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Sample records for zebrafish sex hormone

  1. In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

    SciTech Connect

    Thorsteinson, Nels; Ban, Fuqiang; Santos-Filho, Osvaldo

    2009-01-01

    Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We alsomore » screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [{sup 3}H]5{alpha}-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 {mu}M concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.« less

  2. Zebrafish sex: a complicated affair

    PubMed Central

    Liew, Woei Chang

    2014-01-01

    In this review, we provide a detailed overview of studies on the elusive sex determination (SD) and gonad differentiation mechanisms of zebrafish (Danio rerio). We show that the data obtained from most studies are compatible with polygenic sex determination (PSD), where the decision is made by the allelic combinations of several loci. These loci are typically dispersed throughout the genome, but in some teleost species a few of them might be located on a preferential pair of (sex) chromosomes. The PSD system has a much higher level of variation of SD genotypes both at the level of gametes and the sexual genotype of individuals, than that of the chromosomal sex determination systems. The early sexual development of zebrafish males is a complicated process, as they first develop a ‘juvenile ovary’, that later undergoes a transformation to give way to a testis. To date, three major developmental pathways were shown to be involved with gonad differentiation through the modulation of programmed cell death. In our opinion, there are more pathways participating in the regulation of zebrafish gonad differentiation/transformation. Introduction of additional powerful large-scale genomic approaches into the analysis of zebrafish reproduction will result in further deepening of our knowledge as well as identification of additional pathways and genes associated with these processes in the near future. PMID:24148942

  3. Polygenic Sex Determination System in Zebrafish

    PubMed Central

    Liew, Woei Chang; Bartfai, Richard; Lim, Zijie; Sreenivasan, Rajini; Siegfried, Kellee R.; Orban, Laszlo

    2012-01-01

    Background Despite the popularity of zebrafish as a research model, its sex determination (SD) mechanism is still unknown. Most cytogenetic studies failed to find dimorphic sex chromosomes and no primary sex determining switch has been identified even though the assembly of zebrafish genome sequence is near to completion and a high resolution genetic map is available. Recent publications suggest that environmental factors within the natural range have minimal impact on sex ratios of zebrafish populations. The primary aim of this study is to find out more about how sex is determined in zebrafish. Methodology/Principal Findings Using classical breeding experiments, we found that sex ratios across families were wide ranging (4.8% to 97.3% males). On the other hand, repeated single pair crossings produced broods of very similar sex ratios, indicating that parental genotypes have a role in the sex ratio of the offspring. Variation among family sex ratios was reduced after selection for breeding pairs with predominantly male or female offspring, another indication that zebrafish sex is regulated genetically. Further examinations by a PCR-based “blind assay" and array comparative genomic hybridization both failed to find universal sex-linked differences between the male and female genomes. Together with the ability to increase the sex bias of lines by selective breeding, these data suggest that zebrafish is unlikely to utilize a chromosomal sex determination (CSD) system. Conclusions/Significance Taken together, our study suggests that zebrafish sex is genetically determined with limited, secondary influences from the environment. As we have not found any sign for CSD in the species, we propose that the zebrafish has a polygenic sex determination system. PMID:22506019

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

    PubMed Central

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

    2013-01-01

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

  5. Sex hormones and headache.

    PubMed

    Silberstein, S D

    2000-01-01

    The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. Menarche marks the onset of menses and cyclic changes in hormone levels. Pregnancy is associated with rising noncyclic levels of sex hormones, and menopause with declining noncyclic levels. Hormonal contraceptive use during the reproductive years and hormone replacement in menopause are therapeutic hormonal interventions that alter the levels and cycling of sex hormones. These events and interventions may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions between the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Estrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of Menstrually-related migraine (MM) appears to be the withdrawal of estrogen rather than the maintenance of sustained high or low estrogen levels. However, changes in the sustained estrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches associated with OC use or menopausal hormonal replacement therapy may be related, in part, to periodic discontinuation of oral sex hormone preparations. The treatment of migraine associated with changes in sex hormone levels is frequently difficult and the patients are often refractory to therapy. Based on what is known of the pathophysiology of migraine, we have attempted to provide a logical approach to the treatment of headaches that are associated with menses, menopause, and OCs using abortive and preventive medications and hormonal manipulations. Considerable evidence suggests a link between estrogen and progesterone, the female sex hormones, and migraine. (Silberstein

  6. SHBG (Sex Hormone Binding Globulin)

    MedlinePlus

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  7. "Sex Hormones" in Secondary School Biology Textbooks

    ERIC Educational Resources Information Center

    Nehm, Ross H.; Young, Rebecca

    2008-01-01

    This study explores the extent to which the term "sex hormone" is used in science textbooks, and whether the use of the term "sex hormone" is associated with pre-empirical concepts of sex dualism, in particular the misconceptions that these so-called "sex hormones" are sex specific and restricted to sex-related physiological functioning. We found…

  8. Sex-hormone-binding globulin.

    PubMed

    Anderson, D C

    1974-01-01

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

  9. Sex hormones and the genesis of autoimmunity.

    PubMed

    Ackerman, Lindsay S

    2006-03-01

    The sexually dimorphic prevalence of autoimmune disease remains one of the most intriguing clinical observations among this group of disorders. While sex hormones have long been recognized for their roles in reproductive functions, within the past 2 decades scientists have found that sex hormones are integral signaling modulators of the mammalian immune system. Sex hormones have definitive roles in lymphocyte maturation, activation, and synthesis of antibodies and cytokines. Sex hormone expression is altered among patients with autoimmune disease, and this variation of expression contributes to immune dysregulation. English-language literature from the last 10 years was reviewed to examine the relationship between sex hormones and the function of the mammalian immune system. Approximately 50 publications were included in this review, and the majority were controlled trials with investigator blinding that compared both male and female diseased and normal subjects. The review provided basic knowledge regarding the broad impact of sex hormones on the immune system and how abnormal sex hormone expression contributes to the development and maintenance of autoimmune phenomena, with a focus on systemic lupus erythematosus, as models of "lupus-prone" mice are readily available. Sex hormones affect the function of the mammalian immune system, and sex hormone expression is different in patients with systemic lupus erythematosus than in healthy subjects. Sex hormones play a role in the genesis of autoimmunity. Future research may provide a therapeutic approach that is capable of altering disease pathogenesis, rather than targeting disease sequelae.

  10. Maternal thyroid hormones are essential for neural development in zebrafish.

    PubMed

    Campinho, Marco A; Saraiva, João; Florindo, Claudia; Power, Deborah M

    2014-07-01

    Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition.

  11. Maternal Thyroid Hormones Are Essential for Neural Development in Zebrafish

    PubMed Central

    Saraiva, João; Florindo, Claudia; Power, Deborah M.

    2014-01-01

    Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition. PMID:24877564

  12. Wild Sex in Zebrafish: Loss of the Natural Sex Determinant in Domesticated Strains

    PubMed Central

    Wilson, Catherine A.; High, Samantha K.; McCluskey, Braedan M.; Amores, Angel; Yan, Yi-lin; Titus, Tom A.; Anderson, Jennifer L.; Batzel, Peter; Carvan, Michael J.; Schartl, Manfred; Postlethwait, John H.

    2014-01-01

    Sex determination can be robustly genetic, strongly environmental, or genetic subject to environmental perturbation. The genetic basis of sex determination is unknown for zebrafish (Danio rerio), a model for development and human health. We used RAD-tag population genomics to identify sex-linked polymorphisms. After verifying this “RAD-sex” method on medaka (Oryzias latipes), we studied two domesticated zebrafish strains (AB and TU), two natural laboratory strains (WIK and EKW), and two recent isolates from nature (NA and CB). All four natural strains had a single sex-linked region at the right tip of chromosome 4, enabling sex genotyping by PCR. Genotypes for the single nucleotide polymorphism (SNP) with the strongest statistical association to sex suggested that wild zebrafish have WZ/ZZ sex chromosomes. In natural strains, “male genotypes” became males and some “female genotypes” also became males, suggesting that the environment or genetic background can cause female-to-male sex reversal. Surprisingly, TU and AB lacked detectable sex-linked loci. Phylogenomics rooted on D. nigrofasciatus verified that all strains are monophyletic. Because AB and TU branched as a monophyletic clade, we could not rule out shared loss of the wild sex locus in a common ancestor despite their independent domestication. Mitochondrial DNA sequences showed that investigated strains represent only one of the three identified zebrafish haplogroups. Results suggest that zebrafish in nature possess a WZ/ZZ sex-determination mechanism with a major determinant lying near the right telomere of chromosome 4 that was modified during domestication. Strains providing the zebrafish reference genome lack key components of the natural sex-determination system but may have evolved variant sex-determining mechanisms during two decades in laboratory culture. PMID:25233988

  13. Association between asthma and female sex hormones.

    PubMed

    Baldaçara, Raquel Prudente de Carvalho; Silva, Ivaldo

    2017-01-01

    The relationship between sex hormones and asthma has been evaluated in several studies. The aim of this review article was to investigate the association between asthma and female sex hormones, under different conditions (premenstrual asthma, use of oral contraceptives, menopause, hormone replacement therapy and pregnancy). Narrative review of the medical literature, Universidade Federal do Tocantins (UFT) and Universidade Federal de São Paulo (Unifesp). We searched the CAPES journal portal, a Brazilian platform that provides access to articles in the MEDLINE, PubMed, SciELO, and LILACS databases. The following keywords were used based on Medical Subject Headings: asthma, sex hormones, women and use of oral contraceptives. The associations between sex hormones and asthma remain obscure. In adults, asthma is more common in women than in men. In addition, mortality due to asthma is significantly higher among females. The immune system is influenced by sex hormones: either because progesterone stimulates progesterone-induced blocking factor and Th2 cytokines or because contraceptives derived from progesterone and estrogen stimulate the transcription factor GATA-3. The associations between asthma and female sex hormones remain obscure. We speculate that estrogen fluctuations are responsible for asthma exacerbations that occur in women. Because of the anti-inflammatory action of estrogen, it decreases TNF-α production, interferon-γ expression and NK cell activity. We suggest that further studies that highlight the underlying physiopathological mechanisms contributing towards these interactions should be conducted.

  14. Relation between sex hormones and hepatocellular carcinoma.

    PubMed

    El Mahdy Korah, T; Abd Elfatah Badr, E; Mohamed Emara, M; Ahmed Samy Kohla, M; Gamal Saad Michael, G

    2016-11-01

    Males have higher incidence of hepatocellular carcinoma (HCC) than females. Sex hormones may be a risk factor. The aim was to determine the levels of sex hormones in male and female patients with HCC and cirrhosis versus controls and its possible relationship with HCC. This study was conducted on 90 subjects divided into 40 patients with HCC, 30 patients with liver cirrhosis and 20 apparently healthy subjects complete blood picture, liver function tests. Determination of AFP levels and hormonal assay of oestrogen, progesterone, total testosterone, prolactin, FSH and LH were performed on all subjects. Total testosterone levels were significantly decreased in the two patients groups compared with controls. While oestrogen levels were significantly decreased in the HCC group in comparison with other two groups, prolactin levels were significantly decreased in the HCC group compared with the liver cirrhosis group and increased in the liver cirrhosis group when compared to controls. FSH and LH levels were significantly increased in the HCC group when compared to controls. There is no significant correlation between sex hormones assay and both the size of HCC and degree of cirrhosis in both patient groups. It is concluded that there is no strong relation between sex hormones and HCC when the study was carried out on the levels of sex hormones in patients with HCC. © 2016 Blackwell Verlag GmbH.

  15. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.

    PubMed Central

    Ansar Ahmed, S.; Penhale, W. J.; Talal, N.

    1985-01-01

    Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation. Images Figure 1 PMID:3907369

  16. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action.

    PubMed

    Ansar Ahmed, S; Penhale, W J; Talal, N

    1985-12-01

    Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation.

  17. ``Sex Hormones'' in Secondary School Biology Textbooks

    NASA Astrophysics Data System (ADS)

    Nehm, Ross H.; Young, Rebecca

    2008-11-01

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

  18. Sex in the brain: hormones and sex differences.

    PubMed

    Marrocco, Jordan; McEwen, Bruce S

    2016-12-01

    Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

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

    PubMed

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

    2015-10-01

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

  20. The essential role of endogenous ghrelin in growth hormone expression during zebrafish adenohypophysis development.

    PubMed

    Li, Xi; He, Jiangyan; Hu, Wei; Yin, Zhan

    2009-06-01

    Ghrelin, a multifunctional hormone, including potent GH stimulation activity, has been suggested to be important during embryonic development. Expression of ghrelin has been confirmed in the zebrafish pancreas during embryonic stages. Interfering with ghrelin function using two specific antisense morpholino oligonucleotides causes defects during zebrafish embryonic development. In ghrelin morphants the expression of GH was abolished in zebrafish somatotropes, whereas the expression patterns of the other key molecules involved in hypothalamic-pituitary development and distinct pituitary hormones genes remain largely intact at the appropriate time during zebrafish adenohypophysis development. Effective rescue of the ghrelin morphants with exogenous ghrelin mRNA showed that the correct gene had been targeted. Moreover, by analyzing the efficiencies of the ghrelin morphants rescue experiments with various forms of exogenous mutant ghrelin mRNAs, we also demonstrated the essentiality of the form acyl-ghrelin on GH stimulation during zebrafish adenohypophysis development. Our in vivo experiments, for the first time, also provided evidence of the existence of functional obestatin in the C-terminal part of zebrafish proghrelin peptides. Our research here has demonstrated that zebrafish is a unique model for functional studies of endogenous ghrelin, especially during embryonic development.

  1. Multiple Sex-Associated Regions and a Putative Sex Chromosome in Zebrafish Revealed by RAD Mapping and Population Genomics

    PubMed Central

    Anderson, Jennifer L.; Rodríguez Marí, Adriana; Braasch, Ingo; Amores, Angel; Hohenlohe, Paul; Batzel, Peter; Postlethwait, John H.

    2012-01-01

    Within vertebrates, major sex determining genes can differ among taxa and even within species. In zebrafish (Danio rerio), neither heteromorphic sex chromosomes nor single sex determination genes of large effect, like Sry in mammals, have yet been identified. Furthermore, environmental factors can influence zebrafish sex determination. Although progress has been made in understanding zebrafish gonad differentiation (e.g. the influence of germ cells on gonad fate), the primary genetic basis of zebrafish sex determination remains poorly understood. To identify genetic loci associated with sex, we analyzed F2 offspring of reciprocal crosses between Oregon *AB and Nadia (NA) wild-type zebrafish stocks. Genome-wide linkage analysis, using more than 5,000 sequence-based polymorphic restriction site associated (RAD-tag) markers and population genomic analysis of more than 30,000 single nucleotide polymorphisms in our *ABxNA crosses revealed a sex-associated locus on the end of the long arm of chr-4 for both cross families, and an additional locus in the middle of chr-3 in one cross family. Additional sequencing showed that two SNPs in dmrt1 previously suggested to be functional candidates for sex determination in a cross of ABxIndia wild-type zebrafish, are not associated with sex in our AB fish. Our data show that sex determination in zebrafish is polygenic and that different genes may influence sex determination in different strains or that different genes become more important under different environmental conditions. The association of the end of chr-4 with sex is remarkable because, unique in the karyotype, this chromosome arm shares features with known sex chromosomes: it is highly heterochromatic, repetitive, late replicating, and has reduced recombination. Our results reveal that chr-4 has functional and structural properties expected of a sex chromosome. PMID:22792396

  2. Sex hormones in women with kidney disease.

    PubMed

    Ahmed, Sofia B; Ramesh, Sharanya

    2016-11-01

    Menstrual disorders, infertility and premature menopause are common but often underrecognized phenomena among women with chronic kidney disease. Hypothalamic, rather than ovarian dysfunction, may be the cause of the abnormal reproductive milieu, which can be at least partially reversed by kidney transplantation and increased intensity of hemodialysis. Endogenous sex hormones, and specifically estradiol, appear to be renoprotective in women, although the effects of exogenous estradiol (as an oral contraceptive and postmenopausal hormone therapy) on kidney function are more controversial. Treatment with postmenopausal hormone therapy in women with end-stage kidney disease (ESKD) has been associated with improved quality of life, bone health and markers of cardiovascular risk, as well as an increased risk of arteriovenous access thrombosis. The selective estrogen receptor modulator raloxifene has been associated with both a decreased fracture risk as well as renoprotection in women with kidney disease. Young women with ESKD are more likely to die from infection or develop malignancy, suggesting an immunomodulatory role of estrogen. Whether the premature menopause commonly observed in female patients with kidney disease results in increased cardiovascular morbidity and mortality is unknown, although preliminary studies have suggested a possible therapeutic role for manipulation of the sex hormone milieu to mitigate risk in this population. Large, prospective, randomized studies examining the role of sex hormones in women with kidney disease are required to address the question. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  3. Sex hormones and skeletal muscle weakness.

    PubMed

    Sipilä, Sarianna; Narici, Marco; Kjaer, Michael; Pöllänen, Eija; Atkinson, Ross A; Hansen, Mette; Kovanen, Vuokko

    2013-06-01

    Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

  4. Sex hormones, their receptors and bone health.

    PubMed

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

    2008-11-01

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

  5. Effects of larval-juvenile treatment with perchlorate and co-treatment with thyroxine on zebrafish sex ratios

    USGS Publications Warehouse

    Mukhi, S.; Torres, L.; Patino, R.

    2007-01-01

    The objective of this study was to determine the effect of larval-juvenile exposure to perchlorate, a thyroid hormone synthesis inhibitor, on the establishment of gonadal sex ratios in zebrafish. Zebrafish were exposed to untreated water or water containing perchlorate at 100 or 250 ppm for a period of 30 days starting at 3 days postfertilization (dpf). Recovery treatments consisted of a combination of perchlorate and exogenous thyroxine (T4; 10 nM). Thyroid histology was assessed at the end of the treatment period (33 dpf), and gonadal histology and sex ratios were determined in fish that were allowed an additional 10-day period of growth in untreated water. As expected, exposure to perchlorate caused changes in thyroid histology consistent with hypothyroidism and these effects were reversed by co-treatment with exogenous T4. Perchlorate did not affect fish survival but co-treatment with T4 induced higher mortality. However, relative to the corresponding perchlorate concentration, co-treatment with T4 caused increased mortality only at a perchlorate concentration of 100 ppm. Perchlorate alone or in the presence of T4 suppressed body length at 43 dpf relative to control values. Perchlorate exposure skewed the sex ratio toward female in a concentration-dependent manner, and co-treatment with T4 not only blocked the feminizing effect of perchlorate but also overcompensated by skewing the sex ratio towards male. Moreover, co-treatment with T4 advanced the onset of spermatogenesis in males. There was no clear association between sex ratios and larval survival or growth. We conclude that endogenous thyroid hormone plays a role in the establishment of gonadal sex phenotype during early development in zebrafish. ?? 2006 Elsevier Inc. All rights reserved.

  6. Sex hormones and the elderly male voice.

    PubMed

    Gugatschka, Markus; Kiesler, Karl; Obermayer-Pietsch, Barbara; Schoekler, Bernadette; Schmid, Christoph; Groselj-Strele, Andrea; Friedrich, Gerhard

    2010-05-01

    The objective was to describe influences of sex hormones on the male voice in an elderly cohort. Sixty-three elderly males were recruited to undergo assessment of voice parameters, stroboscopy, voice-related questionnaires, a blood draw, and an ultrasound examination of the laryngeal skeleton. The group was divided into men with normal hormonal status and men with lowered levels of sex hormones, called hypogonades. Depending on the level of androgens, voice parameters did not differ. In subjects with decreased levels of estrogens, a significant increase in mean fundamental frequency, as well as changes of highest and lowest frequency plus a shift of the frequency range could be detected. We could detect significant changes of voice parameters depending on status of estrogens in elderly males. Androgens appear to have no impact on the elderly male voice. To our knowledge, this is the first prospective study that correlates sex hormones with voice parameters in elderly men. (c) 2010 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  7. Why sex hormones matter for neuroscience: A very short review on sex, sex hormones, and functional brain asymmetries.

    PubMed

    Hausmann, Markus

    2017-01-02

    Biological sex and sex hormones are known to affect functional cerebral asymmetries (FCAs). Men are generally more lateralized than women. The effect size of this sex difference is small but robust. Some of the inconsistencies in the literature may be explained by sex-related hormonal differences. Most studies focusing on neuromodulatory properties of sex hormones on FCAs have investigated women during the menstrual cycle. Although contradictions exist, these studies have typically shown that levels of estradiol and/or progesterone correlate with the degree of FCAs, suggesting that sex differences in FCAs partially depend on hormonal state and day of testing. The results indicate that FCAs are not fixed but are hormone dependent, and as such they can dynamically change within relatively short periods throughout life. Many issues raised in this Mini-Review refer not only to FCAs but also to other aspects of functional brain organization, such as functional connectivity within and between the cerebral hemispheres. Our understanding of sex differences in brain and behavior as well as their clinical relevance will improve significantly if more studies routinely take sex and sex hormones into account. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Zebrafish monosex population reveals female dominance in sex determination and earliest events of gonad differentiation.

    PubMed

    Tong, Sok-Keng; Hsu, Hwei-Jan; Chung, Bon-chu

    2010-08-15

    The zebrafish is a popular model for genetic analysis and its sex differentiation has been the focus of attention for breeding purposes. Despite numerous efforts, very little is known about the mechanism of zebrafish sex determination. The lack of discernible sex chromosomes and the difficulty of distinguishing the sex of juvenile fish are two major obstacles that hamper the progress in such studies. To alleviate these problems, we have developed a scheme involving methyltestosterone treatment followed by natural mating to generate fish with predictable sex trait. Female F1 fish that gave rise to all-female offspring were generated. This predictable sex trait enables characterization of gonadal development in juvenile fish by histological examination and gene expression analysis. We found the first sign of zebrafish sex differentiation to be ovarian gonocyte proliferation and differentiation at 10 to 12 days post-fertilization (dpf). Somatic genes were expressed indifferently at 10 to 17 dpf, and then became sexually dimorphic at three weeks. This result indicates clear distinction of male and female gonads derived independently from primordial gonads. We classified the earliest stages of zebrafish sex determination into the initial preparation followed by female germ cell growth, oocyte differentiation, and somatic differentiation. Our genetic selection scheme matches the prediction that female-dominant genetic factors are required to determine zebrafish sex. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Sex-dependent effects of microcystin-LR on hypothalamic-pituitary-gonad axis and gametogenesis of adult zebrafish

    PubMed Central

    Liu, Wanjing; Chen, Chuanyue; Chen, Liang; Wang, Li; Li, Jian; Chen, Yuanyuan; Jin, Jienan; Kawan, Atufa; Zhang, Xuezhen

    2016-01-01

    While microcystins (MCs) have been reported to exert reproductive toxicity on fish with a sex-dependent effect, the underlying mechanism has been rarely investigated. In the present study, zebrafish were exposed to 1, 5 and 20 μg/L MC-LR for 30 d. The gonad-somatic index declined in all treated males. 17β-estradiol (E2), testosterone (T), 11-keto testosterone (11-KT) and follicle-stimulating hormone (FSH) levels increased in serum from all treated females, while T, FSH and luteinizing hormone (LH) levels changed in all treated males. Histomorphological observation showed that MC-LR exposure evidently retarded oogenesis and spermatogenesis. Transcriptional changes of 22 genes of the hypothalamic-pituitary-gonad (HPG) axis exhibited sex-specific responses, and the relationship between gene transcriptions and gametogenesis was evaluated by principle component analysis (PCA). Major contributors to PC1 (gnrh2, gnrhr3, ar, lhr, hmgra, hmgrb and cyp19a) were positively correlated with the number of post-vitellogenic oocytes, while PC1 (gnrh2, lhβ, erβ, fshr, cyp11a and 17βhsd) were positively correlated with the number of spermatozoa. The protein levels of 17βHSD and CYP19a were affected in both females and males. In conclusion, this study first investigated the sex-dependent effects of microcystins on fish reproduction and revealed some important molecular biomarkers related to gametogenesis in zebrafish suffered from MC-LR. PMID:26960901

  10. Sex-dependent effects of microcystin-LR on hypothalamic-pituitary-gonad axis and gametogenesis of adult zebrafish

    NASA Astrophysics Data System (ADS)

    Liu, Wanjing; Chen, Chuanyue; Chen, Liang; Wang, Li; Li, Jian; Chen, Yuanyuan; Jin, Jienan; Kawan, Atufa; Zhang, Xuezhen

    2016-03-01

    While microcystins (MCs) have been reported to exert reproductive toxicity on fish with a sex-dependent effect, the underlying mechanism has been rarely investigated. In the present study, zebrafish were exposed to 1, 5 and 20 μg/L MC-LR for 30 d. The gonad-somatic index declined in all treated males. 17β-estradiol (E2), testosterone (T), 11-keto testosterone (11-KT) and follicle-stimulating hormone (FSH) levels increased in serum from all treated females, while T, FSH and luteinizing hormone (LH) levels changed in all treated males. Histomorphological observation showed that MC-LR exposure evidently retarded oogenesis and spermatogenesis. Transcriptional changes of 22 genes of the hypothalamic-pituitary-gonad (HPG) axis exhibited sex-specific responses, and the relationship between gene transcriptions and gametogenesis was evaluated by principle component analysis (PCA). Major contributors to PC1 (gnrh2, gnrhr3, ar, lhr, hmgra, hmgrb and cyp19a) were positively correlated with the number of post-vitellogenic oocytes, while PC1 (gnrh2, lhβ, erβ, fshr, cyp11a and 17βhsd) were positively correlated with the number of spermatozoa. The protein levels of 17βHSD and CYP19a were affected in both females and males. In conclusion, this study first investigated the sex-dependent effects of microcystins on fish reproduction and revealed some important molecular biomarkers related to gametogenesis in zebrafish suffered from MC-LR.

  11. Sex hormones in the cardiovascular system.

    PubMed

    dos Santos, Roger Lyrio; da Silva, Fabrício Bragança; Ribeiro, Rogério Faustino; Stefanon, Ivanita

    2014-05-01

    Gender-associated differences in the development of cardiovascular diseases have been described in humans and animals. These differences could explain the low incidence of cardiovascular disease in women in the reproductive period, such as stroke, hypertension, and atherosclerosis. The cardiovascular protection observed in females has been attributed to the beneficial effects of estrogen on endothelial function. Besides estrogen, sex hormones are able to modulate blood pressure by acting on important systems as cardiovascular, renal, and neural. They can have complementary or antagonistic actions. For example, testosterone can raise blood pressure by stimulating the renin-angiotensin-aldosterone system, whereas estrogen alone or combined with progesterone has been associated with decreased blood pressure. The effects of testosterone in the development of cardiovascular disease are contradictory. Although some researchers suggest a positive effect, others indicate negative actions of testosterone. Estrogens physiologically stimulate the release of endothelium-derived vasodilator factors and inhibit the renin-angiotensin system. Although the cardioprotective effects of estrogen are widely appreciated, little is known about the effects of progesterone, which is commonly used in hormone replacement therapy. Progesterone has both vasodilatory and vasoconstrictive effects in the vasculature, depending on the location of the vessel and the level of exposure. Nevertheless, the mechanisms through which sex hormones modulate blood pressure have not been fully elucidated. Therefore, the characterization of those could lead to a better understanding of hypertension in women and men and perhaps to improved forms of therapy.

  12. Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in Zebrafish

    USGS Publications Warehouse

    Sharma, Prakash; Tang, Song; Mayer, Gregory D.; Patino, Reynaldo

    2016-01-01

    Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2 nM), goitrogen [methimazole (MZ), 0.15 mM], MZ (0.15 mM) and T4 (2 nM) (rescue treatment), or reconstituted water (control) from 3 to 33 days postfertilization (dpf) and maintained in control water until 45 dpf. Whole fish were collected during early (25 dpf) and late (45 dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45 dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male-biased populations, and T4 alone induced precocious puberty in ∼50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45 dpf and, unexpectedly, reduced expression of dmrt1 at 45 dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45 dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25 dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non-thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its “feminizing” activity on gonadal

  13. Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in Zebrafish.

    PubMed

    Sharma, Prakash; Tang, Song; Mayer, Gregory D; Patiño, Reynaldo

    2016-09-01

    Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2nM), goitrogen [methimazole (MZ), 0.15mM], MZ (0.15mM) and T4 (2nM) (rescue treatment), or reconstituted water (control) from 3 to 33days postfertilization (dpf) and maintained in control water until 45dpf. Whole fish were collected during early (25dpf) and late (45dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male-biased populations, and T4 alone induced precocious puberty in ∼50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45dpf and, unexpectedly, reduced expression of dmrt1 at 45dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non-thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its "feminizing" activity on gonadal sex is not permanent. Published by Elsevier Inc.

  14. Follicle stimulating hormone, its novel association with sex hormone binding globulin in men and postmenopausal women.

    PubMed

    Wang, Ningjian; Zhang, Kun; Han, Bing; Li, Qin; Chen, Yi; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Zhai, Hualing; Jiang, Boren; Shen, Zhoujun; Lu, Yingli

    2017-06-01

    Follicle stimulating hormone plays direct roles in a variety of nongonadal tissues and sex hormone binding globulin is becoming the convergence of the crosstalk among metabolic diseases. However, no studies have explored the association between follicle stimulating hormone and sex hormone binding globulin. We aimed to study this association among men and women. SPECT-China is a population-based study conducted since 2014. This study included 4206 men and 2842 postmenopausal women. Collected serum was assayed for gonadotropins, sex hormone binding globulin, sex hormones etc. Regression analyses were performed to assess the relationship between sex hormone binding globulin and follicle stimulating hormone and other variables including metabolic factors, thyroid function and sex hormones. Treatment with follicle stimulating hormone at different concentrations of 0, 5, 50 and 100 IU/L for 24 h was performed in HepG2 cells. In Spearman correlation, sex hormone binding globulin was significantly correlated with FSH, triglycerides, thyroxins, body mass index and blood pressure in men and postmenopausal women (all P < 0.05). In regression analyses, follicle stimulating hormone was a significant predictor of sex hormone binding globulin in men and postmenopausal women (P < 0.05), independent of above variables. Follicle stimulating hormone induced sex hormone binding globulin expression in a dose-dependent fashion in HepG2 cells. Serum follicle stimulating hormone levels were positively associated with circulating sex hormone binding globulin levels in men and postmenopausal women. This association is independent of age, insulin resistance, hepatic function, lipid profile, thyroid function, adiposity, blood pressure, and endogenous sex hormones.

  15. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

    PubMed

    Cawthon, Peggy M; Schousboe, John T; Harrison, Stephanie L; Ensrud, Kristine E; Black, Dennis; Cauley, Jane A; Cummings, Steven R; LeBlanc, Erin S; Laughlin, Gail A; Nielson, Carrie M; Broughton, Augusta; Kado, Deborah M; Hoffman, Andrew R; Jamal, Sophie A; Barrett-Connor, Elizabeth; Orwoll, Eric S

    2016-03-01

    The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Sex Hormone Metabolism and Threatened Abortion

    PubMed Central

    Xu, Qianhua; Chen, Juan; Wei, Zhaolian; Brandon, Ted; Zava, David; Shi, Yuenian Eric; Cao, Yunxia

    2017-01-01

    Background The aim of this study was to evaluate changes in sex hormone metabolism in patients with threatened miscarriage. Material/Method We recruited 73 women in early pregnancy (6–8 weeks of gestation) and divided them into the following 2 groups based on whether they had vaginal bleeding: group A (n=34), the threatened abortion group; and group B (n=39), the normal pregnancy group. Human chorionic gonadotrophin (hCG), estradiol (E2), progesterone (P4), and testosterone (T) serum levels were tested and sex hormone metabolites in the urine were detected using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). As the control, data for sex hormones and their metabolites were obtained in normal women of childbearing age without pregnancy (group C: n=23). Results E2 and T serum levels were lower in women with threatened miscarriage (group A). Estrone (E1), E2, estriol (E3), 16α-hydroxyestrone (16α-OHE1), 4-methoxyestrone (4-MeOE1), 2-hydroxyestradiol (2-OHE2), and 4-methoxyestradiol (4-MeOE2) levels were significantly lower in group A (P=0.001, 0.003, 0.009, 0.001, 0.012, 0.032, and 0.047, respectively.). Urine levels of dehydroepiandrosterone (DHEA), androstenedione (A2), and the metabolite of (A2) were also significantly lower in group A (P=0.007, 0.009, and 0.011, respectively). The 2-OHE1/E1, 4-OHE1/E1, 2-MeOE1/E1, and 2-MeOE2/E2 ratios were lower in group B, whereas the 2-OHE2/E2, 4-OHE2/E2, and 4-MeOE2/E2 ratios were dramatically lower in all pregnant women (groups A and B) than in group C. Conclusions Deficiency in DHEA and abnormal levels of sex hormone metabolites may cause a reduction in the activity of estrogens in women with threatened abortion. These alterations may result in bleeding during the first trimester of pregnancy. PMID:29056745

  17. Interactive effects of culture and sex hormones on the sex role self-concept

    PubMed Central

    Pletzer, Belinda; Petasis, Ourania; Ortner, Tuulia M.; Cahill, Larry

    2015-01-01

    Sex role orientation, i.e., a person's masculinity or femininity, influences cognitive and emotional performance, like biological sex. While it is now widely accepted that sex differences are modulated by the hormonal status of female participants (menstrual cycle, hormonal contraceptive use), the question, whether hormonal status and sex hormones also modulate participants sex role orientation has hardly been addressed previously. The present study assessed sex role orientation and hormonal status as well as sex hormone levels in three samples of participants from two different cultures (Northern American, Middle European). Menstrual cycle phase did not affect participant's masculinity or femininity, but had a significant impact on reference group. While women in their follicular phase (low levels of female sex hormones) determined their masculinity and femininity in reference to men, women in their luteal phase (high levels of female sex hormones) determined their masculinity and femininity in reference to women. Hormonal contraceptive users rated themselves as significantly more feminine and less masculine than naturally cycling women. Furthermore, the impact of biological sex on the factorial structure of sex role orientation as well as the relationship of estrogen to masculinity/femininity was modulated by culture. We conclude that culture and sex hormones interactively affect sex role orientation and hormonal status of participants should be controlled for when assessing masculinity and/or femininity. PMID:26236181

  18. Gender, sex hormones and pulmonary hypertension

    PubMed Central

    Austin, Eric D.; Lahm, Tim; West, James; Tofovic, Stevan P.; Johansen, Anne Katrine; MacLean, Margaret R.; Alzoubi, Abdallah; Oka, Masahiko

    2013-01-01

    Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this “estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent progress has begun to shed light upon the interplay of sex hormones, the pathogenesis of pulmonary hypertension, and the right ventricular response to stress. For example, emerging data in humans and experimental models suggest that estrogens or differential sex hormone metabolism may modify disease risk among susceptible subjects, and that estrogens may interact with additional local factors such as serotonin to enhance the potentially damaging chronic effects of estrogens on the pulmonary vasculature. Regardless, it remains unclear why not all estrogenic compounds behave equally, nor why estrogens appear to be protective in certain settings but detrimental in others. The contribution of androgens and other compounds, such as dehydroepiandrosterone, to pathogenesis and possibly treatment must be considered as well. In this review, we will discuss the recent understandings on how estrogens, estrogen metabolism, dehydroepiandrosterone, and additional susceptibility factors may all contribute to the pathogenesis or potentially to the treatment of pulmonary hypertension, by evaluating current human, cell-based, and experimental model data. PMID:24015330

  19. THE RELATIONSHIP BETWEEN SEX HORMONES, SEX HORMONE BINDING GLOBULIN AND PERIPHERAL ARTERY DISEASE IN OLDER PERSONS

    PubMed Central

    Maggio, M; Cattabiani, C; Lauretani, F; Artoni, A; Bandinelli, S; Schiavi, G; Vignali, A; Volpi, R; Ceresini, G; Lippi, G; Aloe, R; De Vita, F; Giallauria, F; McDermott, MM; Ferrucci, L; Ceda, GP

    2014-01-01

    Objective The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. Methods Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) <0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. Results The mean age (± SD) of the 419 men and 502 women was 75.0 ± 6.8 years (Sixty two participants (41 men, 21 women) had ABI<0.90. Men with PAD had SHBG levels lower than men without PAD (p=0.03). SHBG was negatively and independently associated with PAD in men (p=0.028). but not in women. The relationship was however attenuated after adjusting for sex hormones (p=0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p=0.01). Conclusions Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively. PMID:23102785

  20. The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons.

    PubMed

    Maggio, M; Cattabiani, C; Lauretani, F; Artoni, A; Bandinelli, S; Schiavi, G; Vignali, A; Volpi, R; Ceresini, G; Lippi, G; Aloe, R; De Vita, F; Giallauria, F; McDermott, M M; Ferrucci, L; Ceda, G P

    2012-12-01

    The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations. Nine hundred and twenty-one elderly subjects with data on SHBG, testosterone (T), estradiol (E2) were selected from InCHIANTI study. PAD was defined as an Ankle-Brachial Index (ABI) < 0.90. Logistic regression models adjusted for age (Model 1), age, BMI, insulin, interleukin-6, physical activity, smoking, chronic diseases including metabolic syndrome (Model 2), and a final model including also sex hormones (Model 3) were performed to test the relationship between SHBG, sex hormones and PAD. The mean age (±SD) of the 419 men and 502 women was 75.0 ± 6.8 years. Sixty two participants (41 men, 21 women) had ABI < 0.90. Men with PAD had SHBG levels lower than men without PAD (p = 0.03). SHBG was negatively and independently associated with PAD in men (p = 0.028) but not in women. The relationship was however attenuated after adjusting for sex hormones (p = 0.07). The E2 was not significantly associated with PAD in both men and women. In women, but not in men, T was positively associated with PAD, even after adjusting for multiple confounders, including E2 (p = 0.01). Low SHBG and high T levels are significantly and independently associated with the presence of PAD in older men and women, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases.

    PubMed

    Arnold, Arthur P; Cassis, Lisa A; Eghbali, Mansoureh; Reue, Karen; Sandberg, Kathryn

    2017-05-01

    This review summarizes recent evidence concerning hormonal and sex chromosome effects in obesity, atherosclerosis, aneurysms, ischemia/reperfusion injury, and hypertension. Cardiovascular diseases occur and progress differently in the 2 sexes, because biological factors differing between the sexes have sex-specific protective and harmful effects. By comparing the 2 sexes directly, and breaking down sex into its component parts, one can discover sex-biasing protective mechanisms that might be targeted in the clinic. Gonadal hormones, especially estrogens and androgens, have long been found to account for some sex differences in cardiovascular diseases, and molecular mechanisms mediating these effects have recently been elucidated. More recently, the inherent sexual inequalities in effects of sex chromosome genes have also been implicated as contributors in animal models of cardiovascular diseases, especially a deleterious effect of the second X chromosome found in females but not in males. Hormonal and sex chromosome mechanisms interact in the sex-specific control of certain diseases, sometimes by opposing the action of the other. © 2017 American Heart Association, Inc.

  2. Sex and the housing: Effects on behavior, cortisol levels and weight in zebrafish.

    PubMed

    Reolon, Gustavo Kellermann; de Melo, Gabriela Madalena; da Rosa, João Gabriel Dos Santos; Barcellos, Leonardo José Gil; Bonan, Carla Denise

    2018-01-15

    Studies with zebrafish use acclimatizing periods of at least one week immediately before the experiments. During this time, animals can be housed in sexually segregated conditions (only females or males in the tank) or in mixed-sex conditions (both sexes in the tank). The influence of sex and housing conditions regarding the presence of one or two sexes is largely unknown in zebrafish. Our aim was to evaluate the influence that sex and housing regarding the sex of animals had in the open tank task, in the inhibitory avoidance memory test, in cortisol levels and weight in zebrafish. Four groups of animals were used: 1) segregated housed females (only females were kept in the tank); 2) segregated housed males (only males were kept in the tank); 3) mixed-sex housed females (only females were analyzed from a tank containing 50% ratio of each sex); 4) mixed-sex housed males (only males were analyzed from a tank containing 50% ratio of each sex). Males showed higher total distance travelled and mean speed when compared to females. In the inhibitory avoidance memory, sexually segregated animals had higher latencies than their mixed-sex counterparts in the 1day test and sexually segregated females presented a memory that persisted longer and was able to be reinstated. Whole-body cortisol levels were higher in mixed-sex animals while weight was lower in these fish. To the best of our knowledge, this is the first time that effects of sex and housing regarding sex were investigated in behavior and physiology of zebrafish. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. [Sex hormones and the metabolism of carbohydrates].

    PubMed

    Boukhris, R

    1987-12-01

    Sex hormones play an important role in the control of glucose metabolism and insulin. Decreased glucose tolerance observed at the end of pregnancy in most cases remains within normal limits. Pregnancy has an important effect on the islets of Langerhans and on the growth of beta cellules. At the end of pregnancy, assimilation of glucose and triglycerides by maternal tissues is slowed and transfer to the fetus is favored. Hyperinsulinism persists but insulin resistance at the level of maternal tissue becomes very strong and the number of receptors declines. This late pregnancy insulin resistance has not been satisfactorily explained. The declining number of receptors may be a mechanism, or the "antiinsulin" pregnancy hormones which includes estrogens and progesterone may play a major role. Although other mechanisms have been proposed to explain the antiinsulin effect, the role of sex hormones and especially of progesterone (and synthetic progestins used in contraception) appears crucial. The presence of estrogen and progesterone receptors in the beta cellules of the islets of Langerhans suggests a direct effect of these hormones on the cellules. Estrogens however work by other mechanisms than insulin secretion. Experimental evidence indicates that during pregnancy, progesterone increases insulin release while human placental lactogen stimulates hyperplasia of the islets. The progestins derived from progesterone used in contraception have a parallel action. A slight elevation of blood sugar and insulinemia have been observed in oral contraceptive (OC) users. Only 3-5% of OC users develop true hyperglycemia. The changes are usually transitory and disappear on termination of OC use except in the small number of women predisposed to diabetes. The decreased glucose tolerance of OC users differs from true diabetes. Combined OCs favor vascular accidents and myocardial infarct in insulin-dependent diabetics. The mechanisms involved include deteriorating control of diabetes

  4. [Gender differences in cognitive functions and influence of sex hormones].

    PubMed

    Torres, A; Gómez-Gil, E; Vidal, A; Puig, O; Boget, T; Salamero, M

    2006-01-01

    To review scientific evidence on gender differences in cognitive functions and influence of sex hormones on cognitive performance. Systematical search of related studies identified in Medline. Women outperform men on verbal fluency, perceptual speed tasks, fine motor skills, verbal memory and verbal learning. Men outperform women on visuospatial ability, mathematical problem solving and visual memory. No gender differences on attention and working memory are found. Researchers distinguish four methods to investigate hormonal influence on cognitive performance: a) patient with hormonal disorders; b) neuroimaging in individuals during hormone administration; c) in women during different phases of menstrual cycle, and d) in patients receiving hormonal treatment (idiopathic hypogonadotropic hypogonadism, postmenopausal women and transsexuals). The findings mostly suggest an influence of sex hormones on some cognitive functions, but they are not conclusive because of limitations and scarcity of the studies. There are gender differences on cognitive functions. Sex hormones seem to influence cognitive performance.

  5. Effects of Barium Chloride Exposure on Hormones and Genes of the Hypothalamic-Pituitary-Gonad Axis, and Reproduction of Zebrafish (Danio rerio).

    PubMed

    Kwon, Bareum; Ha, Nayoung; Jung, Joeun; Kim, Pan-Gyi; Kho, Younglim; Choi, Kyungho; Ji, Kyunghee

    2016-03-01

    Adult zebrafish pairs were exposed to sub-lethal concentrations of BaCl2 for 21 days, and the effects on reproduction, sex steroid hormones, and transcription of the genes belonging to the hypothalamic-pituitary-gonad (HPG) axis were investigated. The adverse effects on performances of F1 generation were further examined with or without subsequent exposure to BaCl2. Egg production was significantly decreased, and parental exposure to BaCl2 resulted in lesser rates of hatching. In males, exposure to BaCl2 resulted in greater concentrations of E2 along with greater mRNA expression of cyp19a. The results demonstrated that BaCl2 could modulate gene transcriptions and hormone production of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.

  6. Sex and Hormonal influences on Seizures and Epilepsy

    PubMed Central

    Velíšková, Jana; DeSantis, Kara A.

    2012-01-01

    Epilepsy is the third most common chronic neurological disorder. Clinical and experimental evidence supports the role of sex and influence of sex hormones on seizures and epilepsy as well as alterations of the endocrine system and levels of sex hormones by epileptiform activity. Conversely, seizures are sensitive to changes in sex hormone levels, which in turn may affect the seizure-induced neuronal damage. The effects of reproductive hormones on neuronal excitability and seizure-induced damage are complex to contradictory and depend on different mechanisms, which have to be accounted for in data interpretation. Both estradiol and progesterone/allopregnanolone may have beneficial effects for patients with epilepsy. Individualized hormonal therapy should be considered as adjunctive treatment in patients with epilepsy to improve seizure control as well as quality of life. PMID:22504305

  7. Relationships between Circulating and Intraprostatic Sex Steroid Hormone Concentrations.

    PubMed

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

    2017-11-01

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

  8. Activational effects of sex hormones on cognition in men.

    PubMed

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

    2009-11-01

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

  9. Sex hormones and sarcopenia in older persons.

    PubMed

    Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo

    2013-01-01

    Sarcopenia is a geriatric syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life, and death. Sarcopenia is a multifactorial process involving the decline of androgens, including dehydroepiandrosterone sulphate (DHEAS) and testosterone. The aim of this review is to highlight the effects of DHEAS and testosterone treatment to counteract sarcopenia, especially in older men. DHEAS and, more importantly, testosterone treatment are associated with increased muscle mass, whereas the effects on muscle function and physical performance are less clear. The results of recent randomized placebo controlled trials with DHEAS in older men and women and testosterone in men with mobility limitation are discussed. The novel current and future scenarios to attenuate the detrimental effects and to optimize the efficacy of sex hormone treatment are also addressed. DHEAS and testosterone are important options in the armamentarium of sarcopenia treatment in older men. Future studies are needed to address new approaches by using selective compounds, targeting the correct form and dosage, tailoring the correct patient to treat, and taking into account the multifactorial origin and the new definition of sarcopenia.

  10. TFOS DEWS II Sex, Gender, and Hormones Report.

    PubMed

    Sullivan, David A; Rocha, Eduardo M; Aragona, Pasquale; Clayton, Janine A; Ding, Juan; Golebiowski, Blanka; Hampel, Ulrike; McDermott, Alison M; Schaumberg, Debra A; Srinivasan, Sruthi; Versura, Piera; Willcox, Mark D P

    2017-07-01

    One of the most compelling features of dry eye disease (DED) is that it occurs more frequently in women than men. In fact, the female sex is a significant risk factor for the development of DED. This sex-related difference in DED prevalence is attributed in large part to the effects of sex steroids (e.g. androgens, estrogens), hypothalamic-pituitary hormones, glucocorticoids, insulin, insulin-like growth factor 1 and thyroid hormones, as well as to the sex chromosome complement, sex-specific autosomal factors and epigenetics (e.g. microRNAs). In addition to sex, gender also appears to be a risk factor for DED. "Gender" and "sex" are words that are often used interchangeably, but they have distinct meanings. "Gender" refers to a person's self-representation as a man or woman, whereas "sex" distinguishes males and females based on their biological characteristics. Both gender and sex affect DED risk, presentation of the disease, immune responses, pain, care-seeking behaviors, service utilization, and myriad other facets of eye health. Overall, sex, gender and hormones play a major role in the regulation of ocular surface and adnexal tissues, and in the difference in DED prevalence between women and men. The purpose of this Subcommittee report is to review and critique the nature of this role, as well as to recommend areas for future research to advance our understanding of the interrelationships between sex, gender, hormones and DED. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Functional behavior and reproduction in androgenic sex reversed zebrafish (Danio rerio).

    PubMed

    Larsen, Mia G; Baatrup, Erik

    2010-08-01

    Endocrine-disrupting chemicals released into natural watercourses may cause biased sex ratios by sex reversal in fish populations. The present study investigated the androgenic sex reversal of zebrafish (Danio rerio) exposed to the androgenic compound 17beta-trenbolone (TB) and whether sex-changed females would revert to the female phenotype after cessation of TB exposure. 17beta-Trenbolone is a metabolite of trenbolone acetate, an anabolic steroid used as a growth promoter in beef cattle. 17beta-Trenbolone in runoff from cattle feedlots may reach concentrations that affect fish sexual development. Zebrafish were exposed to a concentration of 20 ng/L TB in a flow-through system for five months from egg until sexual maturity. This resulted in an all-male population. It was further found that all these phenotypic males displayed normal male courtship behavior and were able to reproduce successfully, implying that the sex reversal was complete and functional. None of the phenotypic males developed into females after six months in clean water, demonstrating that androgenic sex reversal of zebrafish is irreversible. Copyright 2010 SETAC

  12. Sex hormones adjust "sex-specific" reactive and diurnal cortisol profiles.

    PubMed

    Juster, Robert-Paul; Raymond, Catherine; Desrochers, Alexandra Bisson; Bourdon, Olivier; Durand, Nadia; Wan, Nathalie; Pruessner, Jens C; Lupien, Sonia J

    2016-01-01

    Sex differences in stress hormone functions are presumed to depend on sex hormones. And yet, surprisingly few psychoneuroendocrine studies actually assess within-sex variations of testosterone, estradiol, and progesterone when investigating sex-specific activities of the hypothalamic-pituitary-adrenal axis. In this methodological study of 204 healthy adults (60 men), we assessed whether cortisol profiles would differ between the sexes when unadjusted or adjusted for basal sex hormones among both sexes. Reactive cortisol was sampled using 6 saliva samples measured every 10-min as part of the Trier Social Stress Test that generally activates cortisol among men more than women. Diurnal cortisol was sampled over two days at (1) awakening, (2) 30-min thereafter, (3) 1400 h, (4) 1600 h, and (5) bedtime. Sex hormones were collected at baseline before the psychosocial stressor and on two occasions during diurnal cortisol assessment. Repeated-measures analysis of covariance controlled for key covariates in analyses unadjusted or adjusted for sex hormones. Results revealed that men had higher reactive cortisol than women in unadjusted analysis, but this sex difference was attenuated when adjusting for sex hormones. While diurnal cortisol showed no sex differences in unadjusted models, adjusting for sex hormones revealed that women have higher morning cortisol. Correlations using area under the curve formulae revealed intriguing sex-specific associations with progesterone in men and testosterone in women that we propose have implications for social and affective neuroscience. In summary, our results reveal that adjusting for sex hormones alters "sex-specific" reactive and diurnal cortisol profiles. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Sex differences in the pharmacokinetics of antidepressants: influence of female sex hormones and oral contraceptives.

    PubMed

    Damoiseaux, Valérie A; Proost, Johannes H; Jiawan, Vincent C R; Melgert, Barbro N

    2014-06-01

    Women are twice as likely to develop depression as men. Moreover, the symptoms they experience also show sex differences: women tend to develop depression at an earlier age and show more severe symptoms than men. Likewise, the response to antidepressant pharmacotherapy appears to have sex differences. These differences can partially be explained by differences in pharmacokinetic properties (i.e., absorption, distribution, metabolism, and excretion) of drugs in males and females. More recent research has shown that sex hormones may influence all these previously named pharmacokinetic processes. As concentrations of sex hormones vary throughout the female lifespan, these hormonal variations can have effects on therapeutic responses to antidepressants as well as the occurrence of adverse events. The purpose of this paper is therefore to review the literature reporting on the effects of female sex hormones on the pharmacokinetics of antidepressants and to discuss and evaluate the implications of changes in levels of sex hormones throughout life for the treatment of depression.

  14. The role of Fanconi anemia/BRCA genes in zebrafish sex determination.

    PubMed

    Rodríguez-Marí, Adriana; Postlethwait, John H

    2011-01-01

    Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility. Bone marrow transplants improve hematopoietic phenotypes but do not prevent other cancers. FA arises from mutation in any of the 15 FANC genes that cooperate to repair double stranded DNA breaks by homologous recombination. Zebrafish has a single ortholog of each human FANC gene and unexpectedly, mutations in at least two of them (fancl and fancd1(brca2)) lead to female-to-male sex reversal. Investigations show that, as in human, zebrafish fanc genes are required for genome stability and for suppressing apoptosis in tissue culture cells, in embryos treated with DNA damaging agents, and in meiotic germ cells. The sex reversal phenotype requires the action of Tp53 (p53), an activator of apoptosis. These results suggest that in normal sex determination, zebrafish oocytes passing through meiosis signal the gonadal soma to maintain expression of aromatase, an enzyme that converts androgen to estrogen, thereby feminizing the gonad and the individual. According to this model, normal male and female zebrafish differ in genetic factors that control the strength of the late meiotic oocyte-derived signal, probably by regulating the number of meiotic oocytes, which environmental factors can also alter. Transcripts from fancd1(brca2) localize at the animal pole of the zebrafish oocyte cytoplasm and are required for normal oocyte nuclear architecture, for normal embryonic development, and for preventing ovarian tumors. Embryonic DNA repair and sex reversal phenotypes provide assays for the screening of small molecule libraries for therapeutic substances for FA. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Interactions between Age, Sex, and Hormones in Experimental Ischemic Stroke

    PubMed Central

    Liu, Fudong; McCullough, Louise D.

    2012-01-01

    Age, sex, and gonadal hormones have profound effects on ischemic stroke outcomes, although how these factors impact basic stroke pathophysiology remains unclear. There is a plethora of inconsistent data reported throughout the literature, primarily due to differences in the species examined, the timing and methods used to evaluate injury, the models used, and confusion regarding differences in stroke incidence as seen in clinical populations versus effects on acute neuroprotection or neurorepair in experimental stroke models. Sex and gonadal hormone exposure have considerable independent impact on stroke outcome, but these factors also interact with each other, and the contribution of each differs throughout the lifespan. The contribution of sex and hormones to experimental stroke will be the focus of this review. Recent advances and our current understanding of age, sex, and hormone interactions in ischemic stroke with a focus on inflammation will be discussed. PMID:23068990

  16. Transcriptomic and phenotypic profiling in developing zebrafish exposed to thyroid hormone receptor agonists

    SciTech Connect

    Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.

    There is a need to develop novel, high-throughput screening and prioritization methods to identify chemicals with adverse estrogen, androgen, and thyroid activity to protect human health and the environment and is of interest to the Endocrine Disruptor Screening Program. The current aim is to explore the utility of zebrafish as a testing paradigm to classify endocrine activity using phenotypically anchored transcriptome profiling. Transcriptome analysis was conducted on embryos exposed to 25 estrogen-, androgen-, or thyroid-active chemicals at a concentration that elicited adverse malformations or mortality at 120 hours post-fertilization in 80% of the animals exposed. Analysis of the top 1000more » significant differentially expressed transcripts across all treatments identified a unique transcriptional and phenotypic profile for thyroid hormone receptor agonists, which can be used as a biomarker screen for potential thyroid hormone agonists.« less

  17. Change of body height is regulated by thyroid hormone during metamorphosis in flatfishes and zebrafish.

    PubMed

    Xu, Juan; Ke, Zhonghe; Xia, Jianhong; He, Fang; Bao, Baolong

    2016-09-15

    Flatfishes with more body height after metamorphosis should be better adapted to a benthic lifestyle. In this study, we quantified the changes in body height during metamorphosis in two flatfish species, Paralichthys olivaceus and Platichthys stellatus. The specific pattern of cell proliferation along the dorsal and ventral edge of the body to allow fast growth along the dorsal/ventral axis might be related to the change of body height. Thyroid hormone (T4 and T3) and its receptors showed distribution or gene expression patterns similar to those seen for the cell proliferation. 2-Mercapto-1-methylimidazole, an inhibitor of endogenous thyroid hormone synthesis, inhibited cell proliferation and decreased body height, suggesting that the change in body shape was dependent on the local concentration of thyroid hormone to induce cell proliferation. In addition, after treatment with 2-mercapto-1-methylimidazole, zebrafish larvae were also shown to develop a slimmer body shape. These findings enrich our knowledge of the role of thyroid hormone during flatfish metamorphosis, and the role of thyroid hormone during the change of body height during post-hatching development should help us to understand better the biology of metamorphosis in fishes. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Sex differences in the human brain and the impact of sex chromosomes and sex hormones.

    PubMed

    Lentini, E; Kasahara, M; Arver, S; Savic, I

    2013-10-01

    While there has been increasing support for the existence of cerebral sex differences, the mechanisms underlying these differences are unclear. Based on animal data, it has long been believed that sexual differentiation of the brain is primarily linked to organizational effects of fetal testosterone. This view is, however, in question as more recent data show the presence of sex differences before the onset of testosterone production. The present study focuses on the impact that sex chromosomes might have on these differences. Utilizing the inherent differences in sex and X-chromosome dosage among XXY males, XY males, and XX females, comparative voxel-based morphometry was conducted using sex hormones and sex chromosomes as covariates. Sex differences in the cerebellar and precentral gray matter volumes (GMV) were found to be related to X-chromosome dosage, whereas sex differences in the amygdala, the parahippocamus, and the occipital cortex were linked to testosterone levels. An increased number of sex chromosomes was associated with reduced GMV in the amygdala, caudate, and the temporal and insular cortices, with increased parietal GMV and reduced frontotemporal white matter volume. No selective, testosterone independent, effect of the Y-chromosome was detected. Based on these observations, it was hypothesized that programming of the motor cortex and parts of cerebellum is mediated by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of certain limbic structures involves testosterone and X-chromosome escapee genes with Y-homologs.

  19. Effect of rearing temperatures during embryonic development on the phenotypic sex in zebrafish (Danio rerio).

    PubMed

    Abozaid, H; Wessels, S; Hörstgen-Schwark, G

    2011-01-01

    In zebrafish, Danio rerio, a polygenic pattern of sex determination or a female heterogamety with possible influences of environmental factors is assumed. The present study focuses on the effects of an elevated water temperature (35° C) during the embryonic development on sex determination in zebrafish. Eggs derived from 3 golden females were fertilized by the same mitotic gynogenetic male and exposed to a water temperature of 35° C, applied from 5 to 10 h post fertilization (hpf), from 5 to 24 hpf, and from 5 to 48 hpf, which correspond to the following developmental stages: gastrula, gastrula to segmentation, and gastrula to pharyngula stage, respectively. Hatching and survival rates decreased with increasing exposure to high water temperatures. Reductions in the hatching and survival rates were not responsible for differences in sex ratios. Accordingly, exposition of the fertilized eggs to a high temperature (35° C) leads to an increase of the male proportion from 22.0% in the controls to a balanced sex ratio (48.3, 47.5, and 52.6%) in the gastrula, segmentation, and pharyngula groups, respectively. These results prove the possibility to change the pathway of sexual determination during early embryonic stages in zebrafish by exposure to a high water temperature. Copyright © 2011 S. Karger AG, Basel.

  20. Sex Reversal in Zebrafish fancl Mutants Is Caused by Tp53-Mediated Germ Cell Apoptosis

    PubMed Central

    Rodríguez-Marí, Adriana; Cañestro, Cristian; BreMiller, Ruth A.; Nguyen-Johnson, Alexandria; Asakawa, Kazuhide; Kawakami, Koichi; Postlethwait, John H.

    2010-01-01

    The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA–repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination. PMID:20661450

  1. Biological and psychological influences of cross sex hormone in transgender.

    PubMed

    Ling, Ling Shiao; Sidi, Hatta; Lope, Raja Adam Raja; Das, Srijit; Baharudin, Azlin

    2018-05-11

    Transgender is a complex state of bio-psycho-social dimension of human sexuality. It encompasses cognitive-emotional-behavior component that makes the person unique in his or her sexual expression. Transgender tend to use cross sex hormone in order to eradicate their secondary sexual characteristics and to facilitate the shift to their experienced gender. The common masculinising sex hormone use, i.e. Female to Male Treatment Options (FMTO) is testosterone and for feminising hormone i.e. Male to Female Treatment Options (MFTO) is a combination of estrogen with anti-androgen, respectively. Cross sex hormone, i.e. FMTO, or MFTO has biological and psychological influences on the transgender individuals. Nevertheless, cross sex hormone may also poses a range of side effect profiles, varies from the biological to psychosocial impact. The psychological impact can be paramount until it causes severe mental-health problems and even suicide. Numerous ranges of bio-psycho-social influence of cross-sex hormone were highlighted in this review as fundamental core knowledge in the art to know practice when dealing with the treatment options. In psychiatry, the change in the biological appearance may have great influence in the transgender individual, especially in the context of psychosocial and cultural perspective. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Salivary sex hormones in adolescent females with trichotillomania.

    PubMed

    Grant, Jon E; Chamberlain, Samuel R

    2018-05-05

    Trichotillomania is several times more common in women and has peak onset around puberty. The role of sex hormones, however, has received little research. 11 adolescent girls with trichotillomania, post-menarche and not taking birth control, were examined on a variety of clinical measures. Participants provided saliva samples for analysis of estradiol, progesterone, and testosterone levels. Lower progesterone was associated with more severe symptoms and lower levels of all hormones were associated with worse overall functioning. Adolescents with trichotillomania exhibit a range of hormone levels but that lower levels of certain hormones may have important clinical associations. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Sex hormones in the modulation of irritable bowel syndrome.

    PubMed

    Mulak, Agata; Taché, Yvette; Larauche, Muriel

    2014-03-14

    Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.

  4. Natural mixtures of persistent organic pollutants (POP) increase weight gain, advance puberty, and induce changes in gene expression associated with steroid hormones and obesity in female zebrafish.

    PubMed

    Lyche, Jan L; Nourizadeh-Lillabadi, Rasoul; Almaas, Camilla; Stavik, Benedicte; Berg, Vidar; Skåre, Janneche Utne; Alestrøm, Peter; Ropstad, Erik

    2010-01-01

    In the present study, developmental and reproductive effects of lifelong exposure to environmental relevant concentrations of two natural mixtures of persistent organic pollutants (POP) were investigated using classical and molecular methods in a controlled zebrafish model. The mixtures used were extracted from burbot (Lota lota) liver originating from freshwater systems in Norway: one mixture with high levels and one mixture with background levels of polybrominated diphenyl ethers (PBDE), polychlorinated biphenyls (PCB), and dichlorodiphenyltrichloroethane metabolites (DDT). The concentration of POP measured in the zebrafish ranged from levels detected in wild fish from Lake Mjøsa to concentrations reported in human and wildlife populations, indicating that the experimental fish were exposed to concentrations comparable with wild fish. Phenotypic effects observed in both exposure groups included earlier onset of puberty, increased male/female sex ratio, and differences in body weight at 5 mo of age. Interestingly, genome-wide transcription profiling showed changes in regulation of genes involved in endocrine signaling and growth. The transcriptomics changes include key regulator genes for steroid hormone functions (ncoa3), and growth (c/ebp, ncoa3). The effects observed in the experimental zebrafish model raise the question whether chemical pollution represents a risk to reproductive health of wild fish inhabitating the freshwater system.

  5. Associations between dietary acrylamide intake and plasma sex hormone levels

    PubMed Central

    Hogervorst, Janneke G.; Fortner, Renee T.; Mucci, Lorelei A.; Tworoger, Shelley S.; Eliassen, A. Heather; Hankinson, Susan E.; Wilson, Kathryn M.

    2013-01-01

    Background The rodent carcinogen acrylamide was discovered in 2002 in commonly consumed foods. Epidemiological studies have observed positive associations between acrylamide intake and endometrial, ovarian and breast cancer risks, which suggests that acrylamide may have sex-hormonal effects. Methods We cross-sectionally investigated the relationship between acrylamide intake and plasma levels of sex hormones and SHBG among 687 postmenopausal and 1300 premenopausal controls from nested case-control studies within the Nurses’ Health Studies. Results There were no associations between acrylamide and sex hormones or SHBG among premenopausal women overall or among never-smokers. Among normal-weight premenopausal women, acrylamide intake was statistically significantly positively associated with luteal total and free estradiol levels. Among postmenopausal women overall and among never-smokers, acrylamide was borderline statistically significantly associated with lower estrone sulfate levels but not with other estrogens, androgens, prolactin or SHBG. Among normal weight women, (borderline) statistically significant inverse associations were noted for estrone, free estradiol, estrone sulfate, DHEA, and prolactin, while statistically significant positive associations for testosterone and androstenedione were observed among overweight women. Conclusions Overall, this study did not show conclusive associations between acrylamide intake and sex hormones that would lend unequivocal biological plausibility to the observed increased risks of endometrial, ovarian and breast cancer. The association between acrylamide and sex hormones may differ by menopausal and overweight status. We recommend other studies investigate the relationship between acrylamide and sex hormones in women, specifically using acrylamide biomarkers. Impact The present study showed some interesting associations between acrylamide intake and sex hormones that urgently need confirmation. PMID:23983241

  6. Understanding the broad influence of sex hormones and sex differences in the brain.

    PubMed

    McEwen, Bruce S; Milner, Teresa A

    2017-01-02

    Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects on gene expression induce spine synapses, up- or downregulate and alter the distribution of neurotransmitter receptors, and regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, which influence functions not previously regarded as subject to such differences, indicate that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Understanding the Broad Influence of Sex Hormones and Sex Differences in the Brain

    PubMed Central

    McEwen, Bruce S.; Milner, Teresa A.

    2016-01-01

    Sex hormones act throughout the entire brain of both males and females via both genomic and non-genomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes where they are associated with presynaptic terminals, mitochondria, spine apparatus, post-synaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects upon gene expression induce spine synapses, up- or down-regulate and alter the distribution of neurotransmitter receptors, regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not-yet-precisely-defined genetic factors including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, and upon functions not previously regarded as subject to such differences, indicates that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. PMID:27870427

  8. Retinoic Acid Metabolic Genes, Meiosis, and Gonadal Sex Differentiation in Zebrafish

    PubMed Central

    Rodríguez-Marí, Adriana; Cañestro, Cristian; BreMiller, Ruth A.; Catchen, Julian M.; Yan, Yi-Lin; Postlethwait, John H.

    2013-01-01

    To help understand the elusive mechanisms of zebrafish sex determination, we studied the genetic machinery regulating production and breakdown of retinoic acid (RA) during the onset of meiosis in gonadogenesis. Results uncovered unexpected mechanistic differences between zebrafish and mammals. Conserved synteny and expression analyses revealed that cyp26a1 in zebrafish and its paralog Cyp26b1 in tetrapods independently became the primary genes encoding enzymes available for gonadal RA-degradation, showing lineage-specific subfunctionalization of vertebrate genome duplication (VGD) paralogs. Experiments showed that zebrafish express aldh1a2, which encodes an RA-synthesizing enzyme, in the gonad rather than in the mesonephros as in mouse. Germ cells in bipotential gonads of all zebrafish analyzed were labeled by the early meiotic marker sycp3, suggesting that in zebrafish, the onset of meiosis is not sexually dimorphic as it is in mouse and is independent of Stra8, which is required in mouse but was lost in teleosts. Analysis of dead-end knockdown zebrafish depleted of germ cells revealed the germ cell-independent onset and maintenance of gonadal aldh1a2 and cyp26a1 expression. After meiosis initiated, somatic cell expression of cyp26a1 became sexually dimorphic: up-regulated in testes but not ovaries. Meiotic germ cells expressing the synaptonemal complex gene sycp3 occupied islands of somatic cells that lacked cyp26a1 expression, as predicted by the hypothesis that Cyp26a1 acts as a meiosis-inhibiting factor. Consistent with this hypothesis, females up-regulated cyp26a1 in oocytes that entered prophase-I meiotic arrest, and down-regulated cyp26a1 in oocytes resuming meiosis. Co-expression of cyp26a1 and the pluripotent germ cell stem cell marker pou5f1(oct4) in meiotically arrested oocytes was consistent with roles in mouse to promote germ cell survival and to prevent apoptosis, mechanisms that are central for tipping the sexual fate of gonads towards the female

  9. Contribution of stress and sex hormones to memory encoding.

    PubMed

    Merz, Christian J

    2017-08-01

    Distinct stages of the menstrual cycle and the intake of oral contraceptives (OC) affect sex hormone levels, stress responses, and memory processes critically involved in the pathogenesis of mental disorders. To characterize the interaction of sex and stress hormones on memory encoding, 30 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women were exposed to either a stress (socially evaluated cold-pressor test) or a control condition prior to memory encoding and immediate recall of neutral, positive, and negative words. On the next day, delayed free and cued recall was tested. Sex hormone levels verified distinct estradiol, progesterone, and testosterone levels between groups. Stress increased blood pressure, cortisol concentrations, and ratings of stress appraisal in all four groups as well as cued recall performance of negative words in men. Stress exposure in OC women led to a blunted cortisol response and rather enhanced cued recall of neutral words. Thus, pre-encoding stress facilitated emotional cued recall performance in men only, but not women with different sex hormone statuses pointing to the pivotal role of circulating sex hormones in modulation of learning and memory processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2009-01-01

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

  11. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

    PubMed

    Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

    2013-11-01

    The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

  12. Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish.

    PubMed

    Ji, Kyunghee; Liu, Xiaoshan; Lee, Saeram; Kang, Sungeun; Kho, Younglim; Giesy, John P; Choi, Kyungho

    2013-06-15

    This study was conducted in two experiments, to identify non-steroidal anti-inflammatory drugs (NSAIDs) with high endocrine disruption potentials, and to understand consequences of exposure to such NSAIDs in fish. In the first experiment, the effects of five NSAIDs on hormones and gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis were evaluated after 14 d exposure of adult zebrafish. Ibuprofen and mefenamic acids were identified to increase the concentrations of 17β-estradiol and testosterone in females significantly, while decreased those of testosterone among male fish. Significant up-regulation of fshβ, lhβ, fshr and lhr were observed in females, whereas down-regulation was observed in males exposed to each NSAID. In the second experiment, ibuprofen was chosen as a model chemical. Adult zebrafish pairs were exposed to ibuprofen for 21 d, and the effects on reproduction and development of offspring were examined. The egg production was significantly decreased at ≥1 μg/L ibuprofen, and parental exposure resulted in delayed hatching even when they were transferred to clean water for hatching. The results demonstrated that ibuprofen could modulate hormone production and related gene transcription of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis.

    PubMed

    Chatterjee, Aniruddha; Lagisz, Malgorzata; Rodger, Euan J; Zhen, Li; Stockwell, Peter A; Duncan, Elizabeth J; Horsfield, Julia A; Jeyakani, Justin; Mathavan, Sinnakaruppan; Ozaki, Yuichi; Nakagawa, Shinichi

    2016-09-30

    The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Thyroid hormone actions are temperature-specific and regulate thermal acclimation in zebrafish (Danio rerio).

    PubMed

    Little, Alexander G; Kunisue, Tatsuya; Kannan, Kurunthachalam; Seebacher, Frank

    2013-03-26

    Thyroid hormone (TH) is best known for its role in development in animals, and for its control of metabolic heat production (thermogenesis) during cold acclimation in mammals. It is unknown whether the regulatory role of TH in thermogenesis is derived in mammals, or whether TH also mediates thermal responses in earlier vertebrates. Ectothermic vertebrates show complex responses to temperature variation, but the mechanisms mediating these are poorly understood. The molecular mechanisms underpinning TH action are very similar across vertebrates, suggesting that TH may also regulate thermal responses in ectotherms. We therefore aimed to determine whether TH regulates thermal acclimation in the zebrafish (Danio rerio). We induced hypothyroidism, followed by supplementation with 3,5-diiodothyronine (T2) or 3,5,3'-triiodothyronine (T3) in zebrafish exposed to different chronic temperatures. We measured whole-animal responses (swimming performance and metabolic rates), tissue-specific regulatory enzyme activities, gene expression, and free levels of T2 and T3. We found that both T3 and the lesser-known T2, regulate thermal acclimation in an ectotherm. To our knowledge, this is the first such study to show this. Hypothyroid treatment impaired performance measures in cold-acclimated but not warm-acclimated individuals, whereas supplementation with both TH metabolites restored performance. TH could either induce or repress responses, depending on the actual temperature and thermal history of the animal. The low sensitivity to TH at warm temperatures could mean that increasing temperatures (that is, global warming) will reduce the capacity of animals to regulate their physiologies to match demands. We suggest that the properties that underlie the role of TH in thermal acclimation (temperature sensitivity and metabolic control) may have predisposed this hormone for a regulatory role in the evolution of endothermy.

  15. Thyroid hormone actions are temperature-specific and regulate thermal acclimation in zebrafish (Danio rerio)

    PubMed Central

    2013-01-01

    Background Thyroid hormone (TH) is best known for its role in development in animals, and for its control of metabolic heat production (thermogenesis) during cold acclimation in mammals. It is unknown whether the regulatory role of TH in thermogenesis is derived in mammals, or whether TH also mediates thermal responses in earlier vertebrates. Ectothermic vertebrates show complex responses to temperature variation, but the mechanisms mediating these are poorly understood. The molecular mechanisms underpinning TH action are very similar across vertebrates, suggesting that TH may also regulate thermal responses in ectotherms. We therefore aimed to determine whether TH regulates thermal acclimation in the zebrafish (Danio rerio). We induced hypothyroidism, followed by supplementation with 3,5-diiodothyronine (T2) or 3,5,3′-triiodothyronine (T3) in zebrafish exposed to different chronic temperatures. We measured whole-animal responses (swimming performance and metabolic rates), tissue-specific regulatory enzyme activities, gene expression, and free levels of T2 and T3. Results We found that both T3 and the lesser-known T2, regulate thermal acclimation in an ectotherm. To our knowledge, this is the first such study to show this. Hypothyroid treatment impaired performance measures in cold-acclimated but not warm-acclimated individuals, whereas supplementation with both TH metabolites restored performance. TH could either induce or repress responses, depending on the actual temperature and thermal history of the animal. Conclusions The low sensitivity to TH at warm temperatures could mean that increasing temperatures (that is, global warming) will reduce the capacity of animals to regulate their physiologies to match demands. We suggest that the properties that underlie the role of TH in thermal acclimation (temperature sensitivity and metabolic control) may have predisposed this hormone for a regulatory role in the evolution of endothermy. PMID:23531055

  16. Sex hormones and the female voice.

    PubMed

    Abitbol, J; Abitbol, P; Abitbol, B

    1999-09-01

    In the following, the authors examine the relationship between hormonal climate and the female voice through discussion of hormonal biochemistry and physiology and informal reporting on a study of 197 women with either premenstrual or menopausal voice syndrome. These facts are placed in a larger historical and cultural context, which is inextricably bound to the understanding of the female voice. The female voice evolves from childhood to menopause, under the varied influences of estrogens, progesterone, and testosterone. These hormones are the dominant factor in determining voice changes throughout life. For example, a woman's voice always develops masculine characteristics after an injection of testosterone. Such a change is irreversible. Conversely, male castrati had feminine voices because they lacked the physiologic changes associated with testosterone. The vocal instrument is comprised of the vibratory body, the respiratory power source and the oropharyngeal resonating chambers. Voice is characterized by its intensity, frequency, and harmonics. The harmonics are hormonally dependent. This is illustrated by the changes that occur during male and female puberty: In the female, the impact of estrogens at puberty, in concert with progesterone, produces the characteristics of the female voice, with a fundamental frequency one third lower than that of a child. In the male, androgens released at puberty are responsible for the male vocal frequency, an octave lower than that of a child. Premenstrual vocal syndrome is characterized by vocal fatigue, decreased range, a loss of power and loss of certain harmonics. The syndrome usually starts some 4-5 days before menstruation in some 33% of women. Vocal professionals are particularly affected. Dynamic vocal exploration by televideoendoscopy shows congestion, microvarices, edema of the posterior third of the vocal folds and a loss of its vibratory amplitude. The authors studied 97 premenstrual women who were prescribed a

  17. Infantile and early childhood masturbation: Sex hormones and clinical profile.

    PubMed

    Ajlouni, Heitham K; Daoud, Azhar S; Ajlouni, Saleh F; Ajlouni, Kamel M

    2010-01-01

    Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography (n=8) and brain neuroimaging (n=9). We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin (SHBG), and androstenedione in all participants. The median age at the first incident was 19.5 months (range, 4-36 months); the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone (n=10) and supine positions (n=3); two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group (P=.02). Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings.

  18. The epidemiology of serum sex hormones in postmenopausal women

    SciTech Connect

    Cauley, J.A.; Kuller, L.H.; LeDonne, D.

    1989-06-01

    Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sexmore » hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.« less

  19. Sex hormones and female homosexuality: a critical examination.

    PubMed

    Meyer-Bahlburg, H F

    1979-03-01

    To ascertain the validity of hormonal theories of human homosexuality, which are based on animal research, this article reviews psychoendocrine data on lesbian and transsexual women. Sex hormone levels were found to be normal in the majority of homosexual women, but about a third of the subjects studied had elevated androgen levels. In women with prenatal androgen excess, heterosexuality appears to be more frequent than bisexuality, and exclusive homosexuality is rare. Two recent reports suggest abnormalities of the neuroendocrine regulation of LH secretion in female transsexuals. Clearly, prenatal or postpubertal hormone levels do not determine the development of sexual orientation, but a facilitating neuroendocrine predisposition cannot be ruled out at present.

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

    PubMed

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

    2016-03-01

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

  1. Genome-wide association study of sex hormones, gonadotropins and sex hormone-binding protein in Chinese men.

    PubMed

    Chen, Zhuo; Tao, Sha; Gao, Yong; Zhang, Ju; Hu, Yanling; Mo, Linjian; Kim, Seong-Tae; Yang, Xiaobo; Tan, Aihua; Zhang, Haiying; Qin, Xue; Li, Li; Wu, Yongming; Zhang, Shijun; Zheng, S Lilly; Xu, Jianfeng; Mo, Zengnan; Sun, Jielin

    2013-12-01

    Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population. A two-stage GWAS was conducted in a total of 3495 healthy Chinese men (1999 subjects in the GWAS discovery stage and 1496 in the confirmation stage). We identified a novel genetic region at 15q21.2 (rs2414095 in CYP19A1), which was significantly associated with oestradiol and FSH in the Chinese population at a genome-wide significant level (p=6.54×10(-31) and 1.59×10(-16), respectively). Another single nucleotide polymorphism in CYP19A1 gene was significantly associated with oestradiol level (rs2445762, p=7.75×10(-28)). In addition, we confirmed the previous GWAS-identified locus at 17p13.1 for testosterone (rs2075230, p=1.13×10(-8)) and SHBG level (rs2075230, p=4.75×10(-19)) in the Chinese population. This study is the first GWAS investigation of genetic determinants of FSH and LH. The identification of novel susceptibility loci may provide more biological implications for the synthesis and metabolism of these hormones. More importantly, the confirmation of the genetic loci for testosterone and SHBG suggests common genetic components shared among different ethnicities.

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

    PubMed

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

    2016-03-01

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

  3. Adolescent endogenous sex hormones and breast density in early adulthood.

    PubMed

    Jung, Seungyoun; Egleston, Brian L; Chandler, D Walt; Van Horn, Linda; Hylton, Nola M; Klifa, Catherine C; Lasser, Norman L; LeBlanc, Erin S; Paris, Kenneth; Shepherd, John A; Snetselaar, Linda G; Stanczyk, Frank Z; Stevens, Victor J; Dorgan, Joanne F

    2015-06-04

    During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer. Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25-29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV. Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all P trend ≤0.03) but not when measured in postmenarche samples (all P trend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all P trend ≥0.16). Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown. ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999.

  4. Increased and mistimed sex hormone production in night shift workers.

    PubMed

    Papantoniou, Kyriaki; Pozo, Oscar J; Espinosa, Ana; Marcos, Josep; Castaño-Vinyals, Gemma; Basagaña, Xavier; Juanola Pagès, Elena; Mirabent, Joan; Martín, Jordi; Such Faro, Patricia; Gascó Aparici, Amparo; Middleton, Benita; Skene, Debra J; Kogevinas, Manolis

    2015-05-01

    Night shift work has been associated with an increased risk for breast and prostate cancer. The effect of circadian disruption on sex steroid production is a possible underlying mechanism, underinvestigated in humans. We have assessed daily rhythms of sex hormones and melatonin in night and day shift workers of both sexes. We recruited 75 night and 42 day workers, ages 22 to 64 years, in different working settings. Participants collected urine samples from all voids over 24 hours on a working day. Urinary concentrations of 16 sex steroid hormones and metabolites (estrogens, progestagens, and androgens) and 6-sulfatoxymelatonin were measured in all samples. Mean levels and peak time of total and individual metabolite production were compared between night and day workers. Night workers had higher levels of total progestagens [geometric mean ratio (GMR) 1.65; 95% confidence intervals (CI), 1.17-2.32] and androgens (GMR: 1.44; 95% CI, 1.03-2.00), compared with day workers, after adjusting for potential confounders. The increased sex hormone levels among night shift workers were not related to the observed suppression of 6-sulfatoxymelatonin. Peak time of androgens was significantly later among night workers, compared with day workers (testosterone: 12:14 hours; 10:06-14:48 vs. 08:35 hours; 06:52-10:46). We found increased levels of progestagens and androgens as well as delayed peak androgen production in night shift workers compared with day workers. The increase and mistiming of sex hormone production may explain part of the increased risk for hormone-related cancers observed in night shift workers. ©2015 American Association for Cancer Research.

  5. Hormone-mediated adjustment of sex ratio in vertebrates.

    PubMed

    Navara, Kristen J

    2013-12-01

    The ability to adjust sex ratios at the individual level exists among all vertebrate groups studied to date. In many cases, there is evidence for facultative adjustment of sex ratios in response to environmental and/or social cues. Because environmental and social information must be first transduced into a physiological signal to influence sex ratios, hormones likely play a role in the adjustment of sex ratio in vertebrates, because the endocrine system acts as a prime communicator that directs physiological activities in response to changing external conditions. This symposium was developed to bring together investigators whose work on adjustment of sex ratio represents a variety of vertebrate groups in an effort to draw comparisons between species in which the sex-determination process is well-established and those in which more work is needed to understand how adjustments in sex ratio are occurring. This review summarizes potential hormone targets that may underlie the mechanisms of adjustment of sex ratio in humans, non-human mammals, birds, reptiles, and fishes.

  6. Sex Hormones and the QT Interval: A Review

    PubMed Central

    Sedlak, Tara; Shufelt, Chrisandra; Iribarren, Carlos

    2012-01-01

    Abstract A prolonged QT interval is a marker for an increased risk of ventricular tachyarrhythmias. Both endogenous and exogenous sex hormones have been shown to affect the QT interval. Endogenous testosterone and progesterone shorten the action potential, and estrogen lengthens the QT interval. During a single menstrual cycle, progesterone levels, but not estrogen levels, have the dominant effect on ventricular repolarization in women. Studies of menopausal hormone therapy (MHT) in the form of estrogen-alone therapy (ET) and estrogen plus progesterone therapy (EPT) have suggested a counterbalancing effect of exogenous estrogen and progesterone on the QT. Specifically, ET lengthens the QT, whereas EPT has no effect. To date, there are no studies on oral contraception (OC) and the QT interval, and future research is needed. This review outlines the current literature on sex hormones and QT interval, including the endogenous effects of estrogen, progesterone, and testosterone and the exogenous effects of estrogen and progesterone therapy in the forms of MHT and hormone contraception. Further, we review the potential mechanisms and pathophysiology of sex hormones on the QT interval. PMID:22663191

  7. Endogenous sex hormones and cognitive function in the elderly.

    PubMed

    Boss, Lisa; Kang, Duck-Hee; Bergstrom, Nancy; Leasure, J Leigh

    2015-08-01

    Estrogen and testosterone may influence cognitive function in the older adult, but the relationship between sex hormones and cognitive function is complex. To examine associations of sex hormones and cognitive function among older adults ≥65 years old. Using a cross-sectional research design, data were collected once from 71 elderly (mean age 86.4 years). Global cognitive function and executive function were measured with standardized instruments, and saliva samples were collected for salivary estradiol and testosterone. Estradiol was significantly and positively correlated with global cognitive function in men only (r = 0.54, p < 0.05). Testosterone was not significantly correlated with global cognitive function or executive function in either gender. Associations between sex hormones and cognitive function were mostly non-significant. However, higher estradiol was significantly correlated with better global cognitive function in men, suggesting gender-specific differences. Along with sex hormones, other comorbidity may need to be assessed together in relation to cognitive function in the elderly. Accordingly, clinicians play an important role in educating and promoting beneficial actions to preserve cognitive function.

  8. SEX DIFFERENCES AND REPRODUCTIVE HORMONE INFLUENCES ON HUMAN ODOR PERCEPTION

    PubMed Central

    Doty, Richard L.; Cameron, E. Leslie

    2009-01-01

    The question of whether men and women differ in their ability to smell has been the topic of scientific investigation for over a hundred years. Although conflicting findings abound, most studies suggest that, for at least some odorants, women outperform men on tests of odor detection, identification, discrimination, and memory. Most functional imaging and electrophysiological studies similarly imply that, when sex differences are present, they favor women. In this review we examine what is known about sex-related alterations in human smell function, including influences of the menstrual cycle, pregnancy, gonadectomy, and hormone replacement therapy on a range of olfactory measures. We conclude that the relationship between reproductive hormones and human olfactory function is complex and that simple associations between circulating levels of gonadal hormones and measures of olfactory function are rarely present. PMID:19272398

  9. Sex hormonal modulation of interhemispheric transfer time.

    PubMed

    Hausmann, M; Hamm, J P; Waldie, K E; Kirk, I J

    2013-08-01

    It is still a matter of debate whether functional cerebral asymmetries (FCA) of many cognitive processes are more pronounced in men than in women. Some evidence suggests that the apparent reduction in women's FCA is a result of the fluctuating levels of gonadal steroid hormones over the course of the menstrual cycle, making their FCA less static than for men. The degree of lateralization has been suggested to depend on interhemispheric communication that may be modulated by gonadal steroid hormones. Here, we employed visual-evoked EEG potentials to obtain a direct measure of interhemispheric communication during different phases of the menstrual cycle. The interhemispheric transfer time (IHTT) was estimated from the interhemispheric latency difference of the N170 component of the visual-evoked potential from either left or right visual field presentation. Nineteen right-handed women with regular menstrual cycles were tested twice, once during the menstrual phase, when progesterone and estradiol levels are low, and once during the luteal phase when progesterone and estradiol levels are high. Plasma steroid levels were determined by blood-based immunoassay at each session. It was found that IHTT, in particular from right-to-left, was generally longer during the luteal phase relative to the menstrual phase. This effect occurred as a consequence of a slowed absolute N170 latency of the indirect pathway (i.e. left hemispheric response after LVF stimulation) and, in particular, a shortened latency of the direct pathway (i.e. right hemispheric response after LVF stimulation) during the luteal phase. These results show that cycle-related effects are not restricted to modulation of processes between hemispheres but also apply to cortical interactions, especially within the right hemisphere. The findings support the view that plastic changes in the female brain occur during relatively short-term periods across the menstrual cycle. Copyright © 2013 Elsevier Ltd. All rights

  10. Endogenous sex hormones and breast density in young women.

    PubMed

    Jung, Seungyoun; Stanczyk, Frank Z; Egleston, Brian L; Snetselaar, Linda G; Stevens, Victor J; Shepherd, John A; Van Horn, Linda; LeBlanc, Erin S; Paris, Kenneth; Klifa, Catherine; Dorgan, Joanne F

    2015-02-01

    Breast density is a strong risk factor for breast cancer and reflects epithelial and stromal content. Breast tissue is particularly sensitive to hormonal stimuli before it fully differentiates following the first full-term pregnancy. Few studies have examined associations between sex hormones and breast density among young women. We conducted a cross-sectional study among 180 women ages 25 to 29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-up Study. Eighty-five percent of participants attended a clinic visit during their luteal phase of menstrual cycle. Magnetic resonance imaging measured the percentage of dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute nondense breast volume (ANDBV). Multiple-linear mixed-effect regression models were used to evaluate the association of sex hormones and sex hormone-binding globulin (SHBG) with %DBV, ADBV, and ANDBV. Testosterone was significantly positively associated with %DBV and ADBV. The multivariable geometric mean of %DBV and ADBV across testosterone quartiles increased from 16.5% to 20.3% and from 68.6 to 82.3 cm(3), respectively (Ptrend ≤ 0.03). There was no association of %DBV or ADBV with estrogens, progesterone, non-SHBG-bound testosterone, or SHBG (Ptrend ≥ 0.27). Neither sex hormones nor SHBG was associated with ANDBV except progesterone; however, the progesterone result was nonsignificant in analysis restricted to women in the luteal phase. These findings suggest a modest positive association between testosterone and breast density in young women. Hormonal influences at critical periods may contribute to morphologic differences in the breast associated with breast cancer risk later in life. ©2014 American Association for Cancer Research.

  11. Pain and sex hormones: a review of current understanding.

    PubMed

    Maurer, Adrian J; Lissounov, Alexei; Knezevic, Ivana; Candido, Kenneth D; Knezevic, Nebojsa Nick

    2016-01-01

    Multiple epidemiologic studies have demonstrated an increased prevalence for women in several chronic pain disorders. Clinical and experimental investigations have consistently demonstrated sex-specific differences in pain sensitivity and pain threshold. Even though the underlying mechanisms responsible for these differences have not yet been elucidated, the logical possibility of gonadal hormone influence on nociceptive processing has garnered recent attention. In this review, we evaluated the complex literature regarding gonadal hormones and their influence on pain perception. We reviewed the numerous functions of gonadal hormones, discussed the influence of these hormones on several common chronic pain syndromes (migraine, tension and cluster headaches, fibromyalgia, temporomandibular syndrome, rheumatoid arthritis and back pain, among others), and have attempted to draw conclusions from the available data.

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

    PubMed Central

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

    2014-01-01

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

  13. Sex, Gender, and Transgender: Metabolic Impact of Cross Hormone Therapy.

    PubMed

    de Souza Santos, Roberta; Frank, Aaron P; Nelson, Michael Douglas; Garcia, Maurice M; Palmer, Biff F; Clegg, Deborah J

    2017-01-01

    Most preclinical and clinical, animal, and human research has been biased with respect to sex and even more so with respect to gender. In fact, little is known about the impact of sex and even less about the influence of gender on overall metabolic processes. The National Institutes of Health has recognized this gap in scientific knowledge and now mandates that studies be conducted in both sexes and to include gender as variables influencing physiological processes such as metabolism. It is therefore critical to understand and appreciate how to incorporate sex and gender in preclinical and clinical research in order to enhance our understanding of the mechanisms by which metabolic processes differ by sex and gender. In this chapter, we define sex and gender and discuss when sex and gender are not aligned, such as that which occurs in transgender individuals, and how this impacts metabolic processes. We discuss the importance of understanding the influence and interactions between sex hormones and sex chromosomes rather than focusing on their relative contributions to metabolism in isolation. This knowledge will optimize therapies specific for individuals which need to encompass sex and gender.

  14. Thyroid hormone regulates muscle function during cold acclimation in zebrafish (Danio rerio).

    PubMed

    Little, Alexander G; Seebacher, Frank

    2013-09-15

    Thyroid hormone (TH) is a universal regulator of growth, development and metabolism during cold exposure in mammals. In zebrafish (Danio rerio), TH regulates locomotor performance and metabolism during cold acclimation. The influence of TH on locomotor performance may be via its effect on metabolism or, as has been shown in mammals, by modulating muscle phenotypes. Our aim was to determine whether TH influences muscle phenotypes in zebrafish, and whether this could explain changes in swimming capacity in response to thermal acclimation. We used propylthiouracil and iopanoic acid to induce hypothyroidism in zebrafish over a 3-week acclimation period to either 18 or 28°C. To verify that physiological changes following hypothyroid treatment were in fact due to the action of TH, we supplemented hypothyroid fish with 3,5-diiodothryronine (T2) or 3,5,3'-triiodothyronine (T3). Cold-acclimated fish had significantly greater sustained swimming performance (Ucrit) but not burst speed. Greater Ucrit was accompanied by increased tail beat frequency, but there was no change in tail beat amplitude. Hypothyroidism significantly decreased Ucrit and burst performance, as well as tail beat frequency and SERCA activity in cold-acclimated fish. However, myofibrillar ATPase activity increased in cold-acclimated hypothyroid fish. Hypothyroid treatment also decreased mRNA concentrations of myosin heavy chain fast isoforms and SERCA 1 isoform in cold-acclimated fish. SERCA 1 mRNA increased in warm-acclimated hypothyroid fish, and SERCA 3 mRNA decreased in both cold- and warm-acclimated hypothyroid fish. Supplementation with either T2 or T3 restored Ucrit, burst speed, tail beat frequency, SERCA activity and myosin heavy chain and SERCA 1 and 3 mRNA levels of hypothyroid fish back to control levels. We show that in addition to regulating development and metabolism in vertebrates, TH also regulates muscle physiology in ways that affect locomotor performance in fish. We suggest that the

  15. Induction of Female-to-Male Sex Change in Adult Zebrafish by Aromatase Inhibitor Treatment

    NASA Astrophysics Data System (ADS)

    Takatsu, Kanae; Miyaoku, Kaori; Roy, Shimi Rani; Murono, Yuki; Sago, Tomohiro; Itagaki, Hideyuki; Nakamura, Masaru; Tokumoto, Toshinobu

    2013-12-01

    This study investigated whether undifferentiated germ and/or somatic stem cells remain in the differentiated ovary of a species that does not undergo sex changes under natural conditions and retain their sexual plasticity. The effect of aromatase inhibitor (AI)-treatment on sexually mature female zebrafish was examined. A 5-month AI treatment caused retraction of the ovaries after which testes-like organs appeared, and cyst structures filled with spermatozoa-like cells were observed in sections of these tissues. Electron microscopic observations revealed that these cells appeared as large sperm heads without tails. Sperm formation was re-examined after changing the diet to an AI-free food. A large number of normal sperm were obtained after eight weeks, and no formation of ovarian tissue was observed. Artificial fertilization using sperm from the sex-changed females was successful. These results demonstrated that sex plasticity remains in the mature ovaries of this species.

  16. Sex differences and sex hormones in anxiety-like behavior of aging rats.

    PubMed

    Domonkos, Emese; Borbélyová, Veronika; Csongová, Melinda; Bosý, Martin; Kačmárová, Mária; Ostatníková, Daniela; Hodosy, Július; Celec, Peter

    2017-07-01

    Sex differences in the prevalence of affective disorders might be attributable to different sex hormone milieu. The effects of short-term sex hormone deficiency on behavior, especially on anxiety have been studied in numerous animal experiments, mainly on young adult rats and mice. However, sex differences in aged animals and the effects of long-term hypogonadism are understudied. The aim of our study was to analyze sex differences in anxiety-like behavior in aged rats and to prove whether they can be attributed to endogenous sex hormone production in males. A battery of tests was performed to assess anxiety-like behavior in aged female, male and gonadectomized male rats castrated before puberty. In addition, the aged gonadectomized male rats were treated with a single injection of estradiol or testosterone or supplemented with estradiol for two-weeks. Female rats displayed a less anxious behavior than male rats in most of the conducted behavioral tests except the light-dark box. Long-term androgen deficiency decreased the sex difference in anxiety either partially (open field, PhenoTyper cage) or completely (elevated plus maze). Neither single injection of sex hormones, nor two-week supplementation of estradiol in gonadectomized aged male rats significantly affected their anxiety-like behavior in the elevated plus maze. In conclusion, our results confirm sex differences in anxiety in aged rats likely mediated by endogenous testosterone production in males. Whether long-term supplementation with exogenous sex hormones could affect anxiety-like behavior in elderly individuals remains to be elucidated. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Sex bias in paediatric autoimmune disease - Not just about sex hormones?

    PubMed

    Chiaroni-Clarke, Rachel C; Munro, Jane E; Ellis, Justine A

    2016-05-01

    Autoimmune diseases affect up to 10% of the world's population, and approximately 80% of those affected are female. The majority of autoimmune diseases occur more commonly in females, although some are more frequent in males, while others show no bias by sex. The mechanisms leading to sex biased disease prevalence are not well understood. However, for adult-onset autoimmune disease, at least some of the cause is usually ascribed to sex hormones. This is because levels of sex hormones are one of the most obvious physiological differences between adult males and females, and their impact on immune system function is well recognised. While for paediatric-onset autoimmune diseases a sex bias is not as common, there are several such diseases for which one sex predominates. For example, the oligoarticular subtype of juvenile idiopathic arthritis (JIA) occurs in approximately three times more girls than boys, with a peak age of onset well before the onset of puberty, and at a time when levels of androgen and oestrogen are low and not strikingly different between the sexes. Here, we review potential explanations for autoimmune disease sex bias with a particular focus on paediatric autoimmune disease, and biological mechanisms outside of sex hormone differences. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Aging and sex hormones in males

    PubMed Central

    Decaroli, Maria Chiara

    2017-01-01

    ABSTRACT Several large cohort studies have disclosed the trajectories of sex steroids changes overtime in men and their clinical significance. In men the slow, physiological decline of serum testosterone (T) with advancing age overlaps with the clinical condition of overt, pathological hypogonadism. In addition, the increasing number of comorbidities, together with the high prevalence of chronic diseases, all further contribute to the decrease of serum T concentrations in the aging male. For all these reasons both the diagnosis of late-onset hypogonadism (LOH) in men and the decision about starting or not T replacement treatment remain challenging. At present, the biochemical finding of T deficiency alone is not sufficient for diagnosing hypogonadism in older men. Coupling hypogonadal symptoms with documented low serum T represents the best strategy to refine the diagnosis of hypogonadism in older men and to avoid unnecessary treatments. PMID:27831823

  19. Metabolic Impact Of Sex Hormones On Obesity

    PubMed Central

    Brown, Lynda M.; Gent, Lana; Davis, Kathryn; Clegg, Deborah J.

    2010-01-01

    Obesity and its associated health disorders and costs are increasing. Men and postmenopausal women have greater risk of developing complications of obesity than younger women. Within the brain, the hypothalamus is an important regulator of energy homeostasis. Two of its sub-areas, the ventrolateral portion of the ventral medial nucleus (VL VMN) and the arcuate (ARC) respond to hormones and other signals to control energy intake and expenditure. When large lesions are made in the hypothalamus which includes both the VL VMN and the ARC, animals eat more, have reduced energy expenditure, and become obese. The ARC and the VL VMN, in addition to other regions in the hypothalamus, have been demonstrated to contain estrogen receptors. There are two estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). We and others have previously demonstrated that activation of ERα by estrogens reduces food intake and increases body weight. This review focuses on the relative contribution of activation of ERα by estrogens in the ARC and the VL VMN in the regulation of food intake and body weight. Additionally, estrogen receptors have been found in many peripheral tissues including adipose tissue. Estrogens are thought to have direct effects on adipose tissue and estrogens may provide anti-inflammatory properties both in the periphery and the in the central nervous system (CNS) which may protect women from diseases associated with inflammation. Understanding the mechanisms by which estrogens regulate body weight and inflammation will assist in determining potential therapeutic agents for menopausal women to decrease the propensity of diseases associated with obesity. PMID:20441773

  20. The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos

    PubMed Central

    2012-01-01

    Background Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio) embryos with T-box transcription factor 5 (tbx5) deficiencies, mimicking human Holt-Oram syndrome. Methods Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO) antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH) concomitant with tbx5-MO comprised the treatment group. Results The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2), and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2) and cardiomyogenetic genes (amhc, vmhc, and cmlc2). Conclusions Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner. PMID:22776023

  1. Prenatal sex hormone effects on child and adult sex-typed behavior: methods and findings.

    PubMed

    Cohen-Bendahan, Celina C C; van de Beek, Cornelieke; Berenbaum, Sheri A

    2005-04-01

    There is now good evidence that human sex-typed behavior is influenced by sex hormones that are present during prenatal development, confirming studies in other mammalian species. Most of the evidence comes from clinical populations, in which prenatal hormone exposure is atypical for a person's sex, but there is increasing evidence from the normal population for the importance of prenatal hormones. In this paper, we briefly review the evidence, focusing attention on the methods used to study behavioral effects of prenatal hormones. We discuss the promises and pitfalls of various types of studies, including those using clinical populations (concentrating on those most commonly studied, congenital adrenal hyperplasia, androgen insensitivity syndrome, ablatio penis, and cloacal exstrophy), direct measures of hormones in the general population (assayed through umbilical cord blood, amniotic fluid, and maternal serum during pregnancy), and indirect measures of hormones in the general population (inferred from intrauterine position and biomarkers such as otoacoustic emissions, finger length ratios, and dermatoglyphic asymmetries). We conclude with suggestions for interpreting and conducting studies of the behavioral effects of prenatal hormones.

  2. Body fatness and endogenous sex hormones in the menopausal transition.

    PubMed

    Zsakai, Annamaria; Karkus, Zsolt; Utczas, Katinka; Biri, Beata; Sievert, Lynnette L; Bodzsar, Eva B

    2016-05-01

    Age at the final menstrual period is of clinical and public health interest because the age at which natural menopause occurs may be a marker of ageing and health, and in general the menopausal transition increases the risk of many diseases, e.g. redistribution in the pattern of adiposity during the menopausal transition may increase risk of metabolic disease. The purpose of this research was to study the relationship between the menopausal status and body fatness. A random sample of 1932 Hungarian women was studied. Body composition was estimated by body impedance analysis. In a subsample free estradiol and progesterone levels in saliva were quantified. Body fat mass increased until the late 50s and then had a decrease through senescence. Premenopausal women who were much older than the median age at menopause had a higher amount of fat than their postmenopausal age-peers, while postmenopausal women, whose menopause occurred much earlier than the median age at menopause, had less fat than their premenopausal age-peers. The body fat mass in premenopausal women with low levels of sex hormones was always below the age-median value of the menopausal status subgroups, while the body fat mass of postmenopausal women with high levels of sex hormone levels was above the age-median values. The analysis of body fatness in the menopausal transition revealed that (1) the rate of reproductive ageing and the body fat pattern were significantly related, and (2) body fat mass of women with unexpected levels of sex hormones was related more to their hormonal levels than to their menopausal status or their age. Thus future epidemiological screenings of women exposed to higher levels of menopause-related health risks should be expanded beyond the estimation of menopausal status based only on menstrual history to include sex hormone level assessment, as well as body composition analysis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Infantile and early childhood masturbation: Sex hormones and clinical profile

    PubMed Central

    Ajlouni, Heitham K.; Daoud, Azhar S.; Ajlouni, Saleh F.; Ajlouni, Kamel M.

    2010-01-01

    BACKGROUND AND OBJECTIVES: Few studies have explored the hormonal triggers for masturbation in infants and young children. Thus, we aimed to study the sex hormones and clinical profiles of masturbating infants and young children. METHODS: This case-control study involved infants and young children who masturbate and were referred to three pediatric neurology clinics between September 2004 and 2006 (n=13), and a similar control group. All children underwent basic laboratory investigations prior to referral. Other tests included electroencephalography (n=8) and brain neuroimaging (n=9). We measured dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, free testosterone, estradiol, dehydroepiandrosterone, sex hormone-binding globulin (SHBG), and androstenedione in all participants. RESULT: The median age at the first incident was 19.5 months (range, 4-36 months); the median masturbation frequency, 4 times/day; and the median duration of each event, 3.9 min. The subjects masturbated in both prone (n=10) and supine positions (n=3); two subjects used the knee-chest position. All subjects showed facial flushing; 6, friction between the thighs; 5, sweating; 9, sleeping after the event; and 12, disturbance on interruption. EEG was abnormal in one of eight subjects tested, and neuroimages were normal in all of nine subjects examined. The case and control groups had comparable levels of all sex hormones, except estradiol, which showed significantly lower levels in the case group (P=.02). CONCLUSION: Masturbation in children seems to be associated with reduced estradiol levels, but not with other sex hormones. Further studies are needed to confirm our findings. PMID:21060161

  4. Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement.

    PubMed

    Manwani, Bharti; Bentivegna, Kathryn; Benashski, Sharon E; Venna, Venugopal Reddy; Xu, Yan; Arnold, Arthur P; McCullough, Louise D

    2015-02-01

    Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

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

    PubMed Central

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

    2016-01-01

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

  6. Effects of BPF on steroid hormone homeostasis and gene expression in the hypothalamic-pituitary-gonadal axis of zebrafish.

    PubMed

    Yang, Qian; Yang, Xianhai; Liu, Jining; Ren, Wenjuan; Chen, Yingwen; Shen, Shubao

    2017-09-01

    Bisphenol F (BPF) has been frequently detected in various environmental compartments, and previous studies found that BPF exhibits similar estrogenic and anti-androgenic effects on the mammalian endocrine system to those of bisphenol A (BPA). However, the potential disrupting effects of BPF on aquatic organisms and the underling disrupting mechanisms have not been investigated. In this study, the potential disrupting mechanisms of BPF on the hypothalamic-pituitary-gonadal (HPG) axis and liver were probed by employing the OECD 21-day short-term fecundity assay in zebrafish. The results show that BPF exposure (1 mg/L) impaired the reproductive function of zebrafish, as exemplified by alterations to testicular and ovarian histology of the treated zebrafish. Homogenate testosterone (T) levels in male zebrafish decreased in a concentration-dependent manner, and 17β-estradiol (E2) levels increased significantly when fish were exposed to 0.1 and 1 mg/L BPF. The real-time polymerase chain reaction was performed to examine gene expression in the HPG axis and liver. Hepatic vitellogenin expression was significantly upregulated in males, suggesting that BPF possesses estrogenic activity. The disturbed hormone balance was enhanced by the significant changes in gene expression along the HPG axis. These alterations suggest that BPF leads to adverse effects on the endocrine system of teleost fish, and that these effects were more prominent in males than in females.

  7. Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning.

    PubMed

    Hamson, Dwayne K; Roes, Meighen M; Galea, Liisa A M

    2016-06-13

    Sex differences in neurological disease exist in incidence, severity, progression, and symptoms and may ultimately influence treatment. Cognitive disturbances are frequent in neuropsychiatric disease with men showing greater cognitive impairment in schizophrenia, but women showing more severe dementia and cognitive decline with Alzheimer's disease. Although there are no overall differences in intelligence between the sexes, men, and women demonstrate slight but consistent differences in a number of cognitive domains. These include a male advantage, on average, in some types of spatial abilities and a female advantage on some measures of verbal fluency and memory. Sex differences in traits or behaviors generally indicate the involvement of sex hormones, such as androgens and estrogens. We review the literature on whether adult levels of testosterone and estradiol influence spatial ability in both males and females from rodent models to humans. We also include information on estrogens and their ability to modulate verbal memory in men and women. Estrone and progestins are common components of hormone therapies, and we also review the existing literature concerning their effects on cognition. We also review the sex differences in the hippocampus and prefrontal cortex as they relate to cognitive performance in both rodents and humans. There has been greater recognition in the scientific literature that it is important to study both sexes and also to analyze study findings with sex as a variable. Only by examining these sex differences can we progress to finding treatments that will improve the cognitive health of both men and women. © 2016 American Physiological Society. Compr Physiol 6:1295-1337, 2016. Copyright © 2016 John Wiley & Sons, Inc.

  8. Pregnancy, sex and hormonal factors in multiple sclerosis

    PubMed Central

    Miller, David H; Fazekas, Franz; Montalban, Xavier; Reingold, Stephen C; Trojano, Maria

    2014-01-01

    Background: Multiple sclerosis (MS) is influenced by pregnancy, sex and hormonal factors. Objectives: A comprehensive understanding of the role of pregnancy, sex and hormonal factors can provide insights into disease mechanisms, and new therapeutic developments and can provide improved patient care and treatment. Methods: Based on an international conference of experts and a comprehensive PubMed search for publications on these areas in MS, we provide a review of what is known about the impact of these factors on disease demographics, etiology, pathophysiology and clinical course and outcomes. Results and conclusions: Recommendations are provided for counseling and management of people with MS before conception, during pregnancy and after delivery. The use of disease-modifying and symptomatic therapies in pregnancy is problematic and such treatments are normally discontinued. Available knowledge about the impact of treatment on the mother, fetus and newborn is discussed. Recommendations for future research to fill knowledge gaps and clarify inconsistencies in available data are made. PMID:24446387

  9. Sex differences and hormonal modulation of deep tissue pain

    PubMed Central

    Traub, Richard J.; Ji, Yaping

    2013-01-01

    Women disproportionately suffer from many deep tissue pain conditions. Experimental studies show that women have lower pain thresholds, higher pain ratings and less tolerance to a range of painful stimuli. Most clinical and epidemiological reports suggest female gonadal hormones modulate pain for some, but not all, conditions. Similarly, animal studies support greater nociceptive sensitivity in females in many deep tissue pain models. Gonadal hormones modulate responses in primary afferents, dorsal horn neurons and supraspinal sites, but the direction of modulation is variable. This review will examine sex differences in deep tissue pain in humans and animals focusing on the role of gonadal hormones (mainly estradiol) as an underlying component of the modulation of pain sensitivity. PMID:23872333

  10. Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

    PubMed

    Day, Danielle S; Gozansky, Wendolyn S; Bell, Christopher; Kohrt, Wendy M

    2011-10-01

    Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA. MSNA was measured in 9 women (30±2 years; mean±SE) on three separate occasions: during the mid-luteal menstrual cycle phase, on the fifth day of gonadotropin-releasing hormone antagonist (GnRHant) administration, and after 5 days add-back of either estradiol (n=4) or progesterone (n=3) during continued GnRHant administration. In response to GnRHant, there were significant reductions in serum estradiol and progesterone (both p<0.01) and MSNA (25.0±1.9 vs. 19.2±2.4 bursts/min, p=0.04). Continued GnRHant plus add-back estradiol or progesterone resulted in a nonsignificant decrease (19.2±1.7 vs. 12.1±1.9 bursts/min, p=0.07) or increase (16.2±1.7 vs. 21.0±6.0 bursts/min, p=0.39), respectively, in MSNA when compared with GnRHant alone. The findings of this preliminary study suggest that short-term ovarian hormone suppression attenuates MSNA and that this may be related to the suppression of progesterone rather than estradiol.

  11. Sex Hormones Function as Sex Attractant Pheromones in House Mice and Brown Rats.

    PubMed

    Takács, Stephen; Gries, Regine; Gries, Gerhard

    2017-07-18

    Sex hormones of mammals control the expression of sexual characteristics and bodily functions. The male hormone testosterone and the female hormones progesterone and estradiol are known to occur in urine markings of mice. Here, we show that all three hormones are also present in urine of brown rats, and that they are effective sexual communication signals (pheromones) that elicit attraction behavior of prospective mates in both brown rats and house mice. When added as lures to trap boxes in field experiments, synthetic testosterone, for example, increased captures of adult female mice 15-fold, and a blend of progesterone and estradiol increased captures of male mice eightfold and male rats 13-fold. Remarkably, these hormones increased captures even though the food- and pheromone-based baits to which they were added had previously been shown to be superior to current commercial rodent attractants. We predict that these sex hormones will function as sex attractant pheromones in diverse taxa. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Sex hormones, aging, and Alzheimer’s disease

    PubMed Central

    Barron, Anna M.; Pike, Christian J.

    2012-01-01

    A promising strategy to delay and perhaps prevent Alzheimer’s disease (AD) is to identify the age-related changes that put the brain at risk for the disease. A significant normal age change known to result in tissue-specific dysfunction is the depletion of sex hormones. In women, menopause results in a relatively rapid loss of estradiol and progesterone. In men, aging is associated with a comparatively gradual yet significant decrease in testosterone. We review a broad literature that indicates age-related losses of estrogens in women and testosterone in men are risk factors for AD. Both estrogens and androgens exert a wide range of protective actions that improve multiple aspects of neural health, suggesting that hormone therapies have the potential to combat AD pathogenesis. However, translation of experimental findings into effective therapies has proven challenging. One emerging treatment option is the development of novel hormone mimetics termed selective estrogen and androgen receptor modulators. Continued research of sex hormones and their roles in the aging brain is expected to yield valuable approaches to reducing the risk of AD. PMID:22201929

  13. Sex-specific association of sex hormones and gonadotropins, with brain amyloid and hippocampal neurodegeneration.

    PubMed

    Lee, Jun Ho; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Choi, Hyo Jung; Baek, Hyewon; Sohn, Bo Kyung; Lee, Jun-Young; Kim, Hyun Jung; Kim, Jee Wook; Lee, Younghwa; Kim, Yu Kyeong; Sohn, Chul-Ho; Woo, Jong Inn; Lee, Dong Young

    2017-10-01

    This study aimed to examine the sex-specific association between serum sex hormones and gonadotropins and the cerebral beta-amyloid (Aβ) burden and hippocampal neurodegeneration in subjects with normal cognition and impaired cognition. Two hundred sixty-five older subjects received clinical assessments, serum measurements of sex hormones, gonadotropins, 11 C-Pittsburgh compound B-positron emission tomography, and magnetic resonance imaging. In females, higher free testosterone and gonadotropin levels were associated with lower cerebral Aβ positivity. In males, free testosterone was positively related to hippocampal volume with significant interaction with cognitive status. Further subgroup analyses showed that the association was significant only in impaired cognition but not in normal cognition. Free estradiol was not associated with Aβ burden or hippocampal neurodegeneration in either sex. These results suggest that testosterone might inhibit the early pathological accumulation of Aβ in females and delay neurodegeneration in males. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Endocrinology of sex steroid hormones and cell dynamics in the periodontium.

    PubMed

    Mariotti, Angelo; Mawhinney, Michael

    2013-02-01

    Numerous scientific studies assert the existence of hormone-sensitive periodontal tissues. Tissue specificity of hormone localization, identification of hormone receptors and the metabolism of hormones are evidence that periodontal tissues are targets for sex steroid hormones. Although the etiologies of periodontal endocrinopathies are diverse, periodontal pathologies are primarily the consequence of the actions and interactions of sex steroid hormones on specific cells found in the periodontium. This review provides a broad overview of steroid hormone physiology, evidence for the periodontium being a target tissue for sex steroid hormones and theories regarding the roles of sex steroid hormones in periodontal pathogenesis. Using this information, a teleological argument for the actions of steroid hormones in the periodontium is assessed.

  15. The nuclear hormone receptor SEX-1 is an X-chromosome signal that determines nematode sex.

    PubMed

    Carmi, I; Kopczynski, J B; Meyer, B J

    1998-11-12

    Organisms in many phyla determine sexual fate by distinguishing one X chromosome from two. Here we use the model organism Caenorhabditis elegans to dissect such an X-chromosome-counting mechanism in molecular detail. In this nematode, several genes on the X chromosome called X signal elements communicate X-chromosome dose by controlling the activity of the sex-determination gene xol-1. xol-1 specifies male (XO) fate when active and hermaphrodite (XX) fate when inactive. The only X signal element described so far represses xol-1 post-transcriptionally, but xol-1 is repressed in XX animals by transcriptional and post-transcriptional mechanisms. Here we identify a nuclear-hormone-receptor homologue, SEX-1, that regulates the transcription of xol-1. We show that sex-1 is vital to X-chromosome counting: changing sex-1 gene dose in XX or XO embryos causes sexual transformation and death from inadequate dosage compensation (the hermaphrodite-specific process that equalizes X-gene expression between the sexes). The SEX-1 protein acts directly on xol-1, associating with its promoter in vivo and repressing xol-1 transcription in XX embryos. Thus, xol-1 is the direct molecular target of the primary sex-determination signal, and the dose of a nuclear hormone receptor helps to communicate X-chromosome number to determine nematode sex.

  16. Interactive effects of sex hormones and gender stereotypes on cognitive sex differences--a psychobiosocial approach.

    PubMed

    Hausmann, Markus; Schoofs, Daniela; Rosenthal, Harriet E S; Jordan, Kirsten

    2009-04-01

    Biological and social factors have been shown to affect cognitive sex differences. For example, several studies have found that sex hormones have activating effects on sex-sensitive tasks. On the other hand, it has been shown that gender stereotypes can influence the cognitive performance of (gender-) stereotyped individuals. However, few studies have investigated the combined effects of both factors. The present study investigated the interaction between sex hormones and gender stereotypes within a psychobiosocial approach. One hundred and fourteen participants (59 women) performed a battery of sex-sensitive cognitive tasks, including mental rotation, verbal fluency, and perceptual speed. Saliva samples were taken immediately after cognitive testing. Levels of testosterone (T) were analysed using chemiluminescence immunoassay (LIA). To activate gender stereotypes, a questionnaire was applied to the experimental group that referred to the cognitive tasks used. The control group received an identical questionnaire but with a gender-neutral content. As expected, significant sex differences favouring males and females appeared for mental rotation and verbal fluency tasks, respectively. The results revealed no sex difference in perceptual speed. The male superiority in the Revised Vandenberg and Kuse Mental Rotations Tests (MRT-3D) was mainly driven by the stereotype-active group. No significant sex difference in MRT-3D appeared in the control group. The MRT-3D was also the task in which a strong gender-stereotype favouring males was present for both males and females. Interestingly, T levels of the stereotype-activated group were 60% higher than that of male controls. The results suggest that sex hormones mediate the effects of gender stereotypes on specific cognitive abilities.

  17. Pituitary adenylate cyclase activating polypeptide (PACAP), stress, and sex hormones.

    PubMed

    King, S Bradley; Toufexis, Donna J; Hammack, Sayamwong E

    2017-09-01

    Stressor exposure is associated with the onset and severity of many psychopathologies that are more common in women than men. Moreover, the maladaptive expression and function of stress-related hormones have been implicated in these disorders. Evidence suggests that PACAP has a critical role in the stress circuits mediating stress-responding, and PACAP may interact with sex hormones to contribute to sex differences in stress-related disease. In this review, we describe the role of the PACAP/PAC1 system in stress biology, focusing on the role of stress-induced alterations in PACAP expression and signaling in the development of stress-induced behavioral change. Additionally, we present more recent data suggesting potential interactions between stress, PACAP, and circulating estradiol in pathological states, including PTSD. These studies suggest that the level of stress and circulating gonadal hormones may differentially regulate the PACAPergic system in males and females to influence anxiety-like behavior and may be one mechanism underlying the discrepancies in human psychiatric disorders.

  18. Cognitive sex differences are not magnified as a function of age, sex hormones, or puberty development during early adolescence.

    PubMed

    Herlitz, Agneta; Reuterskiöld, Lena; Lovén, Johanna; Thilers, Petra P; Rehnman, Jenny

    2013-01-01

    Are cognitive sex differences magnified by individual differences in age, sex hormones, or puberty development? Cross-sectional samples of 12- to 14-year-old boys (n = 85) and girls (n = 102) completed tasks assessing episodic memory, face recognition, verbal fluency, and mental rotations. Blood estradiol, free testosterone, and self-rated puberty scores were obtained. Sex differences were found on all cognitive measures. However, the magnitude was not larger for older children, hormones and cognitive performance were not associated, and early maturers did not perform better than late maturers. Thus, cognitive sex differences were not associated with age, levels of sex hormones, or puberty development.

  19. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity.

    PubMed

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter; van Loon, Jack J W A; Muller, Marc

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity.

  20. Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity

    PubMed Central

    Aceto, Jessica; Nourizadeh-Lillabadi, Rasoul; Marée, Raphael; Dardenne, Nadia; Jeanray, Nathalie; Wehenkel, Louis; Aleström, Peter

    2015-01-01

    Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and more generally on whole genome gene expression. By combining morphometric tools with an objective scoring system for the state of development for each element in the head skeleton and specific gene expression analysis, we confirmed and characterized in detail the decrease or increase of bone formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure results in a significantly larger head and a significant increase in bone formation for a subset of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential expression of genes involved in the development and function of the skeletal, muscular, nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at 3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days exposure to 3g during these early stages also caused increased bone formation, while gene expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp, egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected by the transition from hyper- to normal gravity. PMID:26061167

  1. Changes of thyroid hormone levels and related gene expression in zebrafish on early life stage exposure to triadimefon.

    PubMed

    Liu, Shaoying; Chang, Juhua; Zhao, Ying; Zhu, Guonian

    2011-11-01

    In this study, zebrafish was exposed to triadimefon. Thyroid hormones levels and the expression of related genes in the hypothalamic-pituitary-thyroid (HPT) axis, including thyroid-stimulating hormone (TSH-beta), deiodinases (dio1 and dio2) and the thyroid hormone receptor (thraa and thrb) were evaluated. After triadimefon exposure, increased T4 can be explained by increased thyroid-stimulating hormone (TSH-beta). The conversion of T4 to T3 (deiodinase type I-dio1) was decreased, which reduced the T3 level. Thyroid hormone receptor beta (thrb) mRNA levels were significantly down-regulated, possibly as a response to the decreased T3 levels. The overall results indicated that triadimefon exposure could alter gene expression in the HPT axis and that mechanisms of disruption of thyroid status by triadimefon could occur at several steps in the synthesis, regulation, and action of thyroid hormones. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  2. The Role of Sex and Sex Hormones in Regulating Obesity-Induced Inflammation.

    PubMed

    Varghese, Mita; Griffin, Cameron; Singer, Kanakadurga

    2017-01-01

    Metabolic and non-metabolic complications due to obesity are becoming more prevalent, yet our understanding of the mechanisms driving these is not. This is due to individual risk factor variability making it difficult to predict disease outcomes such as diabetes and insulin resistance. Gender is a critical factor in obesity outcomes with women having more adiposity but reduced metabolic complications compared to men. The role of immune system activation during obesity is an emerging field that links adiposity to metabolic syndrome. Furthermore, evidence from animal models suggests that sex differences exist in immune responses and, therefore, could be a possible mechanism leading to sex differences in metabolic disease. While there is still much to learn in the area of sex-differences research, this chapter will review the current knowledge and literature detailing the role of sex and sex hormones on adiposity and metabolically induced inflammation in obesity.

  3. Sex assignment of lake sturgeon (Acipenser fluvescens) based on plasma sex hormone and vitellogenin levels

    USGS Publications Warehouse

    Craig, J.M.; Papoulias, D.M.; Thomas, M.V.; Annis, M.L.; Boase, J.

    2009-01-01

    This study focused on identifying the sex of lake sturgeon by measuring the sex hormones estradiol and testosterone, and the phosphoprotein vitellogenin (Vtg) in blood plasma by radioimmunoassay and enzyme-linked immunosorbent assay, respectively, and evaluating these techniques as tools in lake sturgeon population management. Surveys of the St Clair River (SCR) lake sturgeon population have characterized it as rebounding by having steady or increasing recruitment since 1997. However, researchers have not been able to effectively determine the sex for most of the sturgeon they capture because few fish caught during surveys are releasing gametes. A total of 115 fish were sampled from May through June in 2004 and 2005 from the SCR, Michigan, USA. Of these, only four females and eight males were verified (i.e. they were releasing gametes at time of capture), resulting in very few fish with which to validate blood hormone and Vtg biomarkers of sex. Fifty-six percent of the fish were assigned a sex designation based on biomarker criteria. Correspondence between actual gonadal sex and biomarker-directed classification was good for the small subset of fish for which gonadal sex was definitively determined. Moreover, application of the steroid values in a predictive sex assignment model developed for white sturgeon misclassified only the same two fish that were misclassified with the steroid and Vtg biomarkers. The experimental results suggest a sex ratio of 1 : 2.7 (F:M), however more conclusive methods are needed to confirm this ratio because so few fish were available for sex validation. Of the 43 males, 14 were within the legal slot limit, 11 were smaller than 1067 mm total length (TL), and 18 were larger than 1270 mm TL. All 15 females were larger than 1270 mm TL, and thus protected by the slot limit criteria. Considering that lake sturgeon are threatened in Michigan, an advantage to using blood plasma assays was that fish were not harmed, and sample collection was

  4. Effects of TDCPP or TPP on gene transcriptions and hormones of HPG axis, and their consequences on reproduction in adult zebrafish (Danio rerio).

    PubMed

    Liu, Xiaoshan; Ji, Kyunghee; Jo, Areum; Moon, Hyo-Bang; Choi, Kyungho

    2013-06-15

    Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) belong to the group of triester organophosphate flame retardants (OPFRs), which have been used in a wide range of consumer products. These chemicals have been frequently detected in effluents, surface water, and fish, and hence their potential adverse effects on aquatic ecosystem are of concern. The present study was conducted to investigate the reproduction-related effects and possible molecular mechanisms of TDCPP and TPP using a 21 day reproduction test employing adult zebrafish (Danio rerio). After 21 d of exposure to TDCPP or TPP, significant decrease in fecundity along with significant increases of plasma 17β-estradiol (E2) concentrations, vitellogenin (VTG) levels, and E2/testosterone (T) and E2/11-ketotestosterone (11-KT) ratios were observed. The transcriptional profiles of several genes of the hypothalamus-pituitary-gonad (HPG) axis changed as well after the exposure, but the trend was sex-dependent. In male fish, gonadotropin-releasing hormone2 (GnRH2), GnRHR3, cytochrome P450 (CYP) 19B, estrogen receptor α (ERα), ER2 β1, and follicle stimulating hormone β (FSHβ) were upregulated in the brain, while luteinizing hormone β (LHβ) and androgen receptor (AR) were downregulated. Corresponding to the upregulation of FSHβ and downregulation of LHβ in the brain, FSHR was upregulated and LHR was downregulated in the testis. Among the genes that regulate the steroidogenesis pathway, transcription of hydroxyl methyl glutaryl CoA reductase (HMGRA), steroidogenic acute regulatory protein (StAR), and 17β-hydroxysteroid dehydrogenase (17βHSD) decreased, while transcription of CYP11A, CYP17, and CYP19A increased. In female fish, transcription ofGnRH2 and GnRHR3 decreased, but FSHβ, LHβ, CYP19B, ERα, ER2β1, and AR transcription increased in the brain. In the ovary, FSHR and LHR were significantly upregulated, and most steroidogenic genes were significantly upregulated. The observed

  5. BISPHENOL A EXPOSURE DURING EARLY DEVELOPMENT INDUCES SEX-SPECIFIC CHANGES IN ADULT ZEBRAFISH SOCIAL INTERACTIONS

    PubMed Central

    Weber, Daniel N.; Hoffmann, Raymond G.; Hoke, Elizabeth S.; Tanguay, Robert L.

    2014-01-01

    Developmental bisphenol A (BPA) exposure is associated with adverse behavioral effects, although underlying modes of action remain unclear. Because BPA is a suspected xenoestrogen, the objective was to identify sex-based changes in adult zebrafish social behavior developmentally exposed to BPA (0.0, 0.1 or 1 μM) or one of two control compounds (0.1μM 17β-estradiol [E2], and 0.1 μM GSK4716, a synthetic estrogen-related receptor γ ligand). A test chamber was divided lengthwise so each arena held one fish unable to detect the presence of the other fish. A mirror was inserted at one end of each arena; baseline activity levels were determined without mirror. Arenas were divided into 3, computer-generated zones to represent different distances from mirror image. Circadian rhythm patterns were evaluated at 1–3 (= AM) and 5–8 (= PM) hr postprandial. Adult zebrafish were placed into arenas and monitored by digital camera for 5 min. Total distance traveled, % time spent at mirror image, and number of attacks on mirror image were quantified. E2, GSK4716, and all BPA treatments dampened male activity and altered male circadian activity patterns; there was no marked effect on female activity. BPA induced non-monotonic effects (response curve changes direction within range of concentrations examined) on male % time at mirror only in AM. All treatments produced increased % time at the mirror during PM. Male attacks on the mirror were reduced by BPA exposure only during AM. There were sex-specific effects of developmental BPA on social interactions and time-of-day of observation affected results. PMID:25424546

  6. Disorders of sex development expose transcriptional autonomy of genetic sex and androgen-programmed hormonal sex in human blood leukocytes

    PubMed Central

    Holterhus, Paul-Martin; Bebermeier, Jan-Hendrik; Werner, Ralf; Demeter, Janos; Richter-Unruh, Annette; Cario, Gunnar; Appari, Mahesh; Siebert, Reiner; Riepe, Felix; Brooks, James D; Hiort, Olaf

    2009-01-01

    Background Gender appears to be determined by independent programs controlled by the sex-chromosomes and by androgen-dependent programming during embryonic development. To enable experimental dissection of these components in the human, we performed genome-wide profiling of the transcriptomes of peripheral blood mononuclear cells (PBMC) in patients with rare defined "disorders of sex development" (DSD, e.g., 46, XY-females due to defective androgen biosynthesis) compared to normal 46, XY-males and 46, XX-females. Results A discrete set of transcripts was directly correlated with XY or XX genotypes in all individuals independent of male or female phenotype of the external genitalia. However, a significantly larger gene set in the PBMC only reflected the degree of external genital masculinization independent of the sex chromosomes and independent of concurrent post-natal sex steroid hormone levels. Consequently, the architecture of the transcriptional PBMC-"sexes" was either male, female or even "intersex" with a discordant alignment of the DSD individuals' genetic and hormonal sex signatures. Conclusion A significant fraction of gene expression differences between males and females in the human appears to have its roots in early embryogenesis and is not only caused by sex chromosomes but also by long-term sex-specific hormonal programming due to presence or absence of androgen during the time of external genital masculinization. Genetic sex and the androgen milieu during embryonic development might therefore independently modulate functional traits, phenotype and diseases associated with male or female gender as well as with DSD conditions. PMID:19570224

  7. Effect of anticonvulsants on plasma testosterone and sex hormone binding globulin levels.

    PubMed Central

    Barragry, J M; Makin, H L; Trafford, D J; Scott, D F

    1978-01-01

    Plasma sex hormone binding globulin (SHBG) and testosterone levels were measured in 29 patients with epilepsy (16 men and 13 women), most of them on chronic therapy with anticonvulsant drugs. Sex hormone binding globulin concentrations were increased in both sexes and testosterone levels in male patients. It is postulated that anticonvulsants may induce hepatic synthesis of SHBG. PMID:569688

  8. [Establishment of reference ranges of sex hormones for healthy children in Shenzhen, China based on chemiluminescence].

    PubMed

    Sun, Li-Fang; Li, Ying-Ying; Huang, Bao-Xing; Fu, Xiao-Ying; Yang, Fang-Hua; Ma, Dong-Li; Zhang, Qin

    2017-12-01

    To study the reference ranges of six sex hormones, i.e., luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone, for healthy children aged 0-18 years in Shenzhen, China. Stratified cluster sampling was performed to select 2 178 healthy children aged 0-18 years in the districts of Futian, Luohu, Nanshan, Bao'an, and Longgang in Shenzhen between September 2015 and September 2016. There were 1 219 boys and 959 girls, including 81 neonates, 335 infants, 346 young children, 469 preschool children, 419 school-aged children, and 528 adolescents. The American Beckman DXI800 chemiluminescence meter was used to measure the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone. There were significant differences in the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone between different age groups (P<0.05). There were also significant differences in the levels of these sex hormones between boys and girls in the same age group (P<0.05). The reference ranges of six sex hormones were established for healthy children aged 0-18 years in Shenzhen based on the levels of these hormones in different age groups. There are significant differences in sex hormones between different age groups or sex groups. The reference ranges of six sex hormones established for different sexes or ages have great significance in the diagnosis and treatment of endocrine diseases in children.

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

    PubMed

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

    2018-06-01

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

  10. The association of total antioxidant capacity with sex hormones.

    PubMed

    Demirbag, Recep; Yilmaz, Remzi; Erel, Ozcan

    2005-07-01

    Although sex hormones have potential cardioprotective effects, their effects on total antioxidant capacity (TAC) are not very well known. The aim of the study was to evaluate TAC in men who have decreased and normal testosterone levels and in women in menopausal and premenopausal period. Ninety-seven subjects with similar age intervals, men aged <45 years and female aged <50 years, were divided into four groups: 1) 10 men with normal testosterone levels, as control, 2) 36 men with decreased testosterone, 3) 19 women in menopause, surgically induced, and 4) 32 women in premenopausal period. Testosterone and estrogen levels were measured by chemiluminescence assay and TAC were measured by using a more recently developed automated measurement method. The TAC was significantly lower in Group 2 and Group 3 than those of Group 1 and Group 4 (ANOVA, p<0.001). A strong correlation between TAC, and testosterone and estrogen were found (r=0.807, p<0.001; r=0.685, p<0.001, testosterone and estrogen respectively). The observed relationship between sex hormones and TAC may have a role in mechanism of their cardioprotective effect.

  11. Semen quality and sex hormones with reference to metal welding.

    PubMed

    Hjollund, N H; Bonde, J P; Jensen, T K; Ernst, E; Henriksen, T B; Kolstad, H A; Giwercman, A; Skakkebaek, N E; Olsen, J

    1998-01-01

    Welding may involve hazards to the male reproductive system, but previous studies of semen quality have produced inconsistent results. We studied the effects of welding on markers of semen quality in a Danish nationwide sample of 430 first-time pregnancy planners without earlier reproductive experience. Couples were recruited among members of the union of metal workers and three other trade unions and were followed from termination of birth control until pregnancy for a maximum of six menstrual cycles. The males provided semen samples in each cycle. Median sperm density for welders was 56 x 10(6)/mL (52.5 x 10(6)/mL and 50.0 x 10(6)/mL in two reference groups). No statistically significant differences attributable to welding were found in proportions of morphologically normal sperm, sperm motility assessed by computer-aided sperm analysis, or sex hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone). These negative findings may not apply to populations with high-level exposure to welding fume or to welders exposed to other putative hazards, e.g., heat.

  12. Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis.

    PubMed

    Williams, Marlene S; Cushman, Mary; Ouyang, Pamela; Heckbert, Susan R; Kalyani, Rita Rastogi; Vaidya, Dhanajay

    2016-02-01

    Hormone therapy (HT) is associated with increased risk of both venous and arterial thrombosis, which are multifactorial in origin. Our objectives were twofold: first, we sought to examine associations between endogenous serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone nonusers. Second, we separately studied the associations between serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone users considering the fact that pattern of circulating hormones is different in women taking exogenous hormones. We performed a cross-sectional analysis of postmenopausal women enrolled in a large multiethnic community-based cohort study, The Multiethnic Study of Atherosclerosis. We hypothesized that higher levels of estrogen-related sex hormones would be associated with biomarkers of thrombosis, suggesting mechanisms for differences in thrombotic risk from HT. Women (n = 2878) were included if they were postmenopausal and had thrombotic biomarkers (homocysteine, fibrinogen, C-reactive protein [CRP], factor VIII, and d-dimer) and sex hormone levels (total testosterone [T], bioavailable testosterone, sex hormone binding globulin [SHBG], estradiol [E2], and dehydroepiandrosterone [DHEA]) measured. A smaller random sample of 491 women also had von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue factor pathway inhibitor (TFPI) levels measured. We found that elevated levels of estradiol and SHBG in HT users were associated with elevated levels of CRP and lower levels of TFPI, both of which may be related to a prothrombotic milieu in HT users. HT nonusers had far more prothrombotic associations between elevated serum sex hormone levels and thrombotic biomarkers when compared with HT users.

  13. Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms.

    PubMed

    Mahmoud, Rand; Wainwright, Steven R; Galea, Liisa A M

    2016-04-01

    Neurogenesis within the adult hippocampus is modulated by endogenous and exogenous factors. Here, we review the role of sex hormones in the regulation of adult hippocampal neurogenesis in males and females. The review is framed around the potential functional implications of sex hormone regulation of adult hippocampal neurogenesis, with a focus on cognitive function and mood regulation, which may be related to sex differences in incidence and severity of dementia and depression. We present findings from preclinical studies of endogenous fluctuations in sex hormones relating to reproductive function and ageing, and from studies of exogenous hormone manipulations. In addition, we discuss the modulating roles of sex, age, and reproductive history on the relationship between sex hormones and neurogenesis. Because sex hormones have diverse targets in the central nervous system, we overview potential mechanisms through which sex hormones may influence hippocampal neurogenesis. Lastly, we advocate for a more systematic consideration of sex and sex hormones in studying the functional implications of adult hippocampal neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Ischemic stroke and select adipose-derived and sex hormones: a review.

    PubMed

    Meadows, Kristy L

    2018-06-06

    Ischemic stroke is the fifth leading cause of death in the USA and is the leading cause of serious, long-term disability worldwide. The principle sex hormones (estrogen, progesterone, and testosterone), both endogenous and exogenous, have profound effects on various stroke outcomes and have become the focus of a number of studies evaluating risk factors and treatment options for ischemic stroke. In addition, the expression of other hormones that may influence stroke outcome, including select adipose-derived hormones (adiponectin, leptin, and ghrelin), can be regulated by sex hormones and are also the focus of several ischemic stroke studies. This review aims to summarize some of the preclinical and clinical studies investigating the principle sex hormones, as well as select adipose-derived hormones, as risk factors or potential treatments for ischemic stroke. In addition, the potential for relaxin, a lesser studied sex hormone, as a novel treatment option for ischemic stroke is explored.

  15. Cross-sex hormone therapy for gender dysphoria.

    PubMed

    Fabris, B; Bernardi, S; Trombetta, C

    2015-03-01

    Gender identity is the sense one has of being male or female. Gender dysphoria (GD) refers to the distress caused by the incongruence between gender identity and biological sex in gender-nonconforming individuals. Cross-sex hormone therapy (CHT) aims at easing GD, improving well-being, and quality of life of gender-nonconforming individuals. This can be achieved by inducing and maintaining the desired-sex characteristics in accordance with the specific aspirations and expectations of each individual. Nevertheless, CHT can be associated with potentially serious long-term complications. Here, we review when, how, and how long to prescribe CHT to adult transsexuals as well as what to expect and monitor once it has been initiated. In recent years, transsexualism has become more and more recognized and depathologized. To manage GD, National and International Standards of Care have been established. Nevertheless, the needs of transgender patients can still be ignored or dismissed. Moreover, some questions remain unanswered because of the lack of specific retrospective or prospective studies on CHT. Education and culturally sensitive training must be supplied to healthcare professionals to overcome the existing issues on GD management and change the perspectives of transsexual people.

  16. The UV-absorber benzophenone-4 alters transcripts of genes involved in hormonal pathways in zebrafish (Danio rerio) eleuthero-embryos and adult males

    SciTech Connect

    Zucchi, Sara; Bluethgen, Nancy; University of Basel, Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, Klingelbergstrasse 50, CH-4056 Basel

    Benzophenone-4 (BP-4) is frequently used as UV-absorber in cosmetics and materials protection. Despite its frequent detection in the aquatic environment potential effects on aquatic life are unknown. In this study, we evaluate the effects of BP-4 in eleuthero-embryos and in the liver, testis and brain of adult male fish on the transcriptional level by focusing on target genes involved in hormonal pathways to provide a more complete toxicological profile of this important UV-absorber. Eleuthero-embryos and males of zebrafish were exposed up to 3 days after hatching and for 14 days, respectively, to BP-4 concentrations between 30 and 3000 {mu}g/L. Inmore » eleuthero-embryos transcripts of vtg1, vtg3, esr1, esr2b, hsd17ss3, cyp19b cyp19a, hhex and pax8 were induced at 3000 {mu}g/L BP-4, which points to a low estrogenic activity and interference with early thyroid development, respectively. In adult males BP-4 displayed multiple effects on gene expression in different tissues. In the liver vtg1, vtg3, esr1 and esr2b were down-regulated, while in the brain, vtg1, vtg3 and cyp19b transcripts were up-regulated. In conclusion, the transcription profile revealed that BP-4 interferes with the expression of genes involved in hormonal pathways and steroidogenesis. The effects of BP-4 differ in life stages and adult tissues and point to an estrogenic activity in eleuthero-embryos and adult brain, and an antiestrogenic activity in the liver. The results indicate that BP-4 interferes with the sex hormone system of fish, which is important for the risk assessment of this UV-absorber.« less

  17. Fluorochemicals used in food packaging inhibit male sex hormone synthesis

    SciTech Connect

    Rosenmai, A.K., E-mail: akjro@food.dtu.dk; Nielsen, F.K.; Pedersen, M.

    Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact materials (FCMs) of paper and board and have recently been detected in 57% of investigated materials. Human exposure occurs as PAPS have been measured in blood; however knowledge is lacking on the toxicology of PAPS. The aim of this study was to elucidate the effects of six fluorochemicals on sex hormone synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2 FTOH) were tested. Hormone profiles, including eight steroid hormones, generally showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2more » FTOH led to decreases in androgens (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R steroidogenesis assay. Decreases were observed for progesterone and 17-OH-progesterone as well. These observations indicated that a step prior to progestagen and androgen synthesis had been affected. Gene expression analysis of StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol transport to the inner mitochondria. Cortisol, estrone and 17β-estradiol levels were in several cases increased with exposure. In accordance with these data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH exposures indicating that this is a contributing factor to the decreased androgen and the increased estrogen levels. Overall, these results demonstrate that fluorochemicals present in food packaging materials and their metabolites can affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression leading to lower androgen and higher estrogen levels. -- Highlights: ► Fluorochemicals found in 57% of paper and board food packaging were tested. ► Collectively six fluorochemicals were tested for antiandrogenic potential in vitro. ► Three out of six tested fluorochemicals

  18. Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain.

    PubMed

    Sinclair, Duncan; Purves-Tyson, Tertia D; Allen, Katherine M; Weickert, Cynthia Shannon

    2014-04-01

    Adolescence is a developmental period of complex neurobiological change and heightened vulnerability to psychiatric illness. As a result, understanding factors such as sex and stress hormones which drive brain changes in adolescence, and how these factors may influence key neurotransmitter systems implicated in psychiatric illness, is paramount. In this review, we outline the impact of sex and stress hormones at adolescence on dopamine neurotransmission, a signaling pathway which is critical to healthy brain function and has been implicated in psychiatric illness. We review normative developmental changes in dopamine, sex hormone, and stress hormone signaling during adolescence and throughout postnatal life, then highlight the interaction of sex and stress hormones and review their impacts on dopamine neurotransmission in the adolescent brain. Adolescence is a time of increased responsiveness to sex and stress hormones, during which the maturing dopaminergic neural circuitry is profoundly influenced by these factors. Testosterone, estrogen, and glucocorticoids interact with each other and have distinct, brain region-specific impacts on dopamine neurotransmission in the adolescent brain, shaping brain maturation and cognitive function in adolescence and adulthood. Some effects of stress/sex hormones on cortical and subcortical dopamine parameters bear similarities with dopaminergic abnormalities seen in schizophrenia, suggesting a possible role for sex/stress hormones at adolescence in influencing risk for psychiatric illness via modulation of dopamine neurotransmission. Stress and sex hormones may prove useful targets in future strategies for modifying risk for psychiatric illness.

  19. Neurovascular control of blood pressure is influenced by aging, sex, and sex hormones.

    PubMed

    Baker, Sarah E; Limberg, Jacqueline K; Ranadive, Sushant M; Joyner, Michael J

    2016-12-01

    In this review, we highlight that the relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure is complex, differs by sex, and changes with age. In young men there is an inverse relationship between MSNA and cardiac output where high MSNA is compensated for by low cardiac output. This inverse relationship is not seen in older men. In young women sympathetic vasoconstriction is offset by β-adrenoreceptor mediated vasodilation, limiting the ability of young women to maintain blood pressure in response to orthostatic stress. However, β-mediated dilation in women is attenuated with age, leading to unopposed α-adrenergic vasoconstriction and a rise in the direct transduction of MSNA into increases in blood pressure. We propose that these changes with age and menopausal status are major contributing factors in the increased prevalence of hypertension in older women. In addition to aging, we highlight that changes in sex hormones in young women (across the menstrual cycle, with oral contraceptive use, or with pregnancy) influence MSNA and the transduction of MSNA into increases in blood pressure. It is likely that the β-adrenergic receptors and/or changes in baroreflex sensitivity play a large role in these sex differences and changes with alterations in sex hormones. Copyright © 2016 the American Physiological Society.

  20. Combined effects of sex hormone-binding globulin and sex hormones on risk of incident type 2 diabetes.

    PubMed

    Hu, Jinbo; Zhang, Aiping; Yang, Shumin; Wang, Yue; Goswami, Richa; Zhou, Huang; Zhang, Yi; Wang, Zhihong; Li, Rong; Cheng, Qingfeng; Zhen, Qianna; Li, Qifu

    2016-07-01

    The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008-13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62-51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21-4.53], 0.14 [95% CI 0.10-0.74]; Ptrend  = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  1. Exogenously treated mammalian sex hormones affect inorganic constituents of plants.

    PubMed

    Erdal, Serkan; Dumlupinar, Rahmi

    2011-10-01

    The present study was undertaken to reveal the changes in inorganic constituents of plants exposed to mammalian sex hormones (MSH). Chickpea leaves were sprayed with 10(-4), 10(-6), 10(-9), 10(-12), and 10(-15) M concentrations of progesterone, β-estradiol, and androsterone at 7th day after sowing. The plants were harvested at the end of 18 days after treatment of MSH solutions and the inorganic components determined using a wavelength-dispersive X-ray fluorescence spectroscopy technique. At all of the concentrations tested, MSH significantly increased the contents of K, S, Na, Ca, Mg, Zn, Fe, P, Cu, and Ni. Interestingly, only Mn and Cl contents decreased. The maximum changes in the inorganic composition were recorded at 10(-6) M for plants treated with progesterone and 10(-9) M for plants treated with β-estradiol and androsterone.

  2. Association Between Sex and Speech Auditory Brainstem Responses in Adults, and Relationship to Sex Hormone Levels.

    PubMed

    Liu, Jinfeng; Wang, Dan; Li, Xiaoting; Ningyu, Wang

    2017-05-14

    BACKGROUND The aim of this study was to investigate the association between sex and speech-ABR in adults, and its relationship to sex hormone levels. MATERIAL AND METHODS Speech-ABR were elicited with the consonant-vowel syllable (/da/) in a total of 35 adults. Reproductive hormone levels were also measured. RESULTS The transient response of the speech-ABR (waves V, A, and O) in females show a shorter latency (waves V, A and O) and a larger amplitude (waves V and A) than in males (P<0.05), except for the amplitude of peak O (P>0.05). The sustained response of females exhibited a larger amplitude (wave F, P<0.05) and a shorter latency (wave D, E, and F, P<0.05) than in males, except for the amplitude of peak D and E (P>0.05). The latencies of speech-ABR were positively correlated with testosterone level (P<0.05), and were negatively correlated with estradiol (E2) levels (P<0.05), except for wave E (P>0.05). The E2 showed a positive correlation with the absolute value of amplitude of the speech-ABR (P < 0.05). On the contrary, total testosterone showed a negative correlation with the absolute value of amplitude the speech-ABR (P<0.05), except for wave D and wave O (P>0.05). CONCLUSIONS Sex differences in speech-ABR are significant in adults. The latencies and amplitude of the speech-ABR waves were correlated with the E2 concentration and testosterone level. The sex hormones likely affect speech encoding in the brainstem.

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

    PubMed

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

    2003-08-01

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

  4. SHBG, sex hormones, and inflammatory markers in older women.

    PubMed

    Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Corsi, Anna Maria; Giallauria, Francesco; Guralnik, Jack M; Zuliani, Giovanni; Cattabiani, Chiara; Parrino, Stefano; Ablondi, Fabrizio; Dall'aglio, Elisabetta; Ceresini, Graziano; Basaria, Shehzad; Ferrucci, Luigi

    2011-04-01

    In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state.

  5. Conservative Christianity, partnership, hormones, and sex in late life.

    PubMed

    Das, Aniruddha; Nairn, Stephanie

    2014-10-01

    Using nationally representative data from the 2005-2006 U.S. National Social Life, Health, and Aging Project, this study queried relationship, sexual, and sex hormone patterns among married evangelical women and men aged 57-85, relative to those in other religions. Results suggested that despite potentially more unequal gender roles, evangelical older women may have better marital quality, perhaps due to the recent transformation of their male counterparts into authoritative, yet-supportive, "soft patriarchs." Correspondingly, these women, especially those with greater subjective religiosity or more support from a spouse, reported consistently better sexual outcomes than their counterparts in other religions. In addition, they also had lower estradiol, whether due to psychobiological effects of their better relationships or self-selection of those with differential hormone levels into particular partnership patterns. While older men in these communities also experienced more satisfactory marriages, and had lower androgens (testosterone, DHEA), their relational assets were less uniformly matched by better sexual outcomes, perhaps reflecting a gender disparity in the linkage between these factors.

  6. Impact of Sex Hormone Metabolism on the Vascular Effects of Menopausal Hormone Therapy in Cardiovascular Disease

    PubMed Central

    Masood, Durr-e-Nayab; Roach, Emir C.; Beauregard, Katie G.; Khalil, Raouf A.

    2010-01-01

    Epidemiological studies have shown that cardiovascular disease (CVD) is less common in pre-menopausal women (Pre-MW) compared to men of the same age or post-menopausal women (Post-MW), suggesting cardiovascular benefits of estrogen. Estrogen receptors (ERs) have been identified in the vasculature, and experimental studies have demonstrated vasodilator effects of estrogen/ER on the endothelium, vascular smooth muscle (VSM) and extracellular matrix. Several natural and synthetic estrogenic preparations have been developed for relief of menopausal vasomotor symptoms. However, whether menopausal hormone therapy (MHT) is beneficial in postmenopausal CVD remains controversial. Despite reports of vascular benefits of MHT from observational and experimental studies, randomized clinical trials (RCTs), such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), have suggested that, contrary to expectations, MHT may increase the risk of CVD. These discrepancies could be due to age-related changes in sex hormone synthesis and metabolism, which would influence the effective dose of MHT and the sex hormone environment in Post-MW. Age-related changes in the vascular ER subtype, structure, expression, distribution, and post-ER signaling pathways in the endothelium and VSM, along with factors related to the design of RCTs, preexisting CVD condition, and structural changes in the blood vessels architecture have also been suggested as possible causes of MHT failure in CVD. Careful examination of these factors should help in identifying the causes of the changes in the vascular effects of estrogen with age. The sex hormone metabolic pathways, the active versus inactive estrogen metabolites, and their effects on vascular function, the mitochondria, the inflammatory process and angiogenesis should be further examined. Also, the genomic and non-genomic effects of estrogenic compounds should be viewed as integrated rather than discrete

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

    PubMed

    Phuge, S K; Gramapurohit, N P

    2015-09-01

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

  8. Development without germ cells: the role of the germ line in zebrafish sex differentiation.

    PubMed

    Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

    2005-03-15

    The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin-antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males.

  9. Development without germ cells: The role of the germ line in zebrafish sex differentiation

    PubMed Central

    Slanchev, Krasimir; Stebler, Jürg; de la Cueva-Méndez, Guillermo; Raz, Erez

    2005-01-01

    The progenitors of the gametes, the primordial germ cells (PGCs) are typically specified early in the development in positions, which are distinct from the gonad. These cells then migrate toward the gonad where they differentiate into sperms and eggs. Here, we study the role of the germ cells in somatic development and particularly the role of the germ line in the sex differentiation in zebrafish. To this end, we ablated the germ cells using two independent methods and followed the development of the experimental fish. First, PGCs were ablated by knocking down the function of dead end, a gene important for the survival of this lineage. Second, a method to eliminate the PGCs using the toxin–antitoxin components of the parD bacterial genetic system was used. Specifically, we expressed a bacterial toxin Kid preferentially in the PGCs and at the same time protected somatic cells by uniformly expressing the specific antidote Kis. Our results demonstrate an unexpected role for the germ line in promoting female development because PGC-ablated fish invariably developed as males. PMID:15728735

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

    PubMed

    Grgurevic, Neza; Majdic, Gregor

    2016-09-01

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

  11. SHBG, Sex Hormones, and Inflammatory Markers in Older Women

    PubMed Central

    Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Corsi, Anna Maria; Giallauria, Francesco; Guralnik, Jack M.; Zuliani, Giovanni; Cattabiani, Chiara; Parrino, Stefano; Ablondi, Fabrizio; Dall'Aglio, Elisabetta; Ceresini, Graziano; Basaria, Shehzad; Ferrucci, Luigi

    2011-01-01

    Context: In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. Objective: The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. Design and Patients: We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. Results: In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. Conclusion: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state. PMID:21239514

  12. Sex differences in cortical thickness and their possible genetic and sex hormonal underpinnings.

    PubMed

    Savic, I; Arver, S

    2014-12-01

    Although it has been shown that cortical thickness (Cth) differs between sexes, the underlying mechanisms are unknown. Seeing as XXY males have 1 extra X chromosome, we investigated the possible effects of X- and sex-chromosome dosage on Cth by comparing data from 31 XXY males with 39 XY and 47 XX controls. Plasma testosterone and estrogen were also measured in an effort to differentiate between possible sex-hormone and sex-chromosome gene effects. Cth was calculated with FreeSurfer software. Parietal and occipital Cth was greater in XX females than XY males. In these regions Cth was inversely correlated with z-normalized testosterone. In the motor strip, the cortex was thinner in XY males compared with both XX females and XXY males, indicating the possibility of an X-chromosome gene-dosage effect. XXY males had thinner right superior temporal and left middle temporal cortex, and a thicker right orbitofrontal cortex and lingual cortex than both control groups. Based on these data and previous reports from women with XO monosomy, it is hypothesized that programming of the motor cortex is influenced by processes linked to X-escapee genes, which do not have Y-chromosome homologs, and that programming of the superior temporal cortex is mediated by X-chromosome escapee genes with Y-homologs. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

    PubMed Central

    Meleine, Mathieu; Matricon, Julien

    2014-01-01

    According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

  14. Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones.

    PubMed

    Meleine, Mathieu; Matricon, Julien

    2014-06-14

    According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical

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

    PubMed

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

    2015-06-01

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

  16. Sex hormones in gender-specific risk for head and neck cancer: A review.

    PubMed

    Nainani, Purshotam; Paliwal, Aparna; Nagpal, Neelu; Agrawal, Mayank

    2014-11-01

    Despite the fact that numerous researches have been carried out to prevent head and neck cancer (HNC) and treat those patients, there is no reduction in morbidity rate because the underlying molecular pathogenesis is still poorly understood. Endocrine microenvironment is another vital factor besides other traditional risk factors like tobacco smoking, infections, and alcohol. It has been proven that sex hormone receptors are also expressed in larynx and lungs, in addition to sex organs. Sex hormones play a vital role in gene expression involved in the plethora of biological and neoplastic processes. The role of sex hormones in HNC is still divisive and very few researches have been conducted to describe their role. So, this article is an effort to attract the attention of researchers, endocrinologists, pathologists, and clinicians toward the impending role of sex hormones, with special emphasis on progesterone, estrogen, and prolactin in HNC onset and progression, along with their therapeutic role.

  17. Vitamin D metabolism, sex hormones, and male reproductive function.

    PubMed

    Blomberg Jensen, Martin

    2012-08-01

    The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

  18. The gonadotropin-inhibitory hormone (Lpxrfa) system's regulation of reproduction in the brain-pituitary axis of the zebrafish (Danio rerio).

    PubMed

    Spicer, Olivia Smith; Zmora, Nilli; Wong, Ten-Tsao; Golan, Matan; Levavi-Sivan, Berta; Gothilf, Yoav; Zohar, Yonathan

    2017-05-01

    Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (LPXRFamide (Lpxrfa) peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary. In the preoptic area, Lpxrfa fibers interact with gonadotropin-releasing hormone 3 (Gnrh3) soma. In pituitary explants, zebrafish peptide Lpxrfa-3 downregulated luteinizing hormone beta subunit and common alpha subunit expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices, offering another pathway for Lpxrfa to exert its effects on reproduction. Receptor activation studies, in a heterologous cell-based system, revealed that all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kisspeptin-2 (Kiss2) activation of Kisspeptin receptor-1a (Kiss1ra). The fact that kiss1ra-expressing neurons in the preoptic area are innervated by Lpxrfa-ir fibers suggests an additional pathway for Lpxrfa action. Therefore, our results suggest that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish that interacts with Gnrh3 neurons in the brain and with gonadotropes in the pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Sex, age, and sex hormones affect recall of words in a directed forgetting paradigm.

    PubMed

    Kerschbaum, Hubert H; Hofbauer, Ildiko; Gföllner, Anna; Ebner, Birgit; Bresgen, Nikolaus; Bäuml, Karl-Heinz T

    2017-01-02

    During the course of serious discussion, an unexpected interruption may induce forgetting of the original topic of a conversation. Sex, age, and sex hormone levels may affect frequency and extension of forgetting. In a list-method directed forgetting paradigm, subjects have to learn two word lists. After learning list 1, subjects receive either a forget or a remember list 1 cue. When the participants had learned list 2 and completed a distraction task, they were asked to write down as many recalled items as possible, starting either with list 1 or list 2 items. In the present study, 96 naturally cycling women, 60 oral contraceptive users, 56 postmenopausal women, and 41 young men were assigned to one of these different experimental conditions. Forget-cued young subjects recall fewer list 1 items (list 1 forgetting) but more list 2 items (list 2 enhancement) compared with remember-cued subjects. However, forget-cued postmenopausal women showed reduced list 1 forgetting but enhanced list 2 retention. Remember-cued naturally cycling women recalled more list 1 items than oral contraceptive users, young men, and postmenopausal women. In forget-cued follicular women, salivary progesterone correlated positively with recalled list 2 items. Salivary 17β-estradiol did not correlate with recalled list 1 or list 2 items in either remember- or forget-cued young women. However, salivary 17β-estradiol correlated with item recall in remember-cued postmenopausal women. Our findings suggest that sex hormones do not globally modulate verbal memory or forgetting, but selectively affect cue-specific processing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. People with gender dysphoria who self-prescribe cross-sex hormones: prevalence, sources, and side effects knowledge.

    PubMed

    Mepham, Nick; Bouman, Walter P; Arcelus, Jon; Hayter, Mark; Wylie, Kevan R

    2014-12-01

    There is a scarcity of research into the use of non-physician-sourced cross-sex hormones in the transgender population. However, when medication is not prescribed by health professionals, users' knowledge of such medication may be adversely affected. This study aims to define the prevalence of Internet-sourced sex hormone use in a population attending for initial assessment at a gender identity clinic, to compare the prevalence between gender-dysphoric men and women, and to compare knowledge of cross-sex hormone side effects between users who source cross-sex hormones from medical doctors and those who source them elsewhere. In the first part of the study, a cross-sectional design is used to measure the overall prevalence of sex hormone use among individuals referred to a gender clinic. The second part is a questionnaire survey aiming at measuring sex hormone knowledge among individuals referred to this clinic. Main outcome measures were (i) categorical data on the prevalence and source of cross-sex hormone use and (ii) knowledge of sex hormone side effects in a population referred to a gender clinic. Cross-sex hormone use was present in 23% of gender clinic referrals, of whom 70% sourced the hormones via the Internet. Trans men using testosterone had a sex hormone usage prevalence of 6%; one-third of users sourced it from the Internet. Trans women had a sex hormone usage prevalence of 32%; approximately 70% of users sourced hormones from the Internet. Cross-sex hormone users who sourced their hormones from physicians were more aware of side effects than those who used other sources to access hormones. One in four trans women self-prescribe cross-sex hormones before attending gender clinics, most commonly via the Internet. This practice is currently rare among trans men. Self-prescribing without medical advice leaves individuals without the knowledge required to minimize health risks. © 2014 International Society for Sexual Medicine.

  1. Sex hormone-binding globulin b expression in the rainbow trout ovary prior to sex differentiation.

    PubMed

    Pérez, Claudio; Araneda, Cristian; Estay, Francisco; Díaz, Nelson F; Vizziano-Cantonnet, Denise

    2018-04-01

    Salmonids have two sex hormone-binding globulin (Shbg) paralogs. Shbga is mainly expressed in the liver, while Shbgb is secreted by the granulosa cells of the rainbow trout ovary. Coexpression of shbgb and the gonadal aromatase cyp19a1a mRNAs been observed in granulosa cells, suggesting a physiological coordination between Shbgb expression and estrogen synthesis. As estrogens are essential for female sex determination in the fish ovary, we propose that Shbgb participates in early ovarian differentiation, either by binding with estrogen or through another mechanism that remains to be discovered. To elucidate this potential role, monosex populations of female trout were studied during the molecular ovarian differentiation period (28-56 dpf). shbgb mRNA expression was measured using qPCR and compared with expression of genes for other ovarian markers (cyp19a1a, foxl2, follistatin, and estrogen receptors). shbgb transcript expression was detected during the final stages of embryonic development (21-26 dpf) and during molecular ovarian differentiation (32-52 dpf) after hatching (which occurred at 31 dpf). In situ hybridization localized shbgb transcription to the undifferentiated ovary at 42 dpf, and shbgb and cyp19a1a mRNA showed similar expression patterns. These results suggest that Shbgb is involved in early ovarian differentiation, supporting an important role for the salmonid shbgb gene in sex determination. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Do differences in female sex hormone levels contribute to gastro-oesophageal reflux disease?

    PubMed

    Menon, Shyam; Prew, Sandra; Parkes, Gill; Evans, Stephanie; Smith, Lynne; Nightingale, Peter; Trudgill, Nigel

    2013-07-01

    Hormone replacement therapy is associated with both reflux symptoms and oesophagitis. During pregnancy, elevated sex hormones are thought to contribute to the high prevalence of reflux symptoms. Increased female sex hormone levels may thus contribute to the aetiology of gastro-oesophageal reflux disease (GORD). To determine if female sex hormone levels are associated with symptomatic acid reflux. Women with GORD symptoms undergoing oesophageal pH monitoring were prospectively recruited. 'Cases' and 'controls' were defined by normal and excess total acid exposure on pH monitoring and were age-matched and BMI-matched. Case and control groups were further stratified into premenopausal and postmenopausal groups. Demographic data were collected, body morphological parameters were measured and oestradiol, oestrone, progesterone and sex hormone-binding globulin were measured. One hundred and twenty-one women [mean age 52 (SD 11.6) years] were recruited and 104 [mean age 51 (SD 11.6) years] were matched for age and BMI. Increasing BMI, as expected, correlated with increasing acid exposure [premenopausal (r=0.404, P=0.02), postmenopausal (r=0.401, P=0.01)]. Increasing BMI also correlated with sex hormone levels [premenopausal oestradiol (r=0.52, P=0.004), postmenopausal oestrone (r=0.364, P=0.01)]. In premenopausal women, sex hormone binding globulin (r=-0.27, P=0.05) and testosterone (r=0.29, P=0.05) correlated with increasing acid exposure, but oestradiol fell just short of significance (r=0.26, P=0.06). However, on matching for BMI, no association between sex hormones and increased acid exposure on pH monitoring was found on multivariate logistic regression analysis. Female sex hormone levels do not appear to contribute to GORD, once adjustment is made for the influence of increasing BMI.

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

    PubMed

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

    2018-05-04

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

  4. CHALLENGES IN BIODEGRADATION OF TRACE ORGANIC CONTAMINANTS-GASOLINE OXYGENATES AND SEX HORMONES

    EPA Science Inventory

    Advances in analytical methods have led to the identification of several classes of organic chemicals that are associated with adverse environmental impacts. Two such classes of organic chemicals, gasoline oxygenates and sex hormones, are used to illustrate challenges associated ...

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

    PubMed Central

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

    2016-01-01

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

  6. Cross-sex hormone treatment does not change sex-sensitive cognitive performance in gender identity disorder patients.

    PubMed

    Haraldsen, Ira R; Egeland, Thore; Haug, Egil; Finset, Arnstein; Opjordsmoen, Stein

    2005-12-15

    Cognitive performance in untreated early onset gender identity disorder (GID) patients might correspond to their born sex and not to their perceived gender. As a current mode of intervention, cross-sex hormone treatment causes considerable physical changes in GID patients. We asked, as has been suggested, whether this treatment skews cognitive performance towards that of the acquired sex. Somatically healthy male and female early onset GID patients were neuropsychologically tested before, 3 and 12 months after initiating cross-sex hormone treatment, whereas untreated healthy subjects without GID served as controls (C). Performance was assessed by testing six cognitive abilities (perception, arithmetic, rotation, visualization, logic, and verbalization), and controlled for age, education, born sex, endocrine differences and treatment by means of repeated measures analysis of variance. GID patients and controls showed an identical time-dependent improvement in cognitive performance. The slopes were essentially parallel for males and females. There was no significant three-way interaction of born sex by group by time for the six investigated cognitive abilities. Only education and age significantly influenced this improvement. Despite the substantial somatic cross-sex changes in GID patients, no differential effect on cognition over time was found between C and GID participants. The cognitive performance of cross-sex hormone-treated GID patients was virtually identical to that of the control group. The documented test-retest effect should be taken into consideration when evaluating treatment effects generally in psychiatry.

  7. Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

    PubMed

    Guo, Lei; Chen, Yi-Xi; Hu, Yu-Ting; Wu, Xue-Yan; He, Yang; Wu, Juan-Li; Huang, Man-Li; Mason, Matthew; Bao, Ai-Min

    2018-05-21

    Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-03-01

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

  9. FATE OF SEX HORMONES IN TWO PILOT-SCALE MUNICIPAL WASTEWATER TREATMENT PLANTS: CONVENTIONAL TREATMENT

    EPA Science Inventory

    The fate of seven sex hormones (estrone (E1), estradiol (E2), estriol (E3), ethinylestradiol (EE2), testosterone, androstenedione, and progesterone) was determined in two pilot-scale wastewater treatment plants operated under conventional loading conditions. The levels of hormon...

  10. Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

    PubMed

    Chin, Kok-Yong; Soelaiman, Ima-Nirwana; Mohamed, Isa Naina; Ahmad, Fairus; Ramli, Elvy Suhana Mohd; Aminuddin, Amilia; Ngah, Wan Zurinah Wan

    2013-01-01

    Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

  11. Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

    PubMed Central

    Chin, Kok-Yong; Soelaiman, Ima-Nirwana; Mohamed, Isa Naina; Ahmad, Fairus; Ramli, Elvy Suhana Mohd; Aminuddin, Amilia; Ngah, Wan Zurinah Wan

    2013-01-01

    OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia. PMID:23525310

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

    PubMed Central

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

    2016-01-01

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

  13. Local synthesis of sex hormones: are there consequences for the ocular surface and dry eye?

    PubMed

    Gibson, Emma J; Stapleton, Fiona; Wolffsohn, James S; Golebiowski, Blanka

    2017-12-01

    Sex hormones are associated with the physiology and pathophysiology of almost all organs in the body, as well as most diseases. Interest in the associations between sex hormones and ocular tissues has increased in recent years. Androgens may have a positive effect on dry eye, whereas the effects of oestrogen on ocular conditions remain unclear. Intracrinology, the local synthesis and metabolism of hormones that is unique to humans, is of relevance to the eye and may help to explain why studies of the relationship between oestrogens and dry eye signs and symptoms are inconclusive. Knowledge of the pathways of hormone formation and metabolism is crucial to understanding the pathogenesis of ocular disease including dry eye. This review examines the mechanisms of steroidal sex hormone biosynthesis and reviews the significance of locally produced sex hormones, with a focus on ocular surface tissues. Much of the current literature is based on animal studies, which may not be transferable to humans due to the absence of intracrine production in animals. A large proportion of the human studies investigate systemic hormone levels rather than local levels. There is subsequently a need for additional studies to provide a better understanding of the local production of sex hormones within the human eye and ocular surface and to clarify the relationships between ocular levels of sex hormones and conditions including dry eye. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. 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. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

    PubMed Central

    Vellers, Heather L.; Letsinger, Ayland C.; Walker, Nicholas R.; Granados, Jorge Z.; Lightfoot, J. Timothy

    2017-01-01

    Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels. Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity. Results: 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p < 0.0001; female: p < 0.0001) and had significantly higher body fat (male: p < 0.0001; female: p < 0.0001). The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male (p = 0.05, 70 ± 28%) and female mice (p = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat. Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones. PMID:28890701

  16. Conjectures concerning cross-sex hormone treatment of aging transsexual persons.

    PubMed

    Gooren, Louis; Lips, Paul

    2014-08-01

    Guidelines for cross-sex hormone treatment of transsexual people are now in place. However, little attention has been paid to the issue of treatment suitability for older people. Does existing treatment need to be adapted as subjects age, and does it make a difference if treatment is only started when the subject is already older? To assess the necessity of adapting cross-sex hormone administration for elderly transsexual people. Risks/benefits of continued use of cross-sex hormones with regard to bone health, cardiovascular risks, and malignancies. Due to lack of data on the subject population, sex hormone treatment of other conditions in older non-transsexual people has been taken as the best available analogy to determine the extent to which these might be applicable to comparable transsexual persons. Findings in transsexual people receiving cross-sex hormone treatment sometimes modified the above approach of applying guidelines for the elderly to the aging transsexual population. Testosterone administration to female-to-male transsexual persons (FtoM) carries little risk with regard to cardiovascular disease and cancer. For those with high hematocrit or cardiac insufficiency the dose can be reduced. Administration of estrogens to male-to-female transsexual persons (MtoF), particularly when combined with progestins, does significantly increase the risk of developing cardiovascular disease (almost a twofold incidence compared with the general population). This may require dose adjustment or changing from oral to safer transdermal estrogens. Tumors of the breasts, prostate and pituitary may occur. In FtoM, breast cancer can occur even after breast ablation. Older subjects can commence cross-sex hormone treatment without disproportionate risks. Cross-sex hormones may be continued into old age but monitoring for cardiovascular disease and malignancies, both of the old and new sex, is recommended. MtoF will have more health complications in old age than Fto

  17. Nasal embryonic LHRH factor plays a role in the developmental migration and projection of gonadotropin-releasing hormone 3 neurons in zebrafish.

    PubMed

    Palevitch, Ori; Abraham, Eytan; Borodovsky, Natalya; Levkowitz, Gil; Zohar, Yonathan; Gothilf, Yoav

    2009-01-01

    The initiation of puberty and the functioning of the reproductive system depend on proper development of the hypophysiotropic gonadotropin-releasing hormone (GnRH) system. One critical step in this process is the embryonic migration of GnRH neurons from the olfactory area to the hypothalamus. Using a transgenic zebrafish model, Tg(gnrh3:EGFP), in which GnRH3 neurons and axons are fluorescently labeled, we investigated whether zebrafish NELF is essential for the development of GnRH3 neurons. The zebrafish nelf cDNA was cloned and characterized. During embryonic development, nelf is expressed in GnRH3 neurons and in target sites of GnRH3 projections and perikarya, before the initiation of their migration. Nelf knockdown resulted in a disruption of the GnRH3 system which included absence or misguiding of GnRH3 axonal outgrowth and incorrect or arrested migration of GnRH3 perikarya. These results suggest that Nelf is an important factor in the developmental migration and projection of GnRH3 neurons in zebrafish. Copyright (c) 2008 Wiley-Liss, Inc.

  18. Environmental hormones and their impacts on sex differentiation in fathead minnows

    EPA Science Inventory

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

  19. Physical activity and sex hormone levels in estradiol- and placebo-treated postmenopausal women.

    PubMed

    Choudhury, Farzana; Bernstein, Leslie; Hodis, Howard N; Stanczyk, Frank Z; Mack, Wendy J

    2011-10-01

    Postmenopausal changes in the hormonal milieu in women with or without hormone therapy are hypothesized to be the pathway for a number of menopause-associated modifications in physiology and disease risk. Physical activity may modify these changes in women's hormone profiles. The crucial yet complex relationship between physical activity and physiologic and pharmacologic sex hormone levels in postmenopausal women has not been investigated sufficiently. Using structured recall, physical activity was assessed longitudinally during a period of 2 years in 194 postmenopausal women (90 randomized to 1 mg 17β-estradiol treatment daily and 104 randomized to placebo) in the Estrogen in the Prevention of Atherosclerosis Trial. The levels of physical activity were correlated with the serum sex hormone and the serum hormone-binding globulin levels in each treatment group. Among the placebo-treated women, total energy expenditure was positively associated with sex hormone-binding globulin (SHBG; P < 0.001) and inversely associated with testosterones (total, bioavailable, or free) and androstenedione (P < 0.001 for all), as well as with estradiol (P = 0.02). In estradiol-treated women, estradiol levels were inversely associated with total energy expenditure (P = 0.002) and weekly hours spent in moderate or more vigorous physical activity (P = 0.001). Physical activity is associated with lower serum levels of estradiol in both hormone therapy-treated and untreated women. In placebo-treated women only, physical activity is associated with reduced androgen levels and elevated SHBG levels.

  20. Sex differences and hormonal effects on gut microbiota composition in mice.

    PubMed

    Org, Elin; Mehrabian, Margarete; Parks, Brian W; Shipkova, Petia; Liu, Xiaoqin; Drake, Thomas A; Lusis, Aldons J

    2016-07-03

    We previously reported quantitation of gut microbiota in a panel of 89 different inbred strains of mice, and we now examine the question of sex differences in microbiota composition. When the total population of 689 mice was examined together, several taxa exhibited significant differences in abundance between sexes but a larger number of differences were observed at the single strain level, suggesting that sex differences can be obscured by host genetics and environmental factors. We also examined a subset of mice on chow and high fat diets and observed sex-by-diet interactions. We further investigated the sex differences using gonadectomized and hormone treated mice from 3 different inbred strains. Principal coordinate analysis with unweighted UniFrac distances revealed very clear effects of gonadectomy and hormone replacement on microbiota composition in all 3 strains. Moreover, bile acid analyses showed gender-specific differences as well as effects of gonodectomy, providing one possible mechanism mediating sex differences in microbiota composition.

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

    PubMed

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

    2018-02-01

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

  2. Prediagnostic circulating sex hormones are not associated with mortality for men with prostate cancer.

    PubMed

    Gershman, Boris; Shui, Irene M; Stampfer, Meir; Platz, Elizabeth A; Gann, Peter H; Sesso, Howard L; DuPre, Natalie; Giovannucci, Edward; Mucci, Lorelei A

    2014-04-01

    Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa). To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS). We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed. The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality. PCa cases were followed for a mean of 12.0±4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile. We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  3. In vitro effects of sex hormones in human meibomian gland epithelial cells.

    PubMed

    Schröder, Antje; Abrar, Daniel B; Hampel, Ulrike; Schicht, Martin; Paulsen, Friedrich; Garreis, Fabian

    2016-10-01

    Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (β-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -β (ERα, ERβ) and progesterone receptor (PR) in HMGEC. PR, ERα and ERβ expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERβ. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Sex hormones in early infancy seem to predict aspects of later language development.

    PubMed

    Schaadt, Gesa; Hesse, Volker; Friederici, Angela D

    2015-02-01

    Sex differences in the development of cognitive behavior such as language have long been of great research interest. Lately, researchers have started to associate language function and brain differences with diverse sex hormones (e.g., testosterone/estradiol). However, results concerning the impact of early postnatal sex hormone concentration on the child's later language development are rare. Here, we analyze the impact of testosterone and estradiol in girls and boys as well as their neurophysiological phonemic discrimination at age 5months on language development at age 4years. Interestingly, we found strong positive estradiol and negative testosterone impact on later language performance at age 4years, which was true for both girls and boys. These results demonstrate that postnatal sex hormone surge might be viewed as one factor determining later language development, independent of gender. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

    PubMed Central

    Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D

    2011-01-01

    Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329

  6. Sex differences in immune responses: Hormonal effects, antagonistic selection, and evolutionary consequences.

    PubMed

    Roved, Jacob; Westerdahl, Helena; Hasselquist, Dennis

    2017-02-01

    Males and females differ in both parasite load and the strength of immune responses and these effects have been verified in humans and other vertebrates. Sex hormones act as important modulators of immune responses; the male sex hormone testosterone is generally immunosuppressive while the female sex hormone estrogen tends to be immunoenhancing. Different sets of T-helper cells (Th) have important roles in adaptive immunity, e.g. Th1 cells trigger type 1 responses which are primarily cell-mediated, and Th2 cells trigger type 2 responses which are primarily humoral responses. In our review of the literature, we find that estrogen and progesterone enhance type 2 and suppress type 1 responses in females, whereas testosterone suppresses type 2 responses and shows an inconsistent pattern for type 1 responses in males. When we combine these patterns of generally immunosuppressive and immunoenhancing effects of the sex hormones, our results imply that the sex differences in immune responses should be particularly strong in immune functions associated with type 2 responses, and less pronounced with type 1 responses. In general the hormone-mediated sex differences in immune responses may lead to genetic sexual conflicts on immunity. Thus, we propose the novel hypothesis that sexually antagonistic selection may act on immune genes shared by the sexes, and that the strength of this sexually antagonistic selection should be stronger for type 2- as compared with type 1-associated immune genes. Finally, we put the consequences of sex hormone-induced effects on immune responses into behavioral and ecological contexts, considering social mating system, sexual selection, geographical distribution of hosts, and parasite abundance. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    EPA Science Inventory

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

  8. Effect of Nitric Oxide on Neointimal Hyperplasia based on Sex and Hormone Status

    PubMed Central

    Hogg, Melissa E.; Varu, Vinit N.; Vavra, Ashley K.; Popowich, Daniel A.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Saavedra, Joseph E.; Keefer, Larry K.; Kibbe, Melina R.

    2011-01-01

    Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have only been performed in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete media, male VSMC proliferated at greater rates than female VSMC. In hormone-deplete media, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male versus female VSMC. These findings correlated with greater G0/G1 cell cycle arrest and changes in cell cycle protein expression in male versus female VSMC following exposure to NO. Next, the rat carotid artery injury model was performed to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males versus females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in both sexes in castrated animals. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males than females and in hormonally-intact compared to castrated rats, indicating that the effect of NO in the vasculature may be sex- and hormone-dependent. PMID:21256959

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

    PubMed

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

    2017-03-01

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

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

    PubMed

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

    2018-01-01

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

  11. Formation of sex hormone transients resulting from attack of free radicals.

    PubMed

    Getoff, Nikola; Schittl, Heike; Gerschpacher, Marion; Quint, Ruth Maria

    2013-03-01

    Transients of the sex hormones testosterone (TES) and estrone (E1) exhibit an impact on the carcinogenesis of most prostate and breast cancer types. For elucidation of involved reaction mechanisms, in vitro, experiments using γ-ray for generation of attacking hormone transients and UV-light (λ=254 nm) for excitation of hormone molecules were applied. Materials and Methods. Experiments in vitro (Escherichia coli AB1157) incubated with TES and E1, individually as well as in mixture with vitamin C (electron donor), were performed under γ-irradiation in water-alcohol (40/60) medium for clarifying-up the reaction mechanism. The hormone degradation/regeneration processes were studied by high performance liquid chromatography analysis. Independently of hormone molecular structure, the determining factor for the biological properties, such as carcinogenity, were found to be based on the hormone transients. The biological ability of these, however, depends on the chemical properties of the species attacking the corresponding hormone. Hormone degradation can be, at least partly, converted into hormone regeneration by electron transfer from an electron donor (e.g. vitamin C), when available during the period of status nascendi of the hormone radicals.

  12. The role of central and peripheral hormones in sexual and violent recidivism in sex offenders.

    PubMed

    Kingston, Drew A; Seto, Michael C; Ahmed, Adekunle G; Fedoroff, Paul; Firestone, Philip; Bradford, John M

    2012-01-01

    Hormonal factors are important in multifactorial theories of sexual offending. The relationship between hormones and aggression in nonhumans is well established, but the putative effect in humans is more complex, and the direction of the effect is usually unclear. In this study, a large sample (N = 771) of adult male sex offenders was assessed between 1982 and 1996. Gonadotrophic (follicle-stimulating hormone and luteinizing hormone) and androgen hormone (total and free testosterone; T) levels were assessed at Time 1, along with indicators of sex drive and hostility. Individuals were observed up to 20 years in the community, with an average time at risk of 10.9 years (SD 4.6). Gonadotrophic hormones correlated positively with self-reported hostility and were better predictors of recidivism than was T (area under the curve (AUC), 0.58-0.63). Self-reported hostility emerged as a partial mediator of this relationship between gonadotrophic hormones and recidivism. These results point to a potentially new area of investigation for hormones and sexual aggression.

  13. Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice.

    PubMed

    Aguayo, Antonio; Martin, Camille S; Huddy, Timothy F; Ogawa-Okada, Maya; Adkins, Jamie L; Steele, Andrew D

    2018-01-01

    Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice.

  14. Sex differences in circadian food anticipatory activity are not altered by individual manipulations of sex hormones or sex chromosome copy number in mice

    PubMed Central

    Huddy, Timothy F.; Ogawa-Okada, Maya; Adkins, Jamie L.

    2018-01-01

    Recent studies in mice have demonstrated a sexual dimorphism in circadian entrainment to scheduled feeding. On a time restricted diet, males tend to develop food anticipatory activity (FAA) sooner than females and with a higher amplitude of activity. The underlying cause of this sex difference remains unknown. One study suggests that sex hormones, both androgens and estrogens, modulate food anticipatory activity in mice. Here we present results suggesting that the sex difference in FAA is unrelated to gonadal sex hormones. While a sex difference between males and females in FAA on a timed, calorie restricted diet was observed there were no differences between intact and gonadectomized mice in the onset or magnitude of FAA. To test other sources of the sex difference in circadian entrainment to scheduled feeding, we used sex chromosome copy number mutants, but there was no difference in FAA when comparing XX, XY-, XY-;Sry Tg, and XX;Sry Tg mice, demonstrating that gene dosage of sex chromosomes does not mediate the sex difference in FAA. Next, we masculinized female mice by treating them with 17-beta estradiol during the neonatal period; yet again, we saw no difference in FAA between control and masculinized females. Finally, we observed that there was no longer a sex difference in FAA for older mice, suggesting that the sex difference in FAA is age-dependent. Thus, our study demonstrates that singular manipulations of gonadal hormones, sex chromosomes, or developmental patterning are not able to explain the difference in FAA between young male and female mice. PMID:29385171

  15. Hormonal modulation of connective tissue homeostasis and sex differences in risk for osteoarthritis of the knee

    PubMed Central

    2013-01-01

    Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues and the sexual dimorphism in the role of inflammation at the cell, tissue, and organ levels. There is a need to determine if the risk for loss of knee function and integrity in females is restricted to only the knee or if sex-specific changes in other tissues play a role. This paper discusses these gaps in knowledge and suggests remedies. PMID:23374322

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

    PubMed

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

    2013-11-01

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

  17. Endogenous sex hormone exposure and repetitive element DNA methylation in healthy postmenopausal women.

    PubMed

    Boyne, Devon J; Friedenreich, Christine M; McIntyre, John B; Stanczyk, Frank Z; Courneya, Kerry S; King, Will D

    2017-12-01

    Epigenetic mechanisms may help to explain the complex and heterogeneous relation between sex hormones and cancer. Few studies have investigated the effects of sex hormones on epigenetic markers related to cancer risk such as levels of methylation within repetitive DNA elements. Our objective was to describe the association between endogenous sex hormone exposure and levels of LINE-1 and Alu methylation in healthy postmenopausal women. We nested a cross-sectional study within the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2006). Study participants consisted of healthy postmenopausal women who had never been diagnosed with cancer (n = 289). Sex hormone exposures included serum concentrations of estradiol, estrone, testosterone, androstenedione, and sex hormone-binding globulin. We estimated the participants' lifetime number of menstrual cycles (LNMC) as a proxy for cumulative exposure to ovarian sex hormones. Buffy coat samples were assessed for DNA methylation. Linear regression was used to model the associations of interest and to control for confounding. Both estradiol and estrone had a significant positive dose-response association with LINE-1 methylation. LNMC was associated with both LINE-1 and Alu methylation. Specifically, LNMC had a non-linear "U-shaped" association with LINE-1 methylation regardless of folate intake and a negative linear association with Alu methylation, but only amongst low folate consumers. Androgen exposure was not associated with either outcome. Current and cumulative estrogen exposure was associated with repetitive element DNA methylation in a group of healthy postmenopausal women. LINE-1 and Alu methylation may be epigenetic mechanisms through which estrogen exposure impacts cancer risk.

  18. Phthalate exposure and reproductive hormones and sex-hormone binding globulin before puberty - Phthalate contaminated-foodstuff episode in Taiwan.

    PubMed

    Wen, Hui-Ju; Chen, Chu-Chih; Wu, Ming-Tsang; Chen, Mei-Lien; Sun, Chien-Wen; Wu, Wen-Chiu; Huang, I-Wen; Huang, Po-Chin; Yu, Tzu-Yun; Hsiung, Chao A; Wang, Shu-Li

    2017-01-01

    In May 2011, a major incident involving phthalates-contaminated foodstuffs occurred in Taiwan. Di-(2-ethylhexyl) phthalate (DEHP) was added to foodstuffs, mainly juice, jelly, tea, sports drink, and dietary supplements. Concerns arose that normal pubertal development, especially reproductive hormone regulation in children, could be disrupted by DEHP exposure. To investigate the association between phthalate exposure and reproductive hormone levels among children following potential exposure to phthalate-tainted foodstuffs. A total of 239 children aged <12 years old were recruited from 3 hospitals in north, central, and south Taiwan after the episode. Structured questionnaires were used to collect the frequency and quantity of exposures to 5 categories of phthalate-contaminated foodstuffs to assess phthalate exposure in children. Urine samples were collected for the measurement of phthalate metabolites. The estimated daily intake of DEHP exposure at the time of the contamination incident occurred was calculated using both questionnaire data and urinary DEHP metabolite concentrations. Multiple regression analyses were applied to assess associations between phthalate exposure and reproductive hormone levels in children. After excluding children with missing data regarding exposure levels and hormone concentrations and girls with menstruation, 222 children were included in the statistical analyses. After adjustment for age and birth weight, girls with above median levels of urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and sum of mono-(2-ethylhexyl) phthalate concentrations had higher odds of above median follicle-stimulating hormone concentrations. Girls with above median estimated average daily DEHP exposures following the contamination episode also had higher odds of sex hormone-binding globulin above median levels. Phthalate exposure was associated with alterations of reproductive hormone levels in girls.

  19. Clinical review: Breast development in trans women receiving cross-sex hormones.

    PubMed

    Wierckx, Katrien; Gooren, Louis; T'Sjoen, Guy

    2014-05-01

    In trans women (male-to-female transsexual persons), cross-sex hormone therapy is administered to induce feminization. Breast development is an important part of feminization for most trans women. The aim of this study is to assess the effect of cross-sex hormone therapy on breast development in adult trans women. Additionally, we aimed to investigate the benefit or harm of administration of progestogens on breast development. A review of the literature in Embase, Medline, The Cochrane Library, PsycINFO databases, PubMed, and Web of Knowledge until January 2014. Effects of cross-sex hormone therapy and progestogens on breast development in trans women. Only few studies with low quality of evidence addressed these topics. The available evidence suggests that breast development is insufficient for the majority of trans women and that type and dosage of hormonal therapy seem not to have an important role on final breast size. Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions. © 2014 International Society for Sexual Medicine.

  20. Baby babbling at five months linked to sex hormone levels in early infancy.

    PubMed

    Quast, Anja; Hesse, Volker; Hain, Johannes; Wermke, Peter; Wermke, Kathleen

    2016-08-01

    Gender-dependent differentiation of the brain at morphological, neurochemical and functional levels of organization have been shown to be primarily controlled by sex differences in gonadal hormone concentrations during pre- and early postnatal development. Indeed, previous studies have reported that pre- and perinatal hormonal environments influence brain development and, consequently, affect sex specific long-term language outcomes. Herein, we investigated whether postnatal surges of estrogen (estradiol) and androgen (testosterone) may predict properties of pre-speech babbling at five months. This study is the first attempt to investigate a possible correlation between sex hormones and infants' articulatory skills during the typical postnatal period of extended hormonal activity known as 'mini-puberty.' A hierarchical, multiple regression approach revealed a significant, robust positive relationship between 4-week concentrations of estradiol and individual articulatory skills. In contrast, testosterone concentrations at five months negatively correlated with articulatory skills at the same age in both boys and girls. Our findings reinforce the assumption of the importance of sex hormones for auditory-vocal development towards language in human infants. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Sex hormone effects on autonomic mechanisms of thermoregulation in humans.

    PubMed

    Charkoudian, Nisha; Stachenfeld, Nina

    2016-04-01

    Autonomic mechanisms are fundamental to human physiological thermoregulation, and female reproductive hormones have substantial influences on several aspects of these mechanisms. Of these, the best recognized are the thermoregulatory responses that occur at menopause (hot flushes) and the changes in body temperature within the menstrual cycle which may help couples predict ovulation. Our goal in this brief review is to summarize current knowledge regarding the influences of reproductive hormones on autonomic mechanisms in human thermoregulation. In general, estrogens tend to promote lower body temperatures via augmentation of heat dissipation responses, whereas progesterone tends to promote higher body temperatures. Recent evidence suggests specific influences of estrogens on central autonomic nuclei involved in control of skin blood flow and sweating. Estrogens also augment vasodilation by direct effects on peripheral blood vessels. Influences of progesterone are less well understood, but include both centrally regulated changes in thermoregulatory set-point as well as and peripheral effects, including augmented vasoconstriction in the skin. We conclude with a brief discussion of thermoregulatory adjustments associated with changing hormone levels during menopause, pregnancy and polycystic ovary syndrome. Published by Elsevier B.V.

  2. Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women.

    PubMed

    Chavez-MacGregor, Mariana; van Gils, Carla H; van der Schouw, Yvonne T; Monninkhof, Evelyn; van Noord, Paulus A H; Peeters, Petra H M

    2008-03-01

    Lifetime cumulative number of menstrual cycles is related to breast cancer risk. The aim of this study is to investigate the relation between this index and serum sex hormone levels in postmenopausal women. Cross-sectional study including 860 naturally postmenopausal Dutch participants of the European Prospective Investigation into Cancer and Nutrition. Lifetime cumulative number of menstrual cycles was computed using questionnaire data on ages at menarche and menopause, number of pregnancies, breastfeeding, oral contraceptive use (OC) and regularity pattern. Measurements of hormones included estrone (E1), estradiol (E2), andostrenedione, testosterone, sex-hormone binding globulin (SHBG) and dehydroepiandrostenedione sulfate (DHEAS). The relation between the lifetime cumulative number of menstrual cycles and hormone levels was assessed using analysis of covariance. Relations between reproductive characteristics and hormone levels were also studied. Adjustments for characteristics at blood collection included age, years since menopause, BMI, hormone replacement therapy use, OC use, smoking habits, alcohol intake and physical activity were done. Lifetime cumulative number of cycles was related with SHBG; participants in the lowest category had higher SHBG levels. For the separate characteristics, DHEAS and androstenedione increased significantly with increasing age at menarche, while androstenedione and testosterone decreased with increasing age at menopause. For the parity characteristics, SHBG levels increased according to the number of live births. Lifetime cumulative number menstrual cycles was related only to SHBG. Therefore, free levels of estrogens or androgens may be related to this number of menstrual cycles estimate, reflecting lifetime exposure to ovarian hormones.

  3. Effects of male sex hormones on gender identity, sexual behavior, and cognitive function.

    PubMed

    Zhu, Yuan-shan; Cai, Li-qun

    2006-04-01

    Androgens, the male sex hormones, play an essential role in male sexual differentiation and development. However, the influence of these sex hormones extends beyond their roles in sexual differentiation and development. In many animal species, sex hormones have been shown to be essential for sexual differentiation of the brain during development and for maintaining sexually dimorphic behavior throughout life. The principals of sex determination in humans have been demonstrated to be similar to other mammals. However, the hormonal influence on sexual dimorphic differences in the nervous system in humans, sex differences in behaviors, and its correlations with those of other mammals is still an emerging field. In this review, the roles of androgens in gender and cognitive function are discussed with the emphasis on subjects with androgen action defects including complete androgen insensitivity due to androgen receptor mutations and 5alpha-reductase-2 deficiency syndromes due to 5alpha-reductase-2 gene mutations. The issue of the complex interaction of nature versus nurture is addressed.

  4. Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio)

    USGS Publications Warehouse

    Sharma, Prakash; Patino, Reynaldo

    2013-01-01

    We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent.

  5. Regulation of gonadal sex ratios and pubertal development by the thyroid endocrine system in zebrafish (Danio rerio).

    PubMed

    Sharma, Prakash; Patiño, Reynaldo

    2013-04-01

    We examined associations between thyroid condition, gonadal sex and pubertal development in zebrafish. Seventy-two-hour postfertilization larvae were reared in untreated medium or in the presence of goitrogens (sodium perchlorate, 0.82 mM; methimazole, 0.15 and 0.3 mM) or thyroxine (1 and 10 nM) for 30 days. Thyrocyte height, gonadal sex and gonadal development were histologically determined at 45 and 60 days postfertilization (dpf). Thyrocyte hypertrophy, an index of hypothyroidism, was observed at 45 and 60 dpf in perchlorate-treated but only at 45 dpf in methimazole-treated fish. Similarly, gonadal sex ratios were biased toward ovaries relative to control animals at 45 and 60 dpf in perchlorate-treated fish but only at 45 dpf in methimazole-treated fish. Gonadal sex ratios were biased toward testes at 45 and 60 dpf in thyroxine-treated fish. Spermatogenesis was delayed in testes from goitrogen-treated fish at 60 dpf relative to control values, but was unaffected in testes from thyroxine-treated individuals. Oogenesis seemed to be nonspecifically delayed in all treatments relative to control at 60 dpf. This study confirmed the previously reported association between hypothyroid condition and ovarian-skewed ratios, and hyperthyroid condition and testicular-skewed ratios, and also showed that male pubertal development is specifically delayed by experimental hypothyroidism. The simultaneous recovery from the hypothyroid and ovary-inducing effects of methimazole by 60 dpf (27 days post-treatment) suggests that the ovary-skewing effect of goitrogens is reversible when thyroid conditions return to basal levels before developmental commitment of gonadal sex. Conversely, the masculinizing effect of hyperthyroidism seems to be stable and perhaps permanent. Published by Elsevier Inc.

  6. Dmrt1 is necessary for male sexual development in zebrafish

    PubMed Central

    Webster, Kaitlyn A.; Schach, Ursula; Ordaz, Angel; Steinfeld, Jocelyn S.; Draper, Bruce W.; Siegfried, Kellee R.

    2018-01-01

    The dmrt1 (doublesex and mab-3 related transcription factor 1) gene is a key regulator of sex determination and/or gonadal sex differentiation across metazoan animals. This is unusual given that sex determination genes are typically not well conserved. The mechanisms by which zebrafish sex is determined have remained elusive due to the lack of sex chromosomes and the complex polygenic nature of sex determination in domesticated strains. To investigate the role of dmrt1 in zebrafish sex determination and gonad development, we isolated mutations disrupting this gene. We found that the majority of dmrt1 mutant fish develop as fertile females suggesting a complete male-to-female sex reversal in mutant animals that would have otherwise developed as males. A small percentage of mutant animals became males, but were sterile and displayed testicular dysgenesis. Therefore zebrafish dmrt1 functions in male sex determination and testis development. Mutant males had aberrant gonadal development at the onset of gonadal sex-differentiation, displaying reduced oocyte apoptosis followed by development of intersex gonads and failed testis morphogenesis and spermatogenesis. By contrast, female ovaries developed normally. We found that Dmrt1 is necessary for normal transcriptional regulation of the amh (anti-Müllerian hormone) and foxl2 (forkhead box L2) genes, which are thought to be important for male or female sexual development respectively. Interestingly, we identified one dmrt1 mutant allele that cooperates with a linked segregation distorter locus to generate an apparent XY sex determination mechanism. We conclude that dmrt1 is dispensable for ovary development but necessary for testis development in zebrafish, and that dmrt1 promotes male development by transcriptionally regulating male and female genes as has been described in other animals. Furthermore, the strong sex-ratio bias caused by dmrt1 reduction-of-function points to potential mechanisms through which sex

  7. Sex Hormones and Healthy Psychological Aging in Women

    PubMed Central

    Navarro-Pardo, Esperanza; Holland, Carol A.; Cano, Antonio

    2018-01-01

    Besides their key role in reproduction, estrogens have effects in several organs in the body, as confirmed by the identification of estrogen receptors (ER) in multiple tissues. Experimental evidence has shown that estrogens have significant impacts on the central nervous system (CNS), and a key question is to what extent the fall in estrogen levels in the blood that occurs with increasing age, particularly around and following the menopause, has an impact on the cognitive function and psychological health of women, specifically regarding mood. This review will consider direct effects of menopausal changes in estrogens on the brain, including cognitive function and mood. Secondary pathways whereby health factors affected by changes in estrogens may interact with CNS functions, such as cardiovascular factors, will be reviewed as well insofar as they also have an impact on cognitive function. Finally, because decline in estrogens may induce changes in the CNS, there is interest in clarifying whether hormone therapy may offer a beneficial balance and the impact of hormone therapy on cognition will also be considered. PMID:29375366

  8. Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

    PubMed Central

    Romero, María del Mar; Fernández-López, José Antonio; Remesar, Xavier; Alemany, Marià

    2012-01-01

    It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding. PMID:22479617

  9. Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria.

    PubMed

    Kranz, Georg S; Seiger, Rene; Kaufmann, Ulrike; Hummer, Allan; Hahn, Andreas; Ganger, Sebastian; Tik, Martin; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2017-04-15

    Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are - at least in part - responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Associations of lead and cadmium with sex hormones in adult males.

    PubMed

    Kresovich, Jacob K; Argos, Maria; Turyk, Mary E

    2015-10-01

    Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999-2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood lead was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

    PubMed Central

    Zárate, Sandra; Stevnsner, Tinna; Gredilla, Ricardo

    2017-01-01

    Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS) owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD). Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain. PMID:29311911

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2015-05-06

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

  14. nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation.

    PubMed

    Chen, Sijie; Zhang, Hefei; Wang, Fenghua; Zhang, Wei; Peng, Gang

    2016-09-15

    Sex determinations are diverse in vertebrates. Although many sex-determining genes and pathways are conserved, the mechanistic roles of these genes and pathways in the genetic sex determination are not well understood. DAX1 (encoded by the NR0B1 gene) is a vertebrate specific orphan nuclear receptor that regulates gonadal development and sexual determination. In human, duplication of the NR0B1 gene leads to male-to-female sex reversal. In mice, Nr0b1 shows both pro-testis and anti-testis functions. We generated inheritable nr0b1 mutation in the zebrafish and found the nr0b1 mutation caused homozygous mutants to develop as fertile males due to female-to-male sex reversal. The nr0b1 mutation did not increase Caspase-3 labeling nor tp53 expression in the developing gonads. Introduction of a tp53 mutation into the nr0b1 mutant did not rescue the sex-reversal phenotype. Further examination revealed reduction in cell proliferation and abnormal somatic cell differentiation in the nr0b1 mutant gonads at the undifferentiated and bi-potential ovary stages. Together, our results suggest nr0b1 regulates somatic cell differentiation and cell proliferation to ensure normal sex development in the zebrafish. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Population, sex and body size: determinants of behavioural variations and behavioural correlations among wild zebrafish Danio rerio.

    PubMed

    Roy, Tamal; Bhat, Anuradha

    2018-01-01

    This study (1) investigated variation among populations and the effects of sex and body size on boldness, activity and shoal-association tendency among wild zebrafish, and (2) tested for existence of correlations between behaviours, controlling for sex and body size. Individuals across four natural populations were tested for general activity in a novel situation, number of predator inspections undertaken and tendency to associate with a conspecific shoal in the presence of predators. Results showed a significant effect of population on boldness with a population from high-predation habitat being bolder than populations from low-predation habitats. Males showed significantly higher tendencies than females to associate with a conspecific shoal in the presence of predators. Further, a negative relationship was found between activity and boldness only within two low-predation populations. Individual body size had a strong effect on the activity-boldness relationship within the low-predation population from flowing water habitat. Smaller fish were bolder and less active while larger fish were more cautious and active. Overall, the results indicated that while population-level behavioural responses might be shaped by predation pressure, state-dependent factors could determine behavioural correlations among individuals within populations.

  16. Population, sex and body size: determinants of behavioural variations and behavioural correlations among wild zebrafish Danio rerio

    PubMed Central

    Roy, Tamal

    2018-01-01

    This study (1) investigated variation among populations and the effects of sex and body size on boldness, activity and shoal-association tendency among wild zebrafish, and (2) tested for existence of correlations between behaviours, controlling for sex and body size. Individuals across four natural populations were tested for general activity in a novel situation, number of predator inspections undertaken and tendency to associate with a conspecific shoal in the presence of predators. Results showed a significant effect of population on boldness with a population from high-predation habitat being bolder than populations from low-predation habitats. Males showed significantly higher tendencies than females to associate with a conspecific shoal in the presence of predators. Further, a negative relationship was found between activity and boldness only within two low-predation populations. Individual body size had a strong effect on the activity–boldness relationship within the low-predation population from flowing water habitat. Smaller fish were bolder and less active while larger fish were more cautious and active. Overall, the results indicated that while population-level behavioural responses might be shaped by predation pressure, state-dependent factors could determine behavioural correlations among individuals within populations. PMID:29410809

  17. Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women.

    PubMed

    Mason, Caitlin; De Dieu Tapsoba, Jean; Duggan, Catherine; Imayama, Ikuyo; Wang, Ching-Yun; Korde, Larissa A; Stanczyk, Frank; McTiernan, Anne

    2016-06-01

    The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program. Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL ("insufficient") were randomized to either weight loss + 2,000 IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend = 0.01), and larger decreases in free and bioavailable estradiol (Ptrend = 0.04, Ptrend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D ≥32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7 pg/mL), free testosterone (-0.8 vs -0.3 pg/mL), and bioavailable testosterone (-1.8 vs -0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss. Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25

  18. Clinical correlates of sex hormones in women: The study of health in Pomerania.

    PubMed

    Kische, Hanna; Gross, Stefan; Wallaschofski, Henri; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Haring, Robin

    2016-09-01

    Despite associations of sex hormones in women with increased cardiometabolic risk and mortality, the clinical correlates of altered sex hormone concentrations in women are less clearly understood. We investigated a broad range of clinical correlates of sex hormones in women from a large population-based sample. Data from 2560 women from two cohorts of the Study of Health in Pomerania were used. Stepwise multivariable regression models were implemented to investigate a broad range of behavioral, socio-demographic, and cardiometabolic clinical correlates related to total testosterone (TT), free testosterone (fT), androstenedione (ASD), dehydroepiandrosterone-sulfate (DHEAS), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG). Waist circumference and BMI (β-coefficient: -0.03; 95% CI: -0.04; 0.03) were inversely related to SHBG, and BMI was positively related to TT (β-coefficient: 0.005; 95% CI: 0.001; 0.009), fT, E1, and E2. Smoking was positively related to TT (β-coefficient: 0.04; 95% CI: 0.01; 0.06), ASD, and fT. Systolic blood pressure (TT: β-coefficient: 0.002; 95% CI: 0.001; 0.003), hypertension (TT: β-coefficient: 0.05; 95% CI: 0.003; 0.11), low-density lipoprotein (LDL) cholesterol (TT: β-coefficient: 0.02; 95% CI: 0.01; 0.05), and total cholesterol (TT: β-coefficient: -0.03; 95% CI: 0.01; 0.05) were positively related to TT and ASD. Finally, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) were positively related to fT, but inversely related to SHBG. Our population-based study, with sex hormone concentrations measured by liquid chromatography tandem mass spectrometry, revealed associations between clinical correlates including waist circumference, smoking, cohabitation, systolic blood pressure, cholesterol, and MetS with sex hormones. Thus, sex hormones and SHBG may play a role in the cardiovascular risk profile of women. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Effects of head down tilt upon cortisol and sex hormones

    NASA Astrophysics Data System (ADS)

    Strollo, Felice; Pecorelli, Lia; Uva, Bianca Maria; Masini, Maria Angela; More, Massimo; Strollo, Giovanna; Riondino, Giuseppe

    2005-08-01

    Real and modelled μG conditions seem to induce reversible testicular failure. Suitable onground simulation methods are anyway needed in order to better aim further studies in humans in space. A 5- hour head down tilt (5h-HDT) was therefore performed in 22 male and female healthy volunteers looking at adrenal and gonadal hormones as compared to 12 age- and gender- matched controls. Cortisol and A decreased significantly in both genders, being cortisol decrease less pronounced in women, while leptin, LH, testosterone, estradiol and estrone failed to do so. The authors conclude that a 5h-HDT is only acceptable for adrenal adaptation studies whole longer duration HDT protocols are needed for gonadal investigations.

  20. Caffeine and Blood Pressure Response: Sex, Age, and Hormonal Status

    PubMed Central

    Whitsett, Thomas L.; McKey, Barbara S.; Wilson, Michael F.; Vincent, Andrea S.; Everson-Rose, Susan A.; Lovallo, William R.

    2010-01-01

    Abstract Purpose The pressor effect of caffeine has been established in young men and premenopausal women. The effect of caffeine on blood pressure (BP) remains unknown in postmenopausal women and in relation to hormone replacement therapy (HRT) use. Materials and Methods In a randomized, 2-week cross-over design, we studied 165 healthy men and women in 6 groups: men and premenopausal women (35–-49 yrs) vs. men and postmenopausal women (50–-64 yrs), with postmenopausal women divided into those taking no hormone replacements (HR), estrogen alone, or estrogen and progesterone. Testing during one week of the study involved 6 days of caffeine maintenance at home (80 mg, 3x/day) followed by testing of responses to a challenge dose of caffeine (250 mg) in the laboratory. The other week involved ingesting placebos on maintenance and lab days. Resting BP responses to caffeine were measured at baseline and at 45 to 60 min following caffeine vs placebo ingestion, using automated monitors. Results Ingestion of caffeine resulted in a significant increase in systolic BP in all 6 groups (4 ± .6, p < 0.01). Diastolic BP significantly increased in response to caffeine in all (3 ± .4, p < 0.04) but the group of older men (2 ± 1.0, p = 0.1). The observed pressor responses to caffeine did not vary by age. Conclusions Caffeine resulted in an increase in BP in healthy, normotensive, young and older men and women. This finding warrants the consideration of caffeine in the lifestyle interventions recommended for BP control across the age span. PMID:20500126

  1. Association of sex hormones and glucose metabolism with the severity of multiple sclerosis.

    PubMed

    Triantafyllou, Nikolaos; Thoda, Pinelopi; Armeni, Eleni; Rizos, Demetrios; Kaparos, George; Augoulea, Areti; Alexandrou, Andreas; Creatsa, Maria; Tsivgoulis, Georgios; Artemiades, Artemios; Panoulis, Constantinos; Lambrinoudaki, Irene

    2016-09-01

    We evaluated possible associations between the severity of multiple sclerosis (MS) and levels of sex hormones as well as biochemical parameters in a sample of ambulatory patients. This cross-sectional study recruited 133 adults (52 men, 66 premenopausal and 15 postmenopausal women), with relapsing-remitting MS. Fasting venous blood samples were drawn for biochemical and hormonal evaluation. These parameters were tested for possible associations with MS severity, assessed using the Expanded Disability Status Scale (EDSS)-scores. Follicle-stimulating hormone correlated with mean EDSS scores (r = -0.369, p = 0.038) in the premenopausal subgroup. However, this association became non-significant in the age-adjusted multivariate analysis (p = 0.141; power = 67%, type α error 0.10). Free androgen exhibited a borderline negative effect on EDSS-scores in the subgroup of men (r = -0.367, p = 0.093), which was lost after adjusting for age and duration of disease (p = 0.192; statistical power = 93%, type α error 0.05). Levels of estradiol tended to affect disability status of postmenopausal women (normal-mild vs. severe impairment: 23.33 ± 11.73pg/mL vs. 14.74 ± 6.30pg/mL, p = 0.095). Levels of sex hormones or indices of glycemic metabolism did not differ between patients presenting with EDSS scores higher or lower than the median value. Sex hormones and indices of glucose metabolism exhibited only a middle effect on EDSS scoring, which was not independent from the presence of confounders like age and duration of MS. The present study highlights the need for additional research, in order to elucidate the role of sex hormones and insulin resistance in the course of MS.

  2. Association of hair dye use with circulating levels of sex hormones in premenopausal Japanese women.

    PubMed

    Nagata, Chisato; Wada, Keiko; Tsuji, Michiko; Hayashi, Makoto; Takeda, Noriyuki; Yasuda, Keigo

    2015-10-01

    Substances identified as animal carcinogens are no longer used as ingredients of hair dyes. However, hair dyes are diverse groups of chemicals, and certain compounds may affect endogenous sex hormone levels. We examined the association between hair dye use and sex hormone levels among premenopausal women. Study subjects were 431 premenopausal Japanese women who had regular menstrual cycles less than 40 days long. Information on the use of hair dyes or hair bleach, the type of hair coloring used, the duration of use and the frequency of application was collected using a self-administered questionnaire. Fasting plasma samples were obtained to measure estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle-stimulating hormone and luteinizing hormone. After controlling for covariates, the mean plasma total testosterone level was about 14% higher in women who had used hair dyes for 10 or more years than that among women who had never used them (P for trend = 0.02). A similar association was observed when the type of hair dye was restricted to permanent hair dyes. A higher frequency of applying non-permanent hair dyes was marginally significantly associated with higher total and free estradiol levels. Data suggest that long-term use of hair dyes may be associated with an increase in circulating testosterone levels. As this is, to our knowledge, the first study examining the association between hair dye use and sex hormone levels, replication of the results is required. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  3. Sex hormone concentrations and the risk of breast cancer recurrence in postmenopausal women without hot flashes.

    PubMed

    Emond, Jennifer A; Patterson, Ruth E; Natarajan, Loki; Laughlin, Gail A; Gold, Ellen B; Pierce, John P

    2011-05-01

    We examined if the reduced risk of breast cancer events seen among women without baseline hot flash symptoms in the Women's Healthy Eating and Living (WHEL) dietary intervention trial was related to changes in sex hormone concentrations. Baseline and year one concentrations of total and bioavailable estradiol, and testosterone and sex hormone-binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Cox proportional hazard models tested interaction terms between study arm and baseline hormone concentrations adjusted for study site, antiestrogen use, positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use. Sex hormone concentrations did not differ by study arm at baseline nor at year one. Twenty-two (9.8%) events occurred in the intervention arm versus 42 (18.9%) in the comparison arm (P = 0.009). Baseline bioavailable testosterone was significantly, positively associated with additional events (HR 1.69, 95% CI: 1.00-2.84; P = 0.049). There were significant interactions between the intervention and total (P = 0.015), and bioavailable (P = 0.050) testosterone: the intervention was more protective among participants with higher baseline total (HR 0.3, 95% CI: 0.2-0.7) or bioavailable (HR 0.4, 95% CI: 0.2-0.7) testosterone than for participants with lower baseline total (HR 0.8, 95% CI: 0.4-1.5) or bioavailable (HR 0.8, 95% CI: 0.4-1.5) testosterone. No significant effects were seen for estradiol or SHBG. The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone. Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence. ©2011 AACR.

  4. Association of sex hormones with incident 10-year cardiovascular disease and mortality in women.

    PubMed

    Schaffrath, Gotja; Kische, Hanna; Gross, Stefan; Wallaschofski, Henri; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Keevil, Brian G; Brabant, Georg; Haring, Robin

    2015-12-01

    The aims of this study were to ascertain whether women with high levels of serum total testosterone (TT) or low levels of sex hormone-binding globulin (SHBG) are more likely to develop cardiovascular disease (CVD), and to investigate potential associations between sex hormones and mortality (all-cause, as well as cause-specific) in the general population. Data on 2129 women with a mean age of 49.0 years were obtained from the population-based Study of Health in Pomerania over a median follow-up of 10.9 years. Associations of baseline levels of TT, SHBG, and rostenedione (ASD), and free testosterone (fT), and of the free androgen index (FAI), with follow-up CVD morbidity, as well as all-cause and CVD mortality, were analyzed using multivariable regression modeling. At baseline the prevalence rate of CVD was 17.8% (378 women) and the incidence of CVD over the follow-up was 50.9 per 1000 person-years. We detected an inverse association between SHBG and baseline CVD in age-adjusted models (relative risk per standard deviation increase: 0.83; 95% confidence interval: 0.74-0.93). We did not detect any significant associations between sex hormone concentrations and incident CVD in age- and multivariable-adjusted Poisson regression models. Furthermore, none of the sex hormones (TT, SHBG, ASD, fT, FAI) were associated with all-cause mortality. This population-based cohort study did not yield any consistent associations between sex hormones in women and incident CVD or mortality risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Prospective inverse associations of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress.

    PubMed

    Haring, Robin; Baumeister, Sebastian E; Völzke, Henry; Dörr, Marcus; Kocher, Thomas; Nauck, Matthias; Wallaschofski, Henri

    2012-01-01

    The suggested associations between sex hormone concentrations and inflammatory biomarkers in men originate from cross-sectional studies and small-scale clinical trials. But prior studies have not investigated longitudinal associations. Overall, 1344 men aged 20-79 years from the population-based cohort Study of Health in Pomerania were followed up for 5.0 (median) years. We used multivariable regression models to analyze cross-sectional and longitudinal associations of serum sex hormone concentrations (total testosterone [TT], sex hormone-binding globulin [SHBG], calculated free testosterone [free T], and dehydroepiandrosterone sulfate [DHEAS]) with biomarkers of inflammation (fibrinogen, high-sensitive C-reactive protein [hsCRP], and white blood cell count [WBC]) and oxidative stress (γ-glutamyl transferase [GGT]) using ordinary least square regression and generalized estimating equation models, respectively. Cross-sectional models revealed borderline associations of sex hormone concentrations with hsCRP, WBC, and GGT levels that were not retained after multivariable adjustment. Longitudinal multivariable analyses revealed an inverse association of baseline TT, free T, and DHEAS concentrations with change in fibrinogen levels (per SD decrement in TT, 0.25 [95% confidence interval, 0.04-0.45]; in free T, 0.30 [0.09-0.51]; and in DHEAS, 0.23 [0.11-0.36]). Furthermore, baseline DHEAS concentrations were inversely associated with change in WBC levels (per SD decrement, 0.53 [0.24-0.82]). Baseline TT, SHBG, free T, and DHEAS concentrations were also inversely associated with change in GGT after multivariable adjustment. The present study is the first to demonstrate prospective inverse associations between sex hormone concentrations and markers of inflammation and oxidative stress in men. Additional studies are warranted to elucidate potential mechanisms underlying the revealed associations.

  6. [Correlation of serum sex hormone levels with metabolic syndrome in elderly men].

    PubMed

    Xiao, H Y; Lu, Y H; Gong, Y P; Cheng, X L; Tian, H; Li, C L

    2016-03-08

    To investigate the relationship between sex hormones and metabolic syndrome (MS), as well as its components in elderly men. 1 505 elderly men (≥60 years old, mean age 75.4±9.7 years old) who participated in a routine health screening examination in PLA general hospital from May to June in 2012 were enrolled in this cross-sectional study. Serum lipids, glucose and sex hormones were measured along with body height, weight and blood pressure. Free testosterone (FT) and bioavailable testosterone (BT) were calculated. The correlation of serum sex hormones with the presence of MS and its components were analyzed. The prevalence of MS was 21.7% (326/1 505) in this study. Elderly men with MS had lower levels of sex hormone-binding globulin (SHBG), total testosterone (TT), FT and BT than those without MS. The levels of SHBG, TT, FT and BT were significantly lower in the overweight/obesity group, hyperglycemia group and dyslipidemia group than those in the respective control groups (P<0.05). Logistic regression analysis showed that the SHBG level was an independent risk factor for MS in elderly men(OR=0.977, 95%CI: 0.964-0.989, P<0.001), while the levels of TT, FT and BT were not associated with MS. The prevalence of MS gradually increased with decreasing of SHBG values (P<0.001). When comparing subjects in the lowest and highest quartile of SHBG, the former group demonstrated a 2.13-fold increase in the odds ratio for MS after adjusting for age, smoking, drinking and other sex hormone indices. In elderly men, lower SHBG level, not TT, FT or BT may be an independent predictor for the prevalence of MS, in which the mechanism requires further studies.

  7. Associations of lead and cadmium with sex hormones in adult males

    SciTech Connect

    Kresovich, Jacob K., E-mail: jkreso2@uic.edu; Argos, Maria; Turyk, Mary E.

    Heavy metal exposures are ubiquitous in the environment and their relation to sex hormones is not well understood. This paper investigates the associations between selected heavy metals (lead and cadmium) and sex hormones (testosterone, free testosterone, estradiol, free estradiol) as well as other major molecules in the steroid biosynthesis pathway (androstanedione glucuronide and sex-hormone binding globulin (SHBG)). Blood lead and cadmium were selected as biomarkers of exposure, and tested for associations in males using National Health and Nutritional Examination Survey (NHANES) data from 1999–2004. After adjustment for age, race, body mass index, smoking status, diabetes and alcohol intake, blood leadmore » was positively associated with testosterone and SHBG while blood cadmium was positively associated with SHBG. After controlling for additional heavy metal exposure, the associations between lead and testosterone as well as cadmium and SHBG remained significant. Furthermore, the association between blood lead and testosterone was modified by smoking status (P for interaction=0.011), diabetes (P for interaction=0.021) and blood cadmium (P for interaction=0.029). The association between blood cadmium and SHBG levels was modified by blood lead (P for interaction=0.004). This study is the most comprehensive investigation to date regarding the association between heavy metals and sex hormones in males. - Highlights: • We used a nationally representative dataset (NHANES) and employed sample weighting. • We examined associations between lead and cadmium with sex-hormone levels. • Blood lead level was positively associated with serum testosterone and SHBG levels. • Blood cadmium level was positively associated with SHBG levels, modified by lead. • Diabetes, smoking and cadmium modified lead and testosterone association.« less

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

    PubMed

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

    2011-11-09

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

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

    PubMed Central

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

    2011-01-01

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

  10. The influence of sex hormones on seizures in dogs and humans.

    PubMed

    Van Meervenne, Sofie A E; Volk, Holger A; Matiasek, Kaspar; Van Ham, Luc M L

    2014-07-01

    Epilepsy is the most common chronic neurological disorder in both humans and dogs. The effect of sex hormones on seizures is well documented in human medicine. Catamenial epilepsy is defined as an increase in frequency and severity of seizures during certain periods of the menstrual cycle. Oestradiol increases seizure activity and progesterone is believed to exhibit a protective effect. The role of androgens is controversial and there is a lack of research focusing on androgens and epilepsy. Indeed, little is known about the influence of sex hormones on epilepsy in dogs. Sterilisation is believed to improve seizure control, but no systematic research has been conducted in this field. This review provides an overview of the current literature on the influence of sex hormones on seizures in humans. The literature on idiopathic epilepsy in dogs was assessed to identify potential risk factors related to sex and sterilisation status. In general, there appears to be an over-representation of male dogs with idiopathic epilepsy but no explanation for this difference in prevalence between sexes has been reported. In addition, no reliable conclusions can be drawn on the effect of sterilisation due to the lack of focused research and robust scientific evidence. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Effect of gender and sex hormones on immune responses following shock.

    PubMed

    Angele, M K; Schwacha, M G; Ayala, A; Chaudry, I H

    2000-08-01

    Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

  12. Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones.

    PubMed

    Fernández-Guasti, A; Fiedler, J L; Herrera, L; Handa, R J

    2012-07-01

    The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Sex Differences in Anxiety Disorders: Interactions between Fear, Stress, and Gonadal Hormones

    PubMed Central

    Maeng, Lisa Y.; Milad, Mohammed R.

    2015-01-01

    Women are more vulnerable to stress- and fear-based disorders, such as anxiety and post-traumatic stress disorder. Despite the growing literature on this topic, the neural basis of these sex differences remains unclear, and the findings appear inconsistent. The neurobiological mechanisms of fear and stress in learning and memory processes have been extensively studied, and the crosstalk between these systems is beginning to explain the disproportionate incidence and differences in symptomatology and remission within these psychopathologies. In this review, we discuss the intersect between stress and fear mechanisms and their modulation by gonadal hormones and discuss the relevance of this information to sex differences in anxiety and fear-based disorders. Understanding these converging influences is imperative to the development of more effective, individualized treatments that take sex and hormones into account. PMID:25888456

  14. Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones.

    PubMed

    Maeng, Lisa Y; Milad, Mohammed R

    2015-11-01

    This article is part of a Special Issue "SBN 2014". Women are more vulnerable to stress- and fear-based disorders, such as anxiety and post-traumatic stress disorder. Despite the growing literature on this topic, the neural basis of these sex differences remains unclear, and the findings appear inconsistent. The neurobiological mechanisms of fear and stress in learning and memory processes have been extensively studied, and the crosstalk between these systems is beginning to explain the disproportionate incidence and differences in symptomatology and remission within these psychopathologies. In this review, we discuss the intersect between stress and fear mechanisms and their modulation by gonadal hormones and discuss the relevance of this information to sex differences in anxiety and fear-based disorders. Understanding these converging influences is imperative to the development of more effective, individualized treatments that take sex and hormones into account. Published by Elsevier Inc.

  15. Reporter sex and newspaper coverage of the adverse health effects of hormone therapy.

    PubMed

    Nelson, David E; Signorielli, Nancy

    2007-01-01

    Women have used hormone therapy (HT) to relieve menopausal symptoms for decades. Major studies published in JAMA in July 2002 demonstrated adverse health effects from hormone therapy, and the National Institutes of Health halted the Women's Health Initiative clinical trial several years early. We conducted a content analysis of 10 U.S. newspapers in July and August 2002 to examine the role of reporter sex on news coverage on HT. We found substantial sex differences in reporting about HT. Female reporters were much more likely than male reporters to include a self-help frame (66.7% vs. 30.8%, p = 0.002). Female reporters were also much more likely to use women in the public as sources in HT-related articles (33.9% vs. 10.0%, p = 0.039). Reporter sex may play a role in the selection and content of health news articles.

  16. Annual cycle of plasma luteinizing hormone and sex hormones in male and female mallards (Anas platyrhynchos)

    USGS Publications Warehouse

    Donham, R.S.

    1979-01-01

    Comparisons between 'wild'and 'game farm' mallards (Anas platyrhynchos) were made to assess the differences in the temporal changes of plasma hormones. Seasonal variation in the levels of immunoreactive luteinizing hormone (LH), testosterone, 5 -dihydrotestosterone (DHT), estrone, estradiol-17i?? and progesterone were measured in male and female mallards. In all birds there was a vernal increase in the concentrations of LH and testosterone in plasma which were correlated with the development of the testes and ovaries prior to and during the nesting season. The concentrations of estrogens in the plasma of the females were, in general, slightly higher during the nesting season but were much lower than the levels of testosterone. The highest levels of LH and testosterone in the females coincided precisely with the period of egg laying which occurred approximately one month earlier in game farm females than in wild females. The concentrations of LH and testosterone in the plasma of females decreased rapidly during incubation. In wild males, the decline in levels of these hormones temporally coincided with that of females. In contrast, plasma levels of LH and testosterone of males of the game farm stock remained elevated after the beginning of incubation in females to which they were paired. On the basis of these results and an examination of the literature, it appears that domestication results in: 1) increased reproductive potential through earlier initiation of nesting and by delay of the termination of reproduction until later in the summer; and 2) a decrease in the synchronization of the hormonal events supporting reproduction between the male and female of a pair. Testicular weights and plasma levels of testosterone become higher in game farm and domestic males than in the wild stock but levels of LH are similar.

  17. Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormones

    PubMed Central

    McHale, Matthew J.; Sarwar, Zaheer U.; Cardenas, Damon P.; Porter, Laurel; Salinas, Anna S.; Michalek, Joel E.; McManus, Linda M.

    2012-01-01

    Sex differences in skeletal muscle regeneration are controversial; comparisons of regenerative events between sexes have not been rigorously defined in severe injury models. We comprehensively quantified inflammation and muscle regeneration between sexes and manipulated sex-specific hormones to determine effects on regeneration. Cardiotoxin injury was induced in intact, castrated and ovariectomized female and male mice; ovariectomized mice were replaced with low- or high-dose 17-β estradiol (E2) or progesterone (P4). Extent of injury was comparable between intact mice, but females were more efficient in removal of necrotic debris, despite similar tissue levels of inflammatory cells and chemokines. Myofiber size during regeneration was equivalent between intact mice and after castration or ovariectomy (OVX) but was decreased (P < 0.001) in ovariectomized mice with high-dose E2 replacement. Intermuscular adipocytes were absent in uninjured muscle, whereas adipocyte area was increased among regenerated myofibers in all groups. Interestingly, intermuscular fat was greater (P = 0.03) in intact females at day 14 compared with intact males. Furthermore, castration increased (P = 0.01) and OVX decreased adipocyte accumulation. After OVX, E2, but not P4, replacement decreased (P ≤ 0.03) fat accumulation. In conclusion, sex-dependent differences in regeneration consisted of more efficient removal of necrosis and increased fat deposition in females with similar injury, inflammation, and regenerated myofiber size; high-dose E2 decreased myofiber size and fat deposition. Adipocyte accumulation in regenerating muscle was influenced by sex-specific hormones. Recovery following muscle injury was different between males and females, and sex-specific hormones contributed to these differences, suggesting that sex-specific treatments could be beneficial after injury. PMID:22116509

  18. A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Sex Hormone Therapy.

    PubMed

    Mueller, Sven C; Landré, Lionel; Wierckx, Katrien; T'Sjoen, Guy

    2017-01-01

    To date, research findings are inconsistent about whether the neuroanatomy in transgender persons resembles that of their natal sex or their gender identity. Moreover, few studies have examined the effects of long-term cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the present study was to examine neuroanatomical differences in transgender persons after prolonged cross-sex hormone therapy. Eighteen transgender men (female-to-male), 17 transgender women (male-to-female), 30 nontransgender men (natal men), and 27 nontransgender women (natal women) completed a high-resolution structural magnetic resonance imaging scan at 3 T. Eligibility criteria for transgender persons were gender-affirming surgery and at least 2 years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons were presence of psychiatric or neurological disorders. The mean neuroanatomical volume for the amygdala, putamen, and corpus callosum differed between transgender women and natal women but not between transgender women and natal men. Differences between transgender men and natal men were found in several brain structures, including the medial temporal lobe structures and cerebellum. Differences between transgender men and natal women were found in the medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism between nontransgender men and women included larger cerebellar volumes and a smaller anterior corpus callosum in natal men than in natal women. The results remained stable after correcting for additional factors including age, total intracranial volume, anxiety, and depressive symptoms. Neuroanatomical differences were region specific between transgender persons and their natal sex as well as their gender identity, raising the possibility of a localized influence of sex hormones on neuroanatomy. © 2016 S. Karger AG, Basel.

  19. Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

    PubMed

    Sömjen, D; Weisman, Y; Mor, Z; Harell, A; Kaye, A M

    1991-01-01

    We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.

  20. Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women.

    PubMed

    Zhao, Di; Guallar, Eliseo; Ouyang, Pamela; Subramanya, Vinita; Vaidya, Dhananjay; Ndumele, Chiadi E; Lima, Joao A; Allison, Matthew A; Shah, Sanjiv J; Bertoni, Alain G; Budoff, Matthew J; Post, Wendy S; Michos, Erin D

    2018-06-05

    Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results. The authors assessed the associations of sex hormone levels with incident CVD, coronary heart disease (CHD), and heart failure (HF) events among women without CVD at baseline. The authors studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). They used Cox hazard models to evaluate associations of sex hormones with each outcome, adjusting for demographics, CVD risk factors, and hormone therapy use. The mean age was 64.9 ± 8.9 years. During 12.1 years of follow-up, 283 CVD, 171 CHD, and 103 HF incident events occurred. In multivariable-adjusted models, the hazard ratio (95% confidence interval [CI]) associated with 1 SD greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: total testosterone: 1.14 (95% CI: 1.01 to 1.29), 1.20 (95% CI: 1.03 to 1.40), 1.09 (95% CI: 0.90 to 1.34); estradiol: 0.94 (95% CI: 0.80 to 1.11), 0.77 (95% CI: 0.63 to 0.95), 0.78 (95% CI: 0.60 to 1.02); and testosterone/estradiol ratio: 1.19 (95% CI: 1.02 to 1.40), 1.45 (95% CI: 1.19 to 1.78), 1.31 (95% CI: 1.01 to 1.70). Dehydroepiandrosterone and SHBG levels were not associated with these outcomes. Among post-menopausal women, a higher testosterone/estradiol ratio was associated with an elevated risk for incident CVD, CHD, and HF events, higher levels of testosterone associated with increased CVD and CHD, whereas higher estradiol levels were associated with a lower CHD risk. Sex hormone levels after menopause are associated with women's increased CVD risk later in life. Copyright © 2018 American College of Cardiology Foundation. Published by

  1. Perfluorinated compounds affect the function of sex hormone receptors.

    PubMed

    Kjeldsen, Lisbeth Stigaard; Bonefeld-Jørgensen, Eva Cecilie

    2013-11-01

    Perfluorinated compounds (PFCs) are a large group of chemicals used in different industrial and commercial applications. Studies have suggested the potential of some PFCs to disrupt endocrine homeostasis, increasing the risk of adverse health effects. This study aimed to elucidate mechanisms behind PFC interference with steroid hormone receptor functions. Seven PFCs [perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA)] were analyzed in vitro for their potential to affect estrogen receptor (ER) and androgen receptor (AR) transactivity as well as aromatase enzyme activity. The PFCs were assessed as single compounds and in an equimolar mixture. PFHxS, PFOS and PFOA significantly induced the ER transactivity, whereas PFHxS, PFOS, PFOA, PFNA and PFDA significantly antagonized the AR activity in a concentration-dependent manner. Moreover, PFDA weakly decreased the aromatase activity at a high test concentration. A mixture effect more than additive was observed on AR function. We conclude that five of the seven PFCs possess the potential in vitro to interfere with the function of the ER and/or the AR. The observed mixture effect emphasizes the importance of considering the combined action of PFCs in future studies to assess related health risks.

  2. The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment.

    PubMed

    Nota, Nienke M; Wiepjes, Chantal M; de Blok, Christel J M; Gooren, Louis J G; Peerdeman, Saskia M; Kreukels, Baudewijntje P C; den Heijer, Martin

    2018-04-23

    Benign brain tumours may be hormone sensitive. To induce physical characteristics of the desired gender, transgender individuals often receive cross-sex hormone treatment, sometimes in higher doses than hypogonadal individuals. To date, long-term (side) effects of cross-sex hormone treatment are largely unknown. In the present retrospective chart study we aimed to compare the incidence of common benign brain tumours: meningiomas, pituitary adenomas (non-secretive and secretive), and vestibular schwannomas in transgender individuals receiving cross-sex hormone treatment, with those reported in general Dutch or European populations. This study was performed at the VU University Medical Centre in the Netherlands and consisted of 2555 transwomen (median age at start of cross-sex hormone treatment: 31 years, interquartile range 23-41) and 1373 transmen (median age 23 years, interquartile range 18-31) who were followed for 23 935 and 11 212 person-years, respectively. For each separate brain tumour, standardized incidence ratios with 95% confidence intervals were calculated. In transwomen (male sex assigned at birth, female gender identity), eight meningiomas, one non-secretive pituitary adenoma, nine prolactinomas, and two vestibular schwannomas occurred. The incidence of meningiomas was higher in transwomen than in a general European female population (standardized incidence ratio 4.1, 95% confidence interval 1.9-7.7) and male population (11.9, 5.5-22.7). Similar to meningiomas, prolactinomas occurred more often in transwomen compared to general Dutch females (4.3, 2.1-7.9) and males (26.5, 12.9-48.6). Noteworthy, most transwomen had received orchiectomy but still used the progestogenic anti-androgen cyproterone acetate at time of diagnosis. In transmen (female sex assigned at birth, male gender identity), two cases of somatotrophinomas were observed, which was higher than expected based on the reported incidence rate in a general European population (incidence rate

  3. Salivary sex hormone measurement in a national, population-based study of older adults.

    PubMed

    Gavrilova, Natalia; Lindau, Stacy Tessler

    2009-11-01

    To describe the methods used for, correlates of cooperation with, and validity of in-home salivary specimens collected from older adults. Salivary specimens were collected between 2005 and 2006 during in-home interviews with a probability sample of 3,005 U.S. men and women, ages 57-85 years. Sex hormone levels were assessed by enzyme-linked immunoassay conducted at Salimetrics, LLC (State College, PA). Mean salivary sex hormone concentrations were compared by gender and in relation to medication use and health conditions. Self-collected saliva specimens were provided by 2,722 (90.6%) individuals; 95.8% of these were adequate for analysis. Black participants were significantly less likely than individuals of other racial/ethnic groups to provide a salivary specimen; age, gender, education, and self-rated health were not associated with participation. Mean testosterone levels were higher in men compared with women, and estradiol levels were higher in women using estrogens. Salivary hormone measurements obtained in the National Social Life, Health, and Aging Project (NSHAP) and other studies are of similar magnitude. NSHAP is the first large, population-based study of older adults to measure salivary estradiol, progesterone, dehydroepiandrosterone (DHEA), and, in women, testosterone. These data demonstrate a high cooperation rate with in-home salivary specimen collection from older adults and good validity of sex hormone measurements.

  4. Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development.

    PubMed

    Bramble, Matthew S; Lipson, Allen; Vashist, Neerja; Vilain, Eric

    2017-01-02

    Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α-reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α-reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Association between sex hormones and adiposity: qualitative differences in women and men in the multi-ethnic study of atherosclerosis.

    PubMed

    Mongraw-Chaffin, Morgana L; Anderson, Cheryl A M; Allison, Matthew A; Ouyang, Pamela; Szklo, Moyses; Vaidya, Dhananjay; Woodward, Mark; Golden, Sherita Hill

    2015-04-01

    Sex hormones may influence adipose tissue deposition, possibly contributing to sex disparities in cardiovascular disease risk. We hypothesized that associations of sex hormone levels with visceral and subcutaneous fat differ by sex. Participants were from the Multi-Ethnic Study of Atherosclerosis with sex hormone levels at baseline and visceral and subcutaneous fat measurements from computed tomography at visit 2 or 3 (n = 1835). Multivariable linear regression was used to investigate the relationships between sex hormones and adiposity. Testing for interaction by sex, race/ethnicity, and age was conducted. In adjusted models, there was a modest significant positive association between estradiol and visceral fat in both sexes (percent difference in visceral fat for 1% difference in hormone [95% confidence interval] in women, 5.44 [1.82, 9.09]; and in men, 8.22 [0.61, 16.18]). Higher bioavailable T was significantly associated with higher visceral and subcutaneous fat in women and with the reverse in men (women, 14.38 [10.23, 18.69]; men, -7.69 [-13.06, -1.00]). Higher dehydroepiandrosterone was associated with higher visceral fat in women (7.57 [1.71, 13.88]), but not in men (-2.47 [-8.88, 4.29]). Higher SHBG was associated with significantly lower levels of adiposity in both sexes (women, -24.42 [-28.11, -20.55]; men, -27.39 [-32.97, -21.34]). There was no significant interaction by race/ethnicity or age. Sex hormones are significantly associated with adiposity, and the associations of androgens differ qualitatively by sex. This heterogeneity may help explain the complexity of the contribution of sex hormones to sex differences in cardiovascular disease.

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

    PubMed

    Perry, Arlette C; Martin, Lorena

    2014-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-06-30

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

  9. Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

    PubMed

    Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

    2009-12-01

    The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

  10. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.

    PubMed

    Watts, Eleanor L; Appleby, Paul N; Albanes, Demetrius; Black, Amanda; Chan, June M; Chen, Chu; Cirillo, Piera M; Cohn, Barbara A; Cook, Michael B; Donovan, Jenny L; Ferrucci, Luigi; Garland, Cedric F; Giles, Graham G; Goodman, Phyllis J; Habel, Laurel A; Haiman, Christopher A; Holly, Jeff M P; Hoover, Robert N; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J; Mäenpää, Hanna O; Männistö, Satu; Metter, E Jeffrey; Milne, Roger L; Nomura, Abraham M Y; Oliver, Steven E; Parsons, J Kellogg; Peeters, Petra H; Platz, Elizabeth A; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A; Schenk, Jeannette M; Stanczyk, Frank Z; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S; Ziegler, Regina G; Allen, Naomi E; Key, Timothy J; Travis, Ruth C

    2017-01-01

    Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a

  11. Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men

    PubMed Central

    Appleby, Paul N.; Albanes, Demetrius; Black, Amanda; Chan, June M.; Chen, Chu; Cirillo, Piera M.; Cohn, Barbara A.; Cook, Michael B.; Donovan, Jenny L.; Ferrucci, Luigi; Garland, Cedric F.; Giles, Graham G.; Goodman, Phyllis J.; Habel, Laurel A.; Haiman, Christopher A.; Holly, Jeff M. P.; Hoover, Robert N.; Kaaks, Rudolf; Knekt, Paul; Kolonel, Laurence N.; Kubo, Tatsuhiko; Le Marchand, Loïc; Luostarinen, Tapio; MacInnis, Robert J.; Mäenpää, Hanna O.; Männistö, Satu; Metter, E. Jeffrey; Milne, Roger L.; Nomura, Abraham M. Y.; Oliver, Steven E.; Parsons, J. Kellogg; Peeters, Petra H.; Platz, Elizabeth A.; Riboli, Elio; Ricceri, Fulvio; Rinaldi, Sabina; Rissanen, Harri; Sawada, Norie; Schaefer, Catherine A.; Schenk, Jeannette M.; Stanczyk, Frank Z.; Stampfer, Meir; Stattin, Pär; Stenman, Ulf-Håkan; Tjønneland, Anne; Trichopoulou, Antonia; Thompson, Ian M.; Tsugane, Shoichiro; Vatten, Lars; Whittemore, Alice S.; Ziegler, Regina G.

    2017-01-01

    Introduction Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Methods Statistical analyses of individual participant data from 12,330 male controls aged 25–85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Results Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Conclusion Circulating sex hormones in men are strongly associated

  12. Sex- and sex hormone-related variations in energy-metabolic frontal brain asymmetries: A magnetic resonance spectroscopy study.

    PubMed

    Hjelmervik, Helene; Hausmann, Markus; Craven, Alexander R; Hirnstein, Marco; Hugdahl, Kenneth; Specht, Karsten

    2018-05-15

    Creatine is a key regulator of brain energy homeostasis, and well-balanced creatine metabolism is central in healthy brain functioning. Still, the variability of brain creatine metabolism is largely unattended in magnetic resonance spectroscopy (MRS) research. In the human brain, marginal sex differences in creatine levels have been found in the prefrontal cortex. It is however not known to what degree these sex differences are stable or change with varying gonadal hormone levels. The current study therefore investigated creatine in the prefrontal cortex across the menstrual cycle. In addition, we explored cerebral asymmetries. Creatine, Choline (Cho), N-acetylaspartate (NAA), Myo inositol (mI), and glutamate + glutamine (Glx) were assessed three times in 15 women and 14 men using MRS. Women were tested in cycle phases of varying hormone levels (menstrual, follicular, and luteal phase). Prefrontal creatine was found to change across the menstrual cycle, in a hemisphere-specific manner. Women in the follicular phase showed increased left prefrontal creatine accompanied with reduced right prefrontal creatine, while this asymmetry was not present in the luteal phase. In men, the creatine levels remained stable across three testing sessions. In general, both men and women were found to have higher creatine levels in the left as compared to the right prefrontal cortex. Exploratory analyses of other metabolites showed similar asymmetries in NAA, Cho, and mI, while Cho also showed a menstrual cycle effect. This is the first time that sex hormone-related changes in creatine metabolism have been demonstrated in the human brain. These findings may have important methodological implications for MRS research, as it supports previous concerns against uncritical usage of creatine as a reference measure for other metabolites, assumed to be invariant across individuals and conditions. Copyright © 2018 University of Bergen. Published by Elsevier Inc. All rights reserved.

  13. Relevance of stress and female sex hormones for emotion and cognition.

    PubMed

    ter Horst, J P; de Kloet, E R; Schächinger, H; Oitzl, M S

    2012-07-01

    There are clear sex differences in incidence and onset of stress-related and other psychiatric disorders in humans. Yet, rodent models for psychiatric disorders are predominantly based on male animals. The strongest argument for not using female rodents is their estrous cycle and the fluctuating sex hormones per phase which multiplies the number of animals to be tested. Here, we will discuss studies focused on sex differences in emotionality and cognitive abilities in experimental conditions with and without stress. First, female sex hormones such as estrogens and progesterone affect emotions and cognition, contributing to sex differences in behavior. Second, females respond differently to stress than males which might be related to the phase of the estrous cycle. For example, female rats and mice express less anxiety than males in a novel environment. Proestrus females are less anxious than females in the other estrous phases. Third, males perform in spatial tasks superior to females. However, while stress impairs spatial memory in males, females improve their spatial abilities, depending on the task and kind of stressor. We conclude that the differences in emotion, cognition and responses to stress between males and females over the different phases of the estrous cycle should be used in animal models for stress-related psychiatric disorders.

  14. 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

  15. The biological effects of sex hormones on rabbit articular chondrocytes from different genders.

    PubMed

    Chang, Shwu Jen; Kuo, Shyh Ming; Lin, Yen Ting; Yang, Shan-Wei

    2014-01-01

    The aim of this study was to investigate the biological effects of sex hormones (17β-estradiol and testosterone) on rabbit articular chondrocytes from different genders. We cultured primary rabbit articular chondrocytes from both genders with varying concentration of sex hormones. We evaluate cell proliferation and biochemical functions by MTT and GAG assay. The chondrocyte function and phenotypes were analyzed by mRNA level using RT-PCR. Immunocytochemical staining was also used to evaluate the generation of collagen-II. This study demonstrated that 17β-estradiol had greater positive regulation on the biological function and gene expressions of articular chondrocytes than testosterone, with the optimal concentrations of 10(-6) and 10(-7) M, particularly for female chondrocytes.

  16. Role of neuroinflammation and sex hormones in war-related PTSD.

    PubMed

    Mendoza, Cristhian; Barreto, George E; Ávila-Rodriguez, Marco; Echeverria, Valentina

    2016-10-15

    The susceptibility to develop posttraumatic stress disorder (PTSD) is greatly influenced by both innate and environmental risk factors. One of these factors is gender, with women showing higher incidence of trauma-related mental health disorders than their male counterparts. The evidence so far links these differences in susceptibility or resilience to trauma to the neuroprotective actions of sex hormones in reducing neuroinflammation after severe stress exposure. In this review, we discuss the impact of war-related trauma on the incidence of PTSD in civilian and military populations as well as differences associated to gender in the incidence and recovery from PTSD. In addition, the mutually influencing role of inflammation, genetic, and sex hormones in modulating the consequences derived from exposure to traumatic events are discussed in light of current evidence. Published by Elsevier Ireland Ltd.

  17. Sex hormone therapy and progression of cardiovascular disease in menopausal women.

    PubMed

    Alhurani, Rabe E; Chahal, C Anwar A; Ahmed, Ahmed T; Mohamed, Essa A; Miller, Virginia M

    2016-07-01

    One of the most controversial health decisions facing women is deciding upon the use of hormonal treatments for symptoms of menopause. This brief review focuses on the historical context of use of menopausal hormone treatments (MHT), summarizes results of major observational, primary and secondary prevention studies of MHT and cardiovascular (CV) outcomes, provides evidence for how sex steroids modulate CV function and identifies challenges for future research. As medicine enters an era of personalization of treatment options, additional research into sex differences in the aetiology of CV diseases will lead to better risk identification for CV disease in women and identify whether a woman might receive CV benefit from specific formulations and doses of MHT. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  18. Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

    PubMed

    Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

    2018-03-28

    This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

  19. Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women

    SciTech Connect

    Nagata, Chisato, E-mail: chisato@gifu-u.ac.jp

    Background: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. Methods: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. Results: In premenopausal women, the urinarymore » cadmium level either expressed in μg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in μg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. Conclusions: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. - Highlights: • Exposure to cadmium has been suspected as a risk factor for breast cancer. • Urinary cadmium and plasma sex-hormone levels were measured in Japanese women. • Urinary cadmium was inversely associated with testosterone in premenopausal women. • Urinary cadmium was inversely associated with estradiol in

  20. Sex hormones and systemic inflammation are modulators of the obese-asthma phenotype.

    PubMed

    Scott, H A; Gibson, P G; Garg, M L; Upham, J W; Wood, L G

    2016-07-01

    Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese-asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma. Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive-aged (<50 years old; n = 36) or older (>50 years old; n = 45). Thirteen (36.1%) reproductive-aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. Obese reproductive-aged females had higher sputum %neutrophils than nonobese reproductive-aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016); however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C-reactive protein and IL-6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive-aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015). This study suggests that sex hormones and systemic inflammation may be mediating the obese-asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive-aged females warrants further investigation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Optical properties of two types of sex hormones of the cyclopentenephenanthrene series

    NASA Astrophysics Data System (ADS)

    Meshalkin, Yu. P.; Artyukhov, V. Ya.; Pomogaev, V. A.

    2003-09-01

    The spectral and luminescent characteristics of estradiol and testosterone—two basic sex hormones of the cyclopentenephenanthrene series—are calculated by employing quantum-chemical methods. The results of calculations are in good agreement with experimental data. It is shown that fluorescence observed in estrogens is associated with the occurrence of the lowest ππ state, while the absence of fluorescence in androgens is attributed to the existence of the lowest nπ state, from which fluorescence is forbidden.

  2. Sex Hormones, Sleep, and Core Body Temperature in Older Postmenopausal Women

    PubMed Central

    Murphy, Patricia J.; Campbell, Scott S.

    2007-01-01

    Study Objectives: Assessment of relationships between polysomnographic sleep, sex hormones, and core body temperature in postmenopausal women. Design and Participants: Ten women aged 57 to 71 years, at least 5 years past menopause. Setting: Laboratory of Human Chronobiology at Weill Cornell Medical College. Interventions: N/A. Measurements and Results: Lower estradiol (E2) and higher luteinizing hormone (LH) levels were significantly correlated with indices of poor sleep quality. Relationships between LH and polysomnographic variables were more robust than those for E2. Significant increases from basal LH levels (i.e., LH pulses) occurred more frequently after sleep onset than prior to sleep onset, and 30 of 32 of these LH pulses occurred prior to long awakenings from sleep. In addition, higher body core temperature prior to and during sleep was significantly correlated with poorer sleep efficiency and higher LH levels. Conclusions: Most investigations of relationships between sleep, sex hormones, and body temperature have focused on perimenopausal women, menopausal phenomena such as hot flashes, the role of declining estrogen, and treatment with exogenous estrogen. The current results suggest that altered levels of both sex steroids and gonadotropins may contribute to sleep disturbance in older women and confirm the results of previous studies indicating that higher body core temperature is associated with poorer sleep quality, even in women without vasomotor symptoms. The findings also raise the possibility of alternate treatment avenues for menopause- and age-related sleep disturbance that focus on altering LH levels. Citation: Murphy PJ; Campbell SS. Sex hormones, sleep, and core body temperature in older postmenopausal women. SLEEP 2007;30(12):1788-1794. PMID:18246988

  3. Cutaneous microvascular response during local cold exposure - the effect of female sex hormones and cold perception.

    PubMed

    Cankar, Ksenija; Music, Mark; Finderle, Zare

    2016-11-01

    It is generally known that differences exist between males and females with regard to sensitivity to cold. Similar differences even among females in different hormonal balance might influence microvascular response during cold provocation testing. The aim of the present study was to measure sex hormone levels, cold and cold pain perception thresholds and compare them to cutaneous laser-Doppler flux response during local cooling in both the follicular and luteal phases of the menstrual cycle. In the luteal phase a more pronounced decrease in laser-Doppler flux was observed compared to follicular phase during local cooling at 15°C (significant difference by Dunnett's test, p<0.05). In addition, statistically significant correlations between progesterone level and laser-Doppler flux response to local cooling were observed during the follicular (R=-0.552, p=0.0174) and during the luteal phases (R=0.520, p=0.0271). In contrast, the correlation between estradiol level and laser-Doppler flux response was observed only in the follicular phase (R=-0.506, p=0.0324). Our results show that individual sensitivity to cold influences cutaneous microvascular response to local cooling; that microvascular reactivity is more pronounced during the luteal phase of the menstrual cycle; and that reactivity correlates with hormone levels. The effect of specific sex hormone levels is related to the cold-provocation temperature. Copyright © 2016. Published by Elsevier Inc.

  4. The role of plasma female sex hormones on gingivitis in pregnancy: a clinicobiochemical study.

    PubMed

    Nayak, Rashmita; Choudhury, Gopal Krishna; Prakash, Sandeep; Deshpande, Sumit; Ashok, K P; Spoorthi, B R

    2012-11-01

    To correlate the changes in the level of female sex hormones (progesterone, estrogen) in plasma with the changes in severity of gingivitis in various trimesters of pregnancy till the postparturition. This study comprised of 20 pregnant women with good oral hygiene who were followed up in each trimester till 3rd month of postpartum by screening their oral hygiene status following OHI-S index by Greene and Vermillion. Clinically to correlate gingivitis, gingival index by Loe and Sillness was carried out in each trimester till postpartum. For hormonal assay, blood sampling by venipuncture was done and quantative analysis of the hormones was done by ELISA test. The severity of gingivitis gradually increased and reached its peak in 3rd trimester followed by sudden decline in the severity in postpartum which correlated with gradual increase in the plasma level of progesterone and estrogen levels to reach their peak in the 3rd trimester and sudden fall after the postpartum. This study shows the role of female sex hormones in aggravating gingivitis to its peak in the 3rd trimester, even though the oral hygiene remains fairly good constantly. This study signifies the gingivitis status during different trimesters of pregnancy and postpartum indicating the general practitioner to take appropriate oral hygiene measures.

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

    PubMed

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

    2009-02-01

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

  6. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

    PubMed

    Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

  7. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones

    PubMed Central

    Stephens, Mary Ann C.; Mahon, Pamela B.; McCaul, Mary E.; Wand, Gary S.

    2016-01-01

    Summary Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to

  8. Assessment of the effects of sex and sex hormones on spatial cognition in adult rats using the Barnes maze.

    PubMed

    Locklear, M N; Kritzer, M F

    2014-07-01

    Although sex differences and hormone effects on spatial cognition are observed in humans and animals, consensus has not been reached regarding exact impact on spatial working or reference memory. Recent studies in rats suggest that stress and/or reward, which are often different in tasks used to assess spatial cognition, can contribute to the inconsistencies in the literature. To minimize the impact of these sex- and sex hormone-sensitive factors, we used the Barnes maze to compare spatial working memory, spatial reference memory and spatial learning strategy in adult male, female, gonadectomized (GDX) male, and GDX male rats supplemented with 17β-estradiol (E) or testosterone propionate (TP). Rats received four acquisition trials, four trials 24h later, and a single retention trial one week after. Males and females acquired the task during the first four trials and retained the task thereafter. In contrast, GDX rats took longer to acquire the task and showed retention deficits at 1week. All deficits were attenuated similarly by TP and E. Assessment of search patterns also showed that strategies in the males transitioned from random to spatially focused and eventually direct approaches to the goal. However, this transition was faster in control and GDX-TP than in GDX and GDX-E rats. In contrast, the females almost invariantly followed the maze edge in thigmotactic, serial searches. Thus, while Barnes maze reveals activational, in part estrogenic effects on spatial cognition in males, its amenability to animals' use of multiple strategies may limit its ability to resolve mnemonic differences across sex. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. The dermatoglyphic characteristics of transsexuals: is there evidence for an organizing effect of sex hormones.

    PubMed

    Slabbekoorn, D; van Goozen, S H; Sanders, G; Gooren, L J; Cohen-Kettenis, P T

    2000-05-01

    It has been proposed that gender identity and sexual orientation are influenced by the prenatal sex steroid milieu. Human dermatoglyphics and brain asymmetry have also been ascribed to prenatal hormone levels. This study investigated dermatoglyphics (total ridge count and finger ridge asymmetry) in 184 male-to-female transsexuals and 110 female-to-male transsexuals. In a subgroup, the relationship between dermatoglyphic asymmetry and spatial ability was tested. All investigations included controls. For all subjects hand preference and sexual orientation were noted. We hypothesized that the dermatoglyphics of male-to-female transsexuals would show similarities with control women and those of female-to-male transsexuals with control men. Our results showed a trend for a sex difference in total ridge count (P<.1) between genetic males and females, but no difference in directional asymmetry was found. Contrary to our expectations, the total ridge count and finger ridge asymmetry of transsexuals were similar to their genetic sex controls. Additionally, directional asymmetry was neither related to sexual orientation, nor to different aspects of spatial ability. In conclusion, we were unable to demonstrate that our chosen dermatoglyphic variables, total ridge count and finger ridge asymmetry are related to gender identity and sexual orientation in adult transsexuals. Hence, we found no support for a prenatal hormonal influence on these characteristics, at least insofar as dermatoglyphics may be regarded as a biological marker of organizing hormonal effects.

  10. 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

  11. Developmental link between sex and nutrition; doublesex regulates sex-specific mandible growth via juvenile hormone signaling in stag beetles.

    PubMed

    Gotoh, Hiroki; Miyakawa, Hitoshi; Ishikawa, Asano; Ishikawa, Yuki; Sugime, Yasuhiro; Emlen, Douglas J; Lavine, Laura C; Miura, Toru

    2014-01-01

    Sexual dimorphisms in trait expression are widespread among animals and are especially pronounced in ornaments and weapons of sexual selection, which can attain exaggerated sizes. Expression of exaggerated traits is usually male-specific and nutrition sensitive. Consequently, the developmental mechanisms generating sexually dimorphic growth and nutrition-dependent phenotypic plasticity are each likely to regulate the expression of extreme structures. Yet we know little about how either of these mechanisms work, much less how they might interact with each other. We investigated the developmental mechanisms of sex-specific mandible growth in the stag beetle Cyclommatus metallifer, focusing on doublesex gene function and its interaction with juvenile hormone (JH) signaling. doublesex genes encode transcription factors that orchestrate male and female specific trait development, and JH acts as a mediator between nutrition and mandible growth. We found that the Cmdsx gene regulates sex differentiation in the stag beetle. Knockdown of Cmdsx by RNA-interference in both males and females produced intersex phenotypes, indicating a role for Cmdsx in sex-specific trait growth. By combining knockdown of Cmdsx with JH treatment, we showed that female-specific splice variants of Cmdsx contribute to the insensitivity of female mandibles to JH: knockdown of Cmdsx reversed this pattern, so that mandibles in knockdown females were stimulated to grow by JH treatment. In contrast, mandibles in knockdown males retained some sensitivity to JH, though mandibles in these individuals did not attain the full sizes of wild type males. We suggest that moderate JH sensitivity of mandibular cells may be the default developmental state for both sexes, with sex-specific Dsx protein decreasing sensitivity in females, and increasing it in males. This study is the first to demonstrate a causal link between the sex determination and JH signaling pathways, which clearly interact to determine the

  12. Developmental Link between Sex and Nutrition; doublesex Regulates Sex-Specific Mandible Growth via Juvenile Hormone Signaling in Stag Beetles

    PubMed Central

    Gotoh, Hiroki; Miyakawa, Hitoshi; Ishikawa, Asano; Ishikawa, Yuki; Sugime, Yasuhiro; Emlen, Douglas J.; Lavine, Laura C.; Miura, Toru

    2014-01-01

    Sexual dimorphisms in trait expression are widespread among animals and are especially pronounced in ornaments and weapons of sexual selection, which can attain exaggerated sizes. Expression of exaggerated traits is usually male-specific and nutrition sensitive. Consequently, the developmental mechanisms generating sexually dimorphic growth and nutrition-dependent phenotypic plasticity are each likely to regulate the expression of extreme structures. Yet we know little about how either of these mechanisms work, much less how they might interact with each other. We investigated the developmental mechanisms of sex-specific mandible growth in the stag beetle Cyclommatus metallifer, focusing on doublesex gene function and its interaction with juvenile hormone (JH) signaling. doublesex genes encode transcription factors that orchestrate male and female specific trait development, and JH acts as a mediator between nutrition and mandible growth. We found that the Cmdsx gene regulates sex differentiation in the stag beetle. Knockdown of Cmdsx by RNA-interference in both males and females produced intersex phenotypes, indicating a role for Cmdsx in sex-specific trait growth. By combining knockdown of Cmdsx with JH treatment, we showed that female-specific splice variants of Cmdsx contribute to the insensitivity of female mandibles to JH: knockdown of Cmdsx reversed this pattern, so that mandibles in knockdown females were stimulated to grow by JH treatment. In contrast, mandibles in knockdown males retained some sensitivity to JH, though mandibles in these individuals did not attain the full sizes of wild type males. We suggest that moderate JH sensitivity of mandibular cells may be the default developmental state for both sexes, with sex-specific Dsx protein decreasing sensitivity in females, and increasing it in males. This study is the first to demonstrate a causal link between the sex determination and JH signaling pathways, which clearly interact to determine the

  13. Autonomic control of body temperature and blood pressure: influences of female sex hormones.

    PubMed

    Charkoudian, Nisha; Hart, Emma C J; Barnes, Jill N; Joyner, Michael J

    2017-06-01

    Female reproductive hormones exert important non-reproductive influences on autonomic regulation of body temperature and blood pressure. Estradiol and progesterone influence thermoregulation both centrally and peripherally, where estradiol tends to promote heat dissipation, and progesterone tends to promote heat conservation and higher body temperatures. Changes in thermoregulation over the course of the menstrual cycle and with hot flashes at menopause are mediated by hormonal influences on neural control of skin blood flow and sweating. The influence of estradiol is to promote vasodilation, which, in the skin, results in greater heat dissipation. In the context of blood pressure regulation, both central and peripheral hormonal influences are important as well. Peripherally, the vasodilator influence of estradiol contributes to the lower blood pressures and smaller risk of hypertension seen in young women compared to young men. This is in part due to a mechanism by which estradiol augments beta-adrenergic receptor mediated vasodilation, offsetting alpha-adrenergic vasoconstriction, and resulting in a weak relationship between muscle sympathetic nerve activity and total peripheral resistance, and between muscle sympathetic nerve activity and blood pressure. After menopause, with the loss of reproductive hormones, sympathetic nerve activity, peripheral resistance and blood pressure become more strongly related, and sympathetic nerve activity (which increases with age) becomes a more important contributor to the prevailing level of blood pressure. Continuing to increase our understanding of sex hormone influences on body temperature and blood pressure regulation will provide important insight for optimization of individualized health care for future generations of women.

  14. [Comparison between manual acupuncture and electroacupuncture for hot flashes and sex hormone of perimenopausal syndrome].

    PubMed

    Cao, Zhiliang; Tang, Jian; Xue, Yuting; Wang, Qiong; Li, Saiqun; Zhou, Youjun; Zhang, Wei

    2017-03-12

    To compare the effect and differences sex the influence of hormone levels of perimenopau-sal syndrome patients between manual acupuncture and electroacupuncture (EA). A total of 50 cases with perimenopausal syndrome were randomly assigned into an manual acupuncture group (27 cases) and an EA group (23 cases), and 1 case dropped in the EA group. The acupoints in the two groups were Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25), and Sanyinjiao (SP 6). Acupuncture with 3-time small and even manipulation of lifting, thrusting and twirling was used in the acupuncture group, once 10 min. EA with sparse-dense wave and 10 Hz/50 Hz was applied in the EA group for 30 min. The treatments in the two groups were for continuous 8 weeks (24 times in total), once the other day, 3 times a week. The scores of 24-hour hot flashes even, menopausal rating scale (MRS) and menopause-specific quality of life questionnaire (MENQOL) were recorded before treatment and after 4-week and 8-week treatment, as well as 12 and 24 weeks after treatment. Serum sex hormone levels were tested before and after 8-week treatment as well as 12 weeks after treatment, including serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estracliol (E 2 ). Compared with those before treatment, the 24-hour hot flashes even score, MRS and MENQOL scores were significantly lower after 4-week and 8-week treatments, 12 and 24 weeks after treatment (all P <0.05). All the above scores after 8-week treatment were lower than those after 4-week treatment (all P <0.05); and the scores 12 and 24 weeks after treatment were lower than those after 4-week and 8-week treatments (all P <0.05); all the scores after treatment were not significantly different at any time between the two groups (all P >0.05). Compared with those before treatment, serum FSH and E 2 apparently improved in the two groups after 8-week treatment and 12 weeks after treatment (all P <0.05). LH levels did not significantly change in the

  15. Sex and gonadal hormones in mouse models of Alzheimer’s disease: what is relevant to the human condition?

    PubMed Central

    2012-01-01

    Biologic sex and gonadal hormones matter in human aging and diseases of aging such as Alzheimer’s – and the importance of studying their influences relates directly to human health. The goal of this article is to review the literature to date on sex and hormones in mouse models of Alzheimer’s disease (AD) with an exclusive focus on interpreting the relevance of findings to the human condition. To this end, we highlight advances in AD and in sex and hormone biology, discuss what these advances mean for merging the two fields, review the current mouse model literature, raise major unresolved questions, and offer a research framework that incorporates human reproductive aging for future studies aimed at translational discoveries in this important area. Unraveling human relevant pathways in sex and hormone-based biology may ultimately pave the way to novel and urgently needed treatments for AD and other neurodegenerative diseases. PMID:23126652

  16. Sex hormones and breast cancer risk in premenopausal women: collaborative reanalysis of seven prospective studies

    PubMed Central

    2014-01-01

    Background The relationships of circulating concentrations of oestrogens, progesterone and androgens with breast cancer and related risk factors in premenopausal women are not well understood. Methods Individual data on prediagnostic sex hormone and sex hormone binding globulin (SHBG) concentrations were contributed by 7 prospective studies. Analyses were restricted to women who were premenopausal and under age 50 at blood collection, and to breast cancer cases diagnosed before age 50. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for breast cancer associated with hormone concentrations were estimated by conditional logistic regression in up to 767 cases and 1699 controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. The associations of hormones with risk factors for breast cancer in control women were examined by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle and body mass index (BMI). All statistical tests were two-sided. Findings ORs for breast cancer associated with a doubling in hormone concentration were 1.19 (95% CI 1.06–1.35) for oestradiol, 1.17 (1.03–1.33) for calculated free oestradiol, 1.27 (1.05–1.54) for oestrone, 1.30 (1.10–1.55) for androstenedione, 1.17 (1.04–1.32) for dehydroepiandrosterone sulphate, 1.18 (1.03–1.35) for testosterone and 1.08 (0.97–1.21) for calculated free testosterone. Breast cancer risk was not associated with luteal phase progesterone (for a doubling in concentration OR=1.00 (0.92–1.09)), and adjustment for other factors had little effect on any of these ORs. The cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors. Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women. PMID:23890780

  17. Juvenile exposure to vinclozolin shifts sex ratios and impairs reproductive capacity of zebrafish.

    PubMed

    Lor, Yer; Revak, Andrew; Weigand, Jenna; Hicks, Elisabeth; Howard, David R; King-Heiden, Tisha C

    2015-12-01

    Exposure to endocrine disruptors during critical periods of development can impact the sustainability of wild fish populations. Anti-androgenic compounds have received less attention, but are capable of modulating gonad differentiation and maturation, and impairing reproduction in fish. The fungicide vinclozolin (VZ) has been shown to impair reproduction in adult fish, but less is known about its effects following exposure earlier in development. Here we show that waterborne exposure to 400μg VZ/L during critical periods of sex differentiation (21-35 days post fertilization) permanently shifts sex ratios towards females, and alters the maturation of the gonad. Both fecundity and fertility were reduced, even when oogenesis and spermatogenesis recover and sperm motility is not altered. These results demonstrate the need to better understand the impacts of early exposure to anti-androgenic compounds on fish. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Factors associated with sex hormones and erectile dysfunction in male Taiwanese participants with obesity.

    PubMed

    Shi, Ming-Der; Chao, Jian-Kang; Ma, Mi-Chia; Hao, Lyh-Jyh; Chao, I-Chen

    2014-01-01

    Obesity has been receiving an increasing amount of attention recently, but investigations regarding the potential impact of obesity, sexual behaviors, and sex hormones on erectile dysfunction (ED) in men have not completely clarified the association. To identify the relationship between ED, sexual behavior, sexual satisfaction, sex hormones, and obesity in older adult males in Taiwan. Data were obtained from a baseline survey of 476 older adult males (≧40 years old). Their demographic data, body mass index (BMI), sex hormones, sexual desire, sexual satisfaction, and ED status were assessed. The International Index of Erectile Function-5 (IIEF-5), Sexual Desire Inventory (SDI), and Sexual Satisfaction Scale (SSS) were used to assess ED, sexual desire, and sexual satisfaction. In all, 476 men were available for analysis. The mean age of the sample was 51.34 ± 7.84 years (range 40 to 70 years). The IIEF total score had a mean of 19.44 ± 4.98; 264 (55.5%) subjects had ED, 250 (52.9%) were currently obese (BMI ≧27), and 297 (62.4%) had metabolic syndrome. The results showed an increased risk of ED among obese men and subjects with lower levels of sex hormones and lower sexual desire. Testosterone levels were lower in subjects with obesity (P < 0.001). Among the predictors of ED, obesity (odds ratio [OR] = 1.62, 95% CI = 1.07-2.44, P = 0.021), abnormal high sensitivity C-reactive protein (hs-CRP) (OR = 10.59, 95% CI = 4.70-23.87, P < 0.001), and lower serum full testosterone (OR = 3.27, 95% CI = 2.16-4.93, P < 0.001) were significantly independent factors. This study supports the idea of a close relationship between low levels of sex hormones, sexual desire, sexual satisfaction, obesity, and ED, and also shows that low free testosterone and hs-CRP may predict ED, even in obese populations. © 2013 International Society for Sexual Medicine.

  19. The effects of sex hormones on immune function: a meta-analysis.

    PubMed

    Foo, Yong Zhi; Nakagawa, Shinichi; Rhodes, Gillian; Simmons, Leigh W

    2017-02-01

    The effects of sex hormones on immune function have received much attention, especially following the proposal of the immunocompetence handicap hypothesis. Many studies, both experimental and correlational, have been conducted to test the relationship between immune function and the sex hormones testosterone in males and oestrogen in females. However, the results are mixed. We conducted four cross-species meta-analyses to investigate the relationship between sex hormones and immune function: (i) the effect of testosterone manipulation on immune function in males, (ii) the correlation between circulating testosterone level and immune function in males, (iii) the effect of oestrogen manipulation on immune function in females, and (iv) the correlation between circulating oestrogen level and immune function in females. The results from the experimental studies showed that testosterone had a medium-sized immunosuppressive effect on immune function. The effect of oestrogen, on the other hand, depended on the immune measure used. Oestrogen suppressed cell-mediated immune function while reducing parasite loads. The overall correlation (meta-analytic relationship) between circulating sex hormone level and immune function was not statistically significant for either testosterone or oestrogen despite the power of meta-analysis. These results suggest that correlational studies have limited value for testing the effects of sex hormones on immune function. We found little evidence of publication bias in the four data sets using indirect tests. There was a weak and positive relationship between year of publication and effect size for experimental studies of testosterone that became non-significant after we controlled for castration and immune measure, suggesting that the temporal trend was due to changes in these moderators over time. Graphical analyses suggest that the temporal trend was due to an increased use of cytokine measures across time. We found substantial heterogeneity

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

    PubMed

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

    2013-07-01

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

  1. Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.

    PubMed

    Zhang, Zhiwei; Lau, Shuk-Wa; Zhang, Lingling; Ge, Wei

    2015-10-01

    Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

  2. Analysis of the effects of sex hormone background on the rat choroid plexus transcriptome by cDNA microarrays.

    PubMed

    Quintela, Telma; Gonçalves, Isabel; Carreto, Laura C; Santos, Manuel A S; Marcelino, Helena; Patriarca, Filipa M; Santos, Cecília R A

    2013-01-01

    The choroid plexus (CP) are highly vascularized branched structures that protrude into the ventricles of the brain, and form a unique interface between the blood and the cerebrospinal fluid (CSF), the blood-CSF barrier, that are the main site of production and secretion of CSF. Sex hormones are widely recognized as neuroprotective agents against several neurodegenerative diseases, and the presence of sex hormones cognate receptors suggest that it may be a target for these hormones. In an effort to provide further insight into the neuroprotective mechanisms triggered by sex hormones we analyzed gene expression differences in the CP of female and male rats subjected to gonadectomy, using microarray technology. In gonadectomized female and male animals, 3045 genes were differentially expressed by 1.5-fold change, compared to sham controls. Analysis of the CP transcriptome showed that the top-five pathways significantly regulated by the sex hormone background are olfactory transduction, taste transduction, metabolism, steroid hormone biosynthesis and circadian rhythm pathways. These results represent the first overview of global expression changes in CP of female and male rats induced by gonadectomy and suggest that sex hormones are implicated in pathways with central roles in CP functions and CSF homeostasis.

  3. Analysis of the Effects of Sex Hormone Background on the Rat Choroid Plexus Transcriptome by cDNA Microarrays

    PubMed Central

    Quintela, Telma; Gonçalves, Isabel; Carreto, Laura C.; Santos, Manuel A. S.; Marcelino, Helena; Patriarca, Filipa M.; Santos, Cecília R. A.

    2013-01-01

    The choroid plexus (CP) are highly vascularized branched structures that protrude into the ventricles of the brain, and form a unique interface between the blood and the cerebrospinal fluid (CSF), the blood-CSF barrier, that are the main site of production and secretion of CSF. Sex hormones are widely recognized as neuroprotective agents against several neurodegenerative diseases, and the presence of sex hormones cognate receptors suggest that it may be a target for these hormones. In an effort to provide further insight into the neuroprotective mechanisms triggered by sex hormones we analyzed gene expression differences in the CP of female and male rats subjected to gonadectomy, using microarray technology. In gonadectomized female and male animals, 3045 genes were differentially expressed by 1.5-fold change, compared to sham controls. Analysis of the CP transcriptome showed that the top-five pathways significantly regulated by the sex hormone background are olfactory transduction, taste transduction, metabolism, steroid hormone biosynthesis and circadian rhythm pathways. These results represent the first overview of global expression changes in CP of female and male rats induced by gonadectomy and suggest that sex hormones are implicated in pathways with central roles in CP functions and CSF homeostasis. PMID:23585832

  4. The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

    ERIC Educational Resources Information Center

    Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

    2001-01-01

    Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

  5. 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…

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

    PubMed Central

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

    2014-01-01

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

  7. Effects of cross-sex hormone treatment on cortical thickness in transsexual individuals.

    PubMed

    Zubiaurre-Elorza, Leire; Junque, Carme; Gómez-Gil, Esther; Guillamon, Antonio

    2014-05-01

    Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatments are used to masculinize or feminize the bodies of female-to-male (FtMs) or male-to-female (MtFs) transsexuals, respectively. A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs. This study investigated 15 female-to-male (FtMs) and 14 male-to-female (MtFs) transsexuals prior and during at least six months of cross-sex hormone therapy treatment. Brain MRI imaging was performed in a 3-Tesla TIM-TRIO Siemens scanner. T1-weighted images were analyzed with FreeSurfer software to obtain CTh as well as subcortical volumetric values. Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy. After testosterone treatment, FtMs showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs, after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles. Testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system. © 2014 International Society for Sexual Medicine.

  8. Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers.

    PubMed

    Honda, Shozo; Loher, Phillipe; Shigematsu, Megumi; Palazzo, Juan P; Suzuki, Ryusuke; Imoto, Issei; Rigoutsos, Isidore; Kirino, Yohei

    2015-07-21

    Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER(-) breast cancer, AR(-) prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5'- and 3'-SHOT-RNAs, corresponding to 5'- and 3'-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3'-end, respectively. By devising a "cP-RNA-seq" method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5'-SHOT-RNAs. Furthermore, 5'-SHOT-RNA, but not 3'-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets.

  9. Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

    PubMed Central

    Honda, Shozo; Loher, Phillipe; Shigematsu, Megumi; Palazzo, Juan P.; Suzuki, Ryusuke; Imoto, Issei; Rigoutsos, Isidore; Kirino, Yohei

    2015-01-01

    Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER− breast cancer, AR− prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5′- and 3′-SHOT-RNAs, corresponding to 5′- and 3′-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3′-end, respectively. By devising a “cP-RNA-seq” method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5′-SHOT-RNAs. Furthermore, 5′-SHOT-RNA, but not 3′-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets. PMID:26124144

  10. Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

    SciTech Connect

    Ali, Imran; Engström, Annette; Vahter, Marie

    Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), inmore » 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.« less

  11. Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes.

    PubMed

    Chen, Xuqi; Wang, Lixin; Loh, Dawn H; Colwell, Christopher S; Taché, Yvette; Reue, Karen; Arnold, Arthur P

    2015-09-01

    We measured diurnal rhythms of food intake, as well as body weight and composition, while varying three major classes of sex-biasing factors: activational and organizational effects of gonadal hormones, and sex chromosome complement (SCC). Four Core Genotypes (FCG) mice, comprising XX and XY gonadal males and XX and XY gonadal females, were either gonad-intact or gonadectomized (GDX) as adults (2.5months); food intake was measured second-by-second for 7days starting 5weeks later, and body weight and composition were measured for 22weeks thereafter. Gonadal males weighed more than females. GDX increased body weight/fat of gonadal females, but increased body fat and reduced body weight of males. After GDX, XX mice had greater body weight and more fat than XY mice. In gonad-intact mice, males had greater total food intake and more meals than females during the dark phase, but females had more food intake and meals and larger meals than males during the light phase. GDX reduced overall food intake irrespective of gonad type or SCC, and eliminated differences in feeding between groups with different gonads. Diurnal phase of feeding was influenced by all three sex-biasing variables. Gonad-intact females had earlier onset and acrophase (peak) of feeding relative to males. GDX caused a phase-advance of feeding, especially in XX mice, leading to an earlier onset of feeding in GDX XX vs. XY mice, but earlier acrophase in GDX males relative to females. Gonadal hormones and SCC interact in the control of diurnal rhythms of food intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Association of sex hormones with physical, laboratory, and imaging markers of anthropometry in men and women from the general population

    PubMed Central

    Seyfart, Tom; Friedrich, Nele; Bülow, Robin; Wallaschofski, Henri; Völzke, Henry; Nauck, Matthias; Keevil, Brian G.; Haring, Robin

    2018-01-01

    Objectives The aim of this study was to evaluate the association of sex hormones with anthropometry in a large population-based cohort, with liquid chromatography-mass spectrometry (LCMS)-based sex hormone measurements and imaging markers. Study design/Main outcome measures Cross-sectional data from 957 men and women from the population-based Study of Health in Pomerania (SHIP) were used. Associations of a comprehensive panel of LCMS-measured sex hormones with anthropometric parameters, laboratory, and imaging markers were analyzed in multivariable regression models for the full sample and stratified by sex. Sex hormone measures included total testosterone (TT), free testosterone (fT), estrone and estradiol, androstenedione (ASD), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Domains of anthropometry included physical measures (body-mass-index (BMI), waist circumference, waist-to-height-ratio, waist-to-hip-ratio, and hip circumference), laboratory measures of adipokines (leptin and vaspin), and magnet resonance imaging-based measures (visceral and subcutaneous adipose tissue). Results In men, inverse associations between all considered anthropometric parameters with TT were found: BMI (β-coefficient, standard error (SE): -0.159, 0.037), waist-circumference (β-coefficient, SE: -0.892, 0.292), subcutaneous adipose tissue (β-coefficient, SE: -0.156, 0.023), and leptin (β-coefficient, SE: -0.046, 0.009). In women TT (β-coefficient, SE: 1.356, 0.615) and estrone (β-coefficient, SE: 0.014, 0.005) were positively associated with BMI. In analyses of variance, BMI and leptin were inversely associated with TT, ASD, and DHEAS in men, but positively associated with estrone. In women, BMI and leptin were positively associated with all sex hormones. Conclusion The present population-based study confirmed and extended previously reported sex-specific associations between sex hormones and various anthropometric markers of overweight and

  13. Association of sex hormones with physical, laboratory, and imaging markers of anthropometry in men and women from the general population.

    PubMed

    Seyfart, Tom; Friedrich, Nele; Kische, Hanna; Bülow, Robin; Wallaschofski, Henri; Völzke, Henry; Nauck, Matthias; Keevil, Brian G; Haring, Robin

    2018-01-01

    The aim of this study was to evaluate the association of sex hormones with anthropometry in a large population-based cohort, with liquid chromatography-mass spectrometry (LCMS)-based sex hormone measurements and imaging markers. Cross-sectional data from 957 men and women from the population-based Study of Health in Pomerania (SHIP) were used. Associations of a comprehensive panel of LCMS-measured sex hormones with anthropometric parameters, laboratory, and imaging markers were analyzed in multivariable regression models for the full sample and stratified by sex. Sex hormone measures included total testosterone (TT), free testosterone (fT), estrone and estradiol, androstenedione (ASD), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Domains of anthropometry included physical measures (body-mass-index (BMI), waist circumference, waist-to-height-ratio, waist-to-hip-ratio, and hip circumference), laboratory measures of adipokines (leptin and vaspin), and magnet resonance imaging-based measures (visceral and subcutaneous adipose tissue). In men, inverse associations between all considered anthropometric parameters with TT were found: BMI (β-coefficient, standard error (SE): -0.159, 0.037), waist-circumference (β-coefficient, SE: -0.892, 0.292), subcutaneous adipose tissue (β-coefficient, SE: -0.156, 0.023), and leptin (β-coefficient, SE: -0.046, 0.009). In women TT (β-coefficient, SE: 1.356, 0.615) and estrone (β-coefficient, SE: 0.014, 0.005) were positively associated with BMI. In analyses of variance, BMI and leptin were inversely associated with TT, ASD, and DHEAS in men, but positively associated with estrone. In women, BMI and leptin were positively associated with all sex hormones. The present population-based study confirmed and extended previously reported sex-specific associations between sex hormones and various anthropometric markers of overweight and obesity.

  14. Time required for sex change in teleost fishes: Hormonal dynamics shaped by selection.

    PubMed

    Yamaguchi, Sachi

    2016-10-21

    Bidirectional sex change is observed in many teleost fish. When social conditions change, the sex transition may take place over a period of several days to a few months. To understand temporal differences for sex change in either direction, I propose a simple mathematical model for the hormone-enzyme dynamics. Aromatase (P450arom) catalyses the synthesis of estradiol from testosterone. I assume that a change in social conditions for individuals affects the rates of production and degradation of P450arom. I then consider the evolution of parameters in the dynamics. Optimal parameter values are those that minimize total fitness cost, defined as the sum of fitness losses due to delay in being a functional male or female, and the cost of accelerated degradation of P450arom in changing from female to male sex. The model predicts that, in haremic species, sex change promotes a faster degradation of P450arom, resulting in a faster female-to-male transition than male-to-female transition. In contrast, in monogamous species, or with a small number of females, there is no benefit in a faster degradation of P450arom when changing to male, resulting in approximately equal timespans for sex change in either direction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

    PubMed Central

    Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

    2010-01-01

    Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507

  16. Sex differences in stress response circuitry activation dependent on female hormonal cycle.

    PubMed

    Goldstein, Jill M; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

    2010-01-13

    Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

  17. Waterborne fluoride exposure changed the structure and the expressions of steroidogenic-related genes in gonads of adult zebrafish (Danio rerio).

    PubMed

    Li, MeiYan; Cao, Jinling; Chen, Jianjie; Song, Jie; Zhou, Bingrui; Feng, Cuiping; Wang, Jundong

    2016-02-01

    Excessive fluoride in natural water ecosystem has been demonstrated to have adverse effects on reproductive system in humans and mammals, while the most vulnerable aquatic organisms were ignored. In this study, the effects of waterborne fluoride on growth performance, sex steroid hormone, histological structure, and the transcriptional profiles of sex steroid related genes were examined in both female and male zebrafish exposed to different concentrations of 0.79, 18.60, 36.83 mg L(-1) of fluoride for 30 and 60 d to investigate the effects of fluoride on reproductive system and the underlying toxic mechanisms caused by fluoride. The results showed that the body weight was remarkably decreased, the structure of ovary and testis were serious injured, and the T and E2 levels were significantly reduced in male zebrafish. The transcriptional profiles of steroidogenic related genes displayed phenomenal alterations, the expressions of pgr and cyp19a1a were significantly up-regulated, while the transcriptional levels of er, ar and hsd3β were decreased both in the ovary and testis, and hsd17β8 were down-regulated just in males. Taken together, these results demonstrated that fluoride could significantly inhibit the growth of zebrafish, and notably affect the reproductive system in both sex zebrafish by impairing the structure of ovary and testis, altering steroid hormone levels and steroidogenic genes expression related to the synthesis of sex hormones in zebrafish. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-01-01

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

  19. Age, sex, and gonadal hormones differently influence anxiety- and depression-related behavior during puberty in mice.

    PubMed

    Boivin, Josiah R; Piekarski, David J; Wahlberg, Jessica K; Wilbrecht, Linda

    2017-11-01

    Anxiety and depression symptoms increase dramatically during adolescence, with girls showing a steeper increase than boys after puberty onset. The timing of the onset of this sex bias led us to hypothesize that ovarian hormones contribute to depression and anxiety during puberty. In humans, it is difficult to disentangle direct effects of gonadal hormones from social and environmental factors that interact with pubertal development to influence mental health. To test the role of gonadal hormones in anxiety- and depression-related behavior during puberty, we manipulated gonadal hormones in mice while controlling social and environmental factors. Similar to humans, we find that mice show an increase in depression-related behavior from pre-pubertal to late-pubertal ages, but this increase is not dependent on gonadal hormones and does not differ between sexes. Anxiety-related behavior, however, is more complex during puberty, with differences that depend on sex, age, behavioral test, and hormonal status. Briefly, males castrated before puberty show greater anxiety-related behavior during late puberty compared to intact males, while pubertal females are unaffected by ovariectomy or hormone injections in all assays except the marble burying test. Despite this sex-specific effect of pubertal hormones on anxiety-related behavior, we find no sex differences in intact young adults, suggesting that males and females use separate mechanisms to converge on a similar behavioral phenotype. Our results are consistent with anxiolytic effects of testicular hormones during puberty in males but are not consistent with a causal role for ovarian hormones in increasing anxiety- and depression-related behavior during puberty in females. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Selective enhancement of NMDA receptor-mediated locomotor hyperactivity by male sex hormones in mice.

    PubMed

    van den Buuse, Maarten; Low, Jac Kee; Kwek, Perrin; Martin, Sally; Gogos, Andrea

    2017-09-01

    Altered glutamate NMDA receptor function is implicated in schizophrenia, and gender differences have been demonstrated in this illness. This study aimed to investigate the interaction of gonadal hormones with NMDA receptor-mediated locomotor hyperactivity and PPI disruption in mice. The effect of 0.25 mg/kg of MK-801 on locomotor activity was greater in male mice than in female mice. Gonadectomy (by surgical castration) significantly reduced MK-801-induced hyperlocomotion in male mice, but no effect of gonadectomy was seen in female mice or on amphetamine-induced locomotor hyperactivity. The effect of MK-801 on prepulse inhibition of startle (PPI) was similar in intact and castrated male mice and in ovariectomized (OVX) female mice. In contrast, there was no effect of MK-801 on PPI in intact female mice. Forebrain NMDA receptor density, as measured with [ 3 H]MK-801 autoradiography, was significantly higher in male than in female mice but was not significantly altered by either castration or OVX. These results suggest that male sex hormones enhance the effect of NMDA receptor blockade on psychosis-like behaviour. This interaction was not seen in female mice and was independent of NMDA receptor density in the forebrain. Male sex hormones may be involved in psychosis by an interaction with NMDA receptor hypofunction.

  1. Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social recognition.

    PubMed

    Gabor, Christopher S; Phan, Anna; Clipperton-Allen, Amy E; Kavaliers, Martin; Choleris, Elena

    2012-02-01

    Social Recognition is a fundamental skill that forms the basis of behaviors essential to the proper functioning of pair or group living in most social species. We review here various neurobiological and genetic studies that point to an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal hormones, estrogens and testosterone, in the mediation of social recognition. Results of a number of studies have shown that OT and its actions at the medial amygdala seem to be essential for social recognition in both sexes. Estrogens facilitate social recognition, possibly by regulating OT production in the hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect social recognition on a rapid time scale, likely through nongenomic actions. The mechanisms of these rapid effects are currently unknown but available evidence points at the hippocampus as the possible site of action. Male rodents seem to be more dependent on AVP acting at the level of the lateral septum for social recognition than female rodents. Results of various studies suggest that testosterone and its metabolites (including estradiol) influence social recognition in males primarily through the AVP V1a receptor. Overall, it appears that gonadal hormone modulation of OT and AVP regulates and fine tunes social recognition and those behaviors that depend upon it (e.g., social bonds, social hierarchies) in a sex specific manner. This points at an important role for these neuroendocrine systems in the regulation of the sex differences that are evident in social behavior and of sociality as a whole.

  2. Sex Hormones Modulate the Relationship Between Global Advantage, Lateralization, and Interhemispheric Connectivity in a Navon Paradigm

    PubMed Central

    Harris, TiAnni

    2018-01-01

    Abstract Sex, stimulus material, and attention condition have previously been related to global advantage (GA; faster responses to global targets than to local targets) on the one hand and lateralization during global–local processing on the other hand. It is presumed that the lateralization of brain functions is either related to the inhibitory influence of the dominant on the nondominant hemisphere or reduced excitation between hemispheres. However, a direct relationship between the GA and lateralization and interhemispheric connectivity has not been previously established. In this study, 58 participants (29 men, 29 naturally cycling women) completed a Navon paradigm, modulating attention condition (divided vs. focused) and stimulus material (letters vs. shapes) during functional magnetic resonance imaging. The size of the GA effect, lateralization indices, interhemispheric connectivity, and sex hormone levels were assessed. In summary, this study suggests that interhemispheric connectivity during global–local processing is affected by sex and material. Furthermore, the relationship between interhemispheric connectivity, lateralization, and behavior was modulated by sex and sex hormones. Results suggest (1) differential roles of interhemispheric connectivity for lateralization in men and women and (2) differential roles of lateralization for behavior in men and women. Importantly, the classic assumption that a more negative connectivity leads to stronger lateralization, which in turn leads to a stronger GA effect, was observed in men, whereas the opposite pattern was found in women. The relationship between connectivity and lateralization was mediated through testosterone levels, whereas the relationship between lateralization and behavior was mediated through progesterone levels. Results are discussed in light of differential functions of inhibitory and excitatory interhemispheric processes in men and women. PMID:29226703

  3. Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

    PubMed

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

    2013-11-01

    Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

  4. Race and Sex Differences in Small-Molecule Metabolites and Metabolic Hormones in Overweight and Obese Adults

    PubMed Central

    Patel, Mahesh J.; Batch, Bryan C.; Svetkey, Laura P.; Bain, James R.; Turer, Christy Boling; Haynes, Carol; Muehlbauer, Michael J.; Stevens, Robert D.; Newgard, Christopher B.

    2013-01-01

    Abstract In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, p<0.0001), factor 6 (long-chain acylcarnitines, p<0.01), and factor 2 (medium-chain dicarboxylated acylcarnitines, p<0.0001) were higher in males vs. females; factor 6 levels were higher in Caucasians vs. African Americans (p<0.0001). Significant differences were also observed in hormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones. PMID:24117402

  5. Race and sex differences in small-molecule metabolites and metabolic hormones in overweight and obese adults.

    PubMed

    Patel, Mahesh J; Batch, Bryan C; Svetkey, Laura P; Bain, James R; Turer, Christy Boling; Haynes, Carol; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Shah, Svati H

    2013-12-01

    In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, p<0.0001), factor 6 (long-chain acylcarnitines, p<0.01), and factor 2 (medium-chain dicarboxylated acylcarnitines, p<0.0001) were higher in males vs. females; factor 6 levels were higher in Caucasians vs. African Americans (p<0.0001). Significant differences were also observed in hormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones.

  6. Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes.

    PubMed

    Ruth, Katherine S; Campbell, Purdey J; Chew, Shelby; Lim, Ee Mun; Hadlow, Narelle; Stuckey, Bronwyn G A; Brown, Suzanne J; Feenstra, Bjarke; Joseph, John; Surdulescu, Gabriela L; Zheng, Hou Feng; Richards, J Brent; Murray, Anna; Spector, Tim D; Wilson, Scott G; Perry, John R B

    2016-02-01

    Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10(-8)), with minor allele frequencies of 1.3-23.9%. Novel signals included variants for progesterone (P=7.68 × 10(-12)), oestradiol (P=1.63 × 10(-8)) and FAI (P=1.50 × 10(-8)). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10(-8)) and LH (P=3.94 × 10(-9)) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10(-14)) and progesterone (P=6.09 × 10(-14)). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.

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

    PubMed

    Little, Anthony C

    2013-10-01

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

  8. Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring.

    PubMed

    Zhao, Mei; Yuan, Li; Yuan, Man-Man; Huang, Li-Li; Su, Chang; Chen, Yuan-Hua; Yang, Yu-Ying; Hu, Yan; Xu, De-Xiang

    2018-04-01

    An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 μg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERβ expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to

  9. Influence of polluted SY River on child growth and sex hormones.

    PubMed

    Tang, Chun Yu; Li, An Qi; Guan, Yong Bo; Li, Yan; Cheng, Xue Min; Li, Ping; Li, Shi Qun; Luo, Yi Xin; Huang, Qi; Chen, Hong Yang; Cui, Liu Xin

    2012-06-01

    To investigate the influence of the polluted SY River on children's growth and sex hormones, and provide scientific data for assessment of the polluted status of the SY River. The study areas were selected randomly from the SY River Basin. Lead (Pb), mercury (Hg), arsenic (As), phthalates (DEP, DBP, DMP, DEHP), and bisphenol A (BPA) were measured both in the river water and in the drinking water. School children were selected by cluster sampling (n=154). Physical development indexes (height, weight, bust-circumference, and skinfold thickness) and sex hormones [testosterone (T) and estradiol (E2)] were measured for all the children. The contents of Pb and Hg exceeded Class V standards of surface water quality in each section of the river and other indicators exceeded Class III. Compared to the control area, the concentrations of Pb, Hg, As, BPA, DEP, and DBP in the drinking water were significantly higher than in the polluted area (P<0.05). Children from the control area had significantly lower E2 and T than children from the polluted area (P<0.05). Among anthropometric results, only skinfold thickness had statistically significant difference between the two groups (P<0.05), while the other indexes showed no significant differences between the two groups (P>0.05). The drinking water has been polluted by the SY River and affected serum sex hormone levels of children living in the polluted area. Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

  10. Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack.

    PubMed

    Li, Xiao-Yu; Wang, Xiao-Yun

    2017-03-01

    To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups. Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.

  11. Evidence for Gating Roles of Protein Kinase A and Protein Kinase C in Estradiol-Induced Luteinizing Hormone Receptor (lhcgr) Expression in Zebrafish Ovarian Follicle Cells

    PubMed Central

    Liu, Ka-Cheuk; Ge, Wei

    2013-01-01

    Estradiol (E2) stimulates luteinizing hormone receptor (lhcgr) expression in zebrafish follicle cells via nuclear estrogen receptors (nERs) that are likely expressed on the membrane, and lhcgr responds to E2 in a biphasic manner during 24-h treatment. These observations raise an interesting question on the signaling mechanism underlying E2 regulation, in particular the biphasic response of lhcgr expression. In the present study, we demonstrated that E2 regulation of lhcgr was significantly influenced by the activity of cAMP-PKA pathway. Activation of cAMP-PKA pathway by forskolin or db-cAMP suppressed E2-stimulated lhcgr expression in short-term (3 h) but enhanced its effect in long-term (24 h), suggesting differential roles of PKA at these two phases of lhcgr response. PKA inhibitor H89 showed reversed effects. In contrast, PKC pathway had consistent permissive effect on E2-induced lhcgr expression as evidenced by strong inhibition of E2 effect by PKC inhibitors GF109203X and Ro-31-8220 at both 3 and 24 h. One of the mechanisms by which PKA and PKC gated E2 effect might be through regulating nERs, particularly esr2a. Despite the strong influence of PKA and PKC, our data did not suggest direct mediating roles for these two pathways in E2 stimulation of lhcgr expression; yet they likely play critical gating roles in E2 signal transduction. As a follow-up study to our previous report on E2 regulation of gonadotropin receptors in the zebrafish ovary, the present study provides further evidence for the involvement of classical intracellular signal transduction pathways in E2 stimulation of lhcgr expression in the follicle cells. PMID:23658740

  12. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  13. Effects of sex, menstrual cycle phase, and endogenous hormones on cognition in schizophrenia.

    PubMed

    Rubin, Leah H; Carter, C Sue; Drogos, Lauren L; Pournajafi-Nazarloo, Hossein; Sweeney, John A; Maki, Pauline M

    2015-08-01

    In women with schizophrenia, cognition has been shown to be enhanced following administration of hormone therapy or oxytocin. We examined how natural hormonal changes across the menstrual cycle influence cognition in women with schizophrenia. We hypothesized that female patients would perform worse on "female-dominant" tasks (verbal memory/fluency) and better on "male-dominant" tasks (visuospatial) during the early follicular phase (low estradiol and progesterone) compared to midluteal phase (high estradiol and progesterone) in relation to estradiol but not progesterone. Fifty-four women (23 with schizophrenia) completed cognitive assessments and provided blood for sex steroid assays and oxytocin at early follicular (days 2-4) and midluteal (days 20-22) phases. Men were included to verify the expected pattern of sex differences on cognitive tests. Expected sex differences were observed on "female-dominant" and "male-dominant" tasks (p<0.001), but the magnitude of those differences did not differ between patients and controls (p=0.44). Cognitive performance did not change across the menstrual cycle on "female-dominant" or "male-dominant" tasks in either group. Estradiol and progesterone levels were unrelated to cognitive performance. Oxytocin levels did not change across the menstrual cycle but were positively related to performance on "female-dominant" tasks in female patients only (p<0.05). Sex differences in cognitive function are preserved in schizophrenia. Oxytocin levels do not change across the cycle, but relate to enhanced performance on female dominant tests in women. Physiological levels of oxytocin may thus have a more powerful benefit in some cognitive domains than estrogens in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. EFFECT OF ACUTE STRESS ON PLASMA CONCENTRATIONS OF SEX AND STRESS HORMONES IN JUVENILE ALLIGATORS LIVING IN CONTROL AND CONTAMINATED LAKES

    EPA Science Inventory

    Environmental contaminants can act as stressors, inducing elevated circulating concentrations of stress hormones such as corticosterone and cortisol. Development in contaminated eggs has been reported to modify circulating sex steroid hormone concentrations in alligators (Alligat...

  15. The effects of age, sex, and hormones on emotional conflict-related brain response during adolescence

    PubMed Central

    Cservenka, Anita; Stroup, Madison L.; Etkin, Amit; Nagel, Bonnie J.

    2015-01-01

    While cognitive and emotional systems both undergo development during adolescence, few studies have explored top-down inhibitory control brain activity in the context of affective processing, critical to informing adolescent psychopathology. In this study, we used functional magnetic resonance imaging to examine brain response during an Emotional Conflict (EmC) Task across 10–15-year-old youth. During the EmC Task, participants indicated the emotion of facial expressions, while disregarding emotion-congruent and incongruent words printed across the faces. We examined the relationships of age, sex, and gonadal hormones with brain activity on Incongruent vs. Congruent trials. Age was negatively associated with middle frontal gyrus activity, controlling for performance and movement confounds. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Testosterone was negatively related with frontal and striatal brain response in males, and cerebellar and precuneus response in females. Estradiol was negatively related with fronto-cerebellar, cingulate, and precuneus brain activity in males, and positively related with occipital response in females. To our knowledge, this is the first study reporting the effects of age, sex, and sex steroids during an emotion-cognition task in adolescents. Further research is needed to examine longitudinal development of emotion-cognition interactions and deviations in psychiatric disorders in adolescence. PMID:26175008

  16. The effects of age, sex, and hormones on emotional conflict-related brain response during adolescence.

    PubMed

    Cservenka, Anita; Stroup, Madison L; Etkin, Amit; Nagel, Bonnie J

    2015-10-01

    While cognitive and emotional systems both undergo development during adolescence, few studies have explored top-down inhibitory control brain activity in the context of affective processing, critical to informing adolescent psychopathology. In this study, we used functional magnetic resonance imaging to examine brain response during an Emotional Conflict (EmC) Task across 10-15-year-old youth. During the EmC Task, participants indicated the emotion of facial expressions, while disregarding emotion-congruent and incongruent words printed across the faces. We examined the relationships of age, sex, and gonadal hormones with brain activity on Incongruent vs. Congruent trials. Age was negatively associated with middle frontal gyrus activity, controlling for performance and movement confounds. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Testosterone was negatively related with frontal and striatal brain response in males, and cerebellar and precuneus response in females. Estradiol was negatively related with fronto-cerebellar, cingulate, and precuneus brain activity in males, and positively related with occipital response in females. To our knowledge, this is the first study reporting the effects of age, sex, and sex steroids during an emotion-cognition task in adolescents. Further research is needed to examine longitudinal development of emotion-cognition interactions and deviations in psychiatric disorders in adolescence. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2018-05-17

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

  18. Handedness, functional cerebral hemispheric lateralization, and cognition in male-to-female transsexuals receiving cross-sex hormone treatment.

    PubMed

    Wisniewski, Amy B; Prendeville, Mary T; Dobs, Adrian S

    2005-04-01

    This study examined the impact of sex hormones on functional cerebral hemispheric lateralization and cognition in a group of male-to-female transsexuals receiving cross-sex hormone therapy compared to eugonadal men with a male gender identity. Cerebral lateralization was measured with a handedness questionnaire and a visual-split-field paradigm and cognitive tests sensitive to sex hormone exposure (identical pictures, 3-D mental rotation, building memory) were also administered. Endocrine measures on the day of participation for transsexual and control subjects included total testosterone, free testosterone, estradiol, gonadotropins, and sex hormone binding globulin concentrations. Compared to controls, male-to-female transsexuals had elevated estradiol and sex hormone binding globulin concentrations and suppressed testosterone concentrations. Transsexual subjects showed a trend toward less exclusive right-handedness than controls. No group differences were observed on the visual-split-field or cognitive tasks. No direct associations were observed between endocrine measures and the laterality measures and cognitive performance. Previous observations of female-typical patterns in cerebral lateralization and cognitive performance in male-to-female transsexuals were not found in the current study.

  19. Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules.

    PubMed

    Gu, Tao; Wen, Zongmei; Xu, Shufeng; Hua, Haixia; Zhang, Zhi; Wen, Tao; Fu, Zhanzhao; Lv, Xin

    2014-06-01

    An early differentiation of malignant from benign solitary pulmonary nodules (SPNs) is essential for management and prognosis of lung cancer. Here we investigated whether measurement of circulating sex hormones could be useful for an early detection of malignancy among patients with SPNs. We recruited 47 patients with malignant SPNs 45 patients with benign SPNs, and 32 healthy persons. Testosterone, estradiol, and progesterone were measured. Carcinoembryonic antigen (CEA) as well as TNF-α, IL-1 and IL-6 were also measured. We found that sex hormones were decreased significantly in patients with malignant SPNs, as compared to patients with benign SPNs and healthy controls (P<0.05). Sex hormones levels showed a trend to decline in patients with benign SPNs as compared to normal controls, but the difference was not statistically significant (P>0.05). CEA levels were only abnormally elevated in eight patients with lung adenocarcinoma. The inflammatory cytokines were remarkably higher in both patients than in normal controls. However, there was no statistical difference in these cytokines among patients. The reduced sex hormones levels seemed to be uniquely associated with lung cancer. Therefore, measurement of sex hormones may have clinical potential in the diagnosis of malignancy in patients with SPNs.

  20. Risk Factors for Eating Disorder Psychopathology within the Treatment Seeking Transgender Population: The Role of Cross-Sex Hormone Treatment.

    PubMed

    Jones, Bethany Alice; Haycraft, Emma; Bouman, Walter Pierre; Brewin, Nicola; Claes, Laurence; Arcelus, Jon

    2018-03-01

    Many transgender people experience high levels of body dissatisfaction, which is one of the numerous factors known to increase vulnerability to eating disorder symptoms in the cisgender (non-trans) population. Cross-sex hormones can alleviate body dissatisfaction so might also alleviate eating disorder symptoms. This study aimed to explore risk factors for eating disorder symptoms in transgender people and the role of cross-sex hormones. Individuals assessed at a national transgender health service were invited to participate (N = 563). Transgender people not on cross-sex hormones reported higher levels of eating disorder psychopathology than people who were. High body dissatisfaction, perfectionism, anxiety symptoms, and low self-esteem were risk factors for eating psychopathology, but, after controlling for these, significant differences in eating psychopathology between people who were and were not on cross-sex hormones disappeared. Cross-sex hormones may alleviate eating disorder psychopathology. Given the high prevalence of transgender identities, clinicians at eating disorder services should assess for gender identity issues. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

  1. Endothelin and sex hormones modulate the fibronectin synthesis by cultured human skin scleroderma fibroblasts

    PubMed Central

    Soldano, S; Montagna, P; Villaggio, B; Parodi, A; Gianotti, G; Sulli, A; Seriolo, B; Secchi, M E; Cutolo, M

    2009-01-01

    Objective: To evaluate the influence of endothelin-1 (ET-1) and sex hormones on cell proliferation and extracellular matrix (ECM) synthesis (ie, fibronectin, laminin) by cultured normal and scleroderma (SSc) human skin fibroblasts (FBs). Methods: Primary cultures of FBs were treated with ET-1 and sex hormones (17β-oestradiol or testosterone) for 24 h. Cell growth was analysed by methiltetrazolium salt test, ECM synthesis was evaluated by immunocytochemistry and western blot, both at 24 h. Results: In normal FBs, ET-1 and 17β-oestradiol, as well as their combination, increased cell growth (p<0.001, p<0.001, p<0.01 vs untreated cells (control), respectively) and fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). By contrast, testosterone either alone or in combination with ET-1 did not influence cell proliferation, but decreased fibronectin synthesis (p<0.05, testosterone vs control). In SSc FBs, ET-1 and 17β-oestradiol alone or their combination induced an increased fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs control, respectively). Unexpectedly, testosterone induced an increase of fibronectin synthesis (p<0.05 vs control). Conclusions: ET-1 and 17β-oestradiol seem to exert a profibrotic effect in normal and SSc culture FBs and might suggest their synergistic effect in the pathogenesis of the fibrotic process in SSc. PMID:18952637

  2. Induction of calcium-dependent nitric oxide synthases by sex hormones.

    PubMed

    Weiner, C P; Lizasoain, I; Baylis, S A; Knowles, R G; Charles, I G; Moncada, S

    1994-05-24

    We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a > 4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.

  3. Sex hormones affect language lateralisation but not cognitive control in normally cycling women.

    PubMed

    Hodgetts, Sophie; Weis, Susanne; Hausmann, Markus

    2015-08-01

    This article is part of a Special Issue "Estradiol and Cognition". Natural fluctuations of sex hormones during the menstrual cycle have been shown to modulate language lateralisation. Using the dichotic listening (DL) paradigm, a well-established measurement of language lateralisation, several studies revealed that the left hemispheric language dominance was stronger when levels of estradiol were high. A recent study (Hjelmervik et al., 2012) showed, however, that high levels of follicular estradiol increased lateralisation only in a condition that required participants to cognitively control (top-down) the stimulus-driven (bottom-up) response. This finding suggested that sex hormones modulate lateralisation only if cognitive control demands are high. The present study investigated language lateralisation in 73 normally cycling women under three attention conditions that differed in cognitive control demands. Saliva estradiol and progesterone levels were determined by luminescence immunoassays. Women were allocated to a high or low estradiol group. The results showed a reduced language lateralisation when estradiol and progesterone levels were high. The effect was independent of the attention condition indicating that estradiol marginally affected cognitive control. The findings might suggest that high levels of estradiol especially reduce the stimulus-driven (bottom-up) aspect of lateralisation rather than top-down cognitive control. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. The effect of cross-sex hormonal treatment on gender dysphoria individuals’ mental health: a systematic review

    PubMed Central

    Costa, Rosalia; Colizzi, Marco

    2016-01-01

    Cross-sex hormonal treatment represents a main aspect of gender dysphoria health care pathway. However, it is still debated whether this intervention translates into a better mental well-being for the individual and which mechanisms may underlie this association. Although sex reassignment surgery has been the subject of extensive investigation, few studies have specifically focused on hormonal treatment in recent years. Here, we systematically review all studies examining the effect of cross-sex hormonal treatment on mental health and well-being in gender dysphoria. Research tends to support the evidence that hormone therapy reduces symptoms of anxiety and dissociation, lowering perceived and social distress and improving quality of life and self-esteem in both male-to-female and female-to-male individuals. Instead, compared to female-to-male individuals, hormone-treated male-to-female individuals seem to benefit more in terms of a reduction in their body uneasiness and personality-related psychopathology and an amelioration of their emotional functioning. Less consistent findings support an association between hormonal treatment and other mental health-related dimensions. In particular, depression, global psychopathology, and psychosocial functioning difficulties appear to reduce only in some studies, while others do not suggest any improvement in these domains. Results from longitudinal studies support more consistently the association between hormonal treatment and improved mental health. On the contrary, a number of cross-sectional studies do not support this evidence. This review provides possible biological explanation vs psychological explanation (direct effect vs indirect effect) for the hormonal treatment-induced better mental well-being. In conclusion, this review indicates that gender dysphoria-related mental distress may benefit from hormonal treatment intervention, suggesting a transient reaction to the nonsatisfaction connected to the incongruent body

  5. The effect of cross-sex hormonal treatment on gender dysphoria individuals' mental health: a systematic review.

    PubMed

    Costa, Rosalia; Colizzi, Marco

    2016-01-01

    Cross-sex hormonal treatment represents a main aspect of gender dysphoria health care pathway. However, it is still debated whether this intervention translates into a better mental well-being for the individual and which mechanisms may underlie this association. Although sex reassignment surgery has been the subject of extensive investigation, few studies have specifically focused on hormonal treatment in recent years. Here, we systematically review all studies examining the effect of cross-sex hormonal treatment on mental health and well-being in gender dysphoria. Research tends to support the evidence that hormone therapy reduces symptoms of anxiety and dissociation, lowering perceived and social distress and improving quality of life and self-esteem in both male-to-female and female-to-male individuals. Instead, compared to female-to-male individuals, hormone-treated male-to-female individuals seem to benefit more in terms of a reduction in their body uneasiness and personality-related psychopathology and an amelioration of their emotional functioning. Less consistent findings support an association between hormonal treatment and other mental health-related dimensions. In particular, depression, global psychopathology, and psychosocial functioning difficulties appear to reduce only in some studies, while others do not suggest any improvement in these domains. Results from longitudinal studies support more consistently the association between hormonal treatment and improved mental health. On the contrary, a number of cross-sectional studies do not support this evidence. This review provides possible biological explanation vs psychological explanation (direct effect vs indirect effect) for the hormonal treatment-induced better mental well-being. In conclusion, this review indicates that gender dysphoria-related mental distress may benefit from hormonal treatment intervention, suggesting a transient reaction to the nonsatisfaction connected to the incongruent body

  6. Skin test reactivity to female sex hormones in women with primary unexplained recurrent pregnancy loss.

    PubMed

    Ellaithy, Mohamed I; Fathi, Hesham M; Farres, Mohamed N; Taha, Marwa S

    2013-09-01

    The objective was to examine the hypothesis that primary unexplained recurrent pregnancy loss might be associated with an inappropriate immunologically mediated response to progesterone and/or estrogen. This prospective study included 47 women with two or more documented consecutive early pregnancy losses of unknown etiology, and no previous history of deliveries. Intradermal skin testing was performed in the luteal phase of the cycle (days 16-20) using estradiol benzoate, progesterone, and a placebo of refined sesame oil. Immediate (20 min) and late (24h and 1 week) skin test readings for all cases were compared with those of 12 parous women of comparable age with no history of spontaneous miscarriages, premenstrual disorders, pregnancy, or sex hormone-related allergic or autoimmune diseases. Main outcome measure was skin test reactivity to estradiol and/or progesterone. Immediate skin test reactivity to both hormones was observed among half of the cases at 20 min. A papule after 24h, which persisted for up to 1 week, was observed among 32 (68.1%) and 34 (72.3%) cases at the sites of estrogen and progesterone injection, respectively. 55.3% of cases had combined skin test reactivity to both estradiol and progesterone at 1 week. All women in the control group showed absence of skin test reactivity for both estradiol and progesterone at 20 min, 24h, and 1 week. None of the subjects in either group showed skin test reactivity to placebo. There is an association between primary unexplained recurrent pregnancy loss and skin test reactivity to female sex hormones. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Interrelationship Between Alcohol Intake and Endogenous Sex-Steroid Hormones on Diabetes Risk in Postmenopausal Women.

    PubMed

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

    2015-01-01

    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. 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. 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% confidence interval [CI], 0.03, 0.26), compared to 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 odds ratio in the multivariate-adjusted models. 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.

  8. Complex relationship between sex hormones, insulin resistance and leptin in men with and without prostatic disease.

    PubMed

    Grosman, Halina; Fabre, Bibiana; Lopez, Miguel; Scorticati, Carlos; Lopez Silva, Maximiliano; Mesch, Viviana; Mazza, Osvaldo; Berg, Gabriela

    2016-01-01

    To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa. Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups. Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3-28.0) versus 4.8 (1.1-12.3) ng/ml; p < 0.01] and estradiol [median (range) 37.0 (20-90) versus 29.0 (20-118) pg/ml; p = 0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups. It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.

  9. The effects of biological sex and gonadal hormones on learning strategy in adult rats.

    PubMed

    Hawley, Wayne R; Grissom, Elin M; Barratt, Harriet E; Conrad, Taylor S; Dohanich, Gary P

    2012-02-28

    When learning to navigate toward a goal in a spatial environment, rodents employ distinct learning strategies that are governed by specific regions of the brain. In the early stages of learning, adult male rats prefer a hippocampus-dependent place strategy over a striatum-dependent response strategy. Alternatively, female rats exhibit a preference for a place strategy only when circulating levels of estradiol are elevated. Notably, male rodents typically perform better than females on a variety of spatial learning tasks, which are mediated by the hippocampus. However, limited research has been done to determine if the previously reported male spatial advantage corresponds with a greater reliance on a place strategy, and, if the male preference for a place strategy is impacted by removal of testicular hormones. A dual-solution water T-maze task, which can be solved by adopting either a place or a response strategy, was employed to determine the effects of biological sex and hormonal status on learning strategy. In the first experiment, male rats made more correct arm choices than female rats during training and exhibited a bias for a place strategy on a probe trial. The results of the second experiment indicated that testicular hormones modulated arm choice accuracy during training, but not the preference for a place strategy. Together, these findings suggest that the previously reported male spatial advantage is associated with a greater reliance on a place strategy, and that only performance during the training phase of a dual-solution learning task is impacted by removal of testicular hormones. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. The relationships between sex hormones and sexual function in middle-aged and older European men.

    PubMed

    O'Connor, Daryl B; Lee, David M; Corona, Giovanni; Forti, Gianni; Tajar, Abdelouahid; O'Neill, Terence W; Pendleton, Neil; Bartfai, Gyorgy; Boonen, Steven; Casanueva, Felipe F; Finn, Joseph D; Giwercman, Aleksander; Han, Thang S; Huhtaniemi, Ilpo T; Kula, Krzysztof; Labrie, Fernand; Lean, Michael E J; Punab, Margus; Silman, Alan J; Vanderschueren, Dirk; Wu, Frederick C W

    2011-10-01

    Limited data are available exploring the associations between sex hormones, multiple domains of sexual functioning, and sexual function-related distress in nonpatient samples in Europe. The aim of the study was to investigate the relationships between serum testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) and sexual function in a multicenter population-based study of aging in men. Using stratified random sampling, 2838 men aged 40-79 yr completed the European Male Ageing Study-Sexual Function Questionnaire and provided a blood sample for hormone measurements. T, E2, and DHT were measured using gas chromatography-mass spectrometry. We conducted a community-based population survey in eight European centers. Self-reported sexual function (overall sexual function, sexual function-related distress, erectile dysfunction, masturbation) was measured. Total and free T, but not E2 or DHT, was associated with overall sexual function in middle-aged and older men. E2 was the only hormone associated with sexual function-related distress such that higher levels were related to greater distress. Free T levels were associated with masturbation frequency and erectile dysfunction in the fully adjusted models, such that higher T was associated with less dysfunction and greater frequency. Moreover, there was a T threshold for the relationship between total T, sexual function, and erectile dysfunction. At T concentrations of 8 nmol/liter or less, T was associated with worse sexual functioning, whereas at T levels over 8 nmol/liter, the relationship came to a plateau. These findings suggest that different hormonal mechanisms may regulate sexual functioning (T) vs. the psychological aspects (E2) of male sexual behavior. Moreover, there was a T threshold for overall sexual function such that at levels greater than 8 nmol/liter the relationship between T and sexual function did not become stronger.

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

    Frick, Karyn M.

    2012-01-01

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

  13. Absorption and metabolization of sex hormones and their transformation into contraceptive technologies: the paths taken by medical thought in Brazil.

    PubMed

    Bonan, Claudia; Teixeira, Luiz Antonio; Nakano, Andreza Rodrigues

    2017-01-01

    The article analyses knowledge assimilation and the development of clinical and research practices relating to sex hormones among Brazilian gynaecologists. It discusses the paths taken by medical thought from the reception of the hormones to their transformation into contraceptives. Our objective is to comprehend styles of introducing and disseminating medical technologies in the area of reproductive health in Brazil. It uses methods of historical analysis and takes as its source the Anais Brasileiros de Ginecologia, a journal published between 1936 and 1970. From the outset, the accompaniment of scientific breakthroughs in relation to sex hormones and their use to treat diverse female illnesses played a key role in the rapid medical acceptance of hormonal contraception. Scientific and technical questions (side effects, dosages) and the demographic issue formed part of the majority of the debates. Objections from the Catholic Church were considered but did not set the agenda of medical thought on contraceptives. The quest to consolidate gynaecology as a scientific, modern and cosmopolitan area of expertise, along with sanitary and demographic motives that allowed contraceptives to be classed as ethical drugs, are identified as processes underlying the assimilation and metabolization of sex hormones as hormonal contraceptives.

  14. Can exposure to prenatal sex hormones (2D:4D) predict cognitive reflection?

    PubMed

    Bosch-Domènech, Antoni; Brañas-Garza, Pablo; Espín, Antonio M

    2014-05-01

    The Cognitive Reflection Test (CRT) is a test introduced by Frederick (2005). The task is designed to measure the tendency to override an intuitive response that is incorrect and to engage in further reflection that leads to the correct response. The consistent sex differences in CRT performance may suggest a role for prenatal sex hormones. A now widely studied putative marker for relative prenatal testosterone is the second-to-fourth digit ratio (2D:4D). This paper tests to what extent 2D:4D, as a proxy for the prenatal ratio of testosterone/estrogens, can predict CRT scores in a sample of 623 students. After controlling for sex, we observe that a lower 2D:4D (reflecting a relative higher exposure to testosterone) is significantly associated with a higher number of correct answers. The result holds for both hands' 2D:4Ds. In addition, the effect appears to be stronger for females than for males. We also control for patience and math proficiency, which are significantly related to performance in the CRT. But the effect of 2D:4D on performance in CRT is not reduced with these controls, implying that these variables are not mediating the relationship between digit ratio and CRT. Copyright © 2014 The Authors. Published by Elsevier Ltd. All rights reserved.

  15. Fetal sex alters maternal anti-Mullerian hormone during pregnancy in cattle.

    PubMed

    Stojsin-Carter, Anja; Costa, Nathalia N; De Morais, Rodrigo; De Bem, Tiago H; Costa, Mayra P; Carter, Timothy F; Gillis, Daniel J; Neal, Michael S; Ohashi, Otavio M; Miranda, Moyses S; Meirelles, Flavio V; Favetta, Laura A; King, W Allan

    2017-11-01

    Anti-Mullerian hormone (AMH) is expressed by both male and female fetuses during mammalian development, with males expressing AMH earlier and at significantly higher concentration. The aim of the current study was to explore the potential impact of pregnancy and fetal sex on maternal AMH and to determine if plasma (Pl) AMH or placenta intercotyledonary membrane and cotyledonary AMH receptor 2 (AMHR2) mRNA expression differ in pregnant cows carrying male vs. female fetuses. AMH levels in blood were measured using a bovine optimized ELISA kit. Cows pregnant with a male fetus were observed to have a significantly greater difference in Pl AMH between day 35 and 135 of gestation. Average fetal AMH level between 54 and 220days of gestation was also observed to be significantly higher in male vs. female fetuses. Intercotyledonary membranes and cotyledons were found to express AMHR2 between days 38 and 80 of gestation at similar levels in both fetal sexes. These findings support the hypothesis that fetal sex alters maternal Pl AMH during pregnancy in cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

    SciTech Connect

    Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.

    Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was tomore » determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and

  17. Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

    PubMed

    Meler, Erika N; Scott-Moncrieff, J Catharine; Peter, Augustine T; Bennett, Sara; Ramos-Vara, Jose; Salisbury, S Kathleen; Naughton, James F

    2011-06-01

    A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  18. Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults.

    PubMed

    Smith, Katherine P; Madison, Christina M; Milne, Nikki M

    2014-12-01

    Individuals with gender dysphoria experience distress associated with incongruence between their biologic sex and their identified gender. Gender dysphoric natal males receive treatment with antiandrogens and estrogens to become feminized (transsexual females), whereas natal females with gender dysphoria receive treatment with androgens to become masculinized (transsexual males). Because of the permanence associated with cross-sex hormone therapy (CSHT), adolescents diagnosed with gender dysphoria receive gonadotropin-releasing hormone analogs to suppress puberty. High rates of depression and suicide are linked to social marginalization and barriers to care. Behavior, emotional problems, depressive symptoms, and global functioning improve in adolescents receiving puberty suppression therapy. Gender dysphoria, psychological symptoms, quality of life, and sexual function improve in adults who receive CSHT. Within the first 6 months of CSHT, changes in transsexual females include breast growth, decreased testicular volume, and decreased spontaneous erections, and changes in transsexual males include cessation of menses, breast atrophy, clitoral enlargement, and voice deepening. Both transsexual females and males experience changes in body fat redistribution, muscle mass, and hair growth. Desired effects from CSHT can take between 3 and 5 years; however, effects that occur during puberty, such as voice deepening and skeletal structure changes, cannot be reversed with CSHT. Decreased sexual desire is a greater concern in transsexual females than in transsexual males, with testosterone concentrations linked to sexual desire in both. Regarding CSHT safety, bone mineral density is preserved with adequate hormone supplementation, but long-term fracture risk has not been studied. The transition away from high-dose traditional regimens is tied to a lower risk of venous thromboembolism and cardiovascular disease, but data quality is poor. Breast cancer has been reported in

  19. Birth characteristics and female sex hormone concentrations during adolescence: results from the Dietary Intervention Study in Children.

    PubMed

    Ruder, Elizabeth H; Hartman, Terryl J; Rovine, Michael J; Dorgan, Joanne F

    2011-04-01

    Birth characteristics and adult hormone concentrations influence breast cancer risk, but little is known about the influence of birth characteristics on hormone concentrations, particularly during adolescence. We evaluated the association of birth characteristics (birth weight, birth length, and gestational age) with serum sex hormone concentrations during late childhood and adolescence in 278 female participants of the Dietary Intervention Study in Children. Repeated measures analysis of variance models were used to assess the relationships of birth characteristics and serum estrogens and androgens at five different time points over a mean period of 7 years. In analyses that did not take into account time from blood draw until menarche, birth weight was inversely associated with pre-menarche concentrations of estradiol, estrone sulfate, androstenedione, testosterone, and dehydroepiandrosterone sulfate (DHEAS). In the post-menarche analyses, birth weight was not significantly associated with concentration of any of the hormones under investigation. Birth length and gestational age were not associated with hormone concentrations before or after menarche. Birth weight is inversely associated with sex hormone concentrations before menarche in the model unadjusted for time from blood draw until menarche. The in utero environment has long-term influences on the hormonal milieu, which could potentially contribute to breast cancer risk.

  20. Cross-sex hormonal treatment and body uneasiness in individuals with gender dysphoria.

    PubMed

    Fisher, Alessandra D; Castellini, Giovanni; Bandini, Elisa; Casale, Helen; Fanni, Egidia; Benni, Laura; Ferruccio, Naika; Meriggiola, Maria Cristina; Manieri, Chiara; Gualerzi, Anna; Jannini, Emmanuele; Oppo, Alessandro; Ricca, Valdo; Maggi, Mario; Rellini, Alessandra H

    2014-03-01

    Cross-sex hormonal treatment (CHT) used for gender dysphoria (GD) could by itself affect well-being without the use of genital surgery; however, to date, there is a paucity of studies investigating the effects of CHT alone. This study aimed to assess differences in body uneasiness and psychiatric symptoms between GD clients taking CHT and those not taking hormones (no CHT). A second aim was to assess whether length of CHT treatment and daily dose provided an explanation for levels of body uneasiness and psychiatric symptoms. A consecutive series of 125 subjects meeting the criteria for GD who not had genital reassignment surgery were considered. Subjects were asked to complete the Body Uneasiness Test (BUT) to explore different areas of body-related psychopathology and the Symptom Checklist-90 Revised (SCL-90-R) to measure psychological state. In addition, data on daily hormone dose and length of hormonal treatment (androgens, estrogens, and/or antiandrogens) were collected through an analysis of medical records. Among the male-to-female (MtF) individuals, those using CHT reported less body uneasiness compared with individuals in the no-CHT group. No significant differences were observed between CHT and no-CHT groups in the female-to-male (FtM) sample. Also, no significant differences in SCL score were observed with regard to gender (MtF vs. FtM), hormone treatment (CHT vs. no-CHT), or the interaction of these two variables. Moreover, a two-step hierarchical regression showed that cumulative dose of estradiol (daily dose of estradiol times days of treatment) and cumulative dose of androgen blockers (daily dose of androgen blockers times days of treatment) predicted BUT score even after controlling for age, gender role, cosmetic surgery, and BMI. The differences observed between MtF and FtM individuals suggest that body-related uneasiness associated with GD may be effectively diminished with the administration of CHT even without the use of genital surgery for Mt

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

    PubMed

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

    2007-11-05

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

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

    PubMed

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

    2010-12-17

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

  3. Associations between maternal phenolic exposure and cord sex hormones in male newborns.

    PubMed

    Liu, Chunhua; Xu, Xijin; Zhang, Yuling; Li, Weiqiu; Huo, Xia

    2016-03-01

    Are maternal urinary phenol concentrations associated with cord steroid hormone levels and anogenital distance (AGD) in male newborns? High maternal urinary Bisphenol A (BPA) levels are associated with decreases in cord testosterone levels and the ratio of testosterone to estradiol in male newborns, but there was no significant association with AGD. Early life exposure to phenolic endocrine disrupting compounds (EDCs) is known to disrupt hormonal activities and affect reproductive development in males. However, studies on the health effects of prenatal human exposure are scarce. This was a cross-sectional study to investigate the association between maternal phenolic exposure and cord sex steroid hormones and AGD in male newborns. We recruited 100 mother-infant pairs from each of two hospitals, one in a polluted town (Guiyu) and the other in a cleaner town (Haojiang), from September 2010 to September 2011. One hundred and seventy eight maternal urine samples and 137 cord blood samples were available for quantification, thus 137 complete records entered into the final analysis. Of them, 77 pairs were from Guiyu, and 60 were from Haojiang. The chemical concentrations were determined by solid phase extraction and gas chromatography-mass spectrometry (SPE-GC-MS), and cord sex hormones were detected by radioimmunoassay (RIA). Neonatal anthropometric parameters including AGD were measured. Log2-transformed maternal urinary BPA concentration was negatively correlated with testosterone level and the ratio of testosterone to estradiol (T/E2) in male fetal cord blood after adjustment for potential confounders in linear regression models (βadjusted = -31.09 (95% CI, -53.07 to -9.11) and βadjusted = -0.08 (95% CI, -0.13 to -0.01), respectively). Moreover, compared with the lowest quartile group of BPA level, the highest group showed a significant decrease in testosterone level and T/E2 (βadjusted = -179.84 (95% CI, -333.45 to -26.24) and βadjusted = -0.37 (95% CI, -0.81 to

  4. CIRCULATING CONCENTRATIONS OF THYROID HORMONE IN BELUGA WHALES (DELPHINAPTERUS LEUCAS): INFLUENCE OF AGE, SEX, AND SEASON.

    PubMed

    Flower, Jennifer E; Allender, Matthew C; Giovanelli, Richard P; Summers, Sandra D; Spoon, Tracey R; St Leger, Judy A; Goertz, Caroline E C; Dunn, J Lawrence; Romano, Tracy A; Hobbs, Roderick C; Tuttle, Allison D

    2015-09-01

    Thyroid hormones play a critical physiologic role in regulating protein synthesis, growth, and metabolism. To date, because no published compilation of baseline values for thyroid hormones in beluga whales (Delphinapterus leucas) exists, assessment of thyroid hormone concentrations in this species has been underused in clinical settings. The purpose of this study was to document the concentrations of total thyroxine (tT4) and total triiodothyronine (tT3) in healthy aquarium-maintained and free-ranging beluga whales and to determine the influence of age, sex, and season on the thyroid hormone concentrations. Archived serum samples were collected from healthy aquarium-maintained (n=43) and free-ranging (n=39) belugas, and serum tT4 and tT3 were measured using chemiluminescence immunoassay. The mean tT4 concentration in aquarium-maintained belugas was 5.67±1.43 μg/dl and the mean tT3 concentration was 70.72±2.37 ng/dl. Sex comparisons showed that aquarium-maintained males had significantly greater tT4 and tT3 (9.70±4.48 μg/dl and 92.65±30.55 ng/dl, respectively) than females (7.18±2.82 μg/dl and 77.95±20.37 ng/dl) (P=0.004 and P=0.013). Age comparisons showed that aquarium-maintained whales aged 1-5 yr had the highest concentrations of tT4 and tT3 (8.17±0.17 μg/dl and 105.46±1.98 ng/dl, respectively) (P=0.002 and P<0.001). tT4 concentrations differed significantly between seasons, with concentrations in winter (4.59±1.09 μg/dl) being significantly decreased compared with spring (P=0.009), summer (P<0.0001), and fall (P<0.0001) concentrations. There was a significant difference in tT4 and tT3 concentrations between aquarium-maintained whales (5.67±1.43 μg/dl and 70.72±15.57 ng/dl, respectively) and free-ranging whales (11.71±3.36 μg/dl and 103.38±26.45 ng/dl) (P<0.0001 and P<0.001). Clinicians should consider biologic and environmental influences (age, sex, and season) for a more accurate interpretation of thyroid hormone concentrations in belugas

  5. Influences of menstrual cycle position and sex hormone levels on spontaneous intrusive recollections following emotional stimuli.

    PubMed

    Ferree, Nikole K; Kamat, Rujvi; Cahill, Larry

    2011-12-01

    Spontaneous intrusive recollections (SIRs) are known to follow emotional events in clinical and non-clinical populations. Previous work in our lab has found that women report more SIRs than men after exposure to emotional films, and that this effect is driven entirely by women in the luteal phase of the menstrual cycle. To replicate and extend this finding, participants viewed emotional films, provided saliva samples for sex hormone concentration analysis, and estimated SIR frequency following film viewing. Women in the luteal phase reported significantly more SIRs than did women in the follicular phase, and SIR frequency significantly correlated with salivary progesterone levels. The results are consistent with an emerging pattern in the literature suggesting that menstrual cycle position of female participants can potently influence findings in numerous cognitive domains. The potential implications of these results for disorders characterized by intrusions, such as post-traumatic stress disorder, are also discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2016-02-01

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

  7. Leukocyte changes across menstruation, ovulation, and mid-luteal phase and association with sex hormone variation.

    PubMed

    Nowak, Judyta; Borkowska, Barbara; Pawlowski, Boguslaw

    2016-09-10

    Total leukocyte count (white blood cells-WBC) and the count of each subpopulation vary across the menstrual cycle, but results of studies examining the time and direction of these changes are inconsistent and methodologically flawed. Besides, no previous study focused on leukocyte count on the day of ovulation. Blood samples were obtained from 37 healthy and regularly cycling women aged 19.8-36.1 years. Samples were taken three times: during menstruation (M), ovulation (O), and in the mid-luteal phase (ML). WBC, neutrophils, lymphocytes, mixed cells, progesterone (P,) and estradiol (E) were measured in each of the three target phases of the cycle. Compared to menstruation, WBC (P = 0.002) and neutrophils (P < 0.001) increased around ovulation and remained stable in the mid-luteal phase, whereas lymphocyte and mixed cell counts did not change throughout the menstrual cycle. There were some correlations of sex hormone variation with leukocyte changes between M and O (positive for E and WBC, negative for P and WBC and for P and neutrophil count; P < 0.05), but not between O and ML. Peripheral leukocyte changes taking place in the second half of the cycle are already observable on the day of ovulation and they are associated with sex hormone variation. We speculate that these changes may lead to increased immune protection against pathogens at a time when fertilization and implantation typically occur. Am. J. Hum. Biol. 28:721-728, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Circulating Sex Hormones and Terminal Duct Lobular Unit Involution of the Normal Breast

    PubMed Central

    Khodr, Zeina G.; Sherman, Mark E.; Pfeiffer, Ruth M.; Gierach, Gretchen L.; Brinton, Louise A.; Falk, Roni T.; Patel, Deesha A.; Linville, Laura M.; Papathomas, Daphne; Clare, Susan E.; Visscher, Daniel W.; Mies, Carolyn; Hewitt, Stephen M.; Storniolo, Anna Maria V.; Rosebrock, Adrian; Caban, Jesus J.; Figueroa, Jonine D.

    2014-01-01

    Background Terminal duct lobular units (TDLUs) are the predominant source of breast cancers. Lesser degrees of age-related TDLU involution have been associated with increased breast cancer risk, but factors that influence involution are largely unknown. We assessed whether circulating hormones, implicated in breast cancer risk, are associated with levels of TDLU involution using data from the Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (2009-2011). Methods We evaluated three highly reproducible measures of TDLU involution, using normal breast tissue samples from the KTB (n=390): TDLU counts, median TDLU span, and median acini counts per TDLU. Relative risks (RRs, for continuous measures), odds ratios (ORs, for categorical measures), 95% confidence intervals (CIs), and p-trends were calculated to assess the association between tertiles of estradiol, testosterone, sex hormone-binding globulin (SHBG), progesterone, and prolactin with TDLU measures. All models were stratified by menopausal status and adjusted for confounders. Results Among premenopausal women, higher prolactin levels were associated with higher TDLU counts (RRT3vsT1:1.18, 95% CI: 1.07-1.31; p-trend=0.0005), but higher progesterone was associated with lower TDLU counts (RRT3vsT1: 0.80, 95% CI: 0.72-0.89; p-trend<0.0001). Among postmenopausal women, higher levels of estradiol (RRT3vsT1:1.61, 95% CI: 1.32-1.97; p-trend<0.0001) and testosterone (RRT3vsT1: 1.32, 95% CI: 1.09-1.59; p-trend=0.0043) were associated with higher TDLU counts. Conclusions These data suggest that select hormones may influence breast cancer risk potentially through delaying TDLU involution. Impact Increased understanding of the relationship between circulating markers and TDLU involution may offer new insights into breast carcinogenesis. PMID:25472681

  9. Sex hormone influence on hepatitis in young male A/JCr mice infected with Helicobacter hepaticus.

    PubMed

    Theve, Elizabeth J; Feng, Yan; Taghizadeh, Koli; Cormier, Kathleen S; Bell, David R; Fox, James G; Rogers, Arlin B

    2008-09-01

    Hepatitis B virus (HBV), the leading cause of human hepatocellular carcinoma, is especially virulent in males infected at an early age. Likewise, the murine liver carcinogen Helicobacter hepaticus is most pathogenic in male mice infected before puberty. We used this model to investigate the influence of male sex hormone signaling on infectious hepatitis. Male A/JCr mice were infected with H. hepaticus or vehicle at 4 weeks and randomized into surgical and pharmacologic treatment groups. Interruption of androgen pathways was confirmed by hormone measurements, histopathology, and liver gene and Cyp4a protein expression. Castrated males and those receiving the competitive androgen receptor antagonist flutamide had significantly less severe hepatitis as determined by histologic activity index than intact controls at 4 months. Importantly, the powerful androgen receptor agonist dihydrotestosterone did not promote hepatitis. No effect on hepatitis was evident in males treated with the 5alpha-reductase inhibitor dutasteride, the peroxisome proliferator-activated receptor-alpha agonist bezafibrate, or the nonsteroidal anti-inflammatory drug flufenamic acid. Consistent with previous observations of hepatitis-associated liver-gender disruption, transcriptional alterations involved both feminine (cytochrome P450 4a14) and masculine (cytochrome P450 4a12 and trefoil factor 3) genes, as well gender-neutral (H19 fetal liver mRNA, lipocalin 2, and ubiquitin D) genes. Hepatitis was associated with increased unsaturated C(18) long-chain fatty acids (oleic acid and linoleic acid) relative to saturated stearic acid. Our results indicate that certain forms of androgen interruption can inhibit H. hepaticus-induced hepatitis in young male mice, whereas androgen receptor agonism does not worsen disease. This raises the possibility of targeted hormonal therapy in young male patients with childhood-acquired HBV.

  10. Down-regulation of anandamide hydrolase in mouse uterus by sex hormones.

    PubMed

    MacCarrone, M; De Felici, M; Bari, M; Klinger, F; Siracusa, G; Finazzi-Agrò, A

    2000-05-01

    Endocannabinoids are an emerging class of lipid mediators, which mimic several effects of cannabinoids. Anandamide (arachidonoylethanolamide) is a major endocannabinoid, which has been shown to impair pregnancy and embryo development. The activity of anandamide is controlled by cellular uptake through a specific transporter and intracellular degradation by the enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH). We characterized FAAH in mouse uterus by radiochromatographic and immunochemical techniques, showing that the enzyme is confined to the epithelium and its activity decreases appreciably during pregnancy or pseudopregnancy because of lower gene expression at the translational level. Ovariectomy prevented the decrease in FAAH, and both progesterone and estrogen further reduced its basal levels, suggesting hormonal control of the enzyme. Anandamide was shown to induce programmed cell death in mouse blastocysts, through a pathway independent of type-1 cannabinoid receptor. Blastocysts, however, have a specific anandamide transporter and FAAH, which scavenge this lipid. Taken together, these results provide evidence of an interplay between endocannabinoids and sex hormones in pregnancy. These findings may also be relevant for human fertility, as epithelial cells from healthy human uterus showed FAAH activity and expression, which in adenocarcinoma cells was increased fivefold.

  11. Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

    PubMed

    Andersen, Monica L; Ribeiro, Daniel A; Alvarenga, Tathiana A; Silva, Andressa; Araujo, Paula; Zager, Adriano; Tenorio, Neuli M; Tufik, Sergio

    2010-02-01

    The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones. Copyright 2009 Elsevier Inc. All rights reserved.

  12. Sex Determination in Bees. IV. Genetic Control of Juvenile Hormone Production in MELIPONA QUADRIFASCIATA (Apidae)

    PubMed Central

    Kerr, Warwick Estevam; Akahira, Yukio; Camargo, Conceição A.

    1975-01-01

    Cell number and volume of corpora allata was determined for 8 phases of development, the first prepupal stage to adults 30 days old, in the social Apidae Melipona quadrifasciata. In the second prepupal stage a strong correlation was found between cell number and body weight ( r=0.651**), and cell number and corpora allata volume in prepupal stage (r=0.535*), which indicates that juvenile hormone has a definite role in caste determination in Melipona. The distribution of the volume of corpus allatum suggest a 3:1 segregation between bees with high volume of corpora allata against low and medium volume. This implies that genes xa and xb code for an enzyme that directly participates in juvenile hormone production. It was also concluded that the number of cells in the second prepupal stage is more important than the weight of the prepupa for caste determination. A scheme summarizing the genic control of sex and caste determination in Melipona bees in the prepupal phase is given. PMID:1213273

  13. [Changes in molecular forms of sex hormone binding globulin during menstrual cycle and menopause].

    PubMed

    Fonseca, M E; Masón, M; Ochoa, R; Hernández-V, M; Zárate, A

    1996-11-01

    Sex hormone binding globulin (SHBG) is a glycoprotein that transports mainly androgens and estrogens regulating the amount of free and bound hormone which in turn plays a role in the metabolic balance. It is also known that estrogens increase the hepatic production of SHBG which circulates in various molecular forms containing different amounts of sialic acid as the main component of carbohydrates. In the present work we studied physiological variations of molecular forms of SHBG during the normal menstrual cycle and the menopause. During the follicular phase the form 54 KD was the predominant variant, in the periovulatory period was isomers 90 KD, and during the luteal phase corresponded to both 54 and 90 KD. In the menopause dimeric form of 90 KD corresponded to the major proportion and was present a higher molecular forms of 115-135 KD. Following estrogen therapy the chromatographic profile changed as to that observed during the menstrual cycle. Important changes in the proportion of sialic acid were observed in each of the phases of menstrual cycle and following estrogen replacement. And increase in the amount of sialic acid corresponded to higher estrogen concentrations. It is concluded that SHBG concentrations varies during the menstrual cycle according the estrogen levels which in addition regulates the proportion of molecular forms and sialic acid containt.

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

    PubMed

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

    2012-12-01

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

  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. Sex hormone modulation of proinflammatory cytokine and CRP expression in macrophages from older men and postmenopausal women

    USDA-ARS?s Scientific Manuscript database

    Inflammation plays a central role in the development and progression of coronary heart disease (CHD). The sex hormones estrogen and testosterone have been shown to modify the inflammatory response by influencing cytokine expression in human macrophage cells obtained from younger individuals. The eff...

  17. DETERMINATION OF SEX HORMONES AND NONYLPHENOL ETHOXYLATES IN THE AQUEOUS MATRIXES OF TWO PILOT-SCALE MUNICIPAL WASTEWATER TREATMENT PLANTS

    EPA Science Inventory

    Two analytical methods were developed and refined for the detection and quantitation of two groups of endocrine-disrupting chemicals (EDCs) in the liquid matrixes of two pilot-scale municipal wastewater treatment plants. The targeted compounds are seven sex hormones (estradiol, ...

  18. Effects of age and sex on hormonal responses to weightlessness simulation

    NASA Technical Reports Server (NTRS)

    Larochelle, F.; Leach, C.; Vernikos-Danellis, J.

    1982-01-01

    The effects of horizontal bedrest on the excretion of catecholamines, aldosterone, and cortisol by human subjects grouped by age and sex are examined. The responses are assessed by assays of 24-hr urine samples collected throughout the studies. In 36-45-yr-olds, the excretion of epinephrine increases, whereas it decreases in the 46-55- and 56-65-yr-old groups. Norepinephrine excretion decreases (5-27%) in all groups during bedrest. Aldosterone excretion increases in the younger two groups of both males (19 and 6%) and females (47 and 9%). A slight decrease is observed in 56-65-yr-old males (6%), whereas excretion in females is unchanged. Cortisol excretion increases in the youngest groups of both men (12%) and women (13%) but decreases in the 56-65-yr-old groups (6 and 5%). For the two groups of intermediate age (46-55 yr), excretion in females decreases (15%), whereas in males it increases (19%). It is believed that hormone measurements may be of value in explaining variation in stress tolerance due to age and/or sex during space flight.

  19. Olfactory conditioned same-sex partner preference in female rats: Role of ovarian hormones.

    PubMed

    Tecamachaltzi-Silvaran, M B; Barradas-Moctezuma, M; Herrera-Covarrubias, D; Carrillo, P; Corona-Morales, A A; Perez, C A; García, L I; Manzo, J; Coria-Avila, Genaro A

    2017-11-01

    The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24h with lemon-scented stimulus females (CS+), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS+ female and a novel female. In test 2 (male-female) they chose between the CS+ female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS+ female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil.

    PubMed

    Freire, Carmen; Koifman, Rosalina Jorge; Sarcinelli, Paula Novaes; Rosa, Ana Cristina Simões; Clapauch, Ruth; Koifman, Sergio

    2014-03-01

    Several studies have investigated the effects of organochlorine (OC) pesticides on adverse reproductive outcomes. However, few previous studies explored their effects on sex hormones. To examine the association between serum concentrations of OC pesticides and levels of sex hormones in adult population in a rural area in Brazil heavily contaminated with these pesticides. A cross-sectional study with 304 men and 300 women was undertaken. Wet weight serum concentrations of 19 OC pesticides (dichloro-diphenyl-trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were determined in all participants. Testosterone levels were obtained for men and estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for women. Associations between OC pesticides and sex hormones were evaluated using linear regression models. Prevalence of women with non-physiological hyperprolactinemia was 4%. After adjusting for serum lipids and confounders, heptachlor and o,p'-DDT concentrations in men were associated with lower testosterone levels, while peri- and postmenopausal women (N=77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p'-DDT, p,p'-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and mirex, as well as between FSH and p,p'-DDD, endosulfan 1 and aldrin. Premenopausal women (N=210) did not show statistically significant associations between OC pesticides and sex hormones. Inverse associations between OC pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, together with the high proportion of women with elevated prolactin, suggest that these OC compounds may have triggered anti-androgenic effects in men and estrogenic effects in women in this population. Copyright © 2013. Published by Elsevier GmbH.

  1. 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.

  2. Serum sex hormones in men occupationally exposed to dichloro-diphenyl-trichloro ethane (DDT) as young adults.

    PubMed

    Cocco, Pierluigi; Loviselli, Andrea; Fadda, Domenica; Ibba, Antonio; Melis, Massimo; Oppo, Alessandro; Serra, Stefano; Taberlet, Alessandro; Tocco, Maria Giuseppina; Flore, Costantino

    2004-09-01

    To explore endocrine effects in relation to para,para'-dichloro-diphenyl-dichloro ethylene (p,p'-DDE) body burden and past occupational exposure to its precursor dichloro-diphenyl-trichloro ethane (DDT), we assayed serum sex hormones, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol (E2), testosterone and sex hormone binding globulin (SHBG), and p,p'-DDE levels in 107 male participants in a 1946-1950 anti-malarial campaign in Sardinia, Italy. Cumulative DDT exposure during the anti-malarial operations was retrospectively estimated from detailed reports of the anti-malarial agency. Ortho,para-DDE, and its precursor ortho,para-DDT were always below the detection limit. p,p'-DDT was detected in 14/107 subjects, and p,p'-DDE in 106/107 subjects. The median lipid-adjusted p,p'-DDE serum concentration over the total study population was 396 parts per billion (interquartile range 157-1045), and it did not vary according to the job at the time of anti-malarial operations, nor was it affected by cumulative DDT exposure. LH, FSH, and SHBG, but not testosterone or E2, showed a significant positive correlation with age. Neither current serum p,p'-DDE nor past cumulative DDT exposure affected sex hormone concentrations. Our results suggest that (1) the low current p,p'-DDE serum concentration does not affect serum hormone levels, and (2) past cumulative DDT exposure is not correlated with the current p,p'-DDE serum level, nor does it show persistent effects on serum hormone levels.

  3. Effects of levetiracetam monotherapy on sperm parameters and sex hormones: Data from newly diagnosed patients with epilepsy.

    PubMed

    Ceylan, Mustafa; Yalcin, Ahmet; Bayraktutan, Omer Faruk; Karabulut, Ibrahim; Sonkaya, Ali Rıza

    2016-10-01

    Epilepsy has an impact on the reproductive system. Males with epilepsy have lower fertility rates, hypo-sexuality and reduced potency compared with the general population. Anti-epileptic drugs and epilepsy itself are thought to be responsible for this reduced fertility. LEV is a second-generation anti-epileptic agent with low incidences of both adverse effects and drug-drug interactions. In this study, we have investigated the effects of LEV treatment on sex hormones and sperm parameters in newly diagnosed epilepsy patients. We recruited 26 males with newly diagnosed epilepsy and introduced LEV monotherapy. Patients were divided into two groups depending on whether they had partial or generalized seizures. We acquired the results of pre- and post-treatment sperm analyses and serum sex hormone levels. We also recorded the maximum dose, daily dose and treatment duration for each individual. Pre- and post-treatment comparisons and correlations between both sperm and sex hormone parameters and both treatment duration and dose were determined. Pre- and post-treatment sex hormone levels were not significantly different. The total sperm count, percentage of normal morphology and functional sperm count tested after treatment were significantly lower in both groups compared with pre-treatment values (p<0.05). There was a moderate correlation between daily dose and reduction in functional sperm count (r: 0.41, p: 0.034). Our findings confirm that LEV treatment of newly diagnosed epilepsy patients decreases sperm parameters without altering sex hormone levels. Our results may guide the choice of anti-epileptic drug treatment among men with epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. Visuospatial performance on an internet line judgment task and potential hormonal markers: sex, sexual orientation, and 2D:4D.

    PubMed

    Collaer, Marcia L; Reimers, Stian; Manning, John T

    2007-04-01

    We investigated whether performance on a visuospatial line judgment task, the Judgment of Line Angle and Position-15 test (JLAP-15), showed evidence of sensitivity to early sex steroid exposure by examining how it related to sex, as well as to sexual orientation and 2D:4D digit ratios. Participants were drawn from a large Internet study with over 250,000 participants. In the main sample (ages 12-58 years), males outperformed females on the JLAP-15, showing a moderate effect size for sex. In agreement with a prenatal sex hormone hypothesis, line judgment accuracy in adults related to 2D:4D and sexual orientation, both of which are postulated to be influenced by early steroids. In both sexes, better visuospatial performance was associated with lower (more male-typical) digit ratios. For men, heterosexual participants outperformed homosexual/bisexual participants on the JLAP-15 and, for women, homosexual/bisexual participants outperformed heterosexual participants. In children aged 8-10 years, presumed to be a largely prepubertal group, boys also outperformed girls. These findings are consistent with the hypothesis that visuospatial ability is influenced by early sex steroids, although they do not rule out alternative explanations or additional influences. More broadly, such results support a prenatal sex hormone hypothesis that degree of androgen exposure may influence the neural circuitry underlying cognition (visuospatial ability) and sexual orientation as well as aspects of somatic (digit ratio) development.

  5. Sexual dimorphism of gonadotropin-releasing hormone type-III (GnRH3) neurons and hormonal sex reversal of male reproductive behavior in Mozambique tilapia.

    PubMed

    Kuramochi, Asami; Tsutiya, Atsuhiro; Kaneko, Toyoji; Ohtani-Kaneko, Ritsuko

    2011-10-01

    In tilapia, hormone treatment during the period of sexual differentiation can alter the phenotype of the gonads, indicating that endocrine factors can cause gonadal sex reversal. However, the endocrine mechanism underlying sex reversal of reproductive behaviors remains unsolved. In the present study, we detected sexual dimorphism of gonadotropin-releasing hormone type III (GnRH3) neurons in Mozambique tilapia Oreochromis mossambicus. Our immunohistochemical observations showed sex differences in the number of GnRH3 immunoreactive neurons in mature tilapia; males had a greater number of GnRH3 neurons in the terminal ganglion than females. Treatment with androgen (11-ketotestosterone (11-KT) or methyltestosterone), but not that with 17β-estradiol, increased the number of GnRH3 neurons in females to a level similar to that in males. Furthermore, male-specific nest-building behavior was induced in 70% of females treated with 11-KT within two weeks after the onset of the treatment. These results indicate androgen-dependent regulation of GnRH3 neurons and nest-building behavior, suggesting that GnRH3 is importantly involved in sex reversal of male-specific reproductive behavior.

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

    PubMed

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

    2014-11-01

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

  7. Sympathetic arousal increases a negative memory bias in young women with low sex hormone levels

    PubMed Central

    Nielsen, Shawn E.; Barber, Sarah J.; Chai, Audrey; Clewett, David V.; Mather, Mara

    2015-01-01

    Emotionally arousing events are typically better attended to and remembered than neutral ones. Current theories propose that arousal-induced increases in norepinephrine during encoding bias attention and memory in favor of affectively salient stimuli. Here, we tested this hypothesis by manipulating levels of physiological arousal prior to encoding and examining how it influenced memory for emotionally salient images, particularly those that are negative rather than positive in valence. We also tested whether sex steroid hormones interact with noradrenergic activity to influence these emotional memory biases in women. Healthy naturally cycling women and women on hormonal contraception completed one of the following physiological arousal manipulations prior to viewing a series of negative, positive and neutral images: 1) Immediate handgrip arousal – isometric handgrip immediately prior to encoding, 2) Residual handgrip arousal – isometric handgrip 15 min prior to encoding, or 3) No handgrip. Sympathetic arousal was measured throughout the session via pupil diameter changes. Levels of 17β-estradiol and progesterone were measured via salivary samples. Memory performance was assessed approximately 10 minutes after encoding using a surprise free recall test. The results indicated that handgrip successfully increased sympathetic arousal compared to the control task. Under immediate handgrip arousal, women showed enhanced memory for negative images over positive images; this pattern was not observed in women assigned to the residual and no-handgrip arousal conditions. Additionally, under immediate handgrip arousal, both high estradiol and progesterone levels attenuated the memory bias for negative over positive images. Follow-up hierarchical linear models revealed consistent effects when accounting for trial-by-trial variability in normative International Affective Picture System valence and arousal ratings. These findings suggest that heightened sympathetic arousal

  8. Perception of facial profiles: influence of female sex hormones and personality traits.

    PubMed

    Jovic, T; Pavlic, A; Varga, S; Kovacevic Pavicic, D; Slaj, M; Spalj, S

    2016-11-01

    The observational study investigated whether women's perception of the facial profile is related to changes in sex hormones during the menstrual cycle and under the influence of personality traits. Participants were heterosexual Caucasian normally menstruating women not using oral contraceptives (N = 30, aged 20-44 years). The profile attractiveness was assessed by grading of thirteen men's and women's Caucasian profile distortions by a visual analogue scale (0 = least to 100 = most attractive) in the non-ovulating phase and ovulating phase of the menstrual cycle. Male profiles were graded twice-in social and emotional contexts. Personality traits were assessed by Big Five Inventory. The most attractive male profiles in both phases and contexts were a straight profile or mild lip retrusion. According to cluster analysis, non-ovulating females distinguish skeletal from dentoalveolar alterations; however, maxillary retrognathism was considered to be closer to an attractive profile, which were resulting from dentoalveolar manipulations only. Ovulating females, when considering emotional relationship, exhibit lowest preference for males with convex profiles and extreme concave profile, while they consider males with slightly prominent chins due to maxillary retrognathism, mandibular prognathism or pronounced lip retrusion closer to the most attractive males. No clear patterns of influence of personality traits were detected. Moderate lip protrusion was the most attractive female profile in ovulating and straight profile in non-ovulating phase. The favorable profiles, on average, are the same regardless of the female hormonal status and personality traits. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Endogenous sex hormones and memory performance in middle-aged Greek women with subjective memory complaints.

    PubMed

    Armeni, Eleni; Apostolakis, Michail; Christidi, Foteini; Rizos, Demetrios; Kaparos, George; Panoulis, Konstantinos; Augoulea, Areti; Alexandrou, Andreas; Karopoulou, Evangelia; Zalonis, Ioannis; Triantafyllou, Nikolaos; Lambrinoudaki, Irene

    2018-02-01

    The changing hormonal milieu during the menopausal transition may contribute to the development of memory disorders. We aimed to assess the association of sex hormones with memory function in a sample of Greek middle-aged women. This pilot study included 44 women with subjective memory complaints. Memory performance was evaluated using the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory test (BVMT), and the verbal digits backwards test (VSPAN), to assess verbal, visuospatial, and working memory performance, respectively. Menopausal symptoms were assessed using the Green Climacteric Scale. VSPAN backwards scores were positively associated with log-transformed free androgen index (logFAI), in models adjusted for age, education, log-transformed free estrogen index (logFEI), hypertension, and the intensity of menopausal symptoms. BVMT total scores were predicted by logFAI (b-coefficient = 0.424, p value = 0.002), education, and combined climacteric symptomatology, in a model adjusted for age, logFEI, and hypertension. Women with circulating estradiol above the median value of 10 pg/mL had better total HTLV total scores compared to women with estradiol values below the median (HTLV total scores, estradiol ≤ 10 pg/mL vs. > 10 pg/mL: 24.2 ± 3.6 vs. 30.0 ± 7.9, p value = 0.007 unadjusted). This association was affected by education and remained independent of menopausal symptoms and testosterone levels, education, and hypertension (model R 2 = 22.3%; b-coefficient = 0.318, p value = 0.024). Endogenous total estradiol is associated with verbal episodic memory, while logFAI is associated with working memory performance and visuospatial episodic memory in this sample of postmenopausal women. These associations were not influenced by age, education, or menopausal symptoms. Larger studies are necessary to evaluate the significance of our findings.

  10. To fight or mate? Hormonal control of sex recognition, male sexual behavior and aggression in the gecko lizard.

    PubMed

    Schořálková, Tereza; Kratochvíl, Lukáš; Kubička, Lukáš

    2018-01-01

    Squamate reptiles are a highly diversified vertebrate group with extensive variability in social behavior and sexual dimorphism. However, hormonal control of these traits has not previously been investigated in sufficient depth in many squamate lineages. Here, we studied the hormonal control of male sexual behavior, aggressiveness, copulatory organ (hemipenis) size and sex recognition in the gecko Paroedura picta, comparing ovariectomized females, ovariectomized females treated with exogenous dihydrotestosterone (DHT), ovariectomized females treated with exogenous testosterone (T), control females and males. The administration of both T and DHT led to the expression of male-typical sexual behavior in females. However, in contrast to T, increased circulating levels of DHT alone were not enough to initiate the full expression of male-typical offensive aggressive behavior and development of hemipenes in females. Ovariectomized females were as sexually attractive as control females, which does not support the need for the demasculinization of the cues used for sex recognition by ovarian hormones as suggested in other sauropsids. On the other hand, our results point to the masculinization of the sex recognition cues by male gonadal androgens. Previously, we also demonstrated that sexually dimorphic growth is controlled by ovarian hormones in P. picta. Overall, it appears that individual behavioral and morphological sexually-dimorphic traits are controlled by multiple endogenous pathways in this species. Variability in the endogenous control of particular traits could have permitted their disentangling during evolution and the occurrence of (semi)independent changes across squamate phylogeny. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis.

    PubMed

    Yang, Ju Dong; Abdelmalek, Manal F; Guy, Cynthia D; Gill, Ryan M; Lavine, Joel E; Yates, Katherine; Klair, Jagpal; Terrault, Norah A; Clark, Jeanne M; Unalp-Arida, Aynur; Diehl, Anna Mae; Suzuki, Ayako

    2017-01-01

    Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P < .01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P < .05). Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  12. Hepatic Long Intergenic Noncoding RNAs: High Promoter Conservation and Dynamic, Sex-Dependent Transcriptional Regulation by Growth Hormone

    PubMed Central

    Melia, Tisha; Hao, Pengying; Yilmaz, Feyza

    2015-01-01

    Long intergenic noncoding RNAs (lincRNAs) are increasingly recognized as key chromatin regulators, yet few studies have characterized lincRNAs in a single tissue under diverse conditions. Here, we analyzed 45 mouse liver RNA sequencing (RNA-Seq) data sets collected under diverse conditions to systematically characterize 4,961 liver lincRNAs, 59% of them novel, with regard to gene structures, species conservation, chromatin accessibility, transcription factor binding, and epigenetic states. To investigate the potential for functionality, we focused on the responses of the liver lincRNAs to growth hormone stimulation, which imparts clinically relevant sex differences to hepatic metabolism and liver disease susceptibility. Sex-biased expression characterized 247 liver lincRNAs, with many being nuclear RNA enriched and regulated by growth hormone. The sex-biased lincRNA genes are enriched for nearby and correspondingly sex-biased accessible chromatin regions, as well as sex-biased binding sites for growth hormone-regulated transcriptional activators (STAT5, hepatocyte nuclear factor 6 [HNF6], FOXA1, and FOXA2) and transcriptional repressors (CUX2 and BCL6). Repression of female-specific lincRNAs in male liver, but not that of male-specific lincRNAs in female liver, was associated with enrichment of H3K27me3-associated inactive states and poised (bivalent) enhancer states. Strikingly, we found that liver-specific lincRNA gene promoters are more highly species conserved and have a significantly higher frequency of proximal binding by liver transcription factors than liver-specific protein-coding gene promoters. Orthologs for many liver lincRNAs were identified in one or more supraprimates, including two rat lincRNAs showing the same growth hormone-regulated, sex-biased expression as their mouse counterparts. This integrative analysis of liver lincRNA chromatin states, transcription factor occupancy, and growth hormone regulation provides novel insights into the

  13. [Effect of treatment with diet on reducing levels of sex hormones in perimenopausal women with overweight and obesity].

    PubMed

    Łokieć, Katarzyna; Błońska, Aleksandra; Walecka-Kapica, Ewa; Stec-Michalska, Krystyna

    2016-06-01

    Nowadays, fight against obesity is a big challenge for the developed countries. Perimenopausal women are especially prone to becoming overweight and obese. This is due to changes in hormone levels and alterations in the sex hormones synthesis pathway. The aim of this study was to evaluate the levels of sex hormones in overweight and obese women during menopause following the three month period of reducing diet. The study involved women aged 55±4,75 years. Group I - 33 overweight women (BMI 28,06±1,00 kg/m(2)). Group II - 32 obese women (BMI 34,22±3,79 kg/m(2)). Anthropometric measurements, body composition tested with Bodystat QuadScan 4000 analyzer and levels of sex hormones in the blood was determined before and after the three-months of reducing diet in both groups. Statistical data analysis was performed. After three-months of reducing diet it was noticed that levels of BMI, body fat, FSH, DHEA-S and androstenedione were decreased in a statistically significant manner. A significant increase in estradiol levels after reduction of visceral adipose tissue in both groups, overweight and obese women, was observed. However, only in the group of obese women, a decrease in BMI correlated with a significant increase in estradiol levels. Application of appropriate reducing diet in perimenopausal overweight and obese women has positive impact on visceral adipose tissue distribution and causes an increase in sex hormones levels. Perimenopausal overweight and obese women should pursue weight reduction to improve their chances of contracting cardiovascular diseases. © 2016 MEDPRESS.

  14. Histological and transcriptomic effects of 17α-methyltestosterone on zebrafish gonad development.

    PubMed

    Lee, Stephanie Ling Jie; Horsfield, Julia A; Black, Michael A; Rutherford, Kim; Fisher, Amanda; Gemmell, Neil J

    2017-07-24

    Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, ovarian differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. Androgens and aromatase inhibitors can induce female-to-male sex reversal, however, the mechanisms underlying gonadal masculinisation are poorly understood. We used histological analyses together with RNA sequencing to characterise zebrafish gonadal transcriptomes and investigate the effects of 17α-methyltestosterone on gonadal differentiation. At a morphological level, 17α-methyltestosterone (MT) masculinised gonads and accelerated spermatogenesis, and these changes were paralleled in masculinisation and de-feminisation of gonadal transcriptomes. MT treatment upregulated expression of genes involved in male sex determination and differentiation (amh, dmrt1, gsdf and wt1a) and those involved in 11-oxygenated androgen production (cyp11c1 and hsd11b2). It also repressed expression of ovarian development and folliculogenesis genes (bmp15, gdf9, figla, zp2.1 and zp3b). Furthermore, MT treatment altered epigenetic modification of histones in zebrafish gonads. Contrary to expectations, higher levels of cyp19a1a or foxl2 expression in control ovaries compared to MT-treated testes and control testes were not statistically significant during early gonad development (40 dpf). Our study suggests that both androgen production and aromatase inhibition are important for androgen-induced gonadal masculinisation and natural testicular differentiation in zebrafish.

  15. Sex Hormone Effects on Physical Activity Levels: Why Doesn’t Jane Run as Much as Dick?

    PubMed Central

    Bowen, Robert S.; Turner, Michael J.; Lightfoot, J. Timothy

    2010-01-01

    The relationship between physical activity levels and disease rates have become an important health related concern in the developed world. Heart disease, certain cancers, and obesity persist at epidemic rates in the United States and Western Europe. Increased physical activity levels have been shown to reduce the occurrence of many chronic diseases leading to reductions in the burden on the health care system. Activity levels in humans are affected by many cultural and environmental factors, nevertheless current research points to a strong biological input with potential genetic, neurological, and endocrinological origins. Of unique interest, the sex hormones appear to have a very strong influence on activity levels. The current animal literature suggests that females tend to be more active than males due to biological pathways of estrogenic origin. The majority of human epidemiological and anthropological data, on the contrary, suggest women are less active than men in spite of this inherent activity-increasing mechanism. The purpose of this manuscript was to review the current literature regarding the control of physical activity levels by the sex hormones in humans. Using the natural transitional phases of the aging endocrine system, natural periodicity of the menstrual cycle, and pharmacological/hormone replacement therapy as variable experimental stages, some authors have been able to provide some information regarding the existence of an inherent activity-increasing mechanism in humans. In brief, activity levels during life stages prior to and after menopause do not significantly differ, despite the vast changes in sex hormone levels and function. Activity difference throughout a regular menstrual cycle do not appear to influence activity levels in humans either—an effect that is pronounced in the female rodent. The use of hormone replacement therapies provide researchers with more systematic controls over hormone modulation in human subjects; however

  16. A review of the physical and metabolic effects of cross-sex hormonal therapy in the treatment of gender dysphoria.

    PubMed

    Seal, Leighton J

    2016-01-01

    This review focuses on the effect that cross-gender sex steroid therapy has on metabolic and hormonal parameters. There is an emphasis on those changes that result in significant clinical effects such as the positive effects of the development of secondary sexual characteristics and negative effects such as haemostatic effects and thromboembolism in transwomen or dyslipidaemia in transmen. There is also a description of the current hormonal regimens used at the largest UK gender identity clinic. The overall safety of these treatments in the context of long-term outcome data is reviewed. © The Author(s) 2015.

  17. Expression of HOXA10 in endometrial hyperplasia and adenocarcinoma and regulation by sex hormones in vitro.

    PubMed

    Zhong, Gang; Wang, Yan; Liu, Xuemei

    2011-07-01

    The objective of the study was to determine the expression of HOXA10 in human endometrial tissue in endometrial hyperplasia and carcinomas, and regulation by sex steroids in Ishikawa cells. Endometrial tissue was obtained from 133 subjects with normal endometria, endometrial hyperplasia, or endometrial adenocarcinoma. Among 133 specimens, 20 were normal endometria, 19 were simple hyperplasias without atypia, 20 were complex hyperplasias without atypia, 33 were atypical hyperplasias, and 41 were endometrial adenocarcinomas. The expression of HOXA10 was analyzed by immunohistochemistry. Ishikawa cell lines were incubated with 17β estradiol (10⁻⁸ mol/L) alone, medroxyprogesterone acetate (10⁻⁶ mol/L) alone, or the combination of estrogen and progesterone for 48 hours, respectively. In certain experiments, the antiprogestin antagonist, RU486 (10⁻⁵ mol/L), was also added to Ishikawa cells along with estradiol and medroxyprogesterone acetate for 48 hours. The expression of HOXA10 gene was detected by reverse transcriptase-polymerase chain reaction and Western blotting. HOXA10 was expressed in both normal and neoplastic endometria. No significant difference in HOXA10 expression was found between normal and hyperplastic endometrial tissues. The expression of HOXA10 was decreased in endometrial adenocarcinomas compared with normal endometria. Estrogen alone, progestin alone, or progestin combined with estrogen could significantly increase the expression of HOXA10 gene (P<0.05). RU486 could inhibit the effect of up-regulation of HOXA10 expression by progestin. The expression of HOXA10 was deregulated in endometrial carcinomas and up-regulated by sex hormones.

  18. Regulation of onset of female mating and sex pheromone production by juvenile hormone in Drosophila melanogaster

    PubMed Central

    Bilen, Julide; Atallah, Jade; Azanchi, Reza; Levine, Joel D.; Riddiford, Lynn M.

    2013-01-01

    Juvenile hormone (JH) coordinates timing of female reproductive maturation in most insects. In Drosophila melanogaster, JH plays roles in both mating and egg maturation. However, very little is known about the molecular pathways associated with mating. Our behavioral analysis of females genetically lacking the corpora allata, the glands that produce JH, showed that they were courted less by males and mated later than control females. Application of the JH mimic, methoprene, to the allatectomized females just after eclosion rescued both the male courtship and the mating delay. Our studies of the null mutants of the JH receptors, Methoprene tolerant (Met) and germ cell-expressed (gce), showed that lack of Met in Met27 females delayed the onset of mating, whereas lack of Gce had little effect. The Met27 females were shown to be more attractive but less behaviorally receptive to copulation attempts. The behavioral but not the attractiveness phenotype was rescued by the Met genomic transgene. Analysis of the female cuticular hydrocarbon profiles showed that corpora allata ablation caused a delay in production of the major female-specific sex pheromones (the 7,11-C27 and -C29 dienes) and a change in the cuticular hydrocarbon blend. In the Met27 null mutant, by 48 h, the major C27 diene was greatly increased relative to wild type. In contrast, the gce2.5k null mutant females were courted similarly to control females despite changes in certain cuticular hydrocarbons. Our findings indicate that JH acts primarily via Met to modulate the timing of onset of female sex pheromone production and mating. PMID:24145432

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

    PubMed

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

    2017-07-01

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

  20. Sex hormones and quantitative ultrasound parameters at the heel in men and women from the general population.

    PubMed

    Pätzug, Konrad; Friedrich, Nele; Kische, Hanna; Hannemann, Anke; Völzke, Henry; Nauck, Matthias; Keevil, Brian G; Haring, Robin

    2017-12-01

    The present study investigates potential associations between liquid chromatography-mass spectrometry (LC-MS) measured sex hormones, dehydroepiandrosterone sulphate, sex hormone-binding globulin (SHBG) and bone ultrasound parameters at the heel in men and women from the general population. Data from 502 women and 425 men from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Cross-sectional associations of sex hormones including testosterone (TT), calculated free testosterone (FT), dehydroepiandrosterone sulphate (DHEAS), androstenedione (ASD), estrone (E1) and SHBG with quantitative ultrasound (QUS) parameters at the heel, including broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were examined by analysis of variance (ANOVA) and multivariable quantile regression models. Multivariable regression analysis showed a sex-specific inverse association of DHEAS with SI in men (Beta per SI unit = - 3.08, standard error (SE) = 0.88), but not in women (Beta = - 0.01, SE = 2.09). Furthermore, FT was positively associated with BUA in men (Beta per BUA unit = 29.0, SE = 10.1). None of the other sex hormones (ASD, E1) or SHBG was associated with QUS parameters after multivariable adjustment. This cross-sectional population-based study revealed independent associations of DHEAS and FT with QUS parameters in men, suggesting a potential influence on male bone metabolism. The predictive role of DHEAS and FT as a marker for osteoporosis in men warrants further investigation in clinical trials and large-scale observational studies.

  1. Sex Hormones Enhance Gingival Inflammation without Affecting IL-1β and TNF-α in Periodontally Healthy Women during Pregnancy

    PubMed Central

    Wu, Min; Chen, Shao-Wu; Su, Wei-Lan; Zhu, Hong-Ying; Ouyang, Shu-Yuan; Cao, Ya-Ting; Jiang, Shao-Yun

    2016-01-01

    Hormones (progesterone and estradiol) change greatly during pregnancy; however, the mechanism of hormonal changes on gingival inflammation is still unclear. This study is to evaluate the effects of hormonal changes during pregnancy on gingival inflammation and interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid (GCF). 30 periodontally healthy pregnant women were evaluated in the first, second, and third trimesters. 20 periodontally healthy nonpregnant women were evaluated twice (once per subsequent month). Clinical parameters including probing pocket depth (PPD), bleeding index (BI), gingival index (GI), clinical attachment level (CAL), and plaque index (PLI) were recorded. GCF levels of IL-1β and TNF-α and serum levels of progesterone and estradiol were measured. From the data, despite low PLI, BI and GI increased significantly during pregnancy; however, no significant changes in PLI, CAL, IL-1β, or TNF-α GCF levels were observed. Although IL-1β, not TNF-α, was higher in pregnant group than in nonpregnant group, they showed no correlation with serum hormone levels during pregnancy. GI and BI showed significant positive correlation with serum hormone levels during pregnancy. This study suggests that sex hormone increase during pregnancy might have an effect on inflammatory status of gingiva, independent of IL-1β and TNF-α in GCF. PMID:27034591

  2. Sex Hormones Enhance Gingival Inflammation without Affecting IL-1β and TNF-α in Periodontally Healthy Women during Pregnancy.

    PubMed

    Wu, Min; Chen, Shao-Wu; Su, Wei-Lan; Zhu, Hong-Ying; Ouyang, Shu-Yuan; Cao, Ya-Ting; Jiang, Shao-Yun

    2016-01-01

    Hormones (progesterone and estradiol) change greatly during pregnancy; however, the mechanism of hormonal changes on gingival inflammation is still unclear. This study is to evaluate the effects of hormonal changes during pregnancy on gingival inflammation and interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid (GCF). 30 periodontally healthy pregnant women were evaluated in the first, second, and third trimesters. 20 periodontally healthy nonpregnant women were evaluated twice (once per subsequent month). Clinical parameters including probing pocket depth (PPD), bleeding index (BI), gingival index (GI), clinical attachment level (CAL), and plaque index (PLI) were recorded. GCF levels of IL-1β and TNF-α and serum levels of progesterone and estradiol were measured. From the data, despite low PLI, BI and GI increased significantly during pregnancy; however, no significant changes in PLI, CAL, IL-1β, or TNF-α GCF levels were observed. Although IL-1β, not TNF-α, was higher in pregnant group than in nonpregnant group, they showed no correlation with serum hormone levels during pregnancy. GI and BI showed significant positive correlation with serum hormone levels during pregnancy. This study suggests that sex hormone increase during pregnancy might have an effect on inflammatory status of gingiva, independent of IL-1β and TNF-α in GCF.

  3. Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores.

    PubMed

    Key, T J; Roe, L; Thorogood, M; Moore, J W; Clark, G M; Wang, D Y

    1990-07-01

    Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

  4. Diminished hepatic growth hormone receptor binding in sex-linked dwarf broiler and leghorn chickens.

    PubMed

    Leung, F C; Styles, W J; Rosenblum, C I; Lilburn, M S; Marsh, J A

    1987-02-01

    Hepatic growth hormone (GH) receptor binding was compared in normal and sex-linked dwarfs (SLD) from both Hubbard and Cornell strain chickens. At 6, 8, and 20 weeks of age, hepatic GH receptor binding in the Hubbard SLD chickens was significantly lower than that of normal fast-growing birds. At 20 weeks of age, only 2 of 22 SLD chickens in the Hubbard broiler strain showed positive binding at a high enough level to allow for Scatchard analysis. The affinity constants and binding capacities of these two SLD chickens were numerically (but not significantly) lower than those of the normal fast-growing birds. We further examined hepatic GH receptor binding in two closely related White Leghorn strains of chickens that have been maintained as closed breeding populations for many years. We observed no detectable hepatic GH binding in the Cornell SLD chickens (N = 20), as compared to the normal-growing control strain (K strain). In both SLD strains, pretreatment with 4 M MgCl2 did not enhance GH binding, suggesting that there was no endogenous GH binding to the receptor. Based on these data, we suggest that the lack, or greatly reduced number, of GH receptors may be a major contributing factor to the dwarfism observed in these strains.

  5. [Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

    PubMed

    Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

    2013-03-01

    To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

  6. Postinjury biomechanics of Achilles tendon vary by sex and hormone status

    PubMed Central

    Fryhofer, George W.; Freedman, Benjamin R.; Hillin, Cody D.; Salka, Nabeel S.; Pardes, Adam M.; Weiss, Stephanie N.; Farber, Daniel C.

    2016-01-01

    Achilles tendon ruptures are common injuries. Sex differences are present in mechanical properties of uninjured Achilles tendon, but it remains unknown if these differences extend to tendon healing. We hypothesized that ovariectomized females (OVX) and males would exhibit inferior postinjury tendon properties compared with females. Male, female, and OVX Sprague-Dawley rats (n = 32/group) underwent acclimation and treadmill training before blunt transection of the Achilles tendon midsubstance. Injured hindlimbs were immobilized for 1 wk, followed by gradual return to activity and assessment of active and passive hindlimb function. Animals were euthanized at 3 or 6 wk postinjury to assess tendon structure, mechanics, and composition. Passive ankle stiffness and range of motion were superior in females at 3 wk; however, by 6 wk, passive and active function were similar in males and females but remained inferior in OVX. At 6 wk, female tendons had greater normalized secant modulus, viscoelastic behavior, and laxity compared with males. Normalized secant modulus, cross-sectional area and tendon glycosaminoglycan composition were inferior in OVX compared with females at 6 wk. Total fatigue cycles until tendon failure were similar among groups. Postinjury muscle fiber size was better preserved in females compared with males, and females had greater collagen III at the tendon injury site compared with males at 6 wk. Despite male and female Achilles tendons withstanding similar durations of fatigue loading, early passive hindlimb function and tendon mechanical properties, including secant modulus, suggest superior healing in females. Ovarian hormone loss was associated with inferior Achilles tendon healing. PMID:27633741

  7. Prognostic value of sex-hormone receptor expression in non-muscle-invasive bladder cancer.

    PubMed

    Nam, Jong Kil; Park, Sung Woo; Lee, Sang Don; Chung, Moon Kee

    2014-09-01

    We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.

  8. Fetal sex-based differences in maternal hormones, angiogenic factors, and immune mediators during pregnancy and the postpartum period.

    PubMed

    Enninga, Elizabeth Ann L; Nevala, Wendy K; Creedon, Douglas J; Markovic, Svetomir N; Holtan, Shernan G

    2015-03-01

    Several pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences. Using maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum. Male fetal sex was associated with higher levels of proinflammatory cytokines (G-CSF, IL-12p70, IL-21, and IL-33) and angiogenic factors (PlGF and VEGF-A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL-5, IL-9, IL-17, and IL-25). IL-27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex-based difference in analyte concentrations at the postpartum measurement. Women carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus. © 2014 The Authors. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.

  9. Fetal Sex-Based Differences in Maternal Hormones, Angiogenic Factors, and Immune Mediators During Pregnancy and the Postpartum Period

    PubMed Central

    Enninga, Elizabeth Ann L; Nevala, Wendy K; Creedon, Douglas J; Markovic, Svetomir N; Holtan, Shernan G

    2015-01-01

    Problem Several pregnancy complications have disparities based on the sex of the fetus. It is unknown whether the sex of the fetus differentially alters the maternal immune milieu, potentially contributing to the observed differences. Method of study Using maternal plasma collected during 38 uncomplicated pregnancies (19 males, 19 females), we compared levels of cytokines, sex hormones, and angiogenic factors throughout gestation and postpartum. Results Male fetal sex was associated with higher levels of proinflammatory cytokines (G-CSF, IL-12p70, IL-21, and IL-33) and angiogenic factors (PlGF and VEGF-A) compared with female fetal sex at multiple timepoints. Female fetal sex was associated with higher levels of regulatory cytokines (IL-5, IL-9, IL-17, and IL-25). IL-27 increased throughout pregnancy regardless of fetal sex. There was no fetal sex-based difference in analyte concentrations at the postpartum measurement. Conclusion Women carrying a male fetus exhibit a more proinflammatory/proangiogenic immune milieu than women carrying a female fetus. PMID:25091957

  10. Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: a tool for examining OH-BDE toxicity to early life stages.

    PubMed

    Dong, Wu; Macaulay, Laura J; Kwok, Kevin W H; Hinton, David E; Stapleton, Heather M

    2013-05-15

    Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on

  11. Using Whole mount In Situ Hybridization to Examine Thyroid Hormone Deiodinase Expression in Embryonic and Larval Zebrafish: a Tool for examining OH-BDE toxicity to early life stages

    PubMed Central

    Dong, Wu; Macaulay, Laura; Kwok, Kevin WH; Hinton, David E; Stapleton, Heather M.

    2013-01-01

    Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100 nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on

  12. Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes.

    PubMed

    Savic, Ivanka

    2014-01-01

    Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47,XXY). Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis. All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46,XY males than 46,XX females and 47,XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46,XX females and 47,XXY males, but were not related to sex hormone levels. No asymmetry differences between 46,XX females and 47,XXY males, and no overall effects of brain size were detected. The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner.

  13. Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes

    PubMed Central

    Savic, Ivanka

    2014-01-01

    Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47,XXY). Methods: Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis. Results: All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46,XY males than 46,XX females and 47,XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46,XX females and 47,XXY males, but were not related to sex hormone levels. No asymmetry differences between 46,XX females and 47,XXY males, and no overall effects of brain size were detected. Conclusion: The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner. PMID:25505869

  14. Reproductive toxicity of azoxystrobin to adult zebrafish (Danio rerio).

    PubMed

    Cao, Fangjie; Zhu, Lizhen; Li, Hui; Yu, Song; Wang, Chengju; Qiu, Lihong

    2016-12-01

    In the past few decades, extensive application of azoxystrobin has led to great concern regarding its adverse effects on aquatic organisms. The objective of the present study was to evaluate the reproductive toxicity of azoxystrobin to zebrafish. After adult zebrafish of both sexes were exposed to 2, 20 and 200 μg/L azoxystrobin for 21 days, egg production, the fertilization rate, the gonadosomatic index (GSI) and hepatosomatic index (HSI), 17β-estradiol (E2), testosterone (T) and vitellogenin (Vtg) concentrations, and histological alterations in the gonads and livers were measured. Meanwhile, expression alterations of genes encoding gonadotropins and gonadotropin receptors (fshb, lhb, fshr and lhr), steroid hormone receptors (era, er2b and ar), steroidogenic enzymes (cyp11a, cyp11b, cyp17, cyp19a, cyp19b, hsd3b and hsd17b) in the hypothalamic-pituitary-gonad (HPG) axis and vitellogenin (vtg1 and vtg2) in the livers were also investigated. The results showed that reduced egg production and fertilization rates were observed at 200 μg/L azoxystrobin. In female zebrafish, reduced E2 and Vtg concentrations, decreased GSI, increased T concentrations, and histological alterations in the ovaries and livers were observed at 200 μg/L azoxystrobin, along with significant down-regulation of lhb, cyp19b, lhr, cyp19a, vtg1 and vtg2, and up-regulation of cyp17, hsd3b and hsd17b. In male zebrafish, increased E2 and Vtg concentrations, reduced T concentration and GSI, and histological alterations in the testes and livers were observed after exposure to 20 and 200 μg/L azoxystrobin, along with significant up-regulations of cyp19b, cyp11a, cyp17, cyp19a, hsd3b and hsd17b, vtg1 and vtg2. Moreover, cyp11a, hsd3b, cyp19a, vtg1 and vtg2 in male zebrafish were significantly up-regulated after treatment with 2 μg/L azoxystrobin. The results of the present study indicate that azoxystrobin led to reproductive toxicity in zebrafish and male zebrafish were more sensitive to

  15. Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study.

    PubMed

    Chen, Yi; Chen, Yingchao; Wang, Ningjian; Chen, Chi; Nie, Xiaomin; Li, Qin; Han, Bing; Xia, Fangzhen; Zhai, Hualing; Jiang, Boren; Shen, Zhoujun; Lu, Yingli

    2017-08-03

    Little is known about the association between thyroid nodules (TNs) and endogenous sex hormones. We aimed to investigate the relationship between TNs and sex-related hormones among men in China. The data were obtained from a cross-sectional study Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China study, 2014-2015) based on the population. In total, 4024 men over 18 years of age who were not using hormone replacement therapy and who underwent complete assays of the serum total testosterone (T), oestradiol (E 2 ), follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone-binding globulin (SHBG) levels as well as thyroid ultrasonography (US) enrolled in this study. Of the 4024 participants (54.15±13.08 years old), 1667 participants (41.4%) had TNs. Men with TN(s) (TN(+) group) had significantly lower levels of total T and SHBG and higher E 2 /T levels compared with the men without TN(s) (TN(-) group) (p<0.05). The TN prevalence decreased with the quartiles of the SHBG level (p<0.05). Binary logistic analysis showed that lower quartiles of SHBG had a greater risk of TN(s) (all p for trend <0.05). This association persisted in the fully adjusted model (p for trend=0.017), in which, for the lowest compared with the highest quartile of SHBG, the OR of TN(s) was 1.42 (95% CI 1.07 to 1.89). No statistically significant association was found between sex-related hormones and US characteristics associated with malignancy (nodule >10 mm, microcalcification and a 'taller' than 'wider' shape). TNs are highly prevalent in men in China. A lower SHBG level was significantly associated with TN among men. The potential role of SHBG in the pathogenesis of the TN remains to be elucidated. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. 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

  17. Prenatal and Peripubertal Phthalates and Bisphenol-A in Relation to Sex Hormones and Puberty in Boys

    PubMed Central

    Ferguson, Kelly K.; Peterson, Karen E.; Lee, Joyce M.; Mercado-García, Adriana; Goldenberg, Clara B.; Téllez-Rojo, Martha M.; Meeker, John D.

    2014-01-01

    Phthalates and BPA are known endocrine disruptors and exposure in pregnant mothers and children is ubiquitous. We explored the relationship of prenatal and childhood exposures with pubertal onset and sex hormones in boys (ages 8–14). Phthalate metabolites and BPA were measured in maternal 3rd trimester or childhood urine. Sex hormones DHEAS, estradiol, inhibin B, SHBG, and total testosterone were measured in serum. Adrenarche and puberty were assessed by pediatrician. Prenatal exposure to some phthalates was associated with decreased DHEAS and inhibin B levels, and with increased SHBG. Prenatal exposure to most phthalates and BPA was associated with greatly reduced odds of adrenarche (odds ratios [OR] = 0.12 to 0.65) and slightly reduced odds of puberty (OR = 0.50 to 0.98). Childhood exposure was not associated with adrenarche or puberty, but some phthalates and BPA were associated with increased SHBG levels and decreased total and free testosterone levels. PMID:24945889

  18. Sex hormones and the risk of type 2 diabetes mellitus: A 9-year follow up among elderly men in Finland.

    PubMed

    Salminen, Marika; Vahlberg, Tero; Räihä, Ismo; Niskanen, Leo; Kivelä, Sirkka-Liisa; Irjala, Kerttu

    2015-05-01

    To analyze whether sex hormone levels predict the incidence of type2 diabetes among elderly Finnish men. This was a prospective population-based study, with a 9-year follow up period. The study population in the municipality of Lieto, Finland, consisted of elderly (age ≥64 years) men free of type 2 diabetes at baseline in 1998-1999 (n = 430). Body mass index and cardiovascular disease-adjusted hazard ratios and their 95% confidence intervals for type 2 diabetes predicted by testosterone, free testosterone, sex hormone-binding globulin, luteinizing hormone, and testosterone/luteinizing hormone were estimated. A total of 30 new cases of type 2 diabetes developed during the follow-up period. After adjustment, only higher levels of testosterone (hazard ratio for one-unit increase 0.93, 95% confidence interval 0.87-0.99, P = 0.020) and free testosterone (hazard ratio for 10-unit increase 0.96, 95% confidence interval 0.91-1.00, P = 0.044) were associated with a lower risk of incident type 2 diabetes during the follow up. These associations (0.94, 95% confidence interval 0.87-1.00, P = 0.050 and 0.95, 95% confidence interval 0.90-1.00, P = 0.035, respectively) persisted even after additional adjustment of sex hormone-binding globulin. Higher levels of testosterone and free testosterone independently predicted a reduced risk of type 2 diabetes in the elderly men. © 2014 Japan Geriatrics Society.

  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. Associations between Markers of Inflammation and Physiological and Pharmacological Levels of Circulating Sex Hormones in Postmenopausal Women

    PubMed Central

    Karim, Roksana; Stanczyk, Frank Z.; Hodis, Howard N.; Cushman, Mary; Lobo, Roger A.; Hwang, Juliana; Mack, Wendy J.

    2010-01-01

    Objective Hormone therapy has been shown to reduce markers of vascular inflammation in postmenopausal women. C-reactive protein (CRP), a marker of generalized inflammation, is raised by oral estradiol therapy. It is not known how sex hormone concentrations relate to the markers of inflammation in postmenopausal women taking or not taking hormone therapy. Methods This observational study includes postmenopausal women participating in the Estrogen in the Prevention of Atherosclerosis Trial (EPAT). Multiple measures of serum sex hormone and sex hormone binding globulin (SHBG) levels from 107 postmenopausal women taking oral estradiol therapy (ET) and 109 taking placebo over 2 years were correlated with markers of inflammation over the same time period using generalized estimating equations. Results Levels of soluble intercellular adhesion molecule-1 (sICAM-1) were significantly inversely associated with estrone (p = 0.05), total and free estradiol (p = 0.008 and 0.02, respectively), and SHBG (p = 0.03) only among oral ET users. Serum homocysteine levels were also inversely associated with estrone (p = 0.0001), total and free estradiol (p = 0.0006 and 0.0009, respectively) in ET-treated women only. No such associations were observed among women taking placebo. C-reactive protein (CRP) was positively associated with estrogens and SHBG among women taking oral ET but inversely associated with SHBG among the placebo group. Conclusions The inverse associations of estrogens with sICAM-1, and homocysteine support an anti-inflammatory property of estrogen, which was only observed at pharmacologic levels in postmenopausal women. The positive associations between estrogens and CRP in the ET-treated women can be explained by the first-pass hepatic effect rather than a pro-inflammatory response. PMID:20632462

  1. The Effect of Oral Feeding of Tribulus terrestris L. on Sex Hormone and Gonadotropin Levels in Addicted Male Rats

    PubMed Central

    Ghosian Moghaddam, Mohammad Hassan; Khalili, Mohsen; Maleki, Maryam; Ahmad Abadi, Mohammad Esmail

    2013-01-01

    Background: Opioids can exert adverse effects on the body. Morphine, an opioid drug, reduces hormone levels and fertility, and causes sexual activity disorders. Tribulus terrestris (TT) is a traditional herbal medicine used to enhance sexual activities. This study investigates the possible role of TT on sex hormones and gonadotropins with the intent to show its usefulness in treating fertility disorders in opioid users. Materials and Methods: In this experimental study, we randomly divided 48 rats into four groups: i. control, ii. TT-treated, iii. addicted and iv. TT-treated addicted. Watersoluble morphine was administrated orally for 21 days to induce addiction, after which the treated groups 2 and 4 received plant-mixed pelleted food (6.25%) orally for four weeks. At the end of the treatment period, the sex hormone and gonadotropin levels of all rats’ sera were determined by radioimmunoassay and Elisa kits. The data obtained were statistically analyzed using the one-way analysis of variance, followed by post-hoc Tukey test. P<0.05 was considered significant. Results: The addicted group had a significantly lower luteinizing hormone (LH) level than the control group (p<0.027). LH levels increased significantly in the TT-treated addicted group (p<0.031). The testosterone level in the treated addicted group was lower than the treated control group. The addicted group had a significantly low testosterone level (p<0.001). The estrogen level was significantly (p<0.002) lower in the addicted group than in the control group. In addition, there was a significant difference between the treated addicted group and the treated control group (p<0.048). The treated control group had a significant increase in its progesterone level (p<0.002). Overall, except for follicle-stimulating hormone (FSH), morphine reduced most of the gonadotropins and sexual hormones. Whereas TT caused a considerable increase (p<0.05) in the hormones in the treated addicted group, there was only a

  2. Dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS) compared with women with non-PCOS-related infertility.

    PubMed

    Tsai, Ya-Hui; Wang, Ting-Wen; Wei, Hsiao-Jui; Hsu, Chien-Yeh; Ho, Hsin-Jung; Chen, Wen-Hua; Young, Robert; Liaw, Chian-Mey; Chao, Jane C-J

    2013-06-28

    The present study investigated dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS). A total of forty-five women (aged 25–40 years) with PCOS and 161 control women (aged 25–43 years) with non-PCOS-related infertility were recruited. Anthropometry, glucose tolerance and sex hormones were determined and dietary intake was assessed. Women with PCOS had lower serum sex hormone-binding globulin and increased BMI, waist:hip ratio, luteinising hormone, ratio of luteinising hormone: follicle-stimulating hormone, testosterone and free androgen index (FAI). Postprandial glucose, fasting insulin and insulin resistance were elevated in women with PCOS. Women with PCOS had reduced energy and carbohydrate intake but higher fat intake. Serum sex hormone-binding globulin level was negatively associated with BMI in both groups and negatively correlated with macronutrient intake in the PCOS group with hyperandrogenism. However, FAI was positively correlated with BMI, waist circumference and glucose metabolic parameters in both groups. Therefore, women with PCOS consume lower energy and carbohydrate compared with those with non-PCOS-related infertility and macronutrient intake is only negatively associated with serum sex hormone-binding globulin level in the PCOS group with hyperandrogenism.

  3. Endogenous sex hormones, blood pressure change, and risk of hypertension in postmenopausal women: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Wang, Lu; Szklo, Moyses; Folsom, Aaron R; Cook, Nancy R; Gapstur, Susan M; Ouyang, Pamela

    2012-09-01

    Sex steroid hormones have been postulated to involve in blood pressure (BP) regulation. We examine the association of endogenous sex hormone levels with longitudinal change of BP and risk of developing hypertension in initially normotensive postmenopausal women. We conducted prospective analysis among 619 postmenopausal women free of hypertension at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Change of BP and development of incident hypertension were assessed during a mean of 4.8 years follow-up. After adjusting for age, race/ethnicity, and lifestyle factors, baseline serum estradiol (E(2)), total and bioavailable testosterone (T), dehydroepiandrosterone (DHEA) were each positively associated and sex-hormone binding globulin (SHBG) was inversely associated with risk of hypertension. Additional adjustment for body mass index eliminated the associations for E(2) and T but only attenuated the associations for DHEA and SHBG. The corresponding multivariable hazard ratios (95% CIs) in the highest quartile were 1.28 (0.83-1.97) for E(2), 1.38 (0.89-2.14) for total T, 1.42 (0.90-2.23) for bioavailable T, 1.54 (1.02-2.31) for DHEA, and 0.48 (0.30-0.76) for SHBG. Adjustment for fasting glucose, insulin, and C-reactive protein further attenuated the association for DHEA but not for SHBG. Associations of sex hormones with longitudinal BP change were similar. In postmenopausal women, higher endogenous E(2), T, and DHEA and lower SHBG were associated with higher incidence of hypertension and greater longitudinal rise in BP. The associations for E(2), T, and DHEA were mostly explained by adiposity, while the association for SHBG was independent of measures of adiposity, insulin resistance, and systemic inflammation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. The effect of orbital implantation on peripheral blood melatonin and sex hormone levels in child patients with congenital eyeball dysplasia.

    PubMed

    Ma, Junze; Liu, Tao; Qu, Jianqiang

    2017-09-01

    The aim of the study was to examine the effect of orbital implantation on peripheral blood melatonin and sex hormone levels in pediatric patients with congenital eyeball dysplasia. A total of 28 cases of pediatric patients with congenital eyeball dysplasia diagnosed in the Second Affiliated Hospital of Xi'an Jiaotong University from June 2014 to December 2014 were selected for the study. The patients included those that received orbital implantation, and the melatonin levels in the peripheral blood in patients before and after operation was observed. In addition, the sex hormone levels and T lymphocytes, plasma reactive oxygen species (ROS) and VEGF levels, urine 8-OHdG and 8-isoPGF2α levels in patients before and after treatment were detected, followed by statistical analysis. As a result, after 3 months of orbital implantation, the sex hormone levels in peripheral blood in child patients fluctuated significantly, and differences were not statistically significant (P>0.05). The peripheral blood T lymphocytes and ROS levels were significantly lower than those before treatment, and the differences were statistically significant (P<0.05). The correlation analysis revealed that the peripheral blood melatonin levels were negatively related to ROS levels; the correlation coefficient was rs = -0.481 and P<0.05. In conclusion, orbital implantation does not have significant impact on sex hormone levels in child patients with congenital eyeball dysplasia. The hydroxyapatite orbital implantation can achieve more satisfactory curative effects, and there are fewer postoperative complications. It does not affect the appearance of the eye, and therefore, it is suitable for patients with congenital eyeball dysplasia.

  5. Influence of sex hormone levels on gingival enlargement in adolescent patients undergoing fixed orthodontic therapy: A pilot study

    PubMed Central

    Hosadurga, Rajesh; Nabeel Althaf, M. S.; Hegde, Shashikanth; Rajesh, Kashyap S.; Arun Kumar, M. S.

    2016-01-01

    Background: Sex hormones may be a modifying factor in the periodontal disease pathogenesis. Aim: The association between gingival enlargement and sex hormone levels in adolescent patients undergoing fixed orthodontic therapy needs to be determined. Settings and Design: This study was conducted in the Department of Periodontology in association with the Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangaluru. Materials and Methods: A pilot study was conducted on 21 adolescent patients between the age group of 13–19 years, who had undergone fixed orthodontic therapy for at least 3 months. Apicocoronally, the gingival enlargement was assessed by the index described by Miller and Damm. Miranda and Brunet index was used to assess gingival overgrowth in the buccal–lingual direction in the interdental papilla. Furthermore, the patients were assigned to two groups - Group 1-GE and Group 2-non-GE. Sex hormones assessed were estradiol and progesterone in females and testosterone in males in both groups. Results: 57.1% of the study population had enlargement of the gingiva. The mean plaque score was 0.59 and 0.56, respectively, in both groups. A statistically significant relationship was found between estradiol and testosterone levels with gingival enlargement. However, a significant relationship was not obtained for progesterone levels with the gingival enlargement. Conclusion: Direct correlation between estradiol, testosterone, and gingival enlargement was seen. PMID:27994419

  6. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

    PubMed

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

    2016-03-01

    Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

  7. Sex-related differences in fuel utilization and hormonal response to exercise: implications for individuals with type 1 diabetes.

    PubMed

    Brockman, Nicole K; Yardley, Jane E

    2018-06-01

    Sex-related differences in metabolic and neuroendocrine response to exercise in individuals without diabetes have been well established. Men and women differ in fuel selection during exercise, in which women rely to a greater ex