Ramsay, M A; Stirling, I; Bahr, J M

    1988-06-01

    The adaptation of black and polar bears to their environments is proportional to the severity of climate and food restriction. Both black and polar bears mate during the spring, despite differences in their recent metabolic state. Reproductive activity in black bears follows 4 mo of torpor, whereas reproduction in polar bears occurs prior to torpor. The goals of this study were to measure the annual changes in serum sex steroids in male and female black and polar bears, and to determine if changes in serum levels of these steroids were associated with metabolic condition or photoperiod. Serum testosterone (T) concentrations were elevated during spring in black and polar bears. Moreover, this increase in serum T in polar bears during spring was correlated with age and testis size. Serum progesterone (P4) concentrations increased in pregnant polar bears in fall coincident with the time of expected implantation. No increases in serum P4 were observed in nonpregnant black and polar bears. Serum estradiol (E2) was elevated in nonpregnant and pregnant polar bears 2 mo prior to the time of expected implantation. We found that serum sex steroids measured in black and polar bears change independent of torpor. Therefore, our results suggest that photoperiod may be a more important regulator of serum steroid levels and reproduction than metabolic condition. PMID:3408772

  6. Direct evidence for the localization of the steroid-binding site of the plasma sex steroid-binding protein (SBP or SHBG) at the interface between the subunits.

    PubMed Central

    Sui, L. M.; Hughes, W.; Hoppe, A. J.; Pétra, P. H.

    1996-01-01

    Complete dissociation of dimeric plasma sex steroid-binding protein (SBP or SHBG) was obtained in 6 M urea at 10 degrees C. Removal of urea resulted in the refolding of monomers, followed by reformation of dimeric SBP, which migrates with the same mobility as the native protein. Dimerization does not require Ca+2 or steroid. Renatured monomers yield dimers with dissociation constants for 5 alpha-dihydrotesterone (DHT) and 17 beta-estradiol (E2) indistinguishable from those of native human SBP. This phenomenon was also demonstrated by mixing human and rabbit SBPs that, upon renaturation, form a hybrid dimer composed of one human subunit and one rabbit subunit. The hybrid binds both DHT and E2 in contrast to rSBP, which only binds the androgen. Therefore, we conclude that (1) docking of the two subunits creates an asymmetric steroid-binding site located at the interface between the subunits, and (2) only one face of the dimer defines the specificity for binding E2 by encompassing portion of a structural motif that recognizes the flat ring A of E2. The remaining portion, which recognizes the saturated ring A of DHT, is shared by both faces of the dimer. Because native monomers do not exist alone, the often-asked question of whether the SBP monomer binds steroid can be considered meaningless; steroid-binding activity is expressed only in the dimeric state. Finally, formation of the hybrid indicates that SBP dimerization represents a conserved event during the molecular evolution of SBP, suggesting that the structural elements responsible for dimerization will be homologous in SBPs from other species. PMID:8976560

  7. Steroid Sulfatase Deficiency and Androgen Activation Before and After Puberty

    PubMed Central

    Idkowiak, Jan; Taylor, Angela E.; Subtil, Sandra; O'Neil, Donna M.; Vijzelaar, Raymon; Dias, Renuka P.; Amin, Rakesh; Barrett, Timothy G.; Shackleton, Cedric H. L.; Kirk, Jeremy M. W.; Moss, Celia

    2016-01-01

    Context: Steroid sulfatase (STS) cleaves the sulfate moiety off steroid sulfates, including dehydroepiandrosterone (DHEA) sulfate (DHEAS), the inactive sulfate ester of the adrenal androgen precursor DHEA. Deficient DHEA sulfation, the opposite enzymatic reaction to that catalyzed by STS, results in androgen excess by increased conversion of DHEA to active androgens. STS deficiency (STSD) due to deletions or inactivating mutations in the X-linked STS gene manifests with ichthyosis, but androgen synthesis and metabolism in STSD have not been studied in detail yet. Patients and Methods: We carried out a cross-sectional study in 30 males with STSD (age 6–27 y; 13 prepubertal, 5 peripubertal, and 12 postpubertal) and 38 age-, sex-, and Tanner stage-matched healthy controls. Serum and 24-hour urine steroid metabolome analysis was performed by mass spectrometry and genetic analysis of the STS gene by multiplex ligation-dependent probe amplification and Sanger sequencing. Results: Genetic analysis showed STS mutations in all patients, comprising 27 complete gene deletions, 1 intragenic deletion and 2 missense mutations. STSD patients had apparently normal pubertal development. Serum and 24-hour urinary DHEAS were increased in STSD, whereas serum DHEA and testosterone were decreased. However, total 24-hour urinary androgen excretion was similar to controls, with evidence of increased 5α-reductase activity in STSD. Prepubertal healthy controls showed a marked increase in the serum DHEA to DHEAS ratio that was absent in postpubertal controls and in STSD patients of any pubertal stage. Conclusions: In STSD patients, an increased 5α-reductase activity appears to compensate for a reduced rate of androgen generation by enhancing peripheral androgen activation in affected patients. In healthy controls, we discovered a prepubertal surge in the serum DHEA to DHEAS ratio that was absent in STSD, indicative of physiologically up-regulated STS activity before puberty. This may

  8. Sex Steroids Influence Brain-Derived Neurotropic Factor Secretion From Human Airway Smooth Muscle Cells.

    PubMed

    Wang, Sheng-Yu; Freeman, Michelle R; Sathish, Venkatachalem; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

    2016-07-01

    Brain derived neurotropic factor (BDNF) is emerging as an important player in airway inflammation, remodeling, and hyperreactivity. Separately, there is increasing evidence that sex hormones contribute to pathophysiology in the lung. BDNF and sex steroid signaling are thought to be intricately linked in the brain. There is currently little information on BDNF and sex steroid interactions in the airway but is relevant to understanding growth factor signaling in the context of asthma in men versus women. In this study, we assessed the effect of sex steroids on BDNF expression and secretion in human airway smooth muscle (ASM). Human ASM was treated with estrogen (E2 ) or testosterone (T, 10 nM each) and intracellular BDNF and secreted BDNF measured. E2 and T significantly reduced secretion of BDNF; effects prevented by estrogen and androgen receptor inhibitor, ICI 182,780 (1 μM), and flutamide (10 μM), respectively. Interestingly, no significant changes were observed in intracellular BDNF mRNA or protein expression. High affinity BDNF receptor, TrkB, was not altered by E2 or T. E2 (but not T) significantly increased intracellular cyclic AMP levels. Notably, Epac1 and Epac2 expression were significantly reduced by E2 and T. Furthermore, SNARE complex protein SNAP25 was decreased. Overall, these novel data suggest that physiologically relevant concentrations of E2 or T inhibit BDNF secretion in human ASM, suggesting a potential interaction of sex steroids with BDNF in the airway that is different from brain. The relevance of sex steroid-BDNF interactions may lie in their overall contribution to airway diseases such as asthma. J. Cell. Physiol. 231: 1586-1592, 2016. © 2015 Wiley Periodicals, Inc. PMID:26566264

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

    PubMed Central

    Thompson, Amanda L.; Lampl, Michelle

    2014-01-01

    Objectives 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 pre- and post-natal 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. Methods Maternal characteristics and birth size were collected at study enrollment, infant diet was assessed through weekly 24-hr 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. Results 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. Conclusion These results suggest that markers of early energy availability influence sex hormone levels with potential long-term consequences for reproductive development and function. PMID:23904043

  10. 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. PMID:26758306

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

    PubMed

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

    2008-11-01

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

  12. Sex steroids modulate prolactin response to naloxone in postmenopausal women.

    PubMed

    Melis, G B; Gambacciani, M; Paoletti, A M; Mais, V; Cagnacci, A; Petacchi, F D; Fioretti, P

    1985-08-01

    To evaluate whether ovarian steroids modify the prolactin (PRL) response to opioid receptor blockade, the effects of naloxone infusion (1.6 mg/h for 4 h) on PRL secretion were studied in 5 postmenopausal women. Naloxone infusion was performed in basal conditions and after chronic oral treatment with conjugated estrogens (CE) (1.25 mg/day, for 20 days) or CE plus medroxyprogesterone acetate (MPA) (10 mg/day, for 20 days). Under basal conditions, 17 beta-estradiol, estrone, gonadotropin, and PRL plasma levels were in the normal range for postmenopausal women, and naloxone failed to affect PRL secretion. Naloxone induced a significant PRL increase after CE treatment alone (p less than 0.001) or in combination with MPA (p less than 0.001). The increase was significantly higher (p less than 0.05) after CE + MPA treatment than after CE treatment alone. These data suggest that steroids modulate the stimulatory effect of naloxone on PRL secretion in postmenopausal women. PMID:2995857

  13. Seasonal changes in sex and adrenal steroid hormones of gopher tortoises (Gopherus polyphemus).

    PubMed

    Ott, J A; Mendonça, M T; Guyer, C; Michener, W K

    2000-02-01

    We sampled a population of gopher tortoises (Gopherus polyphemus) from May to October 1997 to determine seasonal cycles of steroid hormones (testosterone, T; 17beta-estradiol, E; and progesterone, P) and related them to observations of mating behavior. In males, plasma T levels peaked in July and August and remained elevated through October. This coincides with the reported time of peak mating and spermatogenesis, indicating that males display an associated pattern of reproduction. In females, E levels were high in September and October. Plasma T levels in females were elevated in May, decreased to basal levels in June and July, and rose again in August and September. Elevated E and T levels correspond to the reported time of peak vitellogenic activity, indicating that females also display an associated cycle. Plasma P in females remained basal throughout the active season, suggesting that ovulation occurs in late winter. We also determined levels of corticosterone (B) to assess the influence of capture stress on tortoises and correlated B levels with tortoise activity patterns and sex steroid levels. We found no seasonal variation in levels of B in males or females. Plasma B levels were not correlated with levels of T or E, but were positively correlated with female P levels. Further, we found no relationship between plasma B levels in males and mean distance moved, mean number of burrows used, or mean home range size. However, there was a significant negative correlation between plasma B levels and male body size. In females, there was no relationship between B levels and mean distance moved, but B levels were significantly negatively correlated with the number of burrows females occupied. Lastly, there was no relationship between levels of B and the number of minutes required to obtain blood from an animal. However, B levels increased with the length of time that a tortoise spent in a trap, suggesting that trapped tortoises do exhibit capture stress. PMID

  14. Embryonic sex steroid hormones accumulate in the eggshell of loggerhead sea turtle (Caretta caretta).

    PubMed

    Kobayashi, Shohei; Saito, Yoshimichi; Osawa, Akihisa; Katsumata, Etsuko; Karaki, Isuke; Nagaoka, Kentaro; Taya, Kazuyoshi; Watanabe, Gen

    2015-12-01

    Steroids hormones such as estradiol-17β (E2) and testosterone (T) are involved in gonadal differentiation of oviparous animals with temperature-dependent sex determination (TSD), and are greatly distributed. This hypothesizes that these embryonic steroid hormones probably accumulate in the eggshell throughout blood or/and chorioallantoic fluid in sea turtle species with TSD, producing females at higher temperature. To demonstrate this hypothesis, concentrations of E2 and T in the blood plasma from the hatchling loggerhead sea turtle (Caretta caretta) and in their eggshells were measured by radioimmunoassay. In the present study we propose that both concentrations of E2 and T in the blood plasma are correlated with amounts of these sex steroids in the eggshell. Moreover, contents of E2 in the eggshell showed a significant positive correlation with mean incubation temperatures during a thermosensitive period in the experimental nests, whereas T contents in the eggshell did not. Taken together, these findings indicated that embryonic E2 and T that accumulated in the eggshell can be extracted and measured. Furthermore, the present study suggested that contents of E2 in the eggshell may differ between male and female, and monitoring of these steroids is a useful method to identify the sex of loggerhead sea turtle hatchling. PMID:26050561

  15. Sex steroid levels and response to weight loss interventions among postmenopausal women in the Diabetes Prevention Program

    PubMed Central

    Kim, Catherine; Barrett-Connor, Elizabeth; Randolph, John F.; Kong, Shengchun; Nan, Bin; Mather, Kieren J.; Golden, Sherita H.

    2013-01-01

    Objectives To examine whether estrogen use potentiates weight loss interventions via sex steroid levels and whether endogenous sex steroid levels predict response to weight loss interventions among women not using estrogen. Design and Methods The Diabetes Prevention Program randomized overweight or obese dysglycemic participants to lifestyle change with the goals of weight reduction of >7% of initial weight and 150 minutes per week of exercise; metformin; or placebo. In this secondary analysis, we examined sex steroid levels and reductions in weight and waist circumference (WC) among postmenopausal women using (n=324) and not using (n=382) oral estrogen. Results Estrogen users and non-users randomized to lifestyle change and metformin both lost significant amounts of weight compared to placebo. Reductions in weight and WC over 1 year associated with randomization arm were not associated with baseline sex steroid levels among estrogen users or non-users. Conclusions Among estrogen users, baseline sex steroids were not associated with reductions in weight or WC, suggesting that exogenous estrogen does not potentiate weight loss by altering sex steroids. Among non-estrogen users, baseline sex steroids were not associated with reductions in weight or WC. PMID:23804582

  16. Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

    PubMed Central

    Kalra, Mamta; Mayes, Jary; Assefa, Senait; Kaul, Anil K; Kaul, Rashmi

    2008-01-01

    The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC. PMID:18932272

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Are sex steroids essential for gonadal differentiation of the ornate frog, Microhyla ornata?

    PubMed

    Mali, P V; Gramapurohit, N P

    2016-07-01

    Knowledge about sensitivities and responses of amphibian larvae to sex steroids and the chemicals alike is the first step towards understanding and assessing the effect of diverse chemicals that interfere with gonadal development and other endocrine functions. Herein, we used Microhyla ornata to determine the role of sex steroids on its gonad differentiation and sex ratio. Our results show that the exposure to increasing concentrations of estradiol-17β throughout larval development did not affect gonad differentiation resulting in 1:1 sex ratio at metamorphosis. But, females emerging from estradiol-17β treatment had larger ovaries with larger sized follicles. Further, testes of some males contained lumens, the number of which was dose dependent. Similarly, exposure to testosterone propionate had negligible effects on gonad differentiation. However, the mean diameter of the largest follicles was smaller in treated ovaries. Treatment of tadpoles with tamoxifen had no effect on gonad differentiation and ovary development while testicular development was accelerated at the highest concentration. Similarly, treatment of tadpoles with cyproterone acetate had little effect on gonad differentiation as well as development, hence the sex ratios at the end of metamorphosis. Further, in tadpoles exposed to increasing concentrations of formestane, gonad differentiation was normal resulting in 1:1 sex ratio. Thus, in M. ornata, both estradiol and testosterone are essential for the development of ovaries and testes respectively but, they are not critical to gonadal differentiation. Hence, the effects of sex steroids and other endocrine disrupting chemicals could be species-specific; different species may have differential sensitivities to such chemicals. PMID:27181751

  20. Pregnane steroidal glycosides and their cytostatic activities.

    PubMed

    García, Víctor P; Bermejo, Jaime; Rubio, Sara; Quintana, José; Estévez, Francisco

    2011-05-01

    Four new steroidal glycosides such as 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside-12-β-tigloyl-14-β-hydroxy-17-β-pregnane (1), 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside-12-β-(2'-amino)-benzoyl-14-β-hydroxy-17-β-pregnane (2), 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside-12-β-14-β-dihydroxy-17-α-pregnane (3) and 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside-12-β-14-β-dihydroxy-17-β-pregnane (4) were isolated from the aerial parts of Ceropegia fusca Bolle (Asclepiadaceae), a crassulacean acid metabolism plant, an endemic species to the Canary Islands that has been used in traditional medicine as a cicatrizant, vulnerary and disinfectant. The dichloromethane extract exhibited significant cytostatic activity against HL-60, A-431 and SK-MEL-1 cells, human leukemic, epidermoid carcinoma and melanoma cells, respectively. As shown in Table I, compounds 1 and 2 showed very similar IC(50) values. The acetylation of 1 to give the diacetate 5 increases 5-fold the cytotoxicity against HL-60 cells. Compounds 3 and 4 did not show cytotoxicity at the assayed concentrations. With respect to the compounds containing only the steroid ring (6-8), the presence of a charged O-amino-benzoyl but not a tigloyl group improved the cytotoxicity. PMID:21147757

  1. Sex steroid and prolactin profiles in male American black bears (Ursus americanus) during denning.

    PubMed

    Tsubota, T; Garshelis, D L; Nelson, R A; Bahr, J M

    1999-01-01

    Serum sex steroid and prolactin profiles were examined in the male American black bear, Ursus americanus during denning. Sera collected in December and the following March from 8 denning male black bears in Minnesota, U.S.A. were assayed for testosterone, estradiol-17 beta and prolactin. Eight bears were confirmed to be the denning mode based on a serum urea to creatinine ratio less than 10. Serum testosterone concentrations tended to increase from December to the subsequent March whereas serum estradiol-17 beta concentrations tended to decrease during this period. There were few changes in serum prolactin concentrations between December and March. These findings suggest that spermatogenesis and testicular steroidogenesis initiated during denning may be influenced by changes in serum sex steroid concentrations in the American black bear. PMID:10027172

  2. Sex steroids stimulate leptin gene expression in Atlantic salmon parr hepatocytes in vitro.

    PubMed

    Trombley, Susanne; Rocha, Ana; Schmitz, Monika

    2015-09-15

    In mammals, leptin plays an important role in puberty and reproduction and leptin is regulated by sex steroids. Elevated leptin levels have been associated with sexual maturation in some teleosts such as Atlantic salmon. In the present study, primary cultures of Atlantic salmon hepatocytes were used to investigate the direct effects of different sex steroids on expression of the two salmon leptin-a genes, lepa1 and lepa2. Testosterone (T) stimulated both lepa1 and lepa2 in a dose dependent manner after four days of incubation. The stimulatory effect of T on leptin expression was not prevented by co-incubation with the aromatase inhibitor fadrozole, indicating a direct androgen effect on transcription. The non-aromatizable androgen 11-ketotestosterone (11-KT), which is the main androgen in fish, was generally slightly less potent than T in stimulating lepa1 and lepa2. The strongest stimulatory response was seen for 17β-estradiol (E2). E2 treatment significantly up-regulated lepa1 and lepa2 gene expression at doses of 10nM and 1nM for each gene, respectively. Lepa1, but not lepa2, was stimulated by T and 11-KT in immature male and immature female parr, while E2 stimulated expression of both genes. The sensitivity to sex steroid stimulation differed in maturing males compared to immature. In maturing males, the androgens and E2 stimulated lepa2 but not lepa1, while in immature males, the androgens and E2 stimulated lepa1, but only E2 stimulated lepa2. The differential response of the two leptin paralogues to the sex steroids suggests differences in regulation of the two leptin genes during maturation. Altogether, these results indicate that leptin expression in Atlantic salmon hepatocytes is directly regulated at the transcriptional level by the main teleost androgens and an estrogen, and that the response might depend on the developmental stage of the fish. PMID:25644210

  3. 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-...

  4. 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. PMID:24416184

  5. A Review of the Relationships Between Endogenous Sex Steroids and Incident Ischemic Stroke and Coronary Heart Disease Events

    PubMed Central

    Kim, Catherine; Cushman, Mary; Kleindorfer, Dawn; Lisabeth, Lynda; Redberg, Rita F.; Safford, Monika M.

    2015-01-01

    For decades, it has been recognized that men have a higher age-adjusted risk of ischemic cardiovascular (CVD) events compared to women, thus generating hypotheses that sex steroids contribute to CVD risk. Potential mechanisms include genomic and non-genomic effects of sex steroids as well as mediation through classic CVD risk factors and obesity. However, results from randomized studies suggest that sex steroid supplementation in men and women do not result in improved CVD outcomes and may increase CVD risk. In contrast, prospective observations from endogenous sex steroid studies, i.e. among participants not using sex steroids, have suggested the opposite relationship. We reviewed the findings of prospective observational studies in men (17 studies) and women (8 studies) that examined endogenous sex steroids and CVD risk. These studies suggested a lack of association or that lower levels of testosterone or dihydrotestosterone are associated with higher CVD risk in both men and women. Higher, rather than lower, estradiol levels were associated with higher CVD risk in women. There were several significant gaps in the literature. First, it is unclear whether more sensitive measures of sex steroid levels might detect significant differences. Second, there are few prospective studies in women. Similarly, no studies report outcomes for high-risk groups such as African-Americans and Hispanics. Finally, few studies report upon ischemic coronary disease as opposed to ischemic stroke separately, although relationships between sex steroids and CVD may vary by vascular bed. Future investigations need to examine high risk groups and to distinguish between subtypes of CVD. PMID:25563292

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

    PubMed

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

    2015-02-01

    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 96 h 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 96 h, 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 96 h, 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 <48 h, but not for steroid/endocrine studies. PMID:25283089

  7. 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

  8. 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. PMID:8493300

  9. Augmented transport and metabolism of sex steroids in lymphoid neoplasia in the rat

    SciTech Connect

    Cefalu, W.T.; Pardridge, W.M.

    1987-03-01

    Sex steroid hormones have been shown to influence a number of biological properties of lymphoid neoplastic tissue. Receptor occupancy is a function of the pool size of cellular exchangeable hormone therefore it is important to understand the mechanisms regulating hormone transport from the microcirculation and hormone metabolism. In this study, steroid hormone transport and metabolism were investigated in control and neoplastic lymph nodes after transplanting control rats with the WR-6 leukemic line. Steroid hormone transport and metabolism were studied after pulse labeling the nodal tissue in vivo with arterial bolus injections of (/sup 3/H)testosterone. Residual vascular radioactivity was monitored by simultaneously injecting 113m indium chelated to bovine transferrin. Both testosterone and estradiol were partially available for transport through the capillary barriers of control and neoplastic lymph nodes from the circulating albumin-bound pool. Estradiol was readily available for transport from the circulating sex hormone-binding globulin-bound pool in both control and neoplastic lymph nodes. Testosterone was not available for transport from the sex hormone-binding globulin-bound pool in control lymph nodes, but was readily available for transport in metastatic lymph nodes. Thaw-mount autoradiography and physiological measurements showed that plasma proteins such as albumin or transferrin were confined to the microcirculation compartment. The transport of protein-bound hormones into lymph node represents a mechanism of enhanced steroid hormone dissociation from the binding protein without the plasma protein per se significantly exiting the microcirculation compartment. Metabolic studies showed no measurable metabolism of (/sup 3/H)testosterone in the control lymph nodes by 60 sec after arterial injection.

  10. Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes

    PubMed Central

    Maliqueo, Manuel; Echiburú, Bárbara; Crisosto, Nicolás

    2016-01-01

    Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines, and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia, and fetal growth restriction, exhibit altered sex steroid concentrations. PMID:27199767

  11. Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes.

    PubMed

    Maliqueo, Manuel; Echiburú, Bárbara; Crisosto, Nicolás

    2016-01-01

    Adequate blood supply to the uterine-placental region is crucial to ensure the transport of oxygen and nutrients to the growing fetus. Multiple factors intervene to achieve appropriate uterine blood flow and the structuring of the placental vasculature during the early stages of pregnancy. Among these factors, oxygen concentrations, growth factors, cytokines, and steroid hormones are the most important. Sex steroids are present in extremely high concentrations in the maternal circulation and are important paracrine and autocrine regulators of a wide range of maternal and placental functions. In this regard, progesterone and estrogens act as modulators of uterine vessels and decrease the resistance of the spiral uterine arteries. On the other hand, androgens have the opposite effect, increasing the vascular resistance of the uterus. Moreover, progesterone and estrogens modulate the synthesis and release of angiogenic factors by placental cells, which regulates trophoblastic invasion and uterine artery remodeling. In this scenario, it is not surprising that women with pregnancy-related pathologies, such as early miscarriages, preterm delivery, preeclampsia, and fetal growth restriction, exhibit altered sex steroid concentrations. PMID:27199767

  12. Female sex steroids and glia cells: Impact on multiple sclerosis lesion formation and fine tuning of the local neurodegenerative cellular network.

    PubMed

    Kipp, Markus; Hochstrasser, Tanja; Schmitz, Christoph; Beyer, Cordian

    2016-08-01

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease that shows a female-to-male gender prevalence and alleviation of disease activity during late stage pregnancy. In MS-related animal models, sex steroids ameliorate symptoms and protect from demyelination and neuronal damage. Underlying mechanisms of these protective avenues are continuously discovered, in part by using novel transgenic animal models. In this review article, we highlight the regulation of glia cell function by female sex steroids. We specifically focus on the relevance of glia cells for immune cell recruitment into the central nervous system and show how estrogen and progesterone can modulate these cell-cell communication pathways. Since MS is considered to have a strong neurodegenerative component, principal neuroprotective mechanisms, exerted by sex-steroids will be discussed as well. Activation of steroid receptors might not just act as immunosuppressant but at the same time harmonize brain-intrinsic networks to dampen neurodegeneration and, thus, disease progression in MS. PMID:26698019

  13. 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. PMID:25618443

  14. Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration.

    PubMed

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

    2015-11-01

    The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-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 by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17 pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1-S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values. The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause. PMID:26291918

  15. 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.

  16. Sex steroids and bone mass. A study of changes about the time of menopause.

    PubMed Central

    Slemenda, C; Hui, S L; Longcope, C; Johnston, C C

    1987-01-01

    To examine the relationships between bone loss and sex steroids, 84 peri- and postmenopausal women were studied at 4-mo intervals for 3 yr. At each visit, measurements were made of bone mass at the midshaft and distal radius, of steroids, of gonadotropins, and of bone gla protein (BGP). Bone loss was approximately 1% per yr among late perimenopausal and postmenopausal groups, whereas the early perimenopausal group lost no bone. Mean serum estrogen and BGP concentrations predicted rates of bone loss. BGP was negatively correlated with the rate of bone loss (r = -0.45) and with mean estrogen concentrations (r = -0.40). Multivariate regressions showed estrogen concentrations to be strong independent predictors of the slope of bone mass over time. When BGP concentrations were added to the models, the significance of estrogen was reduced, suggesting that a portion of the estrogen effect was mediated through effects on rates of bone remodelling. PMID:3500182

  17. 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.

  18. 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. PMID:26070167

  19. Serum osteoprotegerin and sex steroid levels in patients with prostate cancer.

    PubMed

    Varsavsky, Mariela; Reyes-Garcia, Rebeca; Avilés Perez, Maria Dolores; Gonzalez Ramírez, Amanda Rocio; Mijan, Jose Luis; Muñoz-Torres, Manuel

    2012-01-01

    The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss. PMID:21903971

  20. Effects of sex, age, and season on plasma steroids in free-ranging Texas horned lizards (Phrynosoma cornutum).

    PubMed

    Wack, Corina L; Fox, Stanley F; Hellgren, Eric C; Lovern, Matthew B

    2008-02-01

    The Texas horned lizard (Phrynosoma cornutum) is protected in several states due to its apparently declining numbers; information on its physiology is therefore of interest from both comparative endocrine and applied perspectives. We collected blood samples from free-ranging P. cornutum in Oklahoma from April to September 2005, spanning their complete active period. We determined plasma concentrations of the steroids, progesterone (P), testosterone (T), and corticosterone (CORT) by radioimmunoassay following chromatographic separation and 17beta-estradiol (E2) by direct radioimmunoassay. T concentrations in breeding males were significantly higher than in non-breeding males. P showed no significant seasonal variation within either sex. CORT was significantly higher during the egg-laying season compared to breeding and non-breeding seasons for adult females and it was marginally higher in breeding than in non-breeding males (P=0.055). CORT concentrations also significantly increased with handling in non-breeding males and egg-laying females. Perhaps most surprisingly, there were no significant sex differences in plasma concentrations of P and E2. Furthermore, with respect to seasonal differences, plasma E2 concentrations were significantly higher in breeding females than in egg-laying or non-breeding females, and they were significantly higher in breeding than in non-breeding males. During the non-breeding season, yearling males exhibited higher E2 concentrations than adult males; no other differences between the steroid concentrations of yearlings and adults were detected. In comparison to other vertebrates, the seasonal steroid profile of P. cornutum exhibited both expected and unexpected patterns, and our results illustrate the value of collecting such baseline data as a springboard for appropriate questions for future research. PMID:18048031

  1. 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

  2. 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. PMID:27154415

  3. Sex Steroids Do Not Modulate TRPM2-Mediated Injury in Females following Middle Cerebral Artery Occlusion1,2,3

    PubMed Central

    Quillinan, Nidia; Grewal, Himmat; Klawitter, Jelena

    2014-01-01

    Abstract Calcium-permeable transient receptor potential M2 (TRPM2) ion channel activation contributes to cerebral ischemic injury specifically in males. In male mice, circulating androgens are required for TRPM2 inhibition with clotrimazole (CTZ) to provide protection following experimental stroke. Sufficient levels of circulating androgens are necessary to support ischemia-induced activation of poly ADP ribose polymerase (PARP) and consequent activation of TRPM2 channels. In this study, we tested whether differences in sex steroids contribute to the lack of CTZ neuroprotection in females. Middle cerebral artery occlusion (MCAO) was performed using adult female mice that were hormonally intact, ovariectomized (OVX) or dihydrotestosterone (DHT) treated. CTZ or vehicle was administered at the time of reperfusion, animals were euthanized 24 h later and brains and serum were collected. Infarct analysis revealed no effect of CTZ in intact females or females lacking endogenous sex steroids (OVX). Interestingly, treatment of female mice with the potent androgen receptor agonist DHT had no effect on ischemic injury and did not permit CTZ neuroprotection. Similarly, DHT-treated females did not exhibit increased levels of ADPribose, the TRPM2 ligand generated by PARP, following ischemia. No differences in TRPM2 or androgen receptor expression were observed between males and females. These data suggest that the lack of TRPM2 activation in females following experimental stroke is not due to the presence of estrogen or the absence of androgens. In conclusion, our data demonstrate that while circulating androgens are necessary for PARP-mediated TRPM2 injury in males, they are not sufficient to produce TRPM2 activation in females. PMID:26464961

  4. Sex Steroids Do Not Modulate TRPM2-Mediated Injury in Females following Middle Cerebral Artery Occlusion(1,2,3).

    PubMed

    Quillinan, Nidia; Grewal, Himmat; Klawitter, Jelena; Herson, Paco S

    2014-01-01

    Calcium-permeable transient receptor potential M2 (TRPM2) ion channel activation contributes to cerebral ischemic injury specifically in males. In male mice, circulating androgens are required for TRPM2 inhibition with clotrimazole (CTZ) to provide protection following experimental stroke. Sufficient levels of circulating androgens are necessary to support ischemia-induced activation of poly ADP ribose polymerase (PARP) and consequent activation of TRPM2 channels. In this study, we tested whether differences in sex steroids contribute to the lack of CTZ neuroprotection in females. Middle cerebral artery occlusion (MCAO) was performed using adult female mice that were hormonally intact, ovariectomized (OVX) or dihydrotestosterone (DHT) treated. CTZ or vehicle was administered at the time of reperfusion, animals were euthanized 24 h later and brains and serum were collected. Infarct analysis revealed no effect of CTZ in intact females or females lacking endogenous sex steroids (OVX). Interestingly, treatment of female mice with the potent androgen receptor agonist DHT had no effect on ischemic injury and did not permit CTZ neuroprotection. Similarly, DHT-treated females did not exhibit increased levels of ADPribose, the TRPM2 ligand generated by PARP, following ischemia. No differences in TRPM2 or androgen receptor expression were observed between males and females. These data suggest that the lack of TRPM2 activation in females following experimental stroke is not due to the presence of estrogen or the absence of androgens. In conclusion, our data demonstrate that while circulating androgens are necessary for PARP-mediated TRPM2 injury in males, they are not sufficient to produce TRPM2 activation in females. PMID:26464961

  5. Vitellogenin, sex steroid levels and gonadal biomarkers in wild Solea solea and Solea senegalensis from NW Mediterranean fishing grounds.

    PubMed

    Solé, M; Mañanós, E; Blázquez, M

    2016-06-01

    Specimens of Solea solea and Solea senegalenesis at different developmental stages were obtained from seven fishing grounds along the NW Mediterranean. Gonad development in males was classified into five stages, from early spermatogenesis to recovery, while four stages were considered in females, from growth to maturation. Vitellogenin (VTG) and sex steroid levels including an estrogen (estradiol, E2), two androgens (testosterone, T and 11-ketotestosterone, 11KT) and a progestin (17,20β-dihydroxy pregn-4-en-3-one, 17,20β-P or maturation inducing steroid, MIS) were analysed in plasma. Their levels were more clearly related to the developmental stage of the gonads than to the sampling site characteristics. In addition, enzyme activities in gonads, such as acetylcholinesterase (AChE) and carboxylesterase (CbE) were gender-dependent and higher in males than in females. Gonadal glutathione S-transferase (GST) activity was enhanced in the most anthropogenic impacted sites. VTG was absent in males and very low or undetectable in immature females, while mature females exhibited high VTG levels, clearly related to the gonado-somatic index. Sex steroid levels (ng/ml) varied in males and females regardless of the species. E2 levels in females ranged from 0.22 to 6.98 while in males ranged from 0.11 to 0.27. T varied from 0.12 to 0.93 in females and from 0.56 to 1.36 in males, while 11KT in females fluctuated from 0.03 to 0.57 and from 0.26 to 6.42 in males. Similarly, MIS in females ranged from 0.75 to 3.71 and from 1.12 to 5.61 in males. The lack of endocrine disturbances was confirmed by histological examination of the gonads. This study informs on basal sex hormone levels and enzyme activities during gonadal maturation of wild Solea spp. that can be useful in the identification and further remediation of possible pollution events. PMID:27088613

  6. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features.

    PubMed

    Melcangi, Roberto C; Giatti, Silvia; Garcia-Segura, Luis M

    2016-08-01

    Neuroactive steroids regulate the physiology of the central and peripheral nervous system, exert neuroprotective actions and represent interesting tools for therapeutic strategies against neurodegenerative and psychiatric disorders. Sex differences in their levels are detected not only under physiological conditions but are also modified in a sex-dependent way in different pathological alterations such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, stroke, diabetic encephalopathy, psychiatric disorders and peripheral neuropathy. Interestingly, many of these disorders show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. The neuroprotective actions of neuroactive steroids, together with the sex specific regulation of its levels might provide the basis to design sex-specific neuroprotective therapies. Indeed, some experiments here discussed suggest the viability of this approach. PMID:26657814

  7. Dual effect of female sex steroids on drug-induced gastroduodenal ulcers in the rat.

    PubMed

    Drago, F; Montoneri, C; Varga, C; Làszlò, F

    1999-01-01

    Since the sexual dimorphism of gastroduodenal ulcers is well known and might possibly relate to the actions of sex hormones, we studied the role of the female sex steroids, progesterone and 17beta-estradiol in cysteamine-induced mucosal ulcers in female Wistar rats (200-220 g). Administration of cysteamine (400 mg/kg, s.c.) provoked macroscopic gastroduodenal mucosa injury as assessed planimetrically, an increase in microvascular permeability in the stomach and the duodenum as assessed by extravasation of radiolabelled albumin, and decreased gastroduodenal mucus levels as assessed by the Alcian blue technique. Ovariectomy (2 weeks before cysteamine) decreased plasma 17beta-estradiol level as assessed by radioimmunoassay, gastroduodenal macroscopic injury and albumin extravasation, and increased mucus levels following cysteamine challenge. Administration of progesterone (10-50 mg/kg/week, s.c.) attenuated in a dose-dependent manner cysteamine-induced gastroduodenal mucosa injury and microvascular leakage, while it increased mucus levels in the stomach and the duodenum. In contrast, administration of 17beta-estradiol (1-5 mg/kg/week, s.c.) dose-dependently augmented gastric and duodenal macroscopic mucosa lesions and microvascular injury provoked by cysteamine, and caused a further reduction in gastroduodenal mucus levels observed after cysteamine administration. In different experiments, ovariectomy decreased indomethacin-induced gastroduodenal injury. The injection of 17beta-estradiol (1-5 mg/kg/week) did not affect gastroduodenal damage, while treatment with progesterone (10-50 mg/kg/week) protected against indomethacin-provoked mucosa ulcers. It is concluded that female sex steroids play a role in drug-induced gastroduodenal ulcers by modulating microvascular permeability and mucus secretion. PMID:10374897

  8. Sex steroid profiles and pair-maintenance behavior of captive wild-caught zebra finches (Taeniopygia guttata).

    PubMed

    Prior, Nora H; Yap, Kang Nian; Adomat, Hans H; Mainwaring, Mark C; Fokidis, H Bobby; Guns, Emma S; Buchanan, Katherine L; Griffith, Simon C; Soma, Kiran K

    2016-01-01

    Here, we studied the life-long monogamous zebra finch, to examine the relationship between circulating sex steroid profiles and pair-maintenance behavior in pairs of wild-caught zebra finches (paired in the laboratory for >1 month). We used liquid chromatography-tandem mass spectrometry to examine a total of eight androgens and progestins [pregnenolone, progesterone, dehydroepiandrosterone (DHEA), androstenediol, pregnan-3,17-diol-20-one, androsterone, androstanediol, and testosterone]. In the plasma, only pregnenolone, progesterone, DHEA, and testosterone were above the limit of quantification. Sex steroid profiles were similar between males and females, with only circulating progesterone levels significantly different between the sexes (female > male). Circulating pregnenolone levels were high in both sexes, suggesting that pregnenolone might serve as a circulating prohormone for local steroid synthesis in zebra finches. Furthermore, circulating testosterone levels were extremely low in both sexes. Additionally, we found no correlations between circulating steroid levels and pair-maintenance behavior. Taken together, our data raise several interesting questions about the neuroendocrinology of zebra finches. PMID:26610331

  9. 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

  10. 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…

  11. Anabolic Steroids

    MedlinePlus

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

  12. Sex and stress steroids in adolescence: Gonadal regulation of the hypothalamic-pituitary-adrenal axis in the rat.

    PubMed

    Green, Matthew R; McCormick, Cheryl M

    2016-08-01

    This review provides an overview of the current understanding of the role of the hypothalamic-pituitary-gonadal (HPG) axis in regulating the hypothalamic-pituitary-adrenal (HPA) axis response to stressors. HPA function is influenced by both organizational (programming) and activational effects of gonadal hormones. Typically, in adult rats, estradiol increases and androgens decrease the HPA response to stressors, thereby contributing to sex differences in HPA function, and sensitivity of the HPA axis to gonadal steroids is in part determined by exposure to these hormones in early development. Although developmental differences in HPA function are well characterized, the extent to which gonadal steroids contribute to age differences in HPA function is not well understood. Deficits in the understanding of the relationships between the HPA and HPG axes are greatest for the adolescent period of development. The critical outstanding questions are, when do gonadal hormones begin to regulate HPA function in adolescence, and what mechanisms precipitate change in sensitivity of the HPA axis to the HPG axis at this stage of life. PMID:26851306

  13. Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain

    PubMed Central

    Grishkovskaya, Irina; Avvakumov, George V.; Sklenar, Gisela; Dales, David; Hammond, Geoffrey L.; Muller, Yves A.

    2000-01-01

    Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and regulates their access to target tissues. In biological fluids, SHBG exists as a homodimer and each monomer comprises two laminin G-like domains (G domains). The crystal structure of the N–terminal G domain of SHBG in complex with 5α–dihydrotestosterone at 1.55 Å resolution reveals both the architecture of the steroid-binding site and the quaternary structure of the dimer. We also show that G domains have jellyroll topology and are struc– turally related to pentraxin. In each SHBG monomer, the steroid intercalates into a hydrophobic pocket within the β–sheet sandwich. The steroid and a 20 Å distant calcium ion are not located at the dimer interface. Instead, two separate steroid-binding pockets and calcium-binding sites exist per dimer. The structure displays intriguing disorder for loop segment Pro130–Arg135. In all other jellyroll proteins, this loop is well ordered. If modelled accordingly, it covers the steroid-binding site and could thereby regulate access of ligands to the binding pocket. PMID:10675319

  14. Sex steroid induced apoptosis as a rational strategy to treat anti-hormone resistant breast and prostate cancer.

    PubMed

    Jordan, V Craig; Fan, Ping; Abderrahman, Balkees; Maximov, Philipp Y; Hawsawi, Yousef M; Bhattacharya, Poulomi; Pokharel, Niranjana

    2016-05-01

    The combined incidence and the extended disease course of breast and prostate cancer is a major challenge for health care systems. The solution for society requires an economically viable treatment strategy to maintain individuals disease free and productive, so as to avoid the fracture of the family unit. Forty years ago, translational research using the antiestrogen tamoxifen was targeted to estrogen receptor (ER) positive micrometastatic tumor cells and established the long-term antihormone adjuvant treatment strategy used universally today. The antihormone strategy was the accepted structure of cancer biology. Sex steroid deprivation therapy remains the orthodox strategy for the treatment of both breast and prostate cancer. Despite major initial therapeutic success, the strategies of long term anti-hormone therapies with either tamoxifen or aromatase inhibitors (AI) or antiandrogens or abiraterone for breast and prostate cancer, respectively, eventually lead to a significant proportion of anti-hormone resistant or stimulated tumor growth. Remarkably, a general principle of anti-hormone resistance has emerged for both breast and prostate cancer based primarily on clinical and supportive laboratory data. Paradoxically, anti-hormone resistant cell populations emerge and grow but are vulnerable to the cytotoxicity of estrogen or androgen-induced apoptosis for both breast and prostate cancer, respectively. These consistent anticancer actions of sex steroids appear to recapitulate the more complex mechanism of bone remodeling in elderly men and women during sex steroid deprivation. Estrogen is the key hormone in both sexes because in men androgen is first converted to estrogen. Estrogen regulates and triggers apoptosis in osteoclasts that develop during estrogen deprivation and destroy bone to cause osteoporosis. Sex steroid deprived breast and prostate cancer has recruited a streamlined natural apoptotic program from the human genome, but this is suppressed in the

  15. 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.

  16. 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. PMID:26373423

  17. Oct-GnRH, the first protostomian gonadotropin-releasing hormone-like peptide and a critical mini-review of the presence of vertebrate sex steroids in molluscs.

    PubMed

    Minakata, Hiroyuki; Tsutsui, Kazuyoshi

    2016-02-01

    In protostome and deuterosome invertebrates, neurosecretory cells play major roles in the endocrine system. The optic glands of cephalopods are indicators of sexual maturation. In mature octopuses, optic glands enlarge and secrete a gonadotropic hormone. A peptide with structural features similar to that of vertebrate gonadotropin-releasing hormone (GnRH) was isolated from the octopus, Octopus vulgaris, and was named oct-GnRH. The discovery of oct-GnRH has triggered structural determinations and predictions of other mollusc GnRH-like peptides in biochemical and in silico studies. Interestingly, cephalopods studied so far are characterized by a single molecular form of oct-GnRH with a C-terminal -Pro-Gly-NH2 sequence, which is critical for gonadotropin-releasing activity in vertebrates. Other molluscan GnRH-like peptides lack the C-terminal -Pro-Gly-NH2 sequence but have -X-NH2 or -Pro-Gly although all protostome GnRH-like peptides have yet to be sequenced. In marine molluscs, relationships between GnRH-like peptides and sex steroids have been studied to verify the hypothesis that molluscs have vertebrate-type sex steroid system. However, it is currently questionable whether such sex steroids are present and whether they play endogenous roles in the reproductive system of molluscs. Because molluscs uptake and store steroids from the environment and fishes release sex steroids into the external environment, it is impossible to rule out the contamination of vertebrate sex steroids in molluscs. The function of key enzymes of steroidogenesis within molluscs remains unclear. Thus, evidence to deny the existence of the vertebrate-type sex steroid system in molluscs has been accumulated. The elucidation of substances, which regulate the maturation and maintenance of gonads and other reproductive functions in molluscs will require rigorous and progressive scientific study. PMID:26319132

  18. 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…

  19. Seasonal variations in plasma vitellogenin and sex steroids in male and female Eastern Box Turtles, Terrapene carolina carolina.

    PubMed

    Currylow, Andrea F; Tift, Michael S; Meyer, Jennifer L; Crocker, Daniel E; Williams, Rod N

    2013-01-01

    The Eastern Box Turtle (Terrapene carolina carolina) is a widespread species that has recently experienced precipitous declines throughout its range. Although many studies have documented aspects of reproduction in box turtles, reproductive physiology of free-ranging animals is unknown and can be crucial in this species' recovery. Over a two-year period, we measured reproductive parameters, (vitellogenin [Vtg], estradiol-17β [E2], and total testosterone [TT]), in plasma of 116 free-ranging Eastern Box Turtles across their active season. We found similar seasonal variations of Vtg and E2 within females. Mid-season, females showed a sharp peak in E2 that correlates with the putative beginning of the ovarian cycle. Individual females lacking these expected peaks of both Vtg and E2 suggest that some female T. c. carolina may not reproduce annually. Females typically expressed undetectable levels of TT, yet there was a small peak in TT early in the active season. Male Eastern Box Turtles exhibited a dual peak in TT. Elevated TT in males was significantly associated with observed sexual behaviors and smaller home ranges. Body condition had no effect on the concentration of TT or E2 in either sex. This is the first study to (1) document Vtg and sex steroid hormones in free-ranging animals of this genus, and (2) relate those metrics to individuals, the population, the purported annual cycle, and to other chelonian species. PMID:23174697

  20. Effect Modification of Obesity on Associations between Endogenous Steroid Sex Hormones and Arterial Calcification in Women at Midlife

    PubMed Central

    El Khoudary, Samar R.; Wildman, Rachel P.; Matthews, Karen; Powell, Lynda; Hollenberg, Steven M.; Edmundowicz, Daniel; Sutton-Tyrrell, Kim

    2011-01-01

    Objective To examine whether obesity modify the effects of endogenous steroid sex hormones on arterial calcification in women at midlife. Methods Associations between estradiol, testosterone, sex hormone binding globulin and free androgen index and the presence and extent of coronary and aortic calcification were evaluated in 187 obese (body mass index ≥30) and 281 non-obese (body mass index <30) women from the Study of Women’s Health Across the Nation. Logistic and linear regressions were used as appropriate. Results Prevalence rates of coronary and aortic calcification were significantly higher among obese compared to non-obese (P <0.001, for both). In multivariable analyses, steroid sex hormones were not associated with presence of coronary calcification. However, for extent of coronary calcification, significant interactions were found between obesity and both sex hormone binding globulin (P<0.0001) and free androgen index (P=0.008). In non-obese women, higher sex hormone binding globulin (P=0.0006) and lower free androgen index (P=0.01) were associated with greater extent of coronary calcification while lower sex hormone binding globulin was associated with greater extent of coronary calcification in obese women (P=0.05). For aortic calcification outcomes, higher sex hormone binding globulin was associated with presence of aortic calcification among non-obese (OR:1.64, 95%CI:1.16, 2.32, for each 1-SD greater sex hormone binding globulin). Conclusions Associations between endogenous steroid sex hormones and arterial calcification vary by obesity status among perimenopausal women. Further research is needed to better understand the possible mechanisms. PMID:21471825

  1. Measurement of sex steroids and analogs with a fiber optic probe using pulsed ultraviolet resonance Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Schulze, H. Georg; Greek, L. Shane; Blades, Michael W.; Bree, Alan V.; Gorzalka, Boris B.; Turner, Robin F. B.

    1997-05-01

    Resonance Raman spectroscopy, performed via an optical fiber probe, can be used in aqueous samples to detect a wide variety of chemical species in situ. It offers a potentially rapid, on-site alternative to the high performance chromatography/mass spectrometry methods currently considered definitive for the detection of sex steroids in human urine. As a first step in the development of a resonance Raman instrument for the rapid detection of sex steroids in biological samples, it had to be shown that these substances, their analogs, and the major components of human urine can be differentiated on the basis of their resonance Raman spectra. A fiber-optic linked Raman and tunable ultraviolet resonance Raman system was assembled with custom designed optical fiber probes. The ultraviolet absorption spectra of some sex steroids, analogs, and components of human urine were measured in order to determine feasible excitation light frequencies. We present here for the first time the UV resonance Raman spectra of these substances obtained via our novel fiber probes. These results indicate that some of the steroids tested can be differentiated from each other and from the major components of human urine on the basis of their resonance Raman spectra.

  2. 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. PMID:10052847

  3. 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

    PubMed Central

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

    2012-01-01

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 hours 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 (0.1-100nM), to determine a dose response for TCDD in our culture system for growth, hormone production, 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 (10μM) 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. PMID:22483799

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

    PubMed

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

    2009-03-01

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

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

    PubMed Central

    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. PMID:26491443

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

    PubMed Central

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

    2015-01-01

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

  7. The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus).

    PubMed

    Kroupova, H K; Trubiroha, A; Lorenz, C; Contardo-Jara, V; Lutz, I; Grabic, R; Kocour, M; Kloas, W

    2014-09-01

    The aim of the present study was to investigate the effects of the synthetic progestin levonorgestrel (LNG) on the reproductive endocrine system of a teleost fish, the roach (Rutilus rutilus). Pubertal roach were exposed for 28 days in a flow-through system to four concentrations of LNG (3, 31, 312, and 3124 ng/l). Both males and females treated with 3124 ng/l LNG exhibited the upregulated levels of vitellogenin and oestrogen receptor 1 mRNA in the liver. At the same concentration, LNG caused a significant upregulation of the mRNA expression of the gene encoding luteinising hormone β-subunit (lhβ) and the suppression of the mRNA expression of the gene encoding follicle-stimulating hormone β-subunit (fshβ) in the pituitary of both male and female roach. A lower LNG concentration (312 ng/l) suppressed mRNA expression of fshβ in males only. Females treated with 3124 ng/l LNG exhibited significantly lower plasma 11-ketotestosterone (11-KT) and oestradiol (E2) concentrations, whereas their testosterone (T) level was higher compared with the control. Females exposed to 312 ng/l LNG presented significantly lower plasma E2 concentrations. Males exposed to ≥31 ng/l LNG exhibited significantly reduced 11-KT levels. As determined through a histological analysis, the ovaries of females were not affected by LNG exposure, whereas the testes of males exposed to 31 and 312 ng/l LNG exhibited a significantly higher percentage of spermatogonia B compared with the control. The results of the present study demonstrate that LNG disrupts the reproductive system of pubertal roach by affecting the pituitary gonadotropin expression and the sex steroid levels. This disruption was determined to occur in males after exposure to an environmentally relevant concentration (31 ng/l). Moreover, the highest tested concentration of LNG (3124 ng/l) exerted an oestrogenic effect on fish of both sexes. PMID:24893273

  8. Longitudinal monitoring of sex steroid hormones in excrement of spectacled eiders (Somateria fischeri).

    PubMed

    Ellsworth, Abigail; Buck, C Loren; Atkinson, Shannon; Hollmén, Tuula

    2014-03-01

    From the 1970s to the 1990s, the breeding population of spectacled eiders (Somateria fischeri) in western Alaska declined by 96%, which led to the listing of this species as threatened under the Endangered Species Act in 1993. Since then, the population has stabilized, but has not recovered to pre-decline numbers. While little is known about reproductive endocrinology in spectacled eiders, in other avian species, estrogen and testosterone are known to initiate and modulate various reproductive processes including yolk protein synthesis, reproductive behaviors and secondary sex characteristics. Measurement of the metabolites of estrogen and testosterone (EM and TM, respectively) in excrement reflect circulating hormone concentrations and provide a non-invasive method to monitor reproductive physiology. We measured concentrations of excreted EM in captive females and TM in males to (1) determine the efficacy of commercially available radioimmunoassay kits to detect EM and TM, (2) describe annual profiles of EM and TM concentrations, and (3) define the reproductive season of captive spectacled eiders using endocrine status. Excrement samples were collected from captive female and male spectacled eiders three times per week throughout 1 year. Female EM and male TM levels were quantified using radioimmunoassay. Mean female EM profile exhibited values exceeding the threshold for "peak" values (EM>193.3 ng/g) from mid-February to early July, and again in September. Additionally, the highest average concentrations of EM were seen in March, May and September. Elevated TM concentrations occurred in mid March, mid May and late June. These data suggest that levels of excreted sex steroids reflect patterns predicted by breeding landmarks in the annual cycle and will assist in field monitoring and captive breeding programs for spectacled eiders. PMID:24406512

  9. 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

  10. Sex steroid correlates of female-specific colouration, behaviour and reproductive state in Lake Eyre dragon lizards, Ctenophorus maculosus.

    PubMed

    Jessop, Tim S; Chan, Rita; Stuart-Fox, Devi

    2009-07-01

    In some species, females develop bright colouration to signal reproductive status and exhibit behavioural repertoires to incite male courtship and/or reduce male harassment and forced copulation. Sex steroids, including progesterone and testosterone, potentially mediate female reproductive colouration and reproductive behaviour. We measured associations among plasma profiles of testosterone and progesterone with variation in colour expression and reproductive behaviour, including unique courtship rejection behaviours, in female Lake Eyre dragon lizards, (Ctenophorus maculosus). At onset of breeding, progesterone and testosterone increased with vitellogenesis, coincident with colour intensification and sexual receptivity, indicated by acceptance of copulations. As steroid levels peaked around the inferred ovulation time, maximal colour development occurred and sexual receptivity declined. When females were gravid and exhibited maximal mate rejection behaviours, progesterone levels remained consistently high, while testosterone exhibited a discrete second peak. At oviposition, significant declines in plasma steroid levels, fading of colouration and a dramatic decrease in male rejection behaviours co-occurred. Our results indicate a generally concordant association among steroid levels, colouration, behaviour and reproductive events. However, the prolonged elevation in progesterone and a second peak of testosterone was unrelated to reproductive state or further colour change, possibly suggesting selection on females to retain high steroid levels for inducing rejection behaviours. PMID:19363614

  11. 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…

  12. 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. PMID:26767421

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

    PubMed

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

    2014-07-01

    Thyroid hormones (THs) are well-known regulators of development and metabolism in vertebrates. There is increasing evidence that THs are also involved in gonadal differentiation and reproductive function. Changes in TH status affect sex ratios in developing fish and frogs and reproduction (e.g., fertility), hormone levels, and gonad morphology in adults of species of different vertebrates. In this review, we have summarized and compared the evidence for cross-talk between the steroid hormone and thyroid axes and present a comparative model. We gave special attention to TH regulation of sex steroid synthesis and action in both the brain and gonad, since these are important for gonad development and brain sexual differentiation and have been studied in many species. We also reviewed research showing that there is a TH system, including receptors and enzymes, in the brains and gonads in developing and adult vertebrates. Our analysis shows that THs influences sex steroid hormone synthesis in vertebrates, ranging from fish to pigs. This concept of crosstalk and conserved hormone interaction has implications for our understanding of the role of THs in reproduction, and how these processes may be dysregulated by environmental endocrine disruptors. PMID:24685768

  14. Novel galanin receptors in teleost fish: identification, expression and regulation by sex steroids.

    PubMed

    Martins, Rute S T; Pinto, Patrícia I S; Guerreiro, Pedro M; Zanuy, Silvia; Carrillo, Manuel; Canário, Adelino V M

    2014-09-01

    In fish, the onset of puberty, the transition from juvenile to sexually reproductive adult animals, is triggered by the activation of pituitary gonadotropin secretion and its timing is influenced by external and internal factors that include the growth/adiposity status of the animal. Kisspeptins have been implicated in the activation of puberty but peripheral signals coming from the immature gonad or associated to the metabolic/nutritional status are also thought to be involved. Therefore we hypothesize the importance of the galinergic system in the brain and testis of pre-pubertal male sea bass as a candidate to translate the signals leading to activation of testicular maturation. Here, the transcripts for four galanin receptors (GALR), named GALR1a, 1b, 2a and 2b, were isolated from European sea bass, Dicentrarchus labrax. Phylogenetic analysis confirmed the previously reported duplication of GALR1 in teleost fish, and unravelled the duplication of GALR2 in teleost fish and in some tetrapod species. Comparison with human showed that the key amino acids involved in ligand binding are present in the corresponding GALR1 and GALR2 orthologs. Transcripts for all four receptors are expressed in brain and testes of adult fish with GALR1a and GALR1b abundant in testes and hardly detected in ovaries. In order to investigate whether GALR1 dimorphic expression was dependent on steroid context we evaluated the effect of 11-ketotestosterone and 17β-estradiol treatments on the receptor expression in brain and testes of pre-pubertal males. Interestingly, steroid treatments had no effect on the expression of GALRs in the brain while in the testes, GALR1a and GALR1b were significantly up regulated by 11KT. Altogether, these results support a role for the galaninergic system, in particular the GALR1 paralog, in fish reproductive function. PMID:25016048

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

    PubMed Central

    2015-01-01

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

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

    PubMed

    Boonyaratanakornkit, Viroj; Pateetin, Prangwan

    2015-01-01

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

  17. 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

  18. Sex-related differences in steroid concentrations in the blue mussel (Mytilus edulis trossulus) from the southern Baltic Sea.

    PubMed

    Zabrzańska, Sandra; Smolarz, Katarzyna; Hallmann, Anna; Konieczna, Lucyna; Bączek, Tomasz; Wołowicz, Maciej

    2015-05-01

    This paper reports on sex-related differences in free steroid hormone concentrations including the concentrations of three naturally occurring estrogens (17β-estradiol E2, estrone E1, and estriol E3) and one androgen (testosterone T) in the tissues (gills and gonads) of the blue mussel Mytilus edulis trossulus sampled from the Gulf of Gdańsk (Baltic Sea, Poland). The dissimilarity in steroid concentrations between tissues was particularly evident in the T concentration with a level in gills almost three times higher compared to gonads (on average, 15.38 ng/g w.w. and 5.31 ng/g w.w., respectively, p=0.00008), suggesting its exogenous origin. In general, a tendency towards a skewed steroid profile related to sex, with E2 more abundant for males and T for females, was observed. Female gonads were characterized by a higher level of T than testis (4.61 ng/g w.w. for females and 0.70 ng/g w.w. for males, p=0.0121). At the same time, the level of E2 found in the testis was higher than in the ovary (4.81 ng/g w.w. and 3.86 ng/g w.w., respectively); however, the difference was not statistically significant. As for gills, similar trend with T and E2 being more abundant in males was observed. At the same time, no disturbances in the sex ratio and gametogenesis process were observed which suggests i) efficient deactivation of free forms of steroids, and/or ii) their little or no physiological role. PMID:25536333

  19. Examination on biological activities and fates of new steroids, steroid-17-yl methyl glycolate derivatives.

    PubMed

    Suzuki, T; Tada, H; Sato, E; Tojima, Y

    1999-02-01

    A variety of acyl derivatives based on the "antedrug" concept were synthesized to evaluate their biological activities, in vitro fate in human serum and examine pharmacokinetics in rats. Among the prepared compounds, acetyl and pivaloyl derivatives (8 and 9) showed strong to vasoconstrictive activity in human, exceeding that of dexamethasone. In rats, topical administration of the compound 8 significantly reduced oxazolone-induced ear edema compared to that of control. These activities were almost equal to that of prednisolone, however 9 did not show any suppression of the oxazolone-induced edema. The in vitro half-lives of 8 and 9 in human serum were 18.2 and 43.8 hours, respectively. Prednisolone and dexamethasone were extremely stable under the used conditions. When compound 8 was intravenously administrated to rats, its metabolites, 20(R)-methyl dexamethasonate (4) and carboxylic acid (18), were found in the systemic blood. The total body clearance of 8 was 1734 ml x hr(-1) x kg(-1), which was about 12 times larger than that of dexamethasone. On the other hand, 9 was found to be metabolized instantaneously to methyl prednisolonate (1) in systemic serum. Acetyl derivative 8 derived from dexamethasone may thus be useful as a topical steroid which offers the advantage of a low potential for systemic and local side effects. PMID:10228984

  20. Sex steroids in green anoles (Anolis carolinensis): uncoupled maternal plasma and yolking follicle concentrations, potential embryonic steroidogenesis, and evolutionary implications.

    PubMed

    Lovern, Matthew B; Wade, Juli

    2003-11-01

    The sex steroids testosterone (T) and estradiol-17beta (E2) play important roles in vertebrate reproduction and development. However, little is known about the relationship between plasma steroid levels (which can influence reproductive function) and yolk steroid levels (which can influence embryonic development) in oviparous species. Therefore, we examined the extent to which T and E2 are coupled in plasma and yolking follicles in adult females and explored the dynamics of yolk and embryo steroid content during egg incubation in green anoles (Anolis carolinensis). T and E2 levels were determined for the plasma and yolking follicles of breeding females and for whole embryos and yolks at several developmental stages by radioimmunoassay. Plasma and yolk concentrations of T and E2 were not correlated. On average, plasma T was only 30% that of plasma E2, but yolking follicle T was over 600% that of yolking follicle E2. Total yolk T and E2 content generally declined over the course of incubation. However, yolk T was an order of magnitude higher than yolk E2, and it showed a secondary peak in magnitude after approximately 75% of incubation was completed. Similarly, total embryonic T content rose by over 400% in the latter half of incubation whereas E2 did not change. These results demonstrate that plasma and yolking follicle steroid levels produced by breeding females can be uncoupled. Furthermore, embryos themselves may begin producing T, but likely not E2, during the latter stages of incubation. Thus, steroid exposure may be independently shaped by selection to serve both reproductive and developmental functions. PMID:14511980

  1. 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

  2. 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

  3. Steroid receptor RNA activator: Biologic function and role in disease.

    PubMed

    Liu, Chan; Wu, Hong-Tao; Zhu, Neng; Shi, Ya-Ning; Liu, Zheng; Ao, Bao-Xue; Liao, Duan-Fang; Zheng, Xi-Long; Qin, Li

    2016-08-01

    Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor α (ERα), ERβ, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor α (TNFα) pathways, play critical roles in the pathogenesis of estrogen-dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases. PMID:27282881

  4. Sniffing human sex-steroid derived compounds modulates mood, memory and autonomic nervous system function in specific behavioral contexts.

    PubMed

    Bensafi, M; Brown, W M; Khan, R; Levenson, B; Sobel, N

    2004-06-01

    We asked whether the effects of exposure to two human sex-steroid derived compounds were context dependent. The effects of sniffing 4,16-androstadien-3-one (AND) and 1,3,5(10),16-estratetraen-3-ol (EST) on mood, memory, and autonomic nervous system responses were explored in 72 participants. Subjects were tested with AND, EST, or a Control compound within four mood contexts: neutral, sexually aroused, sad and happy. These moods were successfully induced using selected film segments (P < 0.0001). During the neutral context, none of the compounds affected mood or autonomic nervous system function. However, compound effects were significantly increased within arousing contexts. During the sexually arousing context, both compounds increased sexual arousal (P < 0.029). During the sad context, AND maintained positive mood in women (P< 0.050) and increased negative mood in men (P < 0.031). Memory for events during the sad context was impaired by AND in women (P < 0.047) but not in men. Finally, effects of AND on physiology were observed during the sexually arousing context whereby AND increased skin temperature in both sexes (P < 0.022) but reduced abdominal respiration rate in men only (P < 0.034). These results suggest that sex-steroidal compounds modulate mood, memory and autonomic nervous system responses and increase their significance within specific behavioral contexts. These findings lend support to a specific role for these compounds in chemical communication between humans. PMID:15135965

  5. Hepatic Overexpression of Steroid Sulfatase Ameliorates Mouse Models of Obesity and Type 2 Diabetes through Sex-specific Mechanisms*

    PubMed Central

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

    2014-01-01

    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. PMID:24497646

  6. 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

  7. Sources of variation in HPG axis reactivity and individually consistent elevation of sex steroids in a female songbird

    PubMed Central

    Rosvall, Kimberly A.; Burns, Christine M. Bergeon; Hahn, Thomas P.; Ketterson, Ellen D.

    2013-01-01

    Understanding sources of individual differences in steroid hormone production has important implications for the evolution of reproductive and social behaviors. In females in particular, little is known about the mechanistic sources of these individual differences, despite established linkages between sex steroids and a variety of fitness-related traits. Using captive female dark-eyed juncos (Junco hyemalis) from two subspecies, we asked how variation in different components of the hypothalamo-pituitary-gonadal (HPG) axis related to variation in testosterone production among females, and we compared females to males in multiple components of the HPG axis. We demonstrated consistent individual differences in testosterone elevation in response to challenges with luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH). These hormone challenges led to more LH production but less testosterone production in females than males, and the sexes differed in some but not all measures of sensitivity to hormones along the HPG axis. Similar to findings in males, variation in testosterone production among females was not related to variation in LH production, gonadal LH-receptor mRNA abundance, or hypothalamic abundance of androgen receptor mRNA or aromatase mRNA. Rather, the primary source of individual variation in circulating steroids appears to the gonad, a conclusion further supported by positive correlations between testosterone and estradiol production. Unlike males, females did not differ by subspecies in any of the endocrine parameters that we assessed, suggesting some degree of independent evolution between the two sexes. Our results highlight the sources of physiological variation that may underlie the evolution of hormone-mediated phenotypes in females. PMID:24090613

  8. 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.

  9. 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. PMID:26300058

  10. Effects of partial or total fish meal replacement by agricultural by-product diets on gonad maturation, sex steroids and vitellogenin dynamics of African catfish (Clarias gariepinus).

    PubMed

    Nyina-wamwiza, L; Defreyne, P S; Ngendahayo, L; Milla, S; Mandiki, S N M; Kestemont, P

    2012-10-01

    The establishment of the first sexual maturation was characterized in African catfish (Clarias gariepinus) in order to study the efficiency of replacement of fish meal (FM) by diets composed of local vegetable ingredients. Four diets were formulated containing decreasing levels of FM (50-0% for diet 1 to diet 4) and increasing proportions of vegetable ingredients (50-100%). Gonadosomatic index (GSI), diameter and percentages of developmental stages of oocytes, plasma sex steroids and vitellogenin dynamics were investigated from February to June using one-year-old fish. Fish were individually tagged, and 12 individuals from each diet were investigated monthly. Replacement of FM with plant ingredients did not affect the GSI neither in males, nor in females. All males were spermiating, and no abnormal gonads were found. In females, GSI and percentages of advanced stages of oocytes decreased during the dry season, indicating seasonal changes in gonad development. Moreover, oocytes were in late exogenous vitellogenesis, but no final maturation stages were observed, whatever the diet. Higher plasma levels of E2 in females and of androgens (T and 11-KT) in both sexes were observed in fish fed diet 4 than in those receiving diet 1 depending on the season. Levels of plasma E2 and ALP (indicator for vitellogenin) in males did not differ among treatments and seasons suggesting no phytoestrogenic activity. The results showed that total replacement of FM by vegetable diets composed of groundnut oilcakes, bean and sunflower meals has no deleterious effect on the onset of sexual maturation in African catfish but, may stimulate the sex steroid production and in turns may potentially exert some positive actions on reproductive success. PMID:22382402

  11. Correlation between steroid sex hormones, egg laying capacity and cercarial shedding in Biomphalaria alexandrina snails after treatment with Haplophyllum tuberculatum.

    PubMed

    Rizk, Maha Z; Metwally, Nadia S; Hamed, Manal A; Mohamed, Azza M

    2012-10-01

    Schistosomiasis is considered the second most pre-valiant worldwide parasitic disease ranked next to malaria. It has significant economic and public health consequences in many developing countries. Several ways have been practiced in order to bring the disease under an adequate control through the breakage of the life cycle of the parasite. Snail control could be regarded as a rapid and efficient of reducing or eliminating transmission and remains among the methods of choice for schistosomiasis control. The aim of this work is to evaluate the role of Haplophyllum tuberculatum (family Rutaceae) as a plant molluscicide. The mortality rate of Biomphalaria alexandrina snails were monitored after treatment with three extracts of the plant aerial parts; petroleum ether, chloroform and ethanol. Chloroform extract that recorded the most potent effect was further evaluated through measuring the toxicity pattern against B. alexandrina snails, egg laying capacity, cercarial shedding, phenol oxidase enzyme and the levels of steroid sex hormones. Histopathological examination of hepatopancreas and ovotestis of treated snails were also done for result confirmation. Treatment of snails by chloroform extract recorded reduction in egg laying capacity, decrease in cercarial shedding, diminution in phenol oxidase enzyme, disturbance in steroid sex hormones and sever alternation of the histopathological picture of snails tissue. In conclusion, H. tuberculatum recorded molluscicidal potency against B. alexandrina snails. Further studies are needed for its environmental applications. PMID:22771439

  12. Subchronic effects of cadmium on the gonads, expressions of steroid hormones and sex-related genes in tilapia Oreochromis niloticus.

    PubMed

    Luo, Yongju; Shan, Dan; Zhong, Huan; Zhou, Yi; Chen, Wenzhi; Cao, Jinling; Guo, Zhongbao; Xiao, Jun; He, Fulin; Huang, Yifan; Li, Jian; Huang, Heming; Xu, Pao

    2015-12-01

    Cadmium (Cd) is one of the most toxic heavy metals in aquatic ecosystem which affects fish health and aquaculture. In the present study, we examined the bioaccumulation of Cd in the gonads of tilapia via dissolved and dietary routes. We evaluated the subchronic effects of Cd on the histology of gonads, steroid hormone levels and sex-related gene expressions in tilapia. In addition, we also studied maternal transfer of Cd. Our results indicated that Cd was accumulated significantly in both ovary and testis from both exposure routes. Histopathological analysis showed that Cd induced ovary and testis injuries. Estradiol levels were significantly increased in dissolved Cd exposed female fish. In addition, the Cd exposure displayed different effects on gene expressions in gonads. In females, the estrogen receptor (ERα) was stimulated in dissolved Cd-exposed fish at 70.32 and 143.78 μg/L for 30 days and in fish at 143.78 μg/L for 60 days. Vitellogenin expression was significantly down-regulated in the ovary of dissolved Cd-exposed fish. In testis, GR expression was elevated after 60 days of dissolved Cd and dietary exposure. Furthermore, Cd level was significantly higher in the eggs than that in the fry. Our results demonstrated that both dissolved and dietary Cd exposures affected gonad development by altering steroid hormone levels and sex-related gene expressions in tilapia. PMID:26471182

  13. Role of genetics and sex steroid hormones in male androgenetic alopecia and female pattern hair loss: an update of what we now know.

    PubMed

    Yip, Leona; Rufaut, Nick; Sinclair, Rod

    2011-05-01

    The role of genetic predisposition and the influence of sex steroid hormones are indisputable to the pathogenesis of male androgenetic alopecia (MAGA). The role of sex steroid hormones in female pattern hair loss (FPHL) is less known. A good knowledge of the pathophysiology underlying MAGA and FPHL empowers the clinician to confidently counsel patients and make informed therapeutic decisions. Vigorous research in recent years has provided greater insight into the role of genetics and sex steroids in physiological hair growth and cycling, as well as in hair follicle miniaturization, the histological hallmark of MAGA and FPHL. In the present review article directed towards clinicians, we discuss the current understanding of the role of androgens and oestrogens, as well as genetic associations with MAGA and FPHL. We also briefly discuss the interpretation of direct-to-consumer genetic testing for baldness to help clinicians understand the limitations of such tests. PMID:21605090

  14. 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.

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

    PubMed

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

    2006-12-01

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

  16. 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. PMID:22688450

  17. Anthelmintic activity of steroidal saponins from Paris polyphylla.

    PubMed

    Wang, G-X; Han, J; Zhao, L-W; Jiang, D-X; Liu, Y-T; Liu, X-L

    2010-12-01

    The present study was undertaken to investigate the anthelmintic activity of crude extracts and pure compounds from the rhizomes of Paris polyphylla. The methanol extract showed a promising anthelmintic activity against Dactylogyrus intermedius (EC(50) value=18.06 mg l(-¹). Based on these finding, the methanol extract was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording two known steroidal saponins showing potent activity, dioscin and polyphyllin D. Both dioscin and polyphyllin D exhibited significant activity against D. intermedius with EC(50) values of 0.44 and 0.70 mg l(-¹), respectively, which were more effective than the positive control, mebendazole (EC(50) value=1.25 mg l(-¹)). The acute toxicities (LC(50)) of dioscin and polyphyllin D for goldfish were 1.37 and 1.08 mg l(-¹), respectively. These results indicated that P. polyphylla extract and the isolated compounds are potential natural agents for the control of Dactylogyrus infestation. This is the first report on in vivo anthelmintic investigation for P. polyphylla. PMID:20576414

  18. Early pregnancy sex steroids and maternal breast cancer: a nested case-control study.

    PubMed

    Fortner, Renée T; Schock, Helena; Kaaks, Rudolf; Lehtinen, Matti; Pukkala, Eero; Lakso, Hans-Åke; Tanner, Minna; Kallio, Raija; Joensuu, Heikki; Grankvist, Kjell; Zeleniuch-Jacquotte, Anne; Toniolo, Paolo; Lundin, Eva; Surcel, Helja-Marja

    2014-12-01

    Pregnancy, parity, and circulating steroid hormone levels are associated with risk of breast cancer, but little is known about hormone concentrations during pregnancy and subsequent breast cancer risk. We evaluated early pregnancy (<140 days gestation) serum estradiol, estrone, progesterone, and testosterone and breast cancer risk in a nested case-control study in the Finnish Maternity Cohort. The cohort includes 98% of pregnancies registered in Finland since 1983. Individuals with samples collected in the first pregnancy leading to a live birth were eligible. Breast cancer cases (n = 1,199) were identified through linkage with the Finnish Cancer Registry; 2,281 matched controls were selected using incidence density sampling. ORs were calculated using conditional logistic regression. Hormone concentrations were not associated with breast cancer overall. Estradiol was positively associated with risk of breast cancer diagnosed age <40 [4th vs. 1st quartile OR 1.60 (1.07-2.39); Ptrend = 0.01], and inversely associated with breast cancer diagnosed at age ≥40 [4th vs. 1st quartile OR 0.71 (0.51-1.00); Ptrend = 0.02]. Elevated concentrations of the steroid hormones were associated with increased risk of estrogen receptor (ER)- and progesterone receptor (PR)-negative tumors in women age <40 at diagnosis. We observed no association between steroid hormones and ER(+)/PR(+) disease. These data suggest a positive association between high concentrations of early pregnancy steroid hormones and risk of ER(-)/PR(-) breast cancer in women diagnosed age <40, and an inverse association for overall breast cancer diagnosed age ≥40. Further research on pregnancy hormones and risk of steroid receptor-negative cancers is needed to further characterize this association. PMID:25281720

  19. 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

  20. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Ahn, Jiyoung; Schumacher, Fredrick R.; Berndt, Sonja I.; Pfeiffer, Ruth; Albanes, Demetrius; Andriole, Gerald L.; Ardanaz, Eva; Boeing, Heiner; Bueno-de-Mesquita, Bas; Chanock, Stephen J.; Clavel-Chapelon, Françoise; Diver, W. Ryan; Feigelson, Heather Spencer; Gaziano, J. Michael; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hoover, Robert N.; Kolonel, Laurence N.; Kraft, Peter; Ma, Jing; Le Marchand, Loïc; Overvad, Kim; Palli, Domenico; Stattin, Pär; Stampfer, Meir; Stram, Daniel O.; Thomas, Gilles; Thun, Michael J.; Travis, Ruth C.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Kaaks, Rudolf; Hunter, David J.; Hayes, Richard B.

    2009-01-01

    Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3α-androstanediol-glucuronide (N = 4767) and 17β-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 × 10−21), consistent with previous studies, and testosterone (P = 7.54 × 10−15), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 × 10−6) and SRD5A2 with 3α-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 × 10−6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones. PMID:19574343

  1. Sex differences in feeding behavior in rats: the relationship with neuronal activation in the hypothalamus.

    PubMed

    Fukushima, Atsushi; Hagiwara, Hiroko; Fujioka, Hitomi; Kimura, Fukuko; Akema, Tatsuo; Funabashi, Toshiya

    2015-01-01

    There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation. Sex differences in feeding seem to occur among species, and responses to fasting (i.e., starvation), gonadal steroids (i.e., testosterone and estradiol), and diet (i.e., western-style diet) vary significantly between sexes. The hypothalamus is the center for controlling feeding behavior. We examined the activation of feeding-related peptides in neurons in the hypothalamus. Phosphorylation of cyclic AMP response element-binding protein (CREB) is a good marker for neural activation, as is the Fos antigen. Therefore, we predicted that sex differences in the activity of melanin-concentrating hormone (MCH) neurons would be associated with feeding behavior. We determined the response of MCH neurons to glucose in the lateral hypothalamic area (LHA) and our results suggested MCH neurons play an important role in sex differences in feeding behavior. In addition, fasting increased the number of orexin neurons harboring phosphorylated CREB in female rats (regardless of the estrous day), but not male rats. Glucose injection decreased the number of these neurons with phosphorylated CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH neurons, but not orexin neurons, expressed phosphorylated CREB. These sex differences in response to fasting and glucose, as well as under normal conditions, suggest a vulnerability to metabolic challenges in females. PMID:25870535

  2. 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., Jr.; 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

  3. 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

  4. In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions.

    PubMed

    Karjalainen, Marjo J; Neuvonen, Pertti J; Backman, Janne T

    2008-08-01

    The cytochrome P450 enzyme CYP1A2 is crucial for the metabolism of many drugs, for example, tizanidine. As the effects of several non-steroidal anti-inflammatory drugs (NSAID) and female sex steroids on CYP1A2 activity in vitro are unknown, their effects on phenacetin O-deethylation were studied and compared with the effects of model inhibitors in human liver microsomes, followed by prediction of their interaction potential with tizanidine in vivo. In vitro, fluvoxamine, tolfenamic acid, mefenamic acid and rofecoxib potently inhibited CYP1A2 [the 50% inhibitory concentration (IC(50)) < 10 microM]. Ethinyloestradiol, celecoxib, desogestrel and zolmitriptan were moderate (IC(50) 20-200 microM), and etodolac, ciprofloxacin, etoricoxib and gestodene weak inhibitors of CYP1A2 (IC(50) > 200 microM). At 100 microM, the other tested NSAIDs and steroids inhibited CYP1A2 less than 35%. Pre-incubation increased the inhibitory effects of rofecoxib, progesterone and desogestrel. Using the free portal plasma inhibitor concentration and the competitive inhibition model, the effect of fluvoxamine and the lack of effects of tolfenamic acid and celecoxib on tizanidine pharmacokinetics in human beings were well predicted. However, the effects of ciprofloxacin, rofecoxib and oral contraceptives were greatly underestimated even when the predictions were based on their total portal plasma concentration. Besides rofecoxib, and possibly mefenamic acid, other NSAIDs were predicted not to significantly inhibit CYP1A2 in human beings. The type of enzyme inhibition, particularly metabolism-dependent inhibition, free inhibitor concentration and accumulation of the inhibitor into the hepatocytes should be considered in extrapolations of in vitro results to human beings. PMID:18816299

  5. Effects of non-steroidal aromatase inhibitor letrozole on sex inversion and spermatogenesis in yellow catfish Pelteobagrus fulvidraco.

    PubMed

    Shen, Zhi-Gang; Fan, Qi-Xue; Yang, Wei; Zhang, Yun-Long; Hu, Pei-Pei; Xie, Cong-Xin

    2013-09-01

    The effects of letrozole (LZ), a potent nonsteroidal aromatase inhibitor (AI), on growth performance, sex inversion, and sex changes were investigated in yellow catfish (Pelteobagrus fulvidraco), which display sexual dimorphic growth. Growth performance was promoted significantly in the low-dose LZ treatment, compared with the control. Four LZ treatments produced dose-dependent male proportions that were significantly higher than that of the control. Histological examination of testes treated by LZ displayed a large amount of spermatozoa and enlarged lobule lumens, indicating that LZ treatments can potentially stimulate spermatogenesis. Changes of sex proportions 45 days after the end of the LZ treatments prove that the female germ cells possess a certain degree of bipotentiality. These results suggest that aromatase activity plays a vital role in sex differentiation, as in other teleosts, with inhibition of aromatase activity by AI bringing about sex inversion. PMID:24088793

  6. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes.

    PubMed

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  7. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes

    PubMed Central

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  8. Sexual Dimorphisms of Adrenal Steroids, Sex Hormones, and Immunological Biomarkers and Possible Risk Factors for Developing Rheumatoid Arthritis

    PubMed Central

    Masi, Alfonse T.; Rehman, Azeem A.; Jorgenson, Laura C.; Smith, Jennifer M.; Aldag, Jean C.

    2015-01-01

    Innate immunity and immunological biomarkers are believed to be interrelated with sex hormones and other neuroendocrine factors. Sexual dimorphism mechanisms may be operating in certain rheumatic and inflammatory diseases which occur more frequently in women than men, as rheumatoid arthritis (RA). Less data have been available on altered interrelations of the combined neuroendocrine and immune (NEI) systems as risk factors for development of certain diseases. In this study, serological interrelations of NEI biomarkers are analyzed before symptomatic onset of RA (pre-RA) versus control (CN) subjects, stratified by sex. Sexual dimorphism was found in serum levels of acute serum amyloid A (ASAA), soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble tumor necrosis factor receptor 1 (sTNF-R1). Multiple steroidal and hormonal (neuroendocrine) factors also showed highly (p < 0.001) significant sexual dimorphism in their assayed values, but less for cortisol (p = 0.012), and not for 17-hydroxyprogesterone (p = 0.176). After stratification by sex and risk of developing RA, differential NEI correlational patterns were observed in the interplay of the NEI systems between the pre-RA and CN groups, which deserve further investigation. PMID:26693225

  9. 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. PMID:14662317

  10. 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.

  11. 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

  12. Influx of testosterone-binding globulin (TeBG) and TeBG-bound sex steroid hormones into rat testis and prostate

    SciTech Connect

    Sakiyama, R.; Pardridge, W.M.; Musto, N.A.

    1988-07-01

    The availability of testosterone and estradiol to Sertoli and prostate cells is dependent upon 1) the permeability properties of the blood-tubular barrier (BTB) of the testis or prostate cell membrane, and 2) sex steroid binding to plasma proteins, such as albumin or testosterone-binding globulin (TeBG). Sex steroid influx into these tissues was studied after in vivo arterial bolus injections of (/sup 3/H)testosterone or (/sup 3/H)estradiol in anesthetized rats. Both testosterone and estradiol were readily cleared across the BTB or prostate cell membrane in the absence of plasma proteins and in the presence of human pregnancy serum, in which testosterone or estradiol are 80-95% distributed to TeBG. The extravascular extraction of (/sup 3/H)TeBG across the BTB or prostate plasma membrane (73 +/- 2% (+/- SE) and 92 +/- 9%, respectively) was significantly greater than extraction of (/sup 3/H)albumin or other plasma space markers and indicative of a rapid first pass clearance of TeBG by Sertoli or prostate cells. In summary, these studies indicate that 1) testosterone and estradiol are readily cleared by Sertoli and prostate cells; 2) albumin- and TeBG-bound sex steroids represent the major circulating pool of bioavailable hormone for testis or prostate; and 3) the TeBG-sex steroid complex may be nearly completely available for influx through the BTB or prostate plasma membrane.

  13. Activated p38 MAPK in Peripheral Blood Monocytes of Steroid Resistant Asthmatics

    PubMed Central

    Li, Ling-bo; Leung, Donald Y. M.; Goleva, Elena

    2015-01-01

    Steroid resistance is a significant problem in management of chronic inflammatory diseases, including asthma. Accessible biomarkers are needed to identify steroid resistant patients to optimize their treatment. This study examined corticosteroid resistance in severe asthma. 24 asthmatics with forced expiratory volume in one second of less then 80% predicted were classified as steroid resistant or steroid sensitive based on changes in their lung function following a week of treatment with oral prednisone. Heparinised blood was collected from patients prior to oral prednisone administration. Phosphorylated mitogen activated kinases (MAPK) (extracellular regulated kinase (ERK), p38 and jun kinase (JNK)) were analyzed in whole blood samples using flow cytometry. Activation of phospho-p38 MAPK and phospho-mitogen- and stress-activated protein kinase 1 (MSK1) in asthmatics’ peripheral blood mononuclear cells (PBMC) were confirmed by Western blot. Dexamethasone suppression of the LPS-induced IL-8 mRNA production by steroid resistant asthmatics PBMC in the presence of p38 and ERK inhibitors was evaluated by real time PCR. Flow cytometry analysis identified significantly stronger p38 phosphorylation in CD14+ monocytes from steroid resistant than steroid sensitive asthmatics (p = 0.014), whereas no difference was found in phosphorylation of ERK or JNK in CD14+ cells from these two groups of asthmatics. No difference in phosphorylated p38, ERK, JNK was detected in CD4+, CD8+ T cells, B cells and NK cells from steroid resistant vs. steroid sensitive asthmatics. P38 MAPK pathway activation was confirmed by Western blot, as significantly higher phospho-p38 and phospho-MSK1 levels were detected in the PBMC lysates from steroid resistant asthmatics. P38 inhibitor significantly enhanced DEX suppression of LPS-induced IL-8 mRNA by PBMC of steroid resistant asthmatics. This is the first report demonstrating selective p38 MAPK pathway activation in blood monocytes of steroid

  14. Steroid osteopathy

    SciTech Connect

    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 to 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.

  15. The Influence of Sex Steroid Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis

    PubMed Central

    Bini, Estela Isabel; Mata Espinosa, Dulce; Marquina Castillo, Brenda; Barrios Payán, Jorge; Colucci, Darío; Cruz, Alejandro Francisco; Zatarain, Zyanya Lucía; Alfonseca, Edgar; Pardo, Marta Romano; Bottasso, Oscar; Pando, Rogelio Hernández

    2014-01-01

    The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator’s inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor. PMID:24722144

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

    PubMed

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

    2013-06-01

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

  17. Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer’s disease

    PubMed Central

    Rosario, Emily R.; Chang, Lilly; Head, Elizabeth H.; Stanczyk, Frank Z.; Pike, Christian J.

    2009-01-01

    We examined the relationships between normal aging, Alzheimer’s disease (AD), and brain levels of sex steroid hormones in men and women. In postmortem brain tissue from neuropathologically normal, postmenopausal women, we found no age-related changes in brain levels of either androgens or estrogens. In comparing women with and without AD at different ages, brain levels of estrogens and androgens were lower in AD cases aged 80 years and older but not significantly different in the 60–79 year age range. In male brains, we observed that normal aging was associated with significant decreases in androgens but not estrogens. Further, in men aged 60–79 years, brain levels of testosterone but not estrogens were lower in cases with mild neuropathological changes as well as those with advanced AD neuropathology. In male cases over age 80, brain levels hormones did not significantly vary by neuropathological status. To begin investigating the relationships between hormone levels and indices of AD neuropathology, we measured brain levels of soluble β-amyloid (Aβ). In male cases with mild neuropathological changes, we found an inverse relationship between brain levels of testosterone and soluble Aβ. Collectively, these findings demonstrate sex-specific relationships between normal, age-related depletion of androgens and estrogens in men and women, which may be relevant to development of AD. PMID:19428144

  18. Sex-specific development of spatial orientation is independent of peripubertal gonadal steroids.

    PubMed

    Wojniusz, Slawomir; Ropstad, Erik; Evans, Neil; Robinson, Jane; Solbakk, Anne-Kristin; Endestad, Tor; Haraldsen, Ira Ronit Hebold

    2013-09-01

    Prenatal exposure to androgens has been shown to modulate brain development, resulting in changed behavioral attitudes, sexual orientation and cognitive functions, including processing of spatial information. Whether later changes in gonadotropic hormones during puberty induce further organizational effects within the brain is still insufficiently understood. The purpose of this study was to assess development of spatial orientation before and after the time of normal pubertal development, in an ovine model where half of the animals did not undergo typical reproductive maturation due to the pharmacological blockade of gonadotropin releasing hormone receptor (GnRHR) signaling. The study formed part of a larger trial and utilized 46 pairs of same sex Scottish Mule Texel Cross twins (22 female and 24 male). One twin remained untreated throughout (control) while the other received a subcutaneous GnRH agonist (GnRHa: Goserelin-Acetate) implant every fourth week. GnRHa treatment began at eight and 28 weeks of age, in males and females respectively, because the timing of the pubertal transition is sexually differentiated in sheep as it is in humans. Spatial orientation was assessed at three different time points: eight weeks of age, before puberty and treatment in both sexes; 28 weeks of age, after 20 weeks GnRHa treatment in males and before puberty and GnRHa treatment in females; and at 48 weeks of age, which is after the normal time of the pubertal transition in both sexes. Spatial orientation was tested in a spatial maze with traverse time as the main outcome measure. GnRHa treatment did not affect spatial maze performance as no significant differences in traverse time between treated and untreated animals were observed at any time-point. Adolescent females (48 weeks of age) traversed the maze significantly faster than adolescent males, whereas no sex differences in traverse time were seen at earlier developmental stages (eight and 28 weeks). Development of sex

  19. Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment.

    PubMed

    Nicholson, Tristan M; Sehgal, Priyanka D; Drew, Sally A; Huang, Wei; Ricke, William A

    2013-01-01

    Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goals of this study were to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR and ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR and ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH. PMID:23792768

  20. Sex steroid receptor expression and localization in benign prostatic hyperplasia varies with tissue compartment

    PubMed Central

    Nicholson, Tristan M.; Sehgal, Priyanka D.; Drew, Sally A.; Huang, Wei; Ricke, William A.

    2013-01-01

    Androgens and estrogens, acting via their respective receptors, are important in benign prostatic hyperplasia (BPH). The goal of this study was to quantitatively characterize the tissue distribution and staining intensity of androgen receptor (AR) and estrogen receptor-alpha (ERα), and assess cells expressing both AR and ERα, in human BPH compared to normal prostate. A tissue microarray composed of normal prostate and BPH tissue was used and multiplexed immunohistochemistry was performed to detect AR and ERα. We used a multispectral imaging platform for automated scanning, tissue and cell segmentation and marker quantification. BPH specimens had an increased number of epithelial and stromal cells and increased percentage of epithelium. In both stroma and epithelium, the mean nuclear area was decreased in BPH relative to normal prostate. AR expression and staining intensity in epithelial and stromal cells was significantly increased in BPH compared to normal prostate. ERα expression was increased in BPH epithelium. However, stromal ERα expression and staining intensity was decreased in BPH compared to normal prostate. Double positive (AR & ERα) epithelial cells were more prevalent in BPH, and fewer double negative (AR & ERα) stromal and epithelial negative cells were observed in BPH. These data underscore the importance of tissue layer localization and expression of steroid hormone receptors in the prostate. Understanding the tissue-specific hormone action of androgens and estrogens will lead to a better understanding of mechanisms of pathogenesis in the prostate and may lead to better treatment for BPH. PMID:23792768

  1. Suppression of sex behavior by kappa opiates and stress steroids occurs via independent neuroendocrine pathways.

    PubMed

    Lombana, Karla; Middleton, Natalie; Coddington, Emma

    2015-01-01

    Endocannabinoids and their receptors are found throughout the brain of all vertebrates. By virtue of their wide distribution, endocannabinoids have the potential to affect many behaviors. Prior research has shown that cannabinoids inhibit courtship-clasping and mediate behavioral responses to stress in male rough-skinned newts, Taricha granulosa, and cannabinoid signaling is initiated by rapid actions of the steroid corticosterone (CORT) at its specific membrane receptor (mCR). This same mCR also recognizes κ-opioid receptor agonists and antagonists. Prior behavioral studies show that κ-opioid agonists suppress clasping behavior in a dose dependent manner. Combined, these studies suggest that κ-opioid agonists might suppress clasping behavior via the same pathway initiated by CORT: up-regulation of endocannabinoid signaling. We examined whether pretreatment with a CB1 antagonist, AM281, would block κ-opioid-mediated suppression of clasping. We found that the CB1 antagonist did not reverse κ-opioid-induced suppression of clasping, revealing that while endocannabinoids mediate CORT-induced suppression of clasping, endocannabinoids do not mediate the κ-opioid-induced suppression of clasping. PMID:25307952

  2. An Immunohistochemical Study on the Expression of Sex Steroid Receptors in Canine Mammary Tumors

    PubMed Central

    Port Louis, Leena Rajathy; Varshney, Khub Chandra; Nair, Madhavan Gopalakrishnan

    2012-01-01

    Steroid hormones are found to play a major role in the genesis and progression of mammary tumors. The aim of this study was to immunohistochemically detect the presence of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and progesterone receptor (PR) and also to study the association between these markers in 29 cases of benign (11) and malignant (18) canine mammary tumors. ERα immunostaining was noticed in only one case of carcinosarcoma specifically in the nuclei of epithelial and a few myoepithelial cells. ERβ immunostaining was noticed in the nuclei and cytoplasm of epithelial cells and smooth muscles lining the blood vessels. Immunoexpression of ERβ was 82% in benign tumors and 78% in malignant tumors. PR immunostaining was expressed in the nuclei of epithelial cells in both benign and malignant tumors. Among the 15 PR+ cases, 6 (55%) were of benign type, and 9 (50%) were of malignant type. The most common group of hormone receptor was the ERα−/PR+/ERβ+ (46%) in benign tumors and ERα−/PR−/ERβ+ (38%) in malignant tumors. Although there was no significant association between ERα and PR with ERβ, the findings indicated that ERβ was consistently expressed in both benign and malignant tumors, irrespective of ERα and PR status. PMID:23738123

  3. Changes in the content of sex steroid hormone receptors in the growing and regressing ovaries of Gallus domesticus during development.

    PubMed

    González-Morán, María Genoveva; González-Arenas, Aliesha; Germán-Castelán, Liliana; Camacho-Arroyo, Ignacio

    2013-08-01

    Sex steroids participate in the regulation of reproduction in female chickens. In this work, we determined the content of androgen receptor (AR), intracellular progesterone receptor isoforms (PR-A and PR-B), membrane progesterone receptor γ (mPRγ) and estrogen receptor α (ER-α) in the left growing and right regressing ovaries of Gallus domesticus from 13-day-old chicken embryos to 1-month-old chickens by western blot analysis. A marked difference in the morphological characteristics of the left and the right ovaries during development was observed. Results show a higher content of AR in the left ovary than in the right one in all ages. In the left ovary, the highest content of AR was observed on day 13 of embryonic development, and diminished with age. In the right ovary, AR was expressed from day 13 of embryonic development to 1-day-old, and became undetectable at 1-week and 1-month-old. In the left ovary, PR isoforms were not detected on day 13 of embryonic development, but they presented a marked expression after hatching. In the right ovary, the highest expression of both PR isoforms was found on 1-day-old, and significantly decreased with age. PR-B was the predominant isoform on 1-day and 1-month old in the left ovary, whereas PR-A was the predominant one on day 13 of embryonic development in the right ovary. Interestingly, mPRγ was detected at 1-week and 1-month-old in the left ovary meanwhile in the right ovary, it was detected from day 13 of embryonic development to 1-day-old. ER-α was only detected in the left ovary from day 13 to 1-week-old, while in 1-month-old chickens, it was expressed in both ovaries. In the left ovary, ER-α content was lower from 1-day to 1-month-old as compared with day 13 of embryonic development. Our results demonstrate a differential expression of sex steroid hormone receptors between the left growing and the right regressing ovary, and throughout chickens' age; and this is the first report about mPR expression in birds

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

    PubMed

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

    2012-06-01

    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

  5. 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

  6. AMP-activated protein kinase is activated by non-steroidal anti-inflammatory drugs.

    PubMed

    King, Tanya S; Russe, Otto Quintus; Möser, Christine V; Ferreirós, Nerea; Kynast, Katharina L; Knothe, Claudia; Olbrich, Katrin; Geisslinger, Gerd; Niederberger, Ellen

    2015-09-01

    AMP-activated kinase (AMPK) is a cellular energy sensor, which is activated in stages of increased adenosine triphosphate (ATP) consumption. Its activation has been associated with a number of beneficial effects such as decrease of inflammatory processes and inhibition of disease progression of diabetes and obesity. A recent study suggested that salicylate, the active metabolite of the non-steroidal anti-inflammatory drug (NSAID) acetyl-salicylic acid (aspirin), is able to activate AMPK pharmacologically. This observation raised the question whether or not other NSAIDs might also act as AMPK activators and whether this action might contribute to their cyclooxygenase (COX)-independent anti-inflammatory properties. In this study, we investigated mouse and human neuronal cells and liver tissue of mice after treatment with various NSAIDs. Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK. In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs. AMPK might therefore contribute to their antinociceptive and anti-inflammatory properties. PMID:26049010

  7. Increased Neurokinin B (Tac2) Expression in the Mouse Arcuate Nucleus Is an Early Marker of Pubertal Onset with Differential Sensitivity to Sex Steroid-Negative Feedback than Kiss1

    PubMed Central

    Navarro, Víctor M.; Kwong, Cecilia; Noel, Sekoni D.; Martin, Cecilia; Xu, Shuyun; Clifton, Donald K.; Carroll, Rona S.; Steiner, Robert A.; Kaiser, Ursula B.

    2012-01-01

    At puberty, neurokinin B (NKB) and kisspeptin (Kiss1) may help to amplify GnRH secretion, but their precise roles remain ambiguous. We tested the hypothesis that NKB and Kiss1 are induced as a function of pubertal development, independently of the prevailing sex steroid milieu. We found that levels of Kiss1 mRNA in the arcuate nucleus (ARC) are increased prior to the age of puberty in GnRH/sex steroid-deficient hpg mice, yet levels of Kiss1 mRNA in wild-type mice remained constant, suggesting that sex steroids exert a negative feedback effect on Kiss1 expression early in development and across puberty. In contrast, levels of Tac2 mRNA, encoding NKB, and its receptor (NK3R; encoded by Tacr3) increased as a function of puberty in both wild-type and hpg mice, suggesting that during development Tac2 is less sensitive to sex steroid-dependent negative feedback than Kiss1. To compare the relative responsiveness of Tac2 and Kiss1 to the negative feedback effects of gonadal steroids, we examined the effect of estradiol (E2) on Tac2 and Kiss1 mRNA and found that Kiss1 gene expression was more sensitive than Tac2 to E2-induced inhibition at both juvenile and adult ages. This differential estrogen sensitivity was tested in vivo by the administration of E2. Low levels of E2 significantly suppressed Kiss1 expression in the ARC, whereas Tac2 suppression required higher E2 levels, supporting differential sensitivity to E2. Finally, to determine whether inhibition of NKB/NK3R signaling would block the onset of puberty, we administered an NK3R antagonist to prepubertal (before postnatal d 30) females and found no effect on markers of pubertal onset in either WT or hpg mice. These results indicate that the expression of Tac2 and Tacr3 in the ARC are markers of pubertal activation but that increased NKB/NK3R signaling alone is insufficient to trigger the onset of puberty in the mouse. PMID:22893725

  8. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    SciTech Connect

    Habibi, H.R.; Ince, B.W.

    1983-12-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-(/sup 14/C)leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

  9. 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. PMID:26352264

  10. Urinary Sex Steroids and Anthropometric Markers of Puberty - A Novel Approach to Characterising Within-Person Changes of Puberty Hormones

    PubMed Central

    Singh, Gurmeet K. S.; Balzer, Ben W. R.; Kelly, Patrick J.; Paxton, Karen; Hawke, Catherine I.; Handelsman, David J.; Steinbeck, Katharine S.

    2015-01-01

    Background/Aims The longitudinal relationships of within-individual hormone and anthropometric changes during puberty have not ever been fully described. The objectives of this study were to demonstrate that 3 monthly urine collection was feasible in young adolescents and to utilise liquid chromatography-tandem mass spectrometry assay methods for serum and urine testosterone (T), estradiol (E2) and luteinizing hormone (LH) in adolescents by relating temporal changes in urine and serum hormones over 12 months to standard measures of pubertal development. Methods A community sample of 104 adolescents (57 female) was studied over 12 months with annual anthropometric assessment, blood sampling and self-rated Tanner staging and urine collected every 3 months. Serum and urine sex steroids (T, E2) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and LH by immunoassay. Results A high proportion (92%) of scheduled samples were obtained with low attrition rate of 6.7% over the 12 months. Urine hormone measurements correlated cross-sectionally and longitudinally with age, anthropometry and Tanner stage. Conclusion We have developed a feasible and valid sampling methodology and measurements for puberty hormones in urine, which allows a sampling frequency by which individual pubertal progression in adolescents can be described in depth. PMID:26599397

  11. Cross-Sectional Associations between Body Size, Circulating Sex-Steroid Hormones and IGF Components among Healthy Chinese Women

    PubMed Central

    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. PMID:26352264

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

    PubMed

    Carson, James A; Manolagas, Stavros C

    2015-11-01

    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. This article is part of a Special Issue entitled "Muscle Bone Interactions". PMID:26453497

  13. Dicer1 Ablation in the Mouse Epididymis Causes Dedifferentiation of the Epithelium and Imbalance in Sex Steroid Signaling

    PubMed Central

    Björkgren, Ida; Saastamoinen, Lauri; Krutskikh, Anton; Huhtaniemi, Ilpo; Poutanen, Matti; Sipilä, Petra

    2012-01-01

    Background The postnatal development of the epididymis is a complex process that results in a highly differentiated epithelium, divided into several segments. Recent studies indicate a role for RNA interference (RNAi) in the development of the epididymis, however, the actual requirement for RNAi has remained elusive. Here, we present the first evidence of a direct need for RNAi in the differentiation of the epididymal epithelium. Methodology/Principal Findings By utilizing the Cre-LoxP system we have generated a conditional knock-out of Dicer1 in the two most proximal segments of the mouse epididymis. Recombination of Dicer1, catalyzed by Defb41iCre/wt, took place before puberty, starting from 12 days postpartum. Shortly thereafter, downregulation of the expression of two genes specific for the most proximal epididymis (lipocalin 8 and cystatin 8) was observed. Following this, segment development continued until week 5 at which age the epithelium started to regress back to an undifferentiated state. The dedifferentiated epithelium also showed an increase in estrogen receptor 1 expression while the expression of androgen receptor and its target genes; glutathione peroxidase 5, lipocalin 5 and cysteine-rich secretory protein 1 was downregulated, indicating imbalanced sex steroid signaling. Conclusions/Significance At the time of the final epididymal development, Dicer1 acts as a regulator of signaling pathways essential for maintaining epithelial cell differentiation. PMID:22701646

  14. Sex Steroids Effects on the Molting Process of the Helminth Human Parasite Trichinella spiralis

    PubMed Central

    Hernández-Bello, Romel; Ramirez-Nieto, Ricardo; Muñiz-Hernández, Saé; Nava-Castro, Karen; Pavón, Lenin; Sánchez-Acosta, Ana Gabriela; Morales-Montor, Jorge

    2011-01-01

    We evaluated the in vitro effects of estradiol, progesterone, and testosterone on the molting process, which is the initial and crucial step in the development of the muscular larvae (ML or L1) to adult worm. Testosterone had no significative effect on the molting rate of the parasite, however, progesterone decreased the molting rate about a 50% in a concentration- and time-independent pattern, while estradiol had a slight effect (10%). The gene expression of caveolin-1, a specific gene used as a marker of parasite development, showed that progesterone and estradiol downregulated its expression, while protein expression was unaffected. By using flow citometry, a possible protein that is recognized by a commercial antiprogesterone receptor antibody was detected. These findings may have strong implications in the host-parasite coevolution, in the sex-associated susceptibility to this infection and could point out to possibilities to use antihormones to inhibit parasite development. PMID:22162638

  15. Interrelationship between alcohol intake and endogenous sex-steroid hormones on diabetes risk in postmenopausal women

    PubMed Central

    Rohwer, Rachelle D.; Liu, Simin; You, Nai-Chieh; Buring, Julie E.; Manson, JoAnn E.; Song, Yiqing

    2014-01-01

    Objective We examined whether circulating concentrations of sex hormones, including estradiol, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS), were associated with alcohol intake or mediated the alcohol-type 2 diabetes (T2D) association. Methods Among women not using hormone replacement therapy and free of baseline cardiovascular disease, cancer, and diabetes in the Women’s Health Study, 359 incident cases of T2D and 359 matched controls were chosen during 10 years of follow-up. Results Frequent alcohol intake (≥1 drink/day) was positively and significantly associated with higher plasma estradiol concentrations in an age-adjusted model (β=0.14, 95% CI, 0.03, 0.26), as compared with rarely/never alcohol intake. After adjusting for additional known covariates, this alcohol-estradiol association remained significant (β=0.19, 95% CI, 0.07, 0.30). Testosterone (β=0.13, 95% CI, −0.05, 0.31), SHBG (β=0.07, 95% CI, −0.07, 0.20), and DHEAS (β=0.14, 95% CI, −0.04, 0.31) showed positive associations without statistical significance. Estradiol alone or in combination with SHBG appeared to influence the observed protective association between frequent alcohol consumption and T2D risk, with a 12–21% reduction in OR in the multivariate-adjusted models. Conclusions Our cross-sectional analysis showed positive associations between alcohol intake and endogenous estradiol concentrations. Our prospective data suggested that baseline concentrations of estradiol, with or without SHBG, might influence the alcohol-T2D association in postmenopausal women. PMID:25759186

  16. Brief exposure of embryos to steroids or aromatase inhibitor induces sex reversal in Nile tilapia (Oreochromis niloticus).

    PubMed

    Gennotte, Vincent; Mafwila Kinkela, Patrick; Ulysse, Bernard; Akian Djétouan, Dieudonné; Bere Sompagnimdi, Frédéric; Tomson, Thomas; Mélard, Charles; Rougeot, Carole

    2015-01-01

    This study aimed to develop sex reversal procedures targeting the embryonic period as tools to study the early steps of sex differentiation in Nile tilapia with XX, XY, and YY sexual genotypes. XX eggs were exposed to masculinizing treatments with androgens (17α-methyltestosterone, 11-ketotestosterone) or aromatase inhibitor (Fadrozole), whereas XY and YY eggs were subjected to feminizing treatments with estrogen analog (17α-ethynylestradiol). All treatments consisted of a single or double 4-hr immersion applied between 1 and 36 hour post-fertilization (hpf). Concentrations of active substances were 1000 or 2000 μg l(-1) in XX and XY, and 2000 or 6500 μg l(-1) in YY. Masculinizing treatments of XX embryos achieved a maximal sex reversal rate of 10% with an exposure at 24 hpf to 1000 μg l(-1) of 11-ketotestosterone or to 2000 μg l(-1) of Fadrozole. Feminization of XY embryos was more efficient and induced up to 91% sex reversal with an exposure to 2000 μg l(-1) of 17α-ethynylestradiol. Interestingly, similar treatments failed to reverse YY fish to females, suggesting either that a sex determinant linked to the Y chromosome prevents the female pathway when present in two copies, or that a gene present on the X chromosome is needed for the development of a female phenotype. PMID:25376842

  17. Development of a combined method to assess the complex effect of atrazine on sex steroid synthesis in H295R cells.

    PubMed

    Háhn, Judit; Szoboszlay, Sándor; Krifaton, Csilla; Kovács, Krisztina J; Ferenczi, Szilamér; Kriszt, Balázs

    2016-07-01

    The aim of the study was to develop a rapid, cost-effective combined testing method to assess the indirect effect of compounds interfering with sex steroid synthesis and to determine complex effects of atrazine on estrogen and androgen synthesis in vitro on H295R human cell line. Steroidogenic assay was performed on H295R human adrenocortical carcinoma cell line. Instead of standard analytical methods, bioluminescence bioreporter assays (Saccharomyces cerevisiae BLYES and BLYAS) were used to measure estrogenic and androgenic effects of sex steroid hormones released by human cells in response to atrazine. Atrazine resulted in elevated estrogen production presumably due to its well documented inductive effect on aromatase on H295R cell line, detected by BLYES. Interestingly, results of BLYAS test showed concentration-dependent increase of androgen production in H295R cells. That indicates that atrazine can not only increase estrogen level via aromatase induction, but may interfere in androgen synthesis as well. The combined method allows us to assess the androgenic and estrogenic effect of sex steroids produced by human cells in increased or decreased quantity as a result of the different chemicals, without determining specific analytical measurement endpoints, by using the yeast based bioluminescent bioreporter test. PMID:27085065

  18. Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood.

    PubMed

    Norjavaara, Ensio; Ankarberg-Lindgren, Carina; Kriström, Berit

    2016-01-01

    The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty. Transdermal E2, compared to oral administration, is the first choice to start pubertal HRT. Transdermal application avoids liver exposure to supraphysiologic estrogen concentrations and provides a more physiologic mechanism for hormone delivery. By cutting E2 matrix patches in doses of 0.05-0.07 µg/kg or administrate E2 gel in doses of 0.1 mg/day, serum concentrations of E2 seen in early spontaneous puberty can be obtained. Patches can be removed in the morning and thereby mimic the normal circadian rhythm. For those clinics with access to sensitive E2 determinations methods (extraction followed by radioimmunoassay or mass spectrometry) monitoring the attained E2 serum levels is recommended in order to optimally mimic the levels seen in early puberty as well as growth velocity, breast and uterus development. Mid- and late pubertal HRT is obtained by increased doses of E2, adding cyclic oral or transdermal progestin, as well as testosterone gel over the pubic area if indicated. PMID:26680580

  19. Genetic variation in sex-steroid receptors and synthesizing enzymes and colorectal cancer risk in women

    PubMed Central

    Lin, Jennifer; Zee, Robert Y.L.; Liu, Kuang-Yu; Zhang, Shumin M.; Lee, I-Min; Manson, JoAnn E.; Giovannucci, Edward; Buring, Julie E.; Cook, Nancy R.

    2010-01-01

    Objectives Several lines of evidence have suggested that female hormones may lower risk for developing colorectal cancer. However, the mechanisms by which sex hormones affect colorectal cancer development remain unknown. We sought to determine whether the association may be under genetic control by evaluating genetic variation in estrogen receptors (ESR1 and ESR2), progesterone receptor (PGR), aromatase cytochrome 450 enzyme (CYP19A1) and 17 beta-hydroxysteroid dehydrogenase type 2 gene (HSD17B2). Methods We included 158 incident cases of colorectal cancer and 563 randomly chosen control subjects from 28,345 women in the Women's Health Study aged 45 years or older who provided blood samples and had no history of cancer or cardiovascular disease at baseline in 1993. All cases and controls were Caucasians of European descent. A total of 63 tagging and putative functional SNPs in the 5 genes were included for analysis. Unconditional logistic regression was used to estimate odds ratio (ORs) and 95% confidence intervals (CIs). Results There was no association between variation in ESR1, ESR2, PGR, CYP19A1 and HSD17B2 and colorectal cancer risk after correction for multiple comparisons (p values after correction ≥0.25). There was also no association with any of the haplotypes examined (p ≥0.15) and no evidence of joint effects of variants in the 5 genes (p ≥0.51). Conclusion Our data offer insufficient support for an association between variation in ESR1, ESR2, PGR, CYP19A1 and HSD17B2 and risk for developing colorectal cancer. PMID:20148360

  20. Effects of Developmental Exposure to 2,2′,4,4′,5-Pentabromodiphenyl Ether (PBDE-99) on Sex Steroids, Sexual Development, and Sexually Dimorphic Behavior in Rats

    PubMed Central

    Lilienthal, Hellmuth; Hack, Alfons; Roth-Härer, Astrid; Grande, Simone Wichert; Talsness, Chris E.

    2006-01-01

    Increasing concentrations of polybrominated flame retardants, including polybrominated diphenyl ethers (PBDEs), in breast milk cause concern about possible developmental effects in nursed babies. Because previous studies in rats have indicated effects on sex steroids and sexually dimorphic behavior after maternal exposure to polychlorinated biphenyls (PCBs), our goal in the present study was to determine if developmental exposure to 2,2′,4,4′,5-pentabromodiphenyl ether (PBDE-99) induces similar endocrine-mediated effects. Pregnant rats were exposed to vehicle or PBDE-99 (1 or 10 mg/kg body weight, daily during gestational days 10–18). For comparison, we also included a group exposed to the technical PCB mixture Aroclor 1254 (30 mg/kg body weight, daily). PBDE exposure resulted in pronounced decreases in circulating sex steroids in male offspring at weaning and in adulthood. Female offspring were less affected. Anogenital distance was reduced in male offspring. Puberty onset was delayed in female offspring at the higher dose level, whereas a slight acceleration was detected in low-dose males. The number of primordial/primary ovarian follicles was reduced in females at the lower dose, whereas decline of secondary follicles was more pronounced at the higher dose. Sweet preference was dose-dependently increased in PBDE-exposed adult males, indicating a feminization of this sexually dimorphic behavior. Aroclor 1254 did not alter sweet preference and numbers of primordial/primary and secondary follicles but it did affect steroid concentrations in males and sexual development in both sexes. PBDE concentrations in tissues of dams and offspring were highest on gestational day 19. These results support the hypothesis that PBDEs are endocrine-active compounds and interfere with sexual development and sexually dimorphic behavior. PMID:16451854

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

    PubMed

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

    2015-09-01

    Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. PMID:25963796

  2. Contraceptive steroid concentrations in women with early active schistosomiasis: lack of effect of antischistosomal drugs.

    PubMed

    el-Raghy, I; Back, D J; Osman, F; Orme, M L; Fathalla, M

    1986-04-01

    Plasma concentrations of the oral contraceptive steroids (OCS) ethinyloestradiol (EE2) and levonorgestrel (LNG) have been determined in women with early active schistosomiasis and compared to those obtained in healthy volunteers. Steroid concentrations following a single dose of Ovral (500 micrograms LNG, 50 micrograms EE2) or during a multiple dose regimen were unaffected by the disease. There was no significant effect of the antischistosomal drugs praziquantel (40 mg X kg-1) or metrifonate (10 mg X kg-1 X 3 at 2-week intervals) on plasma steroid concentrations. In regular users of OCS, significantly higher concentrations of LNG were observed than in women who received only a single dose. We conclude that there is no pharmacokinetic reason for withholding OCS from patients with early active schistosomiasis who are also receiving either praziquantel or metrifonate. PMID:3089682

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

    SciTech Connect

    Craig, Zelieann R.; Leslie, Traci C.; Hatfield, Kimberly P.; Gupta, Rupesh K.; Flaws, Jodi A.

    2010-12-01

    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-OH 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.

  4. Effects of thermal regime on ovarian maturation and plasma sex steroids in farmed white sturgeon, Acipenser transmontanus

    USGS Publications Warehouse

    Webb, M.A.H.; Van Eenennaam, J. P.; Feist, G.W.; Linares-Casenave, J.; Fitzpatrick, M.S.; Schreck, C.B.; Doroshov, S.I.

    2001-01-01

    Recently, commercial aquaculture farms in Northern California have exposed gravid, cultured white sturgeon females to cold water (12 ?? 1??C) throughout the late phase of vitellogenesis and ovarian follicle maturation resulting in improved ovulation rates and egg quality. However, the optimum timing for transfer of broodfish to the cold water and the capacity of transferred broodfish to maintain reproductive competence over an extended time in cold water had not been evaluated. Gravid white sturgeon females that have been raised at water temperatures of 16-20??C were transported to either cold water (12 ?? 1??C; Group 1) in November 1997 or maintained in ambient water temperatures (10-19??C; Group 2) until early spring. In March 1998, half of the fish in Group 2 had regressed ovaries, but the remaining females had intact ovarian follicles and were transported to the cold water. Ovarian follicles and blood were collected from females until they reached the stage of spawning readiness (determined by germinal vesicle position and an oocyte maturation assay) or underwent ovarian regression. Exposure of gravid sturgeon females to ambient water temperatures (14.5 ?? 2.3??C, mean ?? S.D.) from October to March led to a decrease in plasma sex steroids and a high incidence of ovarian regression in fish with a more advanced stage of oocyte development. Transfer of females with intact ovarian follicles to cold water (12 ?? 1??C) in the fall or early spring resulted in normal ovarian development in the majority of females. Holding females in cold water does not seem to override their endogenous reproductive rhythms but extends their capacity to maintain oocyte maturational competence over a longer period of time. A temperature-sensitive phase in ovarian development may occur during the transition from vitellogenic growth to oocyte maturation, and the degree and timing of sensitivity to environmental temperature are dependent on the female's endogenous reproductive rhythm

  5. Sex Steroid Hormone Profiles are Related to Sleep Measures from Polysomnography and the Pittsburgh Sleep Quality Index

    PubMed Central

    Sowers, Mary Fran; Zheng, Huiyong; Kravitz, Howard M.; Matthews, Karen; Bromberger, Joyce T.; Gold, Ellen B.; Owens, Jane; Consens, Flavia; Hall, Martica

    2008-01-01

    Study Objectives: To relate reproductive hormones (and the preceding 7-year rates of their change) to objectively and subjectively assessed sleep measures, independent of age, vasomotor symptom frequency, depressive symptoms, and body size. Design: A cross-sectional sleep substudy nested in the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the menopausal transition. Setting: Community-based. Participants: 365 Caucasian, African American, and Chinese women. Measurements and Results: Sleep duration, continuity, and architecture were measured during two nights of in-home polysomnography (PSG) studies. Participants completed the Pittsburgh Sleep Quality Index (PSQI) for sleep quality, sleep diaries for medication, vasomotor symptoms, lifestyle information and questionnaires for depressive symptoms. Blood collected annually in the years prior to sleep study was assayed for follicle stimulating hormone (FSH), estradiol (E2), and total testosterone (T). More rapid rate of FSH change was significantly associated with higher delta sleep percent, longer total sleep time (TST), but less favorable self-reported sleep quality (PSQI). Baseline E2 was modestly and negatively associated with sleep quality. Women in the lowest total testosterone quartile at baseline had more wake time after sleep onset (WASO) than women in the highest quartile. Lower E2/T ratio, an index reflecting the increasing androgenic environment with the menopause transition, was associated with less WASO. Conclusions: More rapid rate of FSH change was associated with longer sleep duration but poor sleep quality. Women with higher T or who were closer to the completion of the transition process (as indexed by a lower E2/T) had less sleep discontinuity (less WASO). Citation: Sowers MF; Zheng H; Kravitz HM; Matthews K; Bromberger JT; Gold EB; Owens J; Consens F; Hall M. Sex steroid hormone profiles are related to sleep measures From polysomnography and the pittsburgh sleep quality

  6. Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits.

    PubMed

    Zettergren, Anna; Karlsson, Sara; Hovey, Daniel; Jonsson, Lina; Melke, Jonas; Anckarsäter, Henrik; Lichtenstein, Paul; Lundström, Sebastian; Westberg, Lars

    2016-06-01

    Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out. PMID:26930261

  7. Acute exposure to ultraviolet-B radiation modulates sex steroid hormones and receptor expression in the skin and may contribute to the sex bias of melanoma in a fish model.

    PubMed

    Mitchell, David L; Fernandez, André A; Garcia, Rachel; Paniker, Lakshmi; Lin, Kevin; Hanninen, Amanda; Zigelsky, Kyle; May, Matthew; Nuttall, Mark; Lo, Herng-Hsiang; Person, Maria D; Earley, Ryan

    2014-05-01

    Using the Xiphophorus fish melanoma model, we show a strong male bias for sunlight-induced malignant melanoma, consistent with that seen in the human population. To examine underlying factors, we exposed adult X. couchianus fish to a single, sublethal dose of UVB and measured circulating sex steroid hormones and expression of associated hormone receptor genes over a 24-h period. We found that a single exposure had profound effects on circulating levels of steroid hormones with significant decreases for all free sex steroids at 6 and 24 h and increases in conjugated 2-estradiol and 11-ketotestosterone at 6 and 24 h, respectively. Whereas ARα expression increased in male and female skin, neither ARβ nor either of the ERs showed significant responses to UVB in either sex. The rapid response of male androgens and their receptors in the skin after UVB irradiation implicates hormones in the male bias of skin cancer and suggests that the photoendocrine response immediately after UV exposure may be relevant to melanomagenesis. PMID:24406016

  8. Acute exposure to ultraviolet-B radiation modulates sex steroid hormones and receptor expression in the skin and may contribute to the sex-bias of melanoma in a fish model

    PubMed Central

    Mitchell, David L.; Fernandez, André A.; Garcia, Rachel; Paniker, Lakshmi; Lin, Kevin; Hanninen, Amanda; Zigelsky, Kyle; May, Matthew; Nuttall, Mark; Lo, Herng-hsiang; Person, Maria D.; Earley, Ryan

    2014-01-01

    Using the Xiphophorus fish melanoma model we show a strong male bias for cutaneous malignant melanoma, consistent with that seen in the human population. To examine underlying factors, we exposed adult X. couchianus fish to a single, sub-lethal dose of UVB and measured circulating sex steroid hormones and expression of associated hormone receptor genes over a 24 hour period. We found that a single exposure had profound effects on circulating levels of steroid hormones with significant decreases for all free sex steroids at 6 and 24 h and increases in conjugated 2-estradiol and 11-ketotestosterone at 6 and 24 h, respectively. Whereas ARα expression increased in male and female skin, neither ARβ nor either of the ER’s showed significant responses to UVB in either sex. The rapid response of male androgens and their receptors in the skin after UVB irradiation implicates hormones in the male-bias of skin cancer and suggests that the photoendocrine response immediately after UV exposure may be relevant to melanomagenesis. PMID:24406016

  9. Pleasantness, activation, and sex differences in advertising.

    PubMed

    Whissell, C; McCall, L

    1997-10-01

    Advertisements in men's, women's, girls', and boys' magazines (n = 38,195 words) were scored objectively in terms of 15 measures of linguistic style, e.g., use of common words, use of long words, use of specific words and emotional tone (pleasantness and activation, as measured by the Dictionary of Affect). There were several sex- and age-related differences among advertisements from different sources. Advertisements from boys' magazines were extremely active, those from women's and girls' magazines were shorter and unusually pleasant. In two follow-up studies (N = 122 volunteers), objective emotional measures of advertising text proved to be related to ratings of persuasion and of success of appeal for individual advertisements. The most preferred advertisement for women was pleasant and active, that for men unpleasant and active. When men and women created advertisements, women's were shorter and more pleasant. PMID:9354085

  10. 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 Central

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

    2012-01-01

    Context: Whether menopause-related changes in sex steroids account for midlife weight gain in women or whether weight drives changes in sex steroids remains unanswered. Objective: 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. Design, Setting, and Participants: 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. Main Outcome Measures: Waist circumference, SHBG, testosterone, FSH, and estradiol were measured. Results: 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 log2 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. Conclusions: 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. PMID:22723312

  11. Steroids from the roots of Asparagus officinalis and their cytotoxic activity.

    PubMed

    Huang, Xue-Feng; Lin, Yu-Ying; Kong, Ling-Yi

    2008-06-01

    One new (Sarsasapogenin O) and seven known steroids were isolated from the roots of Asparagus officinalis L. Their structures were elucidated on the basis of spectroscopic analysis, including various 2D-NMR techniques, hydrolysis, and by comparison of spectral data of known compounds. These compounds together with nine steroids which were previously isolated from this plant, were tested for cytotoxic activity. Among them, eight compounds displayed significant cytotoxicities against human A2780, HO-8910, Eca-109, MGC-803, CNE, LTEP-a-2, KB and mouse L1210 tumor cells. PMID:18713412

  12. Transgenic male mice expressing human hydroxysteroid dehydrogenase 2 indicate a role for the enzyme independent of its action on sex steroids.

    PubMed

    Zhongyi, Shen; Rantakari, Pia; Lamminen, Tarja; Toppari, Jorma; Poutanen, Matti

    2007-08-01

    Hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2) has been shown to inactivate both estrogens and androgens and activate 20alpha-hydroxyprogesterone to progesterone. In the present study, we generated transgenic (TG) mice ubiquitously expressing human HSD17B2. The TG mice produced showed growth retardation and delayed eye opening at the postnatal age. Disrupted spermatogenesis was evident in the presence of normal serum and intratesticular testosterone, progesterone, and normal circulating LH concentrations. A proper androgen action in the target tissues was confirmed by normal histological appearance of the prostate and epididymis. Furthermore, quantitative RT-PCR analysis indicated only a slight decrease in androgen-dependent gene expression in the prostate. The disrupted spermatogenesis was not associated with increased germ cell apoptosis as analyzed by caspase-3 activation. However, it resulted in infertility in the HSD17B2 TG males after the age of 3 months, and at the age of 6 months the seminiferous tubules showed a Sertoli cell-only phenotype. The data indicate that the growth retardation and disrupted spermatogenesis are not due to a lack of proper estrogen or androgen action. Interestingly, the testicular phenotype and some of the other phenotypic changes described are typically observed in mice with reduced action of retinoic acid signaling. This, together with the rescue of the testis phenotype by a synthetic retinoic acid receptor agonist (4-[(E)-2-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid), suggests a role for HSD17B2 in the action of retinoids, in addition to its oxidative HSD17B activity on sex steroids. PMID:17510238

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

    PubMed Central

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

    2014-01-01

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

  14. Sex steroid and growth hormone supplementation to enhance performance in adolescent athletes.

    PubMed

    Rogol, A D

    2000-08-01

    Ergogenic aids are taken to enhance energy utilization by producing more, controlling its use, or increasing mechanical efficiency. Most athletes are looking toward enhancing performance by proper training modalities and methods; however, some look to the biochemical route for a "quick fix." Thus, the use of chemical agents is on the rise. Herein is provided information on the anabolic-androgenic agents androstenedione, dehydroepiandrosterone, and the "parent" compound, testosterone. The former two, at best, have equivocal activity, but testosterone is both anabolic and androgenic in doses that adolescents might receive. Growth hormone and insulin-like growth factor-1 are anabolic, nonandrogenic compounds with undoubted effects on the lean body mass compartment. Both are expensive, not readily available, and subject to the art of counterfeiting. Thus, very few data are available in non-growth hormone-deficient adolescents. The discussion of these agents ends with issues of fairness, ethics, and the message we attempt to project to our teenagers, whether athletes or not. PMID:10943821

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

    PubMed

    Hammond, Geoffrey L

    2016-07-01

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

  16. 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

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

    PubMed

    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

  18. New steroidal saponins and antiulcer activity from Solanum paniculatum L.

    PubMed

    Vieira Júnior, Gerardo Magela; da Rocha, Cláudia Quintino; de Souza Rodrigues, Tamires; Hiruma-Lima, Clélia Akiko; Vilegas, Wagner

    2015-11-01

    Solanum paniculatum L. (Solanaceae) is a plant species widespread throughout tropical America, especially in the Brazilian Savanna region. It is used in Brazil for culinary purposes and in folk medicine to treat liver and gastric dysfunctions, as well as hangovers. Fractionation of the ethanolic extracts (70%) from aerial parts (leaves and twigs) of S. paniculatum led to the isolation of the two new saponins (22R, 23S, 25R)-3β, 6α, 23-trihydroxy-5α-spirostane 6-O-β-D-xylopyranosyl-(1" → 3"')-O-[β-D-quinovopyranosyl(1″' → 2')]-O-[α-L-rhamnopyranosyl(1" → 3')]-O-β-D-quinovopyranoside (1) and diosgenin 3-O-β-D-glucopyranosyl(1" → 6')-O-β-D-glucopyranoside (2) together with four know compounds: caffeic acid (3), diosgenin β-D-glucopyranoside (4), rutin (5), and quercetin 3-O-α-L-rhamnopyranosyl (1"' → 6 ″)-O-β-D-galactopyranoside (6). The structures of these compounds were elucidated by extensive use of 1D and 2D NMR experiments along with HRESIMS analyses. Different doses (31.25-500 mg/kg) of ethanolic extract of leaves from S. paniculatum were evaluated against gastric ulcer induced by ethanol in rats. The lower dose of extract able to promote antiulcer effect was 125 mg/kg. The treatment with S. paniculatum by oral route was able to decrease gastric lesion area and also reduced levels of myeloperoxidase (MPO) in the gastric mucosa. Our results reveal for the first time, steroidal saponins from S. paniculatum and the antiulcer effect of this species at this lower dose. PMID:25976806

  19. Steroid hormones as biomarkers of endocrine disruption in wildlife

    SciTech Connect

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

    1999-07-01

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

  20. Involvement of pituitary gonadotropins, gonadal steroids and breeding season in sex change of protogynous dusky grouper, Epinephelus marginatus (Teleostei: Serranidae), induced by a non-steroidal aromatase inhibitor.

    PubMed

    Garcia, Carlos Eduardo de O; Araújo, Bruno C; Mello, Paulo H; Narcizo, Amanda de M; Rodrigues-Filho, Jandyr A; Medrado, Andreone T; Zampieri, Ricardo A; Floeter-Winter, Lucile M; Moreira, Renata Guimarães

    2013-10-01

    Two experiments were performed using the aromatase inhibitor (AI) letrozole (100mg/kg) to promote sex change, from female-to-male, in protogynous dusky grouper. One experiment was performed during the breeding season (spring) and the other at the end of the breeding season (summer). During the spring, AI promoted sex change after 9 weeks and the sperm produced was able to fertilize grouper oocytes. During the summer, the sex change was incomplete; intersex individuals were present and sperm was not released by any of the animals. Sex changed gonads had a lamellar architecture; cysts of spermatocytes and spermatozoa in the lumen of the germinal compartment. In the spring, after 4 weeks, 11ketotestosterone (11KT) levels were higher in the AI than in control fish, and after 9 weeks, coincident with semen release, testosterone levels increased in the AI group, while 11KT returned to the initial levels. Estradiol (E2) levels remained unchanged during the experimental period. Instead of decreasing throughout the period, as in control group, 17 α-OH progesterone levels did not change in the AI-treated fish, resulting in higher values after 9 weeks when compared with control fish. fshβ and lhβ gene expression in the AI animals were lower compared with control fish after 9 weeks. The use of AI was effective to obtain functional males during the breeding season. The increase in androgens, modulated by gonadotropins, triggered the sex change, enabling the development of male germ cells, whereas a decrease in E2 levels was not required to change sex in dusky grouper. PMID:23792264

  1. Safe relief of rest pain that eases with activity in achillodynia by intrabursal or peritendinous steroid injection: the rupture rate was not increased by these steroid injections.

    PubMed

    Read, M T

    1999-04-01

    A history of morning and rest pain that eases with activity was found to improve after anti-inflammatory injections around the paratenon or within the Achilles bursae. The reduction in pain morbidity was significant, and the peritendinous steroid injections did not increase the rupture rate. PMID:10205700

  2. Effect of GnRHa, pimozide and Ovaprim on ovulation and plasma sex steroid hormones in African catfish Clarias gariepinus.

    PubMed

    Sharaf, S M

    2012-05-01

    Nine groups each of four fish were injected with a single intramuscular dose of the following preparations: Physiological saline (0.9% NaCl) as a control group, 0.5 ml kg(-1) Ovaprim, 20 and 40 μg kg(-1) BW of GnRHa, 8 and 16 mL kg(-1) pimozide tablets and the following combination of GnRHa with pimozide (GP): 20 μg + 4 mg, 30 μg + 8 mg and 40 μg + 16 mg kg(-1) BW. The primary oocyte diameter (POD) before hormone administration ranged from 943.3 to 1071.0 μm. The latency periods (LP) were in the range of 9.0 to 12.0 h after injection. The highest ovulation ratio (OR) was observed in groups Ovaprim, GP(30 + 8) and GP(40 + 16). Other treatments were effective for ovulation, the ovulation ratio in Groups G(40) and GP(20 + 4) were significantly higher than G(20) treatment. The ovulation index (OI) was in the range 62 to 77% and showed significant differences among groups. There was no significant difference in fertilization ratio (FR) among Ovaprim, GP(30 + 8) and GP(40 + 16) groups, while there were significant difference between the previous group and G(20) and G(40) groups. Control, P8, P16 showed negative results in all the parameters LP, OED, OR, OI and FR. Levels of sex steroids were analyzed on 6 and 12 h after initiation of treatments. A significant increase in plasma E(2) with GP(30 + 8) injection was observed 6 and 12 h after injection, while there were no significant increase between all the other groups 6 h after injection. Treatments with GP(20 + 4) resulted in a significant increase in plasma T concentration in females compared with control after 6 h. In contrast, plasma T and E(2) concentrations were lower during the combined GP(20 + 4), GP(30 + 8) and GP(40 + 16) after 12 h than after 16 h of injection. The combined treatments (GnRHa + PIM) are better compared with Ovaprim which gave the same results, they have some advantages, such as reliable response and low cost. Ovaprim is more than 3 to 5-fold of the cost of (GnRH + PIM). Therefore, this

  3. 5α-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives.

    PubMed

    Al-Mohizea, Abdullah M; Al-Omar, Mohamed A; Abdalla, Mohamed M; Amr, Abdel-Galil E

    2012-01-01

    We herein report the 5α-reductase inhibitors, antiviral and anti-tumor activities of some synthesized heterocyclic cyanopyridone and cyanothiopyridone derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds, except 3b, were interestingly less toxic than the reference drug (Prednisolone(®)). Seventeen heterocyclic derivatives containing a cyanopyridone or cyanothiopyridone rings fused to a steroidal moiety were synthesized and screened for their 5α-reductase inhibitors, antiviral and anti-tumor activities comparable to that of Anastrozole, Bicalutamide, Efavirenz, Capravirine, Ribavirin, Oseltamivir and Amantadine as the reference drugs. Some of the compounds exhibited better 5α-reductase inhibitors, antiviral and anti-tumor activities than the reference drugs. The detailed 5α-reductase inhibitors, antiviral and anti-tumor activities of the synthesized compounds were reported. PMID:22057085

  4. Synthesis and antiproliferative activity of D-ring substituted steroidal benzamidothiazoles.

    PubMed

    Fan, Ning-Juan; He, Qiu-Rui; Duan, Min; Bai, Yu-Bin; Tang, Jiang-Jiang

    2016-08-01

    Using progesterone as the starting material, we synthesized a series of steroidal derivatives possessing a D-ring substituted benzamidothiazole. All of the final structures were reported and identified by NMR and HRMS spectrometry for the first time. The antiproliferative activity of the synthesized compounds against PC-3 (human prostate cancer cell line) and SKOV-3 (ovarian cancer cells) were investigated. The preliminary results showed that compounds 8b, 8d and 8g possessed moderate antiproliferative activities. PMID:27137356

  5. Sex differences, gamma activity and schizophrenia.

    PubMed

    Slewa-Younan, S; Gordon, E; Williams, L; Haig, A R; Goldberg, E

    2001-03-01

    This study explores the possibility that the more favourable clinical prognosis in females with schizophrenia may be associated with their greater network interconnectedness, which is possibly reflected in enhanced "Gamma" (40 Hz) electrical brain activity. An auditory "oddball" task was administered to 35 patients with schizophrenia and 35 age and sex matched controls (25 males and 10 females). Peak Gamma amplitude (from a time series of Gamma activity averaged for 40 target stimuli, as well as the immediately preceding 40 background tones) was examined across 19 sites. Peak Gamma activity occurred 250 to 450 ms in targets and 350 to 550 ms in backgrounds. Multiple within and between group MANOVAs were undertaken analysing both Peak Gamma amplitude (microvolts) and latency (milliseconds). Within-group, the control males showed a pattern of earlier Gamma latency in the right compared with the left hemisphere (F(1, 33)=3.70, p<.06), while control females exhibited delayed latency frontally compared with the posterior region (F(1, 33)=6.25, p<.04). This male lateralization finding and the anterior/posterior gradient in females is consistent with Goldberg's model. The patient group however, failed to show this male lateralized and female frontal-posterior pattern of Gamma activity, suggesting suboptimal network integration in the patient group, in both males and females. PMID:11328687

  6. Suppression of the secretion of luteinizing hormone due to isolation/restraint stress in gonadectomised rams and ewes is influenced by sex steroids.

    PubMed

    Tilbrook, A J; Canny, B J; Serapiglia, M D; Ambrose, T J; Clarke, I J

    1999-03-01

    In this study we used an isolation/restraint stress to test the hypothesis that stress will affect the secretion of LH differently in gonadectomised rams and ewes treated with different combinations of sex steroids. Romney Marsh sheep were gonadectomised two weeks prior to these experiments. In the first experiment male and female sheep were treated with vehicle or different sex steroids for 7 days prior to the application of the isolation/restraint stress. Male sheep received either i.m. oil (control rams) or 6 mg testosterone propionate injections every 12 h. Female sheep were given empty s.c. implants (control ewes), or 2x1 cm s.c. implants containing oestradiol, or an intravaginal controlled internal drug release device containing 0.3 g progesterone, or the combination of oestradiol and progesterone. There were four animals in each group. On the day of application of the isolation/restraint stress, blood samples were collected every 10 min for 16 h for the subsequent measurement of plasma LH and cortisol concentrations. After 8 h the stress was applied for 4 h. Two weeks later, blood samples were collected for a further 16 h from the control rams and ewes, but on this day no stress was imposed. In the second experiment, separate control gonadectomised rams and ewes (n=4/group) were studied for 7 h on 3 consecutive days, when separate treatments were applied. On day 1, the animals received no treatment; on day 2, isolation/restraint stress was applied after 3 h; and on day 3, an i. v. injection of 2 microg/kg ACTH1-24 was given after 3 h. On each day, blood samples were collected every 10 min and the LH response to the i.v. injection of 500 ng GnRH administered after 5 h of sampling was measured. In Experiment 1, the secretion of LH was suppressed during isolation/restraint in all groups but the parameters of LH secretion (LH pulse frequency and amplitude) that were affected varied between groups. In control rams, LH pulse amplitude, and not frequency, was

  7. Inhaled Steroids

    MedlinePlus

    ... potential for side effects than steroid pills or syrups. There have been concerns regarding the possibility of ... treatment. Learn about oral steroids (steroid pills and syrups), and more about steroid side effects. What are ...

  8. Omega-pyridiniumalkylethers of steroidal phenols: new compounds with potent antibacterial and antiproliferative activities.

    PubMed

    Lange, C; Holzhey, N; Schönecker, B; Beckert, R; Möllmann, U; Dahse, H-M

    2004-06-15

    Novel omega-pyridiniumalkylethers of two steroidal phenols were synthesized as compounds with potential antimicrobial activity. 3-Hydroxy-estra-1,3,5(10)-triene-17-one and 1-hydroxy-4-methyl-estra-1,3,5(10)-triene-17-one were reacted with omega,omega'-dibromoalkanes to omega-bromoalkoxy-estra-1,3,5(10)-trienes followed by reaction with pyridine to obtain the desired steroidal omega-pyridiniumalkoxy compounds as bromides. Their antimicrobial activity against strains of multiresistant Staphylococcus aureus (MRSA), a vancomycin resistant Enterococcus faecalis and fast growing mycobacteria depends clearly on the length of the alkyl chain. A strong broadband activity has been found for the compounds with eight or 10 C-atoms; in some cases better than ciprofloxacin or cetylpyridinium salts. In addition, the antiproliferative and cytotoxic activity depends on the chain length, too. The differentiation between antibacterial and cytotoxic activity is better for the steroid hybrid molecules than the cetylpyridinium salts. These new compounds can serve as lead compounds for further optimization. PMID:15158804

  9. Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity.

    PubMed

    Guadalupe, Tulio; Zwiers, Marcel P; Wittfeld, Katharina; Teumer, Alexander; Vasquez, Alejandro Arias; Hoogman, Martine; Hagoort, Peter; Fernandez, Guillen; Buitelaar, Jan; van Bokhoven, Hans; Hegenscheid, Katrin; Völzke, Henry; Franke, Barbara; Fisher, Simon E; Grabe, Hans J; Francks, Clyde

    2015-01-01

    The genetic determinants of cerebral asymmetries are unknown. Sex differences in asymmetry of the planum temporale (PT), that overlaps Wernicke's classical language area, have been inconsistently reported. Meta-analysis of previous studies has suggested that publication bias established this sex difference in the literature. Using probabilistic definitions of cortical regions we screened over the cerebral cortex for sexual dimorphisms of asymmetry in 2337 healthy subjects, and found the PT to show the strongest sex-linked asymmetry of all regions, which was supported by two further datasets, and also by analysis with the FreeSurfer package that performs automated parcellation of cerebral cortical regions. We performed a genome-wide association scan (GWAS) meta-analysis of PT asymmetry in a pooled sample of 3095 subjects, followed by a candidate-driven approach which measured a significant enrichment of association in genes of the 'steroid hormone receptor activity' and 'steroid metabolic process' pathways. Variants in the genes and pathways identified may affect the role of the PT in language cognition. PMID:25239853

  10. A mechanism underlying the sexually dimorphic ACTH response to lipopolysaccharide in rats: sex steroid modulation of cytokine binding sites in the hypothalamus

    PubMed Central

    Watanobe, Hajime; Yoneda, Masashi

    2003-01-01

    It is well established that the hypothalamic-pituitary-adrenal responses to immune stressors are sexually dimorphic in rodents (females > males), but the underlying mechanism is still unclear. To investigate the mechanism, in this study we examined whether the sex steroid environment affects the following variables in male and female rats: (1) plasma levels of ACTH, interleukin (IL)-1β, IL-6 and tumour necrosis factor-α (TNF-α) after systemic lipopolysaccharide (LPS) administration; (2) static concentrations of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the mediobasal hypothalamus (MBH) and those of ACTH in the anterior pituitary (AP); and (3) the binding characteristics of IL-1β, IL-6 and TNF-α in the MBH and AP. LPS-induced ACTH release was significantly higher in female than in male rats, and this sexual difference was abolished by performing gonadectomy in both sexes. Administration of physiological doses of testosterone and oestradiol to gonadectomized males and females, respectively, restored the altered ACTH responses to normal. Changes in the sex steroid milieu did not affect plasma cytokine responses to LPS, tissue contents of CRH, AVP and ACTH, or the IL-6 binding characteristics in the MBH and AP. However, the number of IL-1β and TNF-α binding sites, but not their binding affinities, in the MBH showed significant changes according to altered sex hormone milieu, in the same direction as the LPS-induced ACTH response. These results suggest that the hypothalamic sensitivity to peripheral IL-1β and TNF-α may be an important mechanism underlying the sexually dimorphic ACTH response to LPS in rats. PMID:12562959

  11. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    SciTech Connect

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.

    1988-08-01

    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by (35S)-t-butylbicyclophosphorothionate ((35S)TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of (35S)TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of (35S)TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates (35S)TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All (35S)TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of (3H)promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

  12. Network of nuclear receptor ligands in multiple sclerosis: Common pathways and interactions of sex-steroids, corticosteroids and vitamin D3-derived molecules.

    PubMed

    Rolf, Linda; Damoiseaux, Jan; Hupperts, Raymond; Huitinga, Inge; Smolders, Joost

    2016-09-01

    Sex-steroids, corticosteroids and vitamin D3-derived molecules have all been subject to experimental studies and clinical trials in a plethora of autoimmune diseases. These molecules are all derived from cholesterol metabolites and are ligands for nuclear receptors. Ligation of these receptors results in direct regulation of multiple gene transcription involved in general homeostatic and adaptation networks, including the immune system. Indeed, the distinct ligands affect the function of both myeloid and lymphoid cells, eventually resulting in a less pro-inflammatory immune response which is considered beneficial in autoimmune diseases. Next to the immune system, also the central nervous system is prone to regulation by these nuclear receptor ligands. Understanding of the intricate interactions between sex-steroids, corticosteroids and vitamin D3 metabolites, on the one hand, and the immune and central nervous system, on the other hand, may reveal novel approaches to utilize these nuclear receptor ligands to full extent as putative treatments in multiple sclerosis, the prototypic immune-driven disease of the central nervous system. PMID:27395031

  13. Impact of photoperiod manipulation on day/night changes in melatonin, sex steroids and vitellogenin plasma levels and spawning rhythms in Senegal sole, Solea senegalensis.

    PubMed

    Oliveira, Catarina; Mañanós, Evaristo; Ramos, Jesus; Sánchez-Vázquez, Francisco Javier

    2011-07-01

    Photoperiod and temperature are known as the main synchronizers of seasonal reproduction in fish. This paper studied the role of photoperiod on the synchronization of F1 Senegal sole reproduction rhythms. Fish were maintained under constant short-photoperiod (9L:15D) from the winter solstice onwards (experimental group) or under naturally-changing photoperiod (control group), and water temperature naturally oscillated in both groups. Blood samples were collected during the reproduction season at pre-spawning (March), spawning (April) and post-spawning (May) to determine the endocrine status. Spawning events and egg quality parameters were also monitored. The results revealed a significant increase in nocturnal melatonin concentration from March to May in the control group, while in the experimental group such seasonal change did not occur. As to plasma levels of vitellogenin, testosterone, estradiol and 11keto-testosterone, differences between groups were found mostly in March, while in April and May levels were often similar. Spawning was observed in both groups, although the experimental group started slightly earlier and also finished earlier than the control group, perhaps as a result of the increase in sex steroids and VTG observed at pre-spawning. Briefly, reproduction rhythms persisted in the absence of the natural lengthening of photoperiod, although photoperiod manipulation altered the seasonal modulation of melatonin, increased sex steroids and vitellogenin at pre-spawning, and slightly advanced the timing of spawning. PMID:21466857

  14. Relationship between Sex Steroid and Vitellogenin Concentrations in Flounder (Platichthys flesus) Sampled from an Estuary Contaminated with Estrogenic Endocrine-Disrupting Compounds

    PubMed Central

    Scott, Alexander P.; Katsiadaki, Ioanna; Kirby, Mark F.; Thain, John

    2006-01-01

    High concentrations of vitellogenin (VTG; egg yolk protein) have previously been found in male flounder (Platichthys flesus) from several UK estuaries; these levels have been ascribed to the presence of estrogenic endocrine-disrupting compounds (EDCs). Gonadal abnormalities, including intersex, have also been recorded in these estuaries. However, there is no firm evidence to date that these two findings are causally linked or that the presence of estrogenic EDCs has any adverse population effects. In the present study, we examined the relationship between concentrations of VTG and sex steroids (11-oxotestosterone in males and 17β-estradiol in females) in specimens of flounder captured from the estuary of the River Mersey. We first questioned whether the high concentrations of VTG in male and immature female flounder were indeed caused by a direct effect of exogenous EDCs and not indirectly via the endogenous secretion of 17β-estradiol. The data favored the direct involvement of estrogenic EDCs. We then questioned whether the presence of estrogenic EDCs not only stimulated inappropriate VTG synthesis but whether it might also have had a negative effect on endogenous steroid secretion. It should be noted that the predicted consequences of a drop in steroid secretion include smaller gonads, smaller oocytes, fewer numbers of sperm, and depressed spawning behavior. This question was more difficult to answer because of the strong effect of the seasonal reproductive cycle and stage of maturation on steroid concentrations. However, matched by month of capture and stage of maturation, both 17β-estradiol in females and 11-keto-testosterone in males were in most cases significantly lower in those years when VTG concentrations were higher. PMID:16818243

  15. Reproductive activity in the peninsular pronghorn determined from excreted gonadal steroid metabolites.

    PubMed

    Kersey, David C; Holland, Jeff; Eng, Curtis

    2015-01-01

    Fecal hormone monitoring was employed to better define annual patterns of reproductive steroid metabolites from a breeding pair of peninsular pronghorn (Antilocapra americana peninsularis) maintained at the Los Angeles Zoo. Notably in the female, increased excretion of estrogen metabolites occurred during the breeding season (Jun-Aug), and a biphasic pattern in progestagen activity was measured during gestation. Of additional interest, a preterm increase in estrogen that continued for an additional 64 days post partum. Male androgen activity correlated with the female estrogen patterns, with a single successful copulation occurring during the breeding season; interestingly however, the male exhibited no reproductive behaviors during the female's preterm/post partum estrogen increase. These data are the first reproductive steroid profiles for the peninsular pronghorn and provide valuable insight that will aid efforts that link the species' reproductive physiology with conservation management. PMID:25652944

  16. Synthesis and evaluation of antifungal activity of C21-steroidal derivatives.

    PubMed

    Huang, Lie-Jun; Wang, Bin; Zhang, Jian-Xin; Yuan, Chun-Mao; Gu, Wei; Mu, Shu-Zhen; Hao, Xiao-Jiang

    2016-04-15

    The antifungal activities of eleven C21-steroidal compounds isolated from Cynanchum wilfordii, together with thirty-six derivatives of caudatin and qingyangshengenin were evaluated on Sclerotinia sclerotiorum and other five fungal strains by the mycelium growth rate method. Four derivatives 1k, 1y, 10d, and 10j exhibited much stronger inhibitions on growth of S. sclerotiorum with IC50 values of 0.0084, 0.0049, 0.0053, and 0.0034μM, respectively. PMID:26947608

  17. Antifungal steroidal glycosides from the patagonian starfish anasteriasminuta: structure-activity correlations.

    PubMed

    Chludil, Hugo D; Seldes, Alicia M; Maier, Marta S

    2002-02-01

    Two new sulfated steroidal hexaglycosides, anasterosides A (2) and B (3), along with the known versicoside A (1) have been isolated from the Patagonian starfish Anasterias minuta. Their structures have been elucidated by spectroscopic analysis (NMR and FABMS) and chemical transformations. Compounds 1 and 2 and the synthetic pentaglycoside 1b derived from versicoside A showed antifungal activity against the plant pathogenic fungus Cladosporium cucumerinum. Desulfation of hexaglycoside 1 rendered a totally inactive saponin. PMID:11858747

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

    PubMed

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

    2014-10-01

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

  19. Local modulation of steroid action: rapid control of enzymatic activity

    PubMed Central

    Charlier, Thierry D.; Cornil, Charlotte A.; Patte-Mensah, Christine; Meyer, Laurence; Mensah-Nyagan, A. Guy; Balthazart, Jacques

    2015-01-01

    Estrogens can induce rapid, short-lived physiological and behavioral responses, in addition to their slow, but long-term, effects at the transcriptional level. To be functionally relevant, these effects should be associated with rapid modulations of estrogens concentrations. 17β-estradiol is synthesized by the enzyme aromatase, using testosterone as a substrate, but can also be degraded into catechol-estrogens via hydroxylation by the same enzyme, leading to an increase or decrease in estrogens concentration, respectively. The first evidence that aromatase activity (AA) can be rapidly modulated came from experiments performed in Japanese quail hypothalamus homogenates. This rapid modulation is triggered by calcium-dependent phosphorylations and was confirmed in other tissues and species. The mechanisms controlling the phosphorylation status, the targeted amino acid residues and the reversibility seem to vary depending of the tissues and is discussed in this review. We currently do not know whether the phosphorylation of the same amino acid affects both aromatase and/or hydroxylase activities or whether these residues are different. These processes provide a new general mechanism by which local estrogen concentration can be rapidly altered in the brain and other tissues. PMID:25852459

  20. Four New Sulfated Polar Steroids from the Far Eastern Starfish Leptasterias ochotensis: Structures and Activities

    PubMed Central

    Malyarenko, Timofey V.; Malyarenko (Vishchuk), Olesya S.; Ivanchina, Natalia V.; Kalinovsky, Anatoly I.; Popov, Roman S.; Kicha, Alla A.

    2015-01-01

    Three new sulfated steroid monoglycosides, leptaochotensosides A–C (1–3), and a new sulfated polyhydroxylated steroid (4) were isolated from the alcoholic extract of the Far Eastern starfish Leptasterias ochotensis. The structures of compounds 1–4 were established by extensive nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESIMS) analyses and chemical transformations. Although the isolated compounds did not show any apparent cytotoxicity against melanoma RPMI-7951 and breast cancer T-47D cell lines, leptaochotensoside A (1) demonstrated inhibition of T-47D cell colony formation in a soft agar clonogenic assay at nontoxic doses. In addition, this compound decreased the epidermal growth factor (EGF)-induced colony formation of mouse epidermal JB6 Cl41 cells. The cancer preventive action of 1 is realized through regulation of mitogen-activated protein kinase (MAPK) signaling pathway. PMID:26193286

  1. Chemistry and biological activity of steroidal glycosides from the Lilium genus.

    PubMed

    Munafo, John P; Gianfagna, Thomas J

    2015-03-01

    Plants from the Lilium genus are a rich source of chemical diversity and have been the focus of natural products chemistry research for over twenty years. This manuscript provides a background on the chemistry and nomenclature of steroidal glycosides, as well as a chronological account of the progress between the years of 1989 up to 2014, with respect to their isolation and characterization from the genus. This review highlights the traditional use of lilies, as both food and medicine, and brings attention to the fact that the genus contains 110 accepted species of which the chemistry and biological activity of the steroidal glycosides from the majority have not been investigated to date. Thus, making the genus a relatively untapped resource that contains a potential treasure trove of chemical diversity waiting to be discovered. PMID:25407469

  2. 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. PMID:26006336

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

    PubMed

    Morrow, C J; Monfort, S L

    1998-10-01

    Ultrasonography and radioimmunoassay (RIA) of serum oestradiol-17beta, luteinizing hormone (LH) and progesterone, and faecal oestrogen and progestin was used to assess ovarian activity in the scimitar-horned oryx (Oryx dammah). Ovarian examination using ultrasonography revealed maximal follicle and corpus luteum (CL) diameters of 15 and 32 mm, respectively. Steroid hormone metabolite distribution among individual faecal pellets within the same defaecation was relatively homogeneous with coefficients of variation averaging 10.2+/-1.8% and 16.2+/-4.6% for oestrogens and progestins, respectively. Elevated faecal oestrogen concentrations were associated with large (> 10 mm) antral follicles detected by ultrasonography. Periovulatory peaks in faecal oestrogen excretion, coincident with nadirs in progestin excretion, were detected in three females. Faecal progestin excretion exhibited a similar temporal pattern to serum progesterone concentrations, with a time lag of approximately 16 h. Faecal progestin concentrations corresponded with the presence of functional CL and proved useful for monitoring luteal function, spontaneous and prostaglandin-F2alpha analogue-induced luteolysis and anovulation. In summary, faecal steroid monitoring is a practical, noninvasive method for characterising ovarian steroid excretion and has potential for facilitating the application of assisted reproductive technologies in scimitar-horned oryx. PMID:9835376

  4. Evaluation of plasma enzyme activities using gas chromatography-mass spectrometry based steroid signatures.

    PubMed

    Ha, Young Wan; Moon, Ju-Yeon; Jung, Hyun-Jin; Chung, Bong Chul; Choi, Man Ho

    2009-12-15

    The simultaneous quantification of 65 plasma steroids, including 22 androgens, 15 estrogens, 15 corticoids and 13 progestins, was developed using gas chromatography-mass spectrometry (GC-MS). The extraction efficiency of the catechol estrogens was improved by the addition of l-ascorbic acid in several steps. All steroids, as their trimethylsilyl derivatives, were well separated with good peak shapes within a 50min run. The devised method provided good linearity (correlation coefficient, r(2)>0.993), while the limit of quantification ranged from 0.2 to 2.0ngmL(-1). The precision (% CV) and accuracy (% bias) were 2.0-12.4% and 93.5-109.2%, respectively. The metabolic changes were evaluated by applying this method to plasma samples obtained from 26 healthy male subjects grouped according to the pre- and post-administration of dutasteride, which inhibits 5alpha-reductase isoenzyme types 1 and 2. The levels of three plasma steroids, such as dihydrotestosterone, 5alpha-androstanedione and allotetrahydrocortisol, were decreased significantly after drug administration, while the levels of testosterone and 5beta-androstane-3beta,17alpha-diol were increased. In addition, the ratios of the steroid precursors and their metabolites, which represent the activities of the related enzymes, were z-score transformed for visualization in heat maps generated using supervised hierarchical clustering analysis. These results validated the data transformation because 5alpha-reductase is an indicator for the biological actions of dutasteride. GC-MS base quantitative visualization might be found in the integration with the mining biomarkers in drug evaluations and hormone-dependent diseases. PMID:19939750

  5. Paradoxical effects of GABA-A modulators may explain sex steroid induced negative mood symptoms in some persons.

    PubMed

    Bäckström, T; Haage, D; Löfgren, M; Johansson, I M; Strömberg, J; Nyberg, S; Andréen, L; Ossewaarde, L; van Wingen, G A; Turkmen, S; Bengtsson, S K

    2011-09-15

    Some women have negative mood symptoms, caused by progestagens in hormonal contraceptives or sequential hormone therapy or by progesterone in the luteal phase of the menstrual cycle, which may be attributed to metabolites acting on the GABA-A receptor. The GABA system is the major inhibitory system in the adult CNS and most positive modulators of the GABA-A receptor (benzodiazepines, barbiturates, alcohol, GABA steroids), induce inhibitory (e.g. anesthetic, sedative, anticonvulsant, anxiolytic) effects. However, some individuals have adverse effects (seizures, increased pain, anxiety, irritability, aggression) upon exposure. Positive GABA-A receptor modulators induce strong paradoxical effects including negative mood in 3%-8% of those exposed, while up to 25% have moderate symptoms. The effect is biphasic: low concentrations induce an adverse anxiogenic effect while higher concentrations decrease this effect and show inhibitory, calming properties. The prevalence of premenstrual dysphoric disorder (PMDD) is also 3%-8% among women in fertile ages, and up to 25% have more moderate symptoms of premenstrual syndrome (PMS). Patients with PMDD have severe luteal phase-related symptoms and show changes in GABA-A receptor sensitivity and GABA concentrations. Findings suggest that negative mood symptoms in women with PMDD are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A receptor, which may be explained by one or more of three hypotheses regarding the paradoxical effect of GABA steroids on behavior: (1) under certain conditions, such as puberty, the relative fraction of certain GABA-A receptor subtypes may be altered, and at those subtypes the GABA steroids may act as negative modulators in contrast to their usual role as positive modulators; (2) in certain brain areas of vulnerable women the transmembrane Cl(-) gradient may be altered by factors such as estrogens that favor excitability; (3) inhibition of inhibitory neurons may promote

  6. Steroidal glycosides from the underground parts of Yucca glauca and their cytotoxic activities.

    PubMed

    Yokosuka, Akihito; Suzuki, Tomoka; Tatsuno, Satoru; Mimaki, Yoshihiro

    2014-05-01

    Six steroidal glycosides and 14 known compounds were isolated from the underground parts of Yucca glauca (Agavaceae). Their structures were determined from extensive spectroscopic analysis, including analysis of two-dimensional NMR data, and from chemical transformations. The compounds were also evaluated for cytotoxic activities against HL-60 human leukemia cells and A549 human lung adenocarcinoma cells. Four spirostanol glycosides and three furostanol glycosides exhibited cytotoxic activities against both HL-60 and A549 cells. Two of the compounds induced apoptosis in HL-60 cells. PMID:24612536

  7. [Composition and biological activity of triterpenes and steroids from Inonotus obliquus (chaga)].

    PubMed

    Nikitina, S A; Khabibrakhmanova, V R; Sysoeva, M A

    2016-05-01

    Data on the chemical composition of triterpenic and steroid compounds, isolated from the chaga mushroom grown in natural environment or in a synthetic culture have been summarized. Special attention has been paid to the biological activity of chaga mushroom extracts and these particular compounds against various cancer cell lines in vitro and in vivo. This analysis has demonstrated some common features in inhibition of growth of various cell lines by chaga mushroom components. In this context, the most active are triterpene compounds containing OH group at C-22 and a side chain unsaturated bond. PMID:27562990

  8. 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. PMID:25588539

  9. 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

  10. Sex-Steroid Regulation of Relaxin Receptor Isoforms (RXFP1 & RXFP2) Expression in the Patellar Tendon and Lateral Collateral Ligament of Female WKY Rats

    PubMed Central

    Dehghan, Firouzeh; Muniandy, Sekaran; Yusof, Ashril; Salleh, Naguib

    2014-01-01

    The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee. Methods: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively. Results: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms. Discussion: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee. Conclusion: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male. PMID:24465164

  11. Profiles of sex steroids, fecundity and spawning of a migratory characiform fish from the Paraguay-Paraná basin: a comparative study in a three-river system.

    PubMed

    Perini, Violeta da Rocha; Paschoalini, Alessandro Loureiro; Cruz, Cláudia Kelly Fernandes da; Rocha, Rita de Cássia Gimenes Alcântara de; Senhorini, José Augusto; Ribeiro, Dirceu Marzulo; Formagio, Paulo Sérgio; Bazzoli, Nilo; Rizzo, Elizete

    2013-12-01

    This study investigated for the first time the reproductive biology of Prochilodus lineatus in a system of rivers in southeastern Brasil, relating it to the role of tributary rivers in the reproductive success of this important commercial fish in the Upper Paraná River basin, where a cascade of hydroelectric dams were deployed. Specimens were caught bimonthly in three river sites: (S1) Grande River, downstream from the Porto Colômbia dam; (S2) Pardo River; and (S3) Mogi Guaçu River. Sex steroid plasma levels, fecundity, follicular atresia, oocyte diameter and gonadosomatic index (GSI) were compared among sites. In S1, fish exhibited changes in the reproductive parameters: lower GSI, oocyte diameter and fecundity and higher follicular atresia index, when compared to S2 and S3. Frequency of maturing fish was higher in S3 and spawning was only registered in S3. In sites S2 and S3, plasma concentrations of testosterone and 17β-estradiol in females and testosterone in males showed wide variations following gonadal maturation. Fish from S1 showed few significant variations in sex steroid concentrations throughout the gonadal cycle. These results indicate that P. lineatus does not reproduce in Grande River (S1), but probably uses the Pardo River (S2) as a migratory route towards the Mogi Guaçu River (S3) where they complete gonadal maturation and spawning. Our findings contribute for understanding the reproductive biology of P. lineatus and to highlight the importance of tributaries in impounded rivers as a favourable environment for migration and spawning of fish. PMID:23616136

  12. Effects of sex steroid hormones and their metabolites on neuronal injury caused by oxygen-glucose deprivation/reoxygenation in organotypic hippocampal slice cultures.

    PubMed

    Ishihara, Yasuhiro; Fujitani, Noriko; Sakurai, Hikaru; Takemoto, Takuya; Ikeda-Ishihara, Nami; Mori-Yasumoto, Kanami; Nehira, Tatsuo; Ishida, Atsuhiko; Yamazaki, Takeshi

    2016-09-01

    In this study, protective actions of the sex steroid hormones, progesterone, testosterone, and 17β-estradiol, against oxygen-glucose deprivation (OGD)/reoxygenation-induced neuronal cell death were examined using rat organotypic hippocampal slice cultures. Progesterone, testosterone, and 17β-estradiol significantly attenuated neuronal cell death elicited by OGD/reoxygenation. While the neuroprotection conferred by progesterone was not affected by SU-10603, an inhibitor of cytochrome P45017α, finasteride, a 5α-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone, partially reversed the neuroprotection induced by progesterone. The progesterone metabolite, allopregnanolone attenuated neuronal injury induced by OGD/reoxygenation. Pretreatment with letrozole, a cytochrome P450 aromatase inhibitor or 4-hydroxyphenyl-1-naphthol, a 17β-hydroxysteroid dehydrogenase 2 inhibitor showed no effect on testosterone-mediated neuroprotection, while finasteride completely abolished the protective action of testosterone. Treatment with 5α-dihydrotestosterone significantly suppressed neuronal injury. Pretreatment with mifepristone, a progesterone receptor antagonist and hydroxyflutamid, an androgen receptor antagonist significantly diminished the neuroprotective effects of progesterone and testosterone, respectively. ICI182,780, an estrogen receptor antagonist, showed no effect on neuroprotection mediated by 17β-estradiol. Pretreatment with actinomycin D or cycloheximide clearly abolished the neuroprotective effects of progesterone and testosterone, while actinomycin D and cycloheximide did not show any effect on neuroprotection mediated by 17β-estradiol. Taken together, progesterone protects neurons via progesterone receptor-dependent genomic pathway, and allopregnanolone is involved in progesterone-mediated neuroprotection. Testosterone and its metabolite 5α-dihydrotestosterone protect neurons via the genomic pathway of the androgen receptor

  13. 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

  14. Steroids with anti-inflammatory activity from Vernonia nigritiana Oliv. & Hiern.

    PubMed

    Vassallo, Antonio; De Tommasi, Nunziatina; Merfort, Irmgard; Sanogo, Rokia; Severino, Lorella; Pelin, Marco; Della Loggia, Roberto; Tubaro, Aurelia; Sosa, Silvio

    2013-12-01

    The leaves of Vernonia nigritiana Oliv. & Hiern. (Asteraceae) were investigated for their in vivo topical anti-inflammatory properties, following a bioassay-oriented fractionation approach. Petroleum ether, chloroform and chloroform-methanol extracts inhibited the Croton oil-induced ear dermatitis in mice. The chloroform extract was only about half as active as the non steroidal anti-inflammatory drug indomethacin (ID50=237 and 93 μg/cm(2), respectively). Phytochemical investigation of this extract led to the isolation of nine polyhydroxylated stigmasterol glycosides and six polyhydroxylated stigmasterols. Their structures were elucidated by NMR, MS and chemical methods. Each compound exerted a significant anti-oedema activity, the most active being 1 (3β-O-β-D-glucopyranosyloxy-5α-stigmasta-7,9(11),24(28)Z-triene-6β,16β,26,29-tetrol) and 3 (3β-O-β-D-glucopyranosyloxy-5α-stigmasta-7,9(11),24(28)Z-triene-6β,16β,29-triol), only two and five fold less potent than the steroidal drug hydrocortisone (ID50=0.10, 0.21 and 0.04 μmol/cm(2), respectively). Compound 1 (50 μM) also completely inhibited the transcription factor NF-κB in vitro. PMID:24074552

  15. Reproductive periodicity and steroid hormone profiles in the sex-changing coral-reef fish, Plectropomus leopardus

    NASA Astrophysics Data System (ADS)

    Frisch, A. J.; McCormick, M. I.; Pankhurst, N. W.

    2007-03-01

    The reproductive biology of coral trout, Plectropomus leopardus, from the Great Barrier Reef (Australia) was investigated by correlating gonadal condition with plasma levels of gonadal steroids. Female fish were found to be regressed from mid-summer to early spring, after which rapid and cyclical increases in gonado-somatic index ( I G), maximum oocyte diameter (MOD) and plasma concentrations of estradiol-17β and testosterone were detected. Male fish, in contrast, commenced recrudescence slightly earlier in winter and responded with less dramatic increases in both I G and plasma concentrations of testosterone and 11-ketotestosterone. The mode of oocyte development was multiple group-synchronous, and cyclical fluctuations in reproductive parameters ( I G, MOD and gonadal steroid concentrations) were synchronized with new-moon lunar phases. It is likely, therefore, that individual P. leopardus have the capacity to spawn on multiple occasions, with lunar periodicity. However, evidence suggests that early bouts of reproduction may be more important in terms of reproductive investment than subsequent bouts later in the same season. It is concluded that patterns of gametogenesis and steroidogenesis in P. leopardus are similar to the patterns displayed by other tropical groupers, suggesting that management regimes and propagation protocols developed for these fishes may also be appropriate for use with P. leopardus.

  16. Identification and steroid receptor activity of products formed from the bromination of technical nonylphenol.

    PubMed

    Hill, Elizabeth M; Smith, Michael D

    2006-09-01

    Alkylphenols are commonly present in wastewater effluents and may contribute to the total hormonal loading of receiving waters due to their weakly estrogenic properties. However the presence of reactive bromine species in some treated wastewaters can result in the formation of brominated alkylphenols which may also possess steroid receptor activity. In this study, the products of bromination of technical nonylphenol (NP) were identified, purified and tested in vitro in recombinant yeast steroid receptor transcription assays. Bromination of NP in the presence of acetic acid resulted in the formation of one major product which was identified as 2-bromo-4-nonylphenol (NPBr). In the presence of methanol/water, bromination of NP resulted in the formation 2,6-dibromo-4-nonylphenol (NPBr2) as well as a number of other minor polybrominated products. The EC50 of NPBr in the yeast estrogen receptor transcription (YES) assay was 6.7x10(-6) M, which was 48 fold less active than NP and 86,000 fold less active than the estrogen agonist 17beta-estradiol NPBr2 was not active in the YES assay. NP, NPBr and NPBr2 were all weakly androgenic in the yeast androgen receptor transcription assay but at concentrations which were 100,000 fold less active than the androgen receptor agonist dihydrotestosterone. Neither NP, NPBr or NPBr2 exhibited appreciable anti-estrogenic or anti-androgenic activity in the yeast receptor transcription assays. This study suggests that bromination of NP markedly reduces its estrogen receptor transcription activity but has no effect on the weak androgen receptor transcription activity of the alkylphenol. PMID:16473392

  17. 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

  18. Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2-a]pyridines.

    PubMed

    Rassokhina, Irina V; Volkova, Yulia A; Kozlov, Andrey S; Scherbakov, Alexander M; Andreeva, Olga E; Shirinian, Valerik Z; Zavarzin, Igor V

    2016-09-01

    An elegant approach to unknown steroidal imidazo[1,2-a]pyridine hybrids is disclosed. Unique derivatives of androstene and estrane series containing imidazo[1,2-a]pyridine motifs were prepared from 17-ethynyl steroids in good yields via copper-catalyzed cascade aminomethylation/cycloisomerization with imines. The synthesized compounds were screened for cytotoxicity against human breast (MCF-7, MDA-MB-231, HBL-100, MDA-MB-453) and prostate (LNCaP-LN3, PC-3, DU 145) cancer cell lines. The majority of tested compounds showed activities at μM level in breast cancer cells. The hormone-responsive breast cancer cells MCF-7 were more sensitive to novel compounds than ERα-negative cells; in particular, compounds 6a,b exhibited promising cytotoxicity against this cell line with the IC50 values in the range of 3-4μM. Furthermore, compound 4a showed remarkable effects as a selective ERα receptor modulator. PMID:27263438

  19. Design, synthesis and cytotoxic activity of a novel series of steroidal phenylpyrazoles.

    PubMed

    Li, Jian; Zhao, Ximei; Li, Longbo; Yuan, Zhipeng; Tan, Fangfang; Shi, Baojun; Zhang, Jiwen

    2016-03-01

    Thirty novel steroidal pyrazole derivatives were designed and synthesized via a highly efficient route from pregnenolone (1) as starting material. The key intermediates 3a-c were obtained under Vilsmeier conditions, and the subsequent hydrolysis, acetylation or Borch reduction afforded thirty target compounds. These compounds were mainly characterized by (1)H NMR, (13)C NMR, DEPT135°. The structure of compound 3a was also confirmed by X-ray single crystal diffraction. The cytotoxicity of these compounds was evaluated by the SRB method against four cancer cell lines, including A549, Hela, MCF-7 and HepG2, and the results indicated that compounds 5a, 6a, 7a and 8a exhibited significant cytotoxicity with IC50 values ranging from 0.91 to 5.44 μM. Most importantly, compound 5a exhibited excellent cytotoxicity against A549 with an IC50 value of 0.91 μM. On the basis of our research the structure-activity relationships (SAR) of these compounds were discussed. This work provides some important hints for further structural modification of steroids towards developing novel and highly effective anticancer drugs. PMID:26742627

  20. Arsenic disruption of steroid receptor gene activation: Complex dose-response effects are shared by several steroid receptors.

    PubMed

    Bodwell, Jack E; Gosse, Julie A; Nomikos, Athena P; Hamilton, Joshua W

    2006-12-01

    Chronic intake of arsenic (As) has been associated with increased risk of cancer, diabetes, developmental and reproductive problems, and cardiovascular disease. Recent studies suggest increased health risks with drinking water levels as low as 5-10 ppb. We previously reported that As disrupts glucocorticoid receptor (GR) mediated transcription in a very complex fashion. Low As levels (0.1-0.7 microM) stimulated transcription, whereas slightly higher levels (1-3 microM) were inhibitory. The DNA binding domain (DBD) was the minimal region of GR required for the response to As. Mutations in the DBD that alter the conformation of the dimerization domain (D-loop) to a DNA-bound GR conformation abolished the stimulatory effect and enhanced the inhibitory response to As. Here we report that receptors for progesterone (PR) and mineralocorticoids display a complex As response similar to that of the GR, suggesting a common mechanism for this effect. The complex response to As is not due to altered steroid or receptor levels. Moreover, a well-characterized GR dimerization mutant displayed a wild-type biphasic response to As for several divergent reporter genes, suggesting that dimerization is not critical for the response to As. Fluorescence polarization studies with purified PR and GR demonstrated that the specific PR/GR-DNA interaction is not altered in the presence of As. These results indicate that the numerous and diverse human health effects associated with As exposure may be mediated, at least in part, through its ability to simultaneously disrupt multiple hormone receptor systems. PMID:17173375

  1. Arsenic Disruption of Steroid Receptor Gene Activation: Complex Dose-Response Effects Are Shared by Several Steroid Receptors*

    PubMed Central

    Bodwell, Jack E.; Gosse, Julie A.; Nomikos, Athena P.; Hamilton, Joshua W.

    2008-01-01

    Chronic intake of arsenic (As) has been associated with increased risk of cancer, diabetes, developmental and reproductive problems, and cardiovascular disease. Recent studies suggest increased health risks with drinking water levels as low as 5–10 ppb. We previously reported that As disrupts glucocorticoid receptor (GR) mediated transcription in a very complex fashion. Low As levels (0.1 to 0.7 μM) stimulated transcription whereas slightly higher levels (1 to 3 μM) were inhibitory. The DNA Binding Domain (DBD) was the minimal region of GR required for the response to As. Mutations in the DBD that alter the conformation of the dimerization domain (D-Loop) to a DNA-bound GR conformation abolished the stimulatory effect and enhanced the inhibitory response to As. Here we report that receptors for progesterone (PR) and mineralocorticoids (MR) display a similar complex As response as the GR, suggesting a common mechanism for this effect. The complex response to As is not due to altered steroid or receptor levels. Moreover, a well-characterized GR dimerization mutant displayed a wild-type biphasic response to As for several divergent reporter genes, suggesting that dimerization is not critical for the response to As. Fluorescence polarization studies with purified PR and GR demonstrated that the specific PR/GR-DNA interaction is not altered in the presence of As. These results indicate that the numerous and diverse human health effects associated with As exposure maybe mediated, at least in part, through its ability to simultaneously disrupt multiple hormone receptor systems. PMID:17173375

  2. 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

  3. Sex-dependent alterations in BDNF-TrkB signaling in the hippocampus of reelin heterozygous mice: a role for sex steroid hormones.

    PubMed

    Hill, Rachel A; Wu, Yee-Wen Candace; Gogos, Andrea; van den Buuse, Maarten

    2013-08-01

    Neurodevelopmental psychiatric disorders such as schizophrenia may be caused by a combination of gene × environment, gene × gene, and/or gene × sex interactions. Reduced expression of both Reelin and Brain-Derived Neurotrophic factor (BDNF) has been associated with schizophrenia in human post-mortem studies. However, it remains unclear how Reelin and BDNF interact (gene × gene) and whether this is sex-specific (gene × sex). This study investigated BDNF-TrkB signaling in the hippocampus of male and female Reelin heterozygous (Rln(+/-) ) mice. We found significantly increased levels of BDNF in the ventral hippocampus (VHP) of female, but not male Rln(+/-) compared to wild-type (WT) controls. While levels of TrkB were not significantly altered, phosphorylated TrkB (pTrkB) levels were significantly lower, again only in female Rln(+/-) compared to WT. This translated to downstream effects with a significant decrease in phosphorylated ERK1 (pERK1). No changes in BDNF, TrkB, pTrkB or pERK1/2 were observed in the dorsal hippocampus of Rln(+/-) mice. Ovariectomy (OVX) had no effect in WT controls, but caused a significant decrease in BDNF expression in the VHP of Rln(+/-) mice to the levels of intact WT controls. The high expression of BDNF was restored in OVX Rln(+/-) mice by 17β-estradiol treatment, suggesting that Rln(+/-) mice respond differently to an altered estradiol state than WT controls. In addition, while OVX had no significant effect on TrkB or ERK expression/phosphorylation, OVX + estradiol treatment markedly increased TrkB and ERK1 phosphorylation in Rln(+/-) and, to a lesser extent in WT controls, compared to intact genotype-matched controls. These data may provide a better understanding of the interaction of Reelin and BDNF in the hippocampus, which may be involved in schizophrenia. PMID:23414458

  4. Race and Sex Differences in College Student Physical Activity Correlates

    ERIC Educational Resources Information Center

    McArthur, Laura H.; Raedeke, Thomas D.

    2009-01-01

    Objectives: To assess sex/race differences on psychosocial correlates of physical activity among college students. Methods: Survey research protocol. Results: Students (n = 636) exercised an average of 3.5 days per week, with black females being the least active. Across subgroups, health/fitness was rated as the most important motive for exercise,…

  5. Synthesis, stereochemistry and cytotoxic activity of novel steroidal 16-spiro-1,3,2-dioxaphosphorinanes

    NASA Astrophysics Data System (ADS)

    Wölfling, János; Kovács-Pénzes, Piroska; Zupkó, István; Schneider, Gyula; Frank, Éva

    2012-04-01

    The epimeric pairs a and b of novel steroidal 16-spiro-dioxaphosphorinanes 4-8 were synthetized via the phosphorylation of 16,16-bis(hydroxymethyl)androst-4-ene-3,17-dione (2) and their stereostructures were investigated by NMR methods. The dioxaphosphorinane moiety exists mainly as one of the possible chair conformers or as a chair-twist equilibrium in solution as a consequence of the rigidity of the sterane framework. The contributions of the conformers depend strongly on the configuration of the P atom and the stereoelectronic properties of the substituents on it. The antiproliferative activities of the structurally related products were determined in vitro with the MTT assay on three malignant human cell lines (HeLa, MCF7 and A431).

  6. Solanum incanum and S. heteracanthum as sources of biologically active steroid glycosides: confirmation of their synonymy.

    PubMed

    Manase, Mahenina Jaovita; Mitaine-Offer, Anne-Claire; Pertuit, David; Miyamoto, Tomofumi; Tanaka, Chiaki; Delemasure, Stéphanie; Dutartre, Patrick; Mirjolet, Jean-François; Duchamp, Olivier; Lacaille-Dubois, Marie-Aleth

    2012-09-01

    A new spirostanol saponin (1), along with four known saponins, dioscin (2), protodioscin (3), methyl-protodioscin (4), and indioside D (5), and one known steroid glycoalkaloid solamargine (6) were isolated from the two synonymous species, Solanum incanum and S. heteracanthum. The structure of the new saponin was established as (23S,25R)-spirost-5-en-3β,23-diol 3-O-{β-D-xylopyranosyl-(1→2)-O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside}, by using a combination of 1D and 2D NMR techniques including (1)H, (13)C, COSY, TOCSY, NOESY, HSQC and HMBC experiments and by mass spectrometry. The compounds 1, 3, 4 and 5 were evaluated for cytotoxicity against five cancer cell lines and for antioxidant and cytoprotective activity. PMID:22579841

  7. 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

  8. The effects of pulp mill effluent on the sex steroid binding protein in white sucker (Catostomus commersoni) and longnose sucker (C catostomus).

    PubMed

    Pryce-Hobby, A C; McMaster, M E; Hewitt, L M; Van Der Kraak, G

    2003-02-01

    The objective of this study was to characterize the effects of pulp mill effluent on the properties of the sex steroid binding protein (SBP) in the plasma of white sucker (Catostomus commersoni) and longnose sucker (C. catostomus). SBPs which specifically bind estradiol and testosterone with high affinity (k(D) approximately 3 nM) and low capacity (B(max) approximately 73-81 nM) were identified in both species. Subsequent studies determined if the properties of the SBP in white sucker exposed to bleached kraft mill effluent (BKME) at Terrace Bay, ON, and in longnose sucker exposed to BKME at Grande Prairie, AB. differed from appropriate reference fish. There were no effects of BKME exposure on the binding affinity (k(D)) of the SBP in either species, but there was a significant increase in the binding capacity (B(max)) of longnose sucker SBP exposed to BKME. The livers of nai;ve white sucker exposed to effluent at Terrace Bay or a bleached sulfite/groundwood mill in Edmundston, NB, rapidly accumulated compounds of differing hydrophobicity that bound to both the white sucker and goldfish (Carassius auratus) SBP. Conversely, there was reduced accumulation of SBP ligands in the bile of effluent-exposed fish. We have demonstrated that constituents present within pulp mill effluent bind to both the white sucker and goldfish SBP, and that native species residing downstream of pulp mill effluents may experience modifications in the properties of their SBP. PMID:12600684

  9. [Regulation of the differentiation and proliferation of smooth muscle cells by the sex hormones].

    PubMed

    Guiochon-Mantel, A

    2000-06-01

    Steroids effects are mediated by their receptors. These proteins define the large family of steroid hormone receptors, characterized by the presence of 3 functional domains: a transactivation domain, a DNA-binding domain and a ligand-binding domain. Receptor activation induces the modulation of transcription of specific genes, and as a consequence, the modulation of production of specific proteins. Sex steroid receptors are located in the nucleus. This nuclear localization is in fact a dynamic situation, resulting from a continuous shuttling of the receptor between the cytoplasm and the nucleus. The recent discovery that an additional estrogen receptor is present in various tissues has advanced our understanding of the mechanism underlying estrogen signalling. Non genomic effects of steroids have also been described. Sex steroids inhibit proliferation of smooth muscle cells. On the contrary, they stimulate proliferation of tumoral muscle cells. The mechanisms of sex steroid effects on cellular proliferation are complex, and may involve transcriptional or non transcriptional phenomena. PMID:10939122

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

    EPA Science Inventory

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

  11. New evidence of similarity between human and plant steroid metabolism: 5alpha-reductase activity in Solanum malacoxylon.

    PubMed

    Rosati, Fabiana; Danza, Giovanna; Guarna, Antonio; Cini, Nicoletta; Racchi, Milvia Luisa; Serio, Mario

    2003-01-01

    The physiological role of steroid hormones in humans is well known, and the metabolic pathway and mechanisms of action are almost completely elucidated. The role of plant steroid hormones, brassinosteroids, is less known, but an increasing amount of data on brassinosteroid biosynthesis is showing unexpected similarities between human and plant steroid metabolic pathways. Here we focus our attention on the enzyme 5alpha-reductase (5alphaR) for which a plant ortholog of the mammalian system, DET2, was recently described in Arabidopsis thaliana. We demonstrate that campestenone, the natural substrate of DET2, is reduced to 5alpha-campestanone by both human 5alphaR isozymes but with different affinities. Solanum malacoxylon, which is a calcinogenic plant very active in the biosynthesis of vitamin D-like molecules and sterols, was used to study 5alphaR activity. Leaves and calli were chosen as examples of differentiated and undifferentiated tissues, respectively. Two separate 5alphaR activities were found in calli and leaves of Solanum using campestenone as substrate. The use of progesterone allowed the detection of both activities in calli. Support for the existence of two 5alphaR isozymes in S. malacoxylon was provided by the differential actions of inhibitors of the human 5alphaR in calli and leaves. The evidence for the presence of two isozymes in different plant tissues extends the analogies between plant and mammalian steroid metabolic pathways. PMID:12488348

  12. The steroidal analog GW707 activates the SREBP pathway through disruption of intracellular cholesterol trafficking.

    PubMed

    Zhang, Jessie; Dudley-Rucker, Nicole; Crowley, Jan R; Lopez-Perez, Elvira; Issandou, Marc; Schaffer, Jean E; Ory, Daniel S

    2004-02-01

    Recently, a new class of lipid-lowering agents has been described that upregulate LDL receptor (LDLr) activity. These agents are proposed to activate sterol-regulated gene expression through binding to the sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP). Here, we show that the steroidal LDLr upregulator, GW707, induces accumulation of lysosomal free cholesterol and inhibits LDL-stimulated cholesterol esterification, similar to that observed in U18666A-treated cells and in Niemann-Pick type C1 (NPC1) mutants. Moreover, we demonstrate that induction of the NPC-like phenotype by GW707 is independent of SCAP function. We find that treatment with GW707 does not increase SREBP-dependent gene expression above that observed in lipoprotein-starved cells. Rather, we show that the apparent increase in SREBP-dependent activity in GW707-treated cells is attributable to a failure to appropriately suppress sterol-regulated gene expression, as has been shown previously for U18666A-treated cells and NPC mutant fibroblasts. We further demonstrate that cells treated with either GW707 or U18666A fail to appropriately generate 27-hydroxycholesterol in response to LDL cholesterol. Taken together, these findings support a mechanism in which GW707 exerts its hypolipidemic effects through disruption of late endosomal/lysosomal sterol trafficking and subsequent stimulation of LDLr activity. PMID:14617742

  13. 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

  14. Mechanisms of peroxisome proliferator activated receptor γ regulation by non-steroidal anti-inflammatory drugs

    PubMed Central

    Puhl, Ana C.; Milton, Flora A.; Cvoro, Aleksandra; Sieglaff, Douglas H.; Campos, Jéssica C.L.; Bernardes, Amanda; Filgueira, Carly S.; Lindemann, Jan Lammel; Deng, Tuo; Neves, Francisco A.R.; Polikarpov, Igor; Webb, Paul

    2015-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) display anti-inflammatory, antipyretic and analgesic properties by inhibiting cyclooxygenases and blocking prostaglandin production. Previous studies, however, suggested that some NSAIDs also modulate peroxisome proliferator activated receptors (PPARs), raising the possibility that such off target effects contribute to the spectrum of clinically relevant NSAID actions. In this study, we set out to understand how peroxisome proliferator activated receptor-γ (PPARγ/PPARG) interacts with NSAIDs using X-ray crystallography and to relate ligand binding modes to effects on receptor activity. We find that several NSAIDs (sulindac sulfide, diclofenac, indomethacin and ibuprofen) bind PPARγ and modulate PPARγ activity at pharmacologically relevant concentrations. Diclofenac acts as a partial agonist and binds to the PPARγ ligand binding pocket (LBP) in typical partial agonist mode, near the β-sheets and helix 3. By contrast, two copies of indomethacin and sulindac sulfide bind the LBP and, in aggregate, these ligands engage in LBP contacts that resemble agonists. Accordingly, both compounds, and ibuprofen, act as strong partial agonists. Assessment of NSAID activities in PPARγ-dependent 3T3-L1 cells reveals that NSAIDs display adipogenic activities and exclusively regulate PPARγ-dependent target genes in a manner that is consistent with their observed binding modes. Further, PPARγ knockdown eliminates indomethacin activities at selected endogenous genes, confirming receptor-dependence of observed effects. We propose that it is important to consider how individual NSAIDs interact with PPARγ to understand their activities, and that it will be interesting to determine whether high dose NSAID therapies result in PPAR activation. PMID:26445566

  15. Effects of Interviewer's Sex on Children's Gender-Typing Activities.

    ERIC Educational Resources Information Center

    Levy, Gary G.; And Others

    Young children acquire a knowledge of, and beliefs about, gender-roles at a rapid rate. A total of four studies were conducted to examine some of the factors thought to mediate the impact of examiner's sex on children's gender-typed activities and cognitions. The first two studies looked at children's ratings of videotaped male and female adults…

  16. Topical Steroids.

    PubMed

    Oakley, Gretchen M; Harvey, Richard J

    2016-01-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition with heterogeneous pathophysiology. A cornerstone of the management of this condition is the use of anti-inflammatory agents. Corticosteroids are very effective and the most commonly used, but other drugs with immunodulatory activity such as anti-IL5, doxycycline (Th2), and macrolides (anti-neutrophilic/IL8) have been shown to have efficacy. Although systemic corticosteroids have shown benefit in managing this condition, the frequency of use often required in this condition is associated with significant adverse effects. Topical corticosteroids, particularly when utilized after endoscopic sinus surgery and delivered in a high volume, high pressure manner, provide the desired anti-inflammatory effects with nearly negligible systemic absorption. Studies assessing the long-term use of second generation topical corticosteroids have demonstrated no significant effects on cortisol levels, growth rate, intraocular pressures or lens opacification, or local mucosal atrophy. Patients who often respond most favorably to corticosteroid treatment are those with a Th2-mediated, highly eosinophilic CRSwNP. However, there is a subset of patients who are steroid resistant. In the case of a predominantly neutrophilic CRSwNP, it is important to be aware that patients may respond well to the use of macrolide therapy. Additionally, the use of verapamil has shown promise in increasing steroid responsiveness in a difficult to treat group of patients with steroid resistance. Topical corticosteroids play a key role in the long term management of this complicated inflammatory condition by providing the much needed pharmacologic local control with minimal systemic adverse effects. PMID:27466854

  17. Steroid-induced protein synthesis in giant-toad (Bufo marinus) urinary bladders. Correlation with natriferic activity.

    PubMed Central

    Geheb, M; Alvis, R; Owen, A; Hercker, E; Cox, M

    1984-01-01

    We have identified a group of proteins (Mr approximately 70 000-80 000; pI approximately 5.5-6.0) in giant-toad (Bufo marinus) urinary bladders whose synthesis appears to be related to aldosterone-stimulated Na+ transport. Spironolactone, a specific mineralocorticoid antagonist in renal epithelia, inhibits the synthesis of these proteins as well as the natriferic effect of the hormone. Since a variety of other steroids (some of which are traditionally considered to be glucocorticoids) also stimulate Na+ transport in toad urinary bladders, we examined whether their natriferic activity was expressed in a fashion similar to that of aldosterone. Short-circuit current was used to measure Na+ transport, and epithelial-cell protein synthesis was detected with high-resolution two-dimensional polyacrylamide-gel electrophoresis and autoradiography. At a concentration of approximately 100 nM, dexamethasone, corticosterone and aldosterone were equinatriferic. Dexamethasone and aldosterone had identical dose-response curves, maximal and half-maximal activity being evident at concentrations of approximately 100 nM and 10 nM respectively. In contrast, at a concentration of approximately 10 nM, corticosterone had no effect on Na+ transport. The natriferic activities of these three steroids correlate with their known affinities for the putative mineralocorticoid receptor in toad urinary bladders. Natriferic concentrations of dexamethasone and corticosterone (140 nM) induced the synthesis of proteins with characteristics identical with those induced by aldosterone. Spironolactone, at an antagonist/agonist ratio of 2000:1, inhibited steroid-induced Na+ transport and the synthesis of these proteins. Thus it appears that all natriferic steroids share a common mechanism of action in toad urinary bladders. Natriferic activity can be correlated not only with relative steroid-receptor affinity but also with the induction of a specific group of epithelial-cell proteins. Images Fig. 1. Fig

  18. Triterpenes and Steroids from Euphorbia denticulata Lam. With Anti-Herpes Symplex Virus Activity.

    PubMed

    Shamsabadipour, Sara; Ghanadian, Mustafa; Saeedi, Hojjatollah; Rahimnejad, Mohammad Reza; Mohammadi-Kamalabadi, Marzieh; Ayatollahi, Seyed Majid; Salimzadeh, Loghman

    2013-01-01

    In this research, dried acetone:chloroform extract of aerial parts of E. denticulata as one of the endemic plants to Iran, afforded a number of triterpenes and steroids including: betulin, 24-methylene-cycloart-3-ol, cycloart-23Z-ene-3β,25-diol, cycloart-23E-ene-3β,25- diol, ergosta-8,24-dien-3-ol (obtusifoliol) and beta-sitosterol which were reported for the first time from this plant. The structure of these compounds was elucidated by NMR and mass spectroscopic methods. The MTS assay was used to determine the toxicity and antiviral activity of betulin and (3β,23E)-cycloarta-23-ene-3,25-diol. Betulin showed anti-HSV-1 activity with EC50 value of 84.37±0.02 μg/mL, and toxicity on normal vero cells with CC50 value of 660.718±0.072 μg/mL. (3β,23E)-Cycloarta-23-ene-3,25-diol showed antiviral effect with EC50 value of 86.63±0.03 μg/mL, and toxicity with CC50 value of 1089.21±0.25 μg/mL. The results revealed that these two compounds have the antiviral activity far below the CC50 value with selectivity index (CC50/EC50) values of 7.83, and 12.57, respectively. PMID:24523756

  19. Triterpenes and Steroids from Euphorbia denticulata Lam. With Anti-Herpes Symplex Virus Activity

    PubMed Central

    Shamsabadipour, Sara; Ghanadian, Mustafa; Saeedi, Hojjatollah; Rahimnejad, Mohammad Reza; Mohammadi-Kamalabadi, Marzieh; Ayatollahi, Seyed Majid; Salimzadeh, Loghman

    2013-01-01

    In this research, dried acetone:chloroform extract of aerial parts of E. denticulata as one of the endemic plants to Iran, afforded a number of triterpenes and steroids including: betulin, 24-methylene-cycloart-3-ol, cycloart-23Z-ene-3β,25-diol, cycloart-23E-ene-3β,25- diol, ergosta-8,24-dien-3-ol (obtusifoliol) and beta-sitosterol which were reported for the first time from this plant. The structure of these compounds was elucidated by NMR and mass spectroscopic methods. The MTS assay was used to determine the toxicity and antiviral activity of betulin and (3β,23E)-cycloarta-23-ene-3,25-diol. Betulin showed anti-HSV-1 activity with EC50 value of 84.37±0.02 μg/mL, and toxicity on normal vero cells with CC50 value of 660.718±0.072 μg/mL. (3β,23E)-Cycloarta-23-ene-3,25-diol showed antiviral effect with EC50 value of 86.63±0.03 μg/mL, and toxicity with CC50 value of 1089.21±0.25 μg/mL. The results revealed that these two compounds have the antiviral activity far below the CC50 value with selectivity index (CC50/EC50) values of 7.83, and 12.57, respectively. PMID:24523756

  20. Selective androgen receptor modulator activity of a steroidal antiandrogen TSAA-291 and its cofactor recruitment profile.

    PubMed

    Hikichi, Yukiko; Yamaoka, Masuo; Kusaka, Masami; Hara, Takahito

    2015-10-15

    Selective androgen receptor modulators (SARMs) specifically bind to the androgen receptor and exert agonistic or antagonistic effects on target organs. In this study, we investigated the SARM activity of TSAA-291, previously known as a steroidal antiandrogen, in mice because TSAA-291 was found to possess partial androgen receptor agonist activity in reporter assays. In addition, to clarify the mechanism underlying its tissue selectivity, we performed comprehensive cofactor recruitment analysis of androgen receptor using TSAA-291 and dihydrotestosterone (DHT), an endogenous androgen. The androgen receptor agonistic activity of TSAA-291 was more obvious in reporter assays using skeletal muscle cells than in those using prostate cells. In castrated mice, TSAA-291 increased the weight of the levator ani muscle without increasing the weight of the prostate and seminal vesicle. Comprehensive cofactor recruitment analysis via mammalian two-hybrid methods revealed that among a total of 112 cofactors, 12 cofactors including the protein inhibitor of activated STAT 1 (PIAS1) were differently recruited to androgen receptor in the presence of TSAA-291 and DHT. Prostate displayed higher PIAS1 expression than skeletal muscle. Forced expression of the PIAS1 augmented the transcriptional activity of the androgen receptor, and silencing of PIAS1 by siRNAs suppressed the secretion of prostate-specific antigen, an androgen responsive marker. Our results demonstrate that TSAA-291 has SARM activity and suggest that TSAA-291 may induce different conformational changes of the androgen receptor and recruitment profiles of cofactors such as PIAS1, compared with DHT, to exert tissue-specific activity. PMID:26335395

  1. Sex pheromones and amino acids evoke distinctly different spatial patterns of electrical activity in the goldfish olfactory bulb.

    PubMed

    Hanson, L R; Sorensen, P W; Cohen, Y

    1998-11-30

    Until now, electrophysiological studies of the vertebrate olfactory bulb have tested only 'generalist' cues. These studies suggest that odorants are discriminated by a broadly distributed spatial map. In this study, we tested for the first time in a vertebrate the hypothesis that 'specialist' cues (pheromones) are discriminated by a more restricted component of the olfactory bulb. Our model is the male goldfish, Carassius auratus, for which five sex pheromones with both behavioral and physiological activity have now been identified. Electrical activity (electroencephalography: EEG) was recorded over a 12-point grid from the surface of the olfactory bulb, while fish were exposed to one of ten stimuli including: five sex pheromones, two amino acids, two bile steroids and a control. Evoked activity was evaluated by time series analysis. Power ratios were calculated by dividing the power of the dominant frequency in the power spectrum before stimulation by the power of the dominant frequency during stimulation. Next, the average magnitudes of odorant responses were compared using analysis of variance (ANOVA). The spatial patterning of these responses was also described using cluster analysis, which grouped odorants based on the similarity of their spatial patterns of activity. Although all odorants elicited EEG responses with similar dominant frequencies, odorant-specific differences were evident in the size and distribution of these responses. Sex pheromones and bile steroids elicited relatively small responses that were spatially restricted in distinctive manners, although some overlap was evident. In contrast, amino acids consistently produced large responses at all positions. These results are consistent with the hypothesis that vertebrate pheromones are discriminated by a distinctive subcomponent of the vertebrate olfactory system comprised of a relatively small number of olfactory neurons. PMID:10049233

  2. Modulation of the firing activity of female dorsal raphe nucleus serotonergic neurons by neuroactive steroids.

    PubMed

    Robichaud, M; Debonnel, G

    2004-07-01

    Important gender differences in mood disorders result in a greater susceptibility for women. Accumulating evidence suggests a reciprocal modulation between the 5-hydroxytryptamine (5-HT) system and neuroactive steroids. Previous data from our laboratory have shown that during pregnancy, the firing activity of 5-HT neurons increases in parallel with progesterone levels. This study was undertaken to evaluate the putative modulation of the 5-HT neuronal firing activity by different neurosteroids. Female rats received i.c.v. for 7 days a dose of 50 micro g/kg per day of one of the following steroids: progesterone, pregnenolone, 5beta-pregnane-3,20-dione (5beta-DHP), 5beta-pregnan-3alpha-ol,20-one, 5beta-pregnan-3beta-ol,20-one, 5alpha-pregnane-3,20-dione, 5alpha-pregnan-3alpha-ol,20-one (allopregnanolone, 3alpha,5alpha-THP), 5alpha-pregnane-3beta-ol,20-one and dehydroepiandrosterone (DHEA). 5beta-DHP and DHEA were also administered for 14 and 21 days (50 micro g/kg per day, i.c.v.) as well as concomitantly with the selective sigma 1 (sigma1) receptor antagonist NE-100. In vivo, extracellular unitary recording of 5-HT neurons performed in the dorsal raphe nucleus of these rats revealed that DHEA, 5beta-DHP and 3alpha,5alpha-THP significantly increased the firing activity of the 5-HT neurons. Interestingly, 5beta-DHP and DHEA showed different time-frames for their effects with 5beta-DHP having its greatest effect after 7 days to return to control values after 21 days, whereas DHEA demonstrated a sustained effect over the 21 day period. NE-100 prevented the effect of DHEA but not of 5beta-DHP, thus indicating that its sigma1 receptors mediate the effect of DHEA but not that of 5beta-DHP. In conclusion, our results offer a cellular basis for potential antidepressant effects of neurosteroids, which may prove important particularly for women with affective disorders. PMID:15225127

  3. Steroids from the rhizome of Anemarrhena asphodeloides and their cytotoxic activities.

    PubMed

    Sun, Yu; Wu, Jie; Sun, Xue; Huang, Xiaoxiao; Li, Lingzhi; Liu, Qingbo; Song, ShaoJiang

    2016-07-01

    Cancer remains a major killer worldwide. To search for novel naturally occurring compounds that are cytotoxic to cancer cells to be used as lead structures for drug development, five new steroids (1-5) along with seven known ones (6-12) were isolated from the rhizome of Anemarrhena asphodeloides Bge. Their structures were established by detailed spectral studies, including 1D-NMR, 2D-NMR, HR-ESI-MS and by comparison with literature data. These compounds exhibited different levels of growth inhibition against A549, HepG2, Hep3B, Bcap37 and MCF7 cell lines in vitro. Compounds 9, 10 and 11 showed potent inhibitory against all the tested cell lines with IC50 values ranging from 0.35±0.15 to 25.53±0.31μM. The three compounds displayed stronger inhibitory activities against A549, HepG2 and Hep3B cell lines compared with the positive control 5-fluorouracil. The experimental data obtained permit us to identify the roles of the sugar moieties, hydroxyl group, double bond and F-ring with regard to their cytotoxic activities. PMID:27189676

  4. Steroidal saponins with antimicrobial activity from stems and leaves of Paris polyphylla var. yunnanensis.

    PubMed

    Qin, Xu-Jie; Sun, Dong-Jie; Ni, Wei; Chen, Chang-Xiang; Hua, Yan; He, Li; Liu, Hai-Yang

    2012-10-01

    Rhizoma Paridis, the root of Paris polyphylla var. yunnanensis (Trilliaceae), is a Chinese traditional medicine, which resources become less and less. However, the aerial parts of this herb, which can regenerate every year, were discarded. In order to expand the resources, detailed chemical investigation on the stems and leaves of Paris polyphylla var. yunnanensis led to isolation of one sapogenin and 24 steroidal saponins (1-25), including 6 new glycosides, named chonglouosides SL-1-SL-6 (1-6). Their structures were elucidated on the basis of detailed analyses of their 1D and 2D NMR spectra and acid hydrolysis. Among them, compounds 3 and 4 are the first 23,27-dihydroxydiosgenin saponin having a sugar chain attached to C-23 or C-27, while compound 6 is the first 27-hydroxyruscogenin glycoside bearing 1, 27-di-O-sugar chains. The known compounds 10, 12, 14, 19, 20, 22, and 25 were isolated from the genus Paris for the first time. Antimicrobial testing activities of the selected compounds showed that compound 2, 3, 6, 8, 9, 11, 13, 17, 18, 21, and 24 were active against Propionibacterium acnes with MIC values of 62.5, 62.5, 3.9, 16.5, 17.2, 7.8, 39.0, 17.2, 31.3, 62.5, and 31.3 μg/ml, respectively. PMID:22846376

  5. Drug interaction study of natural steroids from herbs specifically toward human UDP-glucuronosyltransferase (UGT) 1A4 and their quantitative structure activity relationship (QSAR) analysis for prediction.

    PubMed

    Xu, Min; Dong, Peipei; Tian, Xiangge; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Wu, Lijun; Deng, Sa; Ma, Xiaochi

    2016-08-01

    The wide application of herbal medicines and foods containing steroids has resulted in the high risk of herb-drug interactions (HDIs). The present study aims to evaluate the inhibition potential of 43 natural steroids from herb medicines toward human UDP- glucuronosyltransferases (UGTs). A remarkable structure-dependent inhibition toward UGT1A4 was observed in vitro. Some natural steroids such as gitogenin, tigogenin, and solasodine were found to be the novel selective inhibitors of UGT1A4, and did not inhibit the activities of major human CYP isoforms. To clarify the possibility of the in vivo interaction of common steroids and clinical drugs, the kinetic inhibition type and related kinetic parameters (Ki) were measured. The target compounds 2-6 and 15, competitively inhibited the UGT1A4-catalyzed trifluoperazine glucuronidation reaction, with Ki values of 0.6, 0.18, 1.1, 0.7, 0.8, and 12.3μM, respectively. And this inhibition of steroids towards UGT1A4 was also verified in human primary hepatocytes. Furthermore, a quantitative structure-activity relationship (QSAR) of steroids with inhibitory effects toward human UGT1A4 isoform was established using the computational methods. Our findings elucidate the potential for in vivo HDI effects of steroids in herbal medicine and foods, with the clinical dr ugs eliminated by UGT1A4, and reveal the vital pharamcophoric requirement of natural steroids for UGT1A4 inhibition activity. PMID:27208893

  6. Obesity-induced increases in sympathetic nerve activity: sex matters

    PubMed Central

    Brooks, Virginia L.; Shi, Zhigang; Holwerda, Seth W.; Fadel, Paul J.

    2016-01-01

    Abundant evidence obtained largely from male human and animal subjects indicates that obesity increases sympathetic nerve activity (SNA), which contributes to hypertension development. However, recent studies that included women reported that the strong relationships between muscle SNA and waist circumference or body mass index (BMI) found in men are not present in overweight and obese women. A similar sex difference in the association between adiposity and hypertension development has been identified in animal models of obesity. In this brief review, we consider two possible mechanisms for this sex difference. First, visceral adiposity, leptin, insulin, and angiotensin II have been identified as potential culprits in obesity-induced sympathoexcitation in males. We explore if these factors wield the same impact in females. Second, we consider if sex differences in vascular reactivity to sympathetic activation contribute. Our survey of the literature suggests that premenopausal females may be able to resist obesity-induced sympathoexcitation and hypertension in part due to differences in adipose disposition as well as its muted inflammatory response and reduced production of pressor versus depressor components of the renin-angiotensin system. In addition, vascular responsiveness to increased SNA may be reduced. However, more importantly, we identify the urgent need for further study, not only of sex differences per se, but also of the mechanisms that may mediate these differences. This information is required not only to refine treatment options for obese premenopausal women but also to potentially reveal new therapeutic avenues in obese men and women. PMID:25435000

  7. Analysis of the Competence to Respond to KNOTTED1 Activity in Arabidopsis Leaves Using a Steroid Induction System1

    PubMed Central

    Hay, Angela; Jackson, David; Ori, Naomi; Hake, Sarah

    2003-01-01

    Expression of KNOX (KNOTTED1-like homeobox) genes in the shoot apical meristem of Arabidopsis is required for maintenance of a functional meristem, whereas exclusion of KNOX gene expression from leaf primordia is required for the elaboration of normal leaf morphology. We have constructed a steroid-inducible system to regulate both the amount and timing of KN1 (KNOTTED1) misexpression in Arabidopsis leaves. We demonstrate that lobed leaf morphology is produced in a dose-dependent manner, indicating that the amount of KN1 quantitatively affects the severity of lobing. The KN1-glucocorticoid receptor fusion protein is not detected in leaves in the absence of steroid induction, suggesting that it is only stable when associated with steroid in an active state. By using a second inducible fusion protein to mark exposure of leaf primordia to the steroid, we determined the stage of leaf development that produces lobed leaves in response to KN1. Primordia as old as plastochron 7 and as young as plastochron 2 were competent to respond to KN1. PMID:12692326

  8. Synthesis, characterization and antitumor activities of some steroidal derivatives with side chain of 17-hydrazone aromatic heterocycle.

    PubMed

    Cui, Jianguo; Liu, Liang; Zhao, Dandan; Gan, Chunfang; Huang, Xin; Xiao, Qi; Qi, Binbin; Yang, Lei; Huang, Yanmin

    2015-03-01

    Here a series of dehydroepiandrosterone-17-hydrazone and estrone-17-hydrazone derivatives possessing various aromatic heterocycle structures in 17-side chain of their steroidal nucleus were synthesized and their structures were evaluated. The antiproliferative activity of synthesized compounds against some cancer cells was investigated. The results have demonstrated that some dehydroepiandrosterone-17-hydrazone derivatives show distinct antiproliferative activity against some cancer cells through inducing cancer cell apoptosis, and compound 8 with a quinoline structure in 17-side chain displays excellent antiproliferative activity in vitro against SGC 7901 cancer cell (human gastric carcinoma) with an IC50 value of 1 μM. In addition, estrone-17-hydrazone derivatives having a key feature of indole group in the structure showed a special obvious cytotoxicity against HeLa cells, but almost inactive against other cells. The information obtained from the studies is valuable for the design of novel steroidal chemotherapeutic drugs. PMID:25578734

  9. Xenobiotic and steroid biotransformation activities in rainbow trout gill epithelial cells in culture.

    PubMed

    Leguen; Carlsson; Perdu-Durand; Prunet; Pärt; Cravedi

    2000-03-01

    The biotransformation of xenobiotics and steroids was investigated in cultured respiratory epithelial cells from rainbow trout (Oncorhynchus mykiss) gills. As a first approach, ethoxyresorufin-O-deethylase (EROD), chosen as a marker of CYP1A activity, was measured in monolayers of adherent cells. The induction of this enzyme was studied in cells exposed to beta-naphthoflavone (BNF) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in concentrations ranging from 10(-6) to 10(-12) M. After 24 h, TCDD showed a maximal induction at a concentration of 10(-9) M while BNF showed a maximal induction at a concentration of 10(-7) M. Concurrently, a variety of substrates involved in cytochrome P450-dependent metabolism as well as phase II reactions, namely ethoxycoumarin, aniline and testosterone were incubated with cultured gill cells for 2 or 8 h and with freshly isolated hepatocytes for comparison. Our results revealed a significant cytochrome P450-dependent activity in gill cells with ethoxycoumarin and aniline, but no hydroxylation was observed with testosterone as substrate. No trace of sulfate conjugate was detected. With 2.5 µM aniline as substrate, 2-hydroxyaniline accounted for 32.1% of the radioactivity after 2 h incubation whereas acetanilide amounted to 6.4%. Significant differences were found between gill cells and isolated hepatocytes in the capacity of these systems to conduct oxidative and conjugating metabolic pathways. Qualitatively, the main difference was observed for testosterone which is hydroxylated in position 6beta and 16beta and conjugated to glucuronic acid in liver cells, whereas reductive biotransformation giving rise to dihydrotestosterone and androstanediol and traces of androstenedione were observed in gill cells. Quantitatively, the biotransformation activity in gill epithelial cells, expressed as pmol/h per mg protein, was between 1.5 and 14% of the activity level observed in isolated hepatocytes, depending on the substrate. PMID:10686323

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

    PubMed

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

    2014-10-15

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

  11. NF-κB inhibitory activity of polyoxygenated steroids from the Vietnamese soft coral Sarcophyton pauciplicatum.

    PubMed

    Thao, Nguyen Phuong; Luyen, Bui Thi Thuy; Sun, Ya Nan; Song, Seok Bean; Thanh, Nguyen Van; Cuong, Nguyen Xuan; Nam, Nguyen Hoai; Kiem, Phan Van; Kim, Young Ho; Minh, Chau Van

    2014-07-01

    Chromatographic purification of the methanolic extract from the soft coral Sarcophyton pauciplicatum led to the isolation of three polyhydroxylated steroids 1-3, including a new compound, sarcopanol A (1). Their structures were elucidated by spectroscopic analysis and by comparison of the spectroscopic data with those of similar compounds previously reported in literature. The anti-inflammatory effects of isolated compounds were evaluated using nuclear factor kappa B (NF-κB) luciferase and reverse transcription polymerase chain reaction (RT-PCR). The effect of isolated compounds on cell growth was evaluated by MTS assays. Compounds 1 and 2 significantly inhibited TNFα/INFγ-induced NF-κB transcriptional activity in human keratinocyte (HaCaT) cells in a dose-dependent manner, with EC50 values of 8.27±3.28 and 26.07±5.59 μM, respectively. Furthermore, the transcriptional inhibition of these compounds was confirmed by a decrease in cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) gene expression levels in HaCaT cells. PMID:24852121

  12. Pregnane glycosides and steroid saponins from Smilax bockii Warb. and their NGF-potentiating activity.

    PubMed

    Xu, Jing; Li, Xian; Zhao, Chun Chao; Wang, Yi

    2008-01-01

    The chemical constituents of the roots of Smilax bockii Warb. were investigated and two pregnane glycosides and three steroid saponins were isolated. Their structures were established as 3beta-hydroxypregna-5,16-dien-20-one-3-O-alpha-L-rhamnopyranosyl(1 --> 4)-alpha-L-rhamnopyranosyl(1 --> 4)-[alpha-L-rhamnopyranosyl(1 --> 2)]-beta-D-glucopyranoside (1), 3beta-hydroxypregna-5,16-dien-20-one-3-O-alpha-L-rhamnopyranosyl(1 --> 2)-[alpha-L-rhamnopyranosyl(1 --> 4)]-beta-D-glucopyranoside (2), dioscin (3), methyl protodioscin (4), 26-O-beta-D-glucopyranosyl-22alpha-methoxyl-(25R)-furost-5-en-3beta, 26-diol 3-O-alpha-L-rhamnopyranosyl(1 --> 4)-alpha-L-rhamnopyranosyl(1 --> 4)-[alpha-L-rhamnopyranosyl(1 --> 2)]-beta-D-glucopyranoside (5) on the basis of spectral analysis and chemical methods. Compound 1 is a new natural product and compounds 2, 5 were first isolated from the genus Smilax. Compound 5 showed enhancing activity of nerve growth factor (NGF)-induced neurite outgrowth in PC 12D cells. PMID:18626823

  13. Sex- and age-dependent activity of glutathione peroxidase in reproductive organs in pre- and post-pubertal cattle in relation to total antioxidant capacity.

    PubMed

    Kankofer, M; Wawrzykowski, J; Giergiel, M

    2013-08-01

    Antioxidative/oxidative balance is crucial for proper functioning of cells and tissues. It is suggested that this balance can be partly controlled by sex steroid hormones and in consequence can exhibit age- and sex-related dependency. The aim of present study was to describe sex- and age-related changes in the activity of glutathione peroxidase (GSH-Px) with respect to total antioxidant activity (TAC) in reproductive organs of cattle. Biological samples were collected from slaughterhouse and comprised of ovaries, uterus, testes as well as livers as reference tissue. Animals were divided into group of bulls (aged between 13 and 24 months; n = 12), cows (aged between 14 and 27 months; n = 12) and female calves (aged between 2 weeks and 2 months; n = 12). Examined parameters were determined spectrophotometrically and the presence of GSH-Px isoform was confirmed by Western blotting technique. Activity of GSH-Px in genital tissues regardless of sex was significantly higher than in livers, while TAC showed opposite relationship. The differences in antioxidative parameters between testes and mature ovaries (e.g. GSH-Px-1.42 ± 0.47 nkat/mg prot vs. 1.08 ± 0.24 and 1.15 ± 0.23) were noticed as well as in chosen values between cows and female calves. Western blotting allowed the detection of cytosolic GSH-Px in all examined tissues with molecular weight around 21 kDa as monomer and around 84 kDa as tetramer depending on conditions of electrophoresis. The results may confirm the influence and regulatory role of sex steroid hormones on GSH-Px activity because the alterations were sex and age dependent. PMID:23740597

  14. Photochemical induced changes of in vitro estrogenic activity of steroid hormones.

    PubMed

    Whidbey, Christopher M; Daumit, Kelly E; Nguyen, Thanh-Hoa; Ashworth, Danielle D; Davis, Jasmine C C; Latch, Douglas E

    2012-10-15

    Steroid estrogens are endocrine disrupting contaminants frequently detected in natural waters. Because these estrogens can elicit significant biological responses in aquatic organisms, it is important to study their rates and pathways of degradation in natural waters and to identify whether the transformation products retain biological activity. Photochemical kinetics experiments were conducted under simulated solar light for the hormones 17β-estradiol (E2), 17α-ethinylestradiol (EE2), estrone (E1), equilin (EQ), and equilenin (EQN) under direct and indirect photolysis conditions. All of these hormones were susceptible to direct photodegradation, with half-lives ranging from 40 min for E1 to about 8 h for E2 and EE2. Indirect photolysis experiments with added Suwannee River fulvic acid (SRFA) lead to faster degradation rates for E2, EE2, and EQ. Added SRFA caused slower photodegradation rates for E1 and EQN, indicating that it acts primarily as an inner filter for these analytes. The well-established yeast estrogen screen (YES) was used to measure the estrogenicity of the analytes and their photoproducts. Results of YES assay experiments show that only the direct photolysis of E1 gave estrogenic products. Lumiestrone, the major E1 direct photolysis product, was isolated and characterized. It formed in 53% yield and exhibited moderate estrogenic activity. When photolysed in the presence of perinaphthenone, a potent synthetic sensitizer, E1 degraded via an indirect photolysis pathway and did not produce lumiestrone or any other active products. These results suggest that under typical natural water conditions photochemical reactions of E2, EE2, EQ, and EQN are expected to produce inactive products while E1 will give the estrogenic product lumiestrone in moderate yield. PMID:22877877

  15. Inflammation and sex hormone metabolism.

    PubMed

    Schmidt, Martin; Naumann, Heidrun; Weidler, Claudia; Schellenberg, Martina; Anders, Sven; Straub, Rainer H

    2006-06-01

    The incidence of autoimmune diseases is higher in females than in males. In both sexes, adrenal hormones, that is, glucocorticoids, dehydroepiandrosterone (DHEA), and androgens, are inadequately low in patients when compared to healthy controls. Hormonally active androgens are anti-inflammatory, whereas estrogens are pro-inflammatory. Therefore, the mechanisms responsible for the alterations of steroid profiles in inflammation are of major interest. The local metabolism of androgens and estrogens may determine whether a given steroid profile found in a subject's blood results in suppression or promotion of inflammation. The steroid metabolism in mixed synovial cells, fibroblasts, macrophages, and monocytes was assessed. Major focus was on cells from patients with rheumatoid arthritis (RA), while cells from patients with osteoarthritis served as controls. Enzymes directly or indirectly involved in local sex steroid metabolism in RA are: DHEA-sulfatase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and aromatase (CYP19), which are required for the synthesis of sex steroids from precursors, 5alpha-reductase and 16alpha-hydroxylase, which can be involved either in the generation of more active steroids or in the pathways leading to depletion of active hormones, and 3alpha-reductase and 7alpha-hydroxylase (CYP7B), which unidirectionally are involved in the depletion of active hormones. Androgens inhibit aromatization in synovial cells when their concentration is sufficiently high. As large amounts of estrogens are formed in synovial tissue, there may be a relative lack of androgens. Production of 5alpha-reduced androgens should increase the local anti-inflammatory activity; however, it also opens a pathway for the inactivation of androgens. The data discussed here suggest that therapy of RA patients may benefit from the use of nonaromatizable androgens and/or the use of aromatase inhibitors. PMID:16855150

  16. Calmodulin effects on steroids-regulated plasma membrane calcium pump activity.

    PubMed

    Zylinska, Ludmila; Kowalska, Iwona; Ferenc, Bozena

    2009-03-01

    It is now generally accepted that non-genomic steroids action precedes their genomic effects by modulation of intracellular signaling pathways within seconds after application. Ca(2+) is a very potent and ubiquitous ion in all cells, and its concentration is precisely regulated. The most sensitive on Ca(2+) increase is ATP-consuming plasma membrane calcium pump (PMCA). The enzyme is coded by four genes, but isoforms diversity was detected in excitable and non-excitable cells. It is the only ion pump stimulated directly by calmodulin (CaM). We examined the role of PMCA isoforms composition and CaM effect in regulation of Ca(2+) uptake by estradiol, dehydroepiandrosterone (DHEA), pregnenolone (PREG), and their sulfates in a concentration range from 10(-9) to 10(-6) M, using the membranes from rat cortical synaptosomes, differentiated PC12 cells, and human erythrocytes. In excitable membranes with full set of PMCAs steroids apparently increased Ca(2+) uptake, although to a variable extent. In most of the cases, CaM decreased transport by 30-40% below controls. Erythrocyte PMCA was regulated by the steroids somewhat differently than excitable cells. CaM strongly increased the potency for Ca(2+) extrusion in membranes incubated with 17-beta-estradiol and PREG. Our results indicated that steroids may sufficiently control cytoplasmic calcium concentration within physiological and therapeutic range. The response depended on the cell type, PMCA isoforms expression profile, CaM presence, and the steroids structure. PMID:19226536

  17. Sleep Loss Activates Cellular Markers of Inflammation: Sex Differences

    PubMed Central

    Irwin, Michael R.; Carrillo, Carmen; Olmstead, Richard

    2009-01-01

    Sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. Given sex differences in the prevalence of inflammatory disorders with stronger associations in females, this study was undertaken to test the effects of sleep loss on cellular mechanisms that contribute to proinflammatory cytokine activity. In 26 healthy adults (11 females; 15 males), monocyte intracellular proinflammatory cytokine production was repeatedly assessed at 08:00, 12:00, 16:00, 20:00, and 23:00 h during a baseline period and after partial sleep deprivation (awake from 11 PM to 3 AM). In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor- α differentially changed between the two sexes. Whereas both females and males showed a marked increase in the lipopolysaccharide (LPS) - stimulated production of IL-6 and TNF-α in the morning immediately after PSD, production of these cytokines during the early- and late evening was increased in the females as compared to decreases in the males. Sleep loss induces a functional alteration of monocyte proinflammatory cytokine responses with females showing greater cellular immune activation as compared to changes in males. These results have implications for understanding the role of sleep disturbance in the differential risk profile for inflammatory disorders between the sexes. PMID:19520155

  18. Steroidal Saponins from the Mesocarp of the Fruits of Raphia farinifera (Arecaceae) and their Cytotoxic Activity.

    PubMed

    Tapondjou, Léon A; Siems, Kristina J; Böttger, Stefan; Melzig, Matthias F

    2015-11-01

    Eight steroidal saponins (1-8), including one previously unreported derivative (1), have been isolated from the mesocarp of Raphia farinifera fruits by combined column chromatography and RP-HPLC methods. They were characterized by spectroscopic (1D and 2D NMR experiments) and spectrometric (ESIMS) methods, as well as by comparison of their spectral data with those of reported compounds in the literature. All the isolated compounds were tested for cytotoxicity against urinary bladder carcinoma cells (ECV-304). Our results revealed that, for a high cytotoxicity, a sugar chain of at least three sugar moieties attached to C-3 of the steroidal saponin is necessary. PMID:26749832

  19. Medicinal flowers. XII.(1)) New spirostane-type steroid saponins with antidiabetogenic activity from Borassus flabellifer.

    PubMed

    Yoshikawa, Masayuki; Xu, Fengming; Morikawa, Toshio; Pongpiriyadacha, Yutana; Nakamura, Seikou; Asao, Yasunobu; Kumahara, Akira; Matsuda, Hisashi

    2007-02-01

    The methanolic extract from the male flowers of Borassus flabellifer was found to inhibit the increase of serum glucose levels in sucrose-loaded rats at a dose of 250 mg/kg, p.o. From the methanolic extract, six new spirostane-type steroid saponins, borassosides A-F (1-6), were isolated together with 23 known constituents. The structures of borassosides (1-6) were elucidated on the basis of chemical and physicochemical evidences. In addition, the principal steroid saponin, dioscin (13), inhibited the increase of serum glucose levels in sucrose-loaded rats at a dose of 50 mg/kg, p.o. PMID:17268107

  20. Anabolic steroids alter the physiological activity of aggression circuits in the lateral anterior hypothalamus.

    PubMed

    Morrison, T R; Sikes, R W; Melloni, R H

    2016-02-19

    Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. To characterize the electrophysiological profile of the AAS aggression circuit, we recorded LAH neurons in adolescent male hamsters in vivo and microiontophoretically applied agonists and antagonists of aggressive behavior. The interspike interval (ISI) of neurons from AAS-treated animals correlated positively with aggressive behaviors, and adolescent AAS exposure altered parameters of activity in regular firing neurons while also changing the proportion of neuron types (i.e., bursting, regular, irregular). AAS-treated animals had more responsive neurons that were excited by AVP application, while cells from control animals showed the opposite effect and were predominantly inhibited by AVP. Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure. PMID:26691962

  1. Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain.

    PubMed

    Lewis, Susannah S; Hutchinson, Mark R; Frick, Morin M; Zhang, Yingning; Maier, Steven F; Sammakia, Tarek; Rice, Kenner C; Watkins, Linda R

    2015-02-01

    We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signaling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and temporomandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest. PMID:25218902

  2. Select steroid hormone glucuronide metabolites can cause Toll-like receptor 4 activation and enhanced pain

    PubMed Central

    Lewis, Susannah S.; Hutchinson, Mark R.; Frick, Morin M.; Zhang, Yingning; Maier, Steven F.; Sammakia, Tarek; Rice, Kenner C.; Watkins, Linda R.

    2014-01-01

    We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signalling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and tempromandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest. PMID:25218902

  3. Structure activity relationship studies on cytotoxicity and the effects on steroid receptors of AB-functionalized cholestanes.

    PubMed

    Rárová, Lucie; Steigerová, Jana; Kvasnica, Miroslav; Bartůněk, Petr; Křížová, Kateřina; Chodounská, Hana; Kolář, Zdeněk; Sedlák, David; Oklestkova, Jana; Strnad, Miroslav

    2016-05-01

    Structure-activity relationship analysis and profiling of a library of AB-functionalized cholestane derivatives closely related to brassinosteroids (BRs) were performed to examine their antiproliferative activities and activities on steroid hormone receptors. Some of the compounds were found to have strong cytotoxic activity in several human normal and cancer cell lines. The presence of a 3-hydroxy or 3-oxo group and 2,3-vicinal diol or 3,4-vicinal diol moiety were found to be necessary for optimum biological activity, as well as a six-membered B ring. According to the profiling of all steroid receptors in both agonist and antagonist mode, the majority of the cholestanes were weakly active or inactive compared to the natural ligands. Estrogenic activity was detected for two compounds, two compounds possessed antagonistic properties on estrogen receptors and seven compounds showed agonistic activity. Two active cholestane derivatives were shown to strongly influence cell viability, proliferation, cell cycle distribution, apoptosis and molecular pathways responsible for these processes in hormone-sensitive/insensitive (MCF7/MDA-MB-468) breast cancer cell lines. PMID:26976651

  4. Sex differences in body fluid homeostasis: Sex chromosome complement influences on bradycardic baroreflex response and sodium depletion induced neural activity.

    PubMed

    Vivas, L; Dadam, F M; Caeiro, X E

    2015-12-01

    Clinical and basic findings indicate that angiotensin II (ANG II) differentially modulates hydroelectrolyte and cardiovascular responses in male and female. But are only the activational and organizational hormonal effects to blame for such differences? Males and females not only differ in their sex (males are born with testes and females with ovaries) but also carry different sex chromosome complements and are thus influenced throughout life by different genomes. In this review, we discuss our recent studies in order to evaluate whether sex chromosome complement is in part responsible for gender differences previously observed in ANG II bradycardic-baroreflex response and sodium depletion-induced sodium appetite and neural activity. To test the hypothesis that XX or XY contributes to the dimorphic ANG II bradycardic-baroreflex response, we used the four core genotype mouse model, in which the effects of gonadal sex (testes or ovaries) and sex chromosome complement (XX or XY) are dissociated. The results indicate that ANG II bradycardic-baroreflex sexual dimorphic response may be ascribed to differences in sex chromosomes, indicating an XX-sex chromosome complement facilitatory bradycardic-baroreflex control of heart rate. Furthermore, we evaluated whether genetic differences within the sex chromosome complement may differentially modulate the known sexually dimorphic sodium appetite as well as basal or induced brain activity due to physiological stimulation of the renin-angiotensin system by furosemide and low-sodium treatment. Our studies demonstrate an organizational hormonal effect on sexually dimorphic induced sodium intake in mice, while at the brain level (subfornical organ and area postrema) we showed a sex chromosome complement effect in sodium-depleted mice, suggesting a sex chromosome gene participation in the modulation of neural pathways underlying regulatory response to renin-angiotensin stimulation. PMID:26260434

  5. Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.

    PubMed

    van Hemmen, Judy; Veltman, Dick J; Hoekzema, Elseline; Cohen-Kettenis, Peggy T; Dessens, Arianne B; Bakker, Julie

    2016-03-01

    Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure. PMID:25452569

  6. A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity.

    PubMed Central

    Kawashima, Hidenori; Takano, Haruna; Sugita, Syozo; Takahara, Yuki; Sugimura, Kazunobu; Nakatani, Tatsuya

    2003-01-01

    We have cloned a cDNA coding for a novel steroid receptor co-activator protein termed SRAP from a rat prostate library. Although the nucleotide sequence of the SRAP has 78.2% identity to that of the human steroid receptor RNA activator (SRA), a novel RNA molecule which was reported to act as an RNA transcript without being translated into protein [Lanz, McKenna, Onate, Albrecht, Wong, Tsai, Tsai and O'Malley (1999) Cell 97, 17-27], the cDNA of SRAP is capable of generating a functional protein. Glutathione S-transferase pull-down assays showed that SRAP associates with the partial androgen receptor (AR) protein composed of a DNA-binding domain and an activation function 2. Luciferase assays demonstrated that SRAP enhances the transactivation activity of the AR, the glucocorticoid receptor and the peroxisome proliferator-activated receptor gamma(1) in a ligand-dependent manner. Using a green fluorescent protein (GFP) fusion-protein construct, we demonstrated in vivo translation of the GFP-SRAP fusion protein in HeLa cells co-transfected with pSG5AR and reporter gene in the presence of 5 alpha-dihydrotestosterone (DHT). Co-transfection of the GFP-SRAP fusion protein expression plasmid enhanced the transactivation activity of AR whereas incorporation of mutations in SRAP of the fusion protein resulted in loss of enhancement of the transactivation activity. Northern blot analysis and reverse transcriptase PCR assays showed that SRAP and SRA are expressed in rat and human prostate cancer cell lines respectively. In HeLa cells and the human prostate cancer cells line DU-145, co-transfected with SRAP, the DHT-dependent transactivation activities of AR were not completely inhibited by the anti-androgen flutamide, but the transactivation activities still remained high even in the presence of 5 microM flutamide, suggesting that SRAP may play an important role in enhancing AR activity in prostate cancer. PMID:12350225

  7. Sex Differences in Monocyte Activation in Systemic Lupus Erythematosus (SLE)

    PubMed Central

    Jiang, Wei; Zhang, Lumin; Lang, Ren; Li, Zihai; Gilkeson, Gary

    2014-01-01

    Introduction TLR7/8 and TLR9 signaling pathways have been extensively studied in systemic lupus erythematosus (SLE) as possible mediators of disease. Monocytes are a major source of pro-inflammatory cytokines and are understudied in SLE. In the current project, we investigated sex differences in monocyte activation and its implications in SLE disease pathogenesis. Methods Human blood samples from 27 healthy male controls, 32 healthy female controls, and 25 female patients with SLE matched for age and race were studied. Monocyte activation was tested by flow cytometry and ELISA, including subset proportions, CD14, CD80 and CD86 expression, the percentage of IL-6-producing monocytes, plasma levels of sCD14 and IL-6, and urine levels of creatinine. Results Monocytes were significantly more activated in women compared to men and in patients with SLE compared to controls in vivo. We observed increased proportions of non-classic monocytes, decreased proportions of classic monocytes, elevated levels of plasma sCD14 as well as reduced surface expression of CD14 on monocytes comparing women to men and lupus patients to controls. Plasma levels of IL-6 were positively related to sCD14 and serum creatinine. Conclusion Monocyte activation and TLR4 responsiveness are altered in women compared to men and in patients with SLE compared to controls. These sex differences may allow persistent systemic inflammation and resultant enhanced SLE susceptibility. PMID:25485543

  8. 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

  9. Anti-thrombotic activity and chemical characterization of steroidal saponins from Dioscorea zingiberensis C.H. Wright.

    PubMed

    Li, Hua; Huang, Wen; Wen, Yanqing; Gong, Guohua; Zhao, Qingbing; Yu, Gang

    2010-12-01

    Steroidal saponins have long attracted scientific attention, due to their structural diversity and significant biological activities. Total steroidal saponins (TSS) extracted from the rhizomes of Dioscorea zingiberensis C.H. Wright (DZW) constitute an effective treatment for cardiovascular disease. However, the active constituents contained in DZW rhizomes and their pharmacological properties are not fully understood. The aim of this work is to determine and quantify the active constituents in DZW rhizomes using fingerprint technique, and evaluate its anti-thrombotic activity using inferior vena cava ligation thrombosis rat model and pulmonary thrombosis mice model after being gavaged with TSS for 1 or 2weeks. In the study, a chemical fingerprint method was firstly established and validated to quantify and standardize TSS from DZW rhizomes including parvifloside, protodeltonin, protodioscin, protogracillin, zingiberensis saponin, deltonin, dioscin and trillin. TSS extracted from DZW rhizomes were showed to have the inhibitions on platelet aggregation (PAG) and thrombosis, and prolong activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) in a dose-dependent manner in rats. TSS also prolonged the bleeding time and clotting time in a dose-dependent manner in mice. The results indicate that TSS could inhibit thrombosis by both improving the anticoagulation activity and inhibiting PAG action, suggesting that TSS from DZW rhizomes have the potential to reduce the risk of cardiovascular diseases by anti-thrombotic action. PMID:20659537

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

    PubMed

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

    2001-01-01

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

  11. Immunological Adjuvant Activity of Pectinioside A, the Steroidal Saponin from the Starfish Patiria pectinifera.

    PubMed

    Kawase, Osamu; Ohno, Osamu; Suenaga, Kiyotake; Xuan, Xuenan

    2016-05-01

    The steroidal saponin, pectinioside A, was isolated from the starfish, Patiria pectinifera. When it was subcutaneously injected into mice with ovalbumin (OVA), it facilitated the production of OVA-specific total IgG and IgG1 but not IgG2a. To our knowledge, this is the first report suggesting that starfish saponin has the potential to be an immunological adjuvant, stimulating Th2 type immune response. PMID:27319128

  12. Aromatase activity in the mare ovary during estrous cycle. Measurement of endogenous steroids and of their in vitro inhibitory effect.

    PubMed

    Amri, H; Silberzahn, P; al-Timimi, I; Gaillard, J L

    1993-12-01

    This present study was undertaken to clarify estrogen synthesis in the mare ovary. First of all, an evaluation of endogenous steroid contents was carried out in the follicular fluid and in the luteal tissue at different stages of the luteal phase. Radioimmunoassays were performed after separation and purification of each hormone by chromatography. High amounts of conjugated (0.9 mg/l) and unconjugated (4 mg/l) estradiol-17 beta were found in the follicular fluid of the large follicules (50 mm). These concentrations of estrogens decreased drastically in the luteal tissue, and only low levels of circulating estrogens are found during the luteal phase. On the other hand, a high aromatization ability has been evidenced in the cyclic corpus luteum in vitro. In an attempt to clarify the regulation of estrogen synthesis, we have tested the inhibitory effect of several endogenous steroids on equine ovarian aromatase activity. 5 alpha-Dihydrotestosterone appeared to be the most potent competitive inhibitor (Ki = 181 nmol/l) of aromatase activity, while the addition of a 3-sulfate group induced a slump in the inhibitory potency of estrone (Ki = 397 nmol/l vs 2206 nmol/l) and dehydroepiandrosterone (Ki = 291 nmol/l vs 6157 nmol/l). The physiological role of these conjugated steroids has not been known until now; we suggest that they would play a role in protecting aromatase from inhibition, in vivo. The high amounts of progesterone found in the luteal tissue (1.3 g/kg of proteins) might play a role in the regulation of estrogen production either by suppressing the induction of aromatase synthesis or by inhibiting the activity of the enzyme complex. PMID:8109188

  13. Identification and Evaluation of Antiepileptic Activity of C21 Steroidal Glycosides from the Roots of Cynanchum wilfordii.

    PubMed

    Li, Jin-Long; Gao, Zhao-Bing; Zhao, Wei-Min

    2016-01-22

    Nine new C21 steroidal glycosides, named cynawilfosides A-I (1-9), along with 12 known compounds were isolated from the roots of Cynanchum wilfordii. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The five major components, cynawilfoside A (1), cynauricoside A (11), wilfoside C1N (16), wilfoside K1N (17), and cyanoauriculoside G (18), exhibited significant protection activity in a maximal electroshock (MES)-induced mouse seizure model with ED50 values of 48.5, 95.3, 124.1, 72.3, and 88.1 mg/kg, respectively. PMID:26716755

  14. Steroid Receptor-Associated Immunophilins: A Gateway to Steroid Signalling

    PubMed Central

    Ratajczak, Thomas; Cluning, Carmel; Ward, Bryan K

    2015-01-01

    The steroid receptor-associated immunophilins FKBP51, FKBP52, CyP40 and PP5 have specific roles in steroid receptor function that impact steroid hormone-binding affinity, nucleocytoplasmic shuttling and transcriptional activation of target genes in a tissue-specific manner. Aberrant expression of these functionally unique immunophilins has the potential to cause steroid-based diseases, including breast and prostate cancer, diabetes and related metabolic disorders, male and female infertility and major depressive disorders. This review addresses the function of these proteins as co-chaperones in steroid receptor-Hsp90 complexes and extensively covers current knowledge of the link between the steroid receptor-associated immunophilins and human disease. An improved understanding of their mechanisms of action has revealed opportunities for molecular therapies to enhance or inhibit cellular processes under immunophilin control that contribute both to human health and disease. PMID:26224894

  15. 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

  16. Sex and stress hormone influences on the expression and activity of brain-derived neurotrophic factor.

    PubMed

    Carbone, D L; Handa, R J

    2013-06-01

    The neurotrophin, brain-derived neurotrophic factor (BDNF), is recognized as a key component in the regulation of CNS ontogeny, homeostasis and adult neuroplasticity. The importance of BDNF in CNS 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 CNS 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 (GCs), 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 Tropomyosin-Related Kinase B by estradiol, thus implicating sex steroids not only in the regulation of BDNF expression, but also in mechanisms of signaling associated with it. In addition to gonadal steroids, further evidence also suggests functional interaction between BDNF and GCs, 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 CNS. PMID:23211562

  17. 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

  18. 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

  19. Oral Steroids (Steroid Pills and Syrups)

    MedlinePlus

    ... more about steroids? How are steroid pills and syrups used? Steroid pills and syrups are very effective at reducing swelling and mucus ... liver or cause sterility Available as pills and syrups. Often necessary for treating more severe episodes of ...

  20. 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

  1. Extensive esterification of adrenal C19-delta 5-sex steroids to long-chain fatty acids in the ZR-75-1 human breast cancer cell line

    SciTech Connect

    Poulin, R.; Poirier, D.; Merand, Y.; Theriault, C.; Belanger, A.; Labrie, F.

    1989-06-05

    Estrogen-sensitive human breast cancer cells (ZR-75-1) were incubated with the 3H-labeled adrenal C19-delta 5-steroids dehydroepiandrosterone (DHEA) and its fully estrogenic derivative, androst-5-ene-3 beta,17 beta-diol (delta 5-diol) for various time intervals. When fractionated by solvent partition, Sephadex LH-20 column chromatography and silica gel TLC, the labeled cell components were largely present (40-75%) in three highly nonpolar, lipoidal fractions. Mild alkaline hydrolysis of these lipoidal derivatives yielded either free 3H-labeled DHEA or delta 5-diol. The three lipoidal fractions cochromatographed with the synthetic DHEA 3 beta-esters, delta 5-diol 3 beta (or 17 beta)-monoesters and delta 5-diol 3 beta,17 beta-diesters of long-chain fatty acids. DHEA and delta 5-diol were mainly esterified to saturated and mono-unsaturated fatty acids. For delta 5-diol, the preferred site of esterification of the fatty acids is the 3 beta-position while some esterification also takes place at the 17 beta-position. Time course studies show that ZR-75-1 cells accumulate delta 5-diol mostly (greater than 95%) as fatty acid mono- and diesters while DHEA is converted to delta 5-diol essentially as the esterified form. Furthermore, while free C19-delta 5-steroids rapidly diffuse out of the cells after removal of the precursor (3H)delta 5-diol, the fatty acid ester derivatives are progressively hydrolyzed, and DHEA and delta 5-diol thus formed are then sulfurylated prior to their release into the culture medium. The latter process however is rate-limited, since new steady-state levels of free steroids and fatty acid esters are rapidly reached and maintained for extended periods of time after removal of precursor, thus maintaining minimal concentrations of intracellular steroids.

  2. Synergistic effect of 5-HT1A and σ1 receptor activation on prefrontal dopaminergic transmission under circulating steroid deficiency.

    PubMed

    Hiramatsu, Naoki; Ago, Yukio; Hasebe, Shigeru; Nishimura, Akira; Mori, Kazuya; Takuma, Kazuhiro; Matsuda, Toshio

    2013-12-01

    Serotonin (5-HT)1A and σ1 receptors have been implicated in psychiatric disorders. We previously found that combined 5-HT reuptake inhibition and σ1 receptor activation has a synergistic effect on prefrontal dopaminergic transmission in adrenalectomized/castrated mice lacking circulating steroid hormones. In the present study, we examined the mechanisms underlying this neurochemical synergism. Systemic administration of fluvoxamine, a selective 5-HT reuptake inhibitor with agonistic activity towards the σ1 receptor, increased prefrontal dopamine (DA) levels, and adrenalectomy/castration potentiated this fluvoxamine-induced increase in DA. This enhancement of DA release was blocked by WAY100635 (a 5-HT1A receptor antagonist), but not by ritanserin (a 5-HT2 receptor antagonist), azasetron (a 5-HT3 receptor antagonist) or SB269970 (a 5-HT7 receptor antagonist). Individually, osemozotan (a 5-HT1A receptor agonist) and (+)-SKF-10,047 (a σ1 receptor agonist) did not alter prefrontal monoamine levels in adrenalectomized/castrated and sham-operated mice differentially. In contrast, co-administration of these drugs increased prefrontal DA levels to a greater extent in adrenalectomized/castrated mice than in sham-operated animals. Furthermore, co-administration of osemozotan and (+)-SKF-10,047 increased expression of the neuronal activity marker c-Fos in the ventral tegmental area of adrenalectomized/castrated mice, but not in sham-operated animals. These findings suggest that combined activation of 5-HT1A and σ1 receptors has a synergistic effect on prefrontal dopaminergic transmission under circulating steroid deficiency, and that this interaction may play an important role in the regulation of the prefrontal DA system. PMID:23851260

  3. 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…

  4. Regulation of 3β-hydroxysteroid dehydrogenase and sulphotransferase 2A1 gene expression in primary porcine hepatocytes by selected sex-steroids and plant secondary metabolites from chicory (Cichorium intybus L.) and wormwood (Artemisia sp.).

    PubMed

    Rasmussen, Martin Krøyer; Ekstrand, Bo

    2014-02-15

    In pigs the endogenously produced compound androstenone is metabolised in the liver in two steps by 3β-hydroxysteroid dehydrogenase (3β-HSD) and sulphotransferase 2A1 (SULT2A1). The present study investigated the effect of selected sex-steroids (0.01-1 μM androstenone, testosterone and estradiol), skatole (1-100 μM) and secondary plant metabolites (1-100 μM) on the expression of 3β-HSD and SULT2A1 mRNA. Additionally the effect of a global methanolic extract of dried chicory root was investigated and compared to previous obtained in vivo effects. Primary hepatocytes were isolated from the livers of piglets (crossbreed: Landrace×Yorkshire and Duroc) and cultured for 24h before treatment for an additionally 24h. RNA was isolated from the hepatocytes and specific gene expression determined by RT-PCR using TaqMan probes. The investigated sex-steroids had no effect on the mRNA expression of 3β-HSD and SULT2A1, while skatole decreased the content of SULT2A1 30% compared to control. Of the investigated secondary plant metabolites artemisinin and scoparone (found in Artemisia sp.) lowered the content of SULT2A1 by 20 and 30% compared to control, respectively. Moreover, we tested three secondary plant metabolites (lactucin, esculetin and esculin) found in chicory root. Lactucin increased the mRNA content of both 3β-HSD and SULT2A1 by 200% compared to control. An extract of chicory root was shown to decrease the expression of both 3β-HSD and SULT2A1. It is concluded that the gene expression of enzymes with importance for androstenone metabolism is regulated by secondary plant metabolites in a complex manner. PMID:24333270

  5. A Packet of Elementary Classroom Activities To Teach Students about Sex Role Stereotyping.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing. Office for Sex Equity.

    Designed to help elementary school students understand sex role stereotyping, these classroom activities have been compiled from sex equity projects at local, state, and national levels. The selection criteria included: (1) appeal to elementary students; (2) the inclusion of mathematics or language arts exercises within an activity; and (3)…

  6. [Longterm effects of steroid therapy].

    PubMed

    Kuna, P

    1998-01-01

    Asthma is a chronic inflammatory disease of the airways play. Anti-inflammatory drugs the fundamental role in the treatment of asthma and among them steroids are the most important. However, oral steroids may cause many serious side effects. A major breakthrough in the treatment of asthma was introducing inhaled steroids. Inhaled steroids have much less side effects than oral steroids, although they have the same anti-inflammatory activity. Long term effect of inhaled steroids can be divided into wanted and unwanted outcome. The desirable anti-inflammatory effect of steroids is reflected by lowering of bronchial hyperresponsiveness and a better control of asthma symptoms. Inhaled corticosteroid may have systemic side effects similar to those observed with oral steroids such as 1) adrenal suppression, 2) effect on bone metabolism, 3) growth suppression in children, 4) impaired skin collagen synthesis, 5) cataract, 6) metabolic disturbances, 7) effect on central nervous system. Topical side effects of inhaled corticosteroid such as oral candidiasis, dysphonia and cough effect about 10 to 30% of patients taking those drugs. Summing up it is advisable to use inhaled corticosteroid in the lower effective dose. PMID:9610231

  7. Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

    PubMed

    Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

    2015-06-01

    Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected. PMID:25797375

  8. Unconventional endocannabinoid signaling governs sperm activation via the sex hormone progesterone.

    PubMed

    Miller, Melissa R; Mannowetz, Nadja; Iavarone, Anthony T; Safavi, Rojin; Gracheva, Elena O; Smith, James F; Hill, Rose Z; Bautista, Diana M; Kirichok, Yuriy; Lishko, Polina V

    2016-04-29

    Steroids regulate cell proliferation, tissue development, and cell signaling via two pathways: a nuclear receptor mechanism and genome-independent signaling. Sperm activation, egg maturation, and steroid-induced anesthesia are executed via the latter pathway, the key components of which remain unknown. Here, we present characterization of the human sperm progesterone receptor that is conveyed by the orphan enzyme α/β hydrolase domain-containing protein 2 (ABHD2). We show that ABHD2 is highly expressed in spermatozoa, binds progesterone, and acts as a progesterone-dependent lipid hydrolase by depleting the endocannabinoid 2-arachidonoylglycerol (2AG) from plasma membrane. The 2AG inhibits the sperm calcium channel (CatSper), and its removal leads to calcium influx via CatSper and ensures sperm activation. This study reveals that progesterone-activated endocannabinoid depletion by ABHD2 is a general mechanism by which progesterone exerts its genome-independent action and primes sperm for fertilization. PMID:26989199

  9. Unprotected sex among heterosexually active homeless men: results from a multi-level dyadic analysis.

    PubMed

    Kennedy, David P; Wenzel, Suzanne L; Brown, Ryan; Tucker, Joan S; Golinelli, Daniela

    2013-06-01

    HIV is a serious public health problem for homeless populations. Homeless men who have sex with women have received less attention in the HIV risk literature than other homeless populations. This research uses multi-level modeling to investigate the context of unprotected sex among heterosexually active homeless men in the Skid Row area of Los Angeles. Based on interviews with 305 randomly selected men who discussed 665 of their recent female sexual relationships, this project investigates the correlates of unprotected sex during the past 6 months at the partnership, individual, and social network levels. Several different measures of relationship closeness and lack of communication about HIV/condoms were associated with unprotected sex. Controlling for relationship factors, men's negative attitudes towards condoms, mental health, and higher number of male sex partners also were associated with having unprotected sex with female partners. We discuss the implications of these findings for health interventions. PMID:23212852

  10. Sex Differences in Mental Rotation and Cortical Activation Patterns: Can Training Change Them?

    ERIC Educational Resources Information Center

    Jausovec, Norbert; Jausovec, Ksenija

    2012-01-01

    In two experiments the neuronal mechanisms of sex differences in mental rotation were investigated. In Experiment 1 cortical activation was studied in women and men with similar levels of mental rotation ability (high, and average to low), who were equalized with respect to general intelligence. Sex difference in neuroelectric patterns of brain…

  11. Spectrophotometric method for the assay of steroid 5α-reductase activity of rat liver and prostate microsomes.

    PubMed

    Iwai, Atsushi; Yoshimura, Teruki; Wada, Keiji; Watabe, Satoshi; Sakamoto, Yuki; Ito, Etsuro; Miura, Toshiaki

    2013-01-01

    A simple spectrophotometric method for the assay of steroid 5α-reductase (5α-SR) was developed in which 5α-dihydrotestosterone (5α-DHT) and 5α-androstane-3α,17β-diol (5α-diol), metabolites formed in the NADPH-dependent reduction of testosterone with enzyme sources of 5α-SR, were measured by enzymatic cycling using 3α-hydroxysteroid dehydrogenase in the presence of excess thionicotinamide-adenine dinucleotide (thio-NAD) and NADH. It was found that 5α-SR activity was proportional to the accumulated thio-NADH having an absorption maximum at 400 nm. Because of the high cycling rate (> 600 cycle per min) and no interference from testosterone, enzymatic cycling can determine the sum of 5α-DHT and 5α-diol at the picomole level without separation from excess testosterone. The present method was readily applicable to the assay of 5α-SR activity of rat liver and prostate microsomes as well as to the assay of inhibitory activity of finasteride, a synthetic inhibitor of 5α-SR. PMID:23574674

  12. The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area.

    PubMed

    Roselli, C E

    1998-05-11

    The level of aromatase in the preoptic area of rats is transcriptionally regulated through a specific androgen-receptor mediated mechanism and can be used as a measure of central androgenic effect. Therefore, several commonly abused anabolic-androgenic steroids (AAS) were tested for their ability to induce aromatase activity in the preoptic area of castrated rats. In addition, we determined the relative binding affinities of these compounds for the androgen receptor, as well as their ability to bind androgen receptor in vivo following subcutaneous injections. All of the AAS compounds tested significantly stimulated POA aromatase activity above castrate levels. The compounds that produced the greatest stimulation of aromatase activity were those that bound most avidly to the androgen receptor in vitro (i.e., testosterone, dihydrotestosterone and nandrolone). In contrast, the 17alpha-alkylated compounds that were tested (stanozolol, danazol, methandrostenolone) modestly stimulated aromatase and were weak competitors for the androgen receptor. The subcutaneous injection of AAS compounds increased the concentrations of occupied nuclear androgen receptors in the brain, but the magnitude of effect was not related to their potency for inducing aromatase or their relative binding affinity for the androgen receptor suggesting that androgen receptor occupancy in POA is not correlated with the action of androgen on aromatase. The present results help explain the behavioral effects of AAS compounds in rats. PMID:9593936

  13. Epidural Steroid Injections

    MedlinePlus

    ... Assessment Tools Injection Treatments for Spinal Pain Epidural Steroid Injections Lumbar Zygapophysial (Facet) Joint Injections Surgical Options Nonsurgical Treatments Alternative Medicine Epidural Steroid Injections General Information Why Get an Epidural Steroid ...

  14. 76 FR 80966 - Agency Information Collection Activities; Proposed Collection: Age, Sex, and Race of Persons...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... Federal Bureau of Investigation Agency Information Collection Activities; Proposed Collection: Age, Sex... Information Collection Under Review. The Department of Justice, Federal Bureau of Investigation, Criminal..., Federal Bureau of Investigation, CJIS Division, Module E-3, 1000 Custer Hollow Road,......

  15. Effects of selective serotonin reuptake inhibitors on three sex steroids in two versions of the aromatase enzyme inhibition assay and in the H295R cell assay.

    PubMed

    Jacobsen, Naja Wessel; Hansen, Cecilie Hurup; Nellemann, Christine; Styrishave, Bjarne; Halling-Sørensen, Bent

    2015-10-01

    Selective serotonin reuptake inhibitors are known to have a range of disorders that are often linked to the endocrine system e.g. hormonal imbalances, breast enlargement, sexual dysfunction, and menstrual cycle disorders. The mechanisms behind most of these disorders are not known in details. In this study we investigated whether the endocrine effect due to SSRI exposure could be detected in well adopted in vitro steroidogenesis assays, two versions of the aromatase enzyme inhibition assay and the H295R cell assay. The five drugs citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, were shown to inhibit the aromatase enzyme in both types of aromatase assays. The IC50 values ranged from 3 to 600 μM. All five SSRIs, were further investigated in the H295R cell line. All compounds altered the steroid secretion from the cells, the lowest observed effect levels were 0.9 μM and 3.1 μM for sertraline and fluvoxamine, respectively. In general the H295R cell assay was more sensitive to SSRI exposure than the two aromatase assays, up to 20 times more sensitive. This indicates that the H295R cell line is a better tool for screening endocrine disrupting effects. Our findings show that the endocrine effects of SSRIs may, at least in part, be due to interference with the steroidogenesis. PMID:26162595

  16. Structure-activity relationship study of non-steroidal NPC1L1 ligands identified through cell-based assay using pharmacological chaperone effect as a readout.

    PubMed

    Karaki, Fumika; Ohgane, Kenji; Fukuda, Hiromitsu; Nakamura, Masahiko; Dodo, Kosuke; Hashimoto, Yuichi

    2014-07-15

    Niemann-Pick type C1-like 1 (NPC1L1) is an intestinal cholesterol transporter that is known to be the target of the cholesterol absorption inhibitor ezetimibe. We previously discovered steroidal NPC1L1 ligands by using a novel cell-based assay that employs pharmacological chaperone effect as a readout. Those steroid derivatives bound to a site different from both the sterol-binding domain and the ezetimibe-binding site, implying that they may be a novel class of NPC1L1 inhibitors with a distinct mode of action. As an extension of that work, we aimed here to find non-steroidal NPC1L1 ligands, which may be better candidates for clinical application than steroidal ligands, by using the same assay to screen our focused library of ligands for liver X receptor (LXR), a nuclear receptor that recognizes oxysterols as endogenous ligands. Here we describe identification of a novel class of NPC1L1 ligands with a ring-fused quinolinone scaffold, and an analysis of the structure-activity relationships of their derivatives as NPC1L1 ligands. PMID:24906511

  17. Na+-K+-activated adenosine triphosphatase and intestinal electrolyte transport. Effect of adrenal steroids.

    PubMed Central

    Charney, A N; Kinsey, M D; Myers, L; Gainnella, R A; Gots, R E

    1975-01-01

    Sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) is associated with electrolyte transport in many tissues. To help delineate its role in intestinal transport, changes in rat intestinal electrolyte and water transport induced by injecting methylprednisolone acetate 3 mg/100 g or deoxycorticosterone acetate (DOCA) 0.5 mg/100 g per day for 3 days were correlated with changes in Na-K-ATPase activity. Methylprednisolone increased sodium and water absorption, potassium secretion, transmural potential difference, and Na-K-ATPase activity in the jejunum, ileum, and colon. Examination of isolated epithelial cells demonstrated that the jejunal and ileal increase in Na-K-ATPase occurred in both the villus tip and crypermeability, Mg-ATPase, and adenylate cyclase activities were unchanged by methylprednisolone. DOCA increased sodium and water absorption, potassium secretion, transmural potential difference, and Na-K-ATPase activity in the colon alone. Colonic Mg-ATPase and adenylate cyclase activities were unaffected. Jejunal and ileal enzyme activity, electrolyte transport, and permeability were unchanged by DOCA. Methylprednisolone and DOCA were not additive in their effect on colonic Na-K-ATPase activity. Methylprednisolone and DOCA increased electrolyte and water transport and Na-K-ATPase activity concomitantly in specific segments of small intestine and colon. These data are consistent with an important role for Na-K-ATPase in intestinal electrolyte and water transport. PMID:125764

  18. LASTING CHANGES IN NEURONAL ACTIVATION PATTERNS IN SELECT FOREBRAIN REGIONS OF AGGRESSIVE, ADOLESCENT ANABOLIC/ANDROGENIC STEROID-TREATED HAMSTERS

    PubMed Central

    Ricci, Lesley A.; Grimes, Jill M.; Melloni, Richard H.

    2007-01-01

    Repeated exposure to anabolic/androgenic steroids (AAS) during adolescence stimulates high levels of offensive aggression in Syrian hamsters. The current study investigated whether adolescent AAS exposure activated neurons in areas of hamster forebrain implicated in aggressive behavior by examining the expression of FOS, i.e., the protein product of the immediate early gene c-fos shown to be a reliably sensitive marker of neuronal activation. Adolescent AAS-treated hamsters and sesame oil-treated littermates were scored for offensive aggression and then sacrificed 1 day later and examined for the number of FOS immunoreactive (FOS-ir) cells in regions of the hamster forebrain important for aggression control. When compared with non-aggressive, oil-treated controls, aggressive AAS-treated hamsters showed persistent increases in the number of FOS-ir cells in select aggression regions, namely the anterior hypothalamus and lateral septum. However, no differences in FOS-ir cells were found in other areas implicated in aggression such as the ventrolateral hypothalamus, bed nucleus of the stria terminals, central and/or medial amygdala or in non-aggression areas such as the samatosensory cortex and the suprachiasmatic nucleus. These results suggest that adolescent AAS exposure may constitutively activate neurons in select forebrain areas critical for the regulation of aggression in hamsters. A model for how persistent activation of neurons in one of these brain regions (i.e., the anterior hypothalamus) may facilitate the development of the aggressive phenotype in adolescent-AAS exposed animals is presented. PMID:17113655

  19. Unusual anti-leukemia activity of nanoformulated naproxen and other non-steroidal anti-inflammatory drugs.

    PubMed

    Kumar, Raj; Siril, Prem Felix; Javid, Farideh

    2016-12-01

    The non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used pharmaceuticals worldwide. Interestingly, many of them have significant anticancer properties too. However, the poor water solubility of certain NSAIDs limits their application for cancer treatment. Nanosizing of such drugs can help to improve the solubility and this may result in enhanced anticancer activities too. Moreover, over dosages and the accompanying side effects of NSAIDs can be minimized by improving their solubility and bioavailability. Successful nanoformulation of three NSAIDs: ibuprofen (IBP), ketoprufen (KP) and naproxen (NAP) using a novel evaporation assisted solvent-antisolvent interaction (EASAI) method is reported here. Three water soluble and biocompatible polymers: polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxypropyl methylcellulose (HPMC) were used to stabilize the drug nanoparticles. Particles having spherical morphology with average size below 30nm were thoroughly characterized using dynamic light scattering and field emission scanning electron microscopy (FESEM) imaging. The nanoformulation resulted in ten to fifteen fold improvements in the solubility and significant enhancement in the in-vitro drug release profiles of the NSAIDs. Anticancer screening of the nanoformulated NSAIDs against five different cancer cell lines such as MCF-7 (Human breast cancer cell line), (Human pancreatic cancer cell line) MIA-PA-CA-2, (Human colon cancer cell line) HT-29, (Human leukemia cell line) Jurkat and (human ovarian carcinoma cell line) A2780 was performed. All the nanoformulated samples showed improved anticancer activity against the Leukemia cancer cell line, out of which NAP-PVP showed the highest anti-cancer activity. The anti-Leukemia activity of NAP-PVP was more than twice that of doxorubicin which is a standard anticancer drug. PMID:27612834

  20. Electromechanical activities of human uteri during extra-corporeal perfusion with ovarian steroids.

    PubMed

    Bulletti, C; Prefetto, R A; Bazzocchi, G; Romero, R; Mimmi, P; Polli, V; Lanfranchi, G A; Labate, A M; Flamigni, C

    1993-10-01

    A new experimental system was designed to study human uterine activities based on the extra-corporeal perfusion of isolated human uteri. Electromechanical activities in the uterine wall were recorded using bipolar silver-silver electrodes, endoluminal pressure catheters and a dedicated acquisition, storage and analytical system. The electrical signals recorded were isolated spikes and rhythmic activities; the last being primarily associated with organized mechanical events. Perfusion media containing 17 beta-oestradiol alone or with progesterone were used for those uteri obtained during proliferative (n = 5) or secretory (n = 5) phases of the menstrual cycle, respectively. Progesterone caused a reduction of frequency (P < 0.001) and duration (P < 0.001) of the rhythmic electrical activity, and decreased the endoluminal pressure at both detection sites (P < 0.01). 17 beta-Oestradiol increased both frequency (P < 0.001) and duration (P < 0.001) of the rhythmic electrical activity as well as the endoluminal pressure at two different detection sites (3 and 5 cm from the fundus) (P < 0.05). Significant differences between the fundus and cervix sites in the uterine wall were detected. In conclusion, uterine perfusion would be useful to examine the effects of uterotonic and tocolytic drugs before administration to humans, at no risk to the patients. Oestrogens increase and progesterone decreases both electrical and mechanical uterine activities. PMID:8300807

  1. Community environments shaping transactional sex among sexually active men in Malawi, Nigeria, and Tanzania.

    PubMed

    Stephenson, Rob; Winter, Amy; Elfstrom, Miriam

    2013-01-01

    Transactional sex, or the exchange of sex for material goods or money, is a risky sexual behavior that has been linked to HIV/AIDS and gender-based violence. Throughout sub-Saharan Africa, transactional sex remains a common practice, putting men and women at risk of HIV. However, little is known of how community environments shape men's participation in risky transactional sex. This analysis examines community-level influences on participation in risky transactional sex among sexually active men in three African countries (Malawi, Tanzania, and Nigeria). The analysis uses Demographic and Health Survey (DHS) data to examine the association between men's report of risky transactional sex and community characteristics including economic, gender norms, HIV behavior and knowledge, and demographic factors. The results show that men residing in communities with more female education and later age of first birth are less likely to report risky transactional sex, while men who live in communities where men report higher number of sexual partners are more likely to report risky transactional sex. While programmatic interventions should continue to improve women's status individually and relative to men, such efforts should be extended to recognize that many community and cultural influences also affect men's sexual behavior. Programs that understand, discuss, and challenge community factors that influence men's sexual behavior may be able to provide a more effective intervention resulting in opportunities for communities to initiate behavioral change. PMID:23215551

  2. The essence of female-male physiological dimorphism: differential Ca2+-homeostasis enabled by the interplay between farnesol-like endogenous sesquiterpenoids and sex-steroids? The Calcigender paradigm.

    PubMed

    De Loof, Arnold

    2015-01-15

    Ca(2+) is the most omnipresent pollutant on earth, in higher concentrations a real threat to all living cells. When [Ca(2+)]i rises above 100 nM (=resting level), excess Ca(2+) needs to be confined in the SER and mitochondria, or extruded by the different Ca(2+)-ATPases. The evolutionary origin of eggs and sperm cells has a crucial, yet often overlooked link with Ca(2+)-homeostasis. Because there is no goal whatsoever in evolution, gametes did neither originate "with the purpose" of generating a progeny nor of increasing fitness by introducing meiosis. The explanation may simply be that females "invented the trick" to extrude eggs from their body as an escape strategy for getting rid of toxic excess Ca(2+) resulting from a sex-hormone driven increased influx into particular cells and tissues. The production of Ca(2+)-rich milk, seminal fluid in males and all secreted proteins by eukaryotic cells may be similarly explained. This view necessitates an upgrade of the role of the RER-Golgi system in extruding Ca(2+). In the context of insect metamorphosis, it has recently been (re)discovered that (some isoforms of) Ca(2+)-ATPases act as membrane receptors for some types of lipophilic ligands, in particular for endogenous farnesol-like sesquiterpenoids (FLS) and, perhaps, for some steroid hormones as well. A novel paradigm, tentatively named "Calcigender" emerges. Its essence is: gender-specific physiotypes ensue from differential Ca(2+)-homeostasis enabled by genetic differences, farnesol/FLS and sex hormones. Apparently the body of reproducing females gets temporarily more poisoned by Ca(2+) than the male one, a selective benefit rather than a disadvantage. PMID:25540913

  3. Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids

    PubMed Central

    Thiblin, Ingemar; Finn, Anja; Ross, Svante B; Stenfors, Carina

    1999-01-01

    The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. The DOPAC+HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone- and oxymetholone-treated rats, while the 5-HT synthesis rate was not affected by the AAS-treatments. The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were unaffected. The MAO-B activity was not changed. The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems. PMID:10217522

  4. Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids.

    PubMed

    Thiblin, I; Finn, A; Ross, S B; Stenfors, C

    1999-03-01

    1. The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. 2. The DOPAC + HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. 3. The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone- and oxymetholone-treated rats, while the 5-HT synthesis rate was not affected by the AAS-treatments. 4. The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were unaffected. The MAO-B activity was not changed. 5. The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems. PMID:10217522

  5. 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…

  6. Why we should consider sex (and study sex differences) in addiction research.

    PubMed

    Sanchis-Segura, Carla; Becker, Jill B

    2016-09-01

    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 pre-clinical evidences 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

  7. Profiles of sex steroids, fecundity, and spawning of the curimatã-pacu Prochilodus argenteus in the São Francisco River, downstream from the Três Marias Dam, Southeastern Brazil.

    PubMed

    Arantes, Fábio P; Santos, Helio B; Rizzo, Elizete; Sato, Yoshimi; Bazzoli, Nilo

    2010-04-01

    The present study evaluated for the first time sex steroid profiles and fecundity in females of Prochilodus argenteus from two sections of the São Francisco River Brazil, downstream from the Três Marias Dam, which influences characteristics of their water habitat. The model species in the study, P. argenteus, is an important commercial and recreational species in Brazil. In the region closest to the dam (section 1), females did not reach final oocyte maturation, failed to spawn, and displayed lesser circulating concentrations of testosterone, 17(-hydroxyprogesterone (17(-P) and 17beta-estradiol (E2) than those farther downstream of the dam (section 2). The endocrine and fecundity deficiencies probably are attributed to lower water temperature and oxygen concentration in (section 1). The follicular atresia rate in the region closest to the dam (26%) was greater than those fish captured farther downstream of the dam (13%), after the Abaeté River (section 2). Variations in testosterone, E2 and 17(-P concentrations in section 2, followed gonadal maturation which are typical features of species which have seasonal reproduction, group-synchronous oocyte development, and are single batch spawners such as P. argenteus. Results document the first evidence of endocrine and reproductive dysfunctions caused by inadequate water conditions in a wild population of the migratory species P. argenteus in the São Francisco River, downstream from the Três Marias dam. PMID:19683404

  8. ESTROGENIC ACTIVITY AND STEROID HORMONES IN SWINE WASTEWATER PROCESSED THROUGH A LAGOON CONSTRUCTED-WETLAND SYSTEM.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anaerobic lagoons and treatment wetlands are used world-wide to treat wastewater from dense livestock production facilities. However, there is very limited data on the hormonal activity of the wastewater effluent produced by these treatment systems. The objectives of this experiment were to measur...

  9. Serum levels of cartilage oligomeric matrix protein (COMP): a rapid decrease in patients with active rheumatoid arthritis undergoing intravenous steroid treatment.

    PubMed

    Skoumal, M; Haberhauer, G; Feyertag, J; Kittl, E M; Bauer, K; Dunky, A

    2006-09-01

    To examine the influence of intravenous steroid-treatment (IST) on serum levels of Cartilage oligomeric matrix protein (COMP) in patients with active rheumatoid arthritis (RA). Serum levels of COMP and C-reactive protein (CRP) were measured in 12 patients with highly active RA (Steinbrocker stages II-IV) and in 5 patients with highly active reactive arthritis (ReA) (positive testing for HLA-B27) before starting daily IST. Patients received a total steroid dosage between 100 and 500 mg of prednisolone. COMP was measured by a commercially available sandwich-type ELISA-kit developed by AnaMar Medical AB, Sweden. Statistical evaluation was calculated by paired t test. In the RA group, COMP levels ranged from 6.3 to 19.4 U/l (mean 12.9 U/l), CRP from 5 to 195 mg/l (mean 77.8 mg/l), the COMP levels of the ReA group ranged from 5.1 to 7.4 U/l (mean 7.9 U/l), the CRP levels from 13 to 126 mg/l (mean 49 mg/l). We found a significant difference between the initial COMP levels in RA+ and ReA patients (P<0.005). In contrast to the ReA group, serum-COMP levels of RA+ patients (P<0.004) and the VAS (P<0.0001) decreased significantly within 2-10 days after the first treatment with steroids. The CRP levels remained unchanged in both groups. Our results indicate that the intravenous treatment with steroids in patients with highly active RA leads to a significant decrease of cartilage degradation. COMP seems to be a valuable parameter not even as a prognostic factor, but as a marker for monitoring the therapy response in patients with RA. PMID:16485108

  10. Study the antiviral activity of some derivatives of tetracycline and non-steroid anti inflammatory drugs towards dengue virus.

    PubMed

    Rothan, H A; Buckle, M J; Ammar, Y A; Mohammadjavad, P; Shatrah, O; Noorsaadah, A R; Rohana, Y

    2013-12-01

    Various clinical symptoms are caused by dengue virus ranging from mild fever to severe hemorrhagic fever while there is no successful anti-dengue therapeutics available. Among different strategies towards identifying and developing anti-dengue therapeutics, testing anti-dengue properties of known drugs could represent an efficient strategy for which information of its medical approval, toxicity and side effects is readily available. In this study, we evaluated the antiviral activity of some medical compounds towards dengue NS2B-NS3 protease (DENV2 NS2B-NS3pro) as a target to inhibit dengue virus replication. Mefenamic acid, a non-steroid anti inflammatory drug and doxycycline, a derivative antibiotic of tetracycline both showed significant inhibition potential against DENV2 NS2B-NS3pro Ki values 32 ± 2 μM and 55 ± 5 μM respectively. The effective cytotoxic concentrations of 50% (CC50) against Vero cells were evaluated for mefenamic acid (150 ± 5 μM) and doxycycline (125 ± 4 μM). Concentrations lower than CC50 were used to test the inhibition potential of these compounds against DENV2 replication in Vero cells. The results showed significant reduction in viral load after applying mefenamic acid and doxycyline in concentration dependent manner. Mefenamic acid reduced viral RNA at EC50 of 32 ± 4 μM whilst doxycycline EC50 was 40 ± 3 μM. Mefenamic acid showed higher selectivity against dengue virus replication in vitro compared to doxycycline. These findings underline the need for further experimental and clinical studies on these drugs utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue infection. PMID:24522138

  11. Naturally occurring steroids in Xenopus oocyte during meiotic maturation. Unexpected presence and role of steroid sulfates.

    PubMed

    Haccard, Olivier; Dupré, Aude; Liere, Philippe; Pianos, Antoine; Eychenne, Bernard; Jessus, Catherine; Ozon, René

    2012-10-15

    In the ovary, oocytes are surrounded by follicle cells and arrested in prophase of meiosis I. Although steroidogenic activity of follicle cells is involved in oogenesis regulation, clear qualitative and quantitative data about the steroid content of follicles are missing. We measured steroid levels of Xenopus oocytes and follicles by gas chromatography-mass spectrometry. We show that dehydroepiandrosterone sulfate is the main steroid present in oocytes. Lower levels of free steroids are also detected, e.g., androgens, whereas progesterone is almost undetectable. We propose that sulfatation is a protective mechanism against local variations of active steroids that could be deleterious for follicle-enclosed oocytes. Steroid levels were measured after LH stimulation, responsible for the release by follicle cells of a steroid signal triggering oocyte meiosis resumption. Oocyte levels of androgens rise slowly during meiosis re-entry whereas progesterone increases abruptly to micromolar concentration, therefore representing the main physiological mediator of meiosis resumption in Xenopus oocyte. PMID:22687883

  12. [Steroidal saponins from the plant Agave brittoniana with activity against the parasite Trichomona vaginalis].

    PubMed

    Guerra, José Orestes; Meneses, Alfredo; Simonet, Ana María; Macías, Francisco Antonio; Nogueiras, Clara; Gómez, Alicia; Escario, José A

    2008-12-01

    The genus Agave (Agavaceae), includes more than 300 species; around 16 of them show an homogeneous distribution throughout Cuba. Agave brittoniana (ssp. brachypus), is an endemic subspecies that grows in the central region of the country and its leaves are traditionally used in the treatment of parasitic diseases. The parasite Trichomonas vaginalis causes the disease known as trichomoniasis, that infects the genital tract. To test in vitro the plant against Trichomona vaginalis, the dried and powdered leaves were extracted three times with ethanol-water (7:3) by maceration at room temperature. The solvent was removed under reduced pressure and the extract was suspended in distilled water, defatted with n-hexane, and extracted with water-saturated n-butanol. After solvent removal, a portion of the n-butanol extract was hydrolyzed. After extraction with ethyl acetate the hydrolysis products were compared with authentic sapogenins samples using thin layer chromatography (TLC). Most of the sapogenins (yuccagenin and diosgenin) were isolated and their structures were confirmed. using nuclear magnetic resonance (NMR) experiments. The n-butanol extract was subjected to a separation process through column chromatography to obtain five fractions. After multiple separation processes by reversed phase high performance liquid chromatography (HPLC), the most active one produced one refined fraction that contained two saponins with the same aglycone (diosgenin) and one yuccagenin based saponin. Best results of the activity were obtained with the yuccagenin derived glycoside. PMID:19419073

  13. Polyoxygenated Steroids from the Octocoral Leptogorgia punicea and in Vitro Evaluation of Their Cytotoxic Activity

    PubMed Central

    Moritz, Maria Izabel G.; Marostica, Lucas Lourenço; Bianco, Éverson M.; Almeida, Maria Tereza R.; Carraro, João L.; Cabrera, Gabriela M.; Palermo, Jorge A.; Simões, Cláudia M. O.; Schenkel, Eloir P.

    2014-01-01

    Five new polyoxygenated marine steroids—punicinols A–E (1–5)—were isolated from the gorgonian Leptogorgia punicea and characterized by spectroscopic methods (IR, MS, 1H, 13C and 2-D NMR). The five compounds induced in vitro cytotoxic effects against lung cancer A549 cells, while punicinols A and B were the most active, with IC50 values of 9.7 μM and 9.6 μM, respectively. The synergistic effects of these compounds with paclitaxel, as well as their effects on cell cycle distribution and their performance in the clonogenic assay, were also evaluated. Both compounds demonstrated significant synergistic effects with paclitaxel. PMID:25486111

  14. A review of steroids from Sarcophyton species.

    PubMed

    Zubair, Muhammad Sulaiman; Al-Footy, Khalid O; Ayyad, Seif-Eldin N; Al-Lihaibi, Sultan S; Alarif, Walied M

    2016-04-01

    This review reports the structural diversity of steroids from Sarcophyton species based on literature from the beginning of marine steroid research until now. There are 65 compounds studied from eight species. Most of them are polyhydroxy-type steroids of C-27-C-31 carbon skeleton. Their biological activities are highly diverse ranging from cytotoxic, antibacterial, antifungal, antiviral, anti-inflammatory, antidiabetic to antiosteoporosis properties. PMID:26299957

  15. Diagnostic investigation of steroid estrogen removal by activated sludge at varying solids retention time.

    PubMed

    Petrie, Bruce; McAdam, Ewan J; Hassard, Francis; Stephenson, Tom; Lester, John N; Cartmell, Elise

    2014-10-01

    The impact of solids retention time (SRT) on estrone (E1), 17β-estradiol (E2), estriol (E3) and 17α-ethinylestradiol (EE2) removal in an activated sludge plant (ASP) was examined using a pilot plant to closely control operation. Exsitu analytical methods were simultaneously used to enable discrimination of the dominant mechanisms governing estrogen removal following transitions in SRT from short (3d) to medium (10d) and long (27d) SRTs which broadly represent those encountered at full-scale. Total estrogen (∑EST, i.e., sum of E1, E2, E3 and EE2) removals which account for aqueous and particulate concentrations were 70±8, 95±1 and 93±2% at 3, 10 and 27d SRTs respectively. The improved removal observed following an SRT increase from 3 to 10d was attributable to the augmented biodegradation of the natural estrogens E1 and E2. Interestingly, estrogen biodegradation per bacterial cell increased with SRT. These were 499, 1361 and 1750ng 10(12) viable cells(-1)d(-1). This indicated an improved efficiency of the same group or the development of a more responsive group of bacteria. In this study no improvement in absolute ∑EST removal was observed in the ASP when SRT increased from 10 to 27d. However, batch studies identified an augmented biomass sorption capacity for the more hydrophobic estrogens E2 and EE2 at 27d, equivalent to an order of magnitude. The lack of influence on estrogen removal during pilot plant operation can be ascribed to their distribution within activated sludge being under equilibrium. Consequently, lower wastage of excess sludge inherent of long SRT operation counteracts any improvement in sorption. PMID:25065796

  16. Effects of sex and gonadal steroids on arginine vasotocin and mesotocin in the pineal gland and neurohypophysis of White Leghorn fowls.

    PubMed

    Robinzon, B; Sayag, N; Koike, T I; Kinzler, S L; Neldon, H L

    1990-12-01

    1. Pineal and neurohypophysial arginine vasotocin (AVT) and mesotocin (MT) were measured in White Leghorn hens, cockerels and castrated males treated with either testosterone propionate (TP) or oestradiol benzoate (EB) (n = 10/group). The lighting regimen was 14 h light: 10 h dark, supplied by natural diffused sunlight and incandescent bulbs. 2. Both AVT and MT were detected in the pineal gland of all the chickens. 3. There was no significant effect of either sex or treatments on pineal MT. 4. Females had about 4 times more pineal AVT than males, regardless of their treatment. There was no effect of the treatments on pineal AVT in the males. 5. No sexual difference in neurohypophysial AVT was detected, but the neurohypophysis of the castrated males treated with EB contained less AVT than the neurohypophysis of the intact males. 6. Intact males had about twice as much MT in the neurohypophysis as females. Castrated males treated with either TP or EB had similar concentrations of neurohypophysial MT, which were lower than that of the intact males, but higher than that of the females. PMID:2097038

  17. Effects of steroids and verapamil on P-glycoprotein ATPase activity: progesterone, desoxycorticosterone, corticosterone and verapamil are mutually non-exclusive modulators.

    PubMed Central

    Orlowski, S; Mir, L M; Belehradek, J; Garrigos, M

    1996-01-01

    P-glycoprotein (P-gp) is a membranous ATPase responsible for the multidrug resistance (MDR) phenotype. Using membrane vesicles prepared from the highly resistant cell line DC-3F/ADX we studied the influence of P-gp ATPase activity of four progesterone derivatives which specifically bind to P-gp and reverse MDR. Progesterone and desoxycorticosterone stimulate P-gp ATPase activity with, respectively, apparent concentrations giving half-maximal activation of 20-25 microM and 40-50 microM, and activation factors of 2.3 (at 100 microM progesterone) and 1.8 (at 170 microM desoxycorticosterone). Hydrocortisone above 100 microM stimulates P-gp ATPase activity while corticosterone has no apparent stimulating effect. Our data are consistent with the location of the binding sites for the progesterone derivatives on the P-gp membranous domain. The effects of these steroids on verapamil-stimulated P-gp ATPase activity support a non-competitive mechanism, i.e. the binding sites for verapamil and steroids are mutually non-exclusive for P-gp ATPase modulation. A similar non-competitive inhibition of progesterone-stimulated P-gp ATPase activity by desoxycorticosterone or by corticosterone leads to the conclusion that these steroids, although sharing related structures, have distinct modulating sites on P-gp. As expected from their mutually non-exclusive interactions on P-gp, progesterone and verapamil when mixed induce a synergistic modulation of P-gp ATPase activity. Since drug transport by P-gp is believed to be coupled to its ATPase activity, a corresponding synergistic effect of these two modulators for the inhibition of P-gp-mediated drug resistance can be expected. PMID:8713080

  18. Steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota—Study design, methods, and data, 2009–10

    USGS Publications Warehouse

    Erickson, Melinda L.

    2012-01-01

    The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota during 2009–10. This report describes the study design and methods, and presents the data collected on steroidal hormones and other related compounds. Environmental and quality-control samples were collected from 40 wells as part of this study. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 16 steroidal hormones and 4 other related compounds, of which all but 2 compounds are endocrine active compounds. Most of the water samples did not contain detectable concentrations of any of the 20 compounds analyzed. Water samples from three wells had detectable concentrations of one or more compounds. Bisphenol A was detected in samples from three wells, and trans-diethylstilbestrol was detected in one of the samples in which bisphenol A also was detected.

  19. Sex-specific hemispheric differences in cortical activation to a bimodal odor.

    PubMed

    Lundström, Johan N; Hummel, Thomas

    2006-01-30

    Most odorants we experience in every day life are bimodal in that they activate both the main olfactory and the intranasal trigeminal system. Few studies have investigated whether true bimodal odorants are processed differently than unimodal odorants. The aim of the study was to address sex-dependent hemispheric differences in olfactory event-related potentials. Event-related potentials (ERP) of the bimodal stimulant peppermint oil were recorded in 34 healthy subjects (17 women). No sex-related differences in olfactory sensitivity, trigeminal sensitivity or hedonic ratings of the stimuli were found. Although perceived similarly by men and women, results indicated a sex-differentiated hemispheric response to bimodal odors. Women generally expressed larger amplitudes and longer latencies over their left hemisphere, whereas men demonstrated a similar pattern over their right hemisphere. This effect was most evident for the early sensory derived ERP components indicating a sex-dependent difference in the sensory processing of bimodal odors. PMID:16183142

  20. Sex hormones, sexual activity and plasma anticonvulsant levels in male epileptics.

    PubMed Central

    Toone, B K; Wheeler, M; Nanjee, M; Fenwick, P; Grant, R

    1983-01-01

    Testosterone, LH, FSH, PRL, and sex hormone binding globulin (SHBG) were measured in 72 male epileptic patients on chronic anticonvulsant drug regimes. Sexual activity was estimated and plasma anticonvulsants measured. Total testosterone (TT), LH, FSH, PRL, and SHBG were increased; free testosterone (FT) was decreased. Sexual activity appeared diminished particularly in relation to reduced FT. PMID:6413659

  1. Classroom Activities in Sex Equity for Developmental Guidance. Bulletin No. 9204.

    ERIC Educational Resources Information Center

    Wisconsin State Dept. of Public Instruction, Madison.

    Classroom activities focusing on sex equity issues which help students and educators overcome limiting stereotypes, bias, and even discrimination based on gender are described in this document. The activities are arranged by these educational levels: elementary/primary; elementary/intermediate; middle/junior high; and high school. Within each…

  2. Temporal variability of local abundance, sex ratio and activity in the Sardinian chalk hill blue butterfly

    USGS Publications Warehouse

    Casula, P.; Nichols, J.D.

    2003-01-01

    When capturing and marking of individuals is possible, the application of newly developed capture-recapture models can remove several sources of bias in the estimation of population parameters such as local abundance and sex ratio. For example, observation of distorted sex ratios in counts or captures can reflect either different abundances of the sexes or different sex-specific capture probabilities, and capture-recapture models can help distinguish between these two possibilities. Robust design models and a model selection procedure based on information-theoretic methods were applied to study the local population structure of the endemic Sardinian chalk hill blue butterfly, Polyommatus coridon gennargenti. Seasonal variations of abundance, plus daily and weather-related variations of active populations of males and females were investigated. Evidence was found of protandry and male pioneering of the breeding space. Temporary emigration probability, which describes the proportion of the population not exposed to capture (e.g. absent from the study area) during the sampling process, was estimated, differed between sexes, and was related to temperature, a factor known to influence animal activity. The correlation between temporary emigration and average daily temperature suggested interpreting temporary emigration as inactivity of animals. Robust design models were used successfully to provide a detailed description of the population structure and activity in this butterfly and are recommended for studies of local abundance and animal activity in the field.

  3. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus).

    PubMed

    Walaszczyk, Erin J; Johnson, Nicholas S; Steibel, Juan Pedro; Li, Weiming

    2013-06-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p < 0.05) and cause increases in activity during several daytime hours in preovulated and ovulated females. These results are one of the first examples of how sex pheromones modulate a locomotor rhythm in a vertebrate, and they suggest that the interaction between maturity stage and sex pheromone exposure contributes to the differential locomotor rhythms found in adult female sea lamprey. This phenomenon may contribute to the reproductive synchrony of mature adults, thus increasing reproductive success in this species. PMID:23735501

  4. Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus)

    USGS Publications Warehouse

    Walaszczyk, Erin J.; Johnson, Nicholas S.; Steibel, Juan Pedro; Li, Weiming

    2013-01-01

    Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p < 0.05) and cause increases in activity during several daytime hours in preovulated and ovulated females. These results are one of the first examples of how sex pheromones modulate a locomotor rhythm in a vertebrate, and they suggest that the interaction between maturity stage and sex pheromone exposure contributes to the differential locomotor rhythms found in adult female sea lamprey. This phenomenon may contribute to the reproductive synchrony of mature adults, thus increasing reproductive success in this species.

  5. Sex differences in social cognitive factors and physical activity in Korean college students

    PubMed Central

    Choi, Jin Yi; Chang, Ae Kyung; Choi, Eun-Ju

    2015-01-01

    [Purpose] This study examined sex differences in physical activity and social cognitive theory factors in Korean college students. [Subjects and Methods] A cross-sectional survey of 688 college students (285 men and 403 women) in Korea was conducted using a self-reported questionnaire. [Results] There was a significant difference in the level of physical activity between male and female students. The significant predictors of physical activity for male students were physical activity goals, physical activity self-efficacy, and sitting time. Meanwhile, those for female students were perceived weight, physical activity goal, physical activity outcome expectations, and sitting time. [Conclusion] Sex differences should be considered when developing interventions to increase physical activity. PMID:26180293

  6. Sex Differences in Activation of the Hypothalamic-Pituitary-Adrenal Axis by Methamphetamine

    PubMed Central

    Zuloaga, Damian G; Johnson, Lance A; Agam, Maayan; Raber, Jacob

    2014-01-01

    Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activation is associated with changes in addiction-related behaviors. In this study we tested whether sex differences in the acute effects of methamphetamine (MA) exposure involve differential activation of the HPA axis. Male and female mice were injected with MA (1mg/kg) or saline for comparison of plasma corticosterone and analysis of the immediate early gene c-Fos in brain. There was a prolonged elevation in corticosterone levels in female compared to male mice. C-Fos was elevated in both sexes following MA in HPA axis-associated regions, including the hypothalamic paraventricular nucleus (PVN), central amygdala, cingulate, and CA3 hippocampal region. MA increased the number of c-Fos and c-Fos/glucocorticoid receptor (GR) dual-labeled cells to a greater extent in males than females in the cingulate and CA3 regions. MA also increased the number of c-fos/vasopressin dual-labeled cells in the PVN as well as the number and percentage of c-Fos/GR dual-labeled cells in the PVN and central amygdala, although no sex differences in dual-labeling were found in these regions. Thus, sex differences in MA-induced plasma corticosterone levels and activation of distinct brain regions and proteins involved in HPA axis regulation may contribute to sex differences in acute effects of MA on the brain. PMID:24400874

  7. Steroidal Saponins in Oat Bran.

    PubMed

    Yang, Junli; Wang, Pei; Wu, Wenbin; Zhao, Yantao; Idehen, Emmanuel; Sang, Shengmin

    2016-02-24

    Saponins are one type of widespread defense compound in the plant kingdom and have been exploited for the production of lead compounds with diverse pharmacological properties in drug discovery. Oats contain two unique steroidal saponins, avenacoside A, 1, and avenacoside B, 2. However, the chemical composition, the levels of these saponins in commercial oat products, and their health effects are still largely unknown. In this study, we directly purified 5 steroidal saponins (1-5) from a methanol extract of oat bran, characterized their structures by analyzing their MS and NMR spectra, and also tentatively identified 11 steroidal saponins (6-16) on the basis of their tandem mass spectra (MS(n), n = 2-3). Among the five purified saponins, 5 is a new compound and 4 is purified from oats for the first time. Using HPLC-MS techniques, a complete profile of oat steroidal saponins was determined, and the contents of the two primary steroidal saponins, 1 and 2, were quantitated in 15 different commercial oat products. The total levels of these two saponins vary from 49.6 to 443.0 mg/kg, and oat bran or oatmeal has higher levels of these two saponins than cold oat cereal. Furthermore, our results on the inhibitory effects of 1 and 2 against the growth of human colon cancer cells HCT-116 and HT-29 showed that both had weak activity, with 2 being more active than 1. PMID:26852819

  8. Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model.

    PubMed

    Huet, Tiphaine; Miannay, François-Alexandre; Patton, Jeffrey R; Thore, Stéphane

    2014-01-01

    The most abundant of the modified nucleosides, and once considered as the "fifth" nucleotide in RNA, is pseudouridine, which results from the action of pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1 (hPus1p) has been reported to modulate class I and class II nuclear receptor responses through its ability to modify the Steroid receptor RNA Activator (SRA). These findings highlight a new level of regulation in nuclear receptor (NR)-mediated transcriptional responses. We have characterised the RNA association and activity of the human Pus1p enzyme with its unusual SRA substrate. We validate that the minimal RNA fragment within SRA, named H7, is necessary for both the association and modification by hPus1p. Furthermore, we have determined the crystal structure of the catalytic domain of hPus1p at 2.0 Å resolution, alone and in a complex with several molecules present during crystallisation. This model shows an extended C-terminal helix specifically found in the eukaryotic protein, which may prevent the enzyme from forming a homodimer, both in the crystal lattice and in solution. Our biochemical and structural data help to understand the hPus1p active site architecture, and detail its particular requirements with regard to one of its nuclear substrates, the non-coding RNA SRA. PMID:24722331

  9. Transposon Insertions Causing Constitutive Sex-Lethal Activity in Drosophila Melanogaster Affect Sxl Sex-Specific Transcript Splicing

    PubMed Central

    Bernstein, M.; Lersch, R. A.; Subrahmanyan, L.; Cline, T. W.

    1995-01-01

    Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle ``on'' vs. ``off'' reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. ``Male-lethal'' (Sxl(M)) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, Sxl(M) haplo-X animals (chromosomal males) die because of improper dosage compensation, and Sxl(M) chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Five independent spontaneous Sxl(M) alleles were shown previously to be transposon insertions into what was subsequently found to be the region of regulated sex-specific Sxl RNA splicing. We show that these five alleles represent three different mutant types: Sxl(M1), Sxl(M3), and Sxl(M4). Sxl(M1) is an insertion of a roo element 674 bp downstream of the translation-terminating male-specific exon. Sxl(M3) is an insertion of a hobo transposon (not 297 as previously reported) into the 3' splice site of the male exon, and Sxl(M4) is an insertion of a novel transposon into the male-specific exon itself. We show that these three gain-of-function mutants differ considerably in their ability to bypass the sex determination signal, with Sxl(M4) being the strongest and Sxl(M1) the weakest. This difference is also reflected in effects of these mutations on sex-specific RNA splicing and on the rate of

  10. Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing.

    PubMed

    Bernstein, M; Lersch, R A; Subrahmanyan, L; Cline, T W

    1995-02-01

    Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle "on" vs. "off" reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. "Male-lethal" (SxlM) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, SxlM haplo-X animals (chromosomal males) die because of improper dosage compensation, and SxlM chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Five independent spontaneous SxlM alleles were shown previously to be transposon insertions into what was subsequently found to be the region of regulated sex-specific Sxl RNA splicing. We show that these five alleles represent three different mutant types: SxlM1, SxlM3, and SxlM4. SxlM1 is an insertion of a roo element 674 bp downstream of the translation-terminating male-specific exon. SxlM3 is an insertion of a hobo transposon (not 297 as previously reported) into the 3' splice site of the male exon, and SxlM4 is an insertion of a novel transposon into the male-specific exon itself. We show that these three gain-of-function mutants differ considerably in their ability to bypass the sex determination signal, with SxlM4 being the strongest and SxlM1 the weakest. This difference is also reflected in effects of these mutations on sex-specific RNA splicing and on the rate of appearance of SXL protein in

  11. "Screw health": representations of sex as a health-promoting activity in medical and popular literature.

    PubMed

    Gupta, Kristina

    2011-06-01

    Recently, scientific and popular press articles have begun to represent sex as a health-promoting activity. A number of scientific studies have identified possible health benefits of sexual activity, including increased lifespan and decreased risk of certain types of cancers. These scientific findings have been widely reported on in the popular press. This "sex for health" discourse claims that sexual activity leads to quantifiable physical and mental health benefits in areas not directly related to sexuality. Analyzing this discourse provides an opportunity to better understand both broader health promotion discourses and current norms and anxieties about sexuality. In this article, I place this "sex for health" discourse within the context of broader health promotion discourses and within the context of a number of historical and contemporary discourses connecting health and sexuality. I argue that although the "sex for health" discourse may serve to de-stigmatize sexual activity for some, it may also increase pressure on others to be sexually active and may further pathologize sexual "dysfunction." In addition, these representations often serve to further privilege a normative form of sexual behavior - coitus in the context of a monogamous heterosexual partnership - at the expense of non-normative sexual desires, identities, and practices. PMID:21243416

  12. 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

  13. The Inhibitory Effect of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on the Monophenolase and Diphenolase Activities of Mushroom Tyrosinase

    PubMed Central

    Sato, Kazuomi; Toriyama, Masaru

    2011-01-01

    In the present work, we investigated the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the monophenolase and diphenolase activity of mushroom tyrosinase. The results showed that diflunisal and indomethacin inhibited both monophenolase and diphenolase activity. For monophenolase activity, the lag time was extended in the presence of diflunisal. In the presence of indomethacin, the lag time did not change. IC50 values of monophenolase activity were estimated to be 0.112 mM (diflunisal) and 1.78 mM (indomethacin). Kinetic studies of monophenolase activity revealed that both diflunisal and indomethacin were non-competitive inhibitors. For diphenolase activity, IC50 values were estimated to be 0.197 mM (diflunisal) and 0.509 mM (indomethacin). Diflunisal and indomethacin were also found to be non-competitive diphenolase inhibitors. PMID:21747720

  14. Expression of the androgen receptor in the testes and the concentrations of gonadotropins and sex steroid hormones in male turkeys (Meleagris gallopavo) during growth and development.

    PubMed

    Kiezun, J; Leska, A; Kaminska, B; Jankowski, J; Dusza, L

    2015-04-01

    Androgens, including testosterone (T) and androstenedione (A4), are essential for puberty, fertility and sexual functions. The biological activity of those hormones is mediated via the androgen receptor (AR). The regulation of androgen action in birds is poorly understood. Therefore, the present study analysed mRNA and protein expression of AR in the testes, plasma concentrations of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), T, A4 and oestradiol (E2), as well as the levels of T, A4 and E2 in testicular homogenates of male turkeys (Meleagris gallopavo) at the age of 4, 8, 12, 16, 20, 24 and 28weeks. Plasma concentrations of LH and FSH, as well as plasma and testicular levels of T and A4 began to increase at 20weeks of age. The lowest plasma levels of E2 were noted at 20weeks relative to other growth stages. The 20th week of life seems to be the key phase in the development of the reproductive system of turkeys. The AR protein was found in the nuclei of testicular cells in all examined growth stages. Higher expression of AR protein in the testes beginning at 20weeks of age was accompanied by high plasma concentrations of LH and high plasma and testicular levels of androgens. This relationship seems to be necessary to regulate male sexual function. PMID:25072891

  15. Influence of Age, Sex, and Race on College Students' Exercise Motivation of Physical Activity

    ERIC Educational Resources Information Center

    Egli, Trevor; Bland, Helen W.; Melton, Bridget F.; Czech, Daniel R.

    2011-01-01

    Objective: The authors examined differences in exercise motivation between age, sex, and race for college students. Participants: Students from 156 sections of physical activity classes at a midsize university were recruited (n = 2,199; 1,081 men, 1,118 women) in 2005-2006 and volunteered to complete the Exercise Motivation Inventory. Methods:…

  16. Developmental and Individual Differences in Girls' Sex-Typed Activities in Middle Childhood and Adolescence

    ERIC Educational Resources Information Center

    McHale, Susan M.; Shanahan, Lilly; Updegraff, Kimberly A.; Crouter, Ann C.; Booth, Alan

    2004-01-01

    Girls' time in sex-typed leisure activities was studied across 2 years in middle childhood (n=98, M=8.2 years in Year 1), early adolescence (n=106, M=11.7 years), and middle adolescence (n=86, M=14.9 years). In annual home interviews, White middle-class girls, mothers, and fathers rated their gendered attitudes, interests, and personality…

  17. The Mating Game: A Classroom Activity for Undergraduates that Explores the Evolutionary Basis of Sex Roles

    ERIC Educational Resources Information Center

    Moore, Dani; Holbrook, C. Tate; Meadows, Melissa G.; Taylor, Lisa A.

    2012-01-01

    In species that reproduce sexually, an individual's fitness depends on its ability to secure a mate (or mates). Although both males and females are selected to maximize their reproductive output, the mating strategies of the two sexes can differ dramatically. We present a classroom simulation that allows undergraduates to actively experience how…

  18. PCB concentrations and activity of sea lamprey Petromyzon marinus vary by sex

    USGS Publications Warehouse

    Madenjian, Charles P.; Johnson, Nicholas S.; Binder, Thomas R.; Rediske, Richard R.; O'Keefe, James P.

    2013-01-01

    We determined the polychlorinated biphenyl (PCB) concentrations of 40 male and 40 female adult sea lampreys Petromyzon marinus captured in the Cheboygan River, a tributary to Lake Huron, during May 2011. In addition, we performed a laboratory experiment using passive integrated transponder tags to determine whether male adult sea lampreys were more active than female adult sea lampreys. Sex had a significant effect on PCB concentration, and PCB concentration at a given level of sea lamprey condition was approximately 25 % greater in males than in females. Adjusting for the difference in condition between the sexes, males averaged a 17 % greater PCB concentration compared with females. Results from the laboratory experiment indicated that males were significantly more active than females. The observed sex difference in PCB concentrations was not due to female sea lampreys releasing eggs at spawning because the sea lamprey is semelparous, and we caught the sea lampreys before spawning. Rather, we attributed the sex difference in PCB concentrations to a greater rate of energy expenditure in males compared with females. We proposed that this greater rate of energy expenditure was likely due to greater activity. Our laboratory experiment results supported this hypothesis. A greater resting metabolic rate may also have contributed to a greater rate of energy expenditure. Our findings should eventually be applicable toward improving control of sea lamprey, a pest responsible for considerable damage to fisheries in lakes where it is not native.

  19. Built Environment Influences of Children's Physical Activity: Examining Differences by Neighbourhood Size and Sex.

    PubMed

    Mitchell, Christine A; Clark, Andrew F; Gilliland, Jason A

    2016-01-01

    Neighbourhoods can facilitate or constrain moderate-to-vigorous physical activity (MVPA) among children by providing or restricting opportunities for MVPA. However, there is no consensus on how to define a child's neighbourhood. This study examines the influence of the neighbourhood built environment on objectively measured MVPA among 435 children (aged 9-14 years) in London (ON, Canada). As there is no consensus on how to delineate a child's neighbourhood, a geographic information system was used to generate measures of the neighbourhood built environment at two buffer sizes (500 m and 800 m) around each child's home. Linear regression models with robust standard errors (cluster) were used to analyze the relationship between built environment characteristics and average daily MVPA during non-school hours on weekdays. Sex-stratified models assessed sex-specific relationships. When accounting for individual and neighbourhood socio-demographic variables, park space and multi-use path space were found to influence children's MVPA. Sex-stratified models found significant associations between MVPA and park space, with the 800 m buffer best explaining boys' MVPA and the 500 m buffer best explaining girls' MVPA. Findings emphasize that, when designing built environments, programs, and policies to facilitate physical activity, it is important to consider that the size of the neighbourhood influencing a child's physical activity may differ according to sex. PMID:26784212

  20. Built Environment Influences of Children’s Physical Activity: Examining Differences by Neighbourhood Size and Sex

    PubMed Central

    Mitchell, Christine A.; Clark, Andrew F.; Gilliland, Jason A.

    2016-01-01

    Neighbourhoods can facilitate or constrain moderate-to-vigorous physical activity (MVPA) among children by providing or restricting opportunities for MVPA. However, there is no consensus on how to define a child’s neighbourhood. This study examines the influence of the neighbourhood built environment on objectively measured MVPA among 435 children (aged 9–14 years) in London (ON, Canada). As there is no consensus on how to delineate a child’s neighbourhood, a geographic information system was used to generate measures of the neighbourhood built environment at two buffer sizes (500 m and 800 m) around each child’s home. Linear regression models with robust standard errors (cluster) were used to analyze the relationship between built environment characteristics and average daily MVPA during non-school hours on weekdays. Sex-stratified models assessed sex-specific relationships. When accounting for individual and neighbourhood socio-demographic variables, park space and multi-use path space were found to influence children’s MVPA. Sex-stratified models found significant associations between MVPA and park space, with the 800 m buffer best explaining boys’ MVPA and the 500 m buffer best explaining girls’ MVPA. Findings emphasize that, when designing built environments, programs, and policies to facilitate physical activity, it is important to consider that the size of the neighbourhood influencing a child’s physical activity may differ according to sex. PMID:26784212

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. Neurosteroid Analogues. 18. Structure–Activity Studies of ent-Steroid Potentiators of γ-Aminobutyric Acid type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone

    PubMed Central

    Qian, Mingxing; Krishnan, Kathiresan; Kudova, Eva; Li, Ping; Manion, Brad D.; Taylor, Amanda; Elias, George; Akk, Gustav; Evers, Alex S.; Zorumski, Charles F.; Mennerick, Steven; Covey, Douglas F.

    2014-01-01

    A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on γ-aminobutyric acid type A (GABAA) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: 1) a ketone group at position C-16; 2) an axial 4α-OMe group and 3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents as and drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABAA receptor function. PMID:24328079

  4. UV-induced erythema model: a tool in dermatopharmacology for testing the topical activity of non-steroidal anti-inflammatory agents in man.

    PubMed

    Torrent, J; Izquierdo, I; Barbanoj, M J; Moreno, J; Lauroba, J; Jané, F

    1988-05-01

    UV-induced erythema is a well known inflammatory model applied both in animal and human skin to test the activity of topical non-steroidal anti-inflammatory compounds in a great variety of pharmaceutical formulations. The aim of this study was to evaluate the inhibitory efficacy of piroxicam in two different topical formulations (cream 0.5, 1 and 1.5% and gel 1%) as compared to three non-steroidal compounds, benzydamine, etofenamate and indomethacin (cream 5%), on erythema induced after UV-injury on the back of 5 healthy subjects. The results showed that piroxicam in cream formulation, indomethacin cream and etofenamate gel have a similar effect, decreasing the erythema size 7 h after irradiation. However, benzydamine cream and piroxicam gel showed no effect with this method. We may conclude that this model is adequate and precise for selecting the most appropriate galenic dosage form for an active compound in terms of its clinical efficacy when topically administered. PMID:3398651

  5. Three New and Eleven Known Unusual C25 Steroids: Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy using Diethyl Sulphate

    PubMed Central

    Xia, Ming-Wen; Cui, Cheng-Bin; Li, Chang-Wei; Wu, Chang-Jing

    2014-01-01

    Three new (1–3) and 11 known (4–14) C25 steroids with an unusual bicyclo[4.4.1]A/B ring system were isolated by tracing newly produced metabolites in the EtOAc extract of an antitumor mutant AD-1-2 obtained by the diethyl sulphate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. HPLC-PDAD-UV and HPLC-ESI-MS analyses indicated that the G59 strain did not produce these metabolites and the production of 1–14 in the mutant AD-1-2 extract was caused by the activation of silent metabolites in the original G59 strain by DES mutagenesis. The structures of the new compounds, named antineocyclocitrinols A (1) and B (2) and 23-O-methylantineocyclocitrinol (3), including their absolute configurations were determined by various spectroscopic methods, especially the NMR and Mo2-induced CD analyses. Compounds 1–3 provide the first examples of the C25 bicyclo[4.4.1]A/B ring steroids with the Z-configuration of 20,22-double bond. All of 1–14 weakly inhibited several human cancer cell lines to varying extents. These results provided additional examples for the successful application of the chemical mutagenesis strategy using DES to discover new compounds by activating silent metabolites in fungal isolates and supported also the effectiveness and usefulness of this new strategy. PMID:24633254

  6. Transposon insertions causing constitutive sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing

    SciTech Connect

    Berstein, M.; Cline, T.W. |; Lersch, R.A.; Subrahmanyan, L.

    1995-02-01

    Sex-lethal (Sxl) gene products induce female development in Drosophila melanogaster and suppress the transcriptional hyperactivation of X-linked genes responsible for male X-chromosome dosage compensation. Control of Sxl functioning by the dose of X-chromosomes normally ensures that the female-specific functions of this developmental switch gene are only expressed in diplo-X individuals. Although the immediate effect of X-chromosome dose is on Sxl transcription, during most of the life cycle {open_quotes}on{close_quotes} vs. {open_quotes}off{close_quotes} reflects alternative Sxl RNA splicing, with the female (productive) splicing mode maintained by a positive feedback activity of SXL protein on Sxl pre-mRNA splicing. {open_quotes}Male-lethal{close_quotes} (Sxl{sup M}) gain-of-function alleles subvert Sxl control by X-chromosome dose, allowing female Sxl functions to be expressed independent of the positive regulators upstream of Sxl. As a consequence, Sxl{sup M} haplo-X animals (chromosomal males) die because of improper dosage compensation, and Sxl{sup m} chromosomal females survive the otherwise lethal effects of mutations in upstream positive regulators. Transcript analysis of double-mutant male-viable Sxl{sup M} derivatives in which the Sxl{sup M} insertion is cis to loss-of-function mutations, combined with other results reported here, indicates that the constitutive character of these Sxl{sup M} alleles is a consequence of an alteration of the structure of the pre-mRNA that allow some level of female splicing to occur even in the absence of functional SXL protein. Surprisingly, however, most of the constitutive character of Sxl{sup M} alleles appears to depend on the mutant alleles` responsiveness, perhaps greater than wild-type, to the autoregulatory splicing activity of the wild-type SXL proteins they produce. 47 refs., 10 figs., 4 tabs.

  7. Sex-specific foraging behavior in response to fishing activities in a threatened seabird

    PubMed Central

    García-Tarrasón, Manuel; Bécares, Juan; Bateman, Santiago; Arcos, José Manuel; Jover, Lluís; Sanpera, Carolina

    2015-01-01

    Some seabird species have learnt to efficiently exploit fishing discards from trawling activities. However, a discard ban has been proposed as necessary in Europe to ensure the sustainability of the seas. It is of crucial importance for the management and conservation purposes to study the potential consequences of a discard ban on the foraging ecology of threatened seabirds. We assessed the influence of fishing activities on the feeding habits of 22 male and 15 female Audouin's gulls (Larus audouinii) from the Ebro Delta (Mediterranean Sea) during the breeding period using GPS loggers together with Stable Isotope Analysis (SIA), which provided new insights into their foraging behavior and trophic ecology, respectively. GPS data revealed different sex-specific foraging patterns between workdays and weekends. Females were highly consistent in that they foraged at sea throughout the week even though discarding stops at weekends. In contrast, males switched from foraging at sea during the week (when discards are produced) to an increased use of rice field habitats at weekends (when fishermen do not work). This sex-specific foraging behavior could be related to specific nutritional requirements associated with previous egg production, an energetically demanding period for females. However, on a broader time scale integrated by the SIA, both sexes showed a high degree of individual specialization in their trophic ecology. The need to obtain detailed information on the dependence and response of seabirds to fishing activities is crucial in conservation sciences. In this regard, sex-specific foraging behavior in relation to fisheries has been overlooked, despite the ecological and conservation implications. For instance, this situation may lead to sex differentiation in bycatch mortality in longlines when trawlers do not operate. Moreover, any new fisheries policy will need to be implemented gradually to facilitate the adaptation of a specialized species to a discard ban

  8. Sex-specific foraging behavior in response to fishing activities in a threatened seabird.

    PubMed

    García-Tarrasón, Manuel; Bécares, Juan; Bateman, Santiago; Arcos, José Manuel; Jover, Lluís; Sanpera, Carolina

    2015-06-01

    Some seabird species have learnt to efficiently exploit fishing discards from trawling activities. However, a discard ban has been proposed as necessary in Europe to ensure the sustainability of the seas. It is of crucial importance for the management and conservation purposes to study the potential consequences of a discard ban on the foraging ecology of threatened seabirds. We assessed the influence of fishing activities on the feeding habits of 22 male and 15 female Audouin's gulls (Larus audouinii) from the Ebro Delta (Mediterranean Sea) during the breeding period using GPS loggers together with Stable Isotope Analysis (SIA), which provided new insights into their foraging behavior and trophic ecology, respectively. GPS data revealed different sex-specific foraging patterns between workdays and weekends. Females were highly consistent in that they foraged at sea throughout the week even though discarding stops at weekends. In contrast, males switched from foraging at sea during the week (when discards are produced) to an increased use of rice field habitats at weekends (when fishermen do not work). This sex-specific foraging behavior could be related to specific nutritional requirements associated with previous egg production, an energetically demanding period for females. However, on a broader time scale integrated by the SIA, both sexes showed a high degree of individual specialization in their trophic ecology. The need to obtain detailed information on the dependence and response of seabirds to fishing activities is crucial in conservation sciences. In this regard, sex-specific foraging behavior in relation to fisheries has been overlooked, despite the ecological and conservation implications. For instance, this situation may lead to sex differentiation in bycatch mortality in longlines when trawlers do not operate. Moreover, any new fisheries policy will need to be implemented gradually to facilitate the adaptation of a specialized species to a discard ban

  9. Explaining sex differences in mental rotation: role of spatial activity experience.

    PubMed

    Nazareth, Alina; Herrera, Asiel; Pruden, Shannon M

    2013-05-01

    Males consistently outperform females on mental rotation tasks, such as the Vandenberg and Kuse (1978) Perceptual and Motor Skills, 47(2), 599-604, mental rotation test (MRT; e.g. Voyer et al. 1995) in Psychological Bulletin, 117, 250-265. The present study investigates whether these sex differences in MRT scores can be explained in part by early spatial activity experience, particularly those spatial activities that have been sex-typed as masculine/male-oriented. Utilizing an online survey, 571 ethnically diverse adult university students completed a brief demographic survey, an 81-item spatial activity survey, and the MRT. Results suggest that the significant relation between sex of the participant and MRT score is partially mediated by the number of masculine spatial activities participants had engaged in as youth. Closing the gap between males and females in spatial ability, a skill linked to science, technology, engineering, and mathematics success, may be accomplished in part by encouraging female youth to engage in more particular kinds of spatial activities. PMID:23381194

  10. Oral Steroids for Dermatitis.

    PubMed

    Fisher, Andrew D; Clarke, Jesse; Williams, Timothy K

    2015-01-01

    Contact/allergic dermatitis is frequently treated inappropriately with lower-than-recommended doses or inadequate duration of treatment with oral and intramuscular glucocorticoids. This article highlights a case of dermatitis in a Ranger Assessment and Selection Program student who was improperly treated over 2 weeks with oral steroids after being bit by Cimex lectularius, commonly known as bed bugs. The article also highlights the pitfalls of improper oral steroid dosing and provides reasoning for longer-duration oral steroid treatment. PMID:26125159

  11. Sex-dependent activity of the spinal excitatory amino acid transporter: Role of estrous cycle.

    PubMed

    Sajjad, Jahangir; Felice, Valeria D; Golubeva, Anna V; Cryan, John F; O'Mahony, Siobhain M

    2016-10-01

    Females are more likely to experience visceral pain than males, yet mechanisms underlying this sex bias are not fully elucidated. Moreover, pain sensitivity can change throughout the menstrual cycle. Alterations in the glutamatergic system have been implicated in several pain-disorders; however, whether these are sex-dependent is unclear. Thus, we aimed to investigate sex differences in the spinal cord glutamate uptake and how it varies across the estrous cycle. The activity of the glutamate transporters, excitatory amino acid transporters (EAATs) was assessed using an ex vivo aspartate radioactive uptake assay in the lumbosacral spinal cord in Sprague-Dawley male and female rats. The gene expression of EAATs, glutamate receptor subunits NR1 and NR2B and the estrogen receptors ERα & ERβ in the spinal cord were also analyzed. EAAT activity was lower in females, particularly during the estrus phase, and this was the only cycle stage that was responsive to the pharmacological effects of the EAATs activator riluzole. Interestingly, EAAT1 mRNA expression was lower in high-estrogen and high-ERα states compared to diestrus in females. We conclude that the Spinal EAAT activity in females is different to that in males, and varies across the estrous cycle. Furthermore, the expression levels of estrogen receptors also showed a cycle-dependent pattern that may affect EAATs function and expression. PMID:27471194

  12. Active site substitution A82W improves the regioselectivity of steroid hydroxylation by cytochrome P450 BM3 mutants as rationalized by spin relaxation nuclear magnetic resonance studies.

    PubMed

    Rea, V; Kolkman, A J; Vottero, E; Stronks, E J; Ampt, K A M; Honing, M; Vermeulen, N P E; Wijmenga, S S; Commandeur, J N M

    2012-01-24

    Cytochrome P450 BM3 from Bacillus megaterium is a monooxygenase with great potential for biotechnological applications. In this paper, we present engineered drug-metabolizing P450 BM3 mutants as a novel tool for regioselective hydroxylation of steroids at position 16β. In particular, we show that by replacing alanine at position 82 with a tryptophan in P450 BM3 mutants M01 and M11, the selectivity toward 16β-hydroxylation for both testosterone and norethisterone was strongly increased. The A82W mutation led to a ≤42-fold increase in V(max) for 16β-hydroxylation of these steroids. Moreover, this mutation improves the coupling efficiency of the enzyme, which might be explained by a more efficient exclusion of water from the active site. The substrate affinity for testosterone increased at least 9-fold in M11 with tryptophan at position 82. A change in the orientation of testosterone in the M11 A82W mutant as compared to the orientation in M11 was observed by T(1) paramagnetic relaxation nuclear magnetic resonance. Testosterone is oriented in M11 with both the A- and D-ring protons closest to the heme iron. Substituting alanine at position 82 with tryptophan results in increased A-ring proton-iron distances, consistent with the relative decrease in the level of A-ring hydroxylation at position 2β. PMID:22208729

  13. Neural activation during response inhibition is associated with adolescents’ frequency of risky sex and substance use

    PubMed Central

    Feldstein Ewing, Sarah W.; Houck, Jon M.; Bryan, Angela D.

    2015-01-01

    While many have identified the important role of the developing brain in youth risk behavior, few have examined the relationship between salient cognitive factors (response inhibition) and different types of real-world adolescent health risk behaviors (substance use and risky sex) within the same sample of youth. We therefore sought to examine these relationships with 95 high-risk youth (ages 14-18; M age = 16.29 years). We examined the relationship between blood oxygen level dependent (BOLD) response to an fMRI-based cognitive task designed to assess response inhibition (Go/NoGo) and past month risk behavior (number of substance use days; number of unprotected sex days). For this sample of youth, we found significant negative correlations between past month substance use and response inhibition within the left inferior frontal gyrus (IFG) and right insula (uncorrected p < .001; extent threshold ≥ 10 voxels). In addition, in the same contrast, we found significant positive correlations between past month risky sex and activation within the right IFG and left middle occipital gyrus (uncorrected p < .001; extent threshold ≥ 10 voxels). These results suggest the particular relevance of these regions in this compelling, albeit slightly different pattern of response for adolescent substance use and risky sex. PMID:25532443

  14. Steroids in allergic disease.

    PubMed

    Webb, D R

    1981-09-01

    From the experience above, it may be concluded that corticosteroid therapy in allergic disease has become more effective than ever before. The expected variations in usage of new important pharmacologic agents is seen with special clarity in the use of corticosteroids. The wide acclaim for the "miracle drug of the 1950's", which followed penicillin of the 1940's, soon gave away to anguish about side-effects that threatened to abolish its use entirely in the late 1950's. The 1960's brought alternate day therapy for chronic usage and recognition that short term usage was relatively safe. The 1970's saw proliferation of topically active steroids similar to those so important to the practice of Dermatology in the previous decade. Results in treating asthma and nasal diseases have been excellent and extensive research for adverse effects has been largely unrevealing. PMID:6793795

  15. A Supplement to a Packet of Elementary Classroom Activities To Teach Students about Sex Role Stereotyping, Preschool to Second Grade.

    ERIC Educational Resources Information Center

    Michigan State Dept. of Education, Lansing. Office for Sex Equity.

    Sex role identification and socialization occur during early childhood years. Toys, books, materials, and attitudes of child care givers and preschool teachers in organized educational and social activities, such as nursery schools, preschools, and group care, can be used to help combat or reduce sex stereotyping. The materials contained in this…

  16. Sex differences in the use of anticipatory brain activity to encode emotional events.

    PubMed

    Galli, Giulia; Wolpe, Noham; Otten, Leun J

    2011-08-24

    Women and men differ in the way they experience emotional events. Previous work has indicated that the impact of an emotional event depends on how it is anticipated. Separately, it has been shown that anticipation affects memory formation. Here, we assessed whether anticipatory brain activity influences the encoding of emotional events into long-term memory and, in addition, how biological sex affects the use of such activity. Electrical brain activity was recorded from the scalps of healthy men and women while they performed an incidental encoding task (indoor/outdoor judgments) on pleasant, unpleasant, and neutral pictures. Pictures were preceded by a cue that indicated the valence of the upcoming item. Memory was tested after a 20 min delay with a recognition task incorporating the remember/know procedure. Brain activity before picture onset predicted later memory of an event. Crucially, the role of anticipatory activity depended entirely on the valence of a picture and the sex of an individual. Right-lateralized anticipatory activity selectively influenced the encoding of unpleasant pictures in women, but not in men. These findings indicate that anticipatory processes influence the way in which women encode negative events into memory. The selective use of such activity may indicate that anticipatory activity is one mechanism by which individuals regulate their emotions. PMID:21865478

  17. Steroidal Glucosides from the Rhizomes of Tacca chantrieri and Their Inhibitory Activities of NO Production in BV2 Cells.

    PubMed

    Yen, Pham Hai; Chi, Vu Thi Quynh; Kim, Dong-Cheol; Ko, Wonmin; Oh, Hyuncheol; Kim, Youn-Chul; Dung, Duong Thi; Thanh, Nguyen Thi Viet; Quang, Tran Hong; Ngan, Nguyen Thi Thanh; Nhiema, Nguyen Xuan; Anh, Hoang Le Tuan; Minh, Chan Van; Kiem, Phan Van

    2016-01-01

    Two new steroidal glucosides, chantriolides D and E (1 and 2), along with four known compounds, chantriolide A (3), chantriolide B (4), chantriolide C (5), and (25S)-spirost-5-en-3-ol 3-O-α-L-rhamnopyranosyl-(1-->2)-O-[α-L-rhamnopyranosyl-(1-->3)]-β-D-glucopyranoside (6) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by 1D and 2D NMR spectroscopic and HR-ESI-MS data, as well as by comparison with reported data. Compounds 1 and 2 were found to show strong inhibitory NO effect in BV2 cells, with IC₅₀ values of 12.45 and 59.03 µM, respectively. PMID:26996017

  18. Assisted Reproduction Technologies Impair Placental Steroid Metabolism

    PubMed Central

    Collier, Abby C.; Miyagi, Shogo J.; Yamauchi, Yasuhiro; Ward, Monika A.

    2009-01-01

    The placenta plays a vital role in pregnancy by facilitating steroid passage from maternal to fetal circulation and/or direct production of hormones. Using a murine model, we demonstrated the differences in placental steroid metabolism between pregnancies conceived naturally and with assisted reproduction technologies (ART): in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). While the ovarian steroid production was similar (estrone, 17β-estradiol) or higher (estriol) in ART pregnancies compared to mating, the levels of placental estriol were significantly lower in ART group. Placentas from ART had significantly higher activities of the steroid metabolizing enzymes UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT), which in ICSI were also coupled with decreased activity of the steroid regenerating enzymes β-glucuronidase (β-G) and Aryl sulfatase (AS). Levels of steroid metabolites androstane-3α-17β-diol glucuronide and dehydroepiandrosterone sulfate were higher in fetal compared to maternal blood in ART, but not in mating. This study demonstrates that in murine ART pregnancies, higher metabolism and clearance of steroids by the placenta may seriously affect the passage of essential hormones to the fetus. If a similar phenomenon exists in humans, this could provide a plausible explanation for obstetric and neonatal complications associated with ART, including the higher incidence of low birth weight babies. PMID:19406239

  19. Mind Over Matter: Anabolic Steroids

    MedlinePlus

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Anabolic Steroids Print Mind Over Matter: Anabolic Steroids Order Free Publication in: English Spanish Download PDF 830.69 KB Anabolic steroids are ...

  20. Antibacterial properties of cationic steroid antibiotics.

    PubMed

    Savage, Paul B; Li, Chunhong; Taotafa, Uale; Ding, Bangwei; Guan, Qunying

    2002-11-19

    Cationic steroid antibiotics have been developed that display broad-spectrum antibacterial activity. These compounds are comprised of steroids appended with amine groups arranged to yield facially amphiphilic morphology. Examples of these antibiotics are highly bactericidal, while related compounds effectively permeabilize the outer membranes of Gram-negative bacteria sensitizing these organisms to hydrophobic antibiotics. Cationic steroid antibiotics exhibit various levels of eukaryote vs. prokaryote cell selectivity, and cell selectivity can be increased via charge recognition of prokaryotic cells. Studies of the mechanism of action of these antibiotics suggest that they share mechanistic aspects with cationic peptide antibiotics. PMID:12445638

  1. Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism

    SciTech Connect

    Flueck, Christa E.; Mullis, Primus E.; Pandey, Amit V.

    2010-10-08

    Research highlights: {yields} Cytochrome P450 3A4 (CYP3A4), metabolizes 50% of drugs in clinical use and requires NADPH-P450 reductase (POR). {yields} Mutations in human POR cause congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. {yields} We are reporting that mutations in POR may reduce CYP3A4 activity. {yields} POR mutants Y181D, A457H, Y459H, V492E and R616X lost 99%, while A287P, C569Y and V608F lost 60-85% CYP3A4 activity. {yields} Reduction of CYP3A4 activity may cause increased risk of drug toxicities/adverse drug reactions in patients with POR mutations. -- Abstract: Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizes approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations.

  2. Safe sex.

    PubMed

    Mukherjee, G; Ghosh, T K

    1994-01-01

    The main objectives of health care for people with AIDS are to help them adjust to changing sexual status and to provide them with information on safe sex. Sections consider the risks of various types of sexual activity and safe sex education. With regard to the risk of transmitting or contracting HIV, sexual activities may be high risk, medium risk, low risk, or no risk. High-risk activities include unprotected anal or vaginal intercourse, oral-anal sexual contact, sharing sex toys, and traumatic sexual activity. Medium-risk activities include anal and vaginal intercourse using a latex condom with or without spermicide, and sex using a vaginal diaphragm or contraceptive vaginal sponge. Oral sex on a woman or oral sex on a man without ejaculation into the mouth are low-risk activities. Mutual masturbation, erotic touching, caressing and massage, kissing and non-genital licking pose no risk of infection. All general practitioners and family physicians should teach about safe sex. Prevention messages may be conveyed through individual and social counseling as well as with printed media and other forms of mass media. Messages should definitely reach prostitutes and brothel owners, as well as pre-pubertal children and older youths. PMID:8207282

  3. Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.

    PubMed

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Gavalas, Antonios; Rekka, Eleni A

    2016-02-01

    Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis. PMID:26750253

  4. Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

    PubMed

    Jiang, Qi-Wei; Chen, Mei-Wan; Cheng, Ke-Jun; Yu, Pei-Zhong; Wei, Xing; Shi, Zhi

    2016-01-01

    Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases. PMID:25820039

  5. Association between Pregnancy and Active Injection Drug Use and Sex Work among Women Injection Drug Users in Saint Petersburg, Russia.

    PubMed

    Girchenko, P; Ompad, D C; Bikmukhametov, D; Gensburg, L

    2015-06-01

    Widespread use of unsafe sexual practices among women injecting drugs both practicing and not practicing sex work leads to high levels of unplanned pregnancies in this population. The goal of this study was to investigate the association between pregnancy and active drug use and sex work. Data were collected using a convenience sample of 500 women in Saint Petersburg, Russia, in 2013. All women had recent experience of drug use, of which 200 were pregnant at the time of the study. The study consisted of a structured interview followed by a rapid HIV test. Pregnancy was protective against both active drug use and sex work. For HIV-positive women, these associations were stronger than for HIV-negative women: drug use prevalence ratio (PR) was 0.59 vs 0.85; for sex work, the PRs were 0.36 vs 0.64. Higher levels of education were associated with a lower prevalence ratio for active drug use and sex work in all models. Having children was not associated with active drug use or sex work. Pregnancy might be an optimal time for conducting interventions aimed at cessation of drug use and sex work among women injecting drugs. PMID:25835324

  6. Relationship of changing delta 4-steroid 5 alpha-reductase activity to (125I)iododeoxyuridine uptake during regeneration of involuted rat prostates

    SciTech Connect

    Kitahara, S.; Higashi, Y.; Takeuchi, S.; Oshima, H. )

    1989-04-01

    To elucidate the phenotypic expression of proliferating prostatic cells, rats were castrated, and the regenerating process of involuted ventral prostates during testosterone propionate (TP) administration was investigated by examining morphology, (5-{sup 125}I)iododeoxyuridine ({sup 125}I-UdR) uptake, DNA content, weight, acid phosphatase, and delta 4-steroid 5 alpha-reductase (5 alpha-reductase) activities. Morphologically, TP treatment initially increased the number of epithelial cells lining glandular lobules and subsequently restored the shape of epithelial cells. {sup 125}I-UdR uptake peaked on Day 3 of TP treatment and stayed at higher levels than for uncastrated controls until Day 14 of treatment. Prostatic weight, protein content, acid phosphatase, and DNA content returned to uncastrated control levels by Day 14 of TP treatment. TP administration markedly stimulated prostatic 5 alpha-reductase activity, which peaked on the Day 5 of treatment and decreased to uncastrated control levels by Day 14 of treatment. It is concluded that TP administration to castrated rats initially induced active mitotic division of the remaining stem cells, followed by formation of differentiated functional epithelial cells. Prostatic 5 alpha-reductase was highly active at the initial phase of active mitotic cell division. The major portion of the increased enzyme activity can be regarded as a phenotypic expression of stem or transient cells of prostatic epithelium.

  7. Synthesis, crystal structure and spectroscopy of bioactive Cd(II) polymeric complex of the non-steroidal anti-inflammatory drug diclofenac sodium: Antiproliferative and biological activity

    NASA Astrophysics Data System (ADS)

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-02-01

    The interaction of Cd(II) with the non-steroidal anti-inflammatory drug diclofenac sodium (Dic) leads to the formation of the complex [Cd2(L)41.5(MeOH)2(H2O)]n(L = Dic), 1, which has been isolated and structurally characterized by X-ray crystallography. Diclofenac sodium and its metal complex 1 have also been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The results of cytotoxic activity in vitro expressed as IC50 values indicated the diclofenac sodium and cadmium chloride are non active or less active than the metal complex of diclofenac (1). Complex 1 was also found to be a more potent cytotoxic agent against T-24 and MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cisplatin, under the same experimental conditions. The superoxide dismutase activity was measured by Fridovich test which showed that complex 1 shows a low value in comparison with Cu complexes. The binding properties of this complex to biomolecules, bovine or human serum albumin, are presented and evaluated. Antibacterial and growth inhibitory activity is also higher than that of the parent ligand compound.

  8. Synthesis, crystal structure and spectroscopy of bioactive Cd(II) polymeric complex of the non-steroidal anti-inflammatory drug diclofenac sodium: antiproliferative and biological activity.

    PubMed

    Tabrizi, Leila; Chiniforoshan, Hossein; McArdle, Patrick

    2015-02-01

    The interaction of Cd(II) with the non-steroidal anti-inflammatory drug diclofenac sodium (Dic) leads to the formation of the complex [Cd2(L)41.5(MeOH)2(H2O)]n(L = Dic), 1, which has been isolated and structurally characterized by X-ray crystallography. Diclofenac sodium and its metal complex 1 have also been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. The results of cytotoxic activity in vitro expressed as IC50 values indicated the diclofenac sodium and cadmium chloride are non active or less active than the metal complex of diclofenac (1). Complex 1 was also found to be a more potent cytotoxic agent against T-24 and MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cisplatin, under the same experimental conditions. The superoxide dismutase activity was measured by Fridovich test which showed that complex 1 shows a low value in comparison with Cu complexes. The binding properties of this complex to biomolecules, bovine or human serum albumin, are presented and evaluated. Antibacterial and growth inhibitory activity is also higher than that of the parent ligand compound. PMID:25311520

  9. Steroids' transformations in Penicillium notatum culture.

    PubMed

    Bartmańska, Agnieszka; Dmochowska-Gładysz, Jadwiga; Huszcza, Ewa

    2005-03-01

    The application of Penicillium notatum genus for biotransformations of steroids has been investigated. The reactions observed include insertion of an oxygen atom into D-ring of steroids, 15alpha-hydroxylation of 17alpha-methyl testosterone derivatives, ester bond hydrolysis, and degradation of a testosterone derivatives side chain. Microbial production of testolactones, the biologically active compounds, was also achieved using this strain in up to 98% yield. PMID:15763598

  10. Physical activity in patients with heart failure: barriers and motivations with special focus on sex differences

    PubMed Central

    Klompstra, Leonie; Jaarsma, Tiny; Strömberg, Anna

    2015-01-01

    Background Adherence to recommendations for physical activity is low in both male and female patients with heart failure (HF). Men are more physically active than women. In order to successfully promote physical activity, it is therefore essential to explore how much and why HF patients are physically active and if this is related to sex. The aim of this study was therefore to evaluate physical activity in HF patients, to describe the factors related to physical activity, and to examine potential barriers and motivations to physical activity with special focus on sex differences. Methods The study had a cross-sectional survey design. HF patients living at home received a questionnaire during May–July 2014, with questions on physical activity (from the Short Form-International Physical Activity Questionnaire), and potential barriers and motivations to physical activity. Results A total of 154 HF patients, 27% women, with a mean age of 70±10 were included. In total, 23% of the patients reported a high level of physical activity, 46% a moderate level, and 34% a low level. Higher education, self-efficacy, and motivation were significantly associated with a higher amount of physical activity. Symptoms or severity of the disease were not related to physical activity. All the potential barriers to exercise were reported to be of importance. Psychological motivations were most frequently rated as being the most important motivation (41%) to be physically active. Physical motivations (33%) and social motivations were rated as the least important ones (22%). Women had significantly higher total motivation to be physically active. These differences were found in social, physical, and psychological motivations. Discussion One-third of the HF patients had a low level of physical activity in their daily life. Severity of the disease or symptoms were not related, whereas level of education, exercise self-efficacy, and motivation were important factors to take into account when

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

    PubMed Central

    Quignot, Nadia; Bois, Frédéric Y.

    2013-01-01

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

  12. Sex Differences in HIV Outcomes in the Highly Active Antiretroviral Therapy Era: A Systematic Review

    PubMed Central

    Melekhin, Vlada V.; Sterling, Timothy R.

    2014-01-01

    Abstract To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Risk ratios (relative risks, odd ratios, and hazard ratios) and 95% confidence intervals were obtained. Sixty-five articles were included in this review. Thirty-nine studies were from North America and Europe and 26 were from Latin America, Asia, and Africa. Forty-four studies (68%) showed no statistically significant difference in risk of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Decreased risk of death among females compared to males was observed in 24 of the 25 articles that included mortality analyses [pooled risk ratio 0.72 (95% confidence interval=0.69–0.75)], and decreased risk of death or AIDS was observed in 9 of the 13 articles that examined the composite outcome [pooled risk ratio=0.91 (0.84–0.98)]. There was no significant effect of sex on the risk of progression to AIDS [pooled risk ratio=1.15 (0.99–1.31)]. In this systematic review, females starting HAART appeared to have improved survival compared to males. However, this benefit was not associated with decreased progression to either AIDS or to differences in virologic or immunologic treatment outcomes. PMID:24401107

  13. Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts.

    PubMed

    Bermejo-Alvarez, P; Rizos, D; Rath, D; Lonergan, P; Gutierrez-Adan, A

    2010-02-23

    Although genetically identical for autosomal Chrs (Chr), male and female preimplantation embryos could display sex-specific transcriptional regulation. To illustrate sex-specific differences at the mRNA level, we compared gene-expression patterns between male and female blastocysts by DNA microarray comparison of nine groups of 60 bovine in vitro-produced blastocysts of each sex. Almost one-third of the transcripts detected showed sexual dimorphism (2,921 transcripts; false-discovery rate, P < 0.05), suggesting that in the absence of hormonal influences, the sex Chrs impose an extensive transcriptional regulation upon autosomal genes. Six genes were analyzed by qPCR in in vivo-derived embryos, which displayed similar sexual dimorphism. Ontology analysis suggested a higher global transcriptional level in females and a more active protein metabolism in males. A gene homolog to an X-linked gene involved in network interactions during spliceosome assembly was found in the Y-Chr. Most of the X-linked-expressed transcripts (88.5%) were up-regulated in females, but most of them (70%) exhibited fold-changes lower than 1.6, suggesting that X-Chr inactivation is partially achieved at the blastocyst stage. Almost half of the transcripts up-regulated in female embryos exhibiting more than 1.6-fold change were present in the X-Chr and eight of them were selected to determine a putative paternal imprinting by gene expression comparison with parthenogenetic embryos. Five (BEX, CAPN6, BEX2, SRPX2, and UBE2A) exhibited a higher expression in females than in parthenotes, suggesting that they are predominantly expressed by the paternal inherited X-Chr and that imprinting may increase the transcriptional skew caused by double X-Chr dosage. PMID:20133684

  14. Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts

    PubMed Central

    Bermejo-Alvarez, P.; Rizos, D.; Rath, D.; Lonergan, P.; Gutierrez-Adan, A.

    2010-01-01

    Although genetically identical for autosomal Chrs (Chr), male and female preimplantation embryos could display sex-specific transcriptional regulation. To illustrate sex-specific differences at the mRNA level, we compared gene-expression patterns between male and female blastocysts by DNA microarray comparison of nine groups of 60 bovine in vitro-produced blastocysts of each sex. Almost one-third of the transcripts detected showed sexual dimorphism (2,921 transcripts; false-discovery rate, P < 0.05), suggesting that in the absence of hormonal influences, the sex Chrs impose an extensive transcriptional regulation upon autosomal genes. Six genes were analyzed by qPCR in in vivo-derived embryos, which displayed similar sexual dimorphism. Ontology analysis suggested a higher global transcriptional level in females and a more active protein metabolism in males. A gene homolog to an X-linked gene involved in network interactions during spliceosome assembly was found in the Y-Chr. Most of the X-linked-expressed transcripts (88.5%) were up-regulated in females, but most of them (70%) exhibited fold-changes lower than 1.6, suggesting that X-Chr inactivation is partially achieved at the blastocyst stage. Almost half of the transcripts up-regulated in female embryos exhibiting more than 1.6-fold change were present in the X-Chr and eight of them were selected to determine a putative paternal imprinting by gene expression comparison with parthenogenetic embryos. Five (BEX, CAPN6, BEX2, SRPX2, and UBE2A) exhibited a higher expression in females than in parthenotes, suggesting that they are predominantly expressed by the paternal inherited X-Chr and that imprinting may increase the transcriptional skew caused by double X-Chr dosage. PMID:20133684

  15. A preliminary study of sex differences in brain activation during a spatial navigation task in healthy adults.

    PubMed

    Sneider, Jennifer Tropp; Sava, Simona; Rogowska, Jadwiga; Yurgelun-Todd, Deborah A

    2011-10-01

    The hippocampus plays a significant role in spatial memory processing, with sex differences being prominent on various spatial tasks. This study examined sex differences in healthy adults, using functional magnetic resonance imaging (fMRI) in areas implicated in spatial processing during navigation of a virtual analogue of the Morris water-maze. There were three conditions: learning, hidden, and visible control. There were no significant differences in performance measures. However, sex differences were found in regional brain activation during learning in the right hippocampus, right parahippocampal gyrus, and the cingulate cortex. During the hidden condition, the hippocampus, parahippocampal gyrus, and cingulate cortex were activated in both men and women. Additional brain areas involved in spatial processing may be recruited in women when learning information about the environment, by utilizing external cues (landmarks) more than do men, contributing to the observed sex differences in brain activation. PMID:22185061

  16. 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

  17. Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

    PubMed Central

    Seitz, H K; Egerer, G; Simanowski, U A; Waldherr, R; Eckey, R; Agarwal, D P; Goedde, H W; von Wartburg, J P

    1993-01-01

    As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people. Images Figure

  18. Sex Differences in Neural Activation to Facial Expressions Denoting Contempt and Disgust

    PubMed Central

    Aleman, André; Swart, Marte

    2008-01-01

    The facial expression of contempt has been regarded to communicate feelings of moral superiority. Contempt is an emotion that is closely related to disgust, but in contrast to disgust, contempt is inherently interpersonal and hierarchical. The aim of this study was twofold. First, to investigate the hypothesis of preferential amygdala responses to contempt expressions versus disgust. Second, to investigate whether, at a neural level, men would respond stronger to biological signals of interpersonal superiority (e.g., contempt) than women. We performed an experiment using functional magnetic resonance imaging (fMRI), in which participants watched facial expressions of contempt and disgust in addition to neutral expressions. The faces were presented as distractors in an oddball task in which participants had to react to one target face. Facial expressions of contempt and disgust activated a network of brain regions, including prefrontal areas (superior, middle and medial prefrontal gyrus), anterior cingulate, insula, amygdala, parietal cortex, fusiform gyrus, occipital cortex, putamen and thalamus. Contemptuous faces did not elicit stronger amygdala activation than did disgusted expressions. To limit the number of statistical comparisons, we confined our analyses of sex differences to the frontal and temporal lobes. Men displayed stronger brain activation than women to facial expressions of contempt in the medial frontal gyrus, inferior frontal gyrus, and superior temporal gyrus. Conversely, women showed stronger neural responses than men to facial expressions of disgust. In addition, the effect of stimulus sex differed for men versus women. Specifically, women showed stronger responses to male contemptuous faces (as compared to female expressions), in the insula and middle frontal gyrus. Contempt has been conceptualized as signaling perceived moral violations of social hierarchy, whereas disgust would signal violations of physical purity. Thus, our results suggest a

  19. New steps forward in the neuroactive steroid field.

    PubMed

    Giatti, Silvia; Garcia-Segura, Luis Miguel; Melcangi, Roberto Cosimo

    2015-09-01

    Evidence accumulated in recent years suggests that the systemic treatment with neuroactive steroids, or the pharmacological modulation of its production by brain cells, represent therapeutic options to promote neuroprotection. However, new findings, which are reviewed in this paper, suggest that the factors to be considered for the design of possible therapies based on neuroactive steroids are more complex than previously thought. Thus, although as recently reported, the nervous system regulates neuroactive steroid synthesis and metabolism in adaptation to modifications in peripheral steroidogenesis, the neuroactive steroid levels in the brain do not fully reflect its levels in plasma. Even, in some cases, neuroactive steroid level modifications occurring in the nervous tissues, under physiological and pathological conditions, are in the opposite direction than in the periphery. This suggests that the systemic treatment with these molecules may have unexpected outcomes on neural steroid levels. In addition, the multiple metabolic pathways and signaling mechanisms of neuroactive steroids, which may change from one brain region to another, together with the existence of regional and sex differences in its neural levels are additional sources of complexity that should be clarified. This complexity in the levels and actions of these molecules may explain why in some cases these molecules have detrimental rather than beneficial actions for the nervous system. This article is part of a Special Issue entitled 'Steroid Perspectives'. PMID:25797031

  20. Steroids (For Parents)

    MedlinePlus

    ... by some athletes and bodybuilders. Anabolic steroids are synthetic hormones that can boost the body's ability to ... doses every day can significantly increase levels of testosterone, which can lead to a number of health ...

  1. The Role of Sex of Peers and Gender-Typed Activities in Young Children’s Peer Affiliative Networks: A Longitudinal Analysis of Selection and Influence

    PubMed Central

    Martin, Carol Lynn; Kornienko, Olga; Schaefer, David R.; Hanish, Laura D.; Fabes, Richard A.; Goble, Priscilla

    2012-01-01

    A stochastic actor-based model was used to investigate the origins of sex segregation by examining how similarity in sex and time spent in gender-typed activities affected affiliation network selection and how peers influenced children’s (N = 292; M age = 4.3 years) activity involvement. Gender had powerful effects on interactions through direct and indirect pathways. Children selected playmates of the same-sex and with similar levels of gender-typed activities. Selection based on gender-typed activities partially mediated selection based on sex. Children influenced one another’s engagement in gender-typed activities. When mechanisms producing sex segregation were compared, the largest contributor was selection based on sex; less was due to activity-based selection and peer influence. Implications for sex segregation and gender development are discussed. PMID:23252713

  2. Analogs of sex pheromone of processionary moth,Thaumetopoea pityocampa: Synthesis and biological activity.

    PubMed

    Camps, F; Fabriàs, G; Gasol, V; Guerrero, A; Hernández, R; Montoya, R

    1988-05-01

    The synthesis and biological activity of some analogs of (Z)-13-hexadecen-11-ynyl acetate1, the major component of the sex pheromone of the processionary mothThaumetopoea pityocampa is described. The analogs have been formally derived by structural modification of the enyne and acetate functions of the parent compound1. In field tests, trifluoroacetate ester16 and the analog,11, with fluorine substitution at the olefin site, decreased the pheromone action, whereas epoxy derivative,10, from epoxidation of the olefin moiety in1, and propionate ester15 gave synergistic activity. The formate14 had a variable effect according to the composition of the lure. Formal reduction of the enyne to give the acetylene2 was found to retain activity. Alcohols12 and13, resulting from hydrolysis of the enyne1 and acetylene2, respectively, inhibited the action of their parent compounds. PMID:24276283

  3. Mediation of CTCF transcriptional insulation by DEAD-box RNA-binding protein p68 and steroid receptor RNA activator SRA

    PubMed Central

    Yao, Hongjie; Brick, Kevin; Evrard, Yvonne; Xiao, Tiaojiang; Camerini-Otero, R. Daniel; Felsenfeld, Gary

    2010-01-01

    CCCTC-binding factor (CTCF) is a DNA-binding protein that plays important roles in chromatin organization, although the mechanism by which CTCF carries out these functions is not fully understood. Recent studies show that CTCF recruits the cohesin complex to insulator sites and that cohesin is required for insulator activity. Here we showed that the DEAD-box RNA helicase p68 (DDX5) and its associated noncoding RNA, steroid receptor RNA activator (SRA), form a complex with CTCF that is essential for insulator function. p68 was detected at CTCF sites in the IGF2/H19 imprinted control region (ICR) as well as other genomic CTCF sites. In vivo depletion of SRA or p68 reduced CTCF-mediated insulator activity at the IGF2/H19 ICR, increased levels of IGF2 expression, and increased interactions between the endodermal enhancer and IGF2 promoter. p68/SRA also interacts with members of the cohesin complex. Depletion of either p68 or SRA does not affect CTCF binding to its genomic sites, but does reduce cohesin binding. The results suggest that p68/SRA stabilizes the interaction of cohesin with CTCF by binding to both, and is required for proper insulator function. PMID:20966046

  4. Lack of sensorial innervation in the newborn female rats affects the activity of hypothalamic monoaminergic system and steroid hormone secretion during puberty.

    PubMed

    Quiróz, Ubaldo; Morales-Ledesma, Leticia; Morán, Carolina; Trujillo, Angélica; Domínguez, Roberto

    2014-06-01

    There is evidence that sensory innervation plays a role regulating ovarian functions, including fertility.Since sensory denervation by means of capsaicin in newborn female rats results in a lower response togonadotropins, the present study analyzed the effects that sensory denervation by means of capsaicin in neonatal rats has on the concentration of monoamines in the anterior(AH) and medium (MH) hypothalamus, and on steroid hormone levels in serum. Groups of newborn female rats were injected subcutaneously with capsaicin and killed at 10, 20, and 30 days of age and on the first vaginal estrous.The concentrations of noradrenaline, dopamine, serotonin(5-HT), and their metabolites in the AH and MH were measured using HPLC, and the levels of estradiol (E),progesterone (P), testosterone (T), FSH, and luteinizing hormone using radioimmunoanalysis. The results show thatat 20 days of age, capsaicin-treated rats have lowernoradrenergic and serotonergic activities in the AH, and that the dopaminergic activity was lower in the MH. These results suggest that the sensorial system connections within the monoaminergic systems of the AH and MH are different.Capsaicin-treated animals had lower T, E, and P levels than in the control group, suggesting that the lower activity in the AH monoaminergic system and lower hormonesecretion could be explained by the blockade of information mediated by the sensory innervation (probably substance P), mainly between the ovary and the AH. PMID:24122121

  5. Dehydroepiandrosterone: a neuroactive steroid.

    PubMed

    Stárka, Luboslav; Dušková, Michaela; Hill, Martin

    2015-01-01

    Dehydroepiandrosterone (DHEA) and its sulfate bound form (DHEAS) are important steroids of mainly adrenal origin. They are produced also in gonads and in the brain. Dehydroepiandrosterone easily crosses the brain-blood barrier and in part is also produced locally in the brain tissue. In the brain, DHEA exerts its effects after conversion to either testosterone and dihydrotestosterone or estradiol via androgen and estrogen receptors present in the most parts of the human brain, through mainly non-genomic mechanisms, or eventually indirectly via the effects of its metabolites formed locally in the brain. As a neuroactive hormone, DHEA in co-operation with other hormones and transmitters significantly affects some aspects of human mood, and modifies some features of human emotions and behavior. It has been reported that its administration can increase feelings of well-being and is useful in ameliorating atypical depressive disorders. It has neuroprotective and antiglucocorticoid activity and modifies immune reactions, and some authors have also reported its role in degenerative brain diseases. Here we present a short overview of the possible actions of dehydroepiandrosterone and its sulfate in the brain, calling attention to various mechanisms of their action as neurosteroids and to prospects for the knowledge of their role in brain disorders. PMID:24704258

  6. Rapid steroid hormone actions via membrane receptors.

    PubMed

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

    2016-09-01

    Steroid hormones regulate a wide variety of physiological and developmental functions. Traditional steroid hormone signaling acts through nuclear and cytosolic receptors, altering gene transcription and subsequently regulating cellular activity. This is particularly important in hormonally-responsive cancers, where therapies that target classical steroid hormone receptors have become clinical staples in the treatment and management of disease. Much progress has been made in the last decade in detecting novel receptors and elucidating their mechanisms, particularly their rapid signaling effects and subsequent impact on tumorigenesis. Many of these receptors are membrane-bound and lack DNA-binding sites, functionally separating them from their classical cytosolic receptor counterparts. Membrane-bound receptors have been implicated in a number of pathways that disrupt the cell cycle and impact tumorigenesis. Among these are pathways that involve phospholipase D, phospholipase C, and phosphoinositide-3 kinase. The crosstalk between these pathways has been shown to affect apoptosis and proliferation in cardiac cells, osteoblasts, and chondrocytes as well as cancer cells. This review focuses on rapid signaling by 17β-estradiol and 1α,25-dihydroxy vitamin D3 to examine the integrated actions of classical and rapid steroid signaling pathways both in contrast to each other and in concert with other rapid signaling pathways. This new approach lends insight into rapid signaling by steroid hormones and its potential for use in targeted drug therapies that maximize the benefits of traditional steroid hormone-directed therapies while mitigating their less desirable effects. PMID:27288742

  7. Mitochondrial Fusion Is Essential for Steroid Biosynthesis

    PubMed Central

    Cooke, Mariana; Soria, Gastón; Cornejo Maciel, Fabiana; Gottifredi, Vanesa; Podestá, Ernesto J.

    2012-01-01

    Although the contribution of mitochondrial dynamics (a balance in fusion/fission events and changes in mitochondria subcellular distribution) to key biological process has been reported, the contribution of changes in mitochondrial fusion to achieve efficient steroid production has never been explored. The mitochondria are central during steroid synthesis and different enzymes are localized between the mitochondria and the endoplasmic reticulum to produce the final steroid hormone, thus suggesting that mitochondrial fusion might be relevant for this process. In the present study, we showed that the hormonal stimulation triggers mitochondrial fusion into tubular-shaped structures and we demonstrated that mitochondrial fusion does not only correlate-with but also is an essential step of steroid production, being both events depend on PKA activity. We also demonstrated that the hormone-stimulated relocalization of ERK1/2 in the mitochondrion, a critical step during steroidogenesis, depends on mitochondrial fusion. Additionally, we showed that the SHP2 phosphatase, which is required for full steroidogenesis, simultaneously modulates mitochondrial fusion and ERK1/2 localization in the mitochondrion. Strikingly, we found that mitofusin 2 (Mfn2) expression, a central protein for mitochondrial fusion, is upregulated immediately after hormone stimulation. Moreover, Mfn2 knockdown is sufficient to impair steroid biosynthesis. Together, our findings unveil an essential role for mitochondrial fusion during steroidogenesis. These discoveries highlight the importance of organelles’ reorganization in specialized cells, prompting the exploration of the impact that organelle dynamics has on biological processes that include, but are not limited to, steroid synthesis. PMID:23029265

  8. [Anti-inflammatory, analgesic and anti-pyretic activities of a non-steroidal anti-inflammatory drug, etofenamate, in experimental animals].

    PubMed

    Nakamura, H; Motoyoshi, S; Imazu, C; Ishii, K; Yokoyama, Y; Seto, Y; Kadokawa, T; Shimizu, M

    1982-08-01

    Anti-inflammatory, analgesic, and anti-pyretic activities of orally administered etofenamate, the diethylene glycol ester of flufenamic acid, were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice and ultra-violet light-induced erythema in guinea pigs, etofenamate produced a dose related inhibition at doses of 40--320 mg/kg and 5--20 mg/kg, respectively. In rats, felt-pellet-induced granuloma formation and adjuvant-induced arthritis were significantly inhibited by repeated administration of etofenamate at doses of 20 mg/kg/day for 5 days and 40 mg/kg/day for 21 days, respectively. Etofenamate showed an inhibitory activity on the squeak response caused by flexing and extending the silver nitrate-induced arthritic joint in rats; and it produced a dose related anti-writhing activity at doses of 50--300 mg/kg and 10--80 mg/kg in mice and rats, respectively, in the acetic acid-induced writhing test. Etofenamate showed a significant anti-pyretic activity at doses of 0.2 mg/kg or more. These potencies of etofenamate were 0.5 to 1.6 times those of flufenamic acid. In particular, the anti-erythema, anti-arthritis, and anti-pyretic activities of etofenamate were approximately equivalent to or superior to those of flufenamic acid. From these results, it was suggested that etofenamate given orally, like other non-steroidal anti-inflammatory drugs, showed anti-inflammatory, analgesic, and anti-pyretic activities in experimental animals. PMID:6983482

  9. Sex ratio and reproductive activity of benthic copepods in bathyal Sagami Bay (1430 m), central Japan

    NASA Astrophysics Data System (ADS)

    Shimanaga, Motohiro; Shirayama, Yoshihisa

    2003-04-01

    Sex ratios and reproductive activity of benthic copepod assemblages were investigated at the bathyal site (depth 1430 m) in Sagami Bay, central Japan. The ratio of adult females to adult males was approximately 3.5:1, significantly different from 1:1, although this parameter did not show a seasonal pattern. On the other hand, the percentage of ovigerous females among adult females and the ratio of nauplii to total copepods appeared to fluctuate seasonally in 1997 and 1998. Statistical tests, however, could not detect significant difference in either parameter. We discuss the possibility that the reproductive activity of copepods was enhanced by the increased supply of fresh phytodetritus to the sea floor.

  10. Sex differences in the intensity and qualitative dimensions of exertional dyspnea in physically active young adults.

    PubMed

    Cory, Julia M; Schaeffer, Michele R; Wilkie, Sabrina S; Ramsook, Andrew H; Puyat, Joseph H; Arbour, Brandon; Basran, Robbi; Lam, Michael; Les, Christian; MacDonald, Benjamin; Jensen, Dennis; Guenette, Jordan A

    2015-11-01

    Understanding sex differences in the qualitative dimensions of exertional dyspnea may provide insight into why women are more affected by this symptom than men. This study explored the evolution of the qualitative dimensions of dyspnea in 70 healthy, young, physically active adults (35 M and 35 F). Participants rated the intensity of their breathing discomfort (Borg 0-10 scale) and selected phrases that best described their breathing from a standardized list (work/effort, unsatisfied inspiration, and unsatisfied expiration) throughout each stage of a symptom-limited incremental-cycle exercise test. Following exercise, participants selected phrases that described their breathing at maximal exercise from a list of 15 standardized phrases. Intensity of breathing discomfort was significantly higher in women for a given ventilation, but differences disappeared when ventilation was expressed as a percentage of maximum voluntary ventilation. The dominant qualitative descriptor in both sexes throughout exercise was increased work/effort of breathing. At peak exercise, women were significantly more likely to select the following phrases: "my breathing feels shallow," "I cannot get enough air in," "I cannot take a deep breath in," and "my breath does not go in all the way." Women adopted a more rapid and shallow breathing pattern and had significantly higher end-inspiratory lung volumes relative to total lung capacity throughout exercise relative to men. These findings suggest that men and women do not differ in their perceived quality of dyspnea during submaximal exercise, but subjective differences appear at maximal exercise and may be related, at least in part, to underlying sex differences in breathing patterns and operating lung volumes during exercise. PMID:26338458

  11. Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes

    PubMed Central

    Wongtrakoongate, Patompon; Riddick, Gregory; Fucharoen, Suthat; Felsenfeld, Gary

    2015-01-01

    Long non-coding RNAs (lncRNAs) have been recognized as key players in transcriptional regulation. We show that the lncRNA steroid receptor RNA activator (SRA) participates in regulation through complex formation with trithorax group (TrxG) and polycomb repressive complex 2 (PRC2) complexes. Binding of the SRA-associated RNA helicase p68 preferentially stabilizes complex formation between SRA and a TrxG complex but not PRC2. In human pluripotent stem cells NTERA2, SRA binding sites that are also occupied by p68 are significantly enriched for H3K4 trimethylation. Consistent with its ability to interact with TrxG and PRC2 complexes, some SRA binding sites in human pluripotent stem cells overlap with bivalent domains. CTCF sites associated with SRA appear also to be enriched for bivalent modifications. We identify NANOG as a transcription factor directly interacting with SRA and co-localizing with it genome-wide in NTERA2. Further, we show that SRA is important for maintaining the stem cell state and for reprogramming of human fibroblasts to achieve the pluripotent state. Our results suggest a mechanism whereby the lncRNA SRA interacts with either TrxG or PRC2. These complexes may then be recruited by various DNA binding factors to deliver either activating or silencing signals, or both, to establish bivalent domains. PMID:26496121

  12. Heart Rate Variability in Adolescents – Normative Data Stratified by Sex and Physical Activity

    PubMed Central

    Sharma, Vivek Kumar; Arunachalam, Vinayathan; Rajendran, Rajathi

    2015-01-01

    Background Heart rate variability (HRV) refers to the beat-to-beat fluctuations in the cardiac rhythm occurring due to modulation of the pacemaker (sinoatrial node) activity of the heart by the sympathetic and parasympathetic branches of the autonomic nervous system. Nowadays, cardiovascular diseases and their risk factors are increasingly occurring at a younger age (children and adolescents) and recording of HRV in them will help us to identify cardiovascular autonomic derangement earlier. However, to be used clinically, normative data has to be established in this age group considering other major factors that can influence HRV such as sex, physical activity, and BMI. Materials and Methods Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology has provided the standards for measurement of heart rate variability and we have followed the same. In the present study, we have described the normative data for HRV in the adolescent in the age group of 12-17 years, stratified based on sex and physical activity. Results Data given below are expressed as median with interquartile range (Median (IQR)) in the following order: non-athlete girls, non athlete boys, athlete girls and athlete boys. Time domain indices - SDNN - 66.35 (40.78), 63.20 (36.20), 113.00 (31.40) and 94.20 (35.55); RMSSD – 69.00 (50.55), 58.70 (43.40), 94.90 (42.10) and 100.30 (47.50); NN50 - 137.50 (100.25), 116.00 (90.50), 137.00 (81.00) and 156.00 (81.50). The frequency domain indices – LF power 1015.00 (1098.75), 945.00 (831.00), 1465 (642.25), and 1211.00 (811.37); HF power – 1324.00 (1707.00), 988.00 (1426.50), 2409.00 (1387.50), and 2219.00 (1752.00); Total power – 3374.50 (3094.25), 2757.00 (2641.00), 5202.00 (2501.50) and 5273.00 (3507.50); LFnu – 45.44 (16.61), 47.63 (29.98), 38.59 (11.81) and 37.10 (11.21); HFnu – 54.56 (16.61), 52.37 (29.98), 61.41 (11.81) and 62.90 (11.21). Conclusion We have given sex and physical activity

  13. Activity of cholinesterases of blood and heart in rats of different sex and age during muscular loads and hypokinesia

    NASA Technical Reports Server (NTRS)

    Rozanova, V. D.; Antonova, G. A.

    1979-01-01

    The activity of acetylcholinesterase (Ache) and butyrilcholinesterase (Bche) in the blood and the heart of 3 and 13 month old control male rats is considerably lower than in female rats. In 25 month old rats, no sex differences in the Ache and Bche were revealed in the heart. In 3 and 13 month old male and female rats, under conditions of muscular exercises, the Ache and Bche activity is lower, and in hypokinetic male rats -- higher than that in respective control animals. In all the rats, irrespective of sex, age, and motor conditions, Ache and Bche activity tended to decrease from the sinoatrial node to the heart apex.

  14. Local mechanisms in sex specific morphogenesis.

    PubMed

    Drews, U

    2000-01-01

    Sex determination in mammals occurs on three levels. Segregation of sex chromosomes determines the chromosomal sex. Sry on the Y chromosome induces formation of a testis which in turn regulates via AMH and testosterone the development of the genital tract and the external phenotype. Recently a number of new factors have been described, which affect sexual development but have not yet found a place in the above canonical scheme of sex determination. For the purpose of this review, the factors are aligned according to their quality as transcription factors, steroid hormones, or growth factors. In this web of regulatory factors, the classical sex determining factors have evolved as master mechanisms while others function as slaves, or were totally suppressed. In this context, androgens acquired a dominant role in mammalian development. Androgens determine the morphogenesis of the genital tract. The effects of androgens are mediated by local cellular interactions. In the cranial section of the Wolffian duct the androgen receptor appears in the epithelium and mediates maintenance of the duct via an epithelial factor. In the caudal section of the duct the androgen receptor is expressed in the embryonic mesenchyme. Vesicular glands are induced via a morphogenetically active mesenchymal condensation, while the epithelial buds are primarily AR androgen receptor negative. The dominant role of androgens and formation of a vagina evolved together at the transition to eutherian mammals. Under this aspect, the role of androgens in the development of the vagina is analyzed. PMID:11173834

  15. Sex differences in Siberian hamster ultradian locomotor rhythms.

    PubMed

    Prendergast, Brian J; Stevenson, Tyler J; Zucker, Irving

    2013-02-17

    Sex differences in ultradian activity rhythms (URs) and circadian rhythms (CRs) were assessed in Siberian hamsters kept in long day (LD) or short day (SD) photoperiods for 40 weeks. For both sexes URs of locomotor activity were more prevalent, greater in amplitude and more robust in SDs. The UR period was longer in females than males in both day lengths. The reproductive system underwent regression and body mass declined during the initial 10 weeks of SD treatment, and in both sexes these traits spontaneously reverted to the LD phenotype at or before 40 weeks in SD, reflecting the development of neuroendocrine refractoriness to SD patterns of melatonin secretion. Hamsters of both sexes, however, continued to display SD-like URs at the 40 weeks time point. CRs were less prevalent and the waveform less robust and lower in amplitude in SDs than LDs; the SD circadian waveform also did not revert to the long-day phenotype after 40 weeks of SD treatment. Short day lengths enhanced ultradian and diminished circadian rhythms in both sexes. Day length controls several UR characteristics via gonadal steroid and melatonin-independent mechanisms. Sex differences in ultradian timing may contribute to sex diphenisms in rhythms of sleep, food intake and exercise. PMID:23333554

  16. [Comparison of eating habits among students according to sex and level of physical activity].

    PubMed

    Łagowska, Karolina; Woźniewicz, Małgorzata; Jeszka, Jan

    2011-01-01

    The aim of the study was to evaluate nutritional habits of high school students, depending on their sex and physical activity. The investigated population included 147 students in age of 17.5 +/- 1.5 y (girls DZ = 98, boys CH = 49) with different level of physical activity (athletes SPO, moderate physical activity UAF, low physical activity NAF). Nutritional data were obtained by FFQ and calculated for selected food-groups and generally as young healthy eating index YHEI. International IPAQ was used to determine the level of physical activity and anthropometric measured were conducted to estimated BMI and body fat status. It was indicated the YHEI in athletes was significantly higher (p < 0.05) compared to rest of students. Moreover, a significant difference (p < 0.05) in YHEI in DZ compared to CH was also found. The significant differences (p < 0.05) in the frequency of consumption of red meat, vegetable oil and sweetned drinks was revealed between DZ and CH adolescents. The frequency of consumption of vegetable oil, fast - foods, sweets, alcoholic drinks, energy drinks and isotonic drinks varied with the level of physical activity. Frequency of consumption of sweets negatively correlated with skinfold thickness in DZ, whereas positive correlation between consumption frequency of energy drinks, BMI and skinfold thickness was found in CH. The results show, that nutritional habits of the athletes was most approached to nutritional guidelines. CH, nutritional habits may predicted to overweight and obesity in CH group more distinctly than in DZ group. PMID:22171526

  17. Sex on the brain! Associations between sexual activity and cognitive function in older age

    PubMed Central

    Wright, Hayley; Jenks, Rebecca A.

    2016-01-01

    Background: the relationship between cognition and sexual activity in healthy older adults is under-researched. A limited amount of research in this area has shown that sexual activity is associated with better cognition in older men. The current study explores the possible mediating factors in this association in men and women, and attempts to provide an explanation in terms of physiological influences on cognitive function. Methods: using newly available data from Wave 6 of the English Longitudinal Study of Ageing, the current study explored associations between sexual activity and cognition in adults aged 50–89 (n = 6,833). Two different tests of cognitive function were analysed: number sequencing, which broadly relates to executive function, and word recall, which broadly relates to memory. Results: after adjusting for age, education, wealth, physical activity, depression, cohabiting, self-rated health, loneliness and quality of life, there were significant associations between sexual activity and number sequencing and recall in men. However, in women there was a significant association between sexual activity and recall, but not number sequencing. Conclusions: possible mediators of these associations (e.g. neurotransmitters) are discussed. The cross-sectional nature of the analysis is limiting, but provides a promising avenue for future explorations and longitudinal studies. The findings have implications for the promotion of sexual counselling in healthcare settings, where maintaining a healthy sex life in older age could be instrumental in improving cognitive function and well-being. PMID:26826237

  18. Peer Outreach Work as Economic Activity: Implications for HIV Prevention Interventions among Female Sex Workers

    PubMed Central

    George, Annie; Blankenship, Kim M.

    2015-01-01

    Female sex workers (FSWs) who work as peer outreach workers in HIV prevention programs are drawn from poor socio-economic groups and consider outreach work, among other things, as an economic activity. Yet, while successful HIV prevention outcomes by such programs are attributed in part to the work of peers who have dense relations with FSW communities, there is scant discussion of the economic implications for FSWs of their work as peers. Using observational data obtained from an HIV prevention intervention for FSWs in south India, we examined the economic benefits and costs to peers of doing outreach work and their implications for sex workers’ economic security. We found that peers considered their payment incommensurate with their workload, experienced long delays receiving compensation, and at times had to advance money from their pockets to do their assigned peer outreach work. For the intervention these conditions resulted in peer attrition and difficulties in recruitment of new peer workers. We discuss the implications of these findings for uptake of services, and the possibility of reaching desired HIV outcomes. Inadequate and irregular compensation to peers and inadequate budgetary outlays to perform their community-based outreach work could weaken peers’ relationships with FSW community members, undermine the effectiveness of peer-mediated HIV prevention programs and invalidate arguments for the use of peers. PMID:25775122

  19. 3D model of amphioxus steroid receptor complexed with estradiol

    SciTech Connect

    Baker, Michael E.; Chang, David J.

    2009-08-28

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

  20. Rapid comparison of metabolites in humans and rats of different sexes using untargeted UPLC-TOFMS and an in-house software platform.

    PubMed

    Liang, Qiande; Xu, Wangyanjun; Hong, Qian; Xiao, Chengrong; Yang, Liang; Ma, Zengchun; Wang, Yuguang; Tan, Hongling; Tang, Xianglin; Gao, Yue

    2015-01-01

    Metabolite differences between sexes have rarely been observed in a global manner, but it has recently been made possible by the advancement in metabolomics techniques. In this study, untargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry and an in-house software platform were used for a rapid comparison of sex differences in urinary metabolites in humans and in urinary and serum metabolites in Sprague Dawley (SD) rats. In addition, the species differences of urinary metabolites between humans and SD rats were also observed. Principle component analysis showed that all the observed metabolite sex differences were more distinct in SD rats than in humans, indicating that the sex differences of human urinary metabolites is small compared with that of SD rats. In SD rats, the observed metabolite sex differences were more distinct in urine than in serum, indicating the importance of urine analysis for metabolomics studies. The species differences in the urinary metabolites of humans and SD rats were much more distinct than any of the observed sex differences. Many sex- and species-related markers were discovered and putatively identified. In both humans and SD rats, steroid metabolites appeared to constitute a major sex difference in urinary metabolites. This provides new proof of the special importance of steroid metabolites in sex differences from an untargeted metabolomics investigation, which is rare for sex differences. Contrary patterns involving adrenocortical activity appeared to exist between rodents and humans, which agrees with previous reports. In the serum metabolites of SD rats, sex differences in ascorbic acid or its isomer and pantothenic acid or its isomer, but not in steroid metabolites, were prominent. Human-specific α-N- phenylacetyl-l-glutamine and androsterone glucuronide were among the putative identities of the markers discriminating humans and SD rats. This study demonstrated the feasibility of an in

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

    PubMed

    Xu, Dan; Lin, Sheng-Xiang

    2016-07-01

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

  2. It takes a seasoned bird to be a good listener: communication between the sexes.

    PubMed

    Brenowitz, Eliot A; Remage-Healey, Luke

    2016-06-01

    Birds commonly use sound for communication between the sexes. In many songbird species, only males sing and there are pronounced sex differences in the neural song control circuits. By contrast, the auditory circuitry is largely similar in males and females. Both sexes learn to recognize vocalizations heard as juveniles and this shapes auditory response selectivity. Mating vocalizations are restricted to the breeding season, when sex steroid levels are elevated. Auditory cells, from the ear to the cortex, are hormone sensitive. Estrogens are synthesized in the brain and can modulate the activity of auditory neurons. In species that breed seasonally, elevated levels of estradiol in females transiently enhance their auditory responses to conspecific vocalizations, resulting in sex differences in audition. PMID:26820470

  3. Flowers for Algernon: steroid dysgenesis, epigenetics and brain disorders.

    PubMed

    Sanders, Bryan K

    2012-01-01

    While a recent study has reported that early citalopram exposure alters cortical network function and produces autistic-like behaviors in male rats, when evaluating antidepressant animal models of autism spectrum disorder (ASD) it is important to note that some selective serotonin (5-HT) reuptake inhibitors alter 3α-hydroxysteroid dehydrogenase activity, and thus steroidogenesis. At least one study has examined the effect of repeated citalopram administration on the serum and brain concentration of testosterone (T) and its metabolites and shown that citalopram increases serum T. Several in vitro studies also suggest that sex steroid can alter 5-HT homeostasis. While research efforts have demonstrated that transgenic mice expressing the most common of multiple gain-of-function 5-HT reuptake transporter (SERT) coding variants, SERT Ala56, previously identified in children with ASD, exhibit autistic-like behaviors, elevated p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia, a few studies provide some evidence that 5-HT may alter gonadal steroidogenesis. T, 17β-estradiol and synthetic estrogens are known inhibitors of AKR1C21 (BRENDA, E.C. 1.1.1.209), the epitestosterone (epiT) producing enzyme in rodents. EpiT is a naturally occurring steroid in mammals, including man. An analysis of the literature suggests that epiT may be the central mediator in the epigenetic regulation of gene expression. Over thirty years ago, it was shown that rat brain epiT production is higher in females than in males. A similar finding in humans could explain the sex differences in the incidence of autism and other brain disorders. Despite this, the role of epiT in brain development remains a long neglected area of research. PMID:23406739

  4. Glanduliferins A and B, two new glucosylated steroids from Impatiens glandulifera, with in vitro growth inhibitory activity in human cancer cells.

    PubMed

    Cimmino, Alessio; Mathieu, Véronique; Evidente, Marco; Ferderin, Marlène; Moreno Y Banuls, Laetitia; Masi, Marco; De Carvalho, Annelise; Kiss, Robert; Evidente, Antonio

    2016-03-01

    Impatiens glandulifera has been imported from Himalaya in Europe and is considered as an invasive alien plant whose spreading arouses increasing interest among scientific literature. Via anti-cancer bioguiding, two new glucosylated steroids, named glanduliferins A and B, were isolated from the dried stem of I. glandulifera plants, together with the well-known α-spinasterol and 2-methoxy-1,4-naphthoquinone, which are also isolated from roots and leaves. They were characterized as 17-(2-hydroxy-2-pentamethylcyclopropyl-ethyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopents[a]phenathren-3-O-(4-O-acetyl)-α-D-glucopyranoside and 17-(4-ethyl-1,5-dimethyl-hex-2-enyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopents[a]phenathren-3-O-(6-O-acetyl)-β-D-glucopyranoside using various NMR and HRESIMS techniques and chemical methods. In vitro determination of the growth inhibitory activity of the four isolated compounds using the MTT colorimetric assay revealed mean IC50 growth inhibitory value of ~30 μM for glanduliferin A while glanduliferin B and α-spinasterol were poorly active till 100 μM. 2-methoxy-1,4-naphthoquinone revealed to be active in the single micromolar digit range as previously described. Quantitative videomicroscopy analyses of the effects of glanduliferins A and B suggested cytostatic rather than cytotoxic activity in U373 glioblastoma (GBM) cells. PMID:26732071

  5. The Effects of Steroid Implant and Dietary Soybean Hulls on Estrogenic Activity of Sera of Steers Grazing Toxic Endophyte-Infected Tall Fescue Pasture

    PubMed Central

    Shappell, Nancy W.; Flythe, Michael D.; Aiken, Glen E.

    2015-01-01

    Soybean hulls (SBHs) have been fed to cattle pasturing on endophyte-infected tall fescue in attempts to increase rate of gain. Literature reports indicated some symptoms associated with fescue toxicosis were ameliorated by the use of steroidal implants containing estradiol (E2) and progesterone [implantation (IMP)], feeding SBHs, or the combination of the two. While the mechanism for amelioration was unclear, the SBHs were postulated as acting as a diluent of the toxic factors of the fescue. Alternatively, estradiol and phytoestrogens of SBHs might be acting through relaxation of the persistent vasoconstriction found in animals ingesting ergot alkaloids of endophyte-infected fescue. If so, estrogenic activity of serum of steers receiving SBHs, IMP, or a combination of the two should be elevated. Using the cellular proliferation assay of estrogenicity (E-Screen), estradiol equivalents (E2Eqs) were determined on both SBHs and the serum of steers from a previously reported study. Range of SBHs was 5.0–8.5 ng Eqs g−1 DM (mean 6.5, n = 4 from different commercial sources of SBHs). At the rate fed, theoretically calculated blood E2Eq could be physiologically relevant (~80 pg mL−1, based on 2.3 kg SBHs d−1, 300 kg steer, 5.7% blood volume, and 10% absorption). Serum E2Eqs did increase in steers (P ≤ 0.05) with steroidal implants or fed SBHs by 56 and 151% over control, respectively, and treatments were additive (211% increase). Serum prolactin was also greatest for the SBH + IMP group (188 ng mL−1, P < 0.05), concentrations comparable to values reported for steers grazing endophyte-free fescue. Prolactin in the SBH group was higher than IMP or control groups (146 versus 76 and 60 ng mL−1, respectively). Still unknown is if additional E2Eqs from dietary phytoestrogens or exogenous sources of estradiol can further reduce symptoms of fescue toxicosis. The E-Screen assay was an effective tool in monitoring serum for estrogenic effects

  6. REPEATED ANABOLIC/ANDROGENIC STEROID EXPOSURE DURING ADOLESCENCE ALTERS PHOSPHATE-ACTIVATED GLUTAMINASE AND GLUTAMATE RECEPTOR 1 SUBUNIT IMMUNOREACTIVITY IN HAMSTER BRAIN: CORRELATION WITH OFFENSIVE AGGRESSION

    PubMed Central

    Fischer, Shannon G.; Ricci, Lesley A.; Melloni, Richard H.

    2007-01-01

    Male Syrian hamsters (Mesocricetus auratus) treated with moderately high doses (5.0mg/kg/day) of anabolic/androgenic steroids (AAS) during adolescence (P27–P56) display highly escalated offensive aggression. The current study examined whether adolescent AAS-exposure influenced the immunohistochemical localization of phosphate-activated glutaminase (PAG), the rate-limiting enzyme in the synthesis of glutamate, a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models of aggression, as well as glutamate receptor 1 subunit (GluR1). Hamsters were administered AAS during adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for changes in PAG and GluR1 immunoreactivity in areas of the brain implicated in aggression control. When compared with sesame oil-treated control animals, aggressive AAS-treated hamsters displayed a significant increase in the number of PAG- and area density of GluR1- containing neurons in several notable aggression regions, although the differential pattern of expression did not appear to overlap across brain regions. Together, these results suggest that altered glutamate synthesis and GluR1 receptor expression in specific aggression areas may be involved in adolescent AAS-induced offensive aggression. PMID:17418431

  7. Sex work and sex trafficking.

    PubMed

    Ditmore, M; Saunders, P

    1998-01-01

    Preventing HIV infection and other sexually transmitted diseases (STDs), as well as sexual and physical violence, are major occupational health and safety concerns for prostitutes. Considerable evidence shows that anti-prostitution laws facilitate violence and abuse against prostitutes and may increase their risk of contracting HIV/STDs. For example, police often take advantage of existing laws against prostitution to demand money or sex. In general, the strict enforcement of anti-prostitution laws marginalizes prostitutes from services which could help them avoid abuse and promotes an environment in which prostitutes must take risks to avoid detection and arrest. One strategy to improve prostitutes' lives would therefore be to remove laws which prevent them from working safely and from travelling abroad to work legally. Projects in which prostitutes are actively involved have helped break down stereotypes against prostitutes, while police-sex worker liaison projects in Scotland and Australia have led to higher levels of reporting of crimes against prostitutes. The Network of Sex Work Projects (NSWP), an organization which links sex worker health programs around the world, has found that the incidence of HIV/STDs among prostitutes is lowest when they have control over their work conditions; access to condoms, lubricants, and other safe sex materials; and respect of their basic human and legal rights. People need to understand that consensual involvement in sex work is different from forced sex trafficking. PMID:12348692

  8. Anabolic steroid boosts weight.

    PubMed

    1996-09-01

    A randomized study of nandrolone decanoate (Deca-Durabolin) showed that the anabolic steroid can increase weight in people with HIV infections. The group receiving nandrolone experienced a greater increase both in fat-free mass and body cell mass (although the latter measure did not reach statistical significance) than those on placebo. Deca-Durabolin had little to do with two occurrences of Kaposi's sarcoma (KS) in the study group, but until further studies are completed, caution is advised when using this steroid in patients with KS. A new study comparing nandrolone to growth hormone in patients with wasting is slated to begin in the next 3 or 4 months. PMID:11363845

  9. Detection of designer steroids

    PubMed Central

    Yuan, Xiaohui; Forman, Barry Marc

    2005-01-01

    Illicit use of performance-enhancing steroids has proliferated among a wide range of professional and amateur athletes. This problem has attracted broad public attention and has led the United States Congress to draft legislation that proposes frequent testing of athletes. However, current testing protocols are inadequate as athletes can evade detection by using novel steroids that are unknown to authorities. We have developed a strategy that overcomes this limitation by virtue of its ability to detect “designer steroids” without prior knowledge of their existence. PMID:16604170

  10. Steroidal esters from Ferula sinkiangensis.

    PubMed

    Li, Guangzhi; Li, Xiaojin; Cao, Li; Shen, Liangang; Zhu, Jun; Zhang, Jing; Wang, Junchi; Zhang, Lijing; Si, Jianyong

    2014-09-01

    Two new steroidal esters with an unusual framework, Sinkiangenorin A and B, a new organic acid glycoside, Sinkiangenorin C, and four known lignin compounds were isolated from the seeds of Ferula sinkiangensis. The structures of these compounds were established by spectroscopic analysis and single-crystal X-ray diffraction. All of the isolated compounds were tested against Hela, K562 and AGS human cancer cell lines. Sinkiangenorin C showed cytotoxic activity against AGS cells with an IC50 of 36.9 μM. PMID:24979220

  11. Activation of the farnesoid-X receptor protects against gastrointestinal injury caused by non-steroidal anti-inflammatory drugs in mice

    PubMed Central

    Fiorucci, Stefano; Mencarelli, Andrea; Cipriani, Sabrina; Renga, Barbara; Palladino, Giuseppe; Santucci, Luca; Distrutti, Eleonora

    2011-01-01

    BACKGROUND AND PURPOSE Low doses of acetyl salicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage. The farnesoid X receptor (FXR) is a bile acid sensor essential for maintenance of intestinal homeostasis. Here, we have investigated whether FXR is required for mucosal protection in models of gastrointestinal injury caused by ASA and NSAIDs and if FXR activation has potential in the treatment or prevention of gastrointestinal injury caused by these agents. EXPERIMENTAL APPROACH FXR+/+ and FXR−/− mice were given ASA (10 to 100 mg·kg−1) or NSAIDs. Gastric and intestinal mucosal damage assessed by measuring lesion scores. FXR were activated by giving mice natural (chenodeoxycholic acid; CDCA) or synthetic (GW4064) FXR agonists. KEY RESULTS FXR, mRNA and protein, was detected in human and mouse stomach. FXR−/− mice were more prone to develop severe gastric and intestinal injury in response to ASA and NSAIDs and showed a severe reduction in the gastrointestinal expression of cystathionine-γ-lyase (CSE), an enzyme required for generation of hydrogen sulphide. CSE expression was reduced by ≈50% in wild-type mice challenged with ASA. Treating wild-type mice but not FXR−/− mice with CDCA or GW4064 protected against gastric injury caused by ASA and NSAIDs, by a CSE-dependent and cycloxygenase- and NO-independent, mechanism. FXR activation by GW4064 rescued mice from intestinal injury caused by naproxen. CONCLUSIONS AND IMPLICATIONS FXR was essential to maintain gastric and intestinal mucosal barriers. FXR agonists protected against gastric injury caused by ASA and NSAIDs by a CSE-mediated mechanism. PMID:21564085

  12. Synthesis, structure and catechol-oxidase activity of copper(II) complexes of 17-hydroxy-16-(N-3-oxo-prop-1-enyl)amino steroids.

    PubMed

    Wegner, Rainer; Dubs, Manuela; Görls, Helmar; Robl, Christian; Schönecker, Bruno; Jäger, Ernst-G

    2002-09-01

    Copper is next to iron the most important element in the biological transport, storage and in redox reactions of dioxygen. A bioanalogous activation of dioxygen with copper complexes is used for catalytical epoxidation, allylic hydroxylation and oxidative coupling of aromatic substrates, for example. With stereochemical information in form of chiral ligands, enantioselective reactions may be possible. Another aspect of interest on copper catalyzed reactions with dioxygen is that the exact mechanism and biological function of some enzymes (especially catechol oxidase) is yet not fully clear. For studies mimicking the copper-containing catechol oxidase appropriate chiral steroid ligands with defined stereochemistry and conformation have been synthesized. The four diastereomeric 16,17-aminoalcohols of the 3-methoxy-estra-1,3,5(10)-triene series have been condensed with salicylic aldehyde and different beta-ketoenols to the chiral ligand types 1-5. These compounds with different steric and electronic properties and different arrangements of the neighboring hydroxy and nitrogen functions were reacted with copper(II) acetate to copper complexes. The structure of these complexes will be discussed. The bioanalogous oxidation of 3,5-di-tbutyl-catechol (dtbc) to the corresponding quinone was catalyzed by most of the complexes, indicating their ability to activate dioxygen. The trans configurations c and d showed an activity one magnitude higher than the cis configurations a and b. Comparing compounds with the same diastereomeric configuration, the main influence was that of the peripheral R(1-3) substituents at the beta-ketoenaminic group which are useful for the fine-tuning of the properties of the copper atoms like redox potential and Lewis acidity. PMID:12231119

  13. Steroid Signaling and Temperature-Dependent Sex Determination – Reviewing the Evidence for Early Action of Estrogen during Ovarian Determination in the Red-Eared Slider Turtle (Trachemys scripta elegans)

    PubMed Central

    Ramsey, Mary; Crews, David

    2009-01-01

    The developmental processes underlying gonadal differentiation are conserved across vertebrates, but the triggers initiating these trajectories are extremely variable. The red-eared slider turtle (Trachemys scripta elegans) exhibits temperature-dependent sex determination (TSD), a system where incubation temperature during a temperature-sensitive period of development determines offspring sex. However, gonadal sex is sensitive to both temperature and hormones during this period – particularly estrogen. We present a model for temperature-based differences in aromatase expression as a critical step in ovarian determination. Localized estrogen production facilitates ovarian development while inhibiting male-specific gene expression. At male-producing temperatures aromatase is not upregulated, thereby allowing testis development. PMID:18992835

  14. Effects of Interferon-Tau and Steroids on Cytochrome P450 Activity in Bovine Endometrial Epithelial Cells.

    PubMed

    Gilfeather, C L; Lemley, C O

    2016-06-01

    The objective of the current study was to examine cyclooxygenase (COX), cytochrome P450 1A (CYP1A) and 2C (CYP2C) activity in bovine endometrial cell cultures following exposure to oxytocin (OT), interferon-τ (IFN), estradiol (E2) and/or progesterone (P4). Bovine endometrial epithelial cells were treated with OT, IFN, a combination of OT+IFN or control (CON) media for 24 h. For the second experiment, cells were treated with E2, P4, a combination of E2 + P4 or CON media for 24 h. Treatments were performed in triplicate, and the experiment was repeated four times (n = 12 per treatment). Treatment with OT alone increased (p < 0.01) activity of COX compared with CON; however, OT alone did not alter activity of CYP1A (p = 0.55) or CYP2C (p = 0.46) compared with CON. Activity of CYP1A and CYP2C was decreased in cells exposed to IFN (p < 0.01) or OT+IFN (p < 0.01) compared with CON. Treatment with E2 alone did not alter activity of CYP1A (p = 0.64) or CYP2C (p = 0.06) compared with CON. Activity of CYP1A and CYP2C was decreased (p < 0.01) in P4 vs CON. In summary, IFN exposure, irrespective of OT treatment, decreased the activity of CYP1A and CYP2C. Activity of CYP1A was decreased following P4 treatment alone, while that of CYP2C was decreased following both P4 and E2 + P4 treatment. The mixed function monooxygenase enzymes, CYP1A and CYP2C, have been implicated in synthesizing embryotoxic compounds; therefore, downregulation in the endometrium may be necessary during maternal recognition of pregnancy. PMID:27103466

  15. Steroid-Derived Naphthoquinoline Asphaltene Model Compounds: Hydriodic Acid Is the Active Catalyst in I2-Promoted Multicomponent Cyclocondensation Reactions.

    PubMed

    Schulze, Matthias; Scott, David E; Scherer, Alexander; Hampel, Frank; Hamilton, Robin J; Gray, Murray R; Tykwinski, Rik R; Stryker, Jeffrey M

    2015-12-01

    A multicomponent cyclocondensation reaction between 2-aminoanthracene, aromatic aldehydes, and 5-α-cholestan-3-one has been used to synthesize model asphaltene compounds. The active catalyst for this reaction has been identified as hydriodic acid, which is formed in situ from the reaction of iodine with water, while iodine is not a catalyst under anhydrous conditions. The products, which contain a tetrahydro[4]helicene moiety, are optically active, and the stereochemical characteristics have been examined by VT-NMR and VT-CD spectroscopies, as well as X-ray crystallography. PMID:26584791

  16. Sex differences in stroke

    PubMed Central

    Haast, Roy A M; Gustafson, Deborah R; Kiliaan, Amanda J

    2012-01-01

    Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment. PMID:23032484

  17. Effects of interferon-tau and steroids on cytochrome P450 activity in bovine endometrial epithelial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of the current study was to examine cyclooxygenase (COX), cytochrome P450 1A (CYP1A) and 2C (CYP2C) activity in bovine endometrial cell cultures following exposure to oxytocin (OT), interferon-t (IFN), estradiol (E2) and/or progesterone (P4). Bovine endometrial epithelial cells were tr...

  18. Regucalcin Expression as a Diagnostic Tool for the Illicit Use of Steroids in Veal Calves.

    PubMed

    Starvaggi Cucuzza, Laura; Biolatti, Bartolomeo; Sereno, Alessandra; Cannizzo, Francesca T

    2015-06-17

    It has been previously demonstrated that sex steroid hormone treatment down-regulates regucalcin gene expression in the accessory sex glands and testis of prepubertal and adult male bovines. The aim of this study was to investigate whether low doses of sex steroid hormones combined with other drugs significantly affect regucalcin gene expression in the accessory sex glands and testis of veal calves. The regucalcin expression was down-regulated in the bulbo-urethral glands of estrogen-treated calves, whereas it was up-regulated in the prostate of estrogen-treated calves. Only the testis of androgen-treated calves showed a down-regulation of the regucalcin expression. Thus, the administration of sex steroid hormones, even in low doses and combined with other molecules, could affect regucalcin expression in target organs. Particularly, the specific response in the testis suggests regucalcin expression in this organ as a first molecular biomarker of illicit androgen administration in bovine husbandry. PMID:26016660

  19. Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

    PubMed

    Sagae, Sara Cristina; Grassiolli, Sabrina; Raineki, Charlis; Balbo, Sandra Lucinei; Marques da Silva, Ana Carla

    2011-11-01

    Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females. PMID:22039988

  20. Neuroendocrine underpinnings of sex differences in circadian timing systems.

    PubMed

    Yan, Lily; Silver, Rae

    2016-06-01

    There are compelling reasons to study the role of steroids and sex differences in the circadian timing system. A solid history of research demonstrates the ubiquity of circadian changes that impact virtually all behavioral and biological responses. Furthermore, steroid hormones can modulate every attribute of circadian responses including the period, amplitude and phase. Finally, desynchronization of circadian rhythmicity, and either enhancing or damping amplitude of various circadian responses can produce different effects in the sexes. Studies of the neuroendocrine underpinnings of circadian timing systems and underlying sex differences have paralleled the overall development of the field as a whole. Early experimental studies established the ubiquity of circadian rhythms by cataloging daily and seasonal changes in whole organism responses. The next generation of experiments demonstrated that daily changes are not a result of environmental synchronizing cues, and are internally orchestrated, and that these differ in the sexes. This work was followed by the revelation of molecular circadian rhythms within individual cells. At present, there is a proliferation of work on the consequences of these daily oscillations in health and in disease, and awareness that these may differ in the sexes. In the present discourse we describe the paradigms used to examine circadian oscillation, to characterize how these internal timing signals are synchronized to local environmental conditions, and how hormones of gonadal and/or adrenal origin modulate circadian responses. Evidence pointing to endocrinologically and genetically mediated sex differences in circadian timing systems can be seen at many levels of the neuroendocrine and endocrine systems, from the cell, the gland and organ, and to whole animal behavior, including sleep/wake or rest/activity cycles, responses to external stimuli, and responses to drugs. We review evidence indicating that the analysis of the circadian

  1. [Anti-edema activity of a trans-cutaneous non-steroidal anti-inflammatory agent, etofenamate gel, in rats].

    PubMed

    Nakamura, H; Motoyoshi, S; Yokoyama, Y; Kadokawa, T; Shimizu, M

    1982-08-01

    Local anti-inflammatory activity of etofenamate gel (5% etofenamate) was investigated in rats. Etofenamate gel (5--50 mg/paw) produced a dose related inhibition